Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2006-10-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

Gynaecological and obstetric management of women with inherited bleeding disorders.

PubMed

Demers, Christine; Derzko, Christine; David, Michèle; Douglas, Joanne

2005-07-01

The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. This consensus document has been developed by a multidisciplinary committee consisting of an anesthesiologist, 2 hematologists, and an obstetrician/gynaecologist and has been endorsed by their relevant specialty bodies. It has been prepared with the express purpose of providing guidelines for both women with inherited bleeding disorders and for their caregivers regarding the gynaecological and obstetric management of these women, including appropriate anesthesia support where indicated. Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. 1. Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2. Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3. Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4. An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-1B], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (levonorgestrel-releasing IUS [II-1B]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-1B]) as well as desmopressin (II-1B). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5. In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-1B). 6. Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested pre-menarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7. In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8. Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9. Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical indications only (II-2C). 10. Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11. The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised about the possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12. Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B). The quality of evidence reported in this document has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam (Table 1).

Life-threatening subdural hematoma after aortic valve replacement in a patient with Heyde syndrome: a case report.

PubMed

Uchida, Tetsuro; Hamasaki, Azumi; Ohba, Eiichi; Yamashita, Atsushi; Hayashi, Jun; Sadahiro, Mitsuaki

2017-08-08

Heyde syndrome is known as a triad of calcific aortic stenosis, anemia due to gastrointestinal bleeding from angiodysplasia, and acquired type 2A von Willebrand disease. This acquired hemorrhagic disorder is characterized by the loss of the large von Willebrand factor multimers due to the shear stress across the diseased aortic valve. The most frequently observed type of bleeding in these patients is mucosal or skin bleeding, such as epistaxis, followed by gastrointestinal bleeding. On the other hand, intracranial hemorrhage complicating Heyde syndrome is extremely rare. A 77-year-old woman presented to our hospital with severe aortic stenosis and severe anemia due to gastrointestinal bleeding and was diagnosed with Heyde syndrome. Although aortic valve replacement was performed without recurrent gastrointestinal bleeding, postoperative life-threatening acute subdural hematoma occurred with a marked midline shift. Despite prompt surgical evacuation of the hematoma, she did not recover consciousness and she died 1 month after the operation. Postoperative subdural hematoma is rare, but it should be kept in mind as a devastating hemorrhagic complication, especially in patients with Heyde syndrome.

Common management issues in pediatric patients with mild bleeding disorders.

PubMed

O'Brien, Sarah H

2012-10-01

Type 1 von Willebrand disease and mild platelet function defects are among the most common disorders seen by pediatric hematologists. The management and prevention of bleeding in these patients can be challenging, as there are limited published data to guide clinical practice, and a complete lack of randomized clinical trials. Desmopressin (DDAVP) and antifibrinolytics are the mainstays of treatment in these patients, yet the optimal dosing and timing of these agents to prevent or resolve bleeding, while minimizing adverse side effects, is sometimes unclear. DDAVP-induced hyponatremia is a particularly under-recognized complication in children with bleeding disorders who undergo surgery. Clinicians need to be aware of local measures that are equally important in treating problems such as epistaxis and surgical bleeding. This review will discuss the published literature and provide practical suggestions regarding four common management issues in the care of children and adolescents with mild bleeding disorders: epistaxis, heavy menstrual bleeding, dental extractions, and tonsillectomy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Obstetric bleeding among women with inherited bleeding disorders: a retrospective study.

PubMed

Hawke, L; Grabell, J; Sim, W; Thibeault, L; Muir, E; Hopman, W; Smith, G; James, P

2016-11-01

Women with inherited bleeding disorders are at increased risk for bleeding complications during pregnancy and the postpartum period, particularly postpartum haemorrhage (PPH). This retrospective study evaluates pregnancy management through the Inherited Bleeding Disorders Clinic of Southeastern Ontario, the clinical factors associated with pregnancy-related abnormal bleeding and assesses tranexamic acid use in the postpartum treatment of bleeding disorder patients. A chart review of 62 pregnancies, from 33 women, evaluated patient characteristics (age, haemostatic factor levels) and delivery conditions (mode of delivery, postpartum treatment) in relation to abnormal postpartum bleeding. This cohort revealed increased risk of immediate PPH with increased age at delivery (mean age: 30.1 years with PPH, 26.5 years without PPH, P < 0.013), and birth by vaginal delivery (P < 0.042). Low von Willebrand factor (VWF) antigen or factor VIII (FVIII) in the third trimester was not associated with an increased risk of PPH; however, low VWF:RCo was associated with increased immediate PPH despite treatment with continuous factor infusion (P < 0.042). Women treated with tranexamic acid postpartum had less severe bleeding in the 6-week postpartum (P < 0.049) with no thrombotic complications. This study contributes to the growing body of work aimed at optimizing management of bleeding disorder patients through pregnancy and the postpartum period, showing patients are at a higher risk of PPH as they age. Risk factors such as low third trimester VWF:RCo have been identified. Treatment with tranexamic acid in the postpartum period is associated with a reduced incidence of abnormal postpartum bleeding. © 2016 John Wiley & Sons Ltd.

Chitosan-based dressing for the treatment of external/accessible bleedings in children with bleeding tendency.

PubMed

Misgav, Mudi; Kenet, Gili; Martinowitz, Uriel

2014-03-01

Bleeding episodes in patients with congenital or acquired bleeding disorders are usually managed with factor concentrates or blood products. However, external and accessible bleeds may effectively be managed with topical hemostasis. After the application of the Hemcon, a Food and Drug Administration-approved chitosan-based hemostatic dressing was used as the "last resort" to successfully control external bleeds in 2 patients with severe bleeding disorders. We describe a single-center experience with this dressing, including its use in pediatric patients as the first mode of therapy. A total of 5 patients (median age 2 y) with severe bleeding disorders were treated with topical chitosan-based dressing for a total of 6 bleeding episodes. The dressing was used either after the failure of extensive systemic therapy or as the first choice of treatment. In 4 of the 6 episodes, bleeding ceased immediately alleviating the need for systemic therapy. There was no rebleeding after the removal of the dressing and no adverse events or local skin reactions were recorded. Hemostatic dressings, such as the chitosan, should be encouraged for the treatment of external/accessible bleeds, especially among the pediatric patients with bleeding tendency.

Bleeding disorder education in obstetrics and gynecology residency training: a national survey.

PubMed

Dietrich, Jennifer E; Tran, Xuan G; Giardino, Angelo P

2011-04-01

The purpose of this study was to assess the educational approach to the bleeding disorder evaluation in Obstetrics and Gynecology residency training programs in the continental United States. Information was sought from chief residents regarding training experiences and fund of knowledge regarding the evaluation of menorrhagia and diagnosis of bleeding disorders during their residency. A 24-item questionnaire was sent to the chief residents at 241 non-military Obstetrics and Gynecology residency programs. The study was conducted at Texas Children's Health Plan in Houston, Texas. Chief residents at 241 non-military Obstetrics and Gynecology residency programs. Responses to questionnaires. The overall response rate was 30%. Residents reported training in the medical evaluation of menorrhagia during residency with a mean of 9.1 hours per year in the first year of residency and 11.1 hours/year in the 2(nd), 3(rd) and 4(th) years; 67.7% reported they viewed their training in the medical evaluation of menorrhagia and bleeding disorders as sufficient preparation for clinical practice; and over two thirds reported specific training in common bleeding disorders, such as von Willebrand disease. The current state of training in the evaluation of menorrhagia and bleeding disorders appeared to be mixed regarding the evaluation of dysfunctional uterine bleeding. An area for improvement was identified to better approach best clinical practice in the evaluation of women with menorrhagia and underlying bleeding disorders, which can be guided by the thoughtful approach taken in the recent NHLBI von Willebrand disease guidelines. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Detection of mild inherited disorders of blood coagulation: current options and personal recommendations.

PubMed

Lippi, Giuseppe; Pasalic, Leonardo; Favaloro, Emmanuel J

2015-08-01

Although assessment of prior personal and familial bleeding history is an important aspect of the diagnosis of bleeding disorders, patients with mild inherited bleeding disorders are sometimes clinically asymptomatic until presented with a hemostatic challenge. However, bleeding may occur after incursion of trauma or surgery, so detection of these conditions reflects an important facet of clinical and laboratory practice. Mild bleeding disorders may be detected as a result of family studies or following identification of abnormal values in first-line screening tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and global platelet function screen testing, such as the platelet function analyzer. Following determination of abnormal screening tests, subsequent investigation should follow a systematic approach that targets specific diagnostic tests, and including factor assays, full platelet function assays and more extensive specialized hemostasis testing. The current report provides a personal overview on inherited disorders of blood coagulation and their detection.

Genotype and phenotype relationships in 10 Pakistani unrelated patients with inherited factor VII deficiency.

PubMed

Borhany, M; Boijout, H; Pellequer, J-L; Shamsi, T; Moulis, G; Aguilar-Martinez, P; Schved, J-F; Giansily-Blaizot, M

2013-11-01

Inherited factor VII (FVII) deficiency is one of the commonest rare bleeding disorders. It is characterized by a wide molecular and clinical heterogeneity and an autosomal recessive pattern of inheritance. Factor VII-deficient patients are still scarcely explored in Pakistan although rare bleeding disorders became quite common as a result of traditional consanguineous marriages. The aim of the study was to give a first insight of F7 gene mutations in Pakistani population. Ten unrelated FVII-deficient patients living in Pakistan were investigated (median FVII:C = 2%; range = 2-37%). A clinical questionnaire was filled out for each patient and direct sequencing was performed on the coding regions, intron/exon boundaries and 5' and 3' untranslated regions of the F7 gene. Nine different mutations (eight missense mutations and one located within the F7 promoter) were identified on the F7 gene. Five of them were novel (p.Cys82Tyr, p.Cys322Ser, p.Leu357Phe, p.Thr410Ala, c-57C>T, the last being predicted to alter the binding site of transcription factor HNF-4). Half of the patients had single mutations in Cys residues involved in disulfide bridges. The p.Cys82Arg mutation was the most frequent in our series. Six of seven patients with FVII:C levels below 10% were homozygous in connection with the high percentage of consanguinity in our series. In addition, we graded the 10 patients according to three previously published classifications for rare bleeding disorders. The use of the bleeding score proposed by Tosetto and co-workers in 2006 appears to well qualify the bleeding tendency in our series. © 2013 John Wiley & Sons Ltd.

Establishment of a bleeding score as a diagnostic tool for patients with rare bleeding disorders.

PubMed

Palla, Roberta; Siboni, Simona M; Menegatti, Marzia; Musallam, Khaled M; Peyvandi, Flora

2016-12-01

Bleeding manifestations among patients with rare bleeding disorders (RBDs) vary significantly between disorders and patients, even when affected with the same disorder. In response to the challenge represented by the clinical assessment of the presence and severity of bleeding symptoms, a number of bleeding score systems (BSSs) or bleeding assessment tools (BATs) were developed. The majority of these were specifically developed for patients with more common bleeding disorders than RBDs. Few RBDs patients were evaluated with these tools and without conclusive results. A new BSS was developed using data retrieved from a large group of patients with RBDs enrolled in the EN-RBD database and from healthy subjects. These data included previous bleeding symptoms, frequency, spontaneity, extent, localization, and relationship to prophylaxis and acute treatment. The predictive power of this BSS was also compared with the ISTH-BAT and examined for the severity of RBDs based on coagulant factor activity. This BSS was able to differentiate patients with RBDs from healthy individuals with a bleeding score value of 1.5 having the highest sum of sensitivity (67.1%) and specificity (73.8%) in discriminating patients with RBD from those without. An easy-to-use calculation was also developed to assess the probability of having a RBD. Its comparison with the ISTH-BAT confirmed its utility. Finally, in RBDs patients, there was a significant negative correlation between BS and coagulant factor activity level, which was strongest for fibrinogen and FXIII deficiencies. The use of this quantitative method may represent a valuable support tool to clinicians. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of a 6-week, individualized, supervised exercise program for people with bleeding disorders and hemophilic arthritis.

PubMed

Mulvany, Ruth; Zucker-Levin, Audrey R; Jeng, Michael; Joyce, Catherine; Tuller, Janet; Rose, Jonathan M; Dugdale, Marion

2010-04-01

People with bleeding disorders may develop severe arthritis due to joint hemorrhages. Exercise is recommended for people with bleeding disorders, but guidelines are vague and few studies document efficacy. In this study, 65% of people with bleeding disorders surveyed reported participating in minimal exercise, and 50% indicated a fear of exercise-induced bleeding, pain, or physical impairment. The purpose of this study was to examine the feasibility, safety, and efficacy of a professionally designed, individualized, supervised exercise program for people with bleeding disorders. A single-group, pretest-posttest clinical design was used. Thirty-three patients (3 female, 30 male; 7-57 years of age) with mild to severe bleeding disorders were enrolled in the study. Twelve patients had co-existing illnesses, including HIV/AIDS, hepatitis, diabetes, fibromyalgia, neurofibromatosis, osteopenia, osteogenesis imperfecta, or cancer. Pre- and post-program measures included upper- and lower-extremity strength (force-generating capacity), joint range of motion, joint and extremity circumference, and distance walked in 6 minutes. Each patient was prescribed a 6-week, twice-weekly, individualized, supervised exercise program. Twenty participants (61%) completed the program. Pre- and post-program data were analyzed by paired t tests for all participants who completed the program. No exercise-induced injuries, pain, edema, or bleeding episodes were reported. Significant improvements occurred in joint motion, strength, and distance walked in 6 minutes, with no change in joint circumference. The greatest gains were among the individuals with the most severe joint damage and coexisting illness. Limitations included a small sample size with concomitant disease, which is common to the population, and a nonblinded examiner. A professionally designed and supervised, individualized exercise program is feasible, safe, and beneficial for people with bleeding disorders, even in the presence of concomitant disease. A longitudinal study with a larger sample size, a blinded examiner, and a control group is needed to confirm the results.

Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report.

PubMed

Lei, Hongen; Guan, Xing; Han, Hu; Qian, Xiaosong; Zhou, Xiaoguang; Zhang, Xiaodong; Tian, Long

2018-06-01

Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular disorder characterized by a triad of cutaneous port wine capillary malformations, varicose veins, and hemihypertrophy of bone and soft tissues. To report on a rare case of KTS in an adult man manifested by painless urethral bleeding during penile erection briefly review the clinical presentation and management of the genitourinary forms of this syndrome. On presentation, the clinical features of this patient, including medical history, signs and symptoms, and imaging examinations, were recorded. After diagnosis and initial treatment, a literature review of the urethral features of KTS was performed and is discussed in this report. A 35-year-old man with KTS presented with painless urethral bleeding during penile erection that was associated with posterior urethral vascular malformations. The coagulation method was used to treat the malformation, and no urethral bleeding or gross hematuria occurred during a postoperative follow-up period of 6 months. This case demonstrates that coagulation therapy and careful follow-up can be adequate treatment approaches for urethral features of KTS. However, the long-term efficacy of coagulation for this disorder should be investigated further. Lei H, Guan X, Han H, et al. Painless Urethral Bleeding During Penile Erection in an Adult Man With Klippel-Trenaunay Syndrome: A Case Report. Sex Med 2018;6:180-183. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Signs and Symptoms of a Bleeding Disorder in Women

MedlinePlus

... heavy bleeding after dental surgery, other surgery, or childbirth. I have experienced prolonged bleeding episodes that might ... a result of: Dental surgery, other surgery, or childbirth; Frequent nose bleeds (longer than 10 minutes); Bleeding ...

Intracranial hemorrhage in congenital bleeding disorders.

PubMed

Tabibian, Shadi; Motlagh, Hoda; Naderi, Majid; Dorgalaleh, Akbar

2018-01-01

: Intracranial hemorrhage (ICH), as a life-threatening bleeding among all kinds of congenital bleeding disorders (CBDs), is a rare manifestation except in factor XIII (FXIII) deficiency, which is accompanied by ICH, early in life, in about one-third of patients. Most inherited platelet function disorders (IPFDs) are mild to moderate bleeding disorders that can never experience a severe bleeding as in ICH; however, Glanzmann's thrombasthenia, a common and severe inherited platelet function disorder, can lead to ICH and occasional death. This bleeding feature can also be observed in grey platelet syndrome, though less frequently than in Glanzmann's thrombasthenia. In hemophilia, intracerebral hemorrhage is affected by various risk factors one of which is the severity of the disease. The precise prevalence of ICH in these patients is not clear but an estimated incidence of 3.5-4% among newborns with hemophilia is largely ascertained. Although ICH is a rare phenomenon in CBDs, it can be experienced by every patient with severe hemophilia A and B, FXIII deficiency (FXIIID), FVIID, FXD, FVD, FIID, and afibrinogenemia. Upon observing the general signs and symptoms of ICH such as vomiting, seizure, unconsciousness, and headache, appropriate replacement therapies and cranial ultrasound scans must be done to decrease ICH-related morbidity and mortality.

Why Do Patients Bleed?

PubMed Central

Curnow, Jennifer; Pasalic, Leonardo; Favaloro, Emmanuel J.

2016-01-01

Patients undergoing surgical procedures can bleed for a variety of reasons. Assuming that the surgical procedure has progressed well and that the surgeon can exclude surgical reasons for the unexpected bleeding, then the bleeding may be due to structural (anatomical) anomalies or disorders, recent drug intake, or disorders of hemostasis, which may be acquired or congenital. The current review aims to provide an overview of reasons that patients bleed in the perioperative setting, and it also provides guidance on how to screen for these conditions, through consideration of appropriate patient history and examination prior to surgical intervention, as well as guidance on investigating and managing the cause of unexpected bleeding. PMID:28824979

Bleeding risks associated with inheritance of the Quebec platelet disorder.

PubMed

McKay, Heather; Derome, Francine; Haq, M Anwar; Whittaker, Susan; Arnold, Emmy; Adam, Frédéric; Heddle, Nancy M; Rivard, Georges E; Hayward, Catherine P M

2004-07-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with increased urokinase-type plasminogen activator in platelets and alpha-granule protein degradation. To determine bleeding risks and common manifestations of QPD, a history questionnaire was developed and administered to 127 relatives in a family with QPD. Data entry was done blinded to affected and unaffected status, determined by assays for platelet urokinase-type plasminogen activator (u-PA) and fibrinogen degradation. Odds ratios (ORs), with 95% confidence intervals (CIs), were determined for items queried. Summative bleeding scores for each individual were calculated using items with OR more than 1. Mean ages (34 years; range, 1-89 years) were similar for affected (n = 23) and unaffected (n = 104) family members. Affected individuals had higher mean bleeding scores (P <.0001) and a much higher likelihood (OR > 20) of having bleeding that led to lifestyle changes, bruises that spread lower or as large or larger than an orange or both, joint bleeds, bleeding longer than 24 hours after dental extractions or deep cuts, and received or been recommended other treatments (fibrinolytic inhibitors) for bleeding. Individuals with QPD and exposure(s) to hemostatic challenges had experienced excessive bleeding only when fibrinolytic inhibitors had not been used. These data illustrate that QPD is associated with increased risks of bleeding that can be modified by fibrinolytic inhibitors.

During Pregnancy

MedlinePlus

... miscarriages or infant deaths. Top of Page Other Concerns Bleeding and Clotting Disorders : Bleeding and clotting disorders ... anyone affected, but pregnant women often have special concerns. Learn more about infections, medications, vaccinations, and toxins ...

Coagulation Factor Tests

MedlinePlus

... your coagulation factors. Coagulation factors are known by Roman numerals (I, II VIII, etc.) or by name ( ... need this test if you have a family history of bleeding disorders. Most bleeding disorders are inherited . ...

Bleeding Disorders Treatment Options

MedlinePlus

... rare bleeding disorders are usually made from human plasma and are treated to eliminate viruses like HIV ... made in the laboratory and not from human plasma, so they carry no risk of infectious disease. ...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

21 CFR 203.22 - Exclusions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... a bleeding or clotting disorder, or anemia; (2) Blood collection container approved under section... qualifies as a health care entity, any drug indicated for a bleeding or clotting disorder, or anemia, or any...

Hemorrhagic

MedlinePlus

... Hemorrhagic diseases are caused by bleeding, or they result in bleeding (hemorrhaging). Related topics include: Primary thrombocythemia (hemorrhagic thrombocythemia) Stroke Yellow fever Bleeding disorders Ebola fever Dengue hemorrhagic ...

Endometrial haemostasis and menstruation.

PubMed

Davies, Joanna; Kadir, Rezan A

2012-12-01

Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

Heavy Menstrual Bleeding (Menorrhagia)

MedlinePlus

... Facts Signs and Symptoms Heavy Menstrual Bleeding Research Articles & Key Findings Free Materials About Us Information For… Media Policy Makers Blood Disorders Heavy Menstrual Bleeding Recommend ...

Bevacizumab for Refractory Gastrointestinal Bleeding in Rendu-Osler-Weber Disease

PubMed Central

Bernardes, Carlos; Santos, Sara; Loureiro, Rafaela; Borges, Verónica; Ramos, Gonçalo

2018-01-01

Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia, is a rare autosomal dominant disorder which is often characterized by recurrent epistaxis, mucocutaneous and gastrointestinal telangiectasias, and visceral arteriovenous malformations. Patients with gastrointestinal involvement can present with a wide spectrum of severity, which may vary from uncomplicated iron deficiency anemia to continuous and refractory bleeding. We present the case of a 62-year-old female, who was admitted with anemia following several episodes of melena, and whose endoscopic examination revealed multiple angiodysplasias in the stomach and small bowel. Despite endoscopic and medical treatment attempts with hormonal agents and octreotide, she developed persistent hemorrhage and severe anemia, requiring frequent red blood cell transfusions. Immediately after initiating bevacizumab (7.5 mg/kg, every 3 weeks), complete cessation of bleeding episodes was observed. Currently, after 1 year of follow-up, she maintained sustained remission without the occurrence of adverse events. PMID:29662934

A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders.

PubMed

James, Andra H; Cooper, David L; Paidas, Michael J

2017-01-01

Coagulopathy may be a serious complicating or contributing factor to postpartum hemorrhage (PPH), and should be promptly recognized to ensure proper bleeding management. This study aims to evaluate the approaches of obstetrician-gynecologists worldwide towards assessing massive PPH caused by underlying bleeding disorders. A quantitative survey was completed by 302 obstetrician-gynecologists from 6 countries (the UK, France, Germany, Italy, Spain, and Japan). The survey included questions on the use of hematologic laboratory studies, interpretation of results, laboratory's role in coagulation assessments, and experience with bleeding disorders. Overall, the most common definitions of "massive" PPH were >2,000 mL (39%) and >1,500 mL (34%) blood loss. The most common criteria for rechecking a "stat" complete blood count and for performing coagulation studies were a drop in blood pressure (73%) and ongoing visible bleeding (78%), respectively. Laboratory coagulation (prothrombin time/activated partial thromboplastin time [PT/aPTT]) and factor VIII/IX assays were performed on-site more often than were mixing studies (laboratory coagulation studies, 93%; factor VIII/IX assays, 63%; mixing studies, 22%). Most commonly consulted sources of additional information were colleagues within one's own specialty (68%) and other specialists (67%). Most respondents had consulted with a hematologist (78%; least, Germany [56%]; greatest, UK [98%]). The most common reason for not consulting was hematologist unavailability (44%). The most commonly reported thresholds for concern with PT and aPTT were 13 to 20 seconds (36%) and 30 to 45 seconds (50%), respectively. Most respondents reported having discovered an underlying bleeding disorder (58%; least, Japan [35%]; greatest, Spain [74%]). Global survey results highlight similarities and differences between countries in how PPH is assessed and varying levels of obstetrician-gynecologist experience with identification of underlying bleeding disorders and engagement of hematology consultants. Opportunities to improve patient management of PPH associated with bleeding disorders include greater familiarity with interpreting PT/aPTT test results and identification of and consistent consultation with hematologists with relevant expertise.

What Should You Know about Blood Disorders in Women?

MedlinePlus

... Articles & Key Findings About Us Do you have heavy periods? This fact sheet talks about the symptoms ... Bleeding Disorders in Women Facts Signs and Symptoms Heavy Menstrual Bleeding Research Articles & Key Findings Free Materials ...

Vitamin K deficiency bleeding of the newborn

MedlinePlus

Vitamin K deficiency bleeding (VKDB) of the newborn is a bleeding disorder in babies. It most often develops in ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often have a ...

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

PubMed

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

PubMed Central

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%. PMID:29333065

Quebec platelet disorder.

PubMed

Hayward, Catherine P M; Rivard, Georges E

2011-04-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with a unique gain-of-function defect in fibrinolysis. In the past 5 years, there have been important advances in the understanding of the pathogenesis of QPD, including its genetic cause, which is a copy number variation mutation of PLAU, the gene for urokinase plasminogen activator (uPA). QPD is the first bleeding disorder identified to be caused by a PLAU mutation and it is also the first bleeding disorder recognized to result from a gene copy number mutation. The molecular defect of QPD leads to marked overexpression of uPA during megakaryopoiesis, producing profibrinolytic platelets that contain active forms of uPA in their α-granules. This article summarizes expert opinions on the features of QPD and recent advances in the understanding of its pathogenesis and genetic cause.

Platelet von Willebrand factor in Hermansky-Pudlak syndrome.

PubMed

McKeown, L P; Hansmann, K E; Wilson, O; Gahl, W; Gralnick, H R; Rosenfeld, K E; Rosenfeld, S J; Horne, M K; Rick, M E

1998-10-01

The Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive inherited disorder characterized by oculocutaneous albinism, tissue accumulation of ceroid pigment, and a mild to moderate bleeding diathesis attributed to storage-pool deficient (SPD) platlets. Patients have platelet aggregation and release abnormalities. In addition, low levels of plasma von Willebrand factor (vWF) antigen in some HPS patients have been associated with a greater bleeding tendency than would be predicted from either condition alone. Other HPS patients have severe bleeding despite normal levels of plasma vWF, suggesting that at least one additional factor is responsible for their bleeding diathesis. Because platelet vWF levels have been well correlated with clinical bleeding times in patients with von Willebrand's disease, we have measured the platelet vWF activity and antigen levels in 30 HPS patients and have attempted to correlate their clinical bleeding with these values. The platelet vWF activity levels in patients was significantly lower than that of normal subjects (P < 0.0001). The patients as a group also had slightly lower values of plasma vWF activity when compared with normals (P-0.03). In 11 of the HPS patients, the multimeric structure of plasma vWF showed a decrease in the high molecular weight multimers and an increase in the low molecular weight multimers. In correlating the platelet and plasma vWF values with the bleeding histories, we were not able to show a predictable relationship in the majority of the patients.

75 FR 66108 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... as bleeding disorders, trauma, and diseases such as sepsis, cardiovascular disease, stroke, and..., cardiovascular disease, stroke, cancer). Treatment of bleeding disorders or trauma. Treatment of cerebral... poor prognosis. Because HCC is often associated with liver disease, traditional chemotherapy is not an...

Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US.

PubMed

Altomare, Ivy; Cetin, Karynsa; Wetten, Sally; Wasser, Jeffrey S

2016-01-01

Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown. Clinical trial data may not reflect real-world bleeding rates because of the inclusion of highly refractory patients and more frequent use of rescue therapy. We used administrative medical claims data in the US to examine the occurrence of bleeding-related episodes (BREs) - a composite end point including bleeding and/or rescue therapy use - in adults diagnosed with primary ITP (2008-2012). BRE rates were calculated overall and by ITP phase and splenectomy status. Patients were followed from ITP diagnosis until death, disenrollment from the health plan, or June 30, 2013, whichever came first. We identified 6,651 adults diagnosed with primary ITP over the study period (median age: 53 years; 59% female). During 13,064 patient-years of follow-up, 3,768 patients (57%) experienced ≥1 BRE (1.08 BREs per patient-year; 95% confidence interval: 1.06-1.10). The majority (58%) of BREs consisted of rescue therapy use only. Common bleeding types were gastrointestinal hemorrhage, hematuria, ecchymosis, and epistaxis. Intracranial hemorrhage was reported in 74 patients (1%). Just over 7% of patients underwent splenectomy. Newly diagnosed and splenectomized patients had elevated BRE rates. We provide current real-world estimates of BRE rates in adults with primary ITP. The majority of ITP patients experienced ≥1 BRE, and over half were defined by rescue therapy use alone. This demonstrates the importance of examining both bleeding and rescue therapy use to fully assess disease burden.

Munchausen Syndrome Masquerading as Bleeding Disorder in a Group of Pediatric Patients

PubMed Central

Sridharan, Srivani; Shukla, Deepak; Mehta, Ritambhara; Oswal, Rajat

2011-01-01

This short communication is about Munchausen's syndrome in a group of pediatric patients and co morbid Munchausen's syndrome by proxy. A 7-year-old girl presented with spontaneous bleeding from forehead, eyes and scalp. The girl was investigated thoroughly by pediatricians at a tertiary care hospital in western India for all possible bleeding disorders, but there was no conclusive diagnosis. After two days, cases with similar complaints were reported among children residing in the same locality and with similar socioeconomic background. All of them were investigated in detail for possible causes of bleeding but nothing came out. There was a media reporting of the cases as a mysterious bleeding disorder. At this point of time, an expert opinion from the psychiatrist was demanded. Covert video surveillance and series of interviews revealed Munchausen's syndrome and possible Munchausen's syndrome by proxy. An in-depth literature review with special reference to Munchausen's syndrome was carried out to come to a final conclusive diagnosis. PMID:22021962

Munchausen syndrome masquerading as bleeding disorder in a group of pediatric patients.

PubMed

Sridharan, Srivani; Shukla, Deepak; Mehta, Ritambhara; Oswal, Rajat

2011-01-01

This short communication is about Munchausen's syndrome in a group of pediatric patients and co morbid Munchausen's syndrome by proxy. A 7-year-old girl presented with spontaneous bleeding from forehead, eyes and scalp. The girl was investigated thoroughly by pediatricians at a tertiary care hospital in western India for all possible bleeding disorders, but there was no conclusive diagnosis. After two days, cases with similar complaints were reported among children residing in the same locality and with similar socioeconomic background. All of them were investigated in detail for possible causes of bleeding but nothing came out. There was a media reporting of the cases as a mysterious bleeding disorder. At this point of time, an expert opinion from the psychiatrist was demanded. Covert video surveillance and series of interviews revealed Munchausen's syndrome and possible Munchausen's syndrome by proxy. An in-depth literature review with special reference to Munchausen's syndrome was carried out to come to a final conclusive diagnosis.

Post-partum hemorrhage in women with rare bleeding disorders.

PubMed

Peyvandi, Flora; Menegatti, Marzia; Siboni, Simona Maria

2011-02-01

Post-partum hemorrhage (PPH) accounts for a substantial fraction of maternal deaths in the general population. Among all women, however, those affected with rare bleeding disorders (RBDs) represent a particular group since to usual bleeding symptoms, they are likely to experience bleedings associated to obstetrical and gynaecological problems. Pregnancy and childbirth, two important stages in the life of a woman, pose a special clinical challenge in women with RBDs, since information about these issues are really scarce and limited to few case reports. These data show that all women with RBDs, except for FXI deficiency, have to be considered potentially at risk for developing PPH, therefore they should be monitored carefully during and immediately after pregnancy. The implication is that women with bleeding disorders may require prophylaxis and/or close observation for several weeks and should be followed by a multidisciplinary team including expertises such as laboratory haematologist, obstetrician-gynaecologist, anaesthesiologist, family physician, and laboratory technician. © 2011 Elsevier Ltd. All rights reserved.

Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment.

PubMed

Blavignac, Jessica; Bunimov, Natalia; Rivard, Georges E; Hayward, Catherine P M

2011-09-01

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder associated with reduced platelet counts and a unique gain-of-function defect in fibrinolysis due to increased expression and storage of urokinase plasminogen activator (uPA) by megakaryocytes. QPD increases risks for bleeding and its key clinical feature is delayed-onset bleeding, following surgery, dental procedures or trauma, which responds only to treatment with fibrinolytic inhibitors. The genetic cause of the disorder is a tandem duplication mutation of the uPA gene, PLAU, which upregulates uPA expression in megakaryocytes by an unknown mechanism. The increased platelet stores of uPA trigger plasmin-mediated degradation of QPD α-granule proteins. The gain-of-function defect in fibrinolysis is thought to be central to the pathogenesis of QPD bleeding as the activation of QPD platelets leads to release of uPA from α-granules and accelerated clot lysis. The purpose of this review is to summarize current knowledge on QPD pathogenesis and the recommended approaches to QPD diagnosis and treatment. Thieme Medical Publishers.

An institutional pilot study to investigate physical activity patterns in boys with haemophilia.

PubMed

Bouskill, V; Hilliard, P; Stephens, S; Zhang, C; Whitney, K; Carcao, M

2016-09-01

Haemophilia is a bleeding disorder characterized by musculoskeletal bleeding. Trauma-induced bleeding into joints and muscles may be associated with participation in physical activities. Recognizing this, persons with haemophilia may limit physical activities to avoid bleeding. The characterization of physical activity profiles (type, intensity, frequency and duration) in children with differing severities of haemophilia has not been well documented. This is required to better understand the relationship between physical activity and bleeding in children with haemophilia. This study was a prospective, cross-sectional, observational study to compare the quantity, type and intensity of physical activity as measured by accelerometry in boys with different haemophilia severities. Subjects wore an accelerometer daily for 1 week and completed validated self-report PedHAL and 3DPAR questionnaires. Accelerometer activity levels were classified as sedentary, light, moderate or vigorous. A total of 66 males were enrolled, 24 had mild/moderate and 42 had severe haemophilia. Subjects average age was 11.52 years (±3.99) and their average BMI was 20.74 kg m(2) (±5.68). Boys with severe haemophilia reported significantly more time per day spent in sedentary activities compared to those with mild/moderate haemophilia. Furthermore, the amount of time engaged in sedentary activities increased with age in those boys with severe haemophilia, whereas the opposite was true in those with mild/moderate haemophilia. We speculate that prophylaxis in children with severe haemophilia permitted them to engage in similar amounts of moderate to vigorous physical activity (MVPA) as children with mild/moderate haemophilia. Increasing sedentary time in the severe cohort with age may be attributed to increasing arthropathy among other psychosocial factors. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in patients with haematological disorders after chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Murphy, Michael F; Tinmouth, Alan

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in patients with haematological disorders after chemotherapy with or without stem cell transplantation. PMID:25722651

Congenital Disorders of Platelet Function and Number.

PubMed

Sharma, Ruchika; Perez Botero, Juliana; Jobe, Shawn M

2018-06-01

Mucocutaneous bleeding symptoms and/or persistent thrombocytopenia occur in individuals with congenital disorders of platelet function and number. Apart from bleeding, these disorders are often associated with additional hematologic and clinical manifestations, including auditory, immunologic, and oncologic disease. Autosomal recessive, dominant, and X-linked inheritance patterns have been demonstrated. Precise delineation of the molecular cause of the platelet disorder can aid the pediatrician in the detection and prevention of specific disorder-associated manifestations and guide appropriate treatment and anticipatory care for the patient and family. Copyright © 2018 Elsevier Inc. All rights reserved.

Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor.

PubMed

Cunningham, Margaret R; Aungraheeta, Riyaad; Mundell, Stuart J

2017-07-05

Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y 1 and P2Y 12 ), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y 12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems. Copyright © 2017. Published by Elsevier B.V.

Intracranial Hemorrhage: A Devastating Outcome of Congenital Bleeding Disorders-Prevalence, Diagnosis, and Management, with a Special Focus on Congenital Factor XIII Deficiency.

PubMed

Alavi, Seyed Ezatolla Rafiee; Jalalvand, Masumeh; Assadollahi, Vahideh; Tabibian, Shadi; Dorgalaleh, Akbar

2018-04-01

Intracranial hemorrhage (ICH) is a medical emergency. In congenital bleeding disorders, ICH is a devastating presentation accompanied with a high rate of morbidity and mortality. The prevalence of ICH is highly variable among congenital bleeding disorders, with the highest incidence observed in factor (F) XIII deficiency (FXIIID) (∼30%). This life-threatening presentation is less common in afibrinogenemia, FVIII, FIX, FVII, and FX deficiencies, and is rare in severe FV and FII deficiencies, type 3 von Willebrand disease and inherited platelet function disorders (IPFDs). In FXIIID, this diathesis most often occurs after trauma in children, whereas spontaneous ICH is more frequent in adults. About 15% of patients with FXIIID and ICH die; the bleeding causes 80% of deaths in this coagulopathy. Although in FXIIID, the bleed most commonly is intraparenchymal (> 90%), epidural, subdural, and subarachnoid hemorrhages also have been reported, albeit rarely. As this life-threatening bleeding causes neurological complications, early diagnosis can prevent further expansion of the hematoma and secondary damage. Neuroimaging plays a crucial role in the diagnosis of ICH, but signs and symptoms in patients with severe FXIIID should trigger replacement therapy even before establishment of the diagnosis. Although a high dose of FXIII concentrate can reduce the rate of morbidity and mortality of ICH in FXIIID, it may occasionally trigger inhibitor development, thus complicating ICH management and future prophylaxis. Nevertheless, replacement therapy is the mainstay of treatment for ICH in FXIIID. Neurosurgery is performed in patients with FXIIID and epidural hematoma and a hemorrhage diameter exceeding 2 cm or a volume of ICH is more than 30 cm 3 . Contact sports are not recommended in people with FXIIID as they can elicit ICH. However, a considerable number of safe sports and activities have been suggested to have more benefits than dangers for patients with congenital bleeding disorders, and are hence suitable for these patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Yellow fever

MedlinePlus

... the heart, liver, and kidney. Bleeding disorders, seizures, coma, and delirium may also occur. Symptoms may include: ... heartbeats (arrhythmias) Bleeding (may progress to hemorrhage) Seizures Coma

Overview of platelet physiology and laboratory evaluation of platelet function.

PubMed

Rodgers, G M

1999-06-01

Appropriate laboratory testing for the platelet-type bleeding disorders hinges on an adequate assessment in the history and physical examination. Patients with histories and screening laboratory results consistent with coagulation disorders (hemophilia, disseminated intravascular coagulation) are not appropriate candidates for platelet function testing. In contrast, patients with a lifelong history of platelet-type bleeding symptoms and perhaps a positive family history of bleeding would be appropriate for testing. Figure 6 depicts one strategy to evaluate these patients. Platelet morphology can easily be evaluated to screen for two uncommon qualitative platelet disorders: Bernard-Soulier syndrome (associated with giant platelets) and gray platelet syndrome, a subtype of storage pool disorder in which platelet granulation is morphologically abnormal by light microscopy. If the bleeding disorder occurred later in life (no bleeding with surgery or trauma early in life), the focus should be on acquired disorders of platelet function. For those patients thought to have an inherited disorder, testing for vWD should be done initially because approximately 1% of the population has vWD. The complete vWD panel (factor VIII coagulant activity, vWf antigen, ristocetin cofactor activity) should be performed because many patients will have abnormalities of only one particular panel component. Patients diagnosed with vWD should be classified using multimeric analysis to identify the type 1 vWD patients likely to respond to DDAVP. If vWD studies are normal, platelet aggregation testing should be performed, ensuring that no antiplatelet medications have been ingested at least 1 week before testing. If platelet aggregation tests are normal and if suspicion for an inherited disorder remains high, vWD testing should be repeated. The evaluation of thrombocytopenia may require bone marrow examination to exclude primary hematologic disorders. If future studies with thrombopoietin assays confirm preliminary results, however, the bone marrow examination of certain patients may be replaced by a thrombopoietin level.

Brief psychotic disorder mimicking the symptoms of cerebrovascular attack evoked by symptoms that symbolized death in a patient with terminal stage stomach cancer: case report and review of the literature.

PubMed

Onishi, Hideki; Okuno, Shigeko; Yae, Suzu; Sairenji, Motonori; Onose, Masanari; Mizuno, Yasuhiro; Kawanishi, Chiaki

2006-03-01

We report here a terminally ill patient with stomach cancer who developed a brief psychotic disorder mimicking cerebrovascular attack after a short episode of nasal bleeding. Close examination of the patient revealed that nasal bleeding was an event that symbolized deterioration of the general condition leading to death for the patient. A 77-year-old male, who was diagnosed as having stomach cancer and was receiving palliative care, presented with tremor and insomnia just after a short episode of nasal bleeding and showed reduced response to stimuli mimicking cerebrovascular attack. Laboratory data were unremarkable. The next day, catatonic behavior developed. He had no history of psychiatric illness or drug or alcohol abuse. After receiving haloperidol, psychiatric symptoms disappeared and he returned to the previous level of functioning within 3 days. The patient explained that he had seen a patient whose general condition deteriorated after nasal bleeding and regarded nasal bleeding as a symptom of deteriorating general condition leading to death and thereafter became afraid of the nasal bleeding. Although, nasal bleeding is common and usually not severe in medical settings, for the patient, it was an event that symbolized deterioration of the general condition leading to death. Brief psychotic disorder in cancer patients is rare in the literature, although patients receiving terminal care share various kinds of psychological burden. Medical staff in the palliative care unit should be aware of the psychological distress experienced by each patient and consider brief psychotic disorder as part of the differential diagnosis when patients show unexplained neurological-like and/or psychiatric symptoms.

Recombinant activated factor VII for bleeding in patients without inherited bleeding disorders.

PubMed

Selin, S; Tejani, A

2006-03-01

(1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the prevention and treatment of bleeding in hemophiliacs, but it is increasingly used to control bleeding in non-hemophilic patients during surgery, or during treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one clinical trial, there was a significant reduction in mortality among patients with ICH treated with rFVIIa. In another trial, administration of rFVIIa significantly reduced the number of trauma patients needing massive blood transfusions although there was no significant difference in mortality. (3) Adequately powered randomized controlled trials are needed to clarify the efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III trials in ICH and trauma are underway. (4) There is potential for non-hemophilic use, particularly if clinical efficacy and cost effectiveness are established.

Challenges in the Evaluation for Possible Abuse: Presentations of Congenital Bleeding Disorders in Childhood

ERIC Educational Resources Information Center

Jackson, Jami; Carpenter, Shannon; Anderst, Jim

2012-01-01

Objectives: To describe children with congenital bleeding disorders that present in a manner that may be concerning for non-accidental trauma (NAT), and to evaluate associations with disease and demographic characteristics. Methods: Ten year retrospective charts of subjects were reviewed at a Hemophilia Treatment Center. Demographic, historical,…

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

PubMed

MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

2002-06-01

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Juvenile polyposis syndrome: An unusual case report of anemia and gastrointestinal bleeding in young infant.

PubMed

Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

2016-09-01

Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages.

Immune Thrombocytopenia

PubMed Central

Kistanguri, Gaurav; McCrae, Keith R.

2013-01-01

Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP, with the risk of bleeding and related morbidity increased in elderly patients. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Diminished numbers and function of regulatory T cells, as well as the effects of cytotoxic T cells also contribute to the pathogenesis of ITP. Corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous immunoglobulin (IVIg) and anti-Rh(D). However, these agents do not lead to durable remissions in the majority of adults with ITP, and considerable heterogeneity exists in the use of second line approaches, which may include splenectomy, Rituximab, or thrombopoietin receptor agonists (TRAs). This review summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. Remarkable advances in the understanding and management of ITP have been achieved over the last decade, though many questions remain. PMID:23714309

Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A

PubMed Central

PORADA, C. D.; SANADA, C.; LONG, C. R.; WOOD, J. A.; DESAI, J.; FREDERICK, N.; MILLSAP, L.; BORMANN, C.; MENGES, S. L.; HANNA, C.; FLORES-FOXWORTH, G.; SHIN, T.; WESTHUSIN, M. E.; LIU, W.; GLIMP, H.; ZANJANI, E. D.; LOZIER, J. N.; PLISKA, V.; STRANZINGER, G.; JOERG, H.; KRAEMER, D. C.; ALMEIDA-PORADA, G.

2010-01-01

Summary Background Large animal models that accurately mimic human hemophilia A (HA) are in great demand for developing and testing novel therapies to treat HA. Objectives To re-establish a line of sheep exhibiting a spontaneous bleeding disorder closely mimicking severe human HA, fully characterize their clinical presentation, and define the molecular basis for disease. Patients/methods Sequential reproductive manipulations were performed with cryopreserved semen from a deceased affected ram. The resultant animals were examined for hematologic parameters, clinical symptoms, and responsiveness to human FVIII (hFVIII). The full coding region of sheep FVIII mRNA was sequenced to identify the genetic lesion. Results and conclusions The combined reproductive technologies yielded 36 carriers and 8 affected animals. The latter had almost non-existent levels of FVIII:C and extremely prolonged aPTT, with otherwise normal hematologic parameters. These animals exhibited bleeding from the umbilical cord, prolonged tail and nail cuticle bleeding time, and multiple episodes of severe spontaneous bleeding, including hemarthroses, muscle hematomas and hematuria, all of which responded to hFVIII. Inhibitors of hFVIII were detected in four treated animals, further establishing the preclinical value of this model. Sequencing identified a premature stop codon and frame-shift in exon 14, providing a molecular explanation for HA. Given the decades of experience using sheep to study both normal physiology and a wide array of diseases and the high homology between human and sheep FVIII, this new model will enable a better understanding of HA and facilitate the development and testing of novel treatments that can directly translate to HA patients. PMID:19943872

Sertraline-induced periorbital purpura: a case report.

PubMed

Kayhan, Fatih; Eken, Zahide Eriş; Uguz, Faruk

2015-08-01

The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene.

PubMed

Paterson, Andrew D; Rommens, Johanna M; Bharaj, Bhupinder; Blavignac, Jessica; Wong, Isidro; Diamandis, Maria; Waye, John S; Rivard, Georges E; Hayward, Catherine P M

2010-02-11

Quebec platelet disorder (QPD) is an autosomal dominant bleeding disorder linked to a region on chromosome 10 that includes PLAU, the urokinase plasminogen activator gene. QPD increases urokinase plasminogen activator mRNA levels, particularly during megakaryocyte differentiation, without altering expression of flanking genes. Because PLAU sequence changes were excluded as the cause of this bleeding disorder, we investigated whether the QPD mutation involved PLAU copy number variation. All 38 subjects with QPD had a direct tandem duplication of a 78-kb genomic segment that includes PLAU. This mutation was specific to QPD as it was not present in any unaffected family members (n = 114), unrelated French Canadians (n = 221), or other persons tested (n = 90). This new information on the genetic mutation will facilitate diagnostic testing for QPD and studies of its pathogenesis and prevalence. QPD is the first bleeding disorder to be associated with a gene duplication event and a PLAU mutation.

Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management.

PubMed

Stanciakova, Lucia; Kubisz, Peter; Dobrotova, Miroslava; Stasko, Jan

2016-07-01

Congenital afibrinogenemia belongs to the group of autosomal recessive bleeding disorders and represents the absolute deficiency of fibrinogen detected by an antigenic test. This can lead to severe clinical manifestations of the disorder. Therefore, it is very important to take afibrinogenemia into account in the process of the differential diagnostics of the patients. The authors provide a summary of currently available literature about afibrinogenemia. They collected the information from the scientific journals dedicated to thrombosis and hemostasis and searched world-wide databases. Expert commentary: The most frequent clinical manifestation of this disorder is mucosal bleeding, but musculoskeletal bleeding pattern, gynecologic and obstetric issues, spontaneous bleeding, episodes provoked by minor injury or any other intervention, and even paradoxical thromboembolic events have been published. Afibrinogenemia is the consequence of mutations of the homozygous or compound heterozygous type in gene FGA, FGB or FGG encoding fibrinogen. Pregnant women with a family history, or with a history of consanguinity ought to be properly counselled. However, primary prophylaxis of bleeding events is not suggested. The article deals with actual information about afibrinogenemia contributing to its early diagnosis and effective treatment, which in many cases requires multidisciplinary approach.

Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors.

PubMed

Watson, S; Daly, M; Dawood, B; Gissen, P; Makris, M; Mundell, S; Wilde, J; Mumford, A

2010-01-01

Platelet number or function disorders cause a range of bleeding symptoms from mild to severe. Patients with platelet dysfunction but normal platelet number are the most prevalent and typically have mild bleeding symptoms. The study of this group of patients is particularly difficult because of the lack of a gold-standard test of platelet function and the variable penetrance of the bleeding phenotype among affected individuals. The purpose of this short review is to discuss the way in which this group of patients can be investigated through platelet phenotyping in combination with targeted gene sequencing. This approach has been used recently to identify patients with mutations in key platelet activation receptors, namely those for ADP, collagen and thromboxane A2 (TxA2). One interesting finding from this work is that for some patients, mild bleeding is associated with heterozygous mutations in platelet proteins that are co-inherited with other genetic disorders of haemostasis such as type 1 von Willebrand's disease. Thus, the phenotype of mild bleeding may be multifactorial in some patients and may be considered to be a complex trait.

Animal Models of Hemophilia and Related Bleeding Disorders

PubMed Central

Lozier, Jay N.; Nichols, Timothy C.

2013-01-01

Animal models of hemophilia and related diseases are important for development of novel treatments and to understand the pathophysiology of bleeding disorders in humans. Testing in animals with the equivalent human disorder provides informed estimates of doses and measures of efficacy, which aids in design of human trials. Many models of hemophilia A, hemophilia B, and von Willebrand disease have been developed from animals with spontaneous mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and von Willebrand disease pigs and dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD models. Animal models have been used to generate new insights into the pathophysiology of each bleeding disorder and also to perform pre-clinical assessments of standard protein replacement therapies as well as novel gene transfer technology. Both the differences between species and differences in underlying causative mutations must be considered in choosing the best animal for a specific scientific study PMID:23956467

Quebec platelet disorder: features, pathogenesis and treatment.

PubMed

Diamandis, Maria; Veljkovic, D Kika; Maurer-Spurej, Elisabeth; Rivard, Georges E; Hayward, Catherine P M

2008-03-01

Quebec platelet disorder (QPD) is a rare, autosomal-dominant, inherited bleeding disorder that is associated with unique abnormalities in fibrinolysis. Its hallmark features are delayed-onset bleeding following hemostatic challenges that responds to fibrinolytic inhibitor therapy and increased expression and storage of the fibrinolytic enzyme urokinase plasminogen activator in platelets, without increased plasma urokinase plasminogen activator or systemic fibrinolysis. The increased urokinase plasminogen activator in QPD platelets is only partially inhibited, and, as a result, there is intraplatelet generation of plasmin, and secondary degradation of many platelet alpha-granule proteins. During clot formation, the urokinase plasminogen activator released by QPD platelets leads to platelet-dependent increased fibrinolysis, and this is postulated to be a major contributor to QPD bleeding. The focus of the present review is to summarize the current state of knowledge on QPD, including the history of this disorder, its clinical and laboratory features, and recommended approaches for its diagnosis and treatment.

Causes and Diagnosis of Abnormal Vaginal Bleeding.

PubMed

Sokol, Elizabeth; Peddinti, Radhika

2015-07-01

Abnormal vaginal bleeding in a postmenarchal adolescent patient is most often related to dysfunctional uterine bleeding. However, there are other potential etiologies, including hematologic disorders, infections, and oncologic problems. We present a 12-year-old girl who presented with prolonged vaginal bleeding and was ultimately diagnosed with rhabdomyosarcoma. In this article, we discuss the approach to a patient with vaginal bleeding along with a more in-depth review of risk stratification in rhabdomyosarcoma, including treatment options such as chemotherapy, surgery, and radiation therapy. Copyright 2015, SLACK Incorporated.

Direct-to-consumer advertising for bleeding disorders: a content analysis and expert evaluation of advertising claims.

PubMed

Abel, G A; Neufeld, E J; Sorel, M; Weeks, J C

2008-10-01

In the United States, the Food and Drug Administration (FDA) requires that all direct-to-consumer advertising (DTCA) contain both an accurate statement of a medication's effects ('truth') and an even-handed discussion of its benefits and risks/adverse effects ('fair balance'). DTCA for medications to treat rare diseases such as bleeding disorders is unlikely to be given high priority for FDA review. We reviewed all DTCA for bleeding disorder products appearing in the patient-directed magazine HemeAware from January 2004 to June 2006. We categorized the information presented in each advertisement as benefit, risk/adverse effect, or neither, and assessed the amount of text and type size devoted to each. We also assessed the readability of each type of text using the Flesch Reading Ease Score (FRES, where a score of >or=65 is considered of average readability), and assessed the accuracy of the advertising claims utilizing a panel of five bleeding disorder experts. A total of 39 unique advertisements for 12 products were found. On average, approximately twice the amount of text was devoted to benefits as compared with risks/adverse effects, and the latter was more difficult to read [FRES of 32.0 for benefits vs. 20.5 for risks/adverse effects, a difference of 11.5 (95% CI: 4.5-18.5)]. Only about two-thirds of the advertising claims were considered by a majority of the experts to be based on at least low-quality evidence. As measured by our methods, print DTCA for bleeding disorders may not reach the FDA's standards of truth and fair balance.

Congenital platelet function defects

MedlinePlus

Platelet storage pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... This disorder may also cause severe bleeding. Platelet storage pool disorder (also called platelet secretion disorder) occurs ...

Bleeding and Blood Disorders in Clients of Voluntary Medical Male Circumcision for HIV Prevention - Eastern and Southern Africa, 2015-2016.

PubMed

Hinkle, Lawrence E; Toledo, Carlos; Grund, Jonathan M; Byams, Vanessa R; Bock, Naomi; Ridzon, Renee; Cooney, Caroline; Njeuhmeli, Emmanuel; Thomas, Anne G; Odhiambo, Jacob; Odoyo-June, Elijah; Talam, Norah; Matchere, Faustin; Msungama, Wezi; Nyirenda, Rose; Odek, James; Come, Jotamo; Canda, Marcos; Wei, Stanley; Bere, Alfred; Bonnecwe, Collen; Choge, Isaac Ang'Ang'A; Martin, Enilda; Loykissoonlal, Dayanund; Lija, Gissenge J I; Mlanga, Erick; Simbeye, Daimon; Alamo, Stella; Kabuye, Geoffrey; Lubwama, Joseph; Wamai, Nafuna; Chituwo, Omega; Sinyangwe, George; Zulu, James Exnobert; Ajayi, Charles A; Balachandra, Shirish; Mandisarisa, John; Xaba, Sinokuthemba; Davis, Stephanie M

2018-03-23

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

Hemophilic Chronic Synovitis: Therapy of Hemarthrosis using Endovascular Embolization of Knee and Elbow Arteries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galli, E., E-mail: emgalli1@yahoo.com.ar; Baques, A.; Moretti, N.

2013-08-01

PurposeCongenital hemophilia is a hereditary bleeding disorder that affects 1 in 5,000 males and is characterized by repetitive musculoskeletal bleeding episodes. Selective embolization of the knee and elbow arteries can prevent bleeding episodes. To evaluate the long-term efficacy of these procedures, we assessed the outcomes of 30 procedures performed in our center.MethodsWe performed 30 procedures in 27 hemophilic patients, including 23 knee, and 7 elbow procedures. To evaluate the efficacy of selective embolization of knee and elbow arteries in people with hemophilia, we analyzed the number of bleeding episodes during 12 months before the procedure compared with the amount ofmore » episodes that occurred 3, 6, and 12 months after embolization.ResultsTwenty-nine of 30 procedures were classified as successful. The median of 1.25 episodes per month (range 0-3) observed before the procedure was reduced to 0 (range 0-1.67; p < 0.001) at 3 months, 0.17 (range 0-1.67; p < 0.001) at 6 months, and 0.33 (range 0-1.67; p = 0.024) at 12 months. Three patients remained free of bleeding events for more than 6 months. Additionally, after the procedure there was a significant reduction in factor FVIII usage that sustained up to 12 months after the procedures. No serious adverse events were observed.ConclusionsSelective angiographic embolization of knee and elbow arteries is a feasible procedure that can prevent repetitive bleedings, which would translate in better joint outcomes for these patients.« less

Juvenile polyposis syndrome

PubMed Central

Hsiao, Yi-Han; Wei, Chin-Hung; Chang, Szu-Wen; Chang, Lung; Fu, Yu-Wei; Lee, Hung-Chang; Liu, Hsuan-Liang; Yeung, Chun-Yan

2016-01-01

Abstract Background: Juvenile polyposis syndrome, a rare disorder in children, is characterized with multiple hamartomatous polyps in alimentary tract. A variety of manifestations include bleeding, intussusception, or polyp prolapse. In this study, we present an 8-month-old male infant of juvenile polyposis syndrome initially presenting with chronic anemia. To the best of our knowledge, this is the youngest case reported in the literature. Methods: We report a rare case of an 8-month-old male infant who presented with chronic anemia and gastrointestinal bleeding initially. Panendoscopy and abdominal computed tomography showed multiple polyposis throughout the entire alimentary tract leading to intussusception. Technetium-99m-labeled red blood cell (RBC) bleeding scan revealed the possibility of gastrointestinal tract bleeding in the jejunum. Histopathological examination on biopsy samples showed Peutz-Jeghers syndrome was excluded, whereas the diagnosis of juvenile polyposis syndrome was established. Results: Enteroscopic polypectomy is the mainstay of the treatment. However, polyps recurred and occupied the majority of the gastrointestinal tract in 6 months. Supportive management was given. The patient expired for severe sepsis at the age of 18 months. Conclusion: Juvenile polyposis syndrome is an inherited disease, so it is not possible to prevent it. Concerning of its poor outcome and high mortality rate, it is important that we should increase awareness and education of the parents at its earliest stages. PMID:27631205

IgMk paraprotein from gammopathy patient can bind to cardiolipin and interfere with coagulation assay: a case report.

PubMed

Wu, Xin-Yao; Yin, Yu-Feng; Teng, Jia-Lin; Zhang, Li-Wei; Yang, Cheng-de

2017-06-23

The monoclonal gammopathies are a group of plasma-cell proliferative disorders characterized by the secretion of monoclonal immunoglobulin (M protein or paraprotein). Some rare cases have revealed the specific affinity of paraprotein as autoantibody. Here we report a patient with monoclonal gammopathy of undetermined significance (MGUS) accompanied by a remarkable increase of anticardiolipin antibody (aCL) and an extensively decreased coagulation factor activity, however, without any clinical signs of antiphospholipid syndrome (APS) and bleeding. Our further investigation indicated that IgMκ paraprotein of this patient possessed an antibody activity against phospholipids so as to bind to cardiolipin and interfere with coagulation assay in vitro. This case might be indicative that an abnormality of coagulation tests, disturbed by IgMκ paraprotein, does not predict a risk of bleeding in this patient.

The bleeding time may be longer in children than in adults.

PubMed

Sanders, J M; Holtkamp, C A; Buchanan, G R

1990-01-01

The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults. We have reviewed our 9 years of experience with 137 children (mean age 6.5 years) who were referred for diagnostic evaluation of a bleeding disorder but whose history and physical examination were felt by us to be inconsistent with an abnormality of hemostasis. Bleeding time values in these individuals (mean 6.0 min, 95th percentile 9.0 min) were compared with those of 85 normal adult volunteers (mean 4.4 min, 95th percentile 6.5 min). The Simplate-I disposable device and vertical (perpendicular to elbow crease) incision direction were used in both groups. This difference between the pediatric and adult bleeding time values is statistically significant (p less than 0.0001). Neither age nor sex had a significant effect on the pediatric bleeding time measurements. We conclude that the bleeding time, when performed as described, is longer in children than in adults and that pediatric standards for bleeding time should be used in order to avoid a spurious diagnosis of a primary hemostatic disorder in some normal children.

Capacity Building for Rare Bleeding Disorders in the Remote Commonwealth of the Northern Mariana Islands.

PubMed

Lin, Tiffany F; Carhill, Pam; Huang, James N; Baker, Judith R

2016-04-01

The US Pacific Commonwealth of the Northern Mariana Islands is home to an underserved hemophilia population. We developed a strategy in 2014 to build sustainable island-wide medical, patient and family, and community support for this rare disease. Collaboration with regional bleeding disorder leadership galvanized a weeklong conference series. More than 200 participants attended discipline-specific seminars; pre-post test evaluations documented educational benefits. This time-concentrated island-wide education intervention promoted the rapid identification of new cases and stimulated sustainable bleeding disorder care development. The education series proved feasible, efficient, and effective in increasing knowledge and reducing patient and professional isolation, serving as a model for improving capacity for orphan diseases (those that affect fewer than 200 000 people in any particular country) in underresourced areas.

Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study

PubMed Central

Søgaard, Mette; Skjøth, Flemming; Kjældgaard, Jette Nordstrøm; Larsen, Torben Bjerregaard; Hjortshøj, Søren Pihlkjær; Riahi, Sam

2017-01-01

Objectives Outcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders. Design Nationwide registry-based cohort study. Setting Denmark (population 5.6 million), 2000–2015. Participants Patients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders. Exposure Inpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease. Primary and secondary outcome measures HRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT). Results Compared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15). Conclusion Patients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders. PMID:29217725

Detection of bleeding disorders in Lebanon: outcomes of a pilot programme.

PubMed

Djambas Khayat, C; Samaha, H; Noun, P; Bakhos Asmar, J D; Taher, A; Adib, S; Inati, A; Sakr, S

2014-03-01

To promote management and awareness of bleeding disorders in Lebanon, a pilot programme was launched in 2009 by the Lebanese Hemophilia Association assisted by World Federation of Hemophilia. The aim of this study was to diagnose patients with bleeding disorders and to assess the potential challenges in implementing a screening programme. The pilot project was launched in 26 social health centres in the Bekaa valley. The study tools included the evaluation of the Tossetto Bleeding Score and the Pictorial Bleeding Assessment Chart (PBAC) for menstruation. Persons with a bleeding score higher than 2 and PBAC higher than 185 were eligible for further blood tests including the prothrombin time, partial thromboplastin time, complete blood count, bleeding time and von Willebrand ristocetin cofactor activity. 643 patients were enrolled, of whom 60.6% were women. Overall, 91 persons had an abnormal score. 50 eligible patients were tested: 32 had normal tests, nine new patients with severe Von Willebrand were discovered, 4 had VW:RiCo of 40, 3 prolonged APTT and 2 thrombocytopaenia. There was a clear correlation between the severity of the score and the willingness to perform the tests (P = 0.02). Women were reluctant to participate fully when investigators were men. The probability of adherence to the screening protocol is significantly increased when directed by women health care professional. For patients with milder forms, global screening programmes were neither feasible nor acceptable but those more severely affected have to be identified. Providers are crucial in preselecting patients with blood problems who are not coping well. © 2013 John Wiley & Sons Ltd.

[Psychogenic purpura with hematuria and sexual pain disorder: a case report].

PubMed

Ozyildirim, Ilker; Yücel, Başak; Aktan, Melih

2010-01-01

Psychogenic purpura (Gardner-Diamond syndrome) is the occurrence and spontaneous recurrence of painful ecchymosis following emotional stress and minor trauma. Although the exact mechanism of this syndrome remains unknown, apart from skin lesions, different types of hemorrhaging have been reported, such as epistaxis, gastrointestinal bleeding, and bleeding from the ear canals and eyes. We report a psychogenic purpura case that presented with hematuria in addition to skin lesions. Based on the psychiatric evaluation she was diagnosed with major depressive disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Additionally, sexual pain disorder accompanied these disorders. With the help of antidepressant and supportive psychotherapy, the patient's ecchymosis and bleeding disappeared. During 8 months of follow-up the symptoms did not return. Vaginismus has not been reported in patients with psychogenic purpura. The presence of vaginismus, which is seen more frequently in eastern cultures and is thought to be related to sociocultural determinants, suggests that some cultural factors may be common to both psychogenic purpura and vaginismus. The aim of this case report was to call attention to a syndrome that is rarely seen and diagnosed, and to discuss its relationship to psychosocial factors. This syndrome should be considered in the differential diagnosis of not only ecchymotic lesions, but also various types of bleeding, including hematuria. Despite the fact that its etiology and treatment are not clearly understood, it should be noted that psychological factors play a role in this disease and therefore, psychopharmacological and psychotherapeutic approaches can be effective.

Insights into abnormal hemostasis in the Quebec platelet disorder from analyses of clot lysis.

PubMed

Diamandis, M; Adam, F; Kahr, W H A; Wang, P; Chorneyko, K A; Arsenault, A L; Rivard, G E; Hayward, C P M

2006-05-01

The Quebec platelet disorder (QPD) is inherited and characterized by delayed-onset bleeding following hemostatic challenge. Other characteristics include increased expression and storage of active urokinase-type plasminogen activator (u-PA) in platelets in the setting of normal to increased u-PA in plasma. There is also consumption of platelet plasminogen activator inhibitor-1 and increased generation of plasmin in platelets accompanied by proteolysis of stored alpha-granule proteins, including Factor V. Although fibrinolysis has been proposed to contribute to QPD bleeding, the effects of QPD blood and platelets on clot lysis have not been evaluated. We used thromboelastography (TEG), biochemical evaluations of whole blood clot lysis, assessments of clot ultrastructure, and perfusion of blood over preformed fibrin to gain insights into the disturbed hemostasis in the QPD. Thromboelastography was not sensitive to the increased u-PA in QPD blood. However, there was abnormal plasmin generation in QPD whole blood clots, generated at low shear, with biochemical evidence of increased fibrinolysis. The incorporation of QPD platelets into a forming clot led to progressive disruption of fibrin and platelet aggregates unless drugs were added to inhibit plasmin. In whole blood perfusion studies, QPD platelets showed normal adherence to fibrin, but their adhesion was followed by accelerated fibrinolysis. The QPD is associated with "gain-of-function" abnormalities that increase the lysis of forming or preformed clots. These findings suggest accelerated fibrinolysis is an important contributor to QPD bleeding.

Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study.

PubMed

Hill, K; Fearn, M; Williams, S; Mudge, L; Walsh, C; McCarthy, P; Walsh, M; Street, A

2010-01-01

Adults with haemophilia and other bleeding disorders often develop lower limb musculoskeletal problems associated with bleeds into joints and muscles, which may affect balance performance and increase likelihood of falling. The aim of this study was to evaluate the effectiveness of an individualized balance and strength home exercise programme on improving balance and related outcomes for adults with haemophilia and other bleeding disorders. Twenty male adults with haemophilia and other bleeding disorders (mean age 39.4 years, 95% CI = 33.7-45.1) were recruited to participate. They underwent a comprehensive clinical and force platform assessment of balance and related measures. Based on assessment findings, the assessing physiotherapist provided an individualized home exercise programme of balance, strengthening and walking exercises. Re-assessment occurred after the 4-month exercise programme. Twelve participants (60%) completed the programme and were re-assessed. There were no safety problems or dropouts associated with the exercise programme aggravating joint status. Although there were no statistically significant changes in any of the measures (adjusted for multiple comparisons), there were improvements of between 5% and 22% on 10 of the 16 measures, with the Neurocom modified Clinical Test of Sensory Interaction on Balance (P = 0.036) and Timed Sit to Stand (P = 0.064) approaching significance. A tailored home exercise programme targeting balance, strengthening and walking is feasible for adults with haemophilia and other bleeding disorders. These results suggest that positive physical outcomes including improved balance and mobility may be achieved with this type of programme.

Genetics Home Reference: factor XI deficiency

MedlinePlus

... with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. In ... the particular mutation and whether one or both copies of the F11 gene in each cell have ...

Nasal endoscopy

MedlinePlus

... have a bleeding disorder or take blood-thinning medicine, let your provider know so they are extra careful to decrease bleeding. If you have heart disease, there is a small risk that you could feel lightheaded or faint.

Poland's syndrome: report of a variant.

PubMed

Legbo, Jacob Ndas

2006-01-01

Poland's syndrome is a rare congenital anomaly consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle, and ipsilateral symbrachydactyly. Many structural and functional abnormalities have been described in association with the syndrome. However, only a few hemostatic disorders have been reported. The case of a 12-year-old secondary school girl with unilateral hypoplasia of the breast, absence of anterior axillary fold and absence of the pectoralis major muscle is hereby presented. She also had thrombocytopenia and several episodes of spontaneous bleeding from the ipsilateral anterior chest wall. She did well on medical treatment, with no recurrence of bleeding 10 months after treatment. The author is not aware of any previously reported case of Poland's syndrome associated with bleeding disorder in Africa. This case is presented to alert clinicians of its existence and possible association with hematological disorders.

Capacity Building for Rare Bleeding Disorders in the Remote Commonwealth of the Northern Mariana Islands

PubMed Central

Carhill, Pam; Huang, James N.; Baker, Judith R.

2016-01-01

The US Pacific Commonwealth of the Northern Mariana Islands is home to an underserved hemophilia population. We developed a strategy in 2014 to build sustainable island-wide medical, patient and family, and community support for this rare disease. Collaboration with regional bleeding disorder leadership galvanized a weeklong conference series. More than 200 participants attended discipline-specific seminars; pre–post test evaluations documented educational benefits. This time-concentrated island-wide education intervention promoted the rapid identification of new cases and stimulated sustainable bleeding disorder care development. The education series proved feasible, efficient, and effective in increasing knowledge and reducing patient and professional isolation, serving as a model for improving capacity for orphan diseases (those that affect fewer than 200 000 people in any particular country) in underresourced areas. PMID:26890163

Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders.

PubMed

Neerman-Arbez, Marguerite; de Moerloose, Philippe; Casini, Alessandro

2016-06-01

Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Congenital factor V deficiency: comparison of the severity of clinical presentations among patients with rare bleeding disorders.

PubMed

Naderi, Majid; Tabibian, Shadi; Alizadeh, Shaban; Hosseini, Soudabeh; Zaker, Farhad; Bamedi, Taregh; Shamsizadeh, Morteza; Dorgalaleh, Akbar

2015-01-01

Factor V deficiency (FVD) is a rare bleeding disorder (RBD) mostly present in regions with a high rate of consanguinity. FVD after FXIII deficiency is the next more prevalent RBD in Sistan and Baluchistan (S&B) in southeastern Iran. The aim of this study was to evaluate the clinical manifestations and severity of bleeding diathesis in patients with FVD. This descriptive study was conducted on 23 patients with FVD in S&B province. FVD was diagnosed by clinical findings and routine laboratory tests. Bleeding diatheses were classified into three grades (I-III) depending on the severity of symptoms. The severity of bleeding episodes in our patients was compared with other RBDs. Based on residual plasma FV activity, 6 (26%), 16 (69.5%) and 1 (4.5%) patients had mild, moderate and severe factor deficiency, respectively. 24% of the patients had grade III life-threatening bleeding episodes which in comparison with FVII deficiency (17.4%) and FI deficiency (21%) had a higher incidence, and in comparison with FX deficiency (41.7%) and FXIII deficiency (63.1) had a lower incidence. Grade II and grade I bleeding diathesis were observed in 56.2 and 16.7% of the patients, respectively. FVD is the second most common type of RBD in S&B province and grade II bleeding episodes were the major bleeding presentation and observed in more than half of the patients. © 2014 S. Karger AG, Basel.

The Genetics of bleeding disorders: a report on the UK Haemophilia Centre Doctors' Organisation annual scientific symposium, 10th October 2003.

PubMed

Nicolle, A L; Talks, K L; Hanley, J

2004-07-01

The UK Haemophilia Centre Doctors' Organisation (UKHCDO) held its annual scientific symposium in October 2003, at the International Centre for Life, Newcastle-upon-Tyne. The educational day covered a range of topics relating to the genetics of bleeding disorders, including advances in genetics and gene therapy, antenatal diagnosis and counselling. We present the proceedings from the educational day.

Idiopathic portal hypertension and extrahepatic portal venous obstruction.

PubMed

Khanna, Rajeev; Sarin, Shiv Kumar

2018-02-01

Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are non-cirrhotic vascular causes of portal hypertension (PHT). Variceal bleed and splenomegaly are the commonest presentations. The present review is intended to provide the existing literature on etiopathogenesis, clinical profile, diagnosis, natural history and management of IPH and EHPVO. IPH and EHPVO are both characterized by normal hepatic venous pressure gradient, moderate to massive splenomegaly with preserved liver synthetic functions. While the level of block in IPH is presinusoidal, in EHPVO it is at prehepatic level. Infections, autoimmunity, drugs, immunodeficiency and prothrombotic states are possible etiological agents in IPH. Contrastingly in EHPVO, prothrombotic disorders and local factors around the portal vein are the incriminating factors. Diagnosis is often clinical, supported by simple radiological tools. Natural history is defined by episodes of variceal bleed and symptoms related to enlarged spleen. Growth failure, portal biliopathy and minimal hepatic encephalopathy are additional concerns in EHPVO. Long-term survival is reasonably good with endoscopic surveillance; however, parenchymal extinction leading to decompensation is seen in a minority of patients in both the disorders. Surgical shunts revert the complications secondary to PHT. Meso-Rex shunt has become the standard surgery in children with EHPVO. This review gives a detailed summary of these two vascular conditions of liver-IPH and EHPVO. Further research is needed to understand the pathogenesis and natural history of these disorders.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?].

PubMed

García Vallejo, G; Cabellos, M; Kabiri, M; Fraile, J R; Cuesta, J

2014-10-01

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Bleeding and cupping.

PubMed Central

Turk, J. L.; Allen, E.

1983-01-01

Bleeding and cupping have been used in medicine since ancient times in the treatment of fevers and local inflammatory disorders. Local bleeding, by 'wet cupping', was effected by a scarificator or by leeches. John Hunter recommended venesection in moderation but preferred leeches for local bleeding. Bleeding as an accepted therapeutic practice went out of vogue in the middle of the nineteenth century as a result of the introduction of modern scientific methods. Dry cupping and the use of leeches, as counter irritants, persisted until the middle of this century. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6338802

An unexpected cause of vaginal bleeding: the role of pelvic radiography.

PubMed

Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Theodoridis, Theodoros; Galli-Tsinopoulou, Assimina

2014-02-14

Vaginal bleeding and/or discharge in young girls may result from infection, urological problems, endocrine causes, bleeding disorders, dermatological conditions, trauma, sexual abuse, masses or foreign bodies. We report a case of excessive vaginal bleeding caused by a foreign body in a prepubertal girl with emphasis on the diagnostic challenges and pitfalls regarding imaging techniques. In our patient, although invasive and expensive investigations had been initially made, the foreign body was last detected only when a plain pelvic radiography was performed.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy.

PubMed

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-03-28

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition-even in homozygous subjects-to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency.

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

PubMed Central

Napolitano, Mariasanta; Siragusa, Sergio; Mariani, Guglielmo

2017-01-01

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the current review is to depict an updated summary of clinical phenotype, laboratory diagnosis, and treatment of inherited Factor VII deficiency. PMID:28350321

Poland's syndrome: report of a variant.

PubMed Central

Legbo, Jacob Ndas

2006-01-01

Poland's syndrome is a rare congenital anomaly consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle, and ipsilateral symbrachydactyly. Many structural and functional abnormalities have been described in association with the syndrome. However, only a few hemostatic disorders have been reported. The case of a 12-year-old secondary school girl with unilateral hypoplasia of the breast, absence of anterior axillary fold and absence of the pectoralis major muscle is hereby presented. She also had thrombocytopenia and several episodes of spontaneous bleeding from the ipsilateral anterior chest wall. She did well on medical treatment, with no recurrence of bleeding 10 months after treatment. The author is not aware of any previously reported case of Poland's syndrome associated with bleeding disorder in Africa. This case is presented to alert clinicians of its existence and possible association with hematological disorders. Images Figure 1 PMID:16532987

Factitious disorder: a rare cause of haematemesis.

PubMed

McFarlane, Michael; Eaden, Jayne; Burch, Nicola; Disney, Ben

2017-10-01

Acute upper gastrointestinal (GI) bleeding is a common condition in the UK with 50-70,000 admissions per year. In 20% of cases no cause can be found on endoscopy. Here, we present the case of a young female patient who was admitted on three occasions with large volume haematemesis and bleeding from other sites. She was extensively investigated and underwent multiple endoscopic procedures. She was eventually diagnosed with factitious disorder after concerns were raised about the inconsistent nature of her presentations. She was found to be venesecting herself from her intravenous cannula, and ingesting the blood to simulate upper GI bleeding. This is a rare cause of 'haematemesis' but perhaps not as rare as is thought.

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

PubMed

Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

2002-12-01

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Treatment for preventing bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgery.

PubMed

Coppola, Antonio; Windyga, Jerzy; Tufano, Antonella; Yeung, Cindy; Di Minno, Matteo Nicola Dario

2015-02-09

In people with haemophilia or other congenital bleeding disorders undergoing surgical interventions, haemostatic treatment is needed in order to correct the underlying coagulation abnormalities and minimise the bleeding risk. This treatment varies according to the specific haemostatic defect, its severity and the type of surgical procedure. The aim of treatment is to ensure adequate haemostatic coverage for as long as the bleeding risk persists and until wound healing is complete. To assess the effectiveness and safety of different haemostatic regimens (type, dose and duration, modality of administration and target haemostatic levels) administered in people with haemophilia or other congenital bleeding disorders for preventing bleeding complications during and after surgical procedures. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of the last search: 20 November 2014. Randomised and quasi-randomised controlled trials comparing any hemostatic treatment regimen to no treatment or to another active regimen in children and adults with haemophilia or other congenital bleeding disorders undergoing any surgical intervention. Two authors independently assessed trials (eligibility and risks of bias) and extracted data. Meta-analyses were performed on available and relevant data. Of the 16 identified trials, four (112 participants) were eligible for inclusion.Two trials evaluated 59 people with haemophilia A and B undergoing 63 dental extractions. Trials compared the use of a different type (tranexamic acid or epsilon-aminocaproic acid) and regimen of antifibrinolytic agents as haemostatic support to the initial replacement treatment. Neither trial specifically addressed mortality (one of this review's primary outcomes); however, in the frame of safety assessments, no fatal adverse events were reported. The second primary outcome of blood loss was assessed after surgery and these trials showed the reduction of blood loss and requirement of post-operative replacement treatment in people receiving antifibrinolytic agents compared with placebo. The remaining primary outcome of need for re-intervention was not reported by either trial.Two trials reported on 53 people with haemophilia A and B with inhibitors treated with different regimens of recombinant activated factor VII (rFVIIa) for haemostatic coverage of 33 major and 20 minor surgical interventions. Neither of the included trials specifically addressed any of the review's primary outcomes (mortality, blood loss and need for re-intervention). In one trial a high-dose rFVIIa regimen (90 μg/kg) was compared with a low-dose regimen (35 μg/kg); the higher dose showed increased haemostatic efficacy, in particular in major surgery, with shorter duration of treatment, similar total dose of rFVIIa administered and similar safety levels. In the second trial, bolus infusion and continuous infusion of rFVIIa were compared, showing similar haemostatic efficacy, duration of treatment and safety. There is insufficient evidence from randomised controlled trials to assess the most effective and safe haemostatic treatment to prevent bleeding in people with haemophilia or other congenital bleeding disorders undergoing surgical procedures. Ideally large, adequately powered, and well-designed randomised controlled trials would be needed, in particular to address the cost-effectiveness of such demanding treatments in the light of the increasing present economic constraints, and to explore the new challenge of ageing patients with haemophilia or other congenital bleeding disorders. However, performing such trials is always a complex task in this setting and presently does not appear to be a clinical and research priority. Indeed, major and minor surgeries are effectively and safely performed in these individuals in clinical practice, with the numerous national and international recommendations and guidelines providing regimens for treatment in this setting mainly based on data from observational, uncontrolled studies.

Bleeding disorders

MedlinePlus

... disorders: coagulation factor deficiencies. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Current options and new developments in the treatment of haemophilia.

PubMed

Wong, Trisha; Recht, Michael

2011-02-12

Haemophilia A and B are X-linked bleeding disorders due to the inherited deficiency of factor VIII or factor IX, respectively. Of the approximately 1 per 5000-10000 male births affected by haemophilia, 80% are deficient in factor VIII and 20% are deficient in factor IX. Haemophilia is characterized by spontaneous and provoked joint, muscle, gastrointestinal and CNS bleeding leading to major morbidity and even mortality if left untreated or under-treated. The evolution of haemophilia management has been marked by tragedy and triumph over recent decades. Clotting factors and replacement strategies continue to evolve for patients without inhibitors. For patients with an inhibitor, factor replacement for acute bleeding episodes and immune tolerance, immune modulation and extracorporeal methods for inhibitor reduction are the cornerstone of care. In addition, adjuvant therapies such as desmopressin, antifibrinolytics and topical agents also contribute to improved outcomes for patients with and without inhibitors. The future direction of haemophilia care is promising with new longer-acting clotting factors and genetic therapies, including gene transfer and premature termination codon suppressors. With these current and future treatment modalities, the morbidity and mortality rates in patients with haemophilia certainly will continue to improve.

A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

PubMed Central

Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

2011-01-01

Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

Spontaneous thigh hematoma associated with diclofenac.

PubMed

Salemis, Nikolaos S

2009-01-01

Spontaneous nongastrointestinal bleeding in patients treated with nonsteroidal anti-inflammatory drugs is an extremely rare occurrence. Herein, the case of a 60-year-old woman with severe bilateral hip osteoarthritis treated with diclofenac sodium, who presented with manifestations of a spontaneous hematoma of the right thigh, is described. There was no history of trauma or family history of bleeding disorder. Thorough investigation excluded a hemorrhagic disorder. The patient was treated conservatively with success and was advised to discontinue diclofenac.

An innovative outcome-based care and procurement model of hemophilia management.

PubMed

Gringeri, Alessandro; Doralt, Jennifer; Valentino, Leonard A; Crea, Roberto; Reininger, Armin J

2016-06-01

Hemophilia is a rare bleeding disorder associated with spontaneous and post-traumatic bleeding. Each hemophilia patient requires a personalized approach to episodic or prophylactic treatment, but self-management can be challenging for patients, and avoidable bleeding may occur. Patient-tailored care may provide more effective prevention of bleeding, which in turn, may decrease the likelihood of arthropathy and associated chronic pain, missed time from school or work, and progressive loss of mobility. A strategy is presented here aiming to reduce or eliminate bleeding altogether through a holistic approach based on individual patient characteristics. In an environment of budget constraints, this approach would link procurement to patient outcome, adding incentives for all stakeholders to strive for optimal care and, ultimately, a bleed-free world.

The level of laboratory testing required for diagnosis or exclusion of a platelet function disorder using platelet aggregation and secretion assays.

PubMed

Mezzano, Diego; Quiroga, Teresa; Pereira, Jaime

2009-03-01

The major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades have not been adequately translated to clinical laboratory diagnosis. Hereditary platelet function disorders (PFDs) are at least as prevalent in the general population as von Willebrand disease (VWD) although PFDs tend not be as well recognized or evaluated. Clinical mucous and skin bleeding in patients with PFDs is prototypic of primary hemostasis disorders, and the bleeding pattern is not distinguishable from that of other primary hemostasis disorders such as VWD. However, different treatment needs, between these discrete disorders, make a precise diagnosis mandatory. Currently, clinicians receive reliable laboratory reports when testing patients with severe PFDs, such as Glanzmann thrombasthenia and Bernard-Soulier syndrome, due to the distinctive laboratory defects that these disorders present, together with the availability of differential diagnostic tests. This is not the case for the majority of PFDs generically classified as "platelet secretion disorders," which are a heterogeneous group of "mild bleeding disorders," for which there are not universally accepted diagnostic criteria. An important reason for robust diagnostic tests is the high proportion (more than 50% in some reports) of patients with unequivocal bleeding who have no precise diagnosis established after a complete laboratory workup. It is paradoxical that the current "gold standard" test for PFD diagnosis, light transmission aggregometry (LTA), has not been standardized after more than four decades of worldwide clinical use. This review describes current diagnostic assays for PFD in a clinical hemostasis laboratory, relating these with current knowledge on platelet function and pathophysiology. Special emphasis will be given to LTA and platelet secretion tests, as well as to the reasons why sensitive tests are needed to explore the lesser known participation of platelets in blood clotting and fibrinolytic processes.

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

Autologous plasma rich in growth factors in the prevention of severe bleeding after teeth extractions in patients with bleeding disorders: a controlled comparison with fibrin glue

PubMed Central

Cocero, Nadia; Pucci, Fabrizio; Messina, Maria; Pollio, Berardino; Mozzati, Marco; Bergamasco, Laura

2015-01-01

Background Dental extractions in haemophiliacs may cause secondary bleeding, requiring repeated surgical and haematological interventions. As a local haemostatic, fibrin glue has recognised efficacy but, as a plasma-derived product, it carries the risk of viral infections. We, therefore, compared fibrin glue with an autologous haemostatic, plasma rich in growth factors (PRGF), in a controlled trial. Material and methods One hundred and twenty patients with different blood disorders were randomised into two cohorts to undergo dental extraction procedures without hospitalisation. Prior to the extractions, patients underwent systemic haematological treatment. Complications were defined as secondary bleeding after the 7-day follow-up period or protracting after the repair procedure. Results There were 106 extractions (7 retained 3rd molars) in the group managed with fibrin glue: secondary bleeding affected 3/60 patients (5%) on the third day after extraction and necessitated additional surgery and systemic treatment (in one case the procedure had to be repeated on the 7th day). In the PRGF arm there were 98 extractions (23 retained 3rd molars): secondary bleeding affected two patients (3.3%) on the first day after extraction and was arrested with surgery without systemic treatment. Four out of the five secondary bleeds occurred in patients with haemophilia A. Concomitant diabetes or liver disease significantly increased the bleeding risk. Discussion The bleeding rates in the study and control arm prove that PRGF works as well as fibrin glue as a local haemostatic. Further assets are that PRGF has autologous origin, does not require additional systemic treatment in post-extraction repair surgery, is associated with an earlier onset of neo-angiogenesis and, overall, can reduce patients’ distress and costs to the health system. PMID:25369587

Psychiatric disorders related to menstrual bleeding among an ultra-orthodox population: case series and literature review.

PubMed

Vishne, Tali; Misgav, Sagit; Bunzel, Michael E

2008-05-01

The relationship between menstrual cycle and obsessive-compulsive disorder (OCD) has been documented in the past and is related to sexual hormone changes. In the ultra-orthodox Jewish population menstrual bleeding is associated both with meticulous rituals of cleanliness and with stressful meanings related to sin, impurity and punishment. Those aspects of the menstrual cycle can be related to specific OCD symptoms among ultra-orthodox women. The current study presents three cases related to the development of obsessive-compulsive symptoms in relation to the menstrual cycle among ultra-orthodox women, and discusses the biological and social-cultural basis of the disorder.

Traumatic Hemarthrosis of the Knee Secondary to Hemophilia A in a Collegiate Soccer Player: A Case Report

PubMed Central

Fiala, Kelly A.; Hoffmann, Sandra J.; Ritenour, Donna M.

2002-01-01

Objective: To present the case of a collegiate soccer player who suffered from a traumatic knee hemarthrosis secondary to hemophilia A. This case presents an opportunity to discuss the participation status of athletes with hemophilia. Background: Hemophilia is a hereditary blood disease characterized by impaired coagulability of the blood. Hemophilia A is the most common of the severe, inherited bleeding disorders. This type, also called classic hemophilia, is due to a deficiency of clotting factor VIII. The athlete with hemophilia A reported pain and loss of function of his knee during a soccer game despite the absence of injury. Differential Diagnosis: Anterior cruciate ligament tear, intra-articular fracture, meniscus tear, capsular tear, hemarthrosis. Treatment: After the injury, the athlete was admitted to the hospital, where his knee joint was aspirated and he was infused with factor VIII. Later, he participated in traditional knee rehabilitation and was returned to play at the discretion of the orthopaedist and the hematologist. Uniqueness: In past participation guidelines, individuals with bleeding disorders were disqualified from athletic participation; however, with advances in medical care, these individuals may be permitted to participate in accordance with the law. Conclusions: Individuals with hemophilia participate in athletics; therefore, team physicians and athletic trainers must be prepared to care for these individuals. PMID:12937588

Evaluation of factor IX deficiency by interdigitated electrode (IDE)

NASA Astrophysics Data System (ADS)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

Clinical significance of neonatal menstruation.

PubMed

Brosens, Ivo; Benagiano, Giuseppe

2016-01-01

Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diagnosis, clinical manifestations and management of rare bleeding disorders in Iran.

PubMed

Dorgalaleh, Akbar; Alavi, Sayed Ezatolla Rafiee; Tabibian, Shadi; Soori, Shahrzad; Moradi, Es'hagh; Bamedi, Taregh; Asadi, Mansour; Jalalvand, Masumeh; Shamsizadeh, Morteza

2017-05-01

Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly inherited in an autosomal recessive pattern. Iran is a Mideast country with a high rate of consanguinity that has a high rate of RBDs. In this study, we present prevalence and clinical presentation as well as management and genetic defects of Iranian patients with RBDs. For this study, all relevant publications were searched in Medlin until 2015. Iran has the highest global incidence of factor XIII deficiency. Factor VII deficiency also is common in Iran, while factor II deficiency, with a prevalence of 1 per ∼3 million, is the rarest form of RBDs. Factor activity is available for all RBDs except for factor XIII deficiency, in which clot solubility remains as a diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few recurrent, common mutations only in patients with factor XIII deficiency, and considerable novel mutations in other RBDs. Clinical manifestations of these patients are variable and patients with factor XIII, factor X and factor VII more commonly presented severe life-threatening bleeding, while patients with combined factor V and factor VIII presented a milder phenotype. Plasma-derived products are the most common therapeutic choice in Iran, used prophylactically or on-demand for the management of these patients. Since Iran has a high rate of RBDs with life-threatening bleeding, molecular studies can be used for carrier detection and, therefore, prevention of the further expansion of these disorders and their fatal consequence.

The impact of bleeding disorders on the socioeconomic status of adult patients. Results of a comparative single centre cohort study.

PubMed

Holstein, Katharina; von Mackensen, Sylvia; Bokemeyer, Carsten; Langer, Florian

2017-07-10

The impact of inherited bleeding disorders on the socioeconomic status (SES) of affected individuals is not clear. The SES of adult patients with congenital bleeding disorders (PWBD) from a centre in Germany (age 42.3 ± 15.0 years) was compared to that of a gender- and age-matched control group of patients with thrombophilia or a thrombotic event (PWT). Patients completed a questionnaire including aspects of SES, impact of the disease on their lives, and health-related quality of life (HRQoL). Forty-five patients were enrolled in each group; 71 % of PBWD had a severe form of the bleeding disorder (FVIII/IX activity < 1 % or VWD type 3), and 60 % of all PWBD were treated on-demand. PWBD had a lower monthly income (p = 0.029) and a worse occupational status (p = 0.047) than PWT, but there was no difference regarding the project-specific SES index. PWBD also reported a worse HRQoL in the physical summary component score of the SF-36 (p < 0.001). More PWBD (69.8 %) reported a high impact of the disease on their lives than PWT (33.3 %, p < 0.001). In summary, PWBD had a worse occupational status, monthly income, health behaviour, HRQoL, and impact of the disease on their lives compared to PWT, but not a significantly different SES in general.

Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

PubMed

Knoebl, P; Marco, P; Baudo, F; Collins, P; Huth-Kühne, A; Nemes, L; Pellegrini, F; Tengborn, L; Lévesque, H

2012-04-01

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA. © 2012 International Society on Thrombosis and Haemostasis.

Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders.

PubMed

Riddell, A; Chuansumrit, A; El-Ekiaby, M; Nair, S C

2016-07-01

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described. © 2016 John Wiley & Sons Ltd.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

PubMed Central

Christopherson, Pamela A.; Gill, Joan Cox; Friedman, Kenneth D.; Haberichter, Sandra L.; Bellissimo, Daniel B.; Udani, Rupa A.; Dasgupta, Mahua; Hoffmann, Raymond G.; Ragni, Margaret V.; Shapiro, Amy D.; Lusher, Jeanne M.; Lentz, Steven R.; Abshire, Thomas C.; Leissinger, Cindy; Hoots, W. Keith; Manco-Johnson, Marilyn J.; Gruppo, Ralph A.; Boggio, Lisa N.; Montgomery, Kate T.; Goodeve, Anne C.; James, Paula D.; Lillicrap, David; Peake, Ian R.; Montgomery, Robert R.

2016-01-01

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. PMID:26862110

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States.

PubMed

Flood, Veronica H; Christopherson, Pamela A; Gill, Joan Cox; Friedman, Kenneth D; Haberichter, Sandra L; Bellissimo, Daniel B; Udani, Rupa A; Dasgupta, Mahua; Hoffmann, Raymond G; Ragni, Margaret V; Shapiro, Amy D; Lusher, Jeanne M; Lentz, Steven R; Abshire, Thomas C; Leissinger, Cindy; Hoots, W Keith; Manco-Johnson, Marilyn J; Gruppo, Ralph A; Boggio, Lisa N; Montgomery, Kate T; Goodeve, Anne C; James, Paula D; Lillicrap, David; Peake, Ian R; Montgomery, Robert R

2016-05-19

von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. © 2016 by The American Society of Hematology.

The Third, Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial

ClinicalTrials.gov

2018-04-24

Cerebral Hemorrhage; Stroke; Hypertension; Diabetes; Anticoagulant-induced Bleeding; Cerebral Vascular Disorder; Brain Disorder; Hemorrhage; Intracranial Hemorrhages; Cardiovascular Diseases; Central Nervous System Diseases

Genetics Home Reference: MYH9-related disorder

MedlinePlus

... related disorder typically experience easy bruising, and affected women have excessive bleeding during menstruation (menorrhagia). The platelets in people with MYH9 -related disorder are larger than normal. These enlarged platelets have difficulty moving into tiny blood vessels like capillaries . As ...

Canine models of inherited bleeding disorders in the development of coagulation assays, novel protein replacement and gene therapies.

PubMed

Nichols, T C; Hough, C; Agersø, H; Ezban, M; Lillicrap, D

2016-05-01

Animal models of inherited bleeding disorders are important for understanding disease pathophysiology and are required for preclinical assessment of safety prior to testing of novel therapeutics in human and veterinary medicine. Experiments in these animals represent important translational research aimed at developing safer and better treatments, such as plasma-derived and recombinant protein replacement therapies, gene therapies and immune tolerance protocols for antidrug inhibitory antibodies. Ideally, testing is done in animals with the analogous human disease to provide essential safety information, estimates of the correct starting dose and dose response (pharmacokinetics) and measures of efficacy (pharmacodynamics) that guide the design of human trials. For nearly seven decades, canine models of hemophilia, von Willebrand disease and other inherited bleeding disorders have not only informed our understanding of the natural history and pathophysiology of these disorders but also guided the development of novel therapeutics for use in humans and dogs. This has been especially important for the development of gene therapy, in which unique toxicities such as insertional mutagenesis, germ line gene transfer and viral toxicities must be assessed. There are several issues regarding comparative medicine in these species that have a bearing on these studies, including immune reactions to xenoproteins, varied metabolism or clearance of wild-type and modified proteins, and unique tissue tropism of viral vectors. This review focuses on the results of studies that have been performed in dogs with inherited bleeding disorders that closely mirror the human condition to develop safe and effective protein and gene-based therapies that benefit both species. © 2016 International Society on Thrombosis and Haemostasis.

A French National Survey on Clotting Disorders in Mastocytosis.

PubMed

Carvalhosa, Ana B; Aouba, Achille; Damaj, Gandhi; Canioni, Danielle; Brouzes, Chantal; Gyan, Emmanuel; Durupt, Stéphane; Durieu, Isabelle; Cathebras, Pascal; Costédoat-Chalumeau, Nathalie; Launay, David; Pilmis, Benoit; Barete, Stephane; Frenzel, Laurent; Lortholary, Olivier; Hermine, Olivier; Hermans, Cedric; Chandesris, Marie-Olivia

2015-10-01

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

Unmasking an autosomal recessive disorder by a deletion in the DiGeorge/Velo-cardio-facial chromosome region (DGCR) in 22q11.2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budarf, M.L.; Michaud, D.; Emanuel, B.

Unmasking an autosomal recessive disorder by constitutional hemizygosity is well documented for the embryonal tumors RB and WAGR, where the second hit is a somatic event. Few deletion-mediated recessive conditions have been reported in patients with germline mutations. The major platelet receptor for von Willebrand factor, Glycoprotein Ib (GpIb), is a complex of two plasma membrane glycoproteins, Ib{alpha} and Ib{beta}, covalently linked by disulfide bonds. Defects in this receptor have been associated with the rare congenital autosomal recessive bleeding disorder, Bernard-Soulier syndrome (BSS). BSS is characterized by prolonged bleeding times, thrombocytopenia and very large platelets. The GpIb{beta} gene has beenmore » cloned and we have mapped it within the DGCR. We have identified a patient with phenotypic features of both BSS and VCFS. The patient was referred for 22q11-deletion FISH studies because of a conventricular VSD and mild dysmorphia. FISH with the N25 DiGeorge cosmid demonstrated a deletion in 22q11.2. Western blot analysis of the patient`s platelet proteins demonstrates a complete absence of GpIb{beta}. We suggest that haploinsufficiency for the DGCR in this patient unmasks a mutation in the remaining GpIb{beta} allele, resulting in manifestations of BSS. This mechanism, haploinsufficiency coupled with a mutation of the {open_quotes}normal{close_quotes} chromosome, might explain some of the phenotypic variability seen amongst patients with 22q11.2 microdeletions. These results further suggest that patients with contiguous gene deletion syndromes are at increased risk for autosomal recessive disorders and that they provide the opportunity to {open_quotes}map{close_quotes}disease loci.« less

Blood Disorders

MedlinePlus

... become hard, sticky, and shaped like a C. Thalassemia Red blood cell disorder. Von Willebrand Disease Blood ... Hemophilia Hereditary Hemorrhagic Telangiectasia (HHT) Sickle Cell Disease Thalassemia Vitamin K Deficiency Bleeding Von Willebrand Disease Women’s ...

Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis.

PubMed

Martin, Karlyn

2017-10-01

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications. Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET. Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report

PubMed Central

Sugiura, Tsutomu; Yamamoto, Kazuhiko; Murakami, Kazuhiro; Horita, Satoshi; Matsusue, Yumiko; Nakashima, Chie; Kirita, Tadaaki

2018-01-01

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/μL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases. PMID:29854891

Glanzmann Thrombasthenia: State of the Art and Future Directions

PubMed Central

Nurden, Alan T; Pillois, Xavier; Wilcox, David A.

2014-01-01

Glanzmann thrombasthenia (GT) is the principal inherited disease of platelets and the most commonly encountered disorder of an integrin. GT is characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma due to platelets that fail to aggregate when stimulated by physiologic agonists. GT is caused by quantitative or qualitative deficiencies of αIIbβ3, an integrin coded by the ITGA2B and ITGB3 genes and which by binding fibrinogen and other adhesive proteins joins platelets together in the aggregate. Widespread genotyping has revealed mutations spread across both genes, yet the reason for the extensive variation in both the severity and intensity of bleeding between affected individuals remains poorly understood. Furthermore, while genetic defects of ITGB3 affect other tissues with β3 present as αvβ3 (the vitronectin receptor), the bleeding phenotype continues to dominate. Here, we look in detail at mutations that affect (i) the β-propeller region of the αIIb head domain and (ii) the membrane proximal disulfide-rich EGF domains of β3 and which often result in spontaneous integrin activation. We also examine deep vein thrombosis as an unexpected complication of GT and look at curative procedures for the disease including allogeneic stem cell transfer and the potential for gene therapy. PMID:23929305

Perioperative bleeding and blood transfusion are major risk factors for venous thromboembolism following bariatric surgery.

PubMed

Nielsen, Alexander W; Helm, Melissa C; Kindel, Tammy; Higgins, Rana; Lak, Kathleen; Helmen, Zachary M; Gould, Jon C

2018-05-01

Morbidly obese patients are at increased risk for venous thromboembolism (VTE) after bariatric surgery. Perioperative chemoprophylaxis is used routinely with bariatric surgery to decrease the risk of VTE. When bleeding occurs, routine chemoprophylaxis is often withheld due to concerns about inciting another bleeding event. We sought to evaluate the relationship between perioperative bleeding and postoperative VTE in bariatric surgery. The American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) dataset between 2012 and 2014 was queried to identify patients who underwent bariatric surgery. Gastric bypass (n = 28,145), sleeve gastrectomy (n = 30,080), bariatric revision (n = 324), and biliopancreatic diversion procedures (n = 492) were included. Univariate and multivariate regressions were used to determine perioperative factors predictive of postoperative VTE within 30 days in patients who experience a bleeding complication necessitating transfusion. The rate of bleeding necessitating transfusion was 1.3%. Bleeding was significantly more likely to occur in gastric bypass compared to sleeve gastrectomy (1.6 vs. 1.0%) (p < 0.0001). For all surgeries, increased age, length of stay, operative time, and comorbidities including hypertension, dyspnea with moderate exertion, partially dependent functional status, bleeding disorder, transfusion prior to surgery, ASA class III/IV, and metabolic syndrome increased the perioperative bleeding risk (p < 0.05). Multivariate analysis revealed that the rate of VTE was significantly higher after blood transfusion [Odds Ratio (OR) = 4.7; 95% CI 2.9-7.9; p < 0.0001). Predictive risk factors for VTE after transfusion included previous bleeding disorder, ASA class III or IV, and COPD (p < 0.05). Bariatric surgery patients who receive postoperative blood transfusion are at a significantly increased risk for VTE. The etiology of VTE in those who are transfused is likely multifactorial and possibly related to withholding chemoprophylaxis and the potential of a hypercoagulable state induced by the transfusion. In those who bleed, consideration should be given to reinitiating chemoprophylaxis when safe, extending treatment after discharge, and screening ultrasound.

Dysfunctional uterine bleeding in ovulatory women.

PubMed

Strickler, R C

1985-01-01

Ovulatory dysfunctional uterine bleeding (DUB), a disease prevalent in the latter half of the reproductive years, is diagnosed when organic causes for bleeding have been excluded by clinical, laboratory, and surgical diagnostic means. Disordered prostaglandin metabolism within the endometrium explains most cases of DUB. Nonsteroidal antiinflammatory drugs, oral contraceptives, and oral progestin are effective medical alternatives for women who wish to retain their uterus or to avoid surgery. Hysterectomy is a rapid cure for DUB and is a therapy that is acceptable to many, if not most, women.

Adherence and Coagulation Assays in Dabigatran-treated Patients With Atrial Fibrillation

ClinicalTrials.gov

2017-09-12

Atrial Fibrillation; Medication Adherence; Blood Coagulation Tests; Anticoagulants; Circulating, Hemorrhagic Disorder; Drug Effect; Drug Use; Drug Toxicity; Drug Intolerance; Blood Clot; Blood Coagulation Disorder; Laboratory Problem; Bleeding; Thrombosis

Femoral nerve dysfunction

MedlinePlus

... in the groin Diabetes or other causes of peripheral neuropathy Internal bleeding in the pelvis or belly area ( ... Editorial team. Leg Injuries and Disorders Read more Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more A. ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bros, Sebastien, E-mail: sebbros@wanadoo.fr; Chabrot, Pascal, E-mail: pchabrot@chu-clermontferrand.fr; Kastler, Adrian, E-mail: a_kastler@chu-clermontferrand.fr

Purpose: To retrospectively identify predictive factors of recurrent bleeding within 24 h after uterine artery embolization (UAE) for postpartum hemorrhage (PPH). Materials and Methods: A total of 194 patients underwent UAE for PPH between August 1999 and April 2009 at our institution. Twelve patients experienced recurrent bleeding within the next 24 h; a second attempt at UAE was thus necessary, which was successful in 10 cases. In two cases, hemostatic hysterectomy was performed. Epidemiological, gynecological-obstetrical, anatomic, and biological data were analyzed. Results: Complete data were available for 148 of the 194 (76%) included patients. Sixty-four (43%) were primiparous, 18 (12.2%)more » had a placenta accreta, 21 (14%) had a coagulopathy, and 28 (18.9%) had an anatomic variant of the uterine arterial vasculature. Mean age and pregnancy term were similar in both recurring and nonrecurrent bleeding groups. After multivariate analysis, three criteria emerged as risk factors of recurrent bleeding: primiparity (10 patients, 83%; odds ratio [OR] = 18.84; P = 0.014), coagulation disorders (6 patients, 50%; OR = 12.08; P = 0.006), and anatomic variant of the uterine arterial vasculature (28 patients; OR = 9.83; P = 0.003). Conclusions: earch for uterine collaterals must be performed before UAE for PPH. Primiparity and coagulation disorders increase the risk of recurrent bleeding after UAE for PPH.« less

Dental health and oral health-related quality of life in children with congenital bleeding disorders.

PubMed

Salem, K; Eshghi, P

2013-01-01

The purpose of this study was to investigate the dental and some other aspects of oral health status of young patients with congenital bleeding disorders (CBD) and the impact of these on their quality of life (OHR-QoL) compared with controls. DMFS-dmfs (Decayed, Missed, Filled Tooth surfaces in permanent and primary teeth) scores, Simplified oral hygiene index, occurance of hypoplasia of first permanent molars, Temporomandibular joint dysfunction and occlusion of 46 CBD patients at the age range of 2-15 years and 46 of other children as control were compared, and the impact of their oral health situation on quality of life was also investigated. Data were analysed by chi-square, t-test and Pearson correlation. Patients were significantly more caries-free with less decayed teeth in primary-permanent dentition (P = 0.03, t = -2.17).The mean scores of OHR-QoL of CBD patients and controls were not significantly different. Oral Bleeding was the significant variable in relation to 'oral health-related quality of life' in CBD groups (Pearson correlation, r = -0.56, P = 0.000). OHR-QoL in the control group was related to dmfs score (r = -0.392, P = 0.011) and male gender (r = -0.329, P = 0.026). Congenital bleeding disorder CBD patients were found to have a better dental health situation in primary dentition compared with controls; however, their 'oral health-related quality of life' was similar. Oral bleeding was the only significant factor related to OHR-QoL in CBD. It shows an overall importance of development of comprehensive care centres for CBD as the main cause of this achievement. © 2012 Blackwell Publishing Ltd.

The molecular genetic basis of Glanzmann thrombasthenia in the Iraqi-Jewish and Arab populations in Israel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newman, P.J.; Seligsohn, U.; Lyman, S.

1991-04-15

Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by a decrease or absence of functional platelet glycoprotein (GP) IIb-IIIa ({alpha}{sub IIb}{beta}{sub 3}) integrin receptors. Although thrombasthenia is a rare disorder, its occurrence is increased in some regions of the world where intracommunity marriage and consanguinity are commonplace, resulting in increased expression of autosomal recessive traits. The authors have been studying two populations having an unusually high frequency of Glanzmann disease, Iraqi Jews and Arabs living in Israel, and were able to distinguish the populations on the basis of immunodetectable GPIIIa and populations on the basis of immunodetectable GPIIIa andmore » platelet surface vitronectin receptor ({alpha}{sub v}{beta}{sub 3}) expression. In this article, they describe molecular genetic studies based on use of the PCR that have allowed us to characterize platelet mRNA sequences encoding GPIIb and GPIIIa from patients in these populations. These studies demonstrate the heterogeneity of Glanzmann thrombasthenia in different populations, and its homogeneity within geographically restricted populations, and offer insight into the requirements for integrin surface expression.« less

Evaluation and Management of Adolescents with Abnormal Uterine Bleeding.

PubMed

Mullins, Tanya L Kowalczyk; Miller, Rachel J; Mullins, Eric S

2015-09-01

The International Federation of Gynecology and Obstetrics and the American Congress of Obstetricians and Gynecologists support the use of new terminology for abnormal uterine bleeding (AUB) to consistently categorize AUB by etiology. The term AUB can be further classified as AUB/heavy menstrual bleeding (HMB) (replacing the term "menorrhagia") or AUB/intermenstrual bleeding (replacing the term "metrorrhagia"). Although many cases of AUB in adolescent women are attributable to immaturity of the hypothalamic-pituitary-ovarian axis, underlying bleeding disorders should be considered in women with AUB/HMB. This article reviews the new terminology for AUB, discusses important relevant features of history and examination, presents the laboratory evaluation of HMB, and describes hormonal (oral contraceptive pills, progestin-only methods, long-acting reversible contraceptives including intrauterine systems), hematologic (tranexamic acid and desmopressin), and surgical management options for AUB/HMB. Copyright 2015, SLACK Incorporated.

Spontaneous omental bleeding in a 20-year old patient with hemophilia A. A rare cause for emergency laparotomy.

PubMed

Aumann, V; Chiapponi, C; Meyer, F; Wybranski, C; Bruns, C J; Jannasch, O

2016-11-08

Spontaneous intraabdominal hemorrhage is a very rare event even in patients with bleeding disorders like hemophilia. Nevertheless this rare case must be considered in patients with coagulopathies presenting with abdominal pain. Prompt radiologic imaging and surgical consultation are of highest priority. Here we report on a 20-year-old patient with moderate hemophilia A, who underwent emergency laparotomy for a spontaneous idiopathic bleeding of the omentum majus. There are few cases in the literature on this sort of event in patients with hemophilia, who mostly suffer from spontaneous joint bleedings. These patients require an intensive, interdisciplinary perioperative care, involving haematologists, surgeons, radiologists and anesthesists. Finally we discuss, whether an optimized, individually adapted treatment with coagulation factors might possibly have prevented this bleeding event in this patient.

National and international registries of rare bleeding disorders.

PubMed

Peyvandi, Flora; Spreafico, Marta

2008-09-01

Rare bleeding disorders (RBDs) are autosomal recessive disorders, representing 3-5% of all the inherited deficiencies of coagulation factors. Their frequency in the general population ranges from 1:500,000 to 1:2 millions. In countries with a high rate of consanguineous marriages RBDs occur more frequently, representing a significant clinical and social problem. Patients affected by RBDs have a wide spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency to potentially serious or life-threatening haemorrhages. Current treatment is based on both replacement therapy and non-transfusional treatment. However, despite the existence of several concentrates, there is no Factor V concentrate available for the treatment of Factor V deficiency, yet. In 2004, to improve the understanding of RBDs prevalence, diagnosis and treatments, the Rare Bleeding Disorders database (RBDD, www.rbdd.org) was developed. The RBDD project allowed the collection of epidemiological information on 3,230 patients from 66 Centres scattered all over the world. Epidemiological data can also be derived from the annual survey of the World Federation of Hemophilia (www.wfh.org) and from other existing national registries. However, these data are not homogenous and global surveys provide a non-real picture of the distribution of RBDs, as about 50% of data refers to European patients. Hence, we focused on Europe and, thanks to a European project (EN-RBD), we set up a network of 10 Treatment Centres to develop a homogeneous communication tool for inserting, managing and viewing information on RBD patients (www.rbdd.eu). This on-line database resulted to be a powerful tool to improve the quality of data collection. Preliminary results showed that a homogeneous and harmonized data collection using a unique model will help to have more accurate data for statistical analysis.

Hermansky-Pudlak syndrome in a pregnant patient: a case report.

PubMed

Harris-Glocker, Miranda; Thornburg, Loralei L; Pressman, Eva K

2013-01-01

Hermansky-Pudlak syndrome (HPS), a rare autosomal-recessive disorder encompassing multiple organs, is characterized by oculocutaneous albinism, platelet storage pool deficiency resulting in bleeding diathesis, and ceroid lipofuscin deposition which can lead to pulmonary fibrosis, colitis, cardiomyopathy and renal failure. Pregnancy in a patient with HPS can produce multiple complications such as peripartum hemorrhage and difficulties with administration of anesthesia, either regional or general. We present the case of a patient with HPS also complicated by spontaneous triplet pregnancy. A multidisciplinary approach, including the involvement of obstetric, anesthesia, and hematology teams, is the ideal for an HPS patient with the potential for multiple complications in the peripartum period.

Formation of obstructing blood clot in the ureter in a patient with Glanzmann's thrombasthenia.

PubMed

Kilincaslan, Huseyin; Leblebisatan, Goksel; Tepeler, Abdulkadir; Karakus, Suleyman C

2011-12-01

Glanzman thrombasthenia is a rare hematologic disorder characterized by qualitative thrombocyte abnormality. Patients present with episodic mucocutaneous bleeding. Thrombosis is a paradox phenomenon observed in patients with Glanzman thrombasthenia and generally considered as a treatment complication. We present a 16-year-old girl referred for severe flank pain beginning after treatment of hematuria due to Glanzman thrombasthenia. The patient underwent endoscopy for further diagnosis and treatment because of the failure of radiologic evaluation. Although the resolution of the large clots was obtained with streptokinase instillation via the ureteral catheter, clot was mobilized with gentle insertion of ureteral catheter in the present case.

The medical management of abnormal uterine bleeding in reproductive-aged women.

PubMed

Bradley, Linda D; Gueye, Ndeye-Aicha

2016-01-01

In the treatment of women with abnormal uterine bleeding, once a thorough history, physical examination, and indicated imaging studies are performed and all significant structural causes are excluded, medical management is the first-line approach. Determining the acuity of the bleeding, the patient's medical history, assessing risk factors, and establishing a diagnosis will individualize their medical regimen. In acute abnormal uterine bleeding with a normal uterus, parenteral estrogen, a multidose combined oral contraceptive regimen, a multidose progestin-only regimen, and tranexamic acid are all viable options, given the appropriate clinical scenario. Heavy menstrual bleeding can be treated with a levonorgestrel-releasing intrauterine system, combined oral contraceptives, continuous oral progestins, and tranexamic acid with high efficacy. Nonsteroidal antiinflammatory drugs may be utilized with hormonal methods and tranexamic acid to decrease menstrual bleeding. Gonadotropin-releasing hormone agonists are indicated in patients with leiomyoma and abnormal uterine bleeding in preparation for surgical interventions. In women with inherited bleeding disorders all hormonal methods as well as tranexamic acid can be used to treat abnormal uterine bleeding. Women on anticoagulation therapy should consider using progestin-only methods as well as a gonadotropin-releasing hormone agonist to treat their heavy menstrual bleeding. Given these myriad options for medical treatment of abnormal uterine bleeding, many patients may avoid surgical intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of congenital quantitative fibrinogen disorders: a Delphi consensus.

PubMed

Casini, A; de Moerloose, P

2016-11-01

No evidence-based guidelines for the management of patients suffering from afibrinogenaemia and hypofibrinogenaemia are available. The aim of this study was to harmonize patient's care among invited haemophilia experts from Belgium, France and Switzerland. A Delphi-like methodology was used to reach a consensus on: prophylaxis, bleeding, surgery, pregnancy and thrombosis management. The main final statements are as follows: (i) a secondary fibrinogen prophylaxis should be started after a first life-threatening bleeding in patients with afibrinogenaemia; (ii) during prophylaxis the target trough fibrinogen level should be 0.5 g L -1 ; (iii) if an adaptation of dosage is required, the frequency of infusions rather than the fibrinogen amount should be modified; (iv) afibrinogenaemic patients undergoing a surgery at high bleeding risk should receive fibrinogen concentrates regardless of the personal or family history of bleeding; (v) moderate hypofibrinogenaemic patients (i.e. ≥0.5 g L -1 ) without previous bleeding (despite haemostatic challenges) undergoing a surgery at low bleeding risk may not receive fibrinogen concentrates as prophylaxis; (vi) monitoring the trough fibrinogen levels should be performed at least once a month throughout the pregnancy and a foetal growth and placenta development close monitoring by ultrasound is recommended; (vii) fibrinogen replacement should be started concomitantly to the introduction of anticoagulation in afibrinogenaemic patients suffering from a venous thromboembolic event; and (viii) low-molecular-weight heparin is the anticoagulant of choice in case of venous thromboembolism. The results of this initiative should help clinicians in the difficult management of patients with congenital fibrinogen disorders. © 2016 John Wiley & Sons Ltd.

Nonhepatic hyperammonemic encephalopathy due to undiagnosed urea cycle disorder.

PubMed

Mahmood, Tashfeen; Nugent, Kenneth

2015-07-01

Ornithine transcarbamoylase deficiency is the most common inherited urea cycle disorder. In adults, its phenotypes are diverse. In asymptomatic patients with late presentations, symptom onset is often associated with a precipitating factor. We present a case of a woman with urea cycle disorder diagnosed after an acute peptic ulcer bleed and fasting.

Hemophilia Care in the Pediatric Age

PubMed Central

Bertamino, Marta; Riccardi, Francesca; Banov, Laura; Svahn, Johanna; Molinari, Angelo Claudio

2017-01-01

Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures—for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care. PMID:28534860

Labor and delivery in a patient with hemophilia B.

PubMed

Przkora, R; Euliano, T Y; Roussos-Ross, K; Zumberg, M; Robicsek, S A

2011-07-01

Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused. Copyright © 2011 Elsevier Ltd. All rights reserved.

Hematologic Complications of Pregnancy

PubMed Central

Townsley, Danielle M.

2013-01-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

PubMed

Callan, Mary Beth; Haskins, Mark E; Wang, Ping; Zhou, Shangzhen; High, Katherine A; Arruda, Valder R

2016-01-01

Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

Animal Models of Hemophilia

PubMed Central

Sabatino, Denise E.; Nichols, Timothy C.; Merricks, Elizabeth; Bellinger, Dwight A.; Herzog, Roland W.; Monahan, Paul E.

2013-01-01

The X-linked bleeding disorder hemophilia is caused by mutations in coagulation factor VIII (hemophilia A) or factor IX (hemophilia B). Unless prophylactic treatment is provided, patients with severe disease (less than 1% clotting activity) typically experience frequent spontaneous bleeds. Current treatment is largely based on intravenous infusion of recombinant or plasma-derived coagulation factor concentrate. More effective factor products are being developed. Moreover, gene therapies for sustained correction of hemophilia are showing much promise in pre-clinical studies and in clinical trials. These advances in molecular medicine heavily depend on availability of well-characterized small and large animal models of hemophilia, primarily hemophilia mice and dogs. Experiments in these animals represent important early and intermediate steps of translational research aimed at development of better and safer treatments for hemophilia, such a protein and gene therapies or immune tolerance protocols. While murine models are excellent for studies of large groups of animals using genetically defined strains, canine models are important for testing scale-up and for longer-term follow-up as well as for studies that require larger blood volumes. PMID:22137432

Low-level light treatment ameliorates immune thrombocytopenia

PubMed Central

Yang, Jingke; Zhang, Qi; Li, Peiyu; Dong, Tingting; Wu, Mei X.

2016-01-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP. PMID:27901126

Low-level light treatment ameliorates immune thrombocytopenia

NASA Astrophysics Data System (ADS)

Yang, Jingke; Zhang, Qi; Wu, Mei X.

2017-02-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Massive oral bleeding after full-mouth extraction in a patient with B-cell lymphocytic leukemia/small lymphocytic lymphoma reversed with recombinant activated factor VII.

PubMed

Sprenker, Collin; Omar, Hesham R; Powless, R Andrew; Mangar, Devanand; Camporesi, Enrico

2016-02-01

Full-mouth extraction can be associated with intraoral bleeding, which usually is controlled with local hemostatic measures. Recombinant activated factor VII (rFVIIa) occasionally is used to stop bleeding in a variety of off-label indications, with the main argument curtailing its use being thrombotic events. The authors describe the use of rFVIIa for bleeding after full-mouth extraction in a patient with undiagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. A 72-year-old man underwent full-mouth extraction (18 teeth). The next day, the patient experienced massive oral bleeding. The authors administered tranexamic acid, aminocaproic acid, and a total of 12 units of packed red blood cells in addition to local hemostatic measures without control of bleeding. On postoperative day 10, the authors administered 5,000 micrograms of rFVIIa, and within 2 hours oral the bleeding ceased. The authors performed flow cytometry and diagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. Unexplained massive oral bleeding despite adequate local hemostatic measures should prompt further investigations for underlying bleeding or coagulation disorders. The authors describe the successful use of rFVIIa in massive oral bleeding. Further studies are mandatory to study the effectiveness of this drug for this off-label indication. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

[Vitamin K antagonists overdose].

PubMed

Groszek, Barbara; Piszczek, Paweł

2015-01-01

Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed with a malignant disease. Two patients died, the other has been improving and anticoagulant therapy with VKA was continued, in 4 VKA were changed to low-molecular-weight heparin, and on 4 commissioned new generation anticoagulant (rivaroxaban).

Atraumatic haemarthrosis following total knee replacement treated with selective embolisation.

PubMed

Karataglis, Dimitrios; Marlow, Duncan; Learmonth, Duncan J A

2006-06-01

Spontaneous haemarthrosis in the absence of anticoagulant medication or a bleeding disorder is a very rare complication after total knee arthroplasty. A case of recurrent spontaneous haemarthrosis following total knee replacement in a 69-year-old patient is reported. Angiography was used to aid the diagnosis. It demonstrated an abnormal blush of vessels around the anterior aspect of the knee joint, that was fed by genicular branches and a recurrent branch of the anterior tibial artery. Selective embolisation of the bleeding vessels with coils led to immediate control of the bleeding. No further recurrence of haemarthrosis has been recorded.

