Science.gov

Sample records for neonatal alloimmune thrombocytopenia

  1. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Espinoza, J P; Caradeux, J; Norwitz, Errol R; Illanes, S E

    2013-01-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) is a relatively uncommon disease, but is the leading cause of severe thrombocytopenia in the newborn. It can cause severe complications and long-term disabilities. The main objective of screening is to reduce both the morbidity and mortality associated with FMAIT, primarily by preventing intracranial hemorrhage. However, controversy surrounds both pre- and antenatal management. This article discusses pathogenesis, screening, diagnosis, and both pre- and neonatal management of FMAIT. PMID:23687553

  2. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    CONSTANTINESCU, Simona; ZAMFIRESCU, Vlad; VLADAREANU, Prof. Radu

    2012-01-01

    ABSTRACT Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the commonest cause of severe neonatal thrombocytopenia. FNAIT is usually suspected in neonates with bleeding or severe, unexplained, and/or isolated postnatal thrombocytopenia. Affected fetuses should be managed in referral centers with experience in the ante-natal management of FNAIT. Close collaboration is required between specialists in fetal medicine, obstetrics, hematology/transfusion medicine, and pediatrics. The mother and her partner should be provided with detailed information about FNAIT and its potential clinical consequences, and the benefits and risks of different approaches to ante-natal management. There has been huge progress in the ante-natal management of FNAIT over the last 20 years. However, the ideal effective treatment without significant side effects to the mother or fetus has yet to be determined. Key issues: Fetal and neonatal alloimmune thrombocytopenia is a condition that is underdiagnosed. Immunization seldom occurs in the first pregnancy. Immunization takes place in association with delivery in most cases. Anti-HPA-1a level is a predictor for the severity of thrombocytopenia. PMID:23482913

  3. [Fetal-neonatal alloimmune thrombocytopenia].

    PubMed

    Muñiz-Díaz, E; Ginovart Galiana, G

    2003-06-01

    Fetal-neonatal alloimmune thrombocytopenia is the commonest cause of severe thrombocytopenia in the newborn. This disorder is due to the destruction of fetal platelets by a maternal platelet-specific antibody caused by fetal-maternal incompatibility. The most serious complication is intracranial hemorrhage (10-30 % of newborns), which may cause death (10 % of the reported cases) or irreversible neurological sequelae (20 %). The diagnosis is usually