A bleeding assessment tool correlates with intraoperative blood loss in children and adolescents undergoing major spinal surgery.

PubMed

Anadio, Jennifer M; Sturm, Peter F; Forslund, Johan M; Agarwal, Sunil; Lane, Adam; Tarango, Cristina; Palumbo, Joseph S

2017-04-01

Screening laboratory studies for bleeding disorders are of little predictive value for operative bleeding risk in adults. Predicting perioperative bleeding in pediatric patients is particularly difficult as younger patients often have not had significant hemostatic challenges. This issue is distinctly important for high bleeding risk surgeries, such as major spinal procedures. The aim of this study was to determine if the score of a detailed bleeding questionnaire (BQ) correlated with surgical bleeding in pediatric patients undergoing major spinal surgery. A total of 220 consecutive pediatric patients (mean age 14.2years) undergoing major spinal surgery were administered the BQ preoperatively, as well as having routine screening laboratory studies (i.e., PT, aPTT, PFA) drawn. A retrospective analysis was conducted to determine if there was a correlation between either the results of the BQ and/or laboratory studies with operative outcomes. A BQ score>2 showed a strong positive correlation with intraoperative bleeding based on both univariate and multivariate analyses. In contrast, abnormalities in screening laboratory studies showed no significant correlation with operative bleeding outcomes. Relying on screening laboratory studies alone is inadequate. The BQ used here correlated with increased intraoperative hemorrhage, suggesting this tool may be useful for assessing pediatric surgical bleeding risk, and may also be useful in identifying a subset of patients with a very low bleeding risk that may not require laboratory screening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders.

PubMed

Malouf, Reem; Ashraf, Asma; Hadjinicolaou, Andreas V; Doree, Carolyn; Hopewell, Sally; Estcourt, Lise J

2018-05-14

Bone marrow disorders encompass a group of diseases characterised by reduced production of red cells, white cells, and platelets, or defects in their function, or both. The most common bone marrow disorder is myelodysplastic syndrome. Thrombocytopenia, a low platelet count, commonly occurs in people with bone marrow failure. Platetet transfusions are routinely used in people with thrombocytopenia secondary to bone marrow failure disorders to treat or prevent bleeding. Myelodysplastic syndrome is currently the most common reason for receiving a platelet transfusion in some Western countries. To determine whether a therapeutic-only platelet transfusion policy (transfusion given when patient is bleeding) is as effective and safe as a prophylactic platelet transfusion policy (transfusion given to prevent bleeding according to a prespecified platelet threshold) in people with congenital or acquired bone marrow failure disorders. We searched for randomised controlled trials (RCTs), non-RCTs, and controlled before-after studies (CBAs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2017, Issue 9), Ovid MEDLINE (from 1946), Ovid Embase (from 1974), PubMed (e-publications only), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 12 October 2017. We included RCTs, non-RCTs, and CBAs that involved the transfusion of platelet concentrates (prepared either from individual units of whole blood or by apheresis any dose, frequency, or transfusion trigger) and given to treat or prevent bleeding among people with congenital or acquired bone marrow failure disorders.We excluded uncontrolled studies, cross-sectional studies, and case-control studies. We excluded cluster-RCTs, non-randomised cluster trials, and CBAs with fewer than two intervention sites and two control sites due to the risk of confounding. We included all people with long-term bone marrow failure disorders that require platelet transfusions, including neonates. We excluded studies of alternatives to platelet transfusion, or studies of people receiving intensive chemotherapy or a stem cell transplant. We used the standard methodological procedures outlined by Cochrane. Due to the absence of evidence we were unable to report on any of the review outcomes. We identified one RCT that met the inclusion criteria for this review. The study enrolled only nine adults with MDS over a three-year study duration period. The trial was terminated due to poor recruitment rate (planned recruitment 60 participants over two years). Assessment of the risk of bias was not possible for all domains. The trial was a single-centre, single-blind trial. The clinical and demographic characteristics of the participants were never disclosed. The trial outcomes relevant to this review were bleeding assessments, mortality, quality of life, and length of hospital stay, but no data were available to report on any of these outcomes.We identified no completed non-RCTs or CBAs.We identified no ongoing RCTs, non-RCTs, or CBAs. We found no evidence to determine the safety and efficacy of therapeutic platelet transfusion compared with prophylactic platelet transfusion for people with long-term bone marrow failure disorders. This review underscores the urgency of prioritising research in this area. People with bone marrow failure depend on long-term platelet transfusion support, but the only trial that assessed a therapeutic strategy was halted. There is a need for good-quality studies comparing a therapeutic platelet transfusion strategy with a prophylactic platelet transfusion strategy; such trials should include outcomes that are important to patients, such as quality of life, length of hospital admission, and risk of bleeding.

Patterns and predictors of vaginal bleeding in the first trimester of pregnancy

PubMed Central

Hasan, Reem; Baird, Donna D.; Herring, Amy H.; Olshan, Andrew F.; Jonsson Funk, Michele L.; Hartmann, Katherine E.

2010-01-01

Purpose Although first-trimester vaginal bleeding is an alarming symptom, few studies have investigated the prevalence and predictors of early bleeding. This study characterizes first trimester bleeding, setting aside bleeding that occurs at time of miscarriage. Methods Participants (n=4539) were women ages 18–45 enrolled in Right From the Start, a community-based pregnancy study (2000–2008). Bleeding information included timing, heaviness, duration, color, and associated pain, as well as recurrence risk in subsequent pregnancies. Life table analyses were used to describe gestational timing of bleeding. Factors associated with bleeding were investigated using multiple logistic regression, with multiple imputation for missing data. Results Approximately one-fourth of participants (n=1207) reported bleeding (n=1656 episodes), but only 8% of women with bleeding reported heavy bleeding. Of the spotting and light bleeding episodes (n=1555), 28% were associated with pain. Among heavy episodes (n=100), 54% were associated with pain. Most episodes lasted less than 3 days, and most occurred between gestational weeks 5–8. Twelve percent of women with bleeding and 13% of those without experienced miscarriage. Maternal characteristics associated with bleeding included fibroids and prior miscarriage. Conclusions Consistent with the hypothesis that bleeding is a marker for placental dysfunction, bleeding is most likely to be seen around the time of the luteal-placental shift. PMID:20538195

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications

PubMed Central

Koltai, Katalin; Kesmarky, Gabor; Feher, Gergely; Tibold, Antal

2017-01-01

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing. PMID:28820484

Rare platelet GPCR variants: what can we learn?

PubMed

Nisar, S P; Jones, M L; Cunningham, M R; Mumford, A D; Mundell, S J

2015-07-01

Platelet-expressed GPCRs are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side effects. In order to optimize the use of existing anti-platelet drugs and to develop new therapies, more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review, we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic and thromboxane A2 receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders. © 2014 The British Pharmacological Society.

Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

PubMed

van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

2015-12-24

Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched PubMed, Embase and The Cochrane Library. Additional searches were performed in ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP).Date of last search of the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register: 14 December 2015. Randomised and quasi-randomised controlled trials in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures using antifibrinolytic agents (tranexamic acid or epsilon aminocaproic acid) to prevent perioperative bleeding compared to no intervention or usual care with or without placebo. Two authors independently screened the titles and abstracts of all identified articles. Full texts were obtained for potentially relevant abstracts and two authors independently assessed these for inclusion based on the selection criteria. A third author verified trial eligibility. Two authors independently performed data extraction and risk of bias assessments using standardized forms. While there were no eligible trials in people with Von Willebrand disease identified, two randomised, double-blind, placebo-controlled trials (total of 59 participants) in people with haemophilia undergoing dental extraction were included. One trial of tranexamic acid published in 1972 included 28 participants with mild, moderate or severe haemophilia A and B and one of epsilon aminocaproic acid published in 1971 included 31 people with haemophilia with factor VIII or factor IX levels less than 15%. Overall, the two included trials showed a beneficial effect of tranexamic acid and EACA, administered systemically, in reducing the number of bleedings, the amount of blood loss and the need for therapeutic clotting factor concentrates. Regarding postoperative bleeding, the tranexamic acid trial showed a risk difference of -0.64 (95% confidence interval -0.93 to - 0.36) and the EACA trial a risk difference of -0.50 (95% confidence interval 0.77 to -0.22). The combined risk difference of both trials was -0.57 (95% confidence interval -0.76 to -0.37), with the quality of the evidence (GRADE) for this outcome is rated as moderate. Side effects occurred once and required stopping epsilon aminocaproic acid (combined risk difference of -0.03 (95% CI -0.08 to 0.13). There was heterogeneity between the two trials regarding the proportion of people with severe haemophilia included, the concomitant standard therapy and fibrinolytic agent treatment regimens used. We cannot exclude that a selection bias has occurred in the epsilon aminocaproic acid trial, but overall the risk of bias appeared to be low for both trials. Despite the discovery of a beneficial effect of systemically administered tranexamic acid and epsilon aminocaproic acid in preventing postoperative bleeding in people with haemophilia undergoing dental extraction, the limited number of randomised controlled trials identified, in combination with the small sample sizes and heterogeneity regarding standard therapy and treatment regimens between the two trials, do not allow us to conclude definite efficacy of antifibrinolytic therapy in oral or dental procedures in people with haemophilia. No trials were identified in people with Von Willebrand disease.

Granulocytes and Vascularization Regulate Uterine Bleeding and Tissue Remodeling in a Mouse Menstruation Model

PubMed Central

Menning, Astrid; Walter, Alexander; Rudolph, Marion; Gashaw, Isabella; Fritzemeier, Karl-Heinrich; Roese, Lars

2012-01-01

Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery. PMID:22879894

Serendipitous Discovery of Factor VII Deficiency and the Ensuing Dilemma.

PubMed

Umakanthan, Jayadev M; Dhakal, Prajwal; Gundabolu, Krishna; Koepsell, Scott A; Baljevic, Muhamed

2018-03-01

Congenital factor VII deficiency is a challenging disorder to manage, as it is associated with varied genotypes that do not clinically correlate with a bleeding phenotype. Individuals with severe factor VII deficiency (FVII: c <1%) might be asymptomatic, while patients with moderate deficiency (FVII: c level >5%) may experience severe hemorrhages. In modern medicine, due to extensive routine pre-operative laboratory testing, clinically asymptomatic patients without any bleeding history might be incidentally discovered, raising clinical dilemmas. Careful consideration of bleeding versus thrombosis risk has to be made in such cases, especially in the elderly. Clinical history of no prior bleeding complications may be a reassuring factor. Minimal required replacement dosing of recombinant activated factor VII can be given peri-operatively in such situations, with close monitoring.

Abnormal uterine bleeding unrelated to structural uterine abnormalities: management in the perimenopausal period.

PubMed

Sabbioni, Lorenzo; Zanetti, Isabella; Orlandini, Cinzia; Petraglia, Felice; Luisi, Stefano

2017-02-01

Abnormal uterine bleeding (AUB) is one of the commonest health problems encountered by women and a frequent phenomenon during menopausal transition. The clinical management of AUB must follow a standardized classification system to obtain the better diagnostic pathway and the optimal therapy. The PALM-COEIN classification system has been approved by the International Federation of Gynecology and Obstetrics (FIGO); it recognizes structural causes of AUB, which can be measured visually with imaging techniques or histopathology, and non-structural entities such as coagulopathies, ovulatory dysfunctions, endometrial and iatrogenic causes and disorders not yet classified. In this review we aim to evaluate the management of nonstructural causes of AUB during the menopausal transition, when commonly women experience changes in menstrual bleeding patterns and unexpected bleedings which affect their quality of life.

Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.

PubMed

Badin, M S; Graf, L; Iyer, J K; Moffat, K A; Seecharan, J L; Hayward, C P M

2016-12-01

Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. © 2016 John Wiley & Sons Ltd.

Noncirrhotic Portal Hypertension

PubMed Central

Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

2011-01-01

Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

Emergency department care for patients with hemophilia and von Willebrand disease.

PubMed

Singleton, Tammuella; Kruse-Jarres, Rebecca; Leissinger, Cindy

2010-08-01

Patients with bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease (VWD) are routinely treated at home, with their care managed in specialized centers. In emergency situations, these patients often present to their local emergency department (ED), where their management can represent a challenge to the emergency physicians and staff who rarely encounter them. Delays in diagnosis and administration of replacement therapy are the factors most commonly identified as predictive of death. Patients and family members are often very well educated in the disease and its management, which can significantly reduce morbidity and mortality. Children with bleeding disorders confer different challenges to the emergency physician and staff: they may present with no obvious signs of trauma or they may present with bruises consistent with non-accidental injury. All possible causes of bruising/bleeding should be investigated, although treatment should be administered promptly. The initial presentation of a bleeding disorder in the pediatric population is often made in the ED. Treatment of hemophilia A and B requires rapid replacement of the deficient clotting factor, with the desired factor level and dosage dependent on the product used and the hemorrhagic situation encountered. In patients with VWD, the main treatments are desmopressin or intravenous infusion of plasma-derived concentrates containing factor VIII and von Willebrand factor. The aim of this review is to outline some of the issues facing emergency physicians and the options available for the treatment of patients with hemophilia A, hemophilia B, and VWD. Copyright 2010. Published by Elsevier Inc.

Increased Plasma Clot Permeability and Susceptibility to Lysis Are Associated with Heavy Menstrual Bleeding of Unknown Cause: A Case-Control Study

PubMed Central

Szczepaniak, Piotr; Zabczyk, Michał; Undas, Anetta

2015-01-01

Background Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders. Objectives We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB). Methods We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured. Results Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7–18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 – -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 – -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 – -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 – -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 – -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB. Conclusions Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin. PMID:25909989

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

PubMed

Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

2012-07-05

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

PubMed

Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

2017-08-01

To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Acquired hemophilia A: a review of recent data and new therapeutic options.

PubMed

Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

2017-10-01

Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

[TREATMENT DILEMMAS IN BEHÇET'S SYNDROME].

PubMed

Zeller, Lior; Ling, Edoard; Abu-Shakra, Mahmoud

2016-02-01

Behçet's disease is an inflammatory systemic disorder, characterized by a relapsing and remitting course, it manifests with oral and genital ulcerations, skin lesions, uveitis, vasculitis, central nervous system and gastrointestinal involvement. The main histopathological finding is widespread vasculitis of the arteries and veins. Therapy is variable and depends largely on the severity of the disease and organ involvement. There is common practice to treat with anticoagulation in patients suffering from vessel thrombosis, but there are no control trials to support this tendency. Anticoagulation treatment can cause major bleeding events in patients suffering from aneurysms. In this case report we describe a treatment dilemma in a patient suffering from deep vein thrombosis and pulmonary aneurysms.

The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them?

PubMed

Munro, Malcolm G; Critchley, Hilary O D; Fraser, Ian S

2012-10-01

In November 2010, the International Federation of Gynecology and Obstetrics formally accepted a new classification system for causes of abnormal uterine bleeding in the reproductive years. The system, based on the acronym PALM-COEIN (polyps, adenomyosis, leiomyoma, malignancy and hyperplasia-coagulopathy, ovulatory disorders, endometrial causes, iatrogenic, not classified) was developed in response to concerns about the design and interpretation of basic science and clinical investigation that relates to the problem of abnormal uterine bleeding. A system of nomenclature for the description of normal uterine bleeding and the various symptoms that comprise abnormal bleeding has also been included. This article describes the rationale, the structured methods that involved stakeholders worldwide, and the suggested use of the International Federation of Gynecology and Obstetrics system for research, education, and clinical care. Investigators in the field are encouraged to use the system in the design of their abnormal uterine bleeding-related research because it is an approach that should improve our understanding and management of this often perplexing clinical condition. Copyright © 2012. Published by Mosby, Inc.

Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

PubMed

Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

2013-03-01

Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

PubMed Central

Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-01-01

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

[Haemothorax after blunt thoracic trauma].

PubMed

Siller, J; Havlícek, K

2009-05-01

Haemothorax is frequent consequence of blunt and penetrating thoracic trauma and is usually associated with pneumothorax. The occurence of haemothorax in blunt thoracic trauma patients is estimated between 25-75%. The reason of bleeding is impairment of intercostal arteries or lung parenchyma after trauma of the ribs. Uncontrolled bleeding is the main cause of the death. The article is focused on the treatment of this injury. There were enrolled 238 patients with thoracic trauma, who were admitted into our department, into the study. The average age of the patients was 42.5 years. The ISS > or = 16 were in 101 patients. Forty two patients were artefitially ventilated. Conservative treatment prevails, almost in 65%. Special care was indicated in patients with haemothorax (fluidotoraxem). Clinically and based on other screening methods the presence of the fluid in thoracic cavity was in 131 patients. Surgical treatment (punction, drainage, videothoracoscopy and thoracotomy) was necessary in 47 (35.0%). Thoracotomy for the bleeding was indicated in seven cases (5.3 %). In diagnostics and in treatment of the bleeding in thoracic trauma patients the most important factor is clinical status of the patient. Indication for thoracotomy must be unambigous. Massive haemotorax leads to restrictive ventilation disorder with decreased preload and can be activator of the haemocolaguation disorders. This fact decreases chance for the survival of the patient.

Anorectal emergencies.

PubMed

Lohsiriwat, Varut

2016-07-14

Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up.

Etiology and Outcome of Acute Gastrointestinal Bleeding in Iran:A Review Article

PubMed Central

Masoodi, Mohsen; Saberifiroozi, Mehdi

2012-01-01

Upper gastrointestinal bleeding (UGIB) is defined as bleeding that results from lesions located above the ligament of Treitz and is a common cause for emergency hospital admissions in patients with gastrointestinal disorders. UGIB also increases the risk of morbidity and mortality in patients already hospitalized for other reasons. According to epidemiological surveys of acute UGIB in Iran, peptic ulcer is the most common endoscopic diagnosis. Gastric and duodenal erosion accounts for 16.4%-25% of etiologies. Other relatively common causes of UGIB are variceal hemorrhage, Mallory-Weiss tears, and arterial and venous malformations. However, in 9%-13.3% of patients, the endoscopy is normal. PMID:24829656

Hematologic complications of pregnancy.

PubMed

Townsley, Danielle M

2013-07-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. Published by Elsevier Inc.

Clinical and laboratory diagnosis of von Willebrand disease: A synopsis of the 2008 NHLBI/NIH guidelines

PubMed Central

Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

2017-01-01

Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects males and females, and reflects deficiency or defects of VWF that may also cause decreased FVIII. It may also occur less commonly as an acquired disorder (acquired von Willebrand syndrome). This article briefly summarizes selected features of the March 2008 evidence-based clinical and laboratory diagnostic recommendations from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel for assessment for VWD or other bleeding disorders or risks. Management of VWD is also addressed in the NHLBI guidelines, but is not summarized here. The VWD guidelines are available at the NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd). PMID:19415721

Ileal polypoid lymphangiectasia bleeding diagnosed and treated by double balloon enteroscopy

PubMed Central

Park, Min Seon; Lee, Beom Jae; Gu, Dae Hoe; Pyo, Jeung-Hui; Kim, Kyeong Jin; Lee, Yun Ho; Joo, Moon Kyung; Park, Jong-Jae; Kim, Jae Seon; Bak, Young-Tae

2013-01-01

Intestinal lymphangiectasia is a rare disease characterized by focal or diffuse dilated enteric lymphatics with impaired lymph drainage. It causes protein-losing enteropathy and may lead to gastrointestinal bleeding. Commonly, lymphangiectasia presents as whitish spots or specks. To our knowledge, small bowel bleeding resulting from polypoid intestinal lymphangiectasia has not been reported. Here, we report a rare case of active bleeding from the small bowel caused by polypoid lymphangiectasia with a review of the relevant literature. An 80-year-old woman was hospitalized for melena. Esophagogastroduodenoscopy could not identify the source of bleeding. Subsequent colonoscopy showed fresh bloody material gushing from the small bowel. An abdominal-pelvic contrast-enhanced computed tomography scan did not reveal any abnormal findings. Video capsule endoscopy showed evidence of active and recent bleeding in the ileum. To localize the bleeding site, we performed double balloon enteroscopy by the anal approach. A small, bleeding, polypoid lesion was found in the distal ileum and was successfully removed using endoscopic snare electrocautery. PMID:24363538

Bleeding symptoms and laboratory correlation in patients with severe von Willebrand disease.

PubMed

Metjian, A D; Wang, C; Sood, S L; Cuker, A; Peterson, S M; Soucie, J M; Konkle, B A

2009-07-01

Type 3 von Willebrand disease (VWD) is a rare bleeding disorder with markedly decreased or absent von Willebrand factor (VWF) protein, accompanied by a parallel decrease in VWF function and factor VIII (FVIII) activity. The goal of this study was to describe the population of patients enrolled in the USA Centers for Disease Control Universal Data Collection (UDC) study with type 3 VWD, defined as a VWF:Ag of <10%, and to correlate bleeding symptoms with VWF and FVIII levels. Data on 150 patients were analysed. Almost all patients experienced bleeding episodes (98%) and required blood and/or factor product treatment (92%). While oral mucosal bleeding (the site of first bleed in 54%) was most common, subsequent muscle and joint bleeds were also seen (28%, 45%, respectively), and intracranial haemorrhage occurred in 8% of individuals. Mean age of first bleed was lower in those with either a FVIII < or =5% or a VWF:Ag <1%. Univariate marginal model analysis showed lower levels of FVIII and VWF:Ag both predicted a higher risk of joint bleeding. Longitudinal multivariate analysis found a lower FVIII level (P = 0.03), increasing age (P < 0.0001), history of joint bleeding (P = 0.001), higher body mass index (BMI) (P < 0.0001), and use of home infusion (P = 0.02) were all negatively associated with joint mobility. Low levels of VWF:Ag (P = 0.003) and male sex (P = 0.007) were also negatively associated with joint function. This study documents the strong bleeding phenotype in severe VWD and provides data to help target therapy, including prophylaxis, for patients most at risk of bleeding complications.

Laboratory hemostasis: from biology to the bench.

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J

2018-06-27

Physiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops. The activation and amplification of the coagulation cascade is finely modulated by the activity of several physiological inhibitors. Once bleeding has been efficiently stopped by blood clot formation, dissolution of the thrombus is essential to restore vessel permeability. This process, known as fibrinolysis, also develops through coordinate action of a vast array of proteins and enzymes. An accurate diagnosis of hemostasis disturbance entails a multifaceted approach, encompassing family and personal history of hemostatic disorders, accurate collection of clinical signs and symptoms, integrated with laboratory hemostasis testing. Regarding laboratory testing, a reasonable approach entails classifying hemostasis testing according to cost, complexity and available clinical information. Laboratory workout may hence initiate with some rapid and inexpensive "screening" tests, characterized by high negative predictive value, then followed by second- or third-line analyses, specifically aimed to clarify the nature and severity of bleeding or thrombotic phenotype. This article aims to provide a general overview of the hemostatic process, and to provide some general suggestions to optimally facilitate laboratory hemostasis testing.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

Questioning our Questions: Do frequently asked questions adequately cover the aspects of women's lives most affected by abnormal uterine bleeding? Opinions of women with abnormal uterine bleeding participating in focus group discussions

PubMed Central

Matteson, Kristen A.; Clark, Melissa A.

2010-01-01

Objectives: (1) To explore the effects on women's lives by heavy or irregular menstrual bleeding; (2) To examine whether aspects of women's lives most affected by heavy or irregular menstrual bleeding were adequately addressed by questions that are frequently used in clinical encounters and available questionnaires. Methods: We conducted four focus group sessions with a total of 25 English-speaking women who had reported abnormal uterine bleeding. Discussions included open-ended questions that pertained to bleeding, aspects of life affected by bleeding, and questions frequently used in clinical settings about bleeding and quality of life. Results: We identified five themes that reflected how women's lives were affected by heavy or irregular menstrual bleeding: irritation/inconvenience, bleeding-associated pain, self-consciousness about odor, social embarrassment, and ritual like behavior. Although women responded that the frequently used questions about bleeding and quality of life were important, they felt that the questions failed to go into enough depth to adequately characterize their experiences. Conclusions: Based on the themes identified in our focus group sessions, clinicians and researchers may need to change the questions used to capture “patient experience” with abnormal uterine bleeding more accurately. PMID:20437305

Protein Replacement Therapy and Gene Transfer in Canine Models of Hemophilia A, Hemophilia B, von Willebrand Disease, and Factor VII Deficiency

PubMed Central

Nichols, Timothy C.; Dillow, Aaron M.; Franck, Helen W.G.; Merricks, Elizabeth P.; Raymer, Robin A.; Bellinger, Dwight A.; Arruda, Valder R.; High, Katherine A.

2011-01-01

Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders. PMID:19293459

Congenital spherocytic anemia

MedlinePlus

... cells and bleeding disorders. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: ... Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by ...

Pharmacologic Agents in the Management of Bleeding Disorders

DTIC Science & Technology

1990-01-01

and the antifibrinolytic drugs tranexamic acid in preinfusion plasma,2 2 increase platelet adheience.23 (AMCA) and epsilon- aminocaproic acid (EACA...215-9. aminocaproic acid in the treatment of patients with acute pro- 54. Schulman S, Johnsson H, Egberg N, Blomback M. DDAVP- myclocytie leukemia and...shortens the bleeding time in storage pool 79. Gardner Fli, Helmer RE Ill. Aminocaproic acid . Use in control deficiency. Ann Intern Med 1988;108:65-7. of

The experience of girls and young women with inherited bleeding disorders.

PubMed

Khair, K; Holland, M; Pollard, D

2013-09-01

Haemophilia carriers and women with inherited bleeding disorders (IBD) experience menorrhagia, bleed following dentistry, surgery, injury or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis. We explored the experiences of girls and young women (aged 9-34 years) with IBD by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young women with IBD who are managed at haemophilia centres receive appropriate care and feel well supported. Although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources. Most of those who responded to our survey are confident in their lives, able to manage their IBD and take pragmatic views towards the inherited nature of their condition. But there is a substantial subgroup of women who experience stigmatization, isolation and bullying and express concerns relating to fertility and conception. Overall, this cohort would benefit from opportunities for mutual support. This could be via Internet-based social networking and may be of particular value to those who are unable to seek help from traditional medical services due to religious or other cultural barriers. © 2013 John Wiley & Sons Ltd.

Both hemophilia health care providers and hemophilia a carriers report that carriers have excessive bleeding.

PubMed

Paroskie, Allison; Oso, Olatunde; Almassi, Benjamin; DeBaun, Michael R; Sidonio, Robert F

2014-05-01

Hemophilia A, the result of reduced factor VIII activity, is an X-linked recessive bleeding disorder. Previous reports of hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey were used as preliminary data for an ongoing prospective study. An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers, and hemophilia A carriers who were members of Hemophilia Federation of America. The questions focused on the clinical understanding of bleeding symptoms and management of hemophilia A carriers, and the timing and intensity of carrier testing. Our survey indicates that 51% (36/51) of providers compared with 78% (36/46) of carriers believe that hemophilia A carriers with normal factor VIII activity have an increased bleeding tendency (P<0.001); 72% (33/36) of hemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of hemophilia A carriers prefer testing to be done before this age (P<0.001). Hemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status.

Haemoglobin responses to transfusion in severe iron deficiency anaemia: potential impact of gastrointestinal disorders.

PubMed

Bosch, X; Montori, E; Guerra-García, M; Costa-Rodríguez, J; Quintanilla, M H; Tolosa-Chapasian, P E; Moreno, P; Guasch, N; López-Soto, A

2017-04-01

Red blood cell (RBC) transfusion may be justified in iron deficiency anaemia (IDA) when an increase in oxygen delivery is needed, as sometimes occurs in subjects with haemoglobin <8·0 mg/dL, serious comorbidities or at risk of cardiovascular instability. Earlier investigations showed that some patients with severe IDA requiring transfusion had lower than expected post-transfusion haemoglobin levels with poorer clinical outcomes than other patients. After hypothesizing that haemoglobin responses to transfusion were different and that the underlying gastrointestinal (GI) disorders causing IDA could be a confounder explaining this association, these responses were analysed in a prospective cohort of IDA adults referred for outpatient GI investigation. Transfused patients with proven IDA, baseline haemoglobin at referral <9·0 g/dL and no extraintestinal bleeding were eligible. To assess a homogeneous population, only GI disorders known to cause occult bleeding were considered. Haemoglobin increments per 100 mL of RBCs were investigated. In total, 2818 patients were enrolled over 10·5 years. On multivariable regression, diffuse angiodysplasias and GI cancer independently predicted for reduced increments in post-transfusion haemoglobin [adjusted regression coefficients: -0·082 (95% confidence interval, -0·093 to -0·072) and -0·073 (95% confidence interval, -0·081 to -0·066), respectively, P < 0·001 in both]. Haemoglobin responses in the remaining bleeding disorders were adequate and agreed with the principle that one RBC unit increases the haemoglobin an average of 1 g/dL. The potential differential impact of GI disorders on changes in haemoglobin levels after RBC transfusion could be useful for transfusing physicians, especially for diagnostic purposes. © 2017 International Society of Blood Transfusion.

Bleeding Disorders in Women

MedlinePlus

... Emergency Preparedness & Response Environmental Health Healthy Living Injury, Violence & Safety Life Stages & Populations Travelers’ Health Workplace Safety & Health Features Media Sign up for Features Get Email Updates To ...

Treatment tailoring for factor V deficient patients and perioperative management using global hemostatic coagulation assays.

PubMed

Levy-Mendelovich, Sarina; Barg, Assaf Arie; Rosenberg, Nurit; Avishai, Einat; Luboshitz, Jacob; Misgav, Mudi; Kenet, Gili; Livnat, Tami

2018-07-01

Congenital factor V deficiency (FVD) is a rare bleeding disorder with an estimated incidence of 1 in 1000,000 in the general population. Since the common coagulation tests do not correlate with the bleeding tendency there is an unmet need to predict FVD patients' bleeding hazard prior to surgical interventions. To optimize treatment prior to surgical interventions, using global coagulation assays, thrombin generation (TG) and rotating thromboelastogram (ROTEM). Our cohort included 5 patients with FVD, 4 severe and one mild. Two of them underwent TG and ROTEM prior to surgical interventions, including ex vivo spiking assays using bypass agents and platelets spiking. All five patients exhibited prolonged PT and PTT, non-dependent on their bleeding tendency. Patient 1, who demonstrated severe bleeding phenotype, underwent surgery treated by combination of APCC (FEIBA) and platelet transfusion. Therapy was guided by global tests (TG as well as ROTEM) results. During the pre and post-operative period neither excessive bleeding nor any thrombosis was noted. In contrast, TG and ROTEM analysis of patient 4 has lead us to perform the surgery without any blood products' support. Indeed, the patient did not encounter any bleeding. Global coagulation assays may be useful ancillary tools guiding treatment decisions in FVD patients undergoing surgical procedures. Copyright © 2018 Elsevier Inc. All rights reserved.

Translational Data from Adeno-Associated Virus-Mediated Gene Therapy of Hemophilia B in Dogs

PubMed Central

Whitford, Margaret H.; Arruda, Valder R.; Stedman, Hansell H.; Kay, Mark A.; High, Katherine A.

2015-01-01

Abstract Preclinical testing of new therapeutic strategies in relevant animal models is an essential part of drug development. The choice of animal models of disease that are used in these studies is driven by the strength of the translational data for informing about safety, efficacy, and success or failure of human clinical trials. Hemophilia B is a monogenic, X-linked, inherited bleeding disorder that results from absent or dysfunctional coagulation factor IX (FIX). Regarding preclinical studies of adeno-associated virus (AAV)-mediated gene therapy for hemophilia B, dogs with severe hemophilia B (<1% FIX) provide well-characterized phenotypes and genotypes in which a species-specific transgene can be expressed in a mixed genetic background. Correction of the hemophilic coagulopathy by sustained expression of FIX, reduction of bleeding events, and a comprehensive assessment of the humoral and cell-mediated immune responses to the expressed transgene and recombinant AAV vector are all feasible end points in these dogs. This review compares the preclinical studies of AAV vectors used to treat dogs with hemophilia B with the results obtained in subsequent human clinical trials using muscle- and liver-based approaches. PMID:25675273

Translational data from adeno-associated virus-mediated gene therapy of hemophilia B in dogs.

PubMed

Nichols, Timothy C; Whitford, Margaret H; Arruda, Valder R; Stedman, Hansell H; Kay, Mark A; High, Katherine A

2015-03-01

Preclinical testing of new therapeutic strategies in relevant animal models is an essential part of drug development. The choice of animal models of disease that are used in these studies is driven by the strength of the translational data for informing about safety, efficacy, and success or failure of human clinical trials. Hemophilia B is a monogenic, X-linked, inherited bleeding disorder that results from absent or dysfunctional coagulation factor IX (FIX). Regarding preclinical studies of adeno-associated virus (AAV)-mediated gene therapy for hemophilia B, dogs with severe hemophilia B (<1% FIX) provide well-characterized phenotypes and genotypes in which a species-specific transgene can be expressed in a mixed genetic background. Correction of the hemophilic coagulopathy by sustained expression of FIX, reduction of bleeding events, and a comprehensive assessment of the humoral and cell-mediated immune responses to the expressed transgene and recombinant AAV vector are all feasible end points in these dogs. This review compares the preclinical studies of AAV vectors used to treat dogs with hemophilia B with the results obtained in subsequent human clinical trials using muscle- and liver-based approaches.

Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs

PubMed Central

Callan, Mary Beth; Haskins, Mark E.; Wang, Ping; Zhou, Shangzhen; High, Katherine A.; Arruda, Valder R.

2016-01-01

Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1–2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs. PMID:27011017

A 10-year delayed diagnosis of blue rubber bleb nevus syndrome characterized by refractory iron-deficiency anemia: A case report and literature review.

PubMed

Tang, Xue; Gao, Ju; Yang, Xue; Guo, Xia

2018-06-01

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular disorder consisting of multifocal venous malformations. Delayed diagnosis or misdiagnosis frequently occurs in patients without typical cutaneous lesions or gastrointestinal bleeding symptoms. This article reports a 10-year case of delayed diagnosis of BRBNS detected by capsule endoscopy. A 15-year-old girl presented with refractory iron-deficiency anemia (IDA) for 10 years, without any hemorrhagic signs or noticeable cutaneous lesions, which led to her obvious physical growth retardation. Capsule endoscopic examination revealed dozens of vascular blebs distributed from the jejunum to the ileum and a site of active bleeding. Hence, she was diagnosed with BRBNS. Laparotomy was performed with resection of the small bowel lesions, and iron supplementation was prescribed for 3 months. Postoperatively, the patient had an uncomplicated course. On follow-up after 3 years, IDA in this patient was cured and she did not require further blood transfusion and showed excellent vigor. A high index of suspicion for BRBNS and adequate endoscopy examination will help to identify the origin of refractory IDA in older children, particularly in patients with vascular lesions of the skin.

[Haemophilia--then and now].

PubMed

Nilsson, I M

1994-01-01

Haemophilia is a bleeding disorder which has always attracted wide interest both among physicians and the laity--uncontrollable haemorrhage, blood that fails to coagulate and heredity with only males affected. The disease is probably best known to the public through its appearance in European royal families and in the Russian Imperial family. The oldest known description of haemophilia is to be found in the Talmud, the collection of ancient Judaic books from the early centuries of our era. The first clinical account of haemophilia was published by the American, Otto, in 1803. He described the disease as an inheritable bleeding disorder occurring only in males, and transmitted by female carriers who are not themselves affected. The disease manifests itself in early childhood, joint bleedings being its most characteristic feature. Otto called the male patients "bleeders". The term, haemophilia, originated with a German, Friedrich Hopff (1828), who coined the name "haemorrhaphilia" which was later abbreviated to haemophilia. ... As to future prospects, it is hoped that it will soon be possible to cure the disease by means of gene therapy, and to this end promising experimental work is already in progress.

Hemophilia in Sports: A Case Report and Prophylactic Protocol

PubMed Central

Maffet, Mark; Roton, Jimmy

2017-01-01

Objective: To describe a successful prophylactic protocol for managing an athlete with hemophilia playing at a high level of contact sports. Background: Published data show that team physicians are not comfortable either treating athletes with bleeding disorders or allowing them to participate in contact sports. Much of the literature historically has recommended against allowing athletes with bleeding disorders to play sports at all and certainly against playing contact sports. Hemophilia treatment can now include prophylactic injections of recombinant factor VIII to prevent bleeding episodes. Modern treatments hold the promise of allowing athletes with hemophilia to participate in contact sports. Differential Diagnosis: Mild, moderate, or severe hemophilia; von Willebrand disease; other factor deficiencies. Treatment: A treatment protocol was developed that included prophylactic factor VIII injections on a regular basis and when the athlete was injured. Uniqueness: This is the first published case report of an athlete with known hemophilia being successfully treated and participating in National Collegiate Athletic Association collegiate basketball for 2 full seasons. Conclusions: Sports medicine teams can successfully manage an athlete with hemophilia playing a contact sport. PMID:27863189

Familiy Planning and Pregnancy

MedlinePlus

... should be managed to reduce risks to both mother and child; the options available for conception , prenatal diagnosis , and fetal sex determination . Updated November 2012 Bleeding Disorders The Clotting ...

Reticulocyte count

MedlinePlus

Anemia - reticulocyte ... A higher than normal reticulocytes count may indicate: Anemia due to red blood cells being destroyed earlier than normal ( hemolytic anemia ) Bleeding Blood disorder in a fetus or newborn ( ...

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies.

PubMed

Shatzel, J J; Olson, S R; Tao, D L; McCarty, O J T; Danilov, A V; DeLoughery, T G

2017-05-01

Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell-mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared with standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non-steroidal anti-inflammatory drugs, fish oils, vitamin E and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulants should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib. © 2017 International Society on Thrombosis and Haemostasis.

Von Hippel-Lindau Disease: A Rare Familiar Multi-System Disorder and the Impact of the Clinical Nurse Specialist

DTIC Science & Technology

1993-01-01

would undergo removal of both adrenal glands, the renal cell carcinomas, a cholecystectomy and a choledochoduodenostomy for biliary drainage . The...bleeding, renal failure, and pancreatitis. After recovery, a craniotomy would be done to remove the hemangioblastoma that had been bleeding. The...analgesia. After a three month convalescence, the patient had a craniotomy and was home within a week. The patient’s siblings have all had negative eye

Dysfunctional uterine bleeding as an early sign of polycystic ovary syndrome during adolescence.

PubMed

Deligeoroglou, E K; Creatsas, G K

2015-08-01

Excessive uterine bleeding during the early years after menarche can be worrisome to the girl and her parents. The most prevalent diagnosis set is Dysfunctional uterine bleeding (DUB), after thorough examination and exclusion of other causes of abnormal uterine bleeding. The aim of this article was to review our knowledge and share our experience as tertiary reference center of pediatric-adolescent gynecology in Greece. We conducted a review of current literature using Pubmed and MedLine as our primary databases, as well as providing commentary considering work up, treatment and follow-up of our DUB patients. Insufficient progesterone production and subsequent abnormal shedding of the endometrium appears to orchestrate the pathophysiology of DUB in adolescence. Hypothalamic-pituitary-ovarian (HPO) axis immaturity right after menarche, is usually the most plausible cause. Nevertheless, it is necessary to exclude other, possibly even life-threatening causes. Complete work up including physical examination, laboratory and imaging studies (complete blood count, b-HCG, hormonal levels and ultrasonography) is needed, and appropriate treatment with combined oral contraceptives is administered accordingly. Although menstrual disorders are very common in early adolescence, a severe episode of DUB should always be thoroughly attended by any physician. Follow-up should be offered in all young patients due to high incidence of recurrence or subsequent development of endocrine disorders such as Polycystic Ovary Syndrome (PCOS).

Anorectal emergencies

PubMed Central

Lohsiriwat, Varut

2016-01-01

Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

Ileal polypoid lymphangiectasia bleeding diagnosed and treated by double balloon enteroscopy.

PubMed

Park, Min Seon; Lee, Beom Jae; Gu, Dae Hoe; Pyo, Jeung-Hui; Kim, Kyeong Jin; Lee, Yun Ho; Joo, Moon Kyung; Park, Jong-Jae; Kim, Jae Seon; Bak, Young-Tae

2013-12-07

Intestinal lymphangiectasia is a rare disease characterized by focal or diffuse dilated enteric lymphatics with impaired lymph drainage. It causes protein-losing enteropathy and may lead to gastrointestinal bleeding. Commonly, lymphangiectasia presents as whitish spots or specks. To our knowledge, small bowel bleeding resulting from polypoid intestinal lymphangiectasia has not been reported. Here, we report a rare case of active bleeding from the small bowel caused by polypoid lymphangiectasia with a review of the relevant literature. An 80-year-old woman was hospitalized for melena. Esophagogastroduodenoscopy could not identify the source of bleeding. Subsequent colonoscopy showed fresh bloody material gushing from the small bowel. An abdominal-pelvic contrast-enhanced computed tomography scan did not reveal any abnormal findings. Video capsule endoscopy showed evidence of active and recent bleeding in the ileum. To localize the bleeding site, we performed double balloon enteroscopy by the anal approach. A small, bleeding, polypoid lesion was found in the distal ileum and was successfully removed using endoscopic snare electrocautery. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.

Menstrual Disorders

MedlinePlus

... prostaglandins, naturally occurring chemicals that cause cramps. Oral contraceptives can also be used to relieve severe menstrual cramps. Hormone treatments, such as oral contraceptives, can also be used for dysfunctional uterine bleeding. ...

PALM-COEIN Nomenclature for Abnormal Uterine Bleeding.

PubMed

Deneris, Angela

2016-05-01

Approximately 30% of women will experience abnormal uterine bleeding (AUB) during their life time. Previous terms defining AUB have been confusing and imprecisely applied. As a consequence, both clinical management and research on this common problem have been negatively impacted. In 2011, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Group (FMDG) published PALM-COEIN, a new classification system for abnormal bleeding in the reproductive years. Terms such as menorrhagia, menometrorrhagia, metrorrhagia, dysfunctional uterine bleeding, polymenorrhea, oligomenorrhea, and uterine hemorrhage are no longer recommended. The PALM-COEIN system was developed to standardize nomenclature to describe the etiology and severity of AUB. A brief description of the PALM-COEIN nomenclature is presented as well as treatment options for each etiology. Clinicians will frequently encounter women with AUB and should report findings utilizing the PALM-COEIN system. © 2016 by the American College of Nurse-Midwives.

Does non-acetylated salicylate inhibit thromboxane biosynthesis in human platelets?

PubMed

Danesh, B J; McLaren, M; Russell, R I; Lowe, G D; Forbes, C D

1988-08-01

Ingestion of aspirin (acetyl salicylic acid: ASA) may promote bleeding complications due to inhibition of thromboxane biosynthesis, which results in the prolongation of bleeding time. The effect is believed to be achieved by the irreversible acetylation of the enzyme cyclooxygenase by aspirin. This alteration in platelet function by aspirin prohibits its use in patients with bleeding disorders such as haemophiliacs. Choline magnesium trisalicylate (CMT; Napp Laboratories Ltd) is a non-acetylated salicylate with analgesic and anti-inflammatory effects similar to that of aspirin. However, despite a comparable salicylate absorption from the two drugs, CMT is found to have no inhibitory action in platelet aggregation and to cause less gastric mucosal damage and gastrointestinal blood loss than aspirin. To investigate the role of the acetyl moiety in the inhibition of platelet thromboxane biosynthesis, we studied the effect of CMT and ASA on bleeding time, serum thromboxane B2 (TxB2) and thromboxane (Tx) generation in healthy volunteers.

Use of global assays to understand clinical phenotype in congenital factor VII deficiency.

PubMed

Greene, L A; Goldenberg, N A; Simpson, M L; Villalobos-Menuey, E; Bombardier, C; Acharya, S S; Santiago-Borrero, P J; Cambara, A; DiMichele, D M

2013-09-01

Congenital factor VII (FVII) deficiency is characterized by genotypic variability and phenotypic heterogeneity. Traditional screening and factor assays are unable to reliably predict clinical bleeding phenotype and guide haemorrhage prevention strategy. Global assays of coagulation and fibrinolysis may better characterize overall haemostatic balance and aid in haemorrhagic risk assessment. We evaluated the ability of novel global assays to better understand clinical bleeding severity in congenital FVII deficiency. Subjects underwent central determination of factor VII activity (FVII:C) as well as clot formation and lysis (CloFAL) and simultaneous thrombin and plasmin generation (STP) global assay analysis. A bleeding score was assigned to each subject through medical chart review. Global assay parameters were analysed with respect to bleeding score and FVII:C. Subgroup analyses were performed on paediatric subjects and subjects with FVII ≥ 1 IU dL(-1). CloFAL fibrinolytic index (FI2 ) inversely correlated with FVII:C while CloFAL maximum amplitude (MA) and STP maximum velocity of thrombin generation (VT max) varied directly with FVII:C. CloFAL FI2 directly correlated with bleeding score among subjects in both the total cohort and paediatric subcohort, but not among subjects with FVII ≥ 1 IU dL(-1) . Among subjects with FVII ≥ 1 IU dL(-1), STP time to maximum velocity of thrombin generation and time to maximum velocity of plasmin generation inversely correlated with bleeding score. These preliminary findings suggest a novel potential link between a hyperfibrinolytic state in bleeding severity and congenital FVII deficiency, an observation that should be further explored. © 2013 John Wiley & Sons Ltd.

Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

PubMed

Breivik, H; Bang, U; Jalonen, J; Vigfússon, G; Alahuhta, S; Lagerkranser, M

2010-01-01

Central neuraxial blocks (CNBs) for surgery and analgesia are an important part of anaesthesia practice in the Nordic countries. More active thromboprophylaxis with potent antihaemostatic drugs has increased the risk of bleeding into the spinal canal. National guidelines for minimizing this risk in patients who benefit from such blocks vary in their recommendations for safe practice. The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) appointed a task force of experts to establish a Nordic consensus on recommendations for best clinical practice in providing effective and safe CNBs in patients with an increased risk of bleeding. We performed a literature search and expert evaluation of evidence for (1) the possible benefits of CNBs on the outcome of anaesthesia and surgery, for (2) risks of spinal bleeding from hereditary and acquired bleeding disorders and antihaemostatic drugs used in surgical patients for thromboprophylaxis, for (3) risk evaluation in published case reports, and for (4) recommendations in published national guidelines. Proposals from the taskforce were available for feedback on the SSAI web-page during the summer of 2008. Neuraxial blocks can improve comfort and reduce morbidity (strong evidence) and mortality (moderate evidence) after surgical procedures. Haemostatic disorders, antihaemostatic drugs, anatomical abnormalities of the spine and spinal blood vessels, elderly patients, and renal and hepatic impairment are risk factors for spinal bleeding (strong evidence). Published national guidelines are mainly based on experts' opinions (weak evidence). The task force reached a consensus on Nordic guidelines, mainly based on our experts' opinions, but we acknowledge different practices in heparinization during vascular surgery and peri-operative administration of non-steroidal anti-inflammatory drugs during neuraxial blocks. Experts from the five Nordic countries offer consensus recommendations for safe clinical practice of neuraxial blocks and how to minimize the risks of serious complications from spinal bleeding. A brief version of the recommendations is available on http://www.ssai.info.

Both Hemophilia Health Care Providers and Hemophilia A Carriers Report that Carriers have Excessive Bleeding

PubMed Central

Paroskie, Allison; Oso, Olatunde; DeBaun, Michael R.; Sidonio, Robert F

2014-01-01

Introduction Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder. Previous reports of Hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the Hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey was used as preliminary data for an ongoing prospective study. Material and Methods An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers (HTC), and Hemophilia A carriers who were members of Hemophilia Federation of America. Questions focused on the clinical understanding of bleeding symptoms and management of Hemophilia A carriers, and the timing and intensity of carrier testing. Results Our survey indicates that 51% (36/51) of providers compared to 78% (36/46) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (p<0.001); 72% (33/36) of Hemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of Hemophilia A carriers prefer testing to be done prior to this age (p<0.001). Discussion Hemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status. PMID:24309601

Novel Application of Percutaneous Cryotherapy for the Treatment of Recurrent Oral Bleeding From a Noninvoluting Congenital Hemangioma Involving the Right Buccal Space and Maxillary Tuberosity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salehian, Sepand, E-mail: sepand@med.umich.edu; Gemmete, Joseph J., E-mail: gemmete@med.umich.edu; Kasten, Steven, E-mail: skasten@med.umich.edu

2011-02-15

Cryotherapy is the application of varying extremes of cold temperatures to destroy abnormal tissue. The intent of this article is to describe a novel technique using percutaneous cryotherapy for treating a noninvoluting congenital craniofacial hemangioma (NICH). An 18-year-old woman with type 1 von Willebrand's disease, as well as a qualitative platelet aggregation disorder, presented with multiple recurrent episodes of oral bleeding from a NICH involving the right buccal space and maxillary tuberosity. The patient was initially treated with a combination of endovascular particulate embolization, percutaneous sclerotherapy, tissue cauterization, and laser therapy between the ages of 4 and 8 years ofmore » age. At 18 years of age, the patient presented with recurrent episodes of oral bleeding related to the NICH. Endovascular embolization was performed using particulate and a liquid embolic agent with limited success. Due to the refractory nature of this bleeding, the patient underwent successful lesion ablation using percutaneous cryotherapy. At 9-month follow-up, the patient is asymptomatic with no episodes of recurrent bleeding.« less

Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

PubMed

Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

2014-08-28

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

Diagnosis and management of von Willebrand's syndrome.

PubMed

Rick, M E

1994-05-01

von Willebrand's disease is the most common of the inherited bleeding disorders. It is caused by quantitative and/or qualitative abnormalities of von Willebrand factor, and it usually presents with bleeding from mucosal surfaces. The diagnosis is confirmed by measuring von Willebrand factor activity and antigen levels, factor VIII activity, and performing a multimer analysis of von Willebrand factor. Treatment may require plasma-derived concentrates, but can often be accomplished with DDAVP, a vasopressin analogue that causes transient release of von Willebrand factor from body storage sites.

Treatment of hemophilia B: focus on recombinant factor IX

PubMed Central

Franchini, Massimo; Frattini, Francesco; Crestani, Silvia; Sissa, Cinzia; Bonfanti, Carlo

2013-01-01

Hemophilia B is a recessive X-linked bleeding disorder characterized by deficiency of the coagulation factor IX (FIX). In hemophilia B patients the severity of the bleeding phenotype is related to the degree of the FIX defect. Hemophilia B treatment has improved greatly in the last 20 years with the introduction first of plasma-derived and then of recombinant FIX concentrates. Replacement therapy may be administered through on-demand or prophylaxis regimens, but the latter treatment modality has been shown to be superior in prevention of hemophilic arthropathy and in improvement of patients’ quality of life. The purpose of this narrative review is to summarize the current knowledge on treatment strategies for hemophilia B, focusing on recombinant FIX products either clinically used or in development. There is only one rFIX product that is licensed to treat hemophilia B patients; from the analysis of the literature data presented in this review, the authors conclude that this rFIX product has demonstrated an excellent safety profile and excellent clinical efficacy for halting and preventing bleeds in hemophilia B patients. While prophylaxis has emerged as the best therapeutic strategy for such patients because of its ability to prevent hemophilic arthropathy and to improve patients’ quality of life, the pharmacokinetically tailored dosing of rFIX is another key point when planning hemophilia B treatment, as it allows optimization of the factor concentrate usage. Further clinical studies are needed to better assess the safety and efficacy (ie, the incidence of adverse reactions and inhibitor development) of newer rFIX products. PMID:23430394

Design and characterization of an APC-specific serpin for the treatment of hemophilia

PubMed Central

Polderdijk, Stéphanie G. I.; Adams, Ty E.; Ivanciu, Lacramioara; Camire, Rodney M.; Baglin, Trevor P.

2017-01-01

Hemophilia is a bleeding disorder caused by deficiency in factors VIII or IX, the two components of the intrinsic Xase complex. Treatment with replacement factor can lead to the development of inhibitory antibodies, requiring the use of bypassing agents such as factor VIIa and factor concentrates. An alternative approach to bypass the Xase complex is to inhibit endogenous anticoagulant activities. Activated protein C (APC) breaks down the complex that produces thrombin by proteolytically inactivating factor Va. Defects in this mechanism (eg, factor V Leiden) are associated with thrombosis but result in less severe bleeding when co-inherited with hemophilia. Selective inhibition of APC might therefore be effective for the treatment of hemophilia. The endogenous inhibitors of APC are members of the serpin family: protein C inhibitor (PCI) and α1-antitrypsin (α1AT); however, both exhibit poor reactivity and selectivity for APC. We mutated residues in and around the scissile P1-P1′ bond in PCI and α1AT, resulting in serpins with the desired specificity profile. The lead candidate was shown to promote thrombin generation in vitro and to restore fibrin and platelet deposition in an intravital laser injury model in hemophilia B mice. The power of targeting APC was further demonstrated by the complete normalization of bleeding after a severe tail clip injury in these mice. These results demonstrate that the protein C anticoagulant system can be successfully targeted by engineered serpins and that administration of such agents is effective at restoring hemostasis in vivo. PMID:27789479

Excessive bleeding predictors after cardiac surgery in adults: integrative review.

PubMed

Lopes, Camila Takao; Dos Santos, Talita Raquel; Brunori, Evelise Helena Fadini Reis; Moorhead, Sue A; Lopes, Juliana de Lima; Barros, Alba Lucia Bottura Leite de

2015-11-01

To integrate literature data on the predictors of excessive bleeding after cardiac surgery in adults. Perioperative nursing care requires awareness of the risk factors for excessive bleeding after cardiac surgery to assure vigilance prioritising and early correction of those that are modifiable. Integrative literature review. Articles were searched in seven databases. Seventeen studies investigating predictive factors for excessive bleeding after open-heart surgery from 2004-2014 were included. Predictors of excessive bleeding after cardiac surgery were: Patient-related: male gender, higher preoperative haemoglobin levels, lower body mass index, diabetes mellitus, impaired left ventricular function, lower amount of prebypass thrombin generation, lower preoperative platelet counts, decreased preoperative platelet aggregation, preoperative platelet inhibition level >20%, preoperative thrombocytopenia and lower preoperative fibrinogen concentration. Procedure-related: the operating surgeon, coronary artery bypass surgery with three or more bypasses, use of the internal mammary artery, duration of surgery, increased cross-clamp time, increased cardiopulmonary bypass time, lower intraoperative core body temperature and bypass-induced haemostatic disorders. Postoperative: fibrinogen levels and metabolic acidosis. Patient-related, procedure-related and postoperative predictors of excessive bleeding after cardiac surgery were identified. The predictors summarised in this review can be used for risk stratification of excessive bleeding after cardiac surgery. Assessment, documentation and case reporting can be guided by awareness of these factors, so that postoperative vigilance can be prioritised. Timely identification and correction of the modifiable factors can be facilitated. © 2015 John Wiley & Sons Ltd.

Prothrombin time (PT)

MedlinePlus

... of a blood clotting or bleeding disorder Normal Results PT is measured in seconds. Most of the ... meaning of your specific test results. What Abnormal Results Mean If you are not taking blood thinning ...

Gastrointestinal Bleeding Due to Gastrointestinal Tract Malignancy: Natural History, Management, and Outcomes.

PubMed

Schatz, Richard A; Rockey, Don C

2017-02-01

Gastrointestinal (GI) tumor bleeding can vary from occult bleeding to massive hemorrhage and can be the presenting sign of malignancy. Our primary aims were to: (1) characterize the natural history, treatment, and outcomes in patients with GI tumor bleeding and (2) compare and contrast bleeding in upper GI (UGI)/small bowel (SB) and lower GI malignancies. Patients with endoscopically confirmed tumor bleeding were identified through search of consecutive electronic medical records: Bleeding was determined by the presence of melena, hematochezia, hematemesis, or fecal occult blood. Comprehensive clinical and management data were abstracted. A total of 354 patients with GI tumors were identified: 71 had tumor bleeding (42 UGI/SB and 29 colonic). GI bleeding was the initial presenting symptom of malignancy in 55/71 (77%) of patients; 26/71 patients had widely metastatic disease at presentation. Further, 15 of 26 patients with metastatic disease presented with GI bleeding. Visible bleeding was present in 14/42 (33%) and 4/29 (14%) of UGI/SB and colonic tumors, respectively. Endoscopic hemostasis was attempted in 10 patients, and although initial control was successful in all, bleeding recurred in all of these patients. The most common endoscopic lesion was clean-based tumor ulceration. Overall mortality at 1 year was 57% for esophageal/gastric, 14% for SB, and 33% for colonic tumors. When patients with GI malignancy present with GI bleeding, it is often the index symptom. Initial endoscopic hemostasis is often successful, but rebleeding is typical. Esophageal and gastric tumors carry the poorest prognosis, with a high 1-year mortality rate.

Bleeding Disorders

MedlinePlus

... functionality. ------------------------------------------------------------ Find a Health Center ------------------------------------------------------------ Share this page: Twitter MySpace Technorati Facebook StumbleUpon Delicious Email to friend ... such as 20002), address, state, or place Share Twitter Facebook Email to friend Embed Code Embed this ...

Bleeding Peptic Ulcer - Tertiary Center Experience: Epidemiology, Treatment and Prognosis.

PubMed

Budimir, Ivan; Stojsavljević, Sanja; Hrabar, Davor; Kralj, Dominik; Bišćanin, Alen; Kirigin, Lora Stanka; Zovak, Mario; Babić, Žarko; Bohnec, Sven; Budimir, Ivan

2017-12-01

The aim of this study was to demonstrate epidemiological, clinical and endoscopic characteristics of acute upper gastrointestinal bleeding (UGIB) with special reference to peptic ulcer bleeding (PUB). The study included 2198 consecutive patients referred to our emergency department due to acute UGIB from January 2008 to December 2012. All patients underwent urgent upper GI endoscopy within 24 hours of admission, and 842 patients diagnosed with PUB were enrolled and prospectively followed-up. The cumulative incidence of UGIB was 126/100,000 in the 5-year period. Two out of five patients had a bleeding peptic ulcer; in total, 440 (52.3%) had bleeding gastric ulcer, 356 (42.3%) had bleeding duodenal ulcer, 17 (2%) had both bleeding gastric and duodenal ulcers, and 29 (3.5%) patients had bleeding ulcers on gastroenteric anastomoses. PUB was more common in men. The mean patient age was 65.9 years. The majority of patients (57%) with PUB were taking agents that attenuate the cytoprotective function of gastric and duodenal mucosa. Rebleeding occurred in 77 (9.7%) patients and 47 (5.9%) patients required surgical intervention. The 30-day morality was 5.2% and 10% of patients died from uncontrolled bleeding and concomitant diseases. In conclusion, PUB is the main cause of UGIB, characterized by a significant rebleeding rate and mortality.

Menstrual Bleeding Patterns Among Regularly Menstruating Women

PubMed Central

Dasharathy, Sonya S.; Mumford, Sunni L.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Wactawski-Wende, Jean; Schisterman, Enrique F.

2012-01-01

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005–2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle. PMID:22350580

Iron Deficiency Anemia in Adolescents Who Present with Heavy Menstrual Bleeding.

PubMed

Cooke, Amanda G; McCavit, Timothy L; Buchanan, George R; Powers, Jacquelyn M

2017-04-01

To assess the clinical severity and initial treatment of iron deficiency anemia (IDA) in female adolescents with heavy menstrual bleeding (HMB) in our center. Retrospective cohort study of electronic medical records via search of administrative records using International Classification of Diseases Ninth Revision codes for IDA or unspecified anemia and disorders of menstruation. Children's Medical Center in Dallas, Texas. One hundred seven patients with HMB and concomitant IDA (median age, 14.4 years) who presented to the outpatient, emergency department, and/or inpatient settings. The median initial hemoglobin concentration for all patients (n = 107) was 7.4 g/dL, and most (74%, n = 79) presented to the emergency department or via inpatient transfer. Symptomatic IDA was treated with blood transfusion in 46 (43%, n = 46). Ferrous sulfate was the most commonly prescribed oral iron therapy. Seven patients received intravenous iron therapy either initially or after oral iron treatment failure. Combined oral contraceptives were commonly prescribed for abnormal uterine bleeding, yet 10% of patients (n = 11) received no hormonal therapy during their initial management. Evaluation for underlying bleeding disorders was inconsistent. Severe anemia because of IDA and HMB resulting in urgent medical care, including hospitalization and blood transfusion, is a common but underemphasized problem in adolescent girls. In addition to prevention and early diagnosis, meaningful efforts to improve initial management of adolescents with severe HMB and IDA are necessary. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

PHARMACOKINETIC STUDY OF ORAL ε-AMINOCAPROIC ACID IN THE NORTHERN ELEPHANT SEAL (MIROUNGA ANGUSTIROSTRIS).

PubMed

Kaye, Sarrah; Johnson, Shawn; Arnold, Robert D; Nie, Ben; Davis, Joshua T; Gulland, Frances; Abou-Madi, Noha; Fletcher, Daniel J

2016-06-01

ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Its use in zoological medicine is rare, and dosage is anecdotal. One possible application of EACA is to treat bleeding associated with prepatent Otostrongylus arteritis in Northern elephant seals ( Mirounga angustirostris ) presenting to wildlife rehabilitation centers. This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in elephant seals (85 μg/ml, 95% confidence interval = 73.8-96.8 μg/ml). A concurrent pharmacokinetic study of orally administered, single-dose EACA found that doses of 75 and 100 mg/kg achieved therapeutic plasma concentrations (>85 μg/ml), but the drug was rapidly eliminated and remained in the therapeutic range for only 0.4 and 1.5 hr, respectively. Models of repeated oral dosing at 100 mg/kg every 6 hr predict that therapeutic plasma concentration will be maintained for 31.7% (7.6 hr) of a 24-hr period. More frequent dosing would be required to maintain continuous therapeutic concentrations but would be impractical in a wildlife rehabilitation setting. Further pharmacodynamic studies to evaluate the duration of action of EACA in elephant seals and a prospective, placebo-controlled study are needed to determine if EACA is effective in decreasing bleeding associated with prepatent Otostrongylus arteritis and other bleeding disorders in this species.

A systematic review of the management and outcomes of pregnancy in Glanzmann thrombasthenia.

PubMed

Siddiq, S; Clark, A; Mumford, A

2011-09-01

Glanzmann Thrombasthenia (GT) is a rare autosomal recessive disorder which usually manifests as severe mucocutaneous bleeding and is caused by deficiency of the platelet glycoprotein IIb-IIIa. Pregnancy in women with GT presents particular challenges as there is increased risk of both maternal and foetal bleeding. To improve understanding and clarify the optimum management of pregnancy in this disorder, we performed a systematic review of the world literature of pregnancy and GT. This identified three single-centre case series of patients with GT that included brief descriptions of women in pregnancy and 31 detailed case reports of 40 pregnancies in 35 women that resulted in 38 live births. Among the detailed case reports, ante-natal bleeding was described in 50% of pregnancies but was usually mild and occurred at mucocutaneous sites. Primary postpartum haemorrhage (PPH) was reported in 34% of pregnancies and secondary PPH in 24%. PPH was frequently severe and occurred up to 20 days after delivery. There was a wide variation in approach to prevention and treatment of PPH but most women received platelet transfusion, sometimes with additional recombinant FVIIa and anti-fibrinolytics. Maternal alloimmunization against platelet antigens was reported in 73% of pregnancies and was associated with four neonatal deaths. These data emphasize the need for multidisciplinary management of pregnancy in women with GT. Delivery plans should recognize the need for prevention and aggressive treatment of PPH and should minimize foetal bleeding risk in pregnancies complicated by alloimmunization. © 2011 Blackwell Publishing Ltd.

Red cell-derived microparticles (RMP) as haemostatic agent.

PubMed

Jy, Wenche; Johansen, Max E; Bidot, Carlos; Horstman, Lawrence L; Ahn, Yeon S

2013-10-01

Among circulating cell-derived microparticles, those derived from red cells (RMP) have been least well investigated. To exploit potential haemostatic benefit of RMP, we developed a method of producing them in quantity, and here report on their haemostatic properties. High-pressure extrusion of washed RBC was employed to generate RMP. RMP were identified and enumerated by flow cytometry. Their size distribution was assessed by Doppler electrophoretic light scattering analysis (DELSA). Interaction with platelets was studied by platelet aggregometry, and shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue factor (TF) expression was also measured. The effect of RMP on blood samples of patients with bleeding disorders was investigated ex vivo by thromboelastography (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 µm and 50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids (PL). No TF could be detected by flow cytometry. At saturating concentrations of MPs, RMP generated thrombin robustly but after longer delay compared to PMP and EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or AA. In TEG study, RMP corrected or improved haemostatic defects in blood of patients with platelet and coagulation disorders. RMP reduced bleeding time and blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary (platelet) and secondary (coagulation) haemostasis, suggesting potential use as haemostatic agent for treatment of bleeding.

Leopold: the "bleeder prince" and public knowledge about hemophilia in Victorian Britain.

PubMed

Rushton, Alan R

2012-07-01

Hemophilia is a rare bleeding disorder inherited by males born of unaffected female carriers of the trait. British physicians became knowledgeable about this hereditary disease early in the nineteenth century as they investigated families transmitting the character through several generations. Prince Leopold (b. 1853), the fourth son of Queen Victoria, experienced recurrent bleeding episodes and was diagnosed with hemophilia during childhood. His hemorrhagic attacks were first described in the medical journals during 1868, and subsequently in the London and provincial newspapers. The royal family carefully managed news about health matters, and many newspapers reported widespread public sympathy for the travails of the queen and her children. But the republican press argued that the disaffected working classes resented the hyperbole connecting the health of royal individuals with the political future of the entire nation. Public discussion of hemophilia transformed it from a rare medical phenomenon to a matter of national news. Practicing physicians, the royal family, and the general public all came to understand the clinical features and the hereditary nature of the problem. Members of the royal family subsequently utilized this information to guide the marriages of their own children to prevent the spread of this dreaded bleeding disorder.

Receptor homodimerization plays a critical role in a novel dominant negative P2RY12 variant identified in a family with severe bleeding.

PubMed

Mundell, S J; Rabbolini, D; Gabrielli, S; Chen, Q; Aungraheeta, R; Hutchinson, J L; Kilo, T; Mackay, J; Ward, C M; Stevenson, W; Morel-Kopp, M-C

2018-01-01

Essentials Three dominant variants for the autosomal recessive bleeding disorder type-8 have been described. To date, there has been no phenotype/genotype correlation explaining their dominant transmission. Proline plays an important role in P2Y12R ligand binding and signaling defects. P2Y12R homodimer formation is critical for the receptor function and signaling. Background Although inherited platelet disorders are still underdiagnosed worldwide, advances in molecular techniques are improving disease diagnosis and patient management. Objective To identify and characterize the mechanism underlying the bleeding phenotype in a Caucasian family with an autosomal dominant P2RY12 variant. Methods Full blood counts, platelet aggregometry, flow cytometry and western blotting were performed before next-generation sequencing (NGS). Detailed molecular analysis of the identified variant of the P2Y12 receptor (P2Y12R) was subsequently performed in mammalian cells overexpressing receptor constructs. Results All three referred individuals had markedly impaired ADP-induced platelet aggregation with primary wave only, despite normal total and surface P2Y12R expression. By NGS, a single P2RY12:c.G794C substitution (p.R265P) was identified in all affected individuals, and this was confirmed by Sanger sequencing. Mammalian cell experiments with the R265P-P2Y12R variant showed normal receptor surface expression versus wild-type (WT) P2Y12R. Agonist-stimulated R265P-P2Y12R function (both signaling and surface receptor loss) was reduced versus WT P2Y12R. Critically, R265P-P2Y12R acted in a dominant negative manner, with agonist-stimulated WT P2Y12R activity being reduced by variant coexpression, suggesting dramatic loss of WT homodimers. Importantly, platelet P2RY12 cDNA cloning and sequencing in two affected individuals also revealed three-fold mutant mRNA overexpression, decreasing even further the likelihood of WT homodimer formation. R265 located within extracellular loop 3 (EL3) is one of four residues that are important for receptor functional integrity, maintaining the binding pocket conformation and allowing rotation following ligand binding. Conclusion This novel dominant negative variant confirms the important role of R265 in EL3 in the functional integrity of P2Y12R, and suggests that pathologic heterodimer formation may underlie this family bleeding phenotype. © 2017 International Society on Thrombosis and Haemostasis.

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

PubMed

Kahr, W H; Zheng, S; Sheth, P M; Pai, M; Cowie, A; Bouchard, M; Podor, T J; Rivard, G E; Hayward, C P

2001-07-15

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Health of Women after Wartime Deployments: Correlates of Risk for Selected Medical Conditions among Females after Initial and Repeat Deployments to Afghanistan and Iraq, Active Component, U.S. Armed Forces

DTIC Science & Technology

2012-07-01

719.xx Peripheral enthesopathies, allied syndromes 726.xx Reproductive system disorders Disorders of menstruation /other abnormal bleeding 626.xx...range, 2.0%-2.8%), while the percentages diagnosed with “disorders of menstruation ” remained stable (range, 7.6%-8.0%), with increasing number...between the condi- tions. For example, in multivariate analyses, MSMR Vol. 19 No. 7 July 2012Page 6 Reproductive system disorders Menstruation

Genetics Home Reference: factor V deficiency

MedlinePlus

... Twitter Home Health Conditions Factor V deficiency Factor V deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor V deficiency is a rare bleeding disorder. The signs ...

Genetics Home Reference: X-linked thrombocytopenia

MedlinePlus

... Facebook Twitter Home Health Conditions X-linked thrombocytopenia X-linked thrombocytopenia Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description X-linked thrombocytopenia is a bleeding disorder that primarily ...

Genetics Home Reference: factor X deficiency

MedlinePlus

... Twitter Home Health Conditions Factor X deficiency Factor X deficiency Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Factor X deficiency is a rare bleeding disorder that varies ...

Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder.

PubMed

Sheth, Prameet M; Kahr, Walter H A; Haq, M Anwar; Veljkovic, Dragoslava Kika; Rivard, Georges E; Hayward, Catherine P M

2003-08-01

The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet alpha-granule proteins. The increased u-PA and proteolyzed plasminogen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD alpha-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-alpha(2)-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal alpha-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further alpha-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to alpha-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

EFFECT OF ε-AMINOCAPROIC ACID ON FIBRINOLYSIS IN PLASMA OF ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Kaye, Sarrah; Abou-Madi, Noha; Fletcher, Daniel J

2016-06-01

ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Use in zoological medicine is rare and dose recommendations are anecdotal, but EACA may be a valuable therapeutic option for bleeding disorders in exotic species, including Asian elephants ( Elephas maximus ). This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in Asian elephants (61.5 μg/ml, 95% CI = 34.6-88.5 μg/ml). Substantial but incomplete inhibition of lysis was seen at relatively low concentrations of EACA (40 μg/ml). Asian elephants appear sensitive to EACA-mediated inhibition of hyperfibrinolysis. Doses published for domestic animals, targeting higher plasma concentrations, may be inappropriate in this species.

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

PubMed

Ennaifer, Rym; B'chir Hamzaoui, Saloua; Larbi, Thara; Romdhane, Hayfa; Abdallah, Maya; Bel Hadj, Najet; M'rad, Sander

2015-03-01

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD. Copyright © 2015 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Nano- and micro-materials in the treatment of internal bleeding and uncontrolled hemorrhage.

PubMed

Gaston, Elizabeth; Fraser, John F; Xu, Zhi Ping; Ta, Hang T

2018-02-01

Internal bleeding is defined as the loss of blood that occurs inside of a body cavity. After a traumatic injury, hemorrhage accounts for over 35% of pre-hospital deaths and 40% of deaths within the first 24 hours. Coagulopathy, a disorder in which the blood is not able to properly form clots, typically develops after traumatic injury and results in a higher rate of mortality. The current methods to treat internal bleeding and coagulopathy are inadequate due to the requirement of extensive medical equipment that is typically not available at the site of injury. To discover a potential route for future research, several current and novel treatment methods have been reviewed and analyzed. The aim of investigating different potential treatment options is to expand available knowledge, while also call attention to the importance of research in the field of treatment for internal bleeding and hemorrhage due to trauma. Copyright © 2017 Elsevier Inc. All rights reserved.

Giant cell lesions with a Noonan-like phenotype: a case report.

PubMed

Cancino, Claudia Marcela H; Gaião, Léonilson; Sant'Ana Filho, Manoel; Oliveira, Flavio Augusto Marsiaj

2007-05-01

The purpose of this article is to describe a case of multiple giant cell lesions of the mandible that occurred in a 14-year-old girl with phenotypic characteristics associated with Noonan Syndrome (NS). NS is a dysmorphic disorder characterized by hypertelorism, short stature, congenital heart defects, short and webbed neck, skeletal anomalies, and bleeding diathesis. A 14-year-old girl with a previous diagnosis of NS (sporadic case) presented with multiple radiolucent lesions in the body and ramus of her mandible. In terms of clinical behavior and the described radiographic characteristics, giant cells lesions with Noonan-like phenotype can be considered a form of cherubism. Therefore, surgical intervention is not necessary, but radiographic follow-up and observation is very important during the control and gradual regression of the lesions.

Emerging drugs for hemophilia B.

PubMed

Mannucci, Pier Mannuccio; Franchini, Massimo

2014-09-01

Hemophilia B is a rare congenital bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). Hemophilia B patients experience mild-to-severe bleeding complications according to the degree of FIX defect. Prophylaxis, with regular infusion of FIX concentrates, is nowadays, the mainstay of hemophilia care. However, because the relatively short half-life of such products necessitates frequent infusions and thus makes patients' adherence difficult, a number of strategies have been implemented to improve the pharmacokinetics of FIX clotting factors. This review summarizes the main results of Phase I/II and III studies on new FIX molecules engineered to have a longer half-life. Several technologies are being applied to extend FIX half-life, including Fc fusion, recombinant (r) albumin fusion and the addition of PEG polymers. By prolonging the FIX half-life up to 5 times, long-acting FIX products are expected to substantially improve the management of hemophilia B patients, allowing less frequent infusions and improving patients' adherence to prophylactic regimens and individualized treatments. Some of them are at an advanced stage of development, such as the rFIX-Fc which has been launched in March 2014. Along with the ongoing Phase III trials, long-term post-marketing surveillance studies are needed to assess their safety and effectiveness and their impact on patients' quality of life.

Genetics Home Reference: factor VII deficiency

MedlinePlus

... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

A rare combination: congenital factor VII deficiency with Chiari malformation.

PubMed

Bay, Ali; Aktekin, Elif; Erkutlu, Ibrahim

2015-12-01

Congenital factor (VII) deficiency is a rare bleeding disorder. We present a patient with congenital FVII deficiency and congenital hydrocephalus who underwent a ventriculoperitoneal shunt operation and needed no prophylaxis after the procedure.

Onyx(®) in endovascular treatment of cerebral arteriovenous malformations - a review.

PubMed

Szajner, Maciej; Roman, Tomasz; Markowicz, Justyna; Szczerbo-Trojanowska, Małgorzata

2013-07-01

Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. In most cases, the disorder may be asymptomatic. The objective of endovascular AVM treatment is set individually for each case upon consultations with a neurosurgeon and a neurologist. The endpoint of the treatment should consist in prevention of AVM bleeding in a management procedure characterized by a significantly lower risk of complications as compared to the natural history of AVM. Endovascular interventions within AVM may include curative exclusion of AVM from circulation, embolization adjuvant to resection or radiation therapy, targeted closure of a previously identified bleeding site as well as palliative embolization. Onyx was first described in the 1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the lumen of the targeted vessel is obtained by means of precipitation. The process is enhanced peripherally to the main flux of the injected mixture. This facilitates angiographic monitoring of embolization at any stage. The degree of lumen closure is associated with the location of the vessel. Supratentorial and cortical locations are most advantageous. Dense and plexiform structure of AVM nidus as well as a low number of supplying vessels and a single superficial drainage vein are usually advantageous for Onyx administration. Unfavorable factors include nidus drainage into multiple compartments as well as multiarterial supply of the AVM, particularly from meningeal arteries, en-passant arteries or perforating feeders. Onyx appears to be a safe and efficient material for embolization of cerebral AVMs, also in cases of intracranial bleeding associated with AVM. Curative embolization of small cerebral AVMs is an efficient and safe alternative to neurosurgical and radiosurgical methods. Careful angiographic assessment of individual arteriovenous malformations should be performed before each Onyx administration.

Onyx® in endovascular treatment of cerebral arteriovenous malformations – a review

PubMed Central

Szajner, Maciej; Roman, Tomasz; Markowicz, Justyna; Szczerbo-Trojanowska, Małgorzata

2013-01-01

Summary Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. In most cases, the disorder may be asymptomatic. The objective of endovascular AVM treatment is set individually for each case upon consultations with a neurosurgeon and a neurologist. The endpoint of the treatment should consist in prevention of AVM bleeding in a management procedure characterized by a significantly lower risk of complications as compared to the natural history of AVM. Endovascular interventions within AVM may include curative exclusion of AVM from circulation, embolization adjuvant to resection or radiation therapy, targeted closure of a previously identified bleeding site as well as palliative embolization. Onyx was first described in the 1990s. It is a non-adhesive and radiolucent compound. Onyx-based closure of the lumen of the targeted vessel is obtained by means of precipitation. The process is enhanced peripherally to the main flux of the injected mixture. This facilitates angiographic monitoring of embolization at any stage. The degree of lumen closure is associated with the location of the vessel. Supratentorial and cortical locations are most advantageous. Dense and plexiform structure of AVM nidus as well as a low number of supplying vessels and a single superficial drainage vein are usually advantageous for Onyx administration. Unfavorable factors include nidus drainage into multiple compartments as well as multiarterial supply of the AVM, particularly from meningeal arteries, en-passant arteries or perforating feeders. Onyx appears to be a safe and efficient material for embolization of cerebral AVMs, also in cases of intracranial bleeding associated with AVM. Curative embolization of small cerebral AVMs is an efficient and safe alternative to neurosurgical and radiosurgical methods. Careful angiographic assessment of individual arteriovenous malformations should be performed before each Onyx administration. PMID:24115958

Platelet gene therapy improves hemostatic function for integrin αIIbβ3-deficient dogs

PubMed Central

Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

2011-01-01

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects. PMID:21606353

Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.

PubMed

Fang, Juan; Jensen, Eric S; Boudreaux, Mary K; Du, Lily M; Hawkins, Troy B; Koukouritaki, Sevasti B; Cornetta, Kenneth; Wilcox, David A

2011-06-07

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

Physiotherapy home exercise program for haemophiliacs.

PubMed

Pierstorff, K; Seuser, A; Weinspach, S; Laws, H-J

2011-05-01

Regular physiotherapy can improve the stability and flexibility of joints and decrease the bleeding risk in patients with haemophilia. To reduce the appointments for the patients and to make exercising a part of daily live, an individualized home exercise program (HEP) was designed. Retrospectively the number of bleedings during the HEP was compared to number of bleedings before. 8 patients aged between 4 and 16 years with haemophilia A were evaluated. At start and after 13 month patients had a motion analysis via topographic ultrasound. According to the results and clinical findings an individualized HEP was created. Standardised scores for clinical evaluation and the patient based evaluation of exercises were designed. At every appointment exercises were individually adjusted. Patients exercised in median 1.7 times a week. No training related bleeds occurred. 7 of 8 patients showed reduced joint and/or muscle bleeds (p<0.02). Clinical scores raised slightly in every patient. However the second motion analysis of squat and gait showed a worsening in 7 of 8 patients (p>0.05). A HEP can help to advance in physical fitness and coordination and may reduce bleeding tendency, but needs to be accomplished regularly. Patients are interested but the motivation to exercise at home is low. Disorders measured by motion analysis seem not to be sufficiently influenced by our surrogate training program. © Georg Thieme Verlag KG Stuttgart · New York.

Identification of Hospital Outliers in Bleeding Complications After Percutaneous Coronary Intervention

PubMed Central

Hess, Connie N.; Rao, Sunil V.; McCoy, Lisa A.; Neely, Megan L.; Singh, Mandeep; Spertus, John A.; Krone, Ronald J.; Weaver, W. Douglas; Peterson, Eric D.

2014-01-01

Background Post-percutaneous coronary intervention (PCI) bleeding complications are an important quality metric. We sought to characterize site-level variation in post-PCI bleeding and explore the influence of patient and procedural factors on hospital bleeding performance. Methods and Results Hospital-level bleeding performance was compared pre- and post-adjustment using the newly-revised CathPCI Registry® bleeding risk model (c-index 0.77) among 1,292 NCDR® hospitals performing >50 PCIs from 7/2009–9/2012 (n=1,984,998 procedures). Using random effects models, outlier sites were identified based on 95% confidence intervals around the hospital’s random intercept. Bleeding 72 hours post-PCI was defined as: arterial access site, retroperitoneal, gastrointestinal, or genitourinary bleeding; intracranial hemorrhage; cardiac tamponade; non-bypass surgery-related blood transfusion with pre-procedure hemoglobin ≥8 g/dl; or absolute decrease in hemoglobin value ≥3g/dl with pre-procedure hemoglobin ≤16 g/dl. Overall, the median unadjusted post-PCI bleeding rate was 5.2% and varied among hospitals from 2.6%–10.4% (5th, 95th percentiles). Center-level bleeding variation persisted after case-mix adjustment (2.8%–9.5%; 5th, 95th percentiles). While hospitals’ observed and risk-adjusted bleeding ranks were correlated (Spearman’s rho 0.88), individual rankings shifted after risk-adjustment (median Δ rank order ± 91.5; IQR 37.0, 185.5). Outlier classification changed post-adjustment for 29.3%, 16.1%, and 26.5% of low-, non-, and high-outlier sites, respectively. Hospital use of bleeding avoidance strategies (bivalirudin, radial access, or vascular closure device) was associated with risk-adjusted bleeding rates. Conclusions Despite adjustment for patient case-mix, there is wide variation in rates of hospital PCI-related bleeding in the United States. Opportunities may exist for best performers to share practices with other sites. PMID:25424242

Acute generalized, widespread bleeding. Diagnosis and management.

PubMed

Rocha, E; Páramo, J A; Montes, R; Panizo, C

1998-11-01

Acute generalized, widespread bleeding is often related to disseminated intravascular coagulation (DIC), a pathologic process which complicates the clinical course of many diseases and is characterized by huge amounts of thrombin and plasmin within the circulation. The final result is the consumption of platelets, coagulation factors and inhibitors, as well as secondary hyperfibrinolysis, all leading to diffuse hemorrhage and microthromboses. This review article examines the present attitudes to the diagnosis and treatment of overt DIC in clinical practice, emphasizing the importance of an accurate differential diagnosis from some other processes characterized by acute generalized, widespread bleeding. The authors have been working in this field, both at experimental and clinical levels, contributing original papers for many years. In addition, material examined in this review includes articles published in journals covered by MedLine, recent reviews in journals with high impact factor and in relevant books on hemostasis and thrombosis. DIC is an intermediary mechanism of disease which complicates the clinical course of many well-known disorders. Although the systemic hemorrhagic syndrome is the predominant clinical manifestation, massive intravascular thrombosis frequently occurs contributing to ischemia and associated organ damage, making the mortality rate of this condition high. Current concepts on the pathophysiology, laboratory diagnosis and management of DIC are presented. Complex pathophysiological interrelations make the diagnosis of the etiology of the DIC difficult in clinical practice, although simple tests are useful for identification of patients with the process. Laboratory diagnosis of DIC is mainly based on screening assays, which allow a rapid diagnosis, whereas some other highly sensitive but more complex assays are not always available to routine clinical laboratories. The management of DIC is based on the treatment of the underlying disease, supportive and replacement therapies and the control of the coagulation mechanisms. Although some advances have been achieved, management decisions are still controversial, so that therapy should be highly individualized depending on the nature of the DIC and severity of clinical symptoms. Many syndromes sharing common findings with DIC, such as primary hyperfibrinolysis or thrombotic thrombocytopenic purpura, should be excluded. Finally, new therapeutic approaches to the management of this potentially catastrophic syndrome are required.

Plasma Cell Disorders

MedlinePlus

... Time Poses Clot Risk (News) New Hemophilia Treatment Stems Bleeding Episodes (News) Quickly Treating Mini-Stroke Can Cut Risk for Future Stroke (News) Zelboraf Approved for Rare Blood Cancer (Video) Chronic Lymphocytic Leukemia (Video) Blood Clots: Plugging the Breaks Additional Content ...

Hemophilia Data and Statistics

MedlinePlus

... View public health webinars on blood disorders Data & Statistics Language: English (US) Español (Spanish) Recommend on Facebook ... genetic testing is done to diagnose hemophilia before birth. For the one-third ... rates and hospitalization rates for bleeding complications from hemophilia ...

Single-platelet nanomechanics measured by high-throughput cytometry

NASA Astrophysics Data System (ADS)

Myers, David R.; Qiu, Yongzhi; Fay, Meredith E.; Tennenbaum, Michael; Chester, Daniel; Cuadrado, Jonas; Sakurai, Yumiko; Baek, Jong; Tran, Reginald; Ciciliano, Jordan C.; Ahn, Byungwook; Mannino, Robert G.; Bunting, Silvia T.; Bennett, Carolyn; Briones, Michael; Fernandez-Nieves, Alberto; Smith, Michael L.; Brown, Ashley C.; Sulchek, Todd; Lam, Wilbur A.

2017-02-01

Haemostasis occurs at sites of vascular injury, where flowing blood forms a clot, a dynamic and heterogeneous fibrin-based biomaterial. Paramount in the clot's capability to stem haemorrhage are its changing mechanical properties, the major drivers of which are the contractile forces exerted by platelets against the fibrin scaffold. However, how platelets transduce microenvironmental cues to mediate contraction and alter clot mechanics is unknown. This is clinically relevant, as overly softened and stiffened clots are associated with bleeding and thrombotic disorders. Here, we report a high-throughput hydrogel-based platelet-contraction cytometer that quantifies single-platelet contraction forces in different clot microenvironments. We also show that platelets, via the Rho/ROCK pathway, synergistically couple mechanical and biochemical inputs to mediate contraction. Moreover, highly contractile platelet subpopulations present in healthy controls are conspicuously absent in a subset of patients with undiagnosed bleeding disorders, and therefore may function as a clinical diagnostic biophysical biomarker.

Developing a public health research agenda for women with blood disorders.

PubMed

Byams, Vanessa R; Beckman, Michele G; Grant, Althea M; Parker, Christopher S

2010-07-01

Bleeding and clotting in women is an issue that directly affects the life of every woman, child, and family worldwide. This article summarizes recent activities undertaken by the Division of Blood Disorders (DBD) at the Centers for Disease Control and Prevention (CDC) to identify risk factors through evidence-based research and surveillance to prevent complications of blood disorders in women. Specific focus is given to our efforts to improve early identification and diagnosis of blood disorders among women, improve our understanding of maternal and infant outcomes, and develop surveillance systems to monitor the prevalence and incidence of these events.

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. Objectives To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 × 109/L); standard trigger (10 × 109/L); higher trigger (20 × 109/L, 30 × 109/L, 50 × 109/L); or alternative platelet trigger (for example platelet mass)). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 × 109/L) versus a higher trigger (20 × 109/L or 30 × 109/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations. The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review. Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence). One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors’ own results; low-quality evidence). Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence). Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence). Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence). Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference −2.09, 95% CI −3.20 to −0.99; low-quality evidence). One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09). None of the studies reported on quality of life. Authors’ conclusions In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 × 109/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 × 109/L or 30 × 109/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 × 109/L or 30 × 109/L). Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 × 109/L) in the absence of other risk factors for bleeding. PMID:26576687

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

PubMed

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-11-18

Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)). We used the standard methodological procedures expected by Cochrane. Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors' own results; low-quality evidence).Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence).Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence).Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence).Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference -2.09, 95% CI -3.20 to -0.99; low-quality evidence).One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09).None of the studies reported on quality of life. In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 x 10(9)/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L).Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10(9)/L) in the absence of other risk factors for bleeding.

Celiac disease and dysfunctional uterine bleeding; the efficiency of gluten free diet.

PubMed

Ehsani-Ardakani, M J; Fallahian, M; Rostami, K; Rostami-Nejad, M; Lotfi, S; Mohaghegh-Shalmani, H; Dabiri, R; Norouzinia, M; Azizpour-Shoobi, F; Zali, M R

2014-01-01

The aim of this study was to investigate the relation between Celiac disease (CD) and unexplained dysfunctional uterine bleeding (DUB) in celiac women. The celiac patients were selected from women who were referred to celiac department. Controls were selected from those women without any signs of celiac disease and matched with age. Meanwhile, a trained physician was ready to explain the study, and then in case of their allowance, a questionnaire was completed by the physician. 24 % of celiac women reported a past history of at least one menstrual cycle disorder vs 10 % of controls reported these problems (p=0.038) and higher percentage of unexplained DUB has been observed in celiac women. All celiac patients were undertaking gluten free diet for at least 3 months and the celiac patients who reported the history of DUB were again interviewed for any signs of unexplained DUB. From 12 celiac women with DUB, 10 patients reported no more unexplained DUB after getting gluten-free diet (83.3 %). The occurrence of a significant correlation between CD and DUB suggests the possibility of considering CD as one of the potential causes of abnormal uterine bleeding. Therefore, celiac disease must be seriously considered in the screening of patients with reproductive disorders (Tab. 2,Ref. 23).

External Beam Radiotherapy for Prostate Cancer Patients on Anticoagulation Therapy: How Significant is the Bleeding Toxicity?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choe, Kevin S.; Jani, Ashesh B.; Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.ed

Purpose: To characterize the bleeding toxicity associated with external beam radiotherapy for prostate cancer patients receiving anticoagulation (AC) therapy. Methods and Materials: The study cohort consisted of 568 patients with adenocarcinoma of the prostate who were treated with definitive external beam radiotherapy. Of these men, 79 were receiving AC therapy with either warfarin or clopidogrel. All patients were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Bleeding complications were recorded during treatment and subsequent follow-up visits. Results: With a median follow-up of 48 months, the 4-year actuarial risk of Grade 3 or worse bleeding toxicity was 15.5% for those receivingmore » AC therapy compared with 3.6% among those not receiving AC (p < .0001). On multivariate analysis, AC therapy was the only significant factor associated with Grade 3 or worse bleeding (p < .0001). For patients taking AC therapy, the crude rate of bleeding was 39.2%. Multivariate analysis within the AC group demonstrated that a higher radiotherapy dose (p = .0408), intensity-modulated radiotherapy (p = 0.0136), and previous transurethral resection of the prostate (p = .0001) were associated with Grade 2 or worse bleeding toxicity. Androgen deprivation therapy was protective against bleeding, with borderline significance (p = 0.0599). Dose-volume histogram analysis revealed that Grade 3 or worse bleeding was minimized if the percentage of the rectum receiving >=70 Gy was <10% or the rectum receiving >=50 Gy was <50%. Conclusion: Patients taking AC therapy have a substantial risk of bleeding toxicity from external beam radiotherapy. In this setting, dose escalation or intensity-modulated radiotherapy should be used judiciously. With adherence to strict dose-volume histogram criteria and minimizing hotspots, the risk of severe bleeding might be reduced.« less

Leidos Biomed Teams with NCI, DOE, and Argonne National Lab to Support National X-Ray Resource | Poster

Cancer.gov

Scientists are making progress in understanding a bleeding disorder caused by prescription drug interactions, thanks to a high-tech research facility involving two federal national laboratories, Argonne and Frederick.

Dose-distance metric that predicts late rectal bleeding in patients receiving radical prostate external-beam radiotherapy

NASA Astrophysics Data System (ADS)

Lee, Richard; Chan, Elisa K.; Kosztyla, Robert; Liu, Mitchell; Moiseenko, Vitali

2012-12-01

The relationship between rectal dose distribution and the incidence of late rectal complications following external-beam radiotherapy has been previously studied using dose-volume histograms or dose-surface histograms. However, they do not account for the spatial dose distribution. This study proposes a metric based on both surface dose and distance that can predict the incidence of rectal bleeding in prostate cancer patients treated with radical radiotherapy. One hundred and forty-four patients treated with radical radiotherapy for prostate cancer were prospectively followed to record the incidence of grade ≥2 rectal bleeding. Radiotherapy plans were used to evaluate a dose-distance metric that accounts for the dose and its spatial distribution on the rectal surface, characterized by a logistic weighting function with slope a and inflection point d0. This was compared to the effective dose obtained from dose-surface histograms, characterized by the parameter n which describes sensitivity to hot spots. The log-rank test was used to determine statistically significant (p < 0.05) cut-off values for the dose-distance metric and effective dose that predict for the occurrence of rectal bleeding. For the dose-distance metric, only d0 = 25 and 30 mm combined with a > 5 led to statistical significant cut-offs. For the effective dose metric, only values of n in the range 0.07-0.35 led to statistically significant cut-offs. The proposed dose-distance metric is a predictor of rectal bleeding in prostate cancer patients treated with radiotherapy. Both the dose-distance metric and the effective dose metric indicate that the incidence of grade ≥2 rectal bleeding is sensitive to localized damage to the rectal surface.

[Relapse of bleeding ulcer in a 15 year-old boy with collagenous gastritis].

PubMed

Haase, Anne-Mette; Kelsen, Jens

2012-06-18

Collagenous gastritis (CG) is a rare disorder. Two patient groups are known: 1) Children and young adults, presenting with anaemia and abdominal pain, and 2) adults presenting with watery diarrhoea. In the latter group, CG is frequently associated with collagenous colitis and/or coeliac disease. This case concerns a 15-year-old boy with a bleeding ulcer. The biopsies from corpus ventriculi showed a thickened subepithelial collagen band (> 10 micrometres), and the patient was diagnosed with CG. Ulcers are rarely linked to CG. CG should be considered when ulcers are found in children and young adults.

Two Cases of Lethal Complications Following Ultrasound-Guided Percutaneous Fine-Needle Biopsy of the Liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drinkovic, Ivan; Brkljacic, Boris

1996-09-15

Two cases with lethal complications are reported among 1750 ultrasound (US)-guided percutaneous fine-needle liver biopsies performed in our department. The first patient had angiosarcoma of the liver which was not suspected after computed tomography (CT) and US studies had been performed. The other patient had hepatocellular carcinoma in advanced hepatic cirrhosis. Death was due to bleeding in both cases. Pre-procedure laboratory tests did not reveal the existence of major bleeding disorders in either case. Normal liver tissue was interposed in the needle track between the liver capsule and the lesions which were targeted.

Chinese guidelines for treatment of adult primary immune thrombocytopenia.

PubMed

Liu, Xin-Guang; Bai, Xiao-Chuan; Chen, Fang-Ping; Cheng, Yun-Feng; Dai, Ke-Sheng; Fang, Mei-Yun; Feng, Jian-Ming; Gong, Yu-Ping; Guo, Tao; Guo, Xin-Hong; Han, Yue; Hong, Luo-Jia; Hu, Yu; Hua, Bao-Lai; Huang, Rui-Bing; Li, Yan; Peng, Jun; Shu, Mi-Mi; Sun, Jing; Sun, Pei-Yan; Sun, Yu-Qian; Wang, Chun-Sen; Wang, Shu-Jie; Wang, Xiao-Min; Wu, Cong-Ming; Wu, Wen-Man; Yan, Zhen-Yu; Yang, Feng-E; Yang, Lin-Hua; Yang, Ren-Chi; Yang, Tong-Hua; Ye, Xu; Zhang, Guang-Sen; Zhang, Lei; Zheng, Chang-Cheng; Zhou, Hu; Zhou, Min; Zhou, Rong-Fu; Zhou, Ze-Ping; Zhu, Hong-Li; Zhu, Tie-Nan; Hou, Ming

2018-06-01

Primary immune thrombocytopenia (ITP) is a bleeding disorder commonly encountered in clinical practice. The International Working Group (IWG) on ITP has published several landmark papers on terminology, definitions, outcome criteria, bleeding assessment, diagnosis, and management of ITP. The Chinese consensus reports for diagnosis and management of adult ITP have been updated to the 4th edition. Based on current consensus positions and new emerging clinical evidence, the thrombosis and hemostasis group of the Chinese Society of Hematology issued Chinese guidelines for management of adult ITP, which aim to provide evidence-based recommendations for clinical decision making.

Prophylactic treatment of hereditary severe factor VII deficiency in pregnancy.

PubMed

Pfrepper, Christian; Siegemund, Annelie; Hildebrandt, Sven; Kronberg, Juliane; Scholz, Ute; Niederwieser, Dietger

2017-09-01

: Severe hereditary factor VII deficiency is a rare bleeding disorder and may be associated with a severe bleeding phenotype. We describe a pregnancy in a 33-year-old woman with compound heterozygous factor VII deficiency and a history of severe menorrhagia and mucocutaneous bleedings. After discontinuation of contraceptives, menstruation was covered with recombinant activated factor VII (rFVIIa), and during pregnancy, rFVIIa had to be administered in first trimester in doses ranging from 15 to 90 μg/kg per day because of recurrent retroplacental hematomas and vaginal bleedings. Thrombin generation was measured in first trimester at different doses of rFVIIa and showed an increase in lag time when doses of less than 30 μg/kg/day were administered, whereas time to thrombin peak and peak thrombin were not influenced. A low-dose rFVIIa prophylactic treatment of 15 μg/kg every other day in the late second and in the third trimester was sufficient to allow a successful childbirth in this patient with severe factor VII deficiency.

Renal biopsy practice: What is the gold standard?

PubMed

Brachemi, Soumeya; Bollée, Guillaume

2014-11-06

Renal biopsy (RB) is useful for diagnosis and therapy guidance of renal diseases but incurs a risk of bleeding complications of variable severity, from transitory haematuria or asymptomatic hematoma to life-threatening hemorrhage. Several risk factors for complications after RB have been identified, including high blood pressure, age, decreased renal function, obesity, anemia, low platelet count and hemostasis disorders. These should be carefully assessed and, whenever possible, corrected before the procedure. The incidence of serious complications has become low with the use of automated biopsy devices and ultrasound guidance, which is currently the "gold standard" procedure for percutaneous RB. An outpatient biopsy may be considered in a carefully selected population with no risk factor for bleeding. However, controversies persist on the duration of observation after biopsy, especially for native kidney biopsy. Transjugular RB and laparoscopic RB represent reliable alternatives to conventional percutaneous biopsy in patients at high risk of bleeding, although some factors limit their use. This aim of this review is to summarize the issues of complications after RB, assessment of hemorrhagic risk factors, optimal biopsy procedure and strategies aimed to minimize the risk of bleeding.

Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

PubMed

Yates, Sean; Sarode, Ravi

2013-11-01

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

[New knowledge on the diverticular disease of colon].

PubMed

Dolejsí, Mojmír

2011-01-01

The article is a summary paper aimed at new knowledge, concerning the classification, diagnostics, medication and endoscopic treatment of diverticular disease of colon. Briefly mentioned are the issues of functional disorder in the field of diverticulosis--symptomatic uncomplicated diverticular disease of colon. Diverticular bleeding is explained in terms of its pathogenesis and diagnostics. The problem with estimation the ration of diverticular bleedings in the total number of bleedings into the lower digestive tract is caused by diverse criteria for selecting patients and two levels of diagnostic of diverticular bleeding (definite and presumptive). Attention is paid also to diverticular colitis. Synonyms, endoscopic and histological classification are listed. The main endoscopic findings represent areas of erythema, which are visible on the mucosa between diverticula. Diverticulitis is seen as the most significant complication and the diagnostics of diverticulitis is discussed in detail. The first recommended step in the diagnosis is an urgent abdominal ultrasound; the gold standard is a CT examination of the abdomen, in special situations, some other imaging methods should be used: MRI, colonoscopy. The article ends with an overview of modern therapeutic options in the treatment of diverticular colitis and diverticulitis, particularly the use of antibiotics, probiotics, mesalasine and antispasmodics. Negative effect of NSAIDs on the course of diverticulitis and induction diverticular bleeding is listed.

Abnormal uterine bleeding in perimenopause.

PubMed

Goldstein, S R; Lumsden, M A

2017-10-01

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Characterization of an apparently synonymous F5 mutation causing aberrant splicing and factor V deficiency.

PubMed

Nuzzo, F; Bulato, C; Nielsen, B I; Lee, K; Wielders, S J; Simioni, P; Key, N S; Castoldi, E

2015-03-01

Coagulation factor V (FV) deficiency is a rare autosomal recessive bleeding disorder. We investigated a patient with severe FV deficiency (FV:C < 3%) and moderate bleeding symptoms. Thrombin generation experiments showed residual FV expression in the patient's plasma, which was quantified as 0.7 ± 0.3% by a sensitive prothrombinase-based assay. F5 gene sequencing identified a novel missense mutation in exon 4 (c.578G>C, p.Cys193Ser), predicting the abolition of a conserved disulphide bridge, and an apparently synonymous variant in exon 8 (c.1281C>G). The observation that half of the patient's F5 mRNA lacked the last 18 nucleotides of exon 8 prompted us to re-evaluate the c.1281C>G variant for its possible effects on splicing. Bioinformatics sequence analysis predicted that this transversion would activate a cryptic donor splice site and abolish an exonic splicing enhancer. Characterization in a F5 minigene model confirmed that the c.1281C>G variant was responsible for the patient's splicing defect, which could be partially corrected by a mutation-specific morpholino antisense oligonucleotide. The aberrantly spliced F5 mRNA, whose stability was similar to that of the normal mRNA, encoded a putative FV mutant lacking amino acids 427-432. Expression in COS-1 cells indicated that the mutant protein is poorly secreted and not functional. In conclusion, the c.1281C>G mutation, which was predicted to be translationally silent and hence neutral, causes FV deficiency by impairing pre-mRNA splicing. This finding underscores the importance of cDNA analysis for the correct assessment of exonic mutations. © 2014 John Wiley & Sons Ltd.

An unusual cause of stridor in a neonate.

PubMed

Fah, K K; Tan, H K

1994-01-01

We report an unusual case of unilateral vocal fold palsy due to intracranial haemorrhage in a neonate with undiagnosed haemophilia A. Bleeding disorders in neonates are briefly discussed and the importance of a systemic investigation of stridor in children is emphasized.

Central nervous system bleeding in pediatric patients with factor XIII deficiency: a study on 23 new cases.

PubMed

Naderi, Majid; Alizadeh, Shaban; Kazemi, Ahmad; Tabibian, Shadi; Zaker, Farhad; Bamedi, Taregh; Kashani Khatib, Zahra; Dorgalaleh, Akbar

2015-03-01

Factor XIII (FXIII) deficiency is an extremely rare bleeding disorder, which has the highest incidence in Sistan and Baluchistan Province in Iran, compared to its overall incidence around the world. This disorder has different clinical manifestations ranging from mild bleeding tendency to lethal bleeding episodes including central nervous system (CNS) hemorrhage. The aim of this study was to evaluate the demographic data, pattern of CNS bleeding, and the role of plasminogen activator inhibitor-1 (PAI-1) (PAI-1) 4G/5G and thrombin activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphisms in intracranial and extracranial hemorrhages in 23 new cases of FXIII-deficient subjects. This case-control study was conducted on 23 FXIII-deficient patients with CNS bleeding episodes and 23 patients as the control group with FXIII deficiency but without any history of CNS bleeding. Initially, to confirm the molecular defect, both groups were evaluated for the most frequently reported mutation of FXIII (Trp187Arg mutation) in a previous study in Sistan and Baluchistan Province. Then, demographic data, clinical manifestations, and pattern of CNS bleeding were determined. Eventually, the patients were assessed for PAI-14G/5G and TAFI Thr325Ile polymorphisms. The results of this study revealed that all the subjects (including the case and control groups) were homozygous for Trp187Arg mutation. Nineteen patients (82.6%) had intracranial hemorrhage (ICH) and four patients (17.4%) had extracranial hemorrhage (ECH). Intraparenchymal hemorrhage was the most common form of ICH (89.5%), and epidural hemorrhage was observed in two patients (10.5%). Anatomic regions in patients with intraparenchymal hemorrhage were temporal in six (35.3%), occipital in four (23.5%), diffused intraparenchymal in four (23.5%), temporal-occipital in two (11.8%), and subdural with temporal in one (5.9%) patient. We found that in the case group, 14 patients (60.8%) were homozygous for TAFI Thr325Ile polymorphism and 8 cases (34.7%) were heterozygous. In the control group, 4 (17.4%) and 13 (56.5%) patients were homozygous and heterozygous, respectively (P < 0.001 vs. P < 0.01).We also found that an equal number of patients (two individuals) in the case and control groups (8.7% in each group) were heterozygous for PAI-14G/5G polymorphism. It seems that PAI-14G/5G polymorphism does not have any effect on occurrence of ICH and ECH in patients with FXIII deficiency, while TAFI Thr325Ile is a strong genetic risk factor (odds ratio:14.9, 95% confidence interval: 7.4-31.1).

Mortality caused by intracranial bleeding in non-severe hemophilia A patients.

PubMed

Loomans, J I; Eckhardt, C L; Reitter-Pfoertner, S E; Holmström, M; van Gorkom, B Laros; Leebeek, F W G; Santoro, C; Haya, S; Meijer, K; Nijziel, M R; van der Bom, J G; Fijnvandraat, K

2017-06-01

Essentials Data on bleeding-related causes of death in non-severe hemophilia A (HA) patients are scarce. Such data may provide new insights into areas of care that can be improved. Non-severe HA patients have an increased risk of dying from intracranial bleeding. This demonstrates the need for specialized care for non-severe HA patients. Background Non-severe hemophilia (factor VIII concentration [FVIII:C] of 2-40 IU dL -1 ) is characterized by a milder bleeding phenotype than severe hemophilia A. However, some patients with non-severe hemophilia A suffer from severe bleeding complications that may result in death. Data on bleeding-related causes of death, such as fatal intracranial bleeding, in non-severe patients are scarce. Such data may provide new insights into areas of care that can be improved. Aims To describe mortality rates, risk factors and comorbidities associated with fatal intracranial bleeding in non-severe hemophilia A patients. Methods We analyzed data from the INSIGHT study, an international cohort study of all non-severe hemophilia A patients treated with FVIII concentrates during the observation period between 1980 and 2010 in 34 participating centers across Europe and Australia. Clinical data and vital status were collected from 2709 patients. We report the standardized mortality rate for patients who suffered from fatal intracranial bleeding, using a general European male population as a control population. Results Twelve per cent of the 148 deceased patients in our cohort of 2709 patients died from intracranial bleeding. The mortality rate between 1996 and 2010 for all ages was 3.5-fold higher than that in the general population (95% confidence interval [CI] 2.0-5.8). Patients who died from intracranial bleeding mostly presented with mild hemophilia without clear comorbidities. Conclusion Non-severe hemophilia A patients have an increased risk of dying from intracranial bleeding in comparison with the general population. This demonstrates the need for specialized care for non-severe hemophilia A patients. © 2017 International Society on Thrombosis and Haemostasis.

[The causes of recurrent ulcerative gastroduodenal bleeding].

PubMed

Lipnitsky, E M; Alekberzade, A V; Gasanov, M R

To explore microcirculatory changes within the first 48 hours after admission, to compare them with clinical manifestations of bleeding and to define the dependence of recurrent bleeding from the therapy. The study included 108 patients with ulcerative gastroduodenal bleeding who were treated at the Clinical Hospital #71 for the period 2012-2014. There were 80 (74.1%) men and 28 (25.9%) women. Age ranged 20-87 years (mean 54.4±16.8 years). Patients younger than 45 years were predominant (33.4%). J. Forrest classification (1974) was used in endoscopic characterization of bleeding. Roccal Prognostic Scale for gastroduodenal bleeding was applied in all patients at admission to assess the risk of possible recurrence. Patients were divided into 2 groups. Group 1 included 53 (49.1%) patients without recurrent bleeding; group 2-55 (50.1%) patients who had recurrent bleeding within the first two days of treatment. Investigation of microcirculation showed the role of vegetative component including blood circulation centralization, blood flow slowing, blood cells redistribution providing sufficient blood oxygenation. By the end of the first day we observed pronounced hemodilution, decreased blood oxygenation, blood flow restructuring with its acceleration above 1 ml/s, violation of tissue oxygenation, signs of hypovolemia. These changes were significantly different from group 2 and associated with circulatory decentralization with possible pulmonary microcirculation disturbances and interstitial edema. This processes contribute to disruption of tissue oxygenation. We assume that recurrent bleeding in group 2 was caused by fluid therapy in larger volumes than it was necessary in this clinical situation. Infusion therapy should be significantly reduced for the debut of gastroduodenal ulcerative bleeding. Sedative therapy is advisable to reduce the influence of central nervous system.

[Massive hemorrhage of upper gastrointestinal tract caused by gastrointestinal stromal tumor of the stomach--case report].

PubMed

Lalović, Nenad; Dukić Vladicić, Nikolina; Marić, Radmil; Cuk, Mirjana; Simatović, Milan; Jokanović, Dragana

2012-01-01

Acute bleeding from the upper gastrointestinal system is a medical emergency which is followed by high mortality rate, ranging from 6 to 15% in spite of modern diagnostic methods and treatment. Bleeding from the upper gastrointestinal system may be caused by gastrointestinal stromal tumors of the stomach, which are mainly characterized by occult bleeding, while profuse bleeding rarely occurs accompanied by hemorrhagic shock. Gastrointestinal stromal tumors of stomach are the most common mesenchimal tumors of the gastrointestinal tract. In our study we showed a 60-year-old female patient with profuse bleeding from the stomach and the clinical picture of severe hemorrhagic shock, caused by gastrointestinal stromal tumor. An ovoid junction, raised towards the lumen, covered with ulcerated mucosa in several places and followed by massive arterial bleeding was found intraoperatively, after the performed gastrotomy. Histopathological examination with immunohistochemical analysis confirmed that this was a gastrointestinal stromal tumor of the stomach. Acute bleeding from the digestive system is a sudden and serious condition of the body. Urgent esophagogastroduodenoscopy is a sensitive and specific diagnostic and therapeutic method of choice. Massive bleeding from the upper gastrointestinal tract is very rarely caused by gastrointestinal stromal tumors, whose clinical picture is very heterogeneous and depends on tumor size and location. Abundant bleeding from the tumor is an indication for urgent surgical intervention. According to the literature massive hemorrhage of the upper digestive system can rarely be caused by gastrointestinal stromal tumor of the stomach. It is shown that abundant hemorrhage of the upper digestive tract can be caused with gastric gastrointestinal stromal tumor. Surgical resection is the main form of treatment of gastrointestinal stromal tumors of the digestive system and bleeding from these tumors caused by failure of endoscopic hemostasis.

Extended and continuous use of hormonal contraceptives to reduce menstruation.

PubMed

Wiegratz, Inka; Kissler, Stefan; Kuhl, Herbert; Kaufmann, Manfred

2006-09-01

During the use of long-cycle regimens of monophasic oral contraceptives, the total number of bleeding and cycle-dependent complaints is considerably lower than during conventional treatment with oral contraceptives. Despite an initially higher rate of irregular bleeding, the majority of women prefer the long-cycle treatment since it may improve quality of life. As this regimen provides an enhanced ovarian suppression, it may prevent pregnancies, especially in noncompliant women or patients who are concomitantly treated with drugs that may impair the efficacy of oral contraceptives. Postponement or suppression of withdrawal bleeding also reduces menses-associated disorders such as menorrhagia and dysmenorrhea, and has beneficial effects in patients with hemorrhagic diathesis, endometriosis, uterine leiomyomas and polycystic ovary syndrome. Long-term studies are necessary to assess the impact of long-term use of extended regimens of oral contraceptives on safety, for example, the risk of cancer and cardiovascular disease, and on fertility after discontinuation of treatment.

PSYCHOLOGICAL FACTORS IN 155 PATIENTS WITH FUNCTIONAL UTERINE BLEEDING.

PubMed

DUTTON, W A

1965-02-20

One hundred and fifty-five women with functional uterine bleeding were studied to evaluate the importance of concomitant psychological disorders. Psychological illnesses were diagnosed in 128 patients (82.6%), most of which arose from problems directly related to sexual or reproductive functions. The remaining 27 patients (17.4%) were different in that they were psychologically stable and all but two were at puberty or approaching the menopause.Histological studies of endometrial samples from 135 of these patients indicated little evidence of abnormal sex hormone activity; 77 (57%) showed normal secretory phase endometrium and 32 (23.7%), proliferative phase endometrium. The remaining 26 (19.2%) showed evidence of some endocrine dysfunction, 15 such specimens being obtained from psychologically stable patients.It is probable that psychological disturbances are the principal cause of functional uterine bleeding during the prime reproductive years. The psychological component of the illness is the most important and determines the ultimate prognosis.

Pentasaccharides in the prophylaxis and treatment of venous thromboembolism: a systematic review.

PubMed

Nijkeuter, M; Huisman, M V

2004-09-01

The aim of this review is to perform a critical analysis of all completed studies evaluating pentasaccharides-synthetically derived, selective inhibitors of activated factor X-in prophylaxis in major orthopedic surgery and the treatment of venous thromboembolism. Venous thromboembolism is a disorder with considerable morbidity when left untreated. New antithrombotic agents have been developed that selectively inhibit components of the coagulation system, thereby avoiding the difficulties associated with current anticoagulants. The pentasaccharides fondaparinux and idraparinux are the first of a new class of synthetic selective inhibitors of activated factor X. Fondaparinux has been extensively investigated in two areas: orthopedic surgery and venous thromboembolism. It is clear from four thromboprophylaxis studies in major orthopedic surgery that fondaparinux is 50% more effective in reducing venous thromboembolism than enoxaparin. This superior efficacy led to an overall increase in major bleeding, which was however primarily due to more fondaparinux-treated patients with bleeding indexes of 2 or greater. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two groups. In the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, fondaparinux was equally effective as low molecular weight heparins and unfractionated heparin, respectively, without a different incidence in major bleeding in fondaparinux and comparator heparin groups. Fondaparinux, one of the first of a new class of synthetic selective factor Xa inhibitors, is overall 50% more effective in reducing venous thromboembolism than enoxaparin in major orthopedic surgery, with an overall 1% increased rate of major bleeding, when compared with enoxaparin. The incidence of fatal bleeding, critical organ bleeding, or bleeding leading to reoperation did not differ significantly between the two treatment groups. Fondaparinux is equally effective as low molecular weight heparins and unfractionated heparin in the initial treatment of patients with proximal vein thrombosis and pulmonary embolism, respectively. Finally, as with any new drug, fondaparinux should be used cautiously and only in patients who reflect the population of the clinical trials in which the drug was evaluated.

Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders.

PubMed

Croom, Katherine F; McCormack, Paul L

2008-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.

Curative effects of two new endometrial ablation procedures using radiofrequency thermocoagulation for the treatment of severe abnormal uterine bleeding.

PubMed

Yin, Geping; Li, Juan; Zhu, Tongyu; Chen, Ming

2013-07-01

Severe Abnormal Uterine Bleeding (SAUB) is a common gynecological disorder. The clinical characteristics include disordered menstrual cycle and massive bleeding that can cause anemia or secondary infection. Current treatment mainly relies on drug therapy or surgical removal of the uterus, each having its significant disadvantages. How to preserve the uterus, reduce the pain from surgery, and achieve better treatment effects have been well known but remaining as unresolved issues. This study aims at evaluating two types of radiofrequency (RF) thermocoagulation procedures for the treatment of SAUB: the RF-A procedure group included 25 SAUB patients ≥45 years of age treated for amenorrhea; the RF-B procedure group included 51 patients at <45 years of age treated for the control of excessive bleeding. Post-treatment ratings of menstrual satisfaction and pre-/post-treatment menstrual scores-pictorial blood loss assessment chart (PBAC)-and hemoglobin levels were collected; and the mean length of follow-up was 72 months. Also, 38 SAUB patients treated with standard drug regimens served as a control group. The results of the study showed that following RF treatment, the average long-term patient menstrual satisfaction was greater than 92 %. In both the RF groups, PBAC scores and hemoglobin levels were significantly improved from baseline (p < .05). Compared with the control group, PBAC scores and hemoglobin levels were also significantly better for the RF groups at 6-24-month post-operation. Patients experienced no hysterectomy in association with the RF procedures. In conclusion, this pilot study suggests that the novel RF procedures are both safe and effective in treating patients with SAUB. Further investigation is necessary to evaluate their application in broader clinical indication.

Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study

PubMed Central

2012-01-01

Background Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. Patients/methods In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT) and the inhibition of platelet aggregation (IPA) by light transmission aggregometry (LTA). Arachidonic acid (0.625 mmol/L) and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L) were used as platelet agonists. Results Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis) were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32). Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. Conclusion In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L. PMID:22236361

Wavelet-based analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Rodionov, M. A.; Pavlova, O. N.; Semyachkina-Glushkovskaya, O. V.; Berdnikova, V. A.; Kuznetsova, Ya. V.; Semyachkin-Glushkovskij, I. A.

2012-03-01

Studying of nitric oxide (NO) dependent mechanisms of regulation of microcirculation in a stomach can provide important diagnostic markers of the development of stress-induced ulcer bleedings. In this work we use a multiscale analysis based on the discrete wavelet-transform to characterize a latent stage of illness formation in rats. A higher sensitivity of stomach vessels to the NO-level in ill rats is discussed.

Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies.

PubMed

Martin, Isabelle; Kriaa, Fayçal; Proulle, Valérie; Guillet, Benoît; Kaplan, Cécile; D'Oiron, Roseline; Debré, Marianne; Fressinaud, Edith; Laurian, Yyes; Tchernia, Gil; Charpentier, Bernard; Lambert, Thierry; Dreyfus, Marie

2002-12-01

Type I Glanzmann's thrombasthenia is a rare congenital platelet function disorder, characterized by undetectable platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa). Severe bleeding is controlled by transfusion of normal platelets, leading in some cases to the occurrence of anti-GPIIb-IIIa isoantibodies, which induces a loss of transfused platelet efficacy. We used immunoadsorption on protein A Sepharose (IA-PA), which has been shown to be efficient in decreasing the titre of antibodies in several immune diseases, in three patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies on five different occasions. IA-PA was well tolerated with no deleterious side-effects reported. It induced a dramatic decrease of total immunoglobulin (Ig)G, including anti-GPIIb-IIIa isoantibody levels, as assessed by the monoclonal antibody-specific immobilization of platelet antigens test and the ex vivo inhibition of normal platelet aggregation induced by the patient's platelet-rich or platelet-poor plasma. Elimination of the antibody was associated with a correction of the bleeding time following platelet transfusion. IA-PA combined with platelet transfusion made it possible to control two life-threatening haemorrhages, and allowed two surgical procedures and one bone marrow transplantation to be performed safely. Our experience suggests that IA-PA, which restores the haemostatic efficacy of platelet transfusion, is a valuable therapeutic strategy in patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies.

A case of coffee-ground emesis in an elderly patient

PubMed Central

De Palma, Giovanni D; Persico, Marcello; Forestieri, Pietro

2014-01-01

Key Clinical Message Black esophagus is an exceeding rare disorder with a multifactorial etiology. Clinical presentation is generally related to upper gastrointestinal bleeding. Diagnosis is based on endoscopic images. Overall mortality is largely related to the underlying medical condition. PMID:25356232

Gastritis

MedlinePlus

... Less common causes are: Autoimmune disorders (such as pernicious anemia) Backflow of bile into the stomach (bile reflux) ... causing bleeding from the lining of the stomach, symptoms may include: Black stools Vomiting blood ... Complete blood count (CBC) to check for anemia or low blood count Examination of the stomach ...

Sexual harassment and menstrual disorders among Italian university women: A cross-sectional observational study.

PubMed

Romito, P; Cedolin, C; Bastiani, F; Beltramini, L; Saurel-Cubizolles, M J

2017-07-01

Menstrual disorders and sexual harassment are common among young women and interfere with their life and activities. We aimed to describe the association of sexual harassment and menstrual disorders among female university students. This cross-sectional, observational study examined the association between sexual harassment and menstrual disorders in a sample of 349 university students in Italy. Students answered an anonymous self-administered questionnaire. Descriptive bivariate analyses and logistic regression analyses were performed. Main outcome measures were associations between levels of exposure to sexual harassment (none, levels 1 and 2) and five menstrual disorders (premenstrual symptoms, heavy bleeding, pain, irregular cycles, and amenorrhea). Among the women interviewed (mean age 20.4 ± 1.45 years), 146 (41.8%) had experienced sexual harassment in the previous 12 months: 91 (26.1%) level 1 and 55 (15.7%) level 2. The frequency of premenstrual symptoms was 31.9% ( n=110); heavy bleeding, 35.3% ( n=124); pain, 51.4% ( n=181); irregular cycles, 55.5% ( n=195); and amenorrhea, 6.7% ( n=23). After adjustment for age, place of birth, being in a couple relationship and receiving hormone therapy, the frequency of menstrual disorders, except for amenorrhea, was increased with sexual harassment, with a regular gradient from no harassment to level 2 harassment. Introducing factors of depression, specific gynaecological problems and lifetime sexual violence did not change the results. For instance, the adjusted odds ratios of premenstrual symptoms were 2.10 [1.19-3.68] for women with level 1 harassment and 3.58 [1.83-7.03] for women with level 2 compared with women without harassment exposure. Sexual harassment is related to the prevalence of menstrual disorders. Healthcare providers should encourage dialogue with patients and address the issue of sexual violence or harassment.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders.

PubMed

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M; Di Minno, Giovanni; Grazzini, Giuliano

2014-04-01

Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network.

The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center.

PubMed

Bladen, M; Main, E; Khair, K; Hubert, N; Koutoumanou, E; Liesner, R

2016-07-01

Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. © 2016 John Wiley & Sons Ltd.

Definition of an organisational model for the prevention and reduction of health and social impacts of inherited bleeding disorders

PubMed Central

Calizzani, Gabriele; Menichini, Ivana; Candura, Fabio; Lanzoni, Monica; Profili, Samantha; Tamburrini, Maria Rita; Fortino, Antonio; Vaglio, Stefania; Marano, Giuseppe; Facco, Giuseppina; Oliovecchio, Emily; Franchini, Massimo; Coppola, Antonio; Arcieri, Romano; Bon, Cinzia; Saia, Mario; Nuti, Sabina; Morfini, Massimo; Liumbruno, Giancarlo M.; Di Minno, Giovanni; Grazzini, Giuliano

2014-01-01

Introduction Due to the increase in life expectancy, patients with haemophilia and other inherited bleeding disorders are experiencing age-related comorbidities that present new challenges. In order to meet current and emerging needs, a model for healthcare pathways was developed through a project funded by the Italian Ministry of Health. The project aimed to prevent or reduce the social-health burden of the disease and its complications. Material and methods The National Blood Centre appointed a panel of experts comprising clinicians, patients, National and Regional Health Authority representatives. Following an analysis of the scientific and regulatory references, the panel drafted a technical proposal containing recommendations for Regional Health Authorities, which has been formally submitted to the Ministry of Health. Finally, a set of indicators to monitor haemophilia care provision has been defined. Results In the technical document, the panel of experts proposed the adoption of health policy recommendations summarised in areas, such as: multidisciplinary integrated approach for optimal healthcare provision; networking and protocols for emergency care; home therapy; registries/databases; replacement therapy supply and distribution; recruitment and training of experts in bleeding disorders. The recommendations became the content of proposal of agreement between the Government and the Regions. Monitoring and evaluation of haemophilia care through the set of established indicators was partially performed due to limited available data. Conclusions The project provided recommendations for the clinical and organisational management of patient with haemophilia. A particular concern was given to those areas that play a critical role in the comorbidities and complications prevention. Recommendations are expected to harmonise healthcare care delivery across regional networks and building the foundation for the national haemophilia network. PMID:24922299

The Comprehensive Geriatric Assessment and the multidimensional approach. A new look at the older patient with gastroenterological disorders.

PubMed

Pilotto, Alberto; Addante, Filomena; D'Onofrio, Grazia; Sancarlo, Daniele; Ferrucci, Luigi

2009-01-01

The Comprehensive Geriatric Assessment (CGA) is a multidimensional, usually interdisciplinary, diagnostic process intended to determine an elderly person's medical, psychosocial, and functional capacity and problems with the objective of developing an overall plan for treatment and short- and long-term follow-up. The potential usefulness of the CGA in evaluating treatment and follow-up of older patients with gastroenterological disorders is unknown. In the paper we reported the efficacy of a Multidimensional-Prognostic Index (MPI), calculated from information collected by a standardized CGA, in predicting mortality risk in older patients hospitalized with upper gastrointestinal bleeding and liver cirrhosis. Patients underwent a CGA that included six standardized scales, i.e. Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Short-Portable Mental Status Questionnaire (SPMSQ), Mini-Nutritional Assessment (MNA), Exton-Smith Score (ESS) and Comorbity Index Rating Scale (CIRS), as well as information on medication history and cohabitation, for a total of 63 items. The MPI was calculated from the integrated total scores and expressed as MPI 1=low risk, MPI 2=moderate risk and MPI 3=severe risk of mortality. Higher MPI values were significantly associated with higher short- and long-term mortality in older patients with both upper gastrointestinal bleeding and liver cirrhosis. A close agreement was found between the estimated mortality by MPI and the observed mortality. Moreover, MPI seems to have a greater discriminatory power than organ-specific prognostic indices such as Rockall and Blatchford scores (in upper gastrointestinal bleeding patients) and Child-Plugh score (in liver cirrhosis patients). All these findings support the concept that a multidimensional approach may be appropriate for the evaluation of older patients with gastroenterological disorders, like it has been reported for patients with other pathological conditions.

Von Willebrand's disease: case report and review of literature.

PubMed

Echahdi, Hanae; El Hasbaoui, Brahim; El Khorassani, Mohamed; Agadr, Aomar; Khattab, Mohamed

2017-01-01

Von Willebrand Disease (VWD) is the most common human inherited bleeding disorder due to a defect of Von Willebrand Factor (VWF), which a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels < 50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50IU/dL). Von willebrand factor is a complex multimeric protein with two functions: it forms a bridge between the platelets and areas of vascular damage and it binds to and stabilizes factor VIII, which is necessary for the clotting cascade. By taking a clinical history of bleeding (mucocutaneous bleeding symptoms suggestive of a primary haemostatic disorder, a quantitative or qualitative abnormality of VWF is possible) it is important to think about VWD and to make the appropriate diagnosis. If the VWD is suspected diagnostic tests should include an activated partial thromboplastin time, bleeding time, factor VIII: C Ristocetin cofactor and vWF antigen. Additional testing of ristocetin induced plattlet adhesion (RIPA) the multimeric structure and collagen binding test and genanalysis allow diagnosing the different types of von. Willebrand Disease. The treatment of choice in mild forms is the synthetic agent desmopressin. In patients with severe type 1, type 2B, 2N and type 3 or in people who do not response to desmopressin, the appropriate treatment is a factor VIII concentrate that is rich of VWF. We report a case of infant in 27-month-old boy who had been referred due to haemorrhagic shock. His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner face of the lower lip that caused an external acute bleeding loss. The laboratory data showed unfortunately, the most severe form of Von Willebrand's Disease; Type 3. The management was based on erythrocyte and fresh-frozen plasma (FFP) transfusions with administration of factor VII with good evolution.

Predictive factors for the occurrence of idiopathic menorrhagia: evidence for a hereditary trait.

PubMed

Kuzmina, Natalia; Palmblad, Jan; Mints, Miriam

2011-01-01

The aim of the present study was to assess predictive factors for occurrence of idiopathic menorrhagia (IM), a disease characterized by abnormal endometrial blood vessel morphology. It was hypothesized that IM exhibits familial clustering (suggesting inheritance) and is associated with other vascular abnormalities, primarily cutaneous hemangiomas. Women with IM (n=152) and healthy, regularly menstruating (n=56) women answered a questionnaire concerning menstrual pattern, susceptibility to bleeding and family history of abnormal gynecological bleeding. Factor analysis with principal component extraction was used to separate predictive factors that may be associated with IM. A total of 35 different items were analyzed. A strong association was found between IM and a family history of heavy menstrual bleeding (r=0.68), but not with cutaneous vascular abnormalities. Our results revealed that a family history of heavy menstrual bleeding may have the highest predictive value for the diagnosis of IM, indicating a hereditary trait.

Menstrual symptoms: the importance of social factors in women's experiences

PubMed Central

O'Flynn, Norma

2006-01-01

Background Menstrual disorders are a common presentation in primary care. Heavy menstrual bleeding is the most common concern, and is often treated by medical and surgical means despite lack of pathology. Aim To explore women's experiences of menstrual disorders. Design of study Two qualitative studies using semi-structured interviews. Setting Inner-city London. Method An initial study recruited women with heavy menstrual bleeding via their GPs. A follow-up study recruited women with a variety of menstrual problems via general practice and the community. Interviews were taped and transcribed then analysed using the constant comparative method. Results Management of menstruation was a prominent theme in interviews. Women acted to comply with a strong social message that menstruation should be concealed, although this behaviour was often ‘taken for granted.’ The need to conceal evidence or reminders of menstrual bleeding was particularly important. Onset of menstrual symptoms often challenged established strategies for menstrual management. Menstrual management then became a conscious problem and a source of continuing stress. The breakdown of management strategies, by real or threatened episodes of leaking or staining, influenced consultation behaviour and decisions about treatment. Conclusion The social pressure to maintain concealment of menstruation is a strong influence on women's health-related behaviour in response to menstrual concerns. Women's choices may be better understood if attention is paid to the social context in which they live. PMID:17132384

THROMBIN GENERATION AND BLEEDING IN HEMOPHILIA A

PubMed Central

Brummel-Ziedins, Kathleen E.; Whelihan, Matthew F.; Gissel, Matthew; Mann, Kenneth G.; Rivard, Georges E.

2012-01-01

Introduction Hemophilia A displays phenotypic heterogeneity with respect to clinical severity. Aim To determine if tissue factor (TF)-initiated thrombin generation profiles in whole blood in the presence of corn trypsin inhibitor (CTI) are predictive of bleeding risk in hemophilia A. Methods We studied factor(F) VIII deficient individuals (11 mild, 4 moderate and 12 severe) with a well-characterized five-year bleeding history that included hemarthrosis, soft tissue hematoma and annual FVIII concentrate usage. This clinical information was used to generate a bleeding score. The bleeding scores (range 0–32) were separated into three groups (bleeding score groupings: 0, 0 and ≤9.6, >9.6), with the higher bleeding tendency having a higher score. Whole blood collected by phlebotomy and contact pathway suppressed by 100μg/mL CTI was stimulated to react by the addition of 5pM TF. Reactions were quenched at 20min by inhibitors. Thrombin generation, determined by ELISA for thrombin – antithrombin was evaluated in terms of clot time (CT), maximum level (MaxL) and maximum rate (MaxR) and compared to the bleeding score. Results Data are shown as the mean±SD. MaxL was significantly different (p<0.001) between the groups: 504±114nM, 315±117nM, and 194±91nM; with higher thrombin concentrations in the groups with lower bleeding scores. MaxR was higher in the groups with a lower bleeding score; 97±51nM/min, 86±60nM/min and 39±16nM/min (p=0.09). No significant difference was detected in CT among the groups, 5.6±1.3min, 4.7±0.7min, 5.6±1.3min. Conclusions Our empirical study in CTI-inhibited whole blood shows that the MaxL of thrombin generation appears to correlate with the bleeding phenotype of hemophilia A. PMID:19563500

Differential Prognostic Impact on Mortality of Myocardial Infarction Compared With Bleeding Severity in Contemporary Acute Coronary Syndrome Patients.

PubMed

Caneiro-Queija, Berenice; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Manzano-Fernández, Sergio; Flores Blanco, Pedro; López-Cuenca, Ángel; Cobas-Paz, Rafael; Gómez-Molina, Miriam; Rodríguez-Rodríguez, José Manuel; Calvo-Iglesias, Francisco; Valdés-Chávarri, Mariano; Íñiguez-Romo, Andrés

2018-04-12

The impact on mortality of myocardial infarction (MI) compared with the specific degree of bleeding severity occurring after discharge in acute coronary syndrome is poorly characterized. Defining this relationship may help to achieve a favorable therapeutic risk-benefit balance. Using Cox-based shared frailty models, we assessed the relationship between mortality and postdischarge MI and bleeding severity-graded according to Bleeding Academic Research Consortium (BARC)-in 4229 acute coronary syndrome patients undergoing in-hospital coronary arteriography between January 2012 and December 2015. Both MI (HR, 5.8; 95%CI, 3.7-9.8) and bleeding (HR, 5.1; 95%CI, 3.6-7.7) were associated with mortality. Myocardial infarction had a stronger impact on mortality than BARC type 2 and 3a bleedings: (RRr, 3.8 and 1.9; P < .05), respectively, but was equivalent to BARC type 3b (RRr, 0.9; P = .88). Mortality risk after MI was significantly lower than after BARC type 3c bleeding (RRr, 0.25; P < .001). Mortality was higher after an MI in patients on dual antiplatelet therapy (DAPT) at the time of the event (HR, 2.9; 95%CI, 1.8-4.5) than in those off-DAPT (HR, 1.5; 95%CI, 0.7-3.4). In contrast, mortality was lower after a bleeding event in patients on-DAPT (HR, 1.6; 95%CI, 1.1-2.6) than in those off-DAPT (HR, 3.2; 95%CI, 1.7-5.8). The differential effect on mortality of a postdischarge MI vs bleeding largely depends on bleeding severity. The DAPT status at the time of MI or bleeding is a modifier of subsequent mortality risk. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Complete Blood Count: MedlinePlus Lab Test Information

MedlinePlus

... your lungs and to the rest of your body Hematocrit , a measurement of how much of your blood is made ... Internet]. Bethesda (MD): U.S. Department of Health and Human Services; Your Guide to Anemia; [cited ... MedlinePlus Health Topics Bleeding Disorders Blood Count ...

Leidos Biomed Teams with NCI, DOE, and Argonne National Lab to Support National X-Ray Resource | FNLCR Staging

Cancer.gov

Scientists are making progress in understanding a bleeding disorder caused by prescription drug interactions, thanks to a high-tech research facility involving two federal national laboratories, Argonne and Frederick. Miroslawa Dauter is a Senior Res

Management of tooth extraction in a patient with a rare bleeding disorder associated with Hermansky-Pudlak syndrome: a case report.

PubMed

Minkin, Patton; Bertetti, Richard; Lindsey, Sean; Bovino, Brian

2015-02-01

This report describes the case of a 27-year-old man who had been diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient had a major bleeding disorder associated with his syndrome, local and systemic hemostatic protection recommendations had to be considered before tooth extraction. Synthetic vasopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to the extraction site. Treatment with DDAVP, HLA-matched platelets, and local application of a packing with Avitene and Gelfoam resulted in sustained hemostasis and an excellent healing response. Surgical and routine extractions appear to be safe procedures in patients with Hermansky-Pudlak syndrome when appropriate local and systemic hemostatic measures are used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The impact of coagulopathy on traumatic splenic injuries.

PubMed

Smalls, Norma; Obirieze, Augustine; Ehanire, Imudia

2015-10-01

Patients with pre-injury coagulopathy have worse outcomes than those without coagulopathy. This article investigated the risk-adjusted effect of pre-injury coagulopathy on outcomes after splenic injuries. Review of the National Trauma Data Bank from 2007 to 2010 comparing mortality and complications between splenic injury patients with and without a pre-injury bleeding disorder. Of 58,896 patients, 2% had a bleeding disorder. Coagulopathic patients had higher odds of mortality (odds ratio, 1.3), sepsis (odds ratio, 2.0), acute respiratory distress syndrome (odds ratio, 2.6), acute renal failure (odds ratio, 1.5), cardiac arrest (odds ratio, 1.5), and overall complications (odds ratio, 2.4). The higher odds of myocardial infarction did not achieve statistical significance (odds ratio, 1.6). Pre-injury coagulopathy in patients with splenic injury has a negative impact on cardiac arrest, sepsis, acute respiratory distress syndrome, acute renal failure, and mortality. The higher likelihood of myocardial infarction did not reach statistical significance. Copyright © 2015 Elsevier Inc. All rights reserved.

Chromogenic Factor VIII Assays for Improved Diagnosis of Hemophilia A.

PubMed

Rodgers, Susan; Duncan, Elizabeth

2017-01-01

Hemophilia A is an inherited bleeding disorder caused by a reduced level of factor VIII coagulant activity (FVIII:C) in blood. Bleeding episodes may occur spontaneously in the severe form of hemophilia or after trauma in the milder forms. It is important that patients are diagnosed correctly, which includes placing them into the correct severity category of the disorder so that appropriate treatment can be given. Diagnosis is made by determination of the amount of FVIII:C in the blood, usually using a one-stage factor VIII:C assay. However, approximately one third of patients with mild or moderate hemophilia will have much lower results by the chromogenic assay, with some of them having normal results by the one-stage assay. The chromogenic factor VIII assay is used in some specialized hemophilia reference centers and is recommended for the diagnosis of mild hemophilia A, as this assay is considered to better reflect the severity status of hemophilia patients than the one-stage assay.

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence). Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group. Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence). Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups. One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. None of the studies reported quality-of-life. Authors’ conclusions In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy. A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events. Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely. PMID:26505729

Porous and Microporous Honeycomb Composites as Potential Boundary-Layer Bleed Materials

NASA Technical Reports Server (NTRS)

Davis, D. O.; Willis, B. P.; Schoenenberger, M.

1997-01-01

Results of an experimental investigation are presented in which the use of porous and microporous honeycomb composite materials is evaluated as an alternate to perforated solid plates for boundary-layer bleed in supersonic aircraft inlets. The terms "porous" and "microporous," respectively, refer to bleed orifice diameters roughly equal to and much less than the displacement thickness of the approach boundary-layer. A Baseline porous solid plate, two porous honeycomb, and three microporous honeycomb configurations are evaluated. The performance of the plates is characterized by the flow coefficient and relative change in boundary-layer profile parameters across the bleed region. The tests were conducted at Mach numbers of 1.27 and 1.98. The results show the porous honeycomb is not as efficient at removing mass compared to the baseline. The microporous plates were about equal to the baseline with one plate demonstrating a significantly higher efficiency. The microporous plates produced significantly fuller boundary-layer profiles downstream of the bleed region for a given mass flow removal rate than either the baseline or the porous honeycomb plates.

[The use of superselective embolization of the maxillary artery in treatment of bleedings in the Rendu-Osler-Weber syndrome].

PubMed

Kantor, Ireneusz; Winiarski, Michał; Jurkiewicz, Dariusz; Osiecki, Mirosław; Brzozowski, Krzysztof

2005-01-01

Rendu-Osler-Weber syndrome is a rare genetically determined disorder that affects blood vessels throughout the body and results in a tendency for bleeding. Authors describe the case of superselective embolization of the left maxillary artery with polyvinyl alcohol particles in a patient with the Rendu-Osler-Weber syndrome hospitalized and treated in the Department of Otolaryngology and the Department of Radiology of the Military Institute in Warszawa, Poland due to persistent, severe and difficult to manage nasal bleeding. After the procedure had been performed patient condition improved and frequency and severity of nasal bleeding significantly diminished. Authors conclude that superselective embolization of the maxillary artery in a patient with Rendu-Osler-Weber syndrome is safe and effective and can be a valuable alternative to the maxillary artery or the carotis externa artery ligation. Authors also describe other methods of nasal bleeding management: laser photocoagulation, argon plasma coagulation, nasal dermoplasty and pharmacological treatment. Authors indicate that treating patients with Rendu-Osler-Weber syndrome is a diagnostic and therapeutic challenge for a physician and surgeon that require special approach to a patient due to difficult to manage symptoms. Patients with Rendu-Osler-Weber syndrome should be treated in a hospital setting due to access to diagnostic imaging techniques that can be helpful in revealing possible life threatening conditions.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates.

PubMed

Motta, Mario; Guaragni, Brunetta; Pezzotti, Elena; Rodriguez-Perez, Carmen; Chirico, Gaetano

2017-12-01

Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. To evaluate TEG in preterm neonates, and to assess their reference ranges. One hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. Comparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. These results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Spectrum of Autoerythrocyte Sensitization Syndrome: A Series of Five Cases

PubMed Central

Thokchom, Nandakishore Singh; Pradeepa, D.; Hafi, N. A. Bishurul; Verma, Kapila

2018-01-01

Autoerythrocyte sensitization syndrome (Gardner Diamond syndrome or GDS) is a rare syndrome characterized by painful and spontaneous purpura commonly affecting adult women, and is mostly associated with psychiatric illness. Diagnosis is mainly based on clinical presentation, exclusion of other simulating diseases, and psychiatric evaluation. Only few cases have been reported till date. We report five cases of spontaneous purpura with a normal investigation profile, except for iron deficiency anemia in 1 patient, of which three had associated underlying psychiatric illness. Autoerythrocyte sensitization test was positive in all our cases. Patients presenting with painful bruises without significant medical history such as underlying bleeding disorder or drug history or history of trauma should be considered for autoerythrocyte sensitization syndrome, and managed accordingly. The present study is a case series of patients with characteristic features of autoerythrocyte sensitization syndrome, considering the rarity of the reports on its clinical spectra. PMID:29644197

Menstrual management and reproductive concerns in adolescent and young adult women with underlying hematologic or oncologic disease.

PubMed

Quinn, Sheila M; Louis-Jacques, Jennifer

2016-08-01

Heavy menstrual bleeding is common among adolescent and young adult women, and can affect health-related quality of life. The cause of heavy menstrual bleeding is not uncommonly because of an underlying hematologic or oncologic disease process, which substantially influences the way patients are counseled and treated. Options for menstrual management are more numerous today than ever before and range from minimizing monthly blood loss to suppressing the cycle altogether. However, an underlying bleeding disorder or malignancy can introduce many nuances and limits in individual patient care, which this review highlights. Additionally, because survival rates for adolescent and young adult cancers are improving, more of these patients are planning for lives after their disease, which may include starting or adding to a family. Options for fertility preservation during cancer therapy regimens are solidifying and both primary practitioners and subspecialists should be aware of the possibilities. Patients with underlying hematologic or oncologic disease require management of menstrual bleeding, but also deserve a comprehensive evaluation and counseling regarding their individualized contraceptive needs and fertility preservation options during their reproductive years. This review employs the latest evidence from current literature to help guide clinicians caring for this unique demographic.

Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura

PubMed Central

Buchanan, George R.; Imbach, Paul; Bolton-Maggs, Paula H. B.; Bennett, Carolyn M.; Neufeld, Ellis J.; Vesely, Sara K.; Adix, Leah; Blanchette, Victor S.; Kühne, Thomas

2008-01-01

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm3 and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes. PMID:18698007

New method for evaluating irreversible adsorption and stationary phase bleed in gas chromatographic capillary columns.

PubMed

Wright, Bob W; Wright, Cherylyn W

2012-10-26

A novel method is described for the evaluation of irreversible adsorption and column bleed in gas chromatographic (GC) columns using a tandem GC approach. This work specifically determined the degree of irreversible adsorption behavior of specific sulfur and phosphorous containing test probe compounds at levels ranging from approximately 50 picograms (pg) to 1 nanogram (ng) on selected gas chromatographic columns. This method does not replace existing evaluation methods that characterize reversible adsorption but provides an additional tool. The test compounds were selected due to their ease of adsorption and their importance in the specific trace analytical detection methodology being developed. Replicate chromatographic columns with 5% phenylmethylpolysiloxane (PMS), polyethylene glycol (wax), trifluoropropylpolysiloxane (TFP), or 78% cyanopropylpolysiloxane stationary phases from a variety of vendors were evaluated. As expected, the results demonstrate that the different chromatographic phases exhibit differing degrees of irreversible adsorption behavior. The results also indicate that all manufacturers do not produce equally inert columns nor are columns from a given manufacturer identical. The wax-coated columns for the test probes used were more inert as a group than 5% PMS coated columns, and they were more reproducibly manufactured. Both TFP and 78% cyanopropylpolysiloxane columns displayed superior inertness to the test compounds compared to either 5% PMS- or wax-coated columns. Irreversible adsorption behavior was characterized for a limited range of stationary phase film thicknesses. In addition, the method was shown effective for characterizing column bleed and methods to remove bleed components. This method is useful in screening columns for demanding applications and to obtain diagnostic information related to improved preparation methods. Copyright © 2012 Elsevier B.V. All rights reserved.

Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

PubMed Central

Estcourt, Lise J; Desborough, Michael; Brunskill, Susan J; Doree, Carolyn; Hopewell, Sally; Murphy, Michael F; Stanworth, Simon J

2016-01-01

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ‘Risk of bias’ tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) −0.37 to 3.77: consolidation; 18 participants; MD −1.50 bleeding events, 95% CI −3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD −5.60 platelet units, 95% CI −9.02 to −2.18: induction; 38 participants, MD −1.00 platelet units, 95% CI −9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors’ conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020. PMID:26978005

Antiplatelet agents and/or anticoagulants are not associated with worse outcome following nonvariceal upper gastrointestinal bleeding.

PubMed

Teles-Sampaio, Elvira; Maia, Luís; Salgueiro, Paulo; Marcos-Pinto, Ricardo; Dinis-Ribeiro, Mário; Pedroto, Isabel

2016-11-01

Nonvariceal upper gastrointestinal bleeding emerges as a major complication of using antiplatelet agents and/or anticoagulants and represents a clinical challenge in patients undergoing these therapies. To characterize patients with nonvariceal upper gastrointestinal bleeding related to antithrombotics and their management, and to determine clinical predictors of adverse outcomes. Retrospective cohort of adults who underwent upper gastrointestinal endoscopy after nonvariceal upper gastrointestinal bleeding from 2010 to 2012. The outcomes were compared between patients exposed and not exposed to antithrombotics. Five hundred and forty-eight patients with nonvariceal upper gastrointestinal bleeding (67% men; mean age 66.5 ± 16.4 years) were included, of which 43% received antithrombotics. Most patients had comorbidities. Peptic ulcer was the main diagnosis and endoscopic therapy was performed in 46% of cases. The 30-day mortality rate was 7.7% (n = 42), and 36% were bleeding-related. The recurrence rate was 9% and 14% of patients with initial endoscopic treatment needed endoscopic retreatment. There were no significant differences between the exposed and non-exposed groups in most outcomes. Co-morbidities, hemodynamic instability, high Rockall score, low hemoglobin (7.76 ± 2.72 g/dL) and higher international normalized ratio (1.63 ± 1.13) were associated significantly with mortality in a univariate analysis. Adverse outcomes were not associated with antithrombotic use. The management of nonvariceal upper gastrointestinal bleeding constitutes a challenge to clinical performance optimization and clinical cooperation.

A Synthetic Fibrin-Crosslinking Polymer for Modulating Clot Properties and Inducing Hemostasis

PubMed Central

Chan, Leslie W.-G.; Wang, Xu; Wei, Hua; Pozzo, Lilo D.; White, Nathan J.; Pun, Suzie H.

2015-01-01

Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications. PMID:25739763

Continuous infusion of recombinant activated factor VII for bleeding control after lobectomy in a patient with inherited factor VII deficiency.

PubMed

Miyata, Naoko; Isaka, Mitsuhiro; Kojima, Hideaki; Maniwa, Tomohiro; Takahashi, Shoji; Takamiya, Osamu; Ohde, Yasuhisa

2016-03-01

Inherited factor VII (FVII) deficiency is a rare recessive inherited coagulation disorder with limited available information, especially in patients undergoing major thoracic surgery. In addition, an optimal management strategy for the disease has not been defined. We herein report a case involving a 61-year-old man with asymptomatic FVII deficiency who underwent a right middle and lower lobectomy to treat lung cancer. To the best of our knowledge, the present report is the first to describe the use of recombinant activated FVII continuous infusion for bleeding control after a major thoracic surgery in a patient with inherited FVII deficiency.

Isolated acquired factor VII deficiency: review of the literature.

PubMed

Mulliez, Sylvie M N; Devreese, Katrien M J

2016-04-01

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

[Coagulation Monitoring and Bleeding Management in Cardiac Surgery].

PubMed

Bein, Berthold; Schiewe, Robert

2018-05-01

The transfusion of allogeneic blood products is associated with increased morbidity and mortality. An impaired hemostasis is frequently found in patients undergoing cardiac surgery and may in turn cause bleeding and transfusions. A goal directed coagulation management addressing the often complex coagulation disorders needs sophisticated diagnostics. This may improve both patients' outcome and costs. Recent data suggest that coagulation management based on a rational algorithm is more effective than traditional therapy based on conventional laboratory variables such as PT and INR. Platelet inhibitors, cumarins, direct oral anticoagulants and heparin need different diagnostic and therapeutic approaches. An algorithm specifically developed for use during cardiac surgery is presented. Georg Thieme Verlag KG Stuttgart · New York.

Fitness and quality of life in children with haemophilia.

PubMed

Broderick, C R; Herbert, R D; Latimer, J; Curtin, J A

2010-01-01

Prior to the introduction of prophylactic clotting factor, children with haemophilia were discouraged from physical activity due to the risk of bleeds. Reports of children with haemophilia having lower levels of fitness and strength than their healthy peers were therefore well accepted. This study aimed to establish whether these deficits continued, and specifically, whether Australian boys with haemophilia and von Willebrand disorder had lower strength and aerobic capacity than their peers, despite widespread use of prophylaxis. Forty-four boys aged 6.1-17.0 years (mean 10.9, SD 3.2) with haemophilia A and B and von Willebrand disorder participated in the study. Fitness, strength and body mass index (BMI) measures were compared with age- and gender-matched data from a representative cohort of school children. Quality of Life was measured using the Haemo-QoL to obtain baseline measures in an Australian population. There were no statistically significant or clinically important differences in aerobic fitness or BMI between the boys with haemophilia and controls in any age category. Boys with haemophilia in Years 4, 6 and 10 had greater strength than their peers. Australian boys with bleeding disorders do not have impaired aerobic capacity or strength compared with their peers. Quality of life in Australian boys with haemophilia is comparable to their European counterparts.

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K.

PubMed

Zeynelabidin, Sara; Klouwer, Femke C C; Meijers, Joost C M; Suijker, Monique H; Engelen, Marc; Poll-The, Bwee Tien; van Ommen, C Heleen

2018-03-01

Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

Strategies to encourage physical activity in patients with hemophilia to improve quality of life

PubMed Central

Goto, Miwa; Takedani, Hideyuki; Yokota, Kazuhiko; Haga, Nobuhiko

2016-01-01

Hemophilia is a bleeding disorder caused by a congenital abnormality of blood coagulation. Until the mid-1970s, patients with hemophilia (PWH) were advised to refrain from physical activity (PA) because of a perceived increased risk of bleeding. Since then, PA, which is recognized as being essential for health maintenance, is now recommended by the World Federation of Hemophilia. Moreover, a number of studies reported that PA can improve treatment efficacy and prevent bleeding in PWH. Physical assessment and intervention in PA are currently used in clinical practice. However, the necessity of PA is not emphasized, and many PWH generally have low- to- no PA. Therefore, a behavior change approach to encourage patient motivation is becoming ever more important. In this article, we review articles addressing PA in PWH and discuss strategies to encourage PA through a behavior change approach by focusing on factors relevant to hemophilia, such as benefits and bleeding risk of PA, risk management of bleeding, PA characteristics, and difficulty with exercise adherence. The trust relationship between clinicians and patients, a transtheoretical model of behavior change, and motivation theory as approaches to promote PA are introduced. Finally, we review a case report of the clinical success of a behavior change approach to promote PA. Many PWH find it difficult to continue PA because of aging, fear of bleeding, insufficient recognition of PA benefits, and psychological problems. Therefore, it is essential and important to perform prophylaxis with PWH and to heighten their understanding of the benefits and risks of PA, before initiating the exercise regimen. For those patients who find it difficult to participate in PA, it is necessary to plan individual-based behavior change approach and encourage self-efficacy. PMID:27274330

Establishment of a prenatal diagnosis schedule as part of a prophylaxis program of factor XIII deficiency in the southeast of Iran.

PubMed

Naderi, Majid; Reykande, Samira Esmaeili; Dorgalaleh, Akbar; Alizadeh, Shaban; Tabibian, Shadi; Einollahi, Nahid; Moghaddam, Ebrahim Miri

2016-01-01

Factor XIII deficiency (FXIIID) is an extremely rare bleeding disorder with a prevalence of 1 in 3 million in the general population. Compared to its global incidence, it has the greatest prevalence in Sistan and Baluchistan Province in the southeast of Iran. The high incidence of FXIIID in this region causes a high rate of morbidity and mortality among the affected individuals because of life-threatening episodes such as central nervous system (CNS) bleeding, umbilical cord bleeding, as well as miscarriage. CNS bleeding leads to a considerable number of neurological and behavioral complications. Therefore, we have designed an established prenatal diagnosis (PND) program to prevent the increasing incidence of life-threatening bleeding episodes and related complications among neonates with congenital FXIIID. This study was conducted from September 2013 to August 2014. A consent form was signed by the parents. Fetal sampling was done via abdominal chorionic villus sampling passage under local anesthesia and ultrasonic guidance within the first trimester of pregnancy. Fetal DNA was extracted, and PCR-restriction fragment length polymorphism was performed for the only reported mutation of FXIII (Trp187Arg) in the southeast of Iran. During the period of study, PND was performed on eight fetuses. Six fetuses were offspring of parental consanguineous marriages, and all of them had a positive family history of FXIIID. Seven out of the eight fetuses had a family member with CNS bleeding due to FXIIID. Four fetuses had a FXIIID-related death. One of the fetuses bore homozygous Trp187Arg mutation, whereas six were heterozygous, and one of the mothers gave birth to an unaffected fetus. To the best of our knowledge, PND is a possible solution to control high incidence of life-threatening episodes of FXIIID in southeast Iran.

Iron Deficiency without Anemia: A Common Yet Under-Recognized Diagnosis in Young Women with Heavy Menstrual Bleeding.

PubMed

Johnson, Stephen; Lang, Abigail; Sturm, Mollie; O'Brien, Sarah H

2016-12-01

To assess the proportion of iron deficiency that is not detected with a screening hemoglobin or complete blood count (CBC) alone in young women with heavy menstrual bleeding. Retrospective review of electronic medical records. Nationwide Children's Hospital in Columbus, Ohio. One hundred fourteen young women aged 9-19 years consecutively referred to a young women's hematology clinic with a complaint of heavy menstrual bleeding. Fifty-eight (50.9%) of all patients had ferritin <20 ng/mL indicating iron deficiency. Of the 58 patients with iron deficiency, only 24 (41.4%) were anemic and 25 (46.3%) were microcytic. The sensitivity of hemoglobin alone and CBC alone for identifying women with ferritin <20 ng/mL was 41.4% (95% confidence interval [CI], 28.7-54.1) and 46.3% (95% CI, 33.0-59.6), respectively. Both tests had reasonable specificity at 91.1% (95% CI, 83.6-98.5) for hemoglobin and 83.9% for CBC (95% CI, 74.3-93.6). Patients had significantly higher odds of having iron deficiency if they were overweight or obese (odds ratio, 2.81; 95% CI, 1.25-6.29) compared with patients with normal body mass index. Age at presentation for heavy menstrual bleeding, presence of an underlying bleeding disorder, and median household income were not significantly associated with iron deficiency. In adolescents with heavy menstrual bleeding, fewer than half of iron deficiency cases are detected when screening is performed with hemoglobin or blood count alone. Measuring ferritin levels in at-risk patients might allow for earlier implementation of iron therapy and improvement in symptoms. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Molecular aspects in clinical hemostasis research at Karolinska Institutet.

PubMed

Blombäck, Margareta

2010-05-21

The development of hemostasis research at Karolinska Institutet is described, focusing first on the initial findings of the fibrinogen structure and the hereditary bleeding disorders, hemophilia A and von Willebrand's disease. Basic research has focused on new biomarkers for cardiovascular/thromboembolic disorders, such as myocardial infarction and stroke, including preeclampsia and diabetes, with studies on the importance of decreased fibrinolysis in these disorders. Since long, the structure of the fibrin network has been evaluated, and recently the influence of aspirin and new thrombin and factor Xa inhibitors has been investigated. Research on the contact pathway of coagulation has also started at the Unit. 2010 Elsevier Inc. All rights reserved.

Coagulation management in patients undergoing neurosurgical procedures.

PubMed

Robba, Chiara; Bertuetti, Rita; Rasulo, Frank; Bertuccio, Alessando; Matta, Basil

2017-10-01

Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

Bleeding prevalence and transfusion requirement in patients with thrombocytopenia in the emergency department.

PubMed

Turvani, Fabrizio; Pigozzi, Luca; Barutta, Letizia; Pivetta, Emanuele; Pizzolato, Elisa; Morello, Fulvio; Battista, Stefania; Moiraghi, Corrado; Montrucchio, Giuseppe; Lupia, Enrico

2014-10-01

Thrombocytopenia is the most common coagulation disorder in critically ill patients. No studies have investigated the epidemiology and clinical impact of this condition in emergency department (ED) patients. We aimed to investigate epidemiological features, incidence of bleeding, and diagnostic and therapeutic requirements of patients with thrombocytopenia admitted to the ED. We performed a retrospective observational study enrolling all patients admitted to the medical-surgical ED of the "Città della Salute e della Scienza di Torino" Hospital with a platelet count <150×10(9) PLTs/L, during four non-consecutive months. There were no exclusion criteria. The study included 1218 patients. The percentage of patients with severe (<50×10(9) PLTs/L) or very severe (<20×10(9) PLTs/L) thrombocytopenia was about 12%. Thrombocytopenia associated with liver cirrhosis was the most represented etiology. On the contrary, the most frequent cause in patients with newly recognized low platelet count was disseminated intravascular coagulation/sepsis. The incidence of bleeding and hypovolemia, as well as the need of transfusional support and mechanical, surgical or endoscopic hemostasis progressively increased with the severity of thrombocytopenia. Our results suggest that the detection of a platelet count lower than 50×10(9) PLTs/L may help to identify patients with higher bleeding risk in the ED setting. Additional studies are required to evaluate whether, in this setting, thrombocytopenia may represent an independent risk factor for bleeding episodes and increased mortality.

Hawthorn Herb Increases the Risk of Bleeding after Cardiac Surgery: An Evidence-Based Approach.

PubMed

Rababa'h, Abeer M; Altarabsheh, Salah E; Haddad, Osama; Deo, Salil V; Obeidat, Yagthan; Al-Azzam, Sayer

2016-08-22

Hawthorn extract consumption is becoming more widespread among the Jordanian population with cardiovascular disorders. We conducted this prospective observational longitudinal study to determine the impact of hawthorn extract on bleeding risk in patients who undergo cardiac surgery. A prospective observational study was performed on 116 patients who underwent cardiac surgery in the period between June 2014 and May 2015. Patients were divided into two groups: Group I (patients recently consumed hawthorn extract) and Group II (patients never consumed hawthorn extract). Endpoint measures included the rates of reopening to control bleeding, early mortality, duration of intensive care unit stay, total in-hospital stay period, and duration and amount of chest tube drainage. Hawthorn patients had a significantly higher rate of postoperative bleeding necessitating take back to the operating room compared to the control group (10% versus 1%; P = .03) respectively. The overall mortality rate for group I and II was 4% and 0% respectively; P = .17. Chest tubes were kept in for longer times in group I compared to group II (54 ± 14.6 versus 49 ± 14.7 hours respectively; P = .01). Group I stayed longer in the intensive care unit compared to group II (24 versus 22 hours respectively; P = .01). The total in-hospital stay period was comparable between the two groups. Hawthorn extract consumption does increase the potential for bleeding and the amount of chest tube output after cardiac surgery.

Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage.

PubMed

Mattheij, Nadine J A; Braun, Attila; van Kruchten, Roger; Castoldi, Elisabetta; Pircher, Joachim; Baaten, Constance C F M J; Wülling, Manuela; Kuijpers, Marijke J E; Köhler, Ralf; Poole, Alastair W; Schreiber, Rainer; Vortkamp, Andrea; Collins, Peter W; Nieswandt, Bernhard; Kunzelmann, Karl; Cosemans, Judith M E M; Heemskerk, Johan W M

2016-02-01

Scott syndrome is a rare bleeding disorder, characterized by altered Ca(2+)-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano)6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6 min (control 6.4 min, P < 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (-65 to 90%); 2) lowered Ca(2+)-dependent swelling (-80%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome. © FASEB.

Prediction and Reduction of Noise in Pneumatic Bleed Valves

NASA Astrophysics Data System (ADS)

Taghavi Nezhad, Shervin

This study investigates numerically the fluid mechanics and acoustics of pneumatic bleed valves used in turbofan engines. The goal is to characterized the fundamental processes of noise generation and devise strategies for noise reduction. Three different methods are employed for both analysis and redesign of the bleed valve to reduce noise. The bleed valve noise problem is carefully divided into multiple smaller problems. For large separations and tonal noises, the unsteady Reynolds-Averaged Navier-Stokes (URANS) method is utilized. This method is also applied in the re-designing of the bleed valve geometry. For the bleed valve muffler, which is comprised of perforated plates and a honeycomb, a Reynolds-Averaged Navier-Stokes (RANS) method combined with a simplified acoustic analogy is used. The original muffler design is modified to improve noise attenuation. Finally, for sound scattering through perforated plates, a fully implicit linearized Euler solver is developed. The problem of sound interaction with perforated plates is studied from two perspectives. In the first study the effect of high--speed mean flow is considered and it is shown that at Strouhal numbers of around 0.2-0.25 there is an increase in transmitted incident sound. In the second part, the interaction of holes in two--dimensional perforated plates is investigated using three different configurations. The study demonstrates that the hole interaction has a significant impact on sound attenuation, especially at high frequencies.

Analysis of risk factor and clinical characteristics of angiodysplasia presenting as upper gastrointestinal bleeding.

PubMed

Kim, Dae Bum; Chung, Woo Chul; Lee, Seok Jong; Sung, Hea Jung; Woo, Seokyung; Kim, Hyo Suk; Jeong, Yeon Oh; Lee, Hyewon; Kim, Yeon-Ji

2016-07-01

Angiodysplasia is important in the differential diagnosis of upper gastrointestinal bleeding (UGIB), but the clinical features and outcomes associated with UGIB from angiodysplasia have not been characterized. We aimed to analyze the clinical characteristics and outcomes of angiodysplasia presented as UGIB. Between January 2004 and December 2013, a consecutive series of patients admitted with UGIB were retrospectively analyzed. Thirty-five patients with bleeding from angiodysplasia were enrolled. We compared them with an asymptomatic control group (incidental finding of angiodysplasia in health screening, n = 58) and bleeding control group (simultaneous finding of angiodysplasia and peptic ulcer bleeding, n = 28). When patients with UGIB from angiodysplasia were compared with the asymptomatic control group, more frequent rates of nonantral location and large sized lesion (≥ 1 cm) were evident in multivariate analysis. When these patients were compared with the bleeding control group, they were older (mean age: 67.94 ± 9.16 years vs.55.07 ± 13.29 years, p = 0.03) and received less transfusions (p = 0.03). They also had more frequent rate of recurrence (40.0% vs. 20.7%, p = 0.02). Non-antral location and large lesions (≥ 1 cm) could be risk factors of UGIB of angiodysplasia. UGIB due to angiodysplasia was more common in older patients. Transfusion requirement would be less and a tendency of clinical recurrence might be apparent.

A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding.

PubMed

Patel, Y M; Lordkipanidzé, M; Lowe, G C; Nisar, S P; Garner, K; Stockley, J; Daly, M E; Mitchell, M; Watson, S P; Austin, S K; Mundell, S J

2014-05-01

The study of patients with bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets. We have identified a patient with a chronic bleeding disorder expressing a homozygous P2RY(12) mutation, predicting an arginine to cysteine (R122C) substitution in the G-protein-coupled P2Y(12) receptor. This mutation is found within the DRY motif, which is a highly conserved region in G-protein-coupled receptors (GPCRs) that is speculated to play a critical role in regulating receptor conformational states. To determine the functional consequences of the R122C substitution for P2Y(12) function. We performed a detailed phenotypic analysis of an index case and affected family members. An analysis of the variant R122C P2Y(12) stably expressed in cells was also performed. ADP-stimulated platelet aggregation was reduced as a result of a significant impairment of P2Y(12) activity in the patient and family members. Cell surface R122C P2Y(12) expression was reduced both in cell lines and in platelets; in cell lines, this was as a consequence of agonist-independent internalization followed by subsequent receptor trafficking to lysosomes. Strikingly, members of this family also showed reduced thrombin-induced platelet activation, owing to an intronic polymorphism in the F2R gene, which encodes protease-activated receptor 1 (PAR-1), that has been shown to be associated with reduced PAR-1 receptor activity. Our study is the first to demonstrate a patient with deficits in two stimulatory GPCR pathways that regulate platelet activity, further indicating that bleeding disorders constitute a complex trait. © 2014 International Society on Thrombosis and Haemostasis.

Medical Surveillance Monthly Report (MSMR). Volume 18, Number 12, December 2011

DTIC Science & Technology

2011-12-01

pregnancy complications were “other specifi ed complications of preg- nancy” (code 646.8, which includes “fatigue during pregnancy” and “ herpes ...bleeding disorders 623.8, 626.5, 626.6,626.8, 626.9 Pain associated with female genital organs 625.0, 625.3, 625.5, 625.9 Inpatient procedure codes

Building our global family--achieving treatment for all.

PubMed

Skinner, M W

2010-07-01

Building our global family by reaching out to women, children and youth and those in sub-Saharan Africa to achieve Treatment for All. The World Federation of Hemophilia (WFH) has committed to recognizing and incorporating the critical and important challenges that are faced by women with bleeding disorders within our global family. The next crucial steps include the development of outreach and registry programmes which can be adapted globally to accelerate the identification of such women, and to educate and guide them to the appropriate clinical care setting. Equally important, awareness must be raised within the broader medical community where women would typically first present with clinical symptoms. Family practitioners, nurse-midwives, obstetricians, gynaecologists and community health clinics will increasingly be strategic and central to WFH outreach efforts, in addition to serving as new care partners essential to the multidisciplinary model of care. Adapting and implementing the WFH development model regionally within Africa is proving to be a successful approach both for the introduction as well as the development of sustainable national care programmes for patients with bleeding disorders. The targeted development of solid national programmes such as in South Africa, Senegal and Kenya has expanded the training capacity of the WFH, as well as providing key regional examples. Local medical professionals are now responsible for providing the training in many regional programmes. Children with bleeding disorders in low-income countries are at great risk of dying young. WFH data demonstrate that among such patients, as the economic capacity of a country decreases so does the ratio of adults to children. The organization of care, training of a multi-disciplinary healthcare team, and education of patients and their families lead to improved mortality independent of economic capacity or increased clotting factor concentrate availability. Additionally, through enhanced youth education, awareness and engagement, we will assure continuity within WFH national member organizations, build greater unity within our global family and capture the innovation and creativity of their ideas to improve Treatment for All.

Albinism and lung fibrosis in a young man - the first case of adult Hermansky-Pudlak Syndrome reported in Malaysia.

PubMed

Liza, A F; Aziah, A M

2012-12-01

A young gentleman of Indian descent with oculacutaneous albinism (OCA) was found to have severe pulmonary fibrosis at first presentation. Following investigations, he was diagnosed with Hermansky-Pudlak Syndrome (HPS). It is a genetic condition characterised by albinism, bleeding diathesis and multisystem disorder observed in individuals of particular descents. Although there is no curative treatment apart from lung transplantation, preventive measures to minimise pulmonary insult may change the natural history of the disease. Therefore HPS should be actively sought, monitored and risk factors addressed in individuals with OCA and bleeding diathesis particularly those of Indian descent as they may develop serious complications such as pulmonary fibrosis in the future.

[Anterior seromyotomy of the body and the functional part of the stomach combined with posterior truncal vagotomy and ulcer excision in the surgical treatment of complicated stomach ulcer].

PubMed

Petrov, V I; Sytnik, A P; Gorbunov, V N; KOrenev, N N; Naumov, B A; Gordeev, S A

1990-07-01

Anterior seromyotomy of the body and fundus of the stomach was combined with posterior truncal vagotomy and excision of the ulcer in 23 patients with gastric ulcer complicated by bleeding or perforation. Seventeen patients had chronic ulcers of the body of the stomach (type I), 3 patients had concurrent ulcers (type II), and 3 more patients had acute ulcers of the body of the stomach. Operation was undertaken for active bleeding from the ulcer in 20 patients and for perforating ulcer in 3 patients. One patient died. Mild disorders of evacuation of an aqueous barium sulfate suspension from the stomach were noted in 4 patients.

[Nursing measures against adverse reaction from anti-cancer chemotherapy].

PubMed

Goto, Setsuko; Mori, Machiko; Fukaya, Youko; Nakamura, Keiko

2003-06-01

Combination chemotherapy for leukemia develops bone marrow suppression. Infection or hemorrhage disorders the treatment, and may influence the clinical result. The caring staff must understand the pathology of bone marrow suppression. Visitors observe the hospital rules. Foods are also limited, city water and uncooked foods are prohibited. To keep oral cavity clean, pretreatment of some decayed teeth, and frequent gargling with sterilized water are needed. Defecation control is important. Sitz bath or shower toilet is helpful. Hand cleaning is essential for before a meal, after defecation and after a going out. Bathing is fundamental to cleaning body. No bathing is dirty. Medical catheters are checked up every day. Thrombocytopenia(< 30,000/microliter) develops a spontaneous bleeding. Severe thrombocytopenia(< 10,000/microliter) does a fatal organ bleeding.

[Recurrent variceal bleeding in a patient with portal and splenic vein thrombosis secondary to complex thrombophilia].

PubMed

Ławniczak, Małgorzata; Raszeja-Wyszomirska, Joanna; Marlicz, Wojciech; Białek, Andrzej; Wiechowska-Kozłowska, Anna; Lubikowski, Jerzy; Wójcicki, Maciej; Starzyńska, Teresa

2008-08-01

Thrombophilia in adults is one of main causes of portal vein thrombosis. Esophageal and gastric varices, ascites and hypersplenism are well known complications of portal hypertension. There are controversial issues on the management, especially anticoagulant therapy and surgical treatment of these patients. We present a 42-years old woman with a history of three acute coronary episodes suffering from recurrent variceal bleeding due to portal and splenic vein thrombosis in the course of myeloproliferative disorder and protein C deficiency. It was 10 months delay of diagnosis. She was successfully treated with medical and surgical treatment (esophageal stapler transection, cardial devascularization, and splenectomy). In the paper we discuss complexity of diagnosis and surgical treatment.

8(th) Symposium on Hemostasis: Translational and Basic Science Discoveries.

PubMed

Margaritis, Paris; Key, Nigel S

2016-05-01

It has been 14 years since the first symposium on hemostasis at UNC Chapel Hill that focused primarily on the tissue factor (TF) and Factor VIIa (FVIIa) biology, biochemistry and translational work for the treatment of bleeding. Concepts, mechanistic data and therapeutic agents have since emerged that permeate not only aspects of the TF and FVIIa functions, but also broader processes in hemostasis and thrombosis. These processes involve circulating proteins, receptors, cells and cellular components that interact within the coagulation system as well as with additional systems that are dysregulated in disorders seemingly unrelated to bleeding/thrombosis. The reviews in this symposium provide the research background to understand such interactions and integrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular and functional aspects of menstruation in the macaque.

PubMed

Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Vitamin K antagonists and direct thrombin inhibitors: present and future.

PubMed

Pineo, Graham F; Hull, Russell D

2005-02-01

Warfarin and related compounds are efficacious and safe in a variety of clinical thrombotic disorders; however, these drugs have a narrow therapeutic window, whereby inadequate therapy is associated with an increased thrombotic risk and overanticoagulation is associated with bleeding. Therefore, attempts have been made to develop alternatives to warfarin. Ximelagatran, an oral direct thrombin inhibitor, has been shown to be as efficacious and safe as warfarin for the prevention and treatment of different thrombotic disorders. This article reviews the pharmacology of the coumarins, the most commonly used vitamin K antagonists, and the practical aspects regarding their use in the management of thrombotic disorders. The future role of the oral direct thrombin inhibitor ximelagatran also is reviewed.

New daily persistent headache: a syndrome, not a discrete disorder.

PubMed

Goadsby, Peter J

2011-04-01

The term New Daily Persistent Headache (NDPH) has been used for nearly 25 years and yet the entity remains enigmatic. It can be argued the simplest, indeed most appropriate, approach is to use the term to mean simply what it says- i.e. as an umbrella description, rather like chronic daily headache. NDPH should be used as a diagnostic umbrella inviting better characterization, not be an achievement in itself. This would mean the term required no further elaboration- there would be no mimics- simply primary and secondary NDPH. A detailed examination of the literature reveals considerable heterogeneity in the phenotypic descriptions labelled as NDPH. The first effort in a patient with a NDPH presentation is to discern if secondary causes are present; some are obvious, such as subarachnoid bleeds and some can be more troublesome, such as syndromes of abnormal CSF pressure/volume, either high or low. A cohort of primary NDPH headaches can be seen in practice and in the literature and these should be sub-divided into a migrainous type, with appropriate phenotypic manifestations and a featureless type. Patients with any one of the NDPH presentations are best managed according to the more detailed pathophysiology-based diagnosis then lumped together into a single group, since a single disorder is unlikely to exist. © 2011 American Headache Society.

Haemophilia A carriers experience reduced health-related quality of life.

PubMed

Gilbert, L; Paroskie, A; Gailani, D; Debaun, M R; Sidonio, R F

2015-11-01

Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range. Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms. We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups. Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population. © 2015 John Wiley & Sons Ltd.

Gamma Knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part I: Differences in epidemiologic, morphologic, and clinical characteristics, permanent complications, and bleeding in the latency period

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nicolato, Antonio; Lupidi, Francesco; Section of Stereotactic and Functional Neurosurgery, University of Verona and University Hospital, Verona

Purpose: To compare the epidemiologic, morphologic, and clinical characteristics of 92 children/adolescents (Group A) and 362 adults (Group B) with cerebral arteriovenous malformations (cAVMs) considered suitable for radiosurgery; to correlate radiosurgery-related permanent complication and post-radiosurgery bleeding rates in the 75 children/adolescents and 297 adults available for follow-up. Methods and Materials: Radiosurgery was performed with a model C 201-source Co{sup 6} Leksell Gamma Unit (Elekta Instruments, Stockholm, Sweden). Fisher exact two-tailed, Wilcoxon rank-sum, and two-sample binomial exact tests were used for statistical analysis. Results: There were significant differences between the two populations in sex (p = 0.015), clinical presentation (p =more » 0.001), and location (p = 0.008). The permanent complication rate was lower in younger (1.3%) than in older patients (5.4%), although the difference was not significant (p = 0.213). The postradiosurgery bleeding rate was lower in Group A (1.3%) than in Group B (2.7%) (p = 0.694), with global actuarial bleeding rates of 0.56% per year and 1.15% per year, respectively. Conclusions: The different characteristics of child/adolescent and adult cAVMs suggest that they should be considered two distinct vascular disorders. The similar rates of radiosurgery-related complications and latency period bleeding in the two populations show that gamma knife radiosurgery does not expose young patients to a higher risk of sequelae than that for older patients.« less

Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

PubMed Central

Soucie, J. Michael; Gill, Joan Cox

2017-01-01

This analysis of the US Hemophilia Treatment Center Network and the Centers for Disease Control and Prevention surveillance registry assessed trends in prophylaxis use and its impact on key indicators of arthropathy across the life-span among participants with severe hemophilia A. Data on demographics, clinical characteristics, and outcomes were collected prospectively between 1999 and 2010 at annual clinical visits to 134 hemophilia treatment centers. Trends in treatment and outcomes were evaluated using cross-sectional and longitudinal analyses. Data analyzed included 26 614 visits for 6196 males; mean age at first registry visit was 17.7 years; and median was 14 (range, 2 to 69). During this time, prophylaxis use increased from 31% to 59% overall, and by 2010, 75% of children and youths <20 years were on prophylaxis. On cross-sectional analysis, bleeding rates decreased dramatically for the entire population (P < .001) in parallel with increased prophylaxis usage, possibly because frequent bleeders adopted prophylaxis. Joint bleeding decreased proportionately with prophylaxis (22%) and nonprophylaxis (23%), and target joints decreased more with prophylaxis (80% vs 61%). Joint, total, and target joint bleeding on prophylaxis were 33%, 41%, and 27%, respectively, compared with nonprophylaxis. On longitudinal analysis of individuals over time, prophylaxis predicted decreased bleeding at any age (P < .001), but only prophylaxis initiation prior to age 4 years and nonobesity predicted preservation of joint motion (P < .001 for each). Using a national registry, care providers in a specialized health care network for a rare disorder were able to detect and track trends in outcomes over time. PMID:28183693

A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004 and updated in 2012 that addressed four separate questions: therapeutic-only versus prophylactic platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. We have now split this review into four smaller reviews looking at these questions individually; this review is the first part of the original review. Objectives To determine whether a therapeutic-only platelet transfusion policy (platelet transfusions given when patient bleeds) is as effective and safe as a prophylactic platelet transfusion policy (platelet transfusions given to prevent bleeding, usually when the platelet count falls below a given trigger level) in patients with haematological disorders undergoing myelosuppressive chemotherapy or stem cell transplantation. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 July 2015. Selection criteria RCTs involving transfusions of platelet concentrates prepared either from individual units of whole blood or by apheresis, and given to prevent or treat bleeding in patients with malignant haematological disorders receiving myelosuppressive chemotherapy or undergoing HSCT. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine whether there was any difference in the number of participants with severe or life-threatening bleeding between a therapeutic-only transfusion policy and a prophylactic platelet transfusion policy (two RCTs; 801 participants; risk ratio (RR) 4.91, 95% CI 0.86 to 28.12; low-quality evidence). Two RCTs (801 participants) reported time to first bleeding episode. As there was considerable heterogeneity between the studies, we were unable to perform a meta-analysis. Both studies individually found that time to first bleeding episode was shorter in the therapeutic-only group compared with the prophylactic platelet transfusion group. There was insufficient evidence to determine any difference in all-cause mortality within 30 days of the start of the study using a therapeutic-only platelet transfusion policy compared with a prophylactic platelet transfusion policy (two RCTs; 629 participants). Mortality was a rare event, and therefore larger studies would be needed to establish the effect of these alternative strategies. There was a clear reduction in the number of platelet transfusions per participant in the therapeutic-only arm (two RCTs, 991 participants; standardised mean reduction of 0.50 platelet transfusions per participant, 95% CI −0.63 to −0.37; moderate-quality evidence). None of the studies reported quality of life. There was no evidence of any difference in the frequency of adverse events, such as transfusion reactions, between a therapeutic-only and prophylactic platelet transfusion policy (two RCTs; 991 participants; RR 1.02, 95% CI 0.62 to 1.68), although the confidence intervals were wide. Authors’ conclusions We found low- to moderate-grade evidence that a therapeutic-only platelet transfusion policy is associated with increased risk of bleeding when compared with a prophylactic platelet transfusion policy in haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT. There is insufficient evidence to determine any difference in mortality rates and no evidence of any difference in adverse events between a therapeutic-only platelet transfusion policy and a prophylactic platelet transfusion policy. A therapeutic-only platelet transfusion policy is associated with a clear reduction in the number of platelet components administered. PMID:26422767

Management of chronic pancreatitis complicated with a bleeding pseudoaneurysm.

PubMed

Chiang, Kun-Chun; Chen, Tsung-Hsing; Hsu, Jun-Te

2014-11-21

Chronic pancreatitis is an ongoing disease characterized by persistent inflammation of pancreatic tissues. With disease progression, patients with chronic pancreatitis may develop troublesome complications in addition to exocrine and endocrine pancreatic functional loss. Among them, a pseudoaneurysm, mainly induced by digestive enzyme erosion of vessels in proximity to the pancreas, is a rare and life-threatening complication if bleeding of the pseudoaneurysm occurs. At present, no prospective randomized trials have investigated the therapeutic strategy for this rare but critical situation. The role of arterial embolization, the timing of surgical intervention and even surgical procedures are still controversial. In this review, we suggest that dynamic abdominal computed tomography and angiography should be performed first to localize the bleeders and to evaluate the associated complications such as pseudocyst formation, followed by arterial embolization to stop the bleeding and to achieve early stabilization of the patient's condition. With advances and improvements in endoscopic devices and techniques, therapeutic endoscopy for pancreatic pseudocysts is technically feasible, safe and effective. Surgical intervention is recommended for a bleeding pseudoaneurysm in patients with chronic pancreatitis who are in an unstable condition, for those in whom arterial embolization of the bleeding pseudoaneurysm fails, and when endoscopic management of the pseudocyst is unsuccessful. If a bleeding pseudoaneurysm is located over the tail of the pancreas, resection is a preferential procedure, whereas if the lesion is situated over the head or body of the pancreas, relatively conservative surgical procedures are recommended.

Predictors of Co-occurring Neurodevelopmental Disabilities in Children With Autism Spectrum Disorders.

PubMed

Zauche, Lauren Head; Darcy Mahoney, Ashley E; Higgins, Melinda K

Co-occurring neurodevelopmental disabilities (including cognitive and language delays and attention deficit hyperactivity disorder) affect over half of children with ASD and may affect later behavioral, language, and cognitive outcomes beyond the ASD diagnosis. However, no studies have examined predictors of co-occurring neurodevelopmental disabilities in children with ASD. This study investigated whether maternal sociodemographic, perinatal and neonatal factors are associated with co-occurring disabilities. This study involved a retrospective analysis of medical records for children diagnosed with ASD between 2009 and 2010 at an Autism Center in the southeast United States. Logistic regression was used to identify predictors of co-occurring neurodevelopmental disabilities. Of the 385 children in the sample, 61% had a co-occurring neurodevelopmental disability. Children whose mothers had less education (OR: 0.905), had never been married (OR: 1.803), or had bleeding during pregnancy (OR: 2.233) were more likely to have a co-occurring neurodevelopmental disability. Both preterm birth and African American race were associated with bleeding during pregnancy. Several maternal and perinatal risk factors for ASD were found to put children at risk for further diagnoses of co-occurring neurodevelopmental disabilities. While prematurity, a well-established risk factor for ASD, as well as maternal ethnicity was not found to increase the risk of a co-occurring disability, this study suggests that bleeding during pregnancy may moderate these relationships. Understanding maternal, perinatal, and neonatal risk factors may inform healthcare provider screening for ASD and co-occurring neurodevelopmental disabilities by helping providers recognize infants who present with multiple risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

PubMed

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

Abnormal uterine bleeding: advantages of formal classification to patients, clinicians and researchers.

PubMed

Madhra, Mayank; Fraser, Ian S; Munro, Malcolm G; Critchley, Hilary O D

2014-07-01

To highlight the advantages of formal classification of causes of abnormal uterine bleeding from a clinical and scientific perspective. Review and recommendations for local implementation. In the past, research in the field of menstrual disorders has not been funded adequately with respect to the impact of symptoms on individuals, healthcare systems and society. This was confounded by a diverse terminology, which lead to confusion between clinical and scientific groups, ultimately harming the underlying evidence base. To address this, a formal classification system (PALM-COEIN) for the causes of abnormal uterine bleeding has been published for worldwide use by FIGO (International Federation of Gynecology and Obstetrics). This commentary explains problems created by the prior absence of such a system, the potential advantages stemming from its use, and practical suggestions for local implementation. The PALM-COEIN classification is applicable globally and, as momentum gathers, will ameliorate recurrence of historic problems, and harmonise reporting of clinical and scientific research to facilitate future progress in women's health. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Acute Uterine Bleeding Unrelated to Pregnancy: A Southern California Permanente Medical Group Practice Guideline

PubMed Central

Munro, Malcolm G

2013-01-01

Acute uterine bleeding unrelated to pregnancy has been defined as bleeding “sufficient in volume as to, in the opinion of the treating clinician, require urgent or emergent intervention.” The Southern California Permanente Medical Group updated its guidelines for the management of this condition on the basis of the best available evidence, as identified in a systematic review of the available literature. Given the paucity of studies evaluating this condition, the guidelines, by necessity, include recommendations largely based on opinion or other sources such as case series that are, in general, categorized as low-quality evidence. Medical interventions with single or combined gonadal steroidal agents administered parenterally or orally show promise, but more high-quality studies are needed to better define the appropriate drugs, dose, and administrative scheduling. There is also some evidence that intrauterine tamponade may be useful in at least selected cases. Special attention must be paid to both diagnosing and treating inherited disorders of hemostasis, such as von Willebrand disease, that may otherwise be underdiagnosed in both adolescent and adult women. PMID:24355890

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A.

PubMed

Du, Lily M; Nurden, Paquita; Nurden, Alan T; Nichols, Timothy C; Bellinger, Dwight A; Jensen, Eric S; Haberichter, Sandra L; Merricks, Elizabeth; Raymer, Robin A; Fang, Juan; Koukouritaki, Sevasti B; Jacobi, Paula M; Hawkins, Troy B; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A.

Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A

PubMed Central

Du, Lily M.; Nurden, Paquita; Nurden, Alan T.; Nichols, Timothy C.; Bellinger, Dwight A.; Jensen, Eric S.; Haberichter, Sandra L.; Merricks, Elizabeth; Raymer, Robin A.; Fang, Juan; Koukouritaki, Sevasti B.; Jacobi, Paula M.; Hawkins, Troy B.; Cornetta, Kenneth; Shi, Qizhen; Wilcox, David A.

2013-01-01

It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury, we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter, which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus, platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A. PMID:24253479

A disease difficult to diagnose: Gardner-Diamond syndrome accompanied by platelet dysfunction

PubMed Central

Karakaş, Zeynep; Karaman, Serap; Avcı, Burcu; Ünüvar, Ayşegül; Öztürk, Gülyüz; Anak, Sema; Devecioğlu, Ömer

2014-01-01

Gardner Diamond syndrome is a rare condition characterized with painful ecchymoses in different parts of the body and cutaneous and mucosal hemorrhages. The etiology is not known fully and psychogenic factors are thought to be involved. Cutaneous lesions and hemorrhages develop mostly following emotional stress and rarely minor traumas and may recur. Although the extremities are involved with the highest rate, the lesions may be observed in any part of the body. Hemostatic tests are generally normal. The majority of the subjects is composed of young women. It is observed more rarely in men and children. In this article, a patient who presented with recurring painful echymoses and bleeding disorder and diagnosed with Gardner Diamond syndrome by intracutaneous injection of autologous blood was presented to emphasize that this syndrome is observed rarely in the childhood and should be considered not only in the differential diagnosis of cutaneous lesions, but also in the differential diagnosis of various system hemorrhages. PMID:26078671

What Impact Does Venous Thromboembolism and Bleeding Have on Cancer Patients' Quality of Life?

PubMed

Lloyd, Andrew J; Dewilde, Sarah; Noble, Simon; Reimer, Elisabeth; Lee, Agnes Y Y

2018-04-01

Venous thromboembolism (VTE) is common in cancer patients and its treatment is associated with a high risk of recurrent VTE (rVTE) and bleeding. To analyze data from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial to describe the impact of rVTE and bleeding events on health-related quality of life. The three-level EuroQol five-dimensional questionnaire (EQ-5D) data were collected monthly for up to 7 months in patients starting anticoagulation for newly diagnosed VTE. Analyses were designed to describe the impact of rVTE and bleeding on EQ-5D scores while controlling for effects of covariates such as background and clinical variables and longitudinal changes. A repeated-measures model with specification of the variance-covariance matrix to characterize the intrapatient correlation was used to estimate the utility values. The impact of an rVTE or a bleeding event was assumed to be reflected in the utility value when it occurred within 2 weeks from a planned data collection point. Data were available from 883 patients. A total of 76 rVTE and 159 bleeding events occurred during follow-up. rVTE had a significant impact on EQ-5D scores, with a decrement of -0.075 on the basis of our reference case (male, no metastasis, Eastern Cooperative Oncology Group score = 1, Western European), but different patients might have different decrements. Bleeding events had a smaller (nonstatistically significant) impact on EQ-5D scores. This data set study has quantified the decline in EQ-5D scores associated with experiencing rVTE or bleeding events in cancer patients. These results indicate the net gain in quality of life and impact on cost-effectiveness of secondary VTE prevention. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs.

PubMed

Makielski, Kelly M; Brooks, Marjory B; Wang, Chong; Cullen, Jonah N; O'Connor, Annette M; LeVine, Dana N

2018-04-21

A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Client-owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (r s  = -0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (r s  = 0.512, P < .0001) and hospitalization duration (r s  = 0.35, P = .006). The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Blood derived products in pediatrics: New laboratory tools for optimizing potency assignment and reducing side effects.

PubMed

Amiral, Jean; Seghatchian, Jerard

2017-04-01

Neonates and children can develop rare bleeding disorders due to congenital/acquired coagulation Factor deficiencies, or allo-immune/autoimmune complications, or can undergo surgeries at high haemorrhagic risk. They then need specialized transfusion of blood components/products, or purified blood extracted products or recombinant proteins. Blood-derived therapies conventionally used for management of affected infants with genetic/acquired deficiencies, bleeding problems (coagulation Factor reduced or missing) or thrombotic disorders (reduced or missing anticoagulant proteins) pose some additional risks. These remedial therapies can cause tolerance when used very early in life and, sometimes needed, repeatedly. The introduction of recombinant proteins has allowed manufacturers to produce large amounts of the proteins usually present at very low concentration in blood. This has also changed the risk pattern of plasma-extracted products, especially in terms of continual reduction of viral transmission. Many efforts have been made over these past decades to reduce the risks associated with the use of all these products in terms of viral and bacterial safety, as well as immune disorders but they are not the objective of this article. Other associated side effects are the presence of undesired activities in blood products, which can produce thrombotic events or adverse reactions. The progressive introduction of blood derived products has greatly improved the prognosis and quality of life of affected patients. This concerns whole blood, but also blood cell concentrates, mainly platelets and red blood cells, plasma, while the blood extracted products are increasingly replaced by recombinant proteins. All these therapeutic products, i.e. blood extracted drugs, improve health and quality of life for hemophiliac's A or B, or patients with auto/allo-immune thrombocytopenias or with rare bleeding disorders, and those with thrombotic events occurring in childhood, which are mainly due to Protein C or Protein S deficiencies (congenital or acquired). Progress in analytical methods and biotechnology allow better control of the manufacturing processes for all blood derived or plasma extracted products and recombinant proteins, and contribute to improved manufacturing processes to minimize the occurrence of side effects. These adverse events can be due to the aging of the blood cell concentrate with release of their granule content, and generation of EVs, which can produce anaphylactic reactions and risk of thrombosis, but also to the presence of activated coagulation Factors in purified products, such as Factor Xia as recently identified in immunoglobulin concentrates. Characterization and measurement of contaminant products is of special usefulness during product preparation and for optimization of manufacturing processes for purified extracted products, but also for recombinant proteins. The pharmaceutical industry introduces these new methods for validating manufacturing processes, or for quality control assessments. The objective is first to warrant the full quality and safety of the lots produced, and assure the highest efficacy with the lowest risks when used in patients. For cell concentrates and fresh blood, storage conditions are critical and measurement of analytes such as EVs or Annexin V allows evaluation of quality of each individual transfused pouch. In addition to all the rules around viral and bacterial transmission risk, and immune tolerance, our available laboratory methods contribute to reducing the side effects of blood cell concentrates and derived plasma products, as well as those of the therapeutic recombinant proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Towards personalised therapy for von Willebrand disease: a future role for recombinant products.

PubMed

Favaloro, Emmanuel J

2016-05-01

von Willebrand disease (VWD) is reportedly the most common bleeding disorder and is caused by deficiencies and/or defects in the adhesive plasma protein von Willebrand factor (VWF). Functionally, normal VWF prevents bleeding by promoting both primary and secondary haemostasis. In respect to primary haemostasis, VWF binds to both platelets and sub-endothelial matrix components, especially collagen, to anchor platelets to damaged vascular tissue and promote thrombus formation. VWF also stabilises and protects factor VIII in the circulation, delivering FVIII to the site of injury, which then facilitates secondary haemostasis and fibrin formation/thrombus stabilisation. As a result of this, patients with VWD suffer a bleeding diathesis reflective of a primary defect caused by defective/deficient VWF, which in some patients is compounded by a reduction in FVIII. Management of VWD, therefore, chiefly entails replacement of VWF, and sometimes also FVIII, to protect against bleeding. The current report principally focuses on the future potential for "personalised" management of VWD, given the emerging options in recombinant therapies. Recombinant VWF has been developed and is undergoing clinical trials, and this promising therapy may soon change the way in which VWD is managed. In particular, we can envisage a personalised treatment approach using recombinant VWF, with or without recombinant FVIII, depending on the type of VWD, the extent of deficiencies, and the period and duration of treatment.

Clinical predictors and gender-wise variations in dyssynergic defecation disorders.

PubMed

Jain, Mayank; Baijal, Rajiv; Srinivas, Melpakkam; Venkataraman, Jayanthi

2018-06-12

There is insufficient data from India regarding clinical predictors of dyssynergic defecation. To identify demography, symptom, and colonoscopic parameters that can predict dyssynergic defecation (DD) among patients with chronic constipation (CC) and to compare the profile among male and female patients with DD. Data collected from three centers during June 2014 to May 2017 included age, gender, symptom duration, form and consistency of stools, digital examination, colonoscopy, and anorectal manometry (ARM). Patients were grouped based on ARM diagnosis: group I (normal study) and group II (DD). The two groups were compared for demography, symptom profile, and colonoscopy findings. Gender-wise subset analysis was done for those with the normal and abnormal ARM using chi-square and unpaired t tests. Of 236 patients with CC evaluated, 130 (55%) had normal ARM and 106 (45%) had DD. Male sex, straining during defecation, bleeding per rectum, and abnormal colonoscopic diagnosis were significantly more common in group II. While bleeding per rectum and absence of urge to defecate were more common in males (p < 0.02), straining, digital evacuation, and hard stools were commoner in females with DD. Straining during defecation, bleeding per rectum, and abnormal colonoscopy findings were more common in patients with DD. Symptoms of bleeding per rectum and absence of urge to defecate in men and straining during defecation in female patients were significantly associated with DD. Symptoms differ in males and females with DD.

Combined variants in factor VIII and prostaglandin synthase-1 amplify hemorrhage severity across three generations of descendants.

PubMed

Nance, D; Campbell, R A; Rowley, J W; Downie, J M; Jorde, L B; Kahr, W H; Mereby, S A; Tolley, N D; Zimmerman, G A; Weyrich, A S; Rondina, M T

2016-11-01

Essentials Co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. We determined pathogenic variants in a three-generational pedigree with excessive bleeding. Bleeding occurred with concurrent variants in prostaglandin synthase-1 (PTGS-1) and factor VIII. The PTGS-1 variant was associated with functional defects in the arachidonic acid pathway. Background Inherited human variants that concurrently cause disorders of primary hemostasis and coagulation are uncommon. Nevertheless, rare cases of co-existent damaging variants are likely to cause more severe bleeding and may go undiagnosed. Objective We prospectively sought to determine pathogenic variants in a three-generational pedigree with excessive bleeding. Patients/methods Platelet number, size and light transmission aggregometry to multiple agonists were evaluated in pedigree members. Transmission electron microscopy determined platelet morphology and granule content. Thromboxane release studies and light transmission aggregometry in the presence or absence of prostaglandin G 2 assessed specific functional defects in the arachidonic acid pathway. Whole exome sequencing (WES) and targeted nucleotide sequence analysis identified potentially deleterious variants. Results Pedigree members with excessive bleeding had impaired platelet aggregation with arachidonic acid, epinephrine and low-dose ADP, as well as reduced platelet thromboxane B 2 release. Impaired platelet aggregation in response to 2MesADP was rescued with prostaglandin G 2 , a prostaglandin intermediate downstream of prostaglandin synthase-1 (PTGS-1) that aids in the production of thromboxane. WES identified a non-synonymous variant in the signal peptide of PTGS-1 (rs3842787; c.50C>T; p.Pro17Leu) that completely co-segregated with disease phenotype. A variant in the F8 gene causing hemophilia A (rs28935203; c.5096A>T; p.Y1699F) was also identified. Individuals with both variants had more severe bleeding manifestations than characteristic of mild hemophilia A alone. Conclusion We provide the first report of co-existing variants in both F8 and PTGS-1 genes in a three-generation pedigree. The PTGS-1 variant was associated with specific functional defects in the arachidonic acid pathway and more severe hemorrhage. © 2016 International Society on Thrombosis and Haemostasis.

Disseminated intravascular coagulation: pathophysiology and principles of management.

PubMed

Marwaha, R K; Mitra, S; Marwaha, N

1998-03-01

DIC is a thrombohemorrhagic syndrome which occurs in association with well-defined clinical disorders such as septicemia, acute leukemia, snake envenomation, hypoxic states, etc. These disease conditions trigger the coagulation cascade in vivo resulting in formation of microthrombi, activation of fibrinolysis and a bleeding tendency. The important and most frequently observed laboratory abberrations include reduced platelet counts, low levels of fibrinogen, factors V and XIII with increased FDP's. Therapy primarily consists of recognizing the cause of DIC, removing the triggering process and administering anticoagulant therapy in specific situations. Component replacement is required if patients continue to bleed inspite of instituting the above mentioned measures. Rarely, drugs which inhibit fibrinolysis may be indicated. Early recognition and prompt institution of appropriate remedial measures coupled with adequate laboratory monitoring help in reducing morbidity and mortality due to DIC.

[Münchhausen syndrome by proxy].

PubMed

Le Heuzey, M-F; Mouren, M-C

2008-01-01

Münchhausen syndrome by proxy is a factitious disorder, a disease produced or simulated by a parent, the mother in most cases. Clinical presentation is miscellaneous (factitious bleeding, epilepsy, apnea are frequent) and unusual. Physicians participate in the abuse by their therapeutic and diagnostical measures. It is very important to think about this diagnostic in any ambiguous situation in order to evaluate and protect the child.

Acute Arthritis in Crimean-Congo Hemorrhagic Fever

PubMed Central

Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita

2014-01-01

Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus. An atypical manifestation in the form of acute arthritis was found in a confirmed Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune mechanisms or the bleeding disorder underlying CCHF. PMID:24926169

Tissue Factor Pathway Inhibitor: Multiple Anticoagulant Activities for a Single Protein.

PubMed

Mast, Alan E

2016-01-01

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits early phases of the procoagulant response. Alternatively spliced isoforms of TFPI are differentially expressed by endothelial cells and human platelets and plasma. The TFPIβ isoform localizes to the endothelium surface where it is a potent inhibitor of TF-factor VIIa complexes that initiate blood coagulation. The TFPIα isoform is present in platelets. TFPIα contains a stretch of 9 amino acids nearly identical to those found in the B-domain of factor V that are well conserved in mammals. These amino acids provide exosite binding to activated factor V, which allows for TFPIα to inhibit prothrombinase during the initiation phase of blood coagulation. Endogenous inhibition at this point in the coagulation cascade was only recently recognized and has provided a biochemical rationale to explain the pathophysiological mechanisms underlying several clinical disorders. These include the east Texas bleeding disorder that is caused by production of an altered form of factor V with high affinity for TFPI and a paradoxical procoagulant effect of heparins. In addition, these findings have led to ideas for pharmacological targeting of TFPI that may reduce bleeding in hemophilia patients. © 2015 American Heart Association, Inc.

Surgery of a cyanotic heart defect in an 11-year-old boy with thrombocytopenic thrombocytopathy and severe anemia due to a GATA-1 defect: hemostatic therapy.

PubMed

Hoefer, J; Streif, W; Kilo, J; Grimm, M; Berger, G; Velik-Salchner, C

2012-10-01

A child was admitted to our hospital for repair of a ventricular septal defect (VSD) characterized by a predominantly right-to-left shunt and a severe stenosis of the right ventricular outflow tract (Tetralogy of Fallot). Severe congenital anemia (hemoglobin 72 g/L), thrombocytopenia (42×G/L) and profound platelet dysfunction led a stem cell defect to be suspected. X-linked thrombocytopenia (GATA-1 mutation) was diagnosed. GATA-1 defect may complicate medical interventions due to excessive bleeding and partial or complete bone marrow failure. Maintaining a platelet count of 100 G/L and a maximal clot firmness (EXTEM-MCF) >50 mm allowed repair of the congenital heart defect without bleeding or hematological complications. Anemia and thrombocytopenia persisted after cardiac surgery, while the spontaneous bleeding tendency improved. © Georg Thieme Verlag KG Stuttgart · New York.

Blockade of protease-activated receptor-4 (PAR4) provides robust antithrombotic activity with low bleeding.

PubMed

Wong, Pancras C; Seiffert, Dietmar; Bird, J Eileen; Watson, Carol A; Bostwick, Jeffrey S; Giancarli, Mary; Allegretto, Nick; Hua, Ji; Harden, David; Guay, Jocelyne; Callejo, Mario; Miller, Michael M; Lawrence, R Michael; Banville, Jacques; Guy, Julia; Maxwell, Brad D; Priestley, E Scott; Marinier, Anne; Wexler, Ruth R; Bouvier, Michel; Gordon, David A; Schumacher, William A; Yang, Jing

2017-01-04

Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4. A PAR1 antagonist is approved for clinical use, but its use is limited by a substantial bleeding risk. Conversely, the potential of PAR4 as an antiplatelet target has not been well characterized. Using anti-PAR4 antibodies, we demonstrated a low bleeding risk and an effective antithrombotic profile with PAR4 inhibition in guinea pigs. Subsequently, high-throughput screening and an extensive medicinal chemistry effort resulted in the discovery of BMS-986120, an orally active, selective, and reversible PAR4 antagonist. In a cynomolgus monkey arterial thrombosis model, BMS-986120 demonstrated potent and highly efficacious antithrombotic activity. BMS-986120 also exhibited a low bleeding liability and a markedly wider therapeutic window compared to the standard antiplatelet agent clopidogrel tested in the same nonhuman primate model. These preclinical findings define the biological role of PAR4 in mediating platelet aggregation. In addition, they indicate that targeting PAR4 is an attractive antiplatelet strategy with the potential to treat patients at a high risk of atherothrombosis with superior safety compared with the current standard of care. Copyright © 2017, American Association for the Advancement of Science.

Effects of platelet concentrate storage time reduction in patients after blood stem cell transplantation.

PubMed

Heuft, H-G; Goudeva, L; Krauter, J; Peest, D; Buchholz, S; Tiede, A

2013-07-01

To evaluate the clinical effect of platelet concentrate (PC) transfusions after PC storage time reduction to 4 days. This was a single-centre cohort study comparing two 3-month periods of time, before and after the reduction of PC storage time from 5 to 4 days. Seventy-seven consecutive patients with PC transfusions were enrolled after blood stem cell transplantation. Corrected platelet count increment (CCI) on the morning after transfusion, time to next platelet transfusion, need for red blood cell (RBC) transfusion and clinical bleeding symptoms were compared. Platelet concentrate storage time was reduced between period 1 (storage for up to 5 days, median storage time 78 h, range 11-136 h) and period 2 (storage for up to 4 days, median storage time 53 h, range 11-112 h). Patients were comparable for age, weight, body surface area, underlying disorder, type of transplantation and transfused platelet dose. The CCI increased from a median of 4 (range 0-20) to 8 (0-68) × 10(9) /l per 10(11) platelets/m(2) (P < 0·0001). Time to next PC transfusion increased from 1·1 to 2·0 days (P < 0·0001). Any bleeding symptom was noted in 20 of 36 patients (56%) vs. 9/41 patients (22%, P < 0·01). Nose bleeds, haematuria and bleeding at more than one site were significantly reduced. Frequency of RBC transfusion within 5 days after PC transfusion was reduced from 74 to 58% (P < 0·0001). Platelet concentrate storage time shortening was associated with highly significant CCI increase, reduced RC needs and lower patient numbers with bleeding events. © 2013 International Society of Blood Transfusion.

Effect of tranexamic acid on intra- and postoperative haemorrhage in dogs with surgically treated hemoperitoneum.

PubMed

Sigrist, N; Olgiati, L; Jud Schefer, R S

2018-05-01

Tranexamic acid (TXA) is an antifibrinolytic drug that is used for uncontrolled bleeding of various origin. This retrospective study investigated the effect of tranexamic acid administration on bleeding tendency in dogs with surgically managed hemoperitoneum. Thirty dogs were treated with (TXA group) and 25 dogs without (CTR group) tranexamic acid prior to surgery. Various parameters (decrease in haematocrit, number of transfusions, shock index and changes in abdominal fluid accumulation) were used for characterization of bleeding tendency and compared between groups. Groups were similar at presentation and prior to surgery. None of the dogs undergoing rotational thromboelastography analysis showed hyperfibrinolysis prior to surgery. Overall transfusion and erythrocyte transfusion requirements as well as bleeding tendency, hospitalisation time and hospital discharge rate were similar between groups. Dogs of the TXA group received significantly more intraoperative plasma transfusions (P=0.013) and showed a higher systolic and mean arterial blood pressure (P=0.002 and 0.050) and lower shock index (P=0.028) with less dogs being in shock (P=0.012) at 24h. In summary, in this study population of dogs with surgically managed spontaneous hemoperitoneum dogs treated with tranexamic acid received more plasma transfusions intraoperatively and showed a lower shock index 24h after presentation. In dogs with surgically treated hemoabdomen tranexamic acid administration prior to surgery does not reduce red blood cell transfusion requirements or postoperative bleeding tendency.

Elevated prothrombin time on routine preoperative laboratory results in a healthy infant undergoing craniosynostosis repair: Diagnosis and perioperative management of congenital factor VII deficiency.

PubMed

Jones, Kareen L; Greenberg, Robert S; Ahn, Edward S; Kudchadkar, Sapna R

2016-01-01

Congenital factor VII deficiency is a rare bleeding disorder with high phenotypic variability. It is critical that children with congenital Factor VII deficiency be identified early when high-risk surgery is planned. Cranial vault surgery is common for children with craniosynostosis, and these surgeries are associated with significant morbidity mostly secondary to the risk of massive blood loss. A two-month old infant who presented for elective craniosynostosis repair was noted to have an elevated prothrombin time (PT) with a normal activated partial thromboplastin time (aPTT) on preoperative labs. The infant had no clinical history or reported family history of bleeding disorders, therefore a multidisciplinary decision was made to repeat the labs under general anesthesia and await the results prior to incision. The results confirmed the abnormal PT and the case was canceled. Hematologic workup during admission revealed factor VII deficiency. The patient underwent an uneventful endoscopic strip craniectomy with perioperative administration of recombinant Factor VIIa. Important considerations for perioperative laboratory evaluation and management in children with factor VII deficiency are discussed. Anesthetic and surgical management of the child with factor VII deficiency necessitates meticulous planning to prevent life threatening bleeding during the perioperative period. A thorough history and physical examination with a high clinical suspicion are vital in preventing hemorrhage during surgeries in children with coagulopathies. Abnormal preoperative lab values should always be confirmed and addressed before proceeding with high-risk surgery. A multidisciplinary discussion is essential to optimize the risk-benefit ratio during the perioperative period. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Male gender, school attendance and sports participation are positively associated with health-related quality of life in children and adolescents with congenital bleeding disorders.

PubMed

Limperg, P F; Joosten, M M H; Fijnvandraat, K; Peters, M; Grootenhuis, M A; Haverman, L

2018-02-08

This study assesses health-related quality of life (HRQOL), and variables associated with HRQOL, in children and adolescents with haemophilia and congenital bleeding disorders (CBD) in the Netherlands. Patients <18 years with CBD under treatment at the Hemophilia Comprehensive Care Center of the Academic Medical Center were included. Participants completed generic HRQOL questionnaires (TAPQOL 0-5 years; PedsQL 6-18 years). Differences and effect sizes in HRQOL compared to healthy peers, and between hemophilia severity groups, were tested using Mann Whitney U-tests. Multivariate regression analyses were performed to assess variables associated with HRQOL. Data of 145 patients (81%) were analyzed (N = 32 with severe haemophilia). Children (0-12 years) show no significant impairments in HRQOL compared to healthy peers. Adolescent boys (13-18 years) with CBD report a slightly higher HRQOL on the total and emotional functioning scales than healthy peers (small-moderate effect sizes). In contrast, adolescent girls experience lower HRQOL on total, social functioning and psychosocial health scales compared to healthy peers (moderate effect sizes). No differences between severity groups were found in HRQOL, but more problem behaviour was found in young boys (0-5 years) with severe haemophilia. Male gender, participation in sports and school attendance are positively associated with HRQOL. Parental country of birth, type of treatment and number of bleeds are not associated with HRQOL. Continuing monitoring HRQOL in daily clinical practice for children with CBD is important, since possible influencing psychosocial factors can change over time, with special focus on adolescent girls, sports participation and school absence. © 2018 John Wiley & Sons Ltd.

Impaired thromboxane receptor dimerization reduces signaling efficiency: A potential mechanism for reduced platelet function in vivo.

PubMed

Capra, Valérie; Mauri, Mario; Guzzi, Francesca; Busnelli, Marta; Accomazzo, Maria Rosa; Gaussem, Pascale; Nisar, Shaista P; Mundell, Stuart J; Parenti, Marco; Rovati, G Enrico

2017-01-15

Thromboxane A 2 is a potent mediator of inflammation and platelet aggregation exerting its effects through the activation of a G protein-coupled receptor (GPCR), termed TP. Although the existence of dimers/oligomers in Class A GPCRs is widely accepted, their functional significance still remains controversial. Recently, we have shown that TPα and TPβ homo-/hetero-dimers interact through an interface of residues in transmembrane domain 1 (TM1) whose disruption impairs dimer formation. Here, biochemical and pharmacological characterization of this dimer deficient mutant (DDM) in living cells indicates a significant impairment in its response to agonists. Interestingly, two single loss-of-function TPα variants, namely W29C and N42S recently identified in two heterozygous patients affected by bleeding disorders, match some of the residues mutated in our DDM. These two naturally occurring variants display a reduced potency to TP agonists and are characterized by impaired dimer formation in transfected HEK-293T cells. These findings provide proofs that lack of homo-dimer formation is a crucial process for reduced TPα function in vivo, and might represent one molecular mechanism through which platelet TPα receptor dysfunction affects the patient(s) carrying these mutations. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR) Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

PubMed

Stockley, Jacqueline; Nisar, Shaista P; Leo, Vincenzo C; Sabi, Essa; Cunningham, Margaret R; Eikenboom, Jeroen C; Lethagen, Stefan; Schneppenheim, Reinhard; Goodeve, Anne C; Watson, Steve P; Mundell, Stuart J; Daly, Martina E

2015-01-01

The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =), both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N) was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =). Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

Bleeding disorders in pregnant patients with rheumatic diseases.

PubMed

Rick, M E

1989-05-01

Although the bleeding disorders that occur in patients with rheumatic diseases are not different during pregnancy than at other times, their diagnosis and management are often different during pregnancy. In idiopathic thrombocytopenic purpura, for instance, antiplatelet antibodies may cross the placenta and cause life-threatening thrombocytopenia in the fetus while the mother is asymptomatic. Management of this disease has changed significantly in the past 5 years with the use of intravenous gammaglobulin which appears to lessen the degree of fetal as well as maternal thrombocytopenia when administered during the peripartum period. The utilization of plasmapheresis and plasma infusions for patients with thrombotic thrombocytopenic purpura has salvaged both the mother and the fetus in a disease which was fatal in more than 60 per cent of patients prior to their use. The outcome of pregnancy in this patient population has markedly improved with this treatment. The stimulus for the production of factor VIII inhibitors in the postpartum period is still not understood, but guidelines for management have changed, with the increased likelihood of decreasing the antibody and inducing tolerance with regimens including factor VIII, immunosuppressive agents and intravenous gammaglobulin in those patients who require treatment. The diagnosis of von Willebrand's disease during pregnancy is difficult because of the physiologic increase in von Willebrand factor during pregnancy; in this instance family studies may help in the diagnosis of this relatively common, autosomal dominant inherited disorder. Management now includes treatment with desmopressin as well as cryoprecipitate replacement therapy.

ACR appropriateness criteria(®) on abnormal vaginal bleeding.

PubMed

Bennett, Genevieve L; Andreotti, Rochelle F; Lee, Susanna I; Dejesus Allison, Sandra O; Brown, Douglas L; Dubinsky, Theodore; Glanc, Phyllis; Mitchell, Donald G; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Wong-You-Cheong, Jade J; Zelop, Carolyn M

2011-07-01

In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace definitive histologic diagnosis but often plays an important role in screening, characterization of structural abnormalities, and directing appropriate patient care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of choice, with endometrial thickness a well-established predictor of endometrial disease in postmenopausal women. Endometrial thickness measurements of ≤5 mm and ≤4 mm have been advocated as appropriate upper threshold values to reasonably exclude endometrial carcinoma in postmenopausal women with vaginal bleeding; however, the best upper threshold endometrial thickness in the asymptomatic postmenopausal patient remains a subject of debate. Endometrial thickness in a premenopausal patient is a less reliable indicator of endometrial pathology since this may vary widely depending on the phase of menstrual cycle, and an upper threshold value for normal has not been well-established. Transabdominal ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not feasible or there is poor visualization of the endometrium. Hysterosonography may also allow for better delineation of both the endometrium and focal abnormalities in the endometrial cavity, leading to hysteroscopically directed biopsy or resection. Color and pulsed Doppler may provide additional characterization of a focal endometrial abnormality by demonstrating vascularity. MRI may also serve as an important problem-solving tool if the endometrium cannot be visualized on TVUS and hysterosonography is not possible, as well as for pretreatment planning of patients with suspected endometrial carcinoma. CT is generally not warranted for the evaluation of patients with abnormal bleeding, and an abnormal endometrium incidentally detected on CT should be further evaluated with TVUS. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Case report: a 70-year-old man with undiagnosed factor VII deficiency presented with acute ischemic stroke.

PubMed

Ip, Hing-Lung; Chan, Anne Yin-Yan; Ng, Kit-Chung; Soo, Yannie Oi-Yan; Wong, Lawrence Ka-Sing

2013-11-01

Factor VII deficiency is an uncommon coagulation disorder that patient usually presents with bleeding diathesis, but thrombotic event has been reported. We report a case of unusual clinical presentation in a patient with undiagnosed factor VII deficiency who presented with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Pelvic packing with vaginal traction for the management of intractable hemorrhage.

PubMed

Naranjo-Gutiérrez, Leonardo A; Oliva-Cristerna, Joaquín; Ramírez-Montiel, Martha L; Ortiz, Mario I

2014-10-01

To present clinical cases examining the effectiveness and safety of pelvic packing with vaginal traction for inhibiting obstetric hemorrhage among women receiving treatment at a public obstetrics and gynecology tertiary care hospital in Mexico. In a retrospective observational descriptive study, eight cases of obstetric hemorrhage treated by pelvic packing with vaginal traction between January 2012 and December 2013 at Hospital de la Mujer, Mexico City, Mexico, were reviewed. The mean patient age was 28.8±6.8 years. The average blood loss was 4535±897 mL. Uterine atony was the cause of bleeding among six patients: histopathologic examination revealed two cases of placenta accreta, one case of placenta percreta, two cases of uteroplacental apoplexy, and one case of myomatosis. For two patients, placental separation was difficult and required surgical management. The packing technique was effective for all patients. No patients presented with infection or required re-operation for bleeding management. No deaths occurred. For management of bleeding among patients with underlying coagulation disorders, pelvic packing can be useful when standard techniques such as hysterectomy, tubal hypogastric ligation, and/or pharmacologic therapy are unsuccessful. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

[Crisis management during obstetric surgery].

PubMed

Okutomi, Toshiyuki

2009-05-01

Obstetric crisis includes hemorrhagic shock, embolisms and difficult airway. Life will be rapidly threatened with disseminated intravascular coagulation, multiple organ failure or systemic inflammatory response syndrome in these crises. In the face of the crisis, repeated evaluation of parturients and differential diagnosis are necessary along with fetal heart monitoring. For evaluation of bleeding, one should notice that the visual estimation of vaginal bleeding does not reflect the extent of intravascular volume deficit. Treatments for hemorrhagic shock include fluid replacement, blood transfusion as well as fresh frozen plasma, platelet, anticoagulants, anti-thrombin III, and protease inhibitors. When bleeding is still uncontrollable, arterial embolization or hysterectomy will be considered. Embolic disorders are another cause of maternal mortality. The signs and symptoms are all similar (dyspnea, cyanosis and sudden cardiovascular collapse). Strategies against the embolism will be basically symptomatic therapy. The physiological change with pregnancy results in the need of careful pre-anesthetic airway evaluation for parturients. A difficult or failed intubation drill is also extremely important. Recently, laryngeal mask airway has been successfully used in these parturients. During resuscitation of a pregnant woman, left uterine displacement is essential. For a patient who has not responded after 4 to 5 minutes of ACLS, immediate cesarean delivery should be considered.

Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

PubMed

Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

2018-05-01

Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

Heavy menstrual bleeding: An update on management.

PubMed

Davies, Joanna; Kadir, Rezan A

2017-03-01

Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss (MBL) >80 mL per cycle, that interferes with a woman's physical, emotional, social wellbeing and quality of life. Aetiology is due to underlying uterine pathologies, coagulopathy, ovulation dysfunction, or iatrogenic. Up to 20% of women with HMB will have an underlying inherited bleeding disorder (IBD). Assessment of HMB should entail a menstrual and gynaecological history and a bleeding score to distinguish those women who require additional haematological investigations. A pelvic examination and ultrasound scan help to rule out presence of any underlying pathology. Management depends on the underlying cause and the woman's preference and her fertility wishes. Medical therapies include hormonal treatments; levonorgestrel-releasing intrauterine system (LNG-IUS) and combined hormonal contraceptives are most commonly used. Ulipristal acetate is an approved preoperative treatment for uterine fibroids, and has demonstrated efficacy in reducing MBL. Haemostatic therapies include tranexamic acid and DDAVP (1-deamino-8-D-arginine). DDAVP is used for HMB associated with certain IBDs. These therapies can be used in isolation or in combination with hormonal treatments. HMB associated with certain severe IBDs may require factor concentrate administration during menses to alleviate symptoms. Endometrial ablation is a minor surgical procedure that is associated with low operative morbidity and can be performed as an outpatient. Hysterectomy remains the definitive treatment of choice when medical therapies have failed and endometrial ablation is not suitable. Crown Copyright © 2017 Published by Elsevier Ltd. All rights reserved.

A novel F11 mutation in a Korean pediatric patient with recurrent epistaxis.

PubMed

Kim, Juwon; Kim, Yoonjung; Shin, Seam; Lyu, Chuhl Joo; Choi, Jong Rak; Lee, Kyung-A

2013-06-01

Congenital FXI deficiency (hemophilia C) is a rare bleeding disorder that has been documented mostly in Ashkenazi Jews. Unlike other hemophilias, bleeding tendency varies considerably among individuals, and FXI deficiency rarely manifests as spontaneous bleeding. FXI deficiency is caused primarily by mutations in the F11 gene. Herein, we report a case of a 10-year-old boy with recurrent nose bleeding due to FXI deficiency who was confirmed to have a novel mutation in F11. A molecular analysis of DNA extracted from peripheral blood collected from the patient [FXI clotting activity (FXI:C): 11%] revealed compound heterozygous mutations, Q226X and L424F, in F11, consistent with the severe disease phenotype of the patient. Pedigree analysis showed that the patient received L424F from his father (FXI:C = 49%) and Q226X from the mother (FXI:C = 48%). The sister (FXI:C = 47%) of the patient only had L424F, presumably inherited from her father. Multiple sequence alignment demonstrated that L424 is highly conserved across mammals, indicating that it is important for the function of FXI. In-silico analysis indicated that replacement of L424 by phenylalanine had a detrimental influence on FXI, consistent with the severe phenotype of the patient. Compilation of FXI deficiency cases in east Asian populations would be of great value because different populations appear to have different F11 mutation spectra.

Prescribing Warfarin Appropriately to Meet Patient Safety Goals

PubMed Central

Dharmarajan, Lekshmi; Dharmarajan, T.S.

2008-01-01

The anticoagulant warfarin is increasingly used in a variety of disorders associated with risk of thromboembolism. The drug is undoubtedly effective but is linked to numerous nutrient, disease, and drug interactions; safe use of warfarin therefore necessitates close patient monitoring, using the international normalized ratio. The predominant adverse effect is bleeding, and individuals respond to warfarin in different ways. Both high and subtherapeutic international normalized ratios warrant attention, whereas a high international normalized ratio, with or without bleeding, mandates prompt patient evaluation. The 2008 National Patient Safety Goals require medical institutions to develop processes to ensure the safe use and monitoring of anticoagulant use. Last August, the US Food and Drug Administration revised the prescribing information for warfarin to include genetic testing before initiating therapy, although this is still not covered by most health plans. PMID:25126243

Immunoglobulin G4-related acquired hemophilia: A case report

PubMed Central

Li, Xiaoyan; Duan, Wei; Zhu, Xiang; Xu, Jianying

2016-01-01

Acquired hemophilia A (AHA) is a relatively rare and life-threatening bleeding disorder whose pathogenesis is not completely understood. The present study reports a rare case of immunogubulin (IgG)4-related AHA with multisystemic involvement. A 55-year old male patient presented with symptoms of bronchial asthma and multiple subdermal hematomas. Chest computed tomography showed multiple diffuse nodular lesions with thickening of bronchovascular bundles, and scattered high-density spots in both lung lobes. Laboratory investigations showed increased activated partial prothrombin time (120.0 sec), a markedly decreased factor VIII (FVIII) activity (0.5%), a high-titer of FVIII inhibitor (27.2 Bethesda units/ml) and a marked increase in serum IgG4 (>4.03 g/l) level. Left inguinal lymph node biopsy revealed capsular thickening with marked lymphoplasmacytic infiltration, occlusive phlebitis and irregular fibrosis. Immunostaining revealed numerous IgG4-positive plasma cells (>100 cells/human plasma fibronectin) in the nodular lesions, with an IgG4/IgG ratio of >40%. The symptoms were markedly alleviated following corticosteroid therapy. The current study presents the first reported case of a rare IgG4-related AHA that presented with unusual clinical features and multisystemic involvement. The patient responded well to corticosteroid therapy. Documentation of such rare cases will help in characterizing the pathogenesis, and prompt recognition and timely treatment of this rare disorder. PMID:28105131

[Anatomy and pathogenesis of diverticular disease].

PubMed

Wedel, T; Böttner, M

2014-04-01

Although diverticular disease is one of the most frequent gastrointestinal disorders the pathogenesis is not yet sufficiently clarified. The aim is to define the anatomy and pathogenesis of diverticular disease considering the risk factors and description of structural and functional alterations of the bowel wall. This article gives an appraisal of the literature, presentation and evaluation of classical etiological factors, analysis and discussion of novel pathogenetic concepts. Colonic diverticulosis is defined as an acquired out-pouching of multiple and initially asymptomatic pseudodiverticula through muscular gaps in the colon wall. Diverticular disease is characterized by diverticular bleeding and/or inflammatory processes (diverticulitis) with corresponding complications (e.g. abscess formation, fistula, covered and open perforation, peritonitis and stenosis). Risk factors for diverticular disease include increasing age, genetic predisposition, congenital connective tissue diseases, low fiber diet, high meat consumption and pronounced overweight. Alterations of connective tissue cause a weakening of preformed exit sites of diverticula and rigidity of the bowel wall with reduced flexibility. It is assumed that intestinal innervation disorders and structural alterations of the musculature induce abnormal contractile patterns with increased intraluminal pressure, thereby promoting the development of diverticula. Moreover, an increased release of pain-mediating neurotransmitters is considered to be responsible for persistent pain in chronic diverticular disease. According to the present data the pathogenesis of diverticular disease cannot be attributed to a single factor but should be considered as a multifactorial event.

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Neely, Jessica A; Kalipatnapu, Sasank

2014-11-14

Haemophilia is a genetic disorder which is characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 06 November 2014. Eligible trials included randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the effects of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

PubMed Central

Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

2016-01-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes.

PubMed

Hylek, Elaine M; Held, Claes; Alexander, John H; Lopes, Renato D; De Caterina, Raffaele; Wojdyla, Daniel M; Huber, Kurt; Jansky, Petr; Steg, Philippe Gabriel; Hanna, Michael; Thomas, Laine; Wallentin, Lars; Granger, Christopher B

2014-05-27

This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Values and preferences for oral antithrombotic therapy in patients with atrial fibrillation: physician and patient perspectives.

PubMed

Alonso-Coello, Pablo; Montori, Victor M; Díaz, M Gloria; Devereaux, Philip J; Mas, Gemma; Diez, Ana I; Solà, Ivan; Roura, Mercè; Souto, Juan C; Oliver, Sven; Ruiz, Rafael; Coll-Vinent, Blanca; Gich, Ignasi; Schünemann, Holger J; Guyatt, Gordon

2015-12-01

Exploration of values and preferences in the context of anticoagulation therapy for atrial fibrillation (AF) remains limited. To better characterize the distribution of patient and physician values and preferences relevant to decisions regarding anticoagulation in patients with AF, we conducted interviews with patients at risk of developing AF and physicians who manage patients with AF. We interviewed 96 outpatients and 96 physicians in a multicenter study and elicited the maximal increased risk of bleeding (threshold risk) that respondents would tolerate with warfarin vs. aspirin to achieve a reduction in three strokes in 100 patients over a 2-year period. We used the probabilistic version of the threshold technique. The median threshold risk for both patients and physicians was 10 additional bleeds (10 P = 0.7). In both groups, we observed large variability in the threshold number of bleeds, with wider variability in patients than clinicians [patient range: 0-100, physician range: 0-50]. We observed one cluster of patients and physicians who would tolerate <10 bleeds and another cluster of patients, but not physicians, who would accept more than 35. Our findings suggest wide variability in patient and physician values and preferences regarding the trade-off between strokes and bleeds. Results suggest that in individual decision making, physician and patient values and preferences will often be discordant; this mandates tailoring treatment to the individual patient's preferences. © 2014 John Wiley & Sons Ltd.

Acute subdural hematoma because of boxing.

PubMed

Kushi, Hidehiko; Saito, Takeshi; Sakagami, Yuichiro; Ohtsuki, Jyoji; Tanjoh, Katsuhisa

2009-02-01

To identify factors determining the clinical characteristics and prognosis of acute subdural hematoma (ASDH) arising from boxing injuries by comparing with ASDH due to any nonboxing cause. Two groups were selected for this study: 10 patients with ASDH because of boxing injuries and 26 patients with nonboxer ASDH. All of the patients underwent neurologic examination by neurosurgeons. Primary resuscitation and stabilization as well as operative therapy were performed to all patients according to the European Brain Injury Consortium Guidelines. Two groups were compared in terms of age, the Glasgow Coma Scale at admission, neurologic findings, craniogram and brain computed tomography scan findings, operative findings, and prognosis. As potential prognostic indicators for boxers, the time interval until surgery, the Glasgow Outcome Scale, hematoma thickness, midline shift, and the site of bleeding were analyzed. The characteristics of patients because of boxing injuries are that patients were younger, had lucid interval, and had no cerebral contusion or contralateral brain injury. There was no significant difference in initial Glasgow Coma Scale, hematoma thickness, midline shift, and their prognosis. The most peculiar clinical presentation of boxers' ASDH was that all bleedings were limited from "bridging veins" or "cortical veins." The prognosis of boxers was most closely correlated with the site of bleeding (r2 = 0.81; p = 0.0001) and the midline shift (r2 = 0.67; p = 0.007). Our study shows that ASDH because of boxing is characterized by bleeding from bridging or cortical veins, and that the site of bleeding is a significant determinant of their prognosis.

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases.

PubMed

Hapsari Putri, Indri; Tunjungputri, Rahajeng N; De Groot, Philip G; van der Ven, Andre J; de Mast, Quirijn

2018-06-18

Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia.

PubMed

Spindler, Markus; van Eeuwijk, Judith M M; Schurr, Yvonne; Nurden, Paquita; Nieswandt, Bernhard; Stegner, David; Reinhold, Annegret; Bender, Markus

2018-06-27

Bone marrow megakaryocytes (MKs) produce platelets by extending proplatelets into sinusoidal blood vessels. Defects in thrombopoiesis can lead to thrombocytopenia associated with increased bleeding tendency. Recently, the platelet disorder congenital autosomal recessive small-platelet thrombocytopenia (CARST) was described which is caused by mutations in the ADAP (Adhesion and degranulation promoting adaptor protein; synonym: FYB, SLAP130/120) gene, and characterized by microthrombocytopenia and bleeding symptoms. In this study we used constitutive ADAP-deficient mice (Adap -/- ) as a model to investigate mechanisms underlying the microthrombocytopenia in CARST. We show that Adap -/- mice display several characteristics of human CARST, with moderate thrombocytopenia and smaller-sized platelets. Adap -/- platelets had a shorter life span than control platelets, and macrophage depletion, but not splenectomy, increased platelet counts in mutant mice to control levels. Whole sternum 3D confocal imaging and intravital two-photon microscopy revealed altered morphology of ADAP-deficient MKs with signs of fragmentation and ectopic release of (pro)platelet-like particles into the bone marrow compartment. In addition, cultured bone marrow-derived MKs lacking ADAP showed reduced spreading on extracellular matrix proteins as well as activation of β1 integrins, impaired podosome formation, and displayed defective polarization of the demarcation membrane system in vitro. MK-/platelet-specific ADAP deficient mice (PF4-cre) also produced less and smaller-sized platelets and released platelets ectopically. These data demonstrate that the abnormal platelet production in the mutant mice is a MK-intrinsic defect. Taken together, these results point to a so far unidentified role of ADAP in the process of MK polarization and platelet biogenesis. Copyright © 2018 American Society of Hematology.

Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor.

PubMed

Chen, Zengsheng; Mondal, Nandan K; Ding, Jun; Koenig, Steven C; Slaughter, Mark S; Wu, Zhongjun J

2016-07-01

Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that nonphysiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25 Pa, 125 Pa) with an exposure time of 0.5 s, generated by using a novel blood-shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with Western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWMs) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis, while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Paradoxical Effect of Non-Physiological Shear Stress on Platelets and von Willebrand factor

PubMed Central

Chen, Zengsheng; Mondal, Nandan K; Ding, Jun; Koenig, Steven C.; Slaughter, Mark S.; Wu, Zhongjun J.

2016-01-01

Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that non-physiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25Pa, 125Pa) with an exposure time of 0.5 sec., generated by using a novel blood shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWM) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices. PMID:26582038

Gynecologic disorders diagnosed during deployment to Southwest/Central Asia, active component females, U.S. Armed Forces, 2008-2013.

PubMed

2014-08-01

Service women in the U.S. Armed Forces face unique challenges that may lead to or exacerbate gynecologic disorders - particularly during deployment. This report documented that approximately one in 10 military women who served in Southwest/Central Asia were diagnosed with a gynecologic disorder at least once during deployment. In addition, gynecologic disorders accounted for approximately one of every 20 medical evacuations of female service members from the war zone. A majority of clinically significant gynecologic disorder cases were attributable to irregular menstruation/bleeding or unspecified inflammation or pain of the female genital organs. Incidence rates of gynecologic disorder diagnoses were higher among black, non-Hispanic service women, among younger women, and among those in the Army and in motor transport and communications/intelligence occupations. Approximately 50% of gynecologic disorder cases had received gynecologic care within 6 months prior to deployment and nearly 90% had received care within 2 years of deployment. Despite pre-deployment care, it is apparent from this report that service women need continuous access to gynecologic care during deployment, particularly if conditions during deployment lead to and exacerbate gynecologic disorders.

Cerebro-retinal microangiopathy with calcifications and cysts due to recessive mutations in the CTC1 gene.

PubMed

Bisserbe, A; Tertian, G; Buffet, C; Turhan, A; Lambotte, O; Nasser, G; Alvin, P; Tardieu, M; Riant, F; Bergametti, F; Tournier-Lasserve, E; Denier, C

2015-05-01

Cerebro-retinal microangiopathy with calcifications and cysts (CRMCC) or Coats plus syndrome is a pleiotropic disorder affecting the eyes, brain, bone and gastrointestinal tract. Its primary pathogenesis involves small vessel obliterative microangiopathy. Recently, autosomal recessively inherited mutations in CTC1 have been reported in CRMCC patients. We herein report an adolescent referred to our hospital following new seizures in a context of an undefined multisystem disorder. Cerebral imaging disclosed asymmetrical leukopathy, intracranial calcifications and cysts. In addition, he presented other typical CRMCC features i.e. a history of intrauterine growth retardation, skeletal demineralization and osteopenia, bilateral exudative vitreo-retinopathy reminiscent of Coats disease, recurrent gastrointestinal hemorrhages secondary to watermelon stomach and variceal bleeding of the esophagus due to idiopathic portal hypertension and telangiectatic and angiodysplasic changes in the small intestine and colon, and anemia due to recurrent bleeding and bone marrow abnormalities. The patient was diagnosed with Coats plus syndrome. CTC1 gene screening confirmed the diagnosis with the identification of heterozygous deleterious mutations. CRMCC due to CTC1 mutations has a broad clinical expressivity. Our case report illustrates the main possible associated phenotypes and their complications, demonstrating the need for a careful etiological search in order to initiate appropriate therapeutic and preventive measures. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The efficacy and safety of novel oral anticoagulants for the preventive treatment in atrial fibrillation patients: a systematic review and meta-analysis.

PubMed

Liu, Guang Jian; Wang, Yun Fu; Chen, Ping You; Chang, Wei; Tu, Ming Li; Chang, Li Ying; Cheng, Ping; Luo, Jie

2014-09-01

Novel oral anticoagulants, including direct factor Xa inhibitors and direct factor IIa inhibitors, have been used to prevent stroke in patients with atrial fibrillation (AF) for a decade. In this study, the efficacy and safety of the novel oral anticoagulants were assessed in AF patients. No language restrictions were applied. Study selection and data extraction were carried out by searching PubMed, EMBASE, OVID, the BIOSIS, the Web of Science, Clinical Trials Registers, Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. Each database was searched from its inception date to June 2013. Using odds ratio (OR) as an indicator, we systematically evaluated the primary efficacy endpoints and safety endpoints, as well as 10 secondary endpoints. Compared to the control drugs, the novel oral anticoagulants showed an OR decreased by 26% (OR: 0.74, 95% confidence interval (CI): 0.62-0.88) for stroke or systemic embolism, decreased by 24% (OR: 0.76, 95% CI: 0.64-0.90) for major bleeding, decreased by 10% (OR: 0.90, 95% CI: 0.84-0.95) for death from any cause, decreased by 27% for disabling or fatal stroke (OR: 0.73, 95% CI: 0.54-0.97), decreased by 31% (OR: 0.69, 95% CI: 0.60-0.8) for fatal bleeding, and decreased by 8% (OR: 0.92, 95% CI: 0.88-0.95) for serious adverse events. However, there was no significant difference in acute myocardial infarction, systemic embolism, major bleeding or clinically relevant non-major, all bleeding events, all adverse events and liver function disorder, between the novel oral anticoagulants and control drugs (p > 0.05). Compared to the control drugs, the novel oral anticoagulants showed higher efficiency and safety in patients with AF, as evidenced by their superior performance not only in reducing the risk of stroke or systemic embolism with a lower risk of major bleeding but also in decreasing the incidence of death from any cause, disabling or fatal stroke, serious adverse events and fatal bleeding.

Structural Modeling Insights into Human VKORC1 Phenotypes

PubMed Central

Czogalla, Katrin J.; Watzka, Matthias; Oldenburg, Johannes

2015-01-01

Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) catalyses the reduction of vitamin K and its 2,3-epoxide essential to sustain γ-carboxylation of vitamin K-dependent proteins. Two different phenotypes are associated with mutations in human VKORC1. The majority of mutations cause resistance to 4-hydroxycoumarin- and indandione-based vitamin K antagonists (VKA) used in the prevention and therapy of thromboembolism. Patients with these mutations require greater doses of VKA for stable anticoagulation than patients without mutations. The second phenotype, a very rare autosomal-recessive bleeding disorder caused by combined deficiency of vitamin K dependent clotting factors type 2 (VKCFD2) arises from a homozygous Arg98Trp mutation. The bleeding phenotype can be corrected by vitamin K administration. Here, we summarize published experimental data and in silico modeling results in order to rationalize the mechanisms of VKA resistance and VKCFD2. PMID:26287237

Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

PubMed

Reddy, Manasa; Tawfik, Bernard; Gavva, Chakri; Yates, Sean; De Simone, Nicole; Hofmann, Sandra L; Rambally, Siayareh; Sarode, Ravi

2016-12-01

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibitor development after liver transplantation in congenital factor VII deficiency.

PubMed

See, W-S Q; Chang, K-O; Cheuk, D K-L; Leung, Y-Y R; Chan, G C-F; Chan, S-C; Ha, S-Y

2016-09-01

Congenital factor VII (FVII) deficiency is the commonest type of the rare bleeding disorders. Very few cases of congenital FVII deficiency developed inhibitor and liver transplant is considered as definitive treatment. In the literature, twelve patients with congenital FVII deficiency developed inhibitors. Two had spontaneous resolution of inhibitors and one did not respond to high dose recombinant factor VIIa (rFVIIa) and died. Regarding liver transplant in congenital FVII patients, seven patients underwent liver transplant with good prognosis. We report a 5-year-old girl with confirmed severe congenital FVII deficiency since neonatal period. She suffered from recurrent intracranial bleeding despite rFVIIa replacement. After auxiliary liver transplant at the age of 4, she continued to show persistent deranged clotting profile and was found to have inhibitor towards FVII. Interestingly, she was still responsive to rFVIIa replacement. © 2016 John Wiley & Sons Ltd.

Cyclophosphamide Treatment for Acquired Factor VIII Inhibitor in a Patient with AIDS-Associated Progressive Multifocal Leukoencephalopathy.

PubMed

Malhotra, Uma; Aboulafia, David M

2016-01-01

Acquired hemophilia A (AHA) is a severe bleeding disorder with high mortality rates resulting from the development of autoantibodies to factor VIII (FVIII). Patients typically present with hemorrhages in the skin, subcutaneous tissues, and muscles, which are frequently severe. They can also develop life-threatening retroperitoneal hematomas and compartment syndromes. We describe the case of a man with a long history of AIDS complicated by progressive multifocal leukoencephalopathy (PML), who developed AHA while on stable antiretroviral therapy and then presented with new onset bleeding and hypotension. We treated our patient with incrementally increasing doses of cyclophosphamide resulting in resolution of coagulopathy. We review the medical literature for additional cases of HIV-associated AHA and discuss the challenges in the care of our patient, since the immunosuppression needed to eradicate the FVIII inhibitor had the potential to cause recrudescence of his PML. © The Author(s) 2015.

Homozygous factor V Leiden mutation in type IV Ehlers-Danlos patient

PubMed Central

Refaat, Marwan; Hotait, Mostafa; Winston, Brion

2014-01-01

Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting. PMID:24653990

Prothrombin complex concentrate and fatal thrombotic adverse events: A complication to keep in mind.

PubMed

Tabet, Rabih; Shammaa, Youssef; Karam, Boutros; Yacoub, Harout; Lafferty, James

2018-05-13

Thromboembolic events such as deep vein thrombosis and pulmonary embolism are well-known complications that can occur after prothrombin complex concentrate therapy. However, acute myocardial infarction is a very rare but potentially life-threatening complication that was exclusively described in patients with bleeding disorders who received chronic and recurrent concentrate infusions. We report the case of a 70 year-old male patient with cholangiocarcinoma who was admitted to our hospital with worsening fatigue and weakness. His stay was complicated by uncontrolled bleeding secondary to rivaroxaban use and advanced liver disease. By the end of the prothrombin complex concentrate infusion used to reverse his coagulopathy, patient developed ST-segment elevation myocardial infarction with cardiogenic shock and passed away. This is the first reported case of acute myocardial infarction that occurs in a patient without hemophilia and after the first prothrombin complex concentrate infusion.

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

PubMed

Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin

2017-12-01

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Evaluation of a web-based registry of inherited bleeding disorders: a descriptive study of the Brazilian experience with HEMOVIDAweb Coagulopatias.

PubMed

Rezende, Suely Meireles; Rodrigues, Silvia Helena Lacerda; Brito, Kelly Neves Pinheiro; da Silva, Diego Lima Quintino; Santo, Marcos Lázaro; Simões, Bárbara de Jesus; Genovez, Guilherme; Melo, Helder Teixeira; Araújo, João Paulo Baccara; Barca, Danila Augusta Accioly Varella

2017-02-10

Inherited bleeding disorders (IBD) consist of a group of rare heterogeneous diseases, which require treatment for life. Management of these disorders is complex and costly. Therefore, good quality data of the affected population is crucial to guide policy planning. The aim of this manuscript is to describe the impact of a national, web-based registry - the Hemovidaweb Coagulopatias (HWC) - in the management of the IBD in Brazil. The system was developed in PHP 5.0 language and is available on the internet at http://coagulopatiasweb.datasus.gov.br . The system was validated in September 2008 and launched nationally with input from January 1, 2009. HWC collects variables related to socio-demographic, clinical, laboratory and treatment data of patients with IBD. Within 7 years, there was an increment of 90.8% on the diagnosis of IBD altogether, which increased from 11,040 in December 2007 to 21,066 in December 2014. This is now the fourth and third largest world population of patients with haemophilia and von Willebrand's disease (vWD), respectively, according to the most recent (2015) Annual Global Survey of the World Federation of Hemophilia. The data collected provided the basis for planning and implementing home therapy, prophylaxis and immune tolerance induction (ITI), recently initiated in Brazil. HWC was an effective tool in the increment of registration of patients with IBD in Brazil. Furthermore, it was essential to support policy planning, monitoring, evaluation and treatment. Future development should focus on surveillance, health outcomes and research. Every country should implement a national registry on IBD.

Taste disturbance following tonsillectomy--a prospective study.

PubMed

Heiser, Clemens; Landis, Basile N; Giger, Roland; Cao Van, Helene; Guinand, Nils; Hörmann, Karl; Stuck, Boris A

2010-10-01

Persistent taste disturbance is a rare complication after tonsillectomy and mainly documented by case reports or a few retrospective and prospective trials with a limited number of patients. None could clarify frequency, time course, or prognosis of long-lasting dysgeusia after tonsillectomy. The aim of the study was to provide a symptom-based follow-up after tonsillectomy to assess postoperative taste disorders. Prospective clinical trial. From December 2007 to June 2009 adult patients undergoing tonsillectomy were asked to take part in the trial. Two hundred twenty-three patients (119 female, 104 male; mean age, 33 ± 13 years) were included. The day prior to surgery, and 2 weeks and 6 months after tonsillectomy a standardized questionnaire was completed by patients. The questionnaire focused on taste function, taste disorders, pain, foreign body sensation, and bleeding episodes after tonsillectomy. One hundred eighty-eight (2 weeks) and 181 (6 months) patients returned the questionnaires. Thirty-two percent (n = 60) of patients reported taste disorders after tonsillectomy 2 weeks postoperatively and 15 patients (8%) at 6-month follow-up. Metallic and bitter parageusia were most frequently reported. The mean ratings of gustatory function were significantly lower 2 weeks after surgery (P < .001) and reached preoperative values 6 months after surgery. Almost 30% of patients reported postoperative bleeding, 10% long-lasting postoperative pain, and 20% foreign body sensation. Long-lasting taste disturbance (metallic and bitter parageusia) after tonsillectomy is more frequent than previously reported. Long-lasting pain and foreign body sensation seem to be common symptoms. With regard to these results, a thorough preoperative explanation is mandatory.

Population Pharmacokinetics, Pharmacodynamics, and Exploratory Exposure–Response Analyses of Apixaban in Subjects Treated for Venous Thromboembolism

PubMed Central

Sweeney, K; Frost, C; Boyd, RA

2017-01-01

Apixaban is approved for treatment of venous thromboembolism (VTE) and prevention of recurrence. Population pharmacokinetics, pharmacokinetics–pharmacodynamics (anti‐FXa activity), and exposure–response (binary bleeding and thromboembolic endpoints) of apixaban in VTE treatment subjects were characterized using data from phase I–III studies. Apixaban pharmacokinetics were adequately characterized by a two‐compartment model with first‐order absorption and elimination. Age, sex, and Asian race had less than 25% impact on exposure, while subjects with severe renal impairment were predicted to have 56% higher exposure than the reference subject (60‐year‐old non‐Asian male weighing 85 kg with creatinine clearance of 100 mL/min). The relationship between apixaban concentration and anti‐FXa activity was described by a linear model with a slope estimate of 0.0159 IU/ng. The number of subjects with either a bleeding or thromboembolic event was small, and no statistically significant relationship between apixaban exposure and clinical endpoints could be discerned with a logistic regression analysis. PMID:28547774

Therapeutic Decision-Making in Endoscopically Unmanageable Nonvariceal Upper Gastrointestinal Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Defreyne, Luc, E-mail: Luc.Defreyne@UGent.b; Schrijver, Ignace De; Decruyenaere, Johan

2008-09-15

The purpose of this study was to identify endoscopic and clinical parameters influencing the decision-making in salvage of endoscopically unmanageable, nonvariceal upper gastrointestinal hemorrhage (UGIH) and to report the outcome of selected therapy. We retrospectively retrieved all cases of surgery and arteriography for arrest of endoscopically unmanageable UGIH. Only patients with overt bleeding on endoscopy within the previous 24 h were included. Patients with preceding nonendoscopic hemostatic interventions, portal hypertension, malignancy, and transpapillar bleeding were excluded. Potential clinical and endoscopic predictors of allocation to either surgery or arteriography were tested using statistical models. Outcome and survival were regressed on themore » choice of rescue and clinical variables. Forty-six arteriographed and 51 operated patients met the inclusion criteria. Univariate analysis revealed a higher number of patients with a coagulation disorder in the catheterization group (41.4%, versus 20.4% in the laparotomy group; p = 0.044). With multivariate analysis, the identification of a bleeding peptic ulcer at endoscopy significantly steered decision-making toward surgical rescue (OR = 5.2; p = 0.021). Taking into account reinterventions, hemostasis was achieved in nearly 90% of cases in both groups. Overall therapy failure (no survivors), rebleeding within 3 days (OR = 3.7; p = 0.042), and corticosteroid use (OR = 5.2; p = 0.017) had a significant negative impact on survival. The odds of dying were not different for embolotherapy or surgery. In conclusion, decision-making was endoscopy-based, with bleeding peptic ulcer significantly directing the choice of rescue toward surgery. Unsuccessful hemostasis and corticosteroid use, but not the choice of rescue, negatively affected outcome.« less

Platelets and hemophilia: A review of the literature.

PubMed

Riedl, Julia; Ay, Cihan; Pabinger, Ingrid

2017-07-01

Hemophilia A and B are inherited bleeding disorders due to deficiencies of the clotting factors VIII and IX, respectively. The severity of the disease correlates with remaining factor levels, although individual differences in bleeding tendency are seen despite similar factor levels. While thrombin generation is severely impaired in persons with hemophilia, primary hemostasis, i.e. platelet function, has been generally considered to be normal. However, some studies reported prolonged bleeding times in hemophilia, suggesting that also primary hemostasis is affected. In several other studies different aspects of platelet function in hemophilia have been investigated in more detail and various alterations were discovered, such as increased platelet P-selectin expression, a lower number of procoagulant, so-called 'coated' platelets, lower aggregation upon co-incubation with tissue factor, or reduced platelet contractile forces during clot formation in comparison to healthy individuals. An influence of platelet function on clinical phenotype was suggested, which might contribute in part to variations in bleeding tendency in hemophilic patients with similar factor levels. However, the available evidence is currently limited and no clear correlations between platelet function parameters and clinical phenotypes have been demonstrated. The impact of alterations of platelet function in hemophilia remains to be better defined. Another interesting role of platelets in hemophilia has been reported recently by establishing a novel gene-therapeutic strategy using platelets as a delivery system for FVIII, showing promising results in animal models. This review gives an overview on the currently published literature on platelet function and the potential roles of platelets in hemophilia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families.

PubMed

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients' families. Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients' F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson's correlation coefficient and the nonparametric Mann-Whitney test. Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity.

F7 gene variants modulate protein levels in a large cohort of patients with factor VII deficiency. Results from a genotype-phenotype study.

PubMed

Quintavalle, Gabriele; Riccardi, Federica; Rivolta, Gianna Franca; Martorana, Davide; Di Perna, Caterina; Percesepe, Antonio; Tagliaferri, Annarita

2017-08-01

Congenital factor VII (FVII) deficiency is a rare bleeding disorder caused by mutations in F7 gene with autosomal recessive inheritance. A clinical heterogeneity with poor correlation with FVII:C levels has been described. It was the objective of this study to identify genetic defects and to evaluate their relationships with phenotype in a large cohort of patients with FVII:C<50 %. One hundred twenty-three probands were genotyped for F7 mutations and three polymorphic variants and classified according to recently published clinical scores. Forty out of 123 patients (33 %) were symptomatic (43 bleedings). A severe bleeding tendency was observed only in patients with FVII:C<0.10 %. Epistaxis (11 %) and menorrhagia (32 % of females in fertile age) were the most frequent bleedings. Molecular analysis detected 48 mutations, 20 not reported in the F7 international databases. Most mutations (62 %) were missense, large deletions were 6.2 %. Compound heterozygotes/homozygotes for mutations presented lower FVII:C levels compared to the other classes (Chi 2 =43.709, p<0,001). The polymorphisms distribution was significantly different among the three F7 genotypic groups (Chi 2 =72.289, p<0,001). The presence of truncating mutations was associated with lowest FVII:C levels (Chi 2 =21.351, p=0.002). This study confirms the clinical and molecular variability of the disease and the type of symptoms. It shows a good correlation between the type of F7 mutation and/or polymorphisms and FVII:C levels, without a direct link between FVII:C and bleeding tendency. The results suggest that large deletions are underestimated and that they represent a common mechanism of F7 gene inactivation which should always be investigated in the diagnostic testing for FVII deficiency.

Did some 18th and 19th century treatments for mental disorders act on the brain?

PubMed

Leonard, Edward C

2004-01-01

Review of 18th and 19th century psychiatric therapies raises the possibility that several may have altered the activity of vasopressin or Na-K-ATPase. Bleeding, whirling, nausea created by medicines, and vagus nerve stimulation by application of electricity through the skin all perturb the hypothalamic hormone, arginine vasopressin, while helleborus and digitalis inhibit the sodium pump enzyme, Na-K-ATPase. These approaches were used with reported benefit many years ago, acting on the brain in ways ongoing research suggests may play a role in affective disorders. Study of long-abandoned treatments may clarify their mechanisms of action and the characteristics of responsive patients.

Indications and Effects of Plasma Transfusions in Critically Ill Children.

PubMed

Karam, Oliver; Demaret, Pierre; Shefler, Alison; Leteurtre, Stéphane; Spinella, Philip C; Stanworth, Simon J; Tucci, Marisa

2015-06-15

Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. To identify patient characteristics and to characterize indications leading to plasma transfusions in critically ill children, and to assess the effect of plasma transfusions on coagulation tests. Point-prevalence study in 101 pediatric intensive care units in 21 countries, on 6 predefined weeks. All critically ill children admitted to a participating unit were included if they received at least one plasma transfusion. During the 6 study weeks, 13,192 children were eligible. Among these, 443 (3.4%) received at least one plasma transfusion and were included. The primary indications for plasma transfusion were critical bleeding in 22.3%, minor bleeding in 21.2%, planned surgery or procedure in 11.7%, and high risk of postoperative bleeding in 10.6%. No bleeding or planned procedures were reported in 34.1%. Before plasma transfusion, the median international normalized ratio (INR) and activated partial thromboplastin time (aPTT) values were 1.5 and 48, respectively. After plasma transfusion, the median INR and aPTT changes were -0.2 and -5, respectively. Plasma transfusion significantly improved INR only in patients with a baseline INR greater than 2.5. One-third of transfused patients were not bleeding and had no planned procedure. In addition, in most patients, coagulation tests are not sensitive to increases in coagulation factors resulting from plasma transfusion. Studies assessing appropriate plasma transfusion strategies are urgently needed.

Clinical characteristics and outcomes of acquired hemophilia A: experience at a single center in Japan.

PubMed

Ogawa, Yoshiyuki; Yanagisawa, Kunio; Uchiumi, Hideki; Ishizaki, Takuma; Mitsui, Takeki; Gouda, Fumito; Ieko, Masahiro; Ichinose, Akitada; Nojima, Yoshihisa; Handa, Hiroshi

2017-07-01

Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation factor VIII (FVIII) is a rare, life-threatening bleeding disorder, the incidence of which appears to be increasing in Japan as the population ages. However, the clinical characteristics, treatment, and outcomes of AHA remain difficult to establish due to the rarity of this disease. We retrospectively analyzed data from 25 patients (median age 73 years; range 24-92 years; male n = 15) diagnosed with AHA between 1999 and 2015 at Gunma University Hospital. We identified autoimmune diseases and malignancy as underlying conditions in four and three patients, respectively. Factor VIII activity was significantly decreased in all patients (median 2.0%; range <1.0-8.0) by FVIII inhibitor (median 47.0 BU/mL; range 2.0-1010). Among 71 bleeding events, subcutaneous or intramuscular hemorrhage was the most prevalent. Seventeen patients required bypassing agents. Twenty-two (91.7%) of 24 patients treated with immunosuppressive agents achieved complete response (CR) during a median of 57.5 days (range 19-714 days). Although three patients (12%) relapsed and seven (28%) died of infection, none of the deaths were related to bleeding. Although most of our patients achieved CR after immunosuppressive therapy, the rate of infection-related mortality was unsatisfactorily high.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

PubMed

Hickman, DaShawn A; Pawlowski, Christa L; Sekhon, Ujjal D S; Marks, Joyann; Gupta, Anirban Sen

2018-01-01

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Factor XI as a target for antithrombotic therapy

PubMed Central

Bane, Charles E.; Gailani, David

2014-01-01

Anticoagulants currently used in clinical practice to treat thromboembolic disorders are effective but increase the risk of severe bleeding because they target proteins that are essential for normal coagulation (hemostasis). Drugs with better safety profiles are required for prevention and treatment of thromboembolic disease. Coagulation factor XIa has emerged as a novel target for safer anticoagulant therapy because of its role in thrombosis and its relatively small contribution to hemostasis. PMID:24886766

Noonan syndrome

PubMed Central

Roberts, Amy E; Allanson, Judith E; Tartaglia, Marco; Gelb, Bruce D

2014-01-01

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS–MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype–phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments. PMID:23312968

Bypassing agent prophylaxis in people with hemophilia A or B with inhibitors.

PubMed

Chai-Adisaksopha, Chatree; Nevitt, Sarah J; Simpson, Mindy L; Janbain, Maissaa; Konkle, Barbara A

2017-09-25

People with hemophilia A or B with inhibitors are at high risk of bleeding complications. Infusion of bypassing agents, such as recombinant activated FVII (rFVIIa) and plasma-derived activated prothrombin complex concentrate, are suggested as alternative therapies to factor VIII (haemophilia A) or IX (haemophilia B) for individuals who no longer respond to these treatments because they develop inhibitory antibodies. The ultimate goal of treatment is to preserve the individual's joints, otherwise destroyed by recurrent bleeds. To assess the effects of bypassing agent prophylaxis to prevent bleeding in people with hemophilia A or B and inhibitors. We searched for relevant studies from the Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries (16 February 2017) and bibliographic references of retrieved studies were reviewed for potential articles to be included in the review.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Coagulopathies Trials Register: 12 December 2016. We included randomized and quasi-randomized controlled studies (cross-over or parallel design) evaluating the effect of prophylaxis treatment with bypassing agents compared with on-demand treatment, or studies evaluating the effects of high-dose compared with low-dose prophylaxis in males of any age with hemophilia with inhibitors. Two authors independently selected studies and extracted data and assessed the risk of bias according to standard Cochrane criteria. They assessed the quality of the evidence using the GRADE criteria. We included four randomized studies (duration 7 to 15 months) involving 116 males. Risk of bias was judged to be high in two studies due to the open-label study design and in one study due to attrition bias.Two studies compared on-demand treatment to prophylaxis with bypassing agents. In one study (34 males) prophylaxis significantly reduced mean overall bleeding rates, MD - 7.27 (95% CI -9.92 to -4.62) (low quality evidence), mean number of overall bleeding events per month, MD -1.10 (95% CI -1.54 to -0.66), mean number of hemarthrosis, MD -6.60 (95% CI -9.32 to -3.88) (low quality evidence) and mean number of joints that had hemarthrosis, MD -0.90 (95% CI -1.36 to -0.44). The meta-analysis did not conclusively demonstrate significant benefit of prophylaxis on health-related quality of life as measured by Haem-A-QoL score, EQ-5D total score and utility score, EQ-5D VAS and SF-36 physical summary and mental summary score (low quality evidence for all health-related quality of life analyses).The remaining two studies compared dose regimens. The results from one study (22 males) did not conclusively demonstrate benefit or harm of high-dose versus low-dose recombinant activated factor VIIa (rFVIIa) as a prophylaxis for overall bleeding rate, MD -0.82 (95% CI -2.27 to 0.63) (moderate quality evidence), target joint bleeding rate, MD -3.20 (95% CI -7.23 to 0.83) (moderate quality evidence) and serious adverse events, RR 9.00 (95% CI, 0.54 to 149.50) (moderate quality evidence).The overall quality of evidence was moderate to low due to imprecision from limited information provided by studies with small sample sizes and incomplete outcome data in one study. The evidence suggests that prophylaxis with bypassing agents may be effective in reducing bleeding in males with hemophilia with inhibitors. However, there is a lack of evidence for the superiority of one agent over the other or for the optimum dosage regimen. Further studies are needed to evaluate the benefits and harms of prophylaxis treatment on health-related quality of life, as well as the effects of dose of bypassing agents on the outcomes.

Secondary flow and heat transfer control in gas turbine inlet nozzle guide vanes

NASA Astrophysics Data System (ADS)

Burd, Steven Wayne

1998-12-01

Endwall heat transfer is a very serious problem in the inlet nozzle guide vane region of gas turbine engines. To resolve heat transfer concerns and provide the desired thermal protection, modern cooling flows for the vane endwalls tend to be excessive leading to lossy and inefficient designs. Coolant introduction is further complicated by the flow patterns along vane endwall surfaces. They are three-dimensional and dominated by strong, complex secondary flows. To achieve performance goals for next-generation engines, more aerodynamically efficient and advanced cooling concepts, including combustor bleed cooling, must be investigated. To this end, the overall performance characteristics of several combustor bleed flow designs are assessed in this experimental study. In particular, their contributions toward secondary flow control and component cooling are documented. Testing is performed in a large-scale, guide vane simulator comprised of three airfoils encased between one contoured and one flat endwall. Core flow is supplied to this simulator at an inlet chord Reynolds number of 350,000 and turbulence intensity of 9.5%. Combustor bleed cooling flow is injected through the contoured endwall via inclined slots. The slots vary in cross-sectional area, have equivalent slot widths, and are positioned with their leeward edges 10% of the axial chord ahead of the airfoil leading edges. Measurements with hot-wire anemometry characterize the inlet and exit flow fields of the cascade. Total and static pressure measurements document aerodynamic performance. Thermocouple measurements detail thermal fields and permit evaluation of surface adiabatic effectiveness. To elucidate the effects of bleed injection, data are compared to an experiment taken without bleed. The influence of bleed mass flow rate and slot geometry on the aerodynamic losses and thermal protection arc given. This study suggests that such combustor bleed flow cooling offers significant thermal protection without imposing aerodynamic penalties. Such performance is contrary to the performance of present vane cooling schemes. The results of this investigation support designs which incorporate combustor coolant injection upstream of the airfoil leading edges. To complement, a short exploratory study regarding the effects of surface roughness was also performed. Results indicate modified cooling performance and significantly higher aerodynamic losses with rough surfaces.

Bleeding pattern and user satisfaction in second consecutive levonorgestrel-releasing intrauterine system users: results of a prospective 5-year study.

PubMed

Heikinheimo, O; Inki, P; Schmelter, T; Gemzell-Danielsson, K

2014-06-01

What is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use? Consecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women. With increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small. A prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study. A total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2-5 of use. Approximately 70% of women were free of bleeding during Years 2-5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP immediately after the placement of the second IUS, whereafter the number of bleeding/spotting days returned to the level preceding the second IUS insertion or below that. Absence of bleeding was associated with high overall satisfaction and continuation rates. No serious adverse events assessed as related to the LNG-IUS use occurred during the 5-year period. The cumulative expulsion rate during the 5-year study period was 1.2%. The sample size was large enough to study bleeding patterns, and subjects are likely to represent typical consecutive IUS users, and therefore, the role of chance is small. The women represent a selected group as they had already successfully used their first IUS for almost 5 years and were willing to continue its use-however, this is currently a common clinical situation. The results may therefore not be extrapolated to first-time users of the LNG-IUS. These data are of importance when counseling women who are making decisions concerning long-term contraception. This study was funded by Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H. and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication was developed jointly by all authors without third-party involvement and no honoraria were paid for any authors for their contribution to this manuscript. NCT00393198.

Polycystic Ovary Syndrome: An Under-recognized Cause of Abnormal Uterine Bleeding in Adolescents Admitted to a Children's Hospital.

PubMed

Maslyanskaya, Sofya; Talib, Hina J; Northridge, Jennifer L; Jacobs, Amanda M; Coble, Chanelle; Coupey, Susan M

2017-06-01

To evaluate whether ovulatory dysfunction due to polycystic ovary syndrome (PCOS) is a common underlying etiology of abnormal uterine bleeding (AUB) in adolescents who require hospitalization and to explore etiology, treatment, and complications of AUB with severe anemia in adolescents. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We identified female patients aged 8-20 years admitted to a children's hospital for treatment of AUB from January 2000 to December 2014. Our hospital protocol advises hormonal testing for PCOS and other disorders before treatment for AUB. We reviewed medical records and recorded laboratory evaluations, treatments, and final underlying diagnoses as well as recurrences of AUB and readmissions in the subsequent year. Of the 125 subjects, the mean age was 16.5 ± 2.9 years; mean hemoglobin level was 7.0 ± 1.8 g/dL; 54% were overweight/obese; and 41% sexually active. PCOS accounted for 33% of admissions; hypothalamic pituitary ovarian axis immaturity 31%; endometritis 13%; bleeding disorders 10%. Girls with PCOS were more likely to be overweight/obese (74% vs 46%; P < .01) and girls with hypothalamic pituitary ovarian axis immaturity had lower hemoglobin levels (6.4 g/dL vs 7.4 g/dL; P < .05), than girls with all other etiologies of AUB. Treating physicians failed to diagnose endometritis as the etiology for AUB in 4 of 8 girls with positive tests for sexually transmitted infection and no other etiology. PCOS was the most common underlying etiology in adolescents hospitalized with AUB. Screening for hyperandrogenemia is important for early diagnosis of PCOS to allow ongoing management and prevention of comorbidities. Endometritis was frequently underestimated as an etiology for AUB. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Two novel fibrinogen variants in the C-terminus of the Bβ-chain: fibrinogen Rokycany and fibrinogen Znojmo.

PubMed

Kotlín, Roman; Reicheltová, Zuzana; Suttnar, Jirí; Salaj, Peter; Hrachovinová, Ingrid; Riedel, Tomás; Malý, Martin; Oravec, Milan; Kvasnicka, Jan; Dyr, Jan Evangelista

2010-10-01

Hereditary dysfibrinogenemia is a rare disorder wherein an inherited abnormality in fibrinogen structure may result in defective fibrin function and/or structure. Congenital hypofibrinogenemia is a rare autosomal bleeding disorder, either recessive or dominant, characterized by a low fibrinogen plasma level. A 28-year-old asymptomatic woman (fibrinogen Rokycany) and a 54-year-old man with thrombosis and pulmonary embolism (fibrinogen Znojmo) were investigated for a suspected fibrinogen mutation after abnormal coagulation tests results were obtained. DNA sequencing showed the heterozygous point mutation Bβ Asn351Lys in fibrinogen Rokycany and the heterozygous point mutation Bβ Arg237Ser in fibrinogen Znojmo, respectively. The kinetics of fibrinopeptide release was found to be normal in both cases. Fibrinolysis was impaired in the Znojmo variant. The average fibril diameters of Znojmo fibrin was slightly increased, but not differing significantly from normal; formed by less fibrils with abrupt fibril terminations. Rheological studies revealed a softer clot. Rokycany fibrin was formed by significantly narrower fibrils than normal fibrin; and the clot was denser than the control clot. Rheological studies revealed a stiffer clot. Impaired fibrinolysis and abnormal clot morphology may be the cause of thrombotic episodes in the patient with Znojmo mutation. New cases of hypofibrinogenemia and dysfibrinogenemia, found by routine coagulation testing, were genetically identified as a novel fibrinogen variants Bβ Asn351Lys (fibrinogen Rokycany) and Bβ Arg237Ser (fibrinogen Znojmo), respectively.

Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky-Pudlak syndrome type 1 and 3 mutations in Puerto Rico.

PubMed

Santiago Borrero, Pedro J; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y; Izquierdo, Natalio J; Del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A; Cadilla, Carmen L

2006-01-01

Hermansky-Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of approximately 1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population.

Genetic Testing for Oculocutaneous Albinism Type 1 and 2 and Hermansky–Pudlak Syndrome Type 1 and 3 Mutations in Puerto Rico

PubMed Central

Santiago Borrero, Pedro J.; Rodríguez-Pérez, Yolanda; Renta, Jessicca Y.; Izquierdo, Natalio J.; del Fierro, Laura; Muñoz, Daniel; Molina, Norma López; Ramírez, Sonia; Pagán-Mercado, Glorivee; Ortíz, Idith; Rivera-Caragol, Enid; Spritz, Richard A.; Cadilla, Carmen L.

2013-01-01

Hermansky–Pudlak syndrome (HPS) (MIM #203300) is a heterogeneous group of autosomal recessive disorders characterized by oculocutaneous albinism (OCA), bleeding tendency, and lysosomal dysfunction. HPS is very common in Puerto Rico (PR), particularly in the northwest part of the island, with a frequency of ~1:1,800. Two HPS genes and mutations have been identified in PR, a 16-base pair (bp) duplication in HPS1 and a 3,904-bp deletion in HPS3. In Puerto Ricans with more typical OCA, the most common mutation of the tyrosinase (TYR) (human tyrosinase (OCA1) gene) gene was G47D. We describe screening 229 Puerto Rican OCA patients for these mutations, and for mutations in the OCA2 gene. We found the HPS1 mutation in 42.8% of cases, the HPS3 deletion in 17%, the TYR G47D mutation in 3.0%, and a 2.4-kb deletion of the OCA2 gene in 1.3%. Among Puerto Rican newborns, the frequency of the HPS1 mutation is highest in northwest PR (1:21; 4.8%) and lower in central PR (1:64; 1.6%). The HPS3 gene deletion is most frequent in central PR (1:32; 3.1%). Our findings provide insights into the genetics of albinism and HPS in PR, and provide the basis for genetic screening for these disorders in this minority population. PMID:16417222

Gene therapy for haemophilia.

PubMed

Sharma, Akshay; Easow Mathew, Manu; Sriganesh, Vasumathi; Reiss, Ulrike M

2016-12-20

Haemophilia is a genetic disorder characterized by spontaneous or provoked, often uncontrolled, bleeding into joints, muscles and other soft tissues. Current methods of treatment are expensive, challenging and involve regular administration of clotting factors. Gene therapy has recently been prompted as a curative treatment modality. This is an update of a published Cochrane Review. To evaluate the safety and efficacy of gene therapy for treating people with haemophilia A or B. We searched the Cochrane Cystic Fibrosis & Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of last search: 18 August 2016. Eligible trials include randomised or quasi-randomised clinical trials, including controlled clinical trials comparing gene therapy (with or without standard treatment) with standard treatment (factor replacement) or other 'curative' treatment such as stem cell transplantation for individuals with haemophilia A or B of all ages who do not have inhibitors to factor VIII or IX. No trials of gene therapy for haemophilia were found. No trials of gene therapy for haemophilia were identified. No randomised or quasi-randomised clinical trials of gene therapy for haemophilia were identified. Thus, we are unable to determine the safety and efficacy of gene therapy for haemophilia. Gene therapy for haemophilia is still in its nascent stages and there is a need for well-designed clinical trials to assess the long-term feasibility, success and risks of gene therapy for people with haemophilia.

Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects.

PubMed

Johnson, Ben; Lowe, Gillian C; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula Hb; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E; Watson, Steve P; Morgan, Neil V

2016-10-01

Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×10 9 /L to 186×10 9 /L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified "pathogenic" or "likely pathogenic" variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. Copyright© Ferrata Storti Foundation.

Clinical applications of CO2 laser resurfacing in the treatment of various pathologic skin disorders

NASA Astrophysics Data System (ADS)

Giler, Shamai

1997-12-01

CO2 laser skin resurfacing devices are widely used in cosmetic surgery for the treatment of facial rhytides, acne scars and aging skin. This technique is also useful in the treatment of various benign and premalignant or multiple pathological skin conditions and disorders originating in the epidermal, dermal and skin appendages, vascular lesions, epidermal nevi, infected wounds and ulcers, and keloids. Various surgical techniques have been developed in our clinic using laser resurfacing in the treatment of more than 2,000 patients with various skin pathologic disorders. We describe our experience with the various techniques used. The precise depth control and ablation properties combined with the hemostatic and sterilizing effects of the CO2 laser beam, reduction of the possibility of bleeding, infection and damage to healthy tissues, make the CO2 laser resurfacing techniques the treatment of choice for cosmetic surgery and treatment of benign, premalignant and multiple pathologic skin conditions.

Christmas disease: diagnosis and management of a haemorrhagic diathesis following dentofacial trauma

PubMed Central

Tamagond, Sridevi B; Hugar, Santosh I; Patil, Anil; Huddar, SandhyaRani

2015-01-01

Haemorrhagic diathesis has been of much concern to health professionals including dentists. It is not infrequent that a dentist becomes the first person to diagnose a bleeding disorder while performing dental treatment. Haemophilia is an X linked disorder with a frequency of about 1:10 000 births. Haemophilia B is much less common than haemophilia A, and affects only 1:300 000 males born alive. The clinical features of haemophilia B are very similar to those of haemophilia A with a prolongation of activated partial thromboplastin time. This case report describes the dental management of a patient with an uncommon haematological disorder, namely, factor IX deficiency, which remained undiagnosed until the patient had to undergo dentofacial trauma with unexpected severe haemorrhage. Preventive dentistry remains vital to young haemophiliacs. Surgical dental procedures may be performed for haemophiliacs but they must be judiciously coordinated by dental and medical health professionals. PMID:25568261

Anemia Due to Inflammation in an Anti-Coagulated Patient with Blue Rubber Bleb Nevus Syndrome.

PubMed

Bonaventura, Aldo; Liberale, Luca; Hussein El-Dib, Nadia; Montecucco, Fabrizio; Dallegri, Franco

2016-01-01

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by vascular malformations mostly involving skin and gastrointestinal tract. This disease is often associated with sideropenic anemia and occult bleeding. We report the case of chronic severe anemia in an old patient under oral anticoagulation treatment for chronic atrial fibrillation. At admission, the patient also presented fever and increased laboratory parameters of systemic inflammation (ferritin 308 mcg/L, C-reactive protein (CRP) 244 mg/L). A small bluish-colored lesion over the left ear lobe was observed. Fecal occult blood test was negative as well as other signs of active bleeding. Lower gastrointestinal endoscopy revealed internal hemorrhoids and multiple teleangiectasias that were treated with argon plasma coagulation. Videocapsule endoscopy demonstrated multiple bluish nodular lesions in the small intestine. Unexpectedly, chronic severe anemia due to systemic inflammation was diagnosed in an old anticoagulated patient with BRNBS. The patient was treated with blood transfusions, hydration, antibiotic treatment, and long-acting octreotide acetate, without stopping warfarin. Fever and inflammation disappeared without any acute gastrointestinal bleeding and improvement of hemoglobin levels at three-month follow up. This is the oldest patient presenting with chronic anemia, in which BRNBS was also diagnosed. Surprisingly, anemia was mainly caused by systemic inflammation instead of chronic gastrointestinal bleeding. However, we would recommend investigating this disease also in old subjects with mild signs and symptoms.

Diagnostic findings in infants presenting to a pediatric emergency department for lethargy or feeding complaints.

PubMed

Webb, Tara; Nugent, Melodee; Simpson, Pippa; Melzer-Lange, Marlene

2014-03-01

Lethargy is a common complaint among infants in the pediatric emergency department (ED), yet there is little data to guide appropriate evaluation. The objectives of the study were (1) to determine the frequency of diagnoses requiring intervention/monitoring and (2) to identify predictors of these diagnoses. A retrospective chart review of patients aged 0 to 6 months with a chief complaint of lethargy or poor feeding from January 2004 to December 2009 was performed. Patients were excluded if they had a fever, hypothermia, a chronic medical condition, or a history of trauma. Charts were reviewed by a single investigator; 10% were reviewed by a second investigator for agreement. History, examination, laboratory and radiology results, ED and inpatient diagnoses, as well as return visits within 7 days were recorded. Frequencies of diagnoses and interventions were described, and history and examination findings associated with these categories were determined. Two hundred seventy-two patients were included; 34 patients (12.5%; 95% confidence interval [CI], 8.8%-17%) required intervention/monitoring. These patients were classified into 6 categories. Eighteen had hematologic disorders (6.6%; 95% CI, 4.0%-10.3%), 8 had dehydration (2.9%; 95% CI, 1.3%-5.7%), 2 had intracranial bleeds (0.7%; 95% CI, 0.09%-2.6%), 3 had serious bacterial infections (1%; 95% CI, 0.2%-3.2%), 1 had a cardiac disorder (0.4%; 95% CI, 0.009%-2%), and 2 had neurologic disorders (0.7%; 95% CI, 0.9%-2.6%). Of the patients, 76% had conditions that were clinically evident (dehydration and hyperbilirubinemia requiring phototherapy). The patients with cardiac disorders, neurologic disorders, and intracranial bleeds all had abnormal examination findings in the ED. The 3 patients with serious bacterial infections were younger than 2 months of age and ill appearing; all had urinary tract infections. Infants with lethargy or poor feeding who require an intervention are likely to have conditions that are clinically evident or focal examination findings that lead to the diagnosis. Well-appearing infants with normal findings in examinations are unlikely to have a condition requiring intervention and should receive minimal testing.

Female Reproductive Effects of Exposure to Jet Fuel at U.S. Air Force Bases

DTIC Science & Technology

2001-05-01

amenorrhea and dys- strual characteristics of adult Afri- tors associated with menstrual disor- ,e r 4.6, 7 13 Prolonged bleed- can-Americans, and few...smokers than in non-smokers. Al- Stress (measured by life event or strual disorders.4󈧒 The major though vigorous exercise has been perceived stress...bases for both military and civilian the frequency of physical exercise .7 although personal gains (eg, starting women. Specifically, jet fuel, gaso

Invisible Bleeding: The Command Team’s Role in the Identification, Understanding, and Treatment of Traumatic Brain Injury and Post Traumatic Stress Disorder

DTIC Science & Technology

2013-04-11

of loss of or a decreased level of consciousness (LOC) -Any loss of memory for events immediately before or after the injury [post-traumatic amnesia ...diagnosis and is unlikely to change within the medical community. Symptoms of PTSD and TBI Symptom ASD and PTSD TBI Dissociation Emotional... Amnesia Present Present Reexperiencing Recurrent images Present Present Nightmares Present NA Distress on reminders

Hepatic manifestations of telomere biology disorders.

PubMed

Patnaik, Mrinal M; Kamath, Patrick S; Simonetto, Douglas A

2018-06-07

A 51-year-old Caucasian male was referred for evaluation of variceal bleeding. Laboratory tests were remarkable for mild thrombocytopenia and moderate alkaline phosphatase elevation. Synthetic liver function was well preserved. Abdominal computed tomography scan revealed moderate splenomegaly, gastric varices, and normal hepatic contour. A transjugular liver biopsy was performed revealing findings of nodular regenerative hyperplasia with no significant fibrosis or necroinflammatory activity. Hepatic venous pressure gradient was elevated at 31 mmHg, consistent with clinically significant portal hypertension. The clinical course was complicated by refractory gastric variceal bleeding requiring a surgical portosystemic shunt. Approximately seven years after the initial presentation, the patient developed progressive dyspnoea and a diagnosis of idiopathic pulmonary fibrosis was made. Contrast-enhanced echocardiogram was not suggestive of hepatopulmonary syndrome or portopulmonary hypertension. Given this new diagnosis a telomere biology disorder was suspected. A flow-fluorescence in situ hybridisation analysis for telomere length assessment revealed telomere lengths below the first percentile in both lymphocytes and granulocytes. Next generation sequencing analysis identified a heterozygous mutation involving the hTERT gene (Histidine983Threonine). The lung disease unfortunately progressed in the subsequent two years, leading to the patient's death nine years after his initial presentation with portal hypertension. During those nine years two brothers also developed idiopathic pulmonary fibrosis. The questions that arise from this case include. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Revision Knee Arthroplasty in Patients with Inherited Bleeding Disorders: A Single-Center Experience

PubMed Central

Kotela, Andrzej; Wilk-Frańczuk, Magdalena; Żbikowski, Piotr; Łęgosz, Paweł; Ambroziak, Paweł; Kotela, Ireneusz

2017-01-01

Background The results of total knee arthroplasty (TKA) in patients with inherited bleeding disorders (IBDs) are poorer when compared with those in the general population, with a notably higher risk of complications and higher revision rates. Thus, revision procedures are becoming a growing concern in this group of patients. The aim of this study was to evaluate the results of revision TKA in patients with IBD. Material/Methods A retrospective cohort study with longitudinal assessment of hemophilia patients scheduled for revision TKA between January 2010 and September 2015 was performed. The clinical status of the patients was assessed based on the Knee Society Score, and the Numeric Rating Scale was used to assess knee pain severity and patient satisfaction with the surgery. Radiological examination, post-operative complications, and reinterventions were recorded and analyzed. Results Very good results were obtained in all patients treated for aseptic loosening of the implant. However, inferior results were found in cases with infection. All patients operated on for aseptic loosening required only single-stage TKA, whereas patients with infection underwent multiple interventions. Complications were observed only in cases with infection. Conclusions Our study clearly outlined the differences in results based on failure mode, with far inferior results obtained in cases with infection. Given the lack of data in this area as well as the high specificity of this population, further high-quality studies are needed. PMID:28068306

Recombinant Activated Factor VII (Eptacog Alfa Activated, NovoSeven®) in Patients with Rare Congenital Bleeding Disorders. A Systematic Review on its Use in Surgical Procedures.

PubMed

Di Minno, Matteo Nicola Dario; Ambrosino, Pasquale; Myasoedova, Veronika; Amato, Manuela; Ventre, Itala; Tremoli, Elena; Minno, Alessandro Di

2017-01-01

In the absence of definite guidelines in the area, we have carried a systemic review to provide a thorough overview concerning the efficacy and safety of recombinant activated factor VII (rFVIIa, NovoSeven®, Novo Nordisk A/S, Bagsværd, Denmark) in patients with Glanzmann's thrombasthenia (GT) and FVII deficiency, undergoing surgical procedures. PubMed, Web of Science, Scopus and EMBASE databases was employed for the search. Three multicenter registries were identified: the Glanzmann's Thrombasthenia Registry (GTR), the Seven Treatment Evaluation Registry (STER), and a German post-marketing surveillance registry (the WIRK study). In addition, data from 10 case-series and/or single-center experiences have been summarized. We have found that the following; perioperatively, the hemostatic effectiveness of rFVIIa was high in GT patients and in those with FVII deficiency undergoing both minor and major surgical procedures. Moreover, in all studies, rFVIIa was well tolerated. Thus, the current evidence shows an optimal perioperative safety/efficacy profile of rFVIIa in the setting of these rare bleeding disorders, and provides the rationale for further studies aimed at evaluating the optimal perioperative anti-hemorrhagic prophylaxis with rFVIIa in GT and in FVII deficient patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding.

PubMed

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-05-01

To examined the diagnostic value of  dilatation and curettage (D and C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D and C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized  in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to  AUB and who had undergone hysterectomy were investigated. The patients' characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D and C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D and C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding

PubMed Central

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-01-01

Objectives: To examined the diagnostic value of dilatation and curettage (D&C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D&C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to AUB and who had undergone hysterectomy were investigated. The patients’ characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D&C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D&C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps. PMID:28439599

Comprehensive MR imaging of acute gynecologic diseases.

PubMed

Dohke, M; Watanabe, Y; Okumura, A; Amoh, Y; Hayashi, T; Yoshizako, T; Yasui, M; Nakashita, S; Nakanishi, J; Dodo, Y

2000-01-01

Rapid advances in techniques of magnetic resonance (MR) imaging have enabled diagnosis of acute gynecologic conditions, which are characterized by sudden onset of lower abdominal pain, fever, genital bleeding, intraperitoneal bleeding, or symptoms of shock. The chemical-selective fat-suppression technique not only helps establish the characteristics of lesions that contain fat components but also increases the conspicuity of inflammatory lesions. When a T2-weighted image is obtained with a very long effective echo time (>250 msec), even a small amount of ascites can be easily identified and the contrast between urine and complex fluid becomes more conspicuous. T2*-weighted images are useful for identification of hemorrhagic lesions by demonstrating deoxyhemoglobin and hemosiderin. Contrast material-enhanced dynamic subtraction MR imaging performed with a three-dimensional fast field-echo sequence and a rapid bolus injection of gadopentetate dimeglumine allows evaluation of lesion vascularity and the anatomic relationship between pelvic vessels and a lesion and allows identification of the bleeding point by demonstrating extravasation of contrast material. To optimize the MR imaging examination, attention should be given to the parameters of each pulse sequence and proper combination of the sequences.

Surgical management of abnormal uterine bleeding in fertile age women.

PubMed

Finco, Andrea; Centini, Gabriele; Lazzeri, Lucia; Zupi, Errico

2015-07-01

Abnormal uterine bleeding is a common gynecological disease and represents one of the most frequent reasons for hospital admission to a specialist unit, often requiring further surgical treatment. Following the so-called PALM-COEIN system we will attempt to further clarify the surgical treatments available today. The first group (PALM) is characterized by structural lesions, which may be more appropriately treated by means of surgical management. Although hysterectomy remains the definitive and decisive choice, there are many alternative techniques available. These minimally invasive procedures offer the opportunity for a more conservative approach. Precise and accurate counseling facilitates better patient selection, based on the patient's desires, age and disease type, allowing treatment to be individually tailored to each woman.

Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

PubMed Central

Kyriakides, Themis R.; Zhu, Yu-Hong; Smith, Lynne T.; Bain, Steven D.; Yang, Zhantao; Lin, Ming T.; Danielson, Keith G.; Iozzo, Renato V.; LaMarca, Mary; McKinney, Cindy E.; Ginns, Edward I.; Bornstein, Paul

1998-01-01

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2−/− mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration. PMID:9442117

Bowel habits and behaviors related to defecation in 10- to 16-year-olds: impact of socioeconomic characteristics and emotional stress.

PubMed

Devanarayana, Niranga Manjuri; Rajindrajith, Shaman

2011-05-01

Bowel habits vary depending on food consumption and genetic factors. The knowledge regarding this physiological phenomenon is limited. Thorough understanding of normal bowel habits is essential for correct diagnosis of defecation disorders. This study evaluated the normal bowel habits of Sri Lankan children. Children ages 10 to 16 years were randomly selected from 5 schools in 4 districts. Those without defecation disorders were recruited. Details regarding their bowel habits during previous 2 months were collected using a validated, self-administered questionnaire. A total of 2273 children were enrolled (mean age 13.2 years, SD 1.7 years, boys 49.7%). Of them, 1748 (76.9%) opened bowels once daily, whereas 149 (6.6%) and 11 (0.5%) had <3/week and >3/day defecations, respectively. Stool consistency was normal in 1997 (87.9%), hard in 86 (3.8%), and changing consistency in 163 (7.1%). Straining was present in 639 (28.1%), painful defecation in 241 (10.6%), and bleeding in 49 (2.2%). One hundred six (4.7%) children reported stool withholding. Bulky stool was present in 158 (7.0%). Straining, bulky stools, and withholding posture were more common in boys, whereas painful defecation and bleeding were reported more often in girls (P<0.05). Defecation frequency was lower in those from a poor socioeconomic background and war-affected areas (P < 0.05). Bowel frequency < 3/week, bulky stools, painful defecation, straining, and withholding posture were more common in those exposed to stressful life events (P < 0.05). The present study provides data on normal bowel habits of Sri Lankan schoolchildren and provides a firm platform to evaluate defecation disorders in them.

Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

PubMed

Westmoreland, D; Shaw, M; Grimes, W; Metcalf, D J; Burden, J J; Gomez, K; Knight, A E; Cutler, D F

2016-04-01

Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

The haemtrack home therapy reporting system: Design, implementation, strengths and weaknesses: A report from UK Haemophilia Centre Doctors Organisation.

PubMed

Hay, C R M; Xiang, H; Scott, M; Collins, P W; Liesner, R; Dolan, G; Hollingsworth, R

2017-09-01

Haemtrack is an electronic home treatment diary for patients with inherited bleeding disorders, introduced in 2008. It aimed to improve the timeliness and completeness of patient-reported treatment records, to facilitate analysis of treatment and outcome trends. The system is easy to use, responsive and accessible. The software uses Microsoft technologies with a SQL Server database and an ASP.net website front-end, running on personal computers, android and I-phones. Haemtrack interfaces with the UK Haemophilia Centre Information System and the National Haemophilia Database (NHD). Data are validated locally by Haemophilia Centres and centrally by NHD. Data collected include as follows: treatment brand, dose and batch number, time/date of bleed onset and drug administration, reasons for treatment (prophylaxis, bleed, follow-up), bleed site, severity, pain-score and outcome. Haemtrack was used by 90% of haemophilia treatment centres (HTCs) in 2015, registering 2683 patients using home therapy of whom 1923 used Haemtrack, entering >17 000 treatments per month. This included 68% of all UK patients with severe haemophilia A. Reporting compliance varied and 55% of patients reported ≥75% of potential usage. Centres had a median 78% compliance overall. A strategy for progressively improving compliance is in place. Age distribution and treatment intensity were similar in Haemtrack users/non-users with severe haemophilia treated prophylactically. The Haemtrack system is a valuable tool that may improve treatment compliance and optimize treatment regimen. Analysis of national treatment trends and large-scale longitudinal, within-patient analysis of changes in regimen and/or product will provide valuable insights that will guide future clinical practice. © 2017 John Wiley & Sons Ltd.

Clinical feature and management of immune thrombocytopenic purpura in a tertiary hospital in Northwest Nigeria

PubMed Central

Hassan, Abdulaziz; Adebayo, Adeshola; Musa, Abubakar Umar; Suleiman, Aishatu Maude; Ibrahim, Ismaila Nda; Kusfa, Ibrahim Usman; Aminu, Mohammed Sirajo

2017-01-01

Background: Immune thrombocytopenic purpura (ITP) is a rare bleeding disorder that may remit spontaneously. Life-threatening bleeding may require transfusion support, steroids, and other immunosuppressive therapy or splenectomy. Objective: To review the clinical presentation and laboratory features of ITP at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. Subjects and Methods: A retrospective analytic study of case notes and bone marrow (BM) records of patients diagnosed with ITP at Haematology Department, ABUTH, Zaria, from January 1, 2004, to December 31, 2012. Results: There were nine cases (six females, three males), aged 6–20 (mean 11.11) years. The presentations were epistaxis 8 (88.9%), purpura 4 (44.4%), gum bleeding 4 (44.4%), menorrhagia 2 (22.2%), and intracranial hemorrhage (ICH) 1 (11.1%). Only 1 (11.1%) had clinical splenomegaly. Platelet count of <20 × 109/L was found in 4 (44.4%) while 6 (66.7%) had packed cell volume of <25%. All the nine cases had BM megakaryocytic hyperplasia. Six patients had blood transfusion support while 7 (77.8%) patients received oral prednisolone therapy with time to cessation of bleeding of 12–16 (mean of 8) weeks. One case had spontaneous remission while another had anti-D due to relapse after steroid therapy; this resulted in transient rise in platelet counts. None had other immunosuppressive therapy or splenectomy. Six (66.7%) cases were lost to follow-up after achieving remission and one died of ICH. Conclusion: ITP is not common in our center though its clinical presentations are varied. However, prednisolone and blood transfusion therapy are central to the management of these patients with favorable outcome. PMID:29269984

Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa.

PubMed

Jiang, Lilong; Wang, Qiong; Shen, Shu; Xiao, Tongshu; Li, Youbin

2014-03-01

Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flavonoid mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) in the treatment of I-III degree hemorroidal disease: a double-blind multicenter prospective comparative study.

PubMed

Corsale, Italo; Carrieri, Paolo; Martellucci, Jacopo; Piccolomini, Alessandro; Verre, Luigi; Rigutini, Marco; Panicucci, Sonia

2018-06-22

We evaluated the efficacy of new flavonoids mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) to reduce bleeding from I-III degrees hemorrhoidal disease in the short and medium time. One hundred fifty-four consecutive patients with hemorrhoidal disease recruited in four colorectal units were enrolled to the study. Exclusion criteria were allergy to the flavonoids, inflammatory bowel disease, obstructed defecation syndrome, pregnancy and puerperium, associated anal disease or hemorrhoidal thrombosis, proctologic surgical procedures within 1 year before recruitment, contemporary cancer or HIV, previous pelvic radiotherapy, patients receiving oral anticoagulant therapy, or contemporary administration of other therapy for hemorrhoids. Patients with inability to understand the study or mental disorders were also excluded. Seventy-eight were randomized to receive the mixture of diosmin, troxerutin, rutin, hesperidin, and quercetin (study group, SG), and 76 a mixture of diosmin in combination with hesperidin, diosmetin, isoroifolin, and linarin in purified micronized fraction (control group, CG). Bleeding, number of pathological piles, and Golligher's grade were assessed at each scheduled visit and compared using the Chi-square test. During the study period, bleeding improved after 1 and 6 months both in the SG (79.5 and 70.5%) and in the CG (80.2 and 75%) without significant differences between two groups. Satisfaction degree after 6 months was greater in the patients of the SG (4.05) towards the CG (3.25): this result was statistical significant (p 0.003). Use of flavonoids mixture (diosmin, troxerutin, rutin, hesperidin, quercetin) is a safe and effective mean of managing bleeding from hemorrhoidal disease and minimal adverse events are reported.

[Complications of tongue base reduction with radiofrequency tissue ablation on obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Jin-hui; Luo, Zhi-hong; Xu, Hong-xing; Yang, Xi-lin; Zhu, Ming-wan; Tao, Ze-zhang

2010-07-01

To investigate the complications of tongue base reduction with radiofrequency tissue ablation on patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and find out the effective prevention strategies. One hundred and ninety three OSAHS patients diagnosed by polysomnography were received tongue base reduction with radiofrequency tissue ablation between March 2008 and December 2009. The intraoperative and postoperative complications including bleeding, hematoma of tongue base, abscess of tongue base, altered taste, tongue numbness, deviation of tongue extension movement, dysfunctions of pronunciation and swallowing as well as the managements were analyzed retrospectively. No perioperative complications occurred. There were 186 cases with postoperative pain (96.4%), 155 cases with submandibular edema (80.3%). Nocturnal sudden cardiac death was encountered in 1 case and secondary bleeding in 1 case. There was no ulceration of tongue base mucose, hematoma or abscess of tongue base, altered taste, tongue numbness, tongue deviations, speech, swallowing and taste disorder after operation. The scale of postoperative pain claimed by patients was ranged between mild to moderate. Diclofenac suppository had analgesic effect for these patients. The quantity of bleeding in patient with secondary hemorrhage was so little that after proper treatment the bleeding was stopped and never happened again. Patient with nocturnal sudden cardiac death occurred at thirty-seven hours after operation, because of swelling and pain of tongue base aggravated sleep apnea and night hypoxemia inducing fatal arrhythmia. Postoperative pain and submandibular edema were 2 most common postoperative complications which can be easily controlled by antibiotics, Glucocorticoids and Diclofenac suppository. For those severe OSAHS patients accompanied by cardiopulmonary diseases, the tongue base reduction with radiofrequency tissue ablation can induce nocturnal sudden cardiac death. It is important to pay more attention on arrhythmias at night in severe OSAHS patients.

A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.

PubMed

Yoneyama, Koichiro; Schmitt, Christophe; Kotani, Naoki; Levy, Gallia G; Kasai, Ryu; Iida, Satofumi; Shima, Midori; Kawanishi, Takehiko

2017-12-06

Emicizumab (ACE910) is a bispecific antibody mimicking the cofactor function of activated coagulation factor VIII. In phase I-I/II studies, emicizumab reduced the bleeding frequency in patients with severe hemophilia A, regardless of the presence of factor VIII inhibitors, at once-weekly subcutaneous doses of 0.3, 1, and 3 mg/kg. Using the phase I-I/II study data, population pharmacokinetic and repeated time-to-event (RTTE) modeling were performed to quantitatively characterize the relationship between the pharmacokinetics of emicizumab and reduction in bleeding frequency. Simulations were then performed to identify the minimal exposure expected to achieve zero bleeding events for 1 year in at least 50% of patients and to select the dosing regimens to be tested in phase III studies. The RTTE model adequately predicted the bleeding onset over time as a function of plasma emicizumab concentration. Simulations suggested that plasma emicizumab concentrations of ≥  45 μg/mL should result in zero bleeding events for 1 year in at least 50% of patients. This efficacious exposure provided the basis for selecting previously untested dosing regimens of 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks for phase III studies. A pharmacometric approach guided the phase III dose selection of emicizumab in hemophilia A, without conducting a conventional dose-finding study. Phase III studies with the selected dosing regimens are currently ongoing. This case study indicates that a pharmacometric approach can substitute for a conventional dose-finding study in rare diseases and will streamline the drug development process.

Vascular Permeability and Remodelling Coincide with Inflammatory and Reparative Processes after Joint Bleeding in Factor VIII-Deficient Mice.

PubMed

Cooke, Esther J; Zhou, Jenny Y; Wyseure, Tine; Joshi, Shweta; Bhat, Vikas; Durden, Donald L; Mosnier, Laurent O; Drygalski, Annette von

2018-06-01

Vascular remodelling is a prominent feature of haemophilic arthropathy (HA) that may underlie re-bleeding, yet the nature of vascular changes and underlying mechanisms remain largely unknown. Here, we aimed to characterize synovial vascular remodelling and vessel integrity after haemarthrosis, as well as temporal changes in inflammatory and tissue-reparative pathways. Thirty acutely painful joints in patients with haemophilia (PWH) were imaged by musculoskeletal ultrasound with Power Doppler (MSKUS/PD) to detect vascular abnormalities and bloody effusions. Nineteen out of 30 painful joint episodes in PWH were associated with haemarthrosis, and abnormal vascular perfusion was unique to bleeding joints. A model of induced haemarthrosis in factor VIII (FVIII)-deficient mice was used for histological assessment of vascular remodelling (α-smooth muscle actin [αSMA] expression), and monitoring of in vivo vascular perfusion and permeability by MSKUS/PD and albumin extravasation, respectively. Inflammatory (M1) and reparative (M2) macrophage markers were quantified in murine synovium over a 10-week time course by real-time polymerase chain reaction. The abnormal vascular perfusion observed in PWH was recapitulated in FVIII-deficient mice after induced haemarthrosis. Neovascularization and increased vessel permeability were apparent 2 weeks post-bleed in FVIII-deficient mice, after a transient elevation of inflammatory macrophage M1 markers. These vascular changes subsided by week 4, while vascular remodelling, evidenced by architectural changes and pronounced αSMA expression, persisted alongside a reparative macrophage M2 response. In conclusion, haemarthrosis leads to transient inflammation coupled with neovascularization and associated vascular permeability, while subsequent tissue repair mechanisms coincide with vascular remodelling. Together, these vascular changes may promote re-bleeding and HA progression. Schattauer GmbH Stuttgart.

Hyperthyroidism and venous thrombosis: a casual or causal association? A systematic literature review.

PubMed

Franchini, Massimo; Lippi, Giuseppe; Targher, Giovanni

2011-08-01

A kaleidoscope of coagulation disorders have been reported in patients with thyroid dysfunctions. Globally, these disorders involve both primary and secondary hemostasis and range from subclinical laboratory abnormalities to, more rarely, life-threatening hemorrhages or thrombotic events. While overt hypothyroidism appears to be associated with a bleeding tendency, hyperthyroidism emerged to have an increased risk of thrombotic events. In particular, a number of case reports have documented acute venous thrombosis complications in patients with overt hyperthyroidism, especially at cerebral sites. Nevertheless, further observational and intervention studies might be needed to provide a more definitive information on the clinical relevance of this association, along with the potential implication for prevention and treatment of coagulation-fibrinolytic abnormalities in patients with thyroid dysfunction.

Evaluation of wild juglans species for crown gall resistance

USDA-ARS?s Scientific Manuscript database

A. tumefaciens is a soil-borne Gram-negative bacterium which causes crown gall on many dicotyledonous plant species including walnut. Crown gall symptoms on walnut are characterized by large tumors located near the crown of the tree but can occur near wounds caused by bleeding cuts or at the graft u...

[Newborn with phocomelia and thrombocytopenia. Case report].

PubMed

Maas, C; Arand, J; Orlikowsky, Th; Goelz, R

2002-01-01

Associated malformations and symptoms may be decisive in the differential diagnosis of neonatal phocomelia. We report on a neonate with phocomelia, petechiae and thrombocytopenia. This constellation is typical for the phocomelia-thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR) syndrome. During the neonatal period platelet transfusions were necessary. Relevant bleeding and development delays were not evident until the age of seven months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and neonatal thrombocytopenia. The patient presented with phocomelia of the upper extremities which occurs in only 5 - 10 % of the patients with TAR syndrome. Further abnormalities include additional bone and joint disorders and haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur in the first year of life, hence platelet transfusions may be necessary during this period. A new experimental approach is the Interleukin-6-mediated stimulation of thrombopoiesis. Usually platelet counts reach normal values in adults. The main problem remains a satisfactory management of various limb defects.

Transcatheter Arterial Embolization for Spontaneous Rupture of the Omental Artery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumoto, Tomohiro, E-mail: t-matsu@koto.kpu-m.ac.jp; Yamagami, Takuji; Morishita, Hiroyuki

We encountered a rare case of spontaneous rupture of the omental artery. A 25-year-old man without any episode of abdominal trauma or bleeding disorders came to the emergency unit with left upper abdominal pain. Hematoma with extravasation of the greater omentum and a hemoperitoneum was confirmed on abdominal contrast-enhanced computed tomography. Bleeding from the omental artery was suspected based on these findings. Transcatheter arterial embolization was successfully performed after extravasation of the omental artery, which arises from the left gastroepiploic artery, was confirmed on arteriography. Partial ometectomy was performed 10 days after transcatheter arterial embolization, revealing that the hematoma measuredmore » 10 cm in diameter in the greater omentum. Pathological examination showed rupture of the branch of an omental artery without abnormal findings, such as an aneurysm or neoplasm. Thus, we diagnosed him with spontaneous rupture of the omental artery. The patient recovered and was discharged from the hospital 10 days after the surgery, with a favorable postoperative course.« less

[Point-of-care Coagulation Testing in Neurosurgery].

PubMed

Adam, Elisabeth Hannah; Füllenbach, Christoph; Lindau, Simone; Konczalla, Jürgen

2018-06-01

Disorders of the coagulation system can seriously impact the clinical course and outcome of neurosurgical patients. Due to the anatomical location of the central nervous system within the closed skull, bleeding complications can lead to devastating consequences such as an increase in intracranial pressure or enlargement of intracranial hematoma. Point-of-care (POC) devices for the testing of haemostatic parameters have been implemented in various fields of medicine. Major advantages of these devices are that results are available quickly and that analysis can be performed at the bedside, directly affecting patient management. POC devices allow identification of increased bleeding tendencies and therefore may enable an assessment of hemorrhagic risks in neurosurgical patients. Although data regarding the use of POC testing in neurosurgical patients are limited, they suggest that coagulation testing and hemostatic therapy using POC devices might have beneficial effects in this patient population. This article provides an overview of the application of point-of-care coagulation testing in clinical practice in neurosurgical patients. Georg Thieme Verlag KG Stuttgart · New York.

Gene Therapy for Hemophilia.

PubMed

Nienhuis, Arthur W; Nathwani, Amit C; Davidoff, Andrew M

2017-05-03

The X-linked bleeding disorder hemophilia causes frequent and exaggerated bleeding that can be life-threatening if untreated. Conventional therapy requires frequent intravenous infusions of the missing coagulation protein (factor VIII [FVIII] for hemophilia A and factor IX [FIX] for hemophilia B). However, a lasting cure through gene therapy has long been sought. After a series of successes in small and large animal models, this goal has finally been achieved in humans by in vivo gene transfer to the liver using adeno-associated viral (AAV) vectors. In fact, multiple recent clinical trials have shown therapeutic, and in some cases curative, expression. At the same time, cellular immune responses against the virus have emerged as an obstacle in humans, potentially resulting in loss of expression. Transient immune suppression protocols have been developed to blunt these responses. Here, we provide an overview of the clinical development of AAV gene transfer for hemophilia, as well as an outlook on future directions. Copyright © 2017. Published by Elsevier Inc.

Rectus sheath haematoma following exercise testing: a case report

PubMed Central

2009-01-01

Introduction Exercise testing is a safe diagnostic procedure which is widely used in the evaluation of patients suspected of having coronary heart disease or for the assessment of the prognosis in patients with established disease. Its complications are mainly cardiac disorders. Here, we report a rectus sheath haematoma as a complication of this procedure in a patient with acute coronary syndrome. To our knowledge, this is the first case report of rectus sheath haematoma in association with exercise testing. Case presentation A 72-year-old Caucasian woman was admitted for acute coronary syndrome. She received conservative treatment including low molecular weight heparin and anti-platelet agents. On the fifth day of her hospital stay, she underwent an exercise test, where no ischaemic response occurred. Several hours later, she experienced pain in the left side of her abdomen. Subsequent investigations revealed a rectus sheath haematoma. The patient underwent surgical haematoma evacuation. A few days later, re-operation was performed for recurrent bleeding in the abdominal wall. The patient had several characteristics known to increase the risk of bleeding during treatment for acute coronary syndrome. Conclusion Awareness of this possible consequence of exercise testing is important for preventing and treating it correctly. For prevention, an assessment of the bleeding risk of the individual patient is necessary before the test, and excessive anticoagulation must be avoided. PMID:20338023

Study of endometrial tissue in dysfunctional uterine bleeding.

PubMed

Kayastha, S

2013-03-01

Dysfunctional uterine bleeding (DUB) is defined as heavy and or irregular menstruation in the absence of recognizable pelvic pathology, pregnancy or general bleeding disorder. Hyperplastic endometrium is abnormal histology finding found in DUB. Out of three type of hyperplasia, atypical type is associated with co-existent ca endometrium and the chance of progression to ca endometrium is very high. Thus this study was conducted to see the incidence of hyperplasia of endometrium in cases of DUB and to see the risk factors for endometrial hyperplasia. It was a prospective study carried out in span of two years (2010 JULY- 2013 Jan) in Nepal Medical College and Teaching Hospital. Hundred cases DUB who under went D&C or hysterectomy were included to study the age range, the relation of parity, patient symptom, contraceptive method and medical disease with the type of endometrial histology. It was found that DUB was common in perimenopusal age (49%) and the incidence increase with the increase of parity. Abnormal endometrial finding (hyperplasia) was found in 31% of the cases. Atypical and complex hyperplasia were associated with irregular menstruation and one third of the hyperplastic patient had hypertension (32.26%). Thus perimenopausal age, irregular menstruation and hypertension are risk factors for hyperplasia. So it is mandatory to do endometrial sampling in cases of perimenopausal age with irregular menstruation withor without hypertension.

Structured imaging technique in the gynecologic office for the diagnosis of abnormal uterine bleeding.

PubMed

Dueholm, Margit; Hjorth, Ina Marie D

2017-04-01

The aim in the diagnosis of abnormal uterine bleeding (AUB) is to identify the bleeding cause, which can be classified by the PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system. In a gynecologic setting, the first step is most often to identify structural abnormalities (PALM causes). Common diagnostic options for the identification of the PALM include ultrasonography, endometrial sampling, and hysteroscopy. These options alone or in combination are sufficient for the diagnosis of most women with AUB. Contrast sonography with saline or gel infusion, three-dimensional ultrasonography, and magnetic resonance imaging may be included. The aim of this article is to describe how a simple structured transvaginal ultrasound can be performed and implemented in the common gynecologic practice to simplify the diagnosis of AUB and determine when additional invasive investigations are required. Structured transvaginal ultrasound for the identification of the most common endometrial and myometrial abnormalities and the most common ultrasound features are described. Moreover, situations where magnetic resonance imaging may be included are described. This article proposes a diagnostic setup in premenopausal women for the classification of AUB according to the PALM-COEIN system. Moreover, a future diagnostic setup for fast-track identification of endometrial cancer in postmenopausal women based on a structured evaluation of the endometrium is described. Copyright © 2016. Published by Elsevier Ltd.

Inhibitors in Hemophilia B.

PubMed

Santoro, Cristina; Quintavalle, Gabriele; Castaman, Giancarlo; Baldacci, Erminia; Ferretti, Antonietta; Riccardi, Federica; Tagliaferri, Annarita

2018-06-20

Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients. The development of an inhibitor in HB is a rare event (1.5-3% of all patients) but is associated with a significant morbidity, related not only to the bleeding risk but also to the frequent occurrence of allergic/anaphylactic reactions and nephrotic syndrome. Due to the relative rarity of this event, few data exist about risk factors, pathophysiology, and clinical aspects of inhibitors in HB. The induction of immune tolerance is often unsuccessful and can be otherwise affected by many complications in patients with history of allergy or anaphylaxis. Therefore, alternative therapeutic strategies and new approaches are developing. The aim of this narrative review is to discuss current knowledge about risk factors, pathophysiology, and clinical aspects of this rare but serious complication. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Partial spleen embolization reduces the risk of portal hypertension-induced upper gastrointestinal bleeding in patients not eligible for TIPS implantation.

PubMed

Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Dechêne, Alexander; Canbay, Ali; Wetter, Axel; Umutlu, Lale; Theysohn, Jens M

2017-01-01

Upper gastrointestinal bleeding (UGIB) is a severe and life-threatening complication among patients with portal hypertension (PH). Covered transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for patients with refractory or recurrent UGIB despite pharmacological and endoscopic therapy. In some patients, TIPS implantation is not possible due to co-morbidity or vascular disorders. Spleen embolization (SE) may be a promising alternative in this setting. We retrospectively analyzed 9 patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All patients met the following criteria: (i) upper gastrointestinal hemorrhage with primary or secondary failure of endoscopic interventions and (ii) TIPS implantation not possible. Each patient was followed for at least 6 months after embolization. Five patients (56%) suffered from cirrhotic PH, 4 patients (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the patients treated with partial SE experienced re-bleeding episodes or required blood transfusions during a total follow-up time of 159 months, including both patients with cirrhotic- and non-cirrhotic PH. Partial SE, as a minimally invasive intervention with low procedure-associated complications, may be a valuable alternative for patients with recurrent PH-induced UGIB refractory to standard therapy.

[Oral complications of chemotherapy of malignant neoplasms].

PubMed

Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

1999-01-01

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

[Factor V congenital deficiency: about a case].

PubMed

Boujrad, Saloua; El Hasbaoui, Brahim; Echahdi, Hanae; Malih, Mohamed; Agadr, Aomar

2017-01-01

Factor V congenital deficiency is a rare coagulation disorder initially described by Owren in 1947 and known as para hemophilia. It is transmitted through autosomal-recessive inheritance and homozygous cases are usually symptomatic. Factor V is an essential cofactor in the conversion of prothrombin to thrombin by activated factor X. In the absence of factor V, thrombin generation is slowed down and fibrin formation is delayed. This results in a bleeding tendency. We report a case of factor V congenital deficiency in an infant with recurrent epistaxis.

Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy.

PubMed

Gjeorgjievski, Mihajlo; Cappell, Mitchell S

2016-02-08

To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding.

PubMed

Dietrich, Jennifer E; Yee, Donald L; Santos, Xiomara M; Bercaw-Pratt, Jennifer L; Kurkowski, Jennifer; Soni, Heather; Lee-Kim, Youngna J; Shah, Mona D; Mahoney, Donald; Srivaths, Lakshmi V

2017-04-01

STUDY OBJECTIVE, DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Bleeding disorders (BD) occur in up to 50% of adolescents with heavy menstrual bleeding (HMB). This presents unique challenges to health care providers because of the complexity of treating the condition and such complexity can result in difficulty with patients understanding basic information about their condition, limit communication with medical providers, and patient compliance. The aim of the study was to use an electronic approach to enhance patient compliance with medications used to treat their HMB, and to provide educational access to adolescents with BD. This was a prospective cohort study involving patients in a Young Women's Bleeding Disorder Clinic at a single children's hospital. Subjects were given an iPod Touch (Apple Inc, Cupertino, CA) device (ITD), preloaded with the iPeriod (Winkpass Creations) application. Participants recorded information about their BD that they learned about on BD Web sites, and menses, and medications. Electronic and charted data were collected to monitor compliance with prescribed treatment regimens. All ITD allowed Wi-Fi access to allow teens to explore BD Web sites and knowledge was assessed. Twenty-three of 45 subjects completed the study. The mean age was 14.1 ± 1.9 years. Subjects who were compliant with the ITD (group 1), charted on baseline symptoms, menstrual flow (83.3%), cramps (100%, 23/23), breakthrough bleeding (95.6%, 22/23), mood (95.6%, 22/23), and medication use (91.7%) for a mean of 9.3 ± 3.1 months. Subjects who were nonusers (group 2) did not report on symptoms, their condition, or medication use in the device (n = 22). More than 75% (17/23) of subjects in group 1 used hormones alone or hormones with antifibrinolytic agents to control HMB. No subjects stopped or missed medications who were in group 1 intentionally, and also there were 9 enrollees within this same group who missed a medication related to awaiting the prescription to be filled from pharmacy. In group 2, 17 enrollees missed medications, resulting in 19% (4/22) of these enrollees being admitted to hospital for 1-2 days. In addition, enrollees in group 2 missed more medications on average compared with group 1. No subjects in group 1 required admission for HMB treatment failure during the study period, compared with those in group 2 (P = .006). All subjects in group 1 reported accessing Web sites using their ITD to learn about their BD. Groups 1 and 2 did not differ in the number of medications that were prescribed during the time frame (P = .77) or the number of follow-up clinic visits (P = .49). Furthermore, those in group 1 reported fewer breakthrough bleeding episodes than those in group 2 according to clinic notes (P = .03). Users of the ITD were given a set of knowledge questions. Group 2 subjects were not consistent users of the ITD use and did not complete the knowledge questions. Group 1 and 2 could not be compared with regard to knowledge as a result. ITD is an excellent tool for adolescents with HMB and BD to allow self-monitoring, provider monitoring, and improve educational access through engaging technology; compliance with device use was associated with several parameters suggestive of improved clinical outcomes. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Gastrointestinal bleeding in patients with renal failure under hemodialysis treatment: a single-center experience.

PubMed

Can, Özgür; Koç, Gözde; Ocak, Sema Berk; Akbay, Nursel; Ahishali, Emel; Canbakan, Mustafa; Şahin, Gülizar Manga; Apaydin, Süheyla

2017-05-01

Gastrointestinal bleeding remains the leading cause of morbidity and mortality for patients who need hemodialysis treatment. Our aim was to evaluate patients who needed hemodialysis and presented with bleeding during their hospital stay (uremic bleeding patients). Factors that increased the risk of bleeding and death were evaluated. Additionally, uremic bleeding patients were compared to non-uremic bleeding patients regarding gastrointestinal findings. Fifty-one uremic bleeding patients were compared to two control groups which included uremic (hemodialysis dependent and non-bleeding) and non-uremic (no renal insufficiency and bleeding) patients. NSAIDs and anti-ulcer drug usage were more common in uremic bleeding and in uremic non-bleeding groups, respectively. Dialysis vintage was longer in uremic bleeding group. Comparison of uremic bleeding and non-bleeding uremic patients regarding the usage of ACEI or ARB drugs yielded non-significant results. Acute kidney injury, lower plasma albumin level and high CRP level were significantly increased the risk of mortality in uremic bleeding patients. Hospital stay more than 1 week was the only strong factor for mortality when multivariate analysis was performed. Gastroduodenal and duodenal ulcers were significantly detected in uremic bleeding and non-uremic bleeding patients; respectively. Hemodialysis patients presenting with gastrointestinal bleeding should be evaluated regarding use of prescriptions and efforts should be done in order to shorten their hospital stay and decrease their mortality. Effect of ACEI or ARB drugs should also be evaluated in future studies.

MR imaging findings of adenomyosis: correlation with histopathologic features and diagnostic pitfalls.

PubMed

Tamai, Ken; Togashi, Kaori; Ito, Tsuyoshi; Morisawa, Nobuko; Fujiwara, Toshitaka; Koyama, Takashi

2005-01-01

Adenomyosis is a nonneoplastic condition, characterized by benign invasion of ectopic endometrium into the myometrium with hyperplasia of adjacent smooth muscle. The common symptoms include dysmenorrhea, menorrhagia, and abnormal uterine bleeding, but these do not allow diagnosis. Therefore, imaging plays an important role because establishment of the correct preoperative diagnosis is critical to avoid unnecessary intervention. Magnetic resonance (MR) imaging is a highly accurate noninvasive modality for diagnosis of adenomyosis, differentiation of adenomyosis from other gynecologic disorders, and planning of appropriate treatment. Although the typical MR imaging findings are well established, adenomyosis actually varies widely in terms of histopathologic features (adenomyosis with sparse glands), growth patterns (polypoid adenomyoma, adenomyotic cyst, and miniature uterus), responses to hormonal activity (tamoxifen, decidual changes), and responses to treatment (gonadotropin-releasing hormone agonist). The MR imaging findings of adenomyosis occasionally mimic those of uterine malignancy or ovarian cancer. Furthermore, malignancy occasionally develops in otherwise benign adenomyosis. Pitfalls in diagnosis of adenomyosis include myometrial contractions, leiomyoma, adenomatoid tumor, metastases, endometrial carcinoma, and endometrial stromal sarcoma. Knowledge of the various appearances of adenomyosis and the possible pitfalls in differential diagnosis help guide the determination of appropriate treatment options. (c) RSNA, 2005.

The Role of Hysteroscopy in the Diagnosis and Treatment of Adenomyosis.

PubMed

Di Spiezio Sardo, Attilio; Calagna, Gloria; Santangelo, Fabrizia; Zizolfi, Brunella; Tanos, Vasilis; Perino, Antonino; De Wilde, Rudy Leon

2017-01-01

Uterine adenomyosis is a common gynecologic disorder in women of reproductive age, characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Dysmenorrhea, abnormal uterine bleeding, chronic pelvic pain, and deep dyspareunia are common symptoms of this pathological condition. However, adenomyosis is often an incidental finding in specimens obtained from hysterectomy or uterine biopsies. The recent evolution of diagnostic imaging techniques, such as transvaginal sonography, hysterosalpingography, and magnetic resonance imaging, has contributed to improving accuracy in the identification of this pathology. Hysteroscopy offers the advantage of direct visualization of the uterine cavity while giving the option of collecting histological biopsy samples under visual control. Hysteroscopy is not a first-line treatment approach for adenomyosis and it represents a viable option only in selected cases of focal or diffuse "superficial" forms. During office hysteroscopy, it is possible to enucleate superficial focal adenomyomas or to evacuate cystic haemorrhagic lesions of less than 1.5 cm in diameter. Instead, resectoscopic treatment is indicated in cases of superficial adenomyotic nodules > 1.5 cm in size and for diffuse superficial adenomyosis. Finally, endometrial ablation may be performed with the additional removal of the underlying myometrium.

Collagenous gastroduodenitis coexisting repeated Dieulafoy ulcer: A case report and review of collagenous gastritis and gastroduodenitis without colonic involvement.

PubMed

Soeda, Atsuko; Mamiya, Takashi; Hiroshima, Yoshinori; Sugiyama, Hiroaki; Shidara, Sayoko; Dai, Yuichi; Nakahara, Akira; Ikezawa, Kazuto

2014-10-01

Collagenous gastritis (CG) is a rare disorder characterized by the thick collagenous subepithelial bands associated with mucosal inflammation. There have been approximately fifty reports in the literature since it was first described in 1989. According to previous reports, CG is heterogeneous and classified into two groups-(1) cases limited to the gastric mucosa in children or young adults, and (2) CG associated with collagenous colitis in elderly adults presenting with chronic watery diarrhea. In Japan, only nine previous cases were reported, and all of them were young adults. We report a case of CG with collagenous duodenitis in a 22-year-old female. She had repeated upper gastrointestinal bleeding from a Dieulafoy lesion of the fornix, but had no symptoms of malabsorption or diarrhea. Endoscopic findings revealed striking nodularity with a smooth islet-shaped normal area in the antrum and the body. The pathological findings of nodular mucosa showed the deposition of collagen bands just under the mucoepithelial lesion. In addition, she had collagenous duodenitis in part of the bulbs, and a colonoscopy showed no abnormalities. We provide a literature review of CG and collagenous gastroduodenitis without colonic involvement.

Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

PubMed Central

Vega-Najera, Carlos; Leal-Contreras, Carlos; Leal-Berumen, Irene

2013-01-01

The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis. PMID:24392235

Blue rubber bleb nevus syndrome with simultaneous neurological and skeletal involvement.

PubMed

Tzoufi, Meropi S; Sixlimiri, Polyxeni; Nakou, Iliada; Argyropoulou, Maria I; Stefanidis, Constantinos J; Siamopoulou-Mavridou, Antigone

2008-08-01

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder characterized by venous malformations usually affecting the skin and the gastrointestinal tract. These skin haemangiomas are present at birth and deteriorate as the body grows, causing primarily cosmetic problems. The haemangiomas of the gastrointestinal tract may appear later in life and may bleed, causing chronic anaemia, or may present with severe complications such as rupture, intestinal torsion, and intussusception. Other organs may also be involved. This article describes a 13-year-old boy with multiple haemangiomas of the skin, the mucous membranes, and the gastrointestinal tract, which caused anaemia and ileoileic intussusception. In this patient, the nervous system was significantly affected with a haemangioma of the left occipital lobe, with complications of stroke. He also had multiple paravertebral heamangiomas, which caused pressure signs and symptoms. This boy suffered from complex partial and generalized seizures and cerebral palsy. Multiple skeletal anomalies were also present from birth. In the relevant literature, this is the first case of BRBNS with simultaneous neurological and skeletal involvement. Such cases should be recognized early, as they can lead to serious multiple health problems and handicaps.

Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review.

PubMed

Albuquerque, Andreia

2014-11-16

Nodular lymphoid hyperplasia of the gastrointestinal tract is characterized by the presence of multiple small nodules, normally between between 2 and 10 mm in diameter, distributed along the small intestine (more often), stomach, large intestine, or rectum. The pathogenesis is largely unknown. It can occur in all age groups, but primarily in children and can affect adults with or without immunodeficiency. Some patients have an associated disease, namely, common variable immunodeficiency, selective IgA deficiency, Giardia infection, or, more rarely, human immunodeficiency virus infection, celiac disease, or Helicobacter pylori infection. Nodular lymphoid hyperplasia generally presents as an asymptomatic disease, but it may cause gastrointestinal symptoms like abdominal pain, chronic diarrhea, bleeding or intestinal obstruction. A diagnosis is made at endoscopy or contrast barium studies and should be confirmed by histology. Its histological characteristics include markedly hyperplasic, mitotically active germinal centers and well-defined lymphocyte mantles found in the lamina propria and/or in the superficial submucosa, distributed in a diffuse or focal form. Treatment is directed towards associated conditions because the disorder itself generally requires no intervention. Nodular lymphoid hyperplasia is a risk factor for both intestinal and, very rarely, extraintestinal lymphoma. Some authors recommend surveillance, however, the duration and intervals are undefined.

Molecular genetic analysis of the F11 gene in 14 Turkish patients with factor XI deficiency: identification of novel and recurrent mutations and their inheritance within families

PubMed Central

Colakoglu, Seyma; Bayhan, Turan; Tavil, Betül; Keskin, Ebru Yılmaz; Cakir, Volkan; Gümrük, Fatma; Çetin, Mualla; Aytaç, Selin; Berber, Ergul

2018-01-01

Background Factor XI (FXI) deficiency is an autosomal bleeding disease associated with genetic defects in the F11 gene which cause decreased FXI levels or impaired FXI function. An increasing number of mutations has been reported in the FXI mutation database, most of which affect the serine protease domain of the protein. FXI is a heterogeneous disorder associated with a variable bleeding tendency and a variety of causative F11 gene mutations. The molecular basis of FXI deficiency in 14 patients from ten unrelated families in Turkey was analysed to establish genotype-phenotype correlations and inheritance of the mutations in the patients’ families. Material and methods Fourteen index cases with a diagnosis of FXI deficiency and family members of these patients were enrolled into the study. The patients’ F11 genes were amplified by polymerase chain reaction and subjected to direct DNA sequencing analysis. The findings were analysed statistically using bivariate correlations, Pearson’s correlation coefficient and the nonparametric Mann-Whitney test. Results Direct DNA sequencing analysis of the F11 genes revealed that all of the 14 patients had a F11 gene mutation. Eight different mutations were identified in the apple 1, apple 2 or serine protease domains, except one which was a splice site mutation. Six of the mutations were recurrent. Two of the mutations were novel missense mutations, p.Val522Gly and p.Cys581Arg, within the catalytic domain. The p.Trp519Stop mutation was observed in two families whereas all the other mutations were specific to a single family. Discussion Identification of mutations confirmed the genetic heterogeneity of FXI deficiency. Most of the patients with mutations did not have any bleeding complications, whereas some had severe bleeding symptoms. Genetic screening for F11 gene mutations is important to decrease the mortality and morbidity rate associated with FXI deficiency, which can be life-threatening if bleeding occurs in tissues with high fibrinolytic activity. PMID:27723456

Early laparoscopic management of acute postoperative hemorrhage after initial laparoscopic surgery.

PubMed

Gong, Edward M; Zorn, Kevin C; Gofrit, Ofer N; Lucioni, Alvaro; Orvieto, Marcelo A; Zagaja, Gregory P; Shalhav, Arieh L

2007-08-01

The use of laparoscopic surgery has been well established for the management of abdominal emergencies. However, the value of this technique for postoperative hemorrhage in urology has not been characterized. We present our favorable experience with laparoscopic exploration after urologic surgery and suggest guidelines for laparoscopic management of post-laparoscopy bleeding. Three patients who developed hemorrhage shortly after laparoscopic urologic surgery and were managed by laparoscopic exploration were identified from a series of 910 laparoscopic urologic procedures performed at our institution from October 2002 to June 2006. Three patients, who were hemodynamically stable (two after robot-assisted laparoscopic prostatectomy, one after laparoscopic radical nephrectomy), required prompt surgical exploration for postoperative hemorrhage not stabilized by blood transfusion (mean 2.7 units) at a mean of 19.4 hours after initial surgery. Clots were evacuated with a 10-mm suction-irrigator. Two patients were found to have abdominal-wall arterial bleeding and were managed with suture ligation. The third patient demonstrated diffuse bleeding from the prostatic bed, which was controlled with Surgicel and FloSeal. Bleeding was efficiently controlled in all patients, and none required post-exploration transfusion. The mean post-exploration hospital stay was 2.3 days. Significant hemorrhage after urologic laparoscopy is a rare event. We found laparoscopic exploration to be an excellent way to diagnose and correct such hemorrhage in certain patients. Early diagnosis with clinical and hematologic studies, a lowered threshold for surgical exploration, and specific operative equipment may decrease patient morbidity and the need for open surgical exploration.

Abnormal Uterine Bleeding

MedlinePlus

... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

Differential proteomics study of platelets in asymptomatic constitutional macrothrombocytopenia: altered levels of cytoskeletal proteins.

PubMed

Karmakar, Shilpita; Saha, Sutapa; Banerjee, Debasis; Chakrabarti, Abhijit

2015-01-01

Harris platelet syndrome (HPS), also known as asymptomatic constitutional macrothrombocytopenia (ACMT), is an autosomal dominant platelet disorder characterized by mild-to-severe thrombocytopenia and giant platelets with normal platelet aggregation and absence of bleeding symptoms. We have attempted a comparative proteomics study for profiling of platelet proteins in healthy vs. pathological states to discover characteristic protein expression changes in macrothrombocytes and decipher the factors responsible for the functionally active yet morphologically distinct platelets. We have used 2-D gel-based protein separation techniques coupled with MALDI-ToF/ToF-based mass spectrometric identification and characterization of the proteins to investigate the differential proteome profiling of platelet proteins isolated from the peripheral blood samples of patients and normal volunteers. Our study revealed altered levels of actin-binding proteins such as myosin light chain, coactosin-like protein, actin-related protein 2/3 complex, and transgelin2 that hint toward the cytoskeletal changes necessary to maintain the structural and functional integrity of macrothrombocytes. We have also observed over expressed levels of peroxiredoxin2 that signifies the prevailing oxidative stress in these cells. Additionally, altered levels of protein disulfide isomerase and transthyretin provide insights into the measures adapted by the macrothrombocytes to maintain their normal functional activity. This first proteomics study of platelets from ACMT may provide an understanding of the structural stability and normal functioning of these platelets in spite of their large size. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Standardizing a simpler, more sensitive and accurate tail bleeding assay in mice

PubMed Central

Liu, Yang; Jennings, Nicole L; Dart, Anthony M; Du, Xiao-Jun

2012-01-01

AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay. METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 °C, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2Y receptor inhibitor prasugrel at various doses or in mice deficient of FcRγ, a signaling protein of the glycoprotein VI receptor. RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleeding pattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels (r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet’s haemostatic activity (P < 0.01). Similarly, in mice with genetic disruption of FcRγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time. CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited. PMID:24520531

Acute on chronic gastrointestinal bleeding: a unique clinical entity.

PubMed

Rockey, Don C; Hafemeister, Adam C; Reisch, Joan S

2017-06-01

Gastrointestinal bleeding is defined in temporal-spatial terms-as acute or chronic, and/or by its location in the gastrointestinal tract. Here, we define a distinct type of bleeding, which we have coined 'acute on chronic' gastrointestinal bleeding. We prospectively identified all patients who underwent endoscopic evaluation for any form of gastrointestinal bleeding at a University Hospital. Acute on chronic bleeding was defined as the presence of new symptoms or signs of acute bleeding in the setting of chronic bleeding, documented as iron deficiency anemia. Bleeding lesions were categorized using previously established criteria. We identified a total of 776, 254, and 430 patients with acute, chronic, or acute on chronic bleeding, respectively. In patients with acute on chronic gastrointestinal bleeding, lesions were most commonly identified in esophagus (28%), colon and rectum (27%), and stomach (21%) (p<0.0001 vs locations for acute or chronic bleeding). In those specifically with acute on chronic upper gastrointestinal bleeding (n=260), bleeding was most commonly due to portal hypertensive lesions, identified in 47% of subjects compared with 29% of acute and 25% of chronic bleeders, (p<0.001). In all patients with acute on chronic bleeding, 30-day mortality was less than that after acute bleeding alone (2% (10/430) vs 7% (54/776), respectively, p<0.001). Acute on chronic gastrointestinal bleeding is common, and in patients with upper gastrointestinal bleeding was most often a result of portal hypertensive upper gastrointestinal tract pathology. Reduced mortality in patients with acute on chronic gastrointestinal bleeding compared with those with acute bleeding raises the possibility of an adaptive response. Copyright © 2017 American Federation for Medical Research.

Bleeding pattern and user satisfaction in second consecutive levonorgestrel-releasing intrauterine system users: results of a prospective 5-year study

PubMed Central

Heikinheimo, O.; Inki, P.; Schmelter, T.; Gemzell-Danielsson, K.

2014-01-01

STUDY QUESTION What is the bleeding pattern during second consecutive levonorgestrel-releasing intrauterine system (LNG-IUS) use? SUMMARY ANSWER Consecutive use of LNG-IUS is associated with a predictable bleeding pattern, characterized by the absence of the initial period of irregular bleeding seen after interval insertion of an LNG-IUS and a non-bleeding pattern in the vast majority of women. WHAT IS KNOWN ALREADY With increased popularity of the LNG-IUS for long-term birth control and treatment of heavy menstrual bleeding (HMB), consecutive use of the system is becoming more frequent. One previous study showed 60% amenorrhea rate in consecutive IUS users; however, the sample size was small. STUDY DESIGN, SIZE, DURATION A prospective multicenter study in four European countries recruited women who wished to continue with LNG-IUS use immediately after the first 5-year period. A total of 204 women were followed up until the end of the first year of the second IUS. Thereafter 170 women continued into the extension phase of the study up to the full 5 years of use of the second IUS and 144 women continued to the end of the study. PARTICIPANTS, SETTING, METHODS A total of 170 women (mean age 39 years) who had been using their first LNG-IUS for between 4 years 3 months and 4 years 9 months, either for contraception or for treatment of HMB, and who planned to replace the device with a new LNG-IUS, were recruited and followed up to 5 years of the second IUS use. A total of 17 centers in four European countries were involved in the study. Bleeding patterns were analyzed using daily bleeding diaries using 90-day reference periods (RP) for the first year of the second IUS use and for the last RP of each year during Years 2–5 of use. MAIN RESULTS AND THE ROLE OF CHANCE Approximately 70% of women were free of bleeding during Years 2–5 and up to 49% were amenorrheic. There was a slight increase in the number of bleeding/spotting days of ∼3 days during the first RP immediately after the placement of the second IUS, whereafter the number of bleeding/spotting days returned to the level preceding the second IUS insertion or below that. Absence of bleeding was associated with high overall satisfaction and continuation rates. No serious adverse events assessed as related to the LNG-IUS use occurred during the 5-year period. The cumulative expulsion rate during the 5-year study period was 1.2%. The sample size was large enough to study bleeding patterns, and subjects are likely to represent typical consecutive IUS users, and therefore, the role of chance is small. LIMITATIONS, REASONS FOR CAUTION The women represent a selected group as they had already successfully used their first IUS for almost 5 years and were willing to continue its use—however, this is currently a common clinical situation. The results may therefore not be extrapolated to first-time users of the LNG-IUS. WIDER IMPLICATIONS OF THE FINDINGS These data are of importance when counseling women who are making decisions concerning long-term contraception. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Bayer Pharma AG. P.I. and T.S. are full-time employees of Bayer Pharma AG. O.H. and K. G-D. have received consultancy fees from Bayer Pharma AG. The publication was developed jointly by all authors without third-party involvement and no honoraria were paid for any authors for their contribution to this manuscript. TRIAL REGISTRATION NUMBER NCT00393198. PMID:24682613

Incidence of Gastrointestinal Bleeding After Percutaneous Coronary Intervention: A Single Center Experience.

PubMed

Aziz, Fahad

2014-02-01

Gastrointestinal (GI) bleeding is a hemorrhagic complication after percutaneous coronary intervention in patients with acute myocardial infarction. The purpose of the study is to determine predictors of GI bleeding and impact of GI bleeding on the patients undergoing percutaneous coronary intervention. GI bleeding occurred in 6 (7.1%) of 84 patients with STEMI/NSETMI (ST-segment elevated myocardial infarction/Non ST-segment elevated myocardial infarction) undergoing primary percutaneous coronary intervention. Univariate analysis demonstrates that patients with GI bleeding had a significantly higher previous GI bleeding (16.66% vs. 8.6%, P < 0.001). Higher Killip classification at presentation was associated with higher incidence of GI bleeding (61% vs. 18%, P < 0.01). The use of proton pump inhibitors did not reduce the risk of GI bleeding. The GI bleeding in these patients was associated with higher mortality and morbidity in the post percutaneous coronary intervention period. Although, GI bleeding in patients with MI significantly increases mortality and morbidity, previous GI bleeding and higher Killip class are associated with higher incidence of GI bleeding. High-risk patients for GI bleeding can be identified at presentation.

The Effects of the Contact Activation System on Hemorrhage

PubMed Central

Simão, Fabrício; Feener, Edward P.

2017-01-01

The contact activation system (CAS) exerts effects on coagulation via multiple mechanisms, which modulate both the intrinsic and extrinsic coagulation cascades as well as fibrinolysis and platelet activation. While the effects of the CAS on blood coagulation measured as activated partial thromboplastin time shortening are well documented, genetic mutations that result in deficiencies in the expression of either plasma prekallikrein (PPK) or factor XII (FXII) are not associated with spontaneous bleeding or increased bleeding risk during surgery. Deficiencies in these proteins are often undiagnosed for decades and detected later in life during routine coagulation assays without an apparent clinical phenotype. Increased interest in the CAS as a potentially safe target for antithrombotic therapies has emerged, in large part, from studies on animal models with provoked thrombosis, which have shown that deficiencies in PPK or FXII can reduce thrombus formation without increasing bleeding. Gene targeting and pharmacological studies in healthy animals have confirmed that PPK and FXII blockade does not cause coagulopathies. These findings support the conclusion that CAS is not required for hemostasis. However, while deficiencies in FXII and PPK do not significantly affect bleeding associated with peripheral wounds, recent reports have demonstrated that these proteins can promote hemorrhage in the retina and brain. Intravitreal injection of plasma kallikrein (PKal) induces retinal hemorrhage and intracerebral injection of PKal increases intracranial bleeding. PPK deficiency and PKal inhibition ameliorates hematoma formation following cerebrovascular injury in diabetic animals. Moreover, both PPK and FXII deficiency are protective against intracerebral hemorrhage caused by tissue plasminogen activator-mediated thrombolytic therapy in mice with thrombotic middle cerebral artery occlusion. Thus, while the CAS is not required for hemostasis, its inhibition may provide an opportunity to reduce hemorrhage in the retina and brain. Characterization of the mechanisms and potential clinical implications associated with the effects of the CAS on hemorrhage requires further consideration of the effects of PPK and FXII on hemorrhage beyond their putative effects on coagulation cascades. Here, we review the experimental and clinical evidence on the effects of the CAS on bleeding and hemostatic mechanisms. PMID:28824910

[A patient with Noonan syndrome].

PubMed

Bins, A; Gortzak, R A Th

2013-12-01

Noonan syndrome is a relatively common autosomal dominant genetic disorder which is characterised by typical facial features, congenital heart diseases and small stature. In 50% of the cases the syndrome is caused by a mutation on the PTPN11-gen. The expression of symptoms associated with Noonan syndrome can be very mild in nature and facial features usually become less pronounced with age, which can sometimes make a correct diagnosis more difficult. Despite a wide range of associated symptoms most adults with Noonan syndrome can be self-sustaining, with a good quality of life. It is important that the dentist is well-informed about this syndrome due to the heart diseases and bleeding disorders which can be present with these patients and may influence a dentist's choice of therapy when invasive treatment is indicated.

Perioperative Physiotherapy for Total Ankle Replacement in Patients with Inherited Bleeding Disorders: Outline of an Algorithm.

PubMed

Kotela, Andrzej; Wilk-Frańczuk, Magdalena; Jaczewska, Joanna; Żbikowski, Piotr; Łęgosz, Paweł; Ambroziak, Paweł; Kotela, Ireneusz

2017-01-27

The treatment of end-stage hemophilic arthropathy of the ankle joint remains a controversial problem, and total ankle replacement (TAR) is considered to be a valuable management option. Physiotherapy continues to be an extremely important part of TAR and has a tremendous impact on the outcomes of this procedure. Given the lack of data on the latter, this study details a protocol of perioperative physiotherapy in TAR in patients with inherited bleeding disorders (IBD). The protocol outlined in this paper was devised via consultations within an interdisciplinary group, the authors' own experiences with TAR in hemophilic and non-hemophilic patients, previous reports on this issue in the literature, and patient opinions. Our working group followed the criteria of the International Classification of Functioning, Disability and Health. The algorithm includes 4 physiotherapy phases with specified time frames, aims, interventions, and examples of exercises for each phase. We emphasize the importance of preoperative rehabilitation, and recommend introducing intensive physiotherapy immediately after the surgery, with regard to the wound protection and avoiding full weight-bearing in the first weeks. The intensity of physiotherapy should be adjusted individually depending on individual patient progress. This study details a rehabilitation protocol for TAR in patients with IBDs, which can be equally applicable to clinicians and researchers. Further scientific studies are required to investigate the beneficial effect of different protocols as well as to clarify the effectiveness of various frequencies, durations, and intensities of selected interventions.

Psychosocial correlates of physical activity in adolescents with haemophilia.

PubMed

Buxbaum, N P; Ponce, M; Saidi, P; Michaels, L A

2010-07-01

Boys with haemophilia are now encouraged to exercise and take part in physical activities, but actual measures of time spent in active participation is lacking. The aim of this study was to obtain an objective measure of daily physical activity in boys with haemophilia as compared with healthy controls. The study also aimed to ascertain the social and cognitive factors associated with exercise in this population. Seventeen patients (aged 11-18 years) with haemophilia were studied and compared with 44 healthy controls (aged 10-16.5 years). Physical activity was measured by accelerometry. Psychosocial correlates were assessed using validated questionnaires. Measured physical activity levels in subjects with haemophilia were slightly higher than for the control group. Both groups spent 70% of the day inactive, with similar proportions of time in moderate and vigorous activity. Subjects with haemophilia had a favourable self-image and similar levels of anxiety as peers without a bleeding disorder. Self-efficacy scores were lower than for controls suggesting increased sensitivity to barriers and lack of acceptance of alternatives. Health beliefs did not influence physical activity, but a negative correlation of time spent in high or vigorous activity with scores for support-seeking was observed. The data demonstrate that in the appropriate social environment and with medical support, patients with haemophilia may be as physically active as their peers without a bleeding disorder. Further investigation into the psychosocial barriers of physical activity in patients with haemophilia is needed to more effectively encourage healthy behaviours.

Aortic Replacement with Sutureless Intraluminal Grafts

PubMed Central

Lemole, Gerald M.

1990-01-01

To avoid the anastomotic complications and long cross-clamp times associated with standard suture repair of aortic lesions, we have implanted sutureless intraluminal grafts in 122 patients since 1976. Forty-nine patients had disorders of the ascending aorta, aortic arch, or both: their operative mortality was 14% (7 patients), and the group's 5-year actuarial survival rate has been 64%. There have been no instances of graft dislodgment, graft infection, aortic bleeding, or pseudoaneurysm formation. Forty-two patients had disorders of the descending aorta and thoracoabdominal aorta: their early mortality was 10% (4 patients), and the group's 5-year actuarial survival rate has been 56%. There was 1 early instance of graft dislodgment, but no pseudoaneurysm formation, graft erosion, aortic bleeding, intravascular hemolysis, or permanent deficits in neurologic, renal, or vascular function. Thirty-one patients had the sutureless intraluminal graft implanted in the abdominal aortic position: their early mortality was 6% (2 patients), and the 5-year actuarial survival rate for this group has been 79%. There were no instances of renal failure, ischemic complication, postoperative paraplegia, pseudoaneurysm, or anastomotic true aneurysm. Our recent efforts have been directed toward developing an adjustable spool that can adapt to the widest aorta or the narrowest aortic arch vessel; but in the meanwhile, the present sutureless graft yields shorter cross-clamp times, fewer intraoperative complications, and both early and late results as satisfactory as those afforded by traditional methods of aortic repair. (Texas Heart Institute Journal 1990; 17:302-9) Images PMID:15227522

[Efficacy and safety of a combined oral contraceptive containing drospirenone 3 mg and ethinylestradiol 20 µg in the treatment of premenstrual dysphoric disorder: a randomized, double blind placebo-controlled study].

PubMed

Fu, Yi; Mi, Weifeng; Li, Lingzhi; Zhang, Hongyan; Wang, Jia; Cheng, Wenjun; Sun, Lizhou; Li, Lingjiang; Xie, Shiping; Zhang, Jinbei

2014-07-01

To compare the efficacy and safety of a new low-dose oral contraceptive pill (YAZ) containing drospirenone 3 mg and ethinylestradiol 20 µg with placebo in reducing symptoms of premenstrual dysphoric disorder (PMDD). This multicenter, double- blind, randomized clinical trial consisted of 2 run- in and 3 treatment cycles (84 days) with daily symptom charting; 187 women with symptoms of PMDD were randomized to either placebo group (n = 94) or YAZ group (n = 93), and assessed with daily record of severity of problems scale (DRSP) and clinical global impressions scale (CGI) before, during and after the treatments. Hormones were administered for 24 days, followed by 4 days of inactive pills. Compared with baseline level of DRSP, both groups got improvement after treatment; the YAZ group (median -28.7, range: -82.5 to 2.3) had greater improvement than that in the placebo group (median -23.7, range: -86.0 to 11.8), while there was not significant difference (P > 0.05). The main adverse effects of YAZ included intermenstrual bleeding [13% (12/93) versus 3% (3/94)], menorrhagia [9% (8/93) versus 1% (1/94)], nausea [5% (5/93) versus 4% (4/94)] and skin rash [4% (4/93) versus 2% (2/94)]. YAZ could improve symptoms of PMDD better than placebo, while without statistic significance in this study. The most common adverse effects are intermenstrual bleeding, menorrhagia, nausea and rash.

Frequency and prognostic significance of access site and non-access site bleeding and impact of choice of antithrombin therapy in patients undergoing primary percutaneous coronary intervention. The EUROMAX trial.

PubMed

Kilic, Sinem; Van't Hof, Arnoud W J; Ten Berg, Jurrien; Lopez, Ana Ayesta; Zeymer, Uwe; Hamon, Martial; Soulat, Louis; Bernstein, Debra; Deliargyris, Efthymios N; Steg, Phillippe Gabriel

2016-05-15

The overall impact of post percutaneous coronary intervention (PCI) bleeding on long term prognosis after acute coronary syndromes (ACS) has been established, but it may differ between access and non-access related bleeding events. The impact of antithrombin choice on bleeding may also differ according to the origin of the bleed. We sought to determine the origin of bleeding relative to the access site, its prognostic significance and the respective impact of antithrombin therapy in the EUROMAX trial. We performed a blinded review of the case records of all TIMI major or minor bleeds in the EUROMAX trial and assigned them in one of 2 categories: access site bleeds (ASB), or rest of bleeds (ROB). Incidence of bleeding for each category was assessed according to randomization to antithrombotic treatment. A total of 231 out of 2198 patients suffered a TIMI major/minor bleed (10.5%) and ASB accounted for 48.5%, while ROB for 51.5% of the bleeds. Thirty day mortality was 2.5% (50/1967) for patients without a bleed, 2.7% (3/112, p=0.76 vs. no bleed) for patients with ASB, and 10.9% (13/119, p<0.0001 vs. no bleed) for ROB patients. The use of bivalirudin reduced both ASB and ROB with relative risk reductions of 34% and 46% respectively. In contemporary primary PCI, bleeding originates with equal frequency either at or away from the access site. Access site bleeds were not associated with an excess in 30day mortality, but the rest of the bleeds were. Bivalirudin is associated with a lower risk of bleeding irrespective of origin. ClinicalTrials.gov identifier NCT01087723. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study.

PubMed

Ljubičić, Neven; Budimir, Ivan; Pavić, Tajana; Bišćanin, Alen; Puljiz, Zeljko; Bratanić, Andre; Troskot, Branko; Zekanović, Dražen

2014-04-01

The aim of this study was to identify the predictive factors influencing mortality in patients with bleeding Mallory-Weiss syndrome in comparison with peptic ulcer bleeding. Between January 2005 and December 2009, 281 patients with endoscopically confirmed Mallory-Weiss syndrome and 1530 patients with peptic ulcer bleeding were consecutively evaluated. The 30-day mortality and clinical outcome were related to the patients' demographic data, endoscopic, and clinical characteristics. The one-year cumulative incidence for bleeding Mallory-Weiss syndrome was 7.3 cases/100,000 people and for peptic ulcer bleeding 40.4 cases/100,000 people. The age-standardized incidence for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding remained unchanged during the observational five-year period. The majority of patients with bleeding Mallory-Weiss syndrome were male patients with significant overall comorbidities (ASA class 3-4). Overall 30-day mortality rate was 5.3% for patients with bleeding Mallory-Weiss syndrome and 4.6% for patients with peptic ulcer bleeding (p = 0.578). In both patients with bleeding Mallory-Weiss syndrome and peptic ulcer bleeding, mortality was significantly higher in patients over 65 years of age and those with significant overall comorbidities (ASA class 3-4). The incidence of bleeding Mallory-Weiss syndrome and peptic ulcer bleeding has not changed over a five-year observational period. The overall 30-day mortality was almost equal for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding and was positively correlated to older age and underlying comorbid illnesses.

Mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease.

PubMed

Bunevicius, Robertas; Velickiene, Dzilda; Prange, Arthur J

2005-01-01

To evaluate the prevalence of mood and anxiety disorders in women with treated hyperthyroidism caused by Graves' disease and to compare them with the prevalence of such findings in women without past or present thyroid disease. Thirty inpatient women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease and 45 women hospitalized for treatment of gynecologic disorders such as abnormal vaginal bleeding, benign tumors or infertility were evaluated for the prevalence of mood and anxiety diagnoses using a standard Mini-International Neuropsychiatric Interview and for mood and anxiety ratings using the Profile of Mood States (POMS). At the time of assessment, it was discovered that 14 of 30 women with treated hyperthyroidism caused by Graves' disease were still hyperthyroid, while 16 women were euthyroid. Significantly greater prevalence of social anxiety disorder, generalized anxiety disorder, major depression and total mood and anxiety disorders, as well as higher symptom scores on the POMS, was found in hyperthyroid women with Graves' disease in comparison with the control group. A prevalence of total anxiety disorder, as well as history of mania or hypomania and lifetime bipolar disorder, but not lifetime unipolar depression, was more frequent in both the euthyroid and the hyperthyroid subgroups of study women in comparison with the control group. These results confirm a high prevalence of mood and anxiety disorders in women with treated hyperthyroidism and ophthalmopathy caused by Graves' disease. Hyperthyroidism plays a major role in psychiatric morbidity in Graves' disease.

Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia.

PubMed

Cavalcante de Andrade Silva, Marcela; Krepischi, Ana Cristina Victorino; Kulikowski, Leslie Domenici; Zanardo, Evelin Aline; Nardinelli, Luciana; Leal, Aline Medeiros; Costa, Silvia Souza; Muto, Nair Hideki; Rocha, Vanderson; Velloso, Elvira Deolinda Rodrigues Pereira

2018-04-01

Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RUNX1 mutations is an autosomal dominant disorder included in the group of the myeloid neoplasms with germ line predisposition. We describe two brothers who were diagnosed with hematological malignancies (one with AML and the other with T-cell lymphoblastic lymphoma). There was a history of leukemia in the paternal family and two of their siblings presented with low platelet counts and no history of significant bleeding. A microdeletion encompassing exons 1-2 of RUNX1 (outside the cluster region of the Runt Homology domain and the transactivation domain) was detected in six family members using array-CGH and MLPA validation. A low platelet count was not present in all deletion carriers and, therefore, it should not be used as an indication for screening in suspected families and family members. Copyright © 2018 Elsevier Inc. All rights reserved.

Coagulation is more affected by quick than slow bleeding in patients with massive blood loss.

PubMed

Zhao, Juan; Yang, Dejuan; Zheng, Dongyou

2017-03-01

Profuse blood loss affects blood coagulation to various degrees. However, whether bleeding speed affects coagulation remains uncertain. This study aimed to evaluate the effect of bleeding speed on coagulation function. A total of 141 patients in the Department of Thoracic Surgery of our hospital were evaluated between January 2007 and February 2014. There are two groups of patients, those who received decortication for chronic encapsulated empyema were called the slow-bleeding group, and those who received thoracoscopic upper lobectomy were called the fast bleeding group; each group was further subdivided into three: group A, 1000 ml ≤ bleeding amount < 1500 ml; group B, 1500 ml ≤ bleeding amount < 1700 ml; group C, 1700 ml ≤ bleeding amount < 2000 ml. Then, coagulation function was assessed in all patients before and during surgery and at 1, 2, and 24 h after surgery, measuring prothrombin time, activated partial thromboplastin time (APTT), fibrinogen, blood pressure, hematocrit, hemoglobin, and platelets. Bleeding duration was overtly longer in the slow-bleeding group than that in quick bleeding individuals (2.3 ± 0.25 h vs. 0.41 ± 0.13 h, P < 0.001). Fibrinogen, hematocrit, hemoglobin, and platelets strikingly decreased, whereas prothrombin time and APTT values significantly increased with bleeding amounts in both quick and slow-bleeding groups. Interestingly, compared with slow-bleeding patients, coagulation indices at each time point and bleeding amounts had significant differences in the quick bleeding group.Increased consumption of coagulation factors in quick bleeding may have greater impact on coagulation function.

External Validation of Risk Scores for Major Bleeding in a Population-Based Cohort of Transient Ischemic Attack and Ischemic Stroke Patients.

PubMed

Hilkens, Nina A; Li, Linxin; Rothwell, Peter M; Algra, Ale; Greving, Jacoba P

2018-03-01

The S 2 TOP-BLEED score may help to identify patients at high risk of bleeding on antiplatelet drugs after a transient ischemic attack or ischemic stroke. The score was derived on trial populations, and its performance in a real-world setting is unknown. We aimed to externally validate the S 2 TOP-BLEED score for major bleeding in a population-based cohort and to compare its performance with other risk scores for bleeding. We studied risk of bleeding in 2072 patients with a transient ischemic attack or ischemic stroke on antiplatelet agents in the population-based OXVASC (Oxford Vascular Study) according to 3 scores: S 2 TOP-BLEED, REACH, and Intracranial-B 2 LEED 3 S. Performance was assessed with C statistics and calibration plots. During 8302 patient-years of follow-up, 117 patients had a major bleed. The S 2 TOP-BLEED score showed a C statistic of 0.69 (95% confidence interval [CI], 0.64-0.73) and accurate calibration for 3-year risk of major bleeding. The S 2 TOP-BLEED score was much more predictive of fatal bleeding than nonmajor bleeding (C statistics 0.77; 95% CI, 0.69-0.85 and 0.50; 95% CI, 0.44-0.58). The REACH score had a C statistic of 0.63 (95% CI, 0.58-0.69) for major bleeding and the Intracranial-B 2 LEED 3 S score a C statistic of 0.60 (95% CI, 0.51-0.70) for intracranial bleeding. The ratio of ischemic events versus bleeds decreased across risk groups of bleeding from 6.6:1 in the low-risk group to 1.8:1 in the high-risk group. The S 2 TOP-BLEED score shows modest performance in a population-based cohort of patients with a transient ischemic attack or ischemic stroke. Although bleeding risks were associated with risks of ischemic events, risk stratification may still be useful to identify a subgroup of patients at particularly high risk of bleeding, in whom preventive measures are indicated. © 2018 The Authors.

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency.

PubMed

Kulkarni, R; James, A H; Norton, M; Shapiro, A

2018-05-01

Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg -1 was effective and safe in women/girls with factor X deficiency. Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL -1 ) received on-demand or preventive pdFX (25 IU kg -1 ) for ≤ 2 years. Results Of 16 enrolled subjects, 10 women and girls (aged 14-58 years [median, 25.5 years]) received 267 pdFX infusions. Mean monthly infusions per subject were higher among women and girls (2.48) than among men and boys (1.62). In women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeds, 47 joint bleeds, 15 muscle bleeds, and nine other bleeds) were treated with pdFX, with a 98% treatment success rate versus 100% in men and boys. Mean pdFX incremental recovery was similar in the two groups (2.05 IU dL -1 versus 1.91 IU dL -1 per IU kg -1 ), as was the mean half-life (29.3 h versus 29.5 h). Of 142 adverse events in women and girls, headache was the most common (12 events in six subjects). Six events (two infusion-site erythema, two fatigue, one back pain, one infusion-site pain) in two subjects were considered to be possibly pdFX-related. Following the trial, pdFX was used to successfully maintain hemostasis in two subjects undergoing obstetric delivery. Conclusions pdFX was well tolerated and effective in women and girls with FX deficiency. Although women and girls had different bleeding symptoms and sites than men and boys, their pdFX pharmacokinetic profile was comparable. © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Correlation Between Findings of Multislice Helical Computed Tomography (CT), Endoscopic Examinations, Endovascular Procedures, and Surgery in Patients with Symptoms of Acute Gastrointestinal Bleeding.

PubMed

Konecki, Dariusz; Grabowska-Derlatka, Laretta; Pacho, Ryszard; Rowiński, Olgierd

2017-01-01

Endoscopic methods (gastroscopy and colonoscopy) are considered fundamental for the diagnosis of gastrointestinal bleeding. In recent years, multidetector computed tomography (MDCT) has also gained importance in diagnosing gastrointestinal bleeding, particularly in hemodynamically unstable patients and in cases with suspected lower gastrointestinal tract bleeding. CT can detect both the source and the cause of active gastrointestinal bleeding, thereby expediting treatment initiation. The study group consisted of 16 patients with clinical symptoms of gastrointestinal bleeding in whom features of active bleeding were observed on CT. In all patients, bleeding was verified by means of other methods such as endoscopic examinations, endovascular procedures, or surgery. The bleeding source was identified on CT in all 16 patients. In 14 cases (87.5%), bleeding was confirmed by other methods. CT is an efficient, fast, and readily available tool for detecting the location of acute gastrointestinal bleeding.

The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis.

PubMed

Chai-Adisaksopha, Chatree; Crowther, Mark; Isayama, Tetsuya; Lim, Wendy

2014-10-09

Vitamin K antagonists (VKAs) have been the standard of care for treatment of thromboembolic diseases. Target-specific oral anticoagulants (TSOACs) have been developed and found to be at least noninferior to VKAs with regard to efficacy, but the risk of bleeding with TSOACs remains controversial. We performed a systematic review and meta-analysis of phase-3 randomized controlled trials (RCTs) to assess the bleeding side effects of TSOACs compared with VKAs in patients with venous thromboembolism or atrial fibrillation. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials; conference abstracts; and www.clinicaltrials.gov with no language restriction. Two reviewers independently performed study selection, data extraction, and study quality assessment. Twelve RCTs involving 102 607 patients were retrieved. TSOACs significantly reduced the risk of overall major bleeding (relative risk [RR] 0.72, P < .01), fatal bleeding (RR 0.53, P < .01), intracranial bleeding (RR 0.43, P < .01), clinically relevant nonmajor bleeding (RR 0.78, P < .01), and total bleeding (RR 0.76, P < .01). There was no significant difference in major gastrointestinal bleeding between TSOACs and VKAs (RR 0.94, P = .62). When compared with VKAs, TSOACs are associated with less major bleeding, fatal bleeding, intracranial bleeding, clinically relevant nonmajor bleeding, and total bleeding. Additionally, TSOACs do not increase the risk of gastrointestinal bleeding. © 2014 by The American Society of Hematology.

Delayed hematologic toxicity following rattlesnake envenomation unresponsive to crotalidae polyvalent antivenom.

PubMed

Bailey, Abby M; Justice, Stephanie; Davis, George A; Weant, Kyle

2017-07-01

North American rattlesnake envenomations are known to produce coagulopathies and thrombocytopenia. However, the occurrence of delayed hematologic toxicity (less than seven days after envenomation) is poorly characterized in the medical literature. While the recurrence of hematologic derangements has been documented following envenomation, it is usually in the absence of clinically significant bleeding. Although commonly recommended to treat delayed coagulopathies, the effectiveness of crotalidae polyvalent immune Fab ovine (CroFab®) in managing this condition remains in question and warrants further investigation and exploration. We describe the case of a 19-year-old male who presented following rattlesnake envenomation at a church service who was treated with antivenin for 48 h and discharged home only to return four days later with profound thrombocytopenia, coagulopathy, and clinically significant bleeding. Copyright © 2017 Elsevier Inc. All rights reserved.

Prospective analysis of delayed colorectal post-polypectomy bleeding.

PubMed

Park, Soo-Kyung; Seo, Jeong Yeon; Lee, Min-Gu; Yang, Hyo-Joon; Jung, Yoon Suk; Choi, Kyu Yong; Kim, Hungdai; Kim, Hyung Ook; Jung, Kyung Uk; Chun, Ho-Kyung; Park, Dong Il

2018-01-17

Although post-polypectomy bleeding is the most frequent complication after colonoscopic polypectomy, only few studies have investigated the incidence of bleeding prospectively. The aim of this study was to investigate the incidence of delayed post-polypectomy bleeding and its associated risk factors prospectively. Patients who underwent colonoscopic polypectomy at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively enrolled in this study. Trained nurses contacted patients via telephone 7 and 30 days after polypectomy and completed a standardized questionnaire regarding the development of bleeding. Delayed post-polypectomy bleeding was categorized as minor or major and early or late bleeding. Major delayed bleeding was defined as a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of bleeding or blood transfusion; late delayed bleeding was defined as bleeding occurring later than 24 h after polypectomy. A total of 8175 colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%) patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and 43 (1.1%) patients developed minor and major delayed bleeding, respectively, and 39 (1.0%) patients developed late delayed bleeding. In the polyp-based multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95% confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35-5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk factors for late delayed bleeding. Young age, aspirin use, polyp size, and immediate bleeding were found to be independent risk factors for delayed post-polypectomy bleeding.

Factor XIII deficiency in Iran: a comprehensive review of the literature.

PubMed

Dorgalaleh, Akbar; Naderi, Majid; Hosseini, Maryam Sadat; Alizadeh, Shaban; Hosseini, Soudabeh; Tabibian, Shadi; Eshghi, Peyman

2015-04-01

Factor XIII deficiency (FXIIID) is a rare bleeding disorder with an estimated prevalence of 1 in 2-million population worldwide. In Iran, a Middle Eastern country with a high rate of consanguineous marriages, there are approximately 473 patients afflicted with FXIIID. An approximately 12-fold higher prevalence of FXIIID is estimated in Iran in comparison with overall worldwide frequency. In this study, we have undertaken a comprehensive review on different aspects of FXIIID in the Iranian population. The distribution of this disease in different regions of Iran reveals that Sistan and Baluchestan Province has not only the highest number of patients with FXIIID in Iran but the highest global incidence of this condition. Among Iranian patients, umbilical cord bleeding, hematoma, and prolonged wound bleeding are the most frequent clinical manifestations. There are several disease causing mutations in Iranian patients with FXIIID, with Trp187Arg being the most common mutation in FXIIID in Iran. Traditionally, the management of FXIIID in Iran was only based on administration of fresh frozen plasma or cryoprecipitate, until 2009 when FXIII concentrate became available for patient management. Various studies have evaluated the efficacy and safety of prophylactic regimens in different situations with valuable findings. Although the focus of this study is on Iran, it offers considerable insight into FXIIID, which can be applied more extensively to improve the management and quality of life in all affected patients. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Evaluation of a new polyvalent antivenom against snakebite envenomation (Inoserp® Panafricain) in two different epidemiological settings: Northern Benin and Maritime Guinea].

PubMed

Chippaux, J-P; Baldé, M C; Sessinou, É; Yéro Boiro, M; Massougbodji, A

2015-01-01

The authors evaluated the safety and efficacy of Inoserp(®) Pan Africa, a new polyvalent antivenom composed of highly purified and lyophilized fragments of F(ab')2 immunoglobulins, recently registered in Benin and Guinea. We treated 100 patients in northern Benin (Atacora) and 109 in Maritime Guinea (Kindia) with confirmed envenomation. Treatment consisted of intravenous administration of 1 vial for uncomplicated envenomation, and 2 vials for hemorrhagic or neurotoxic envenomation. The dose was repeated when bleeding or signs of neurotoxicity persisted or appeared. In Atacora, on arrival at the hospital, 90% of patients had incoagulable blood, and 50% were bleeding. The resolution of these bleeding disorders was obtained in less than 3 hours for 50% of the patients and in less than 24 hours for 98%. Four patients died. In Kindia, 96 patients (88%) presented viper bites with pain + edema and 13 (12 %) others showed elapid (ptosis, dyspnea) envenomation. One patient bitten by a member of the Elapidae family, died despite early treatment. In Benin, protocol deviations for 60% of patients led to significant underdosing of the antivenom; the proportion was much lower (2%) in Guinea. Signs of intolerance after Inoserp(®) Pan Africa administration were reported in 8% of patients. All these symptoms were mild and disappeared rapidly after an antihistamine or corticosteroid treatment. Treatment using intravenous Inoserp(®) Pan Africa appeared to be well tolerated and effective against snakebite envenomation in both epidemiological settings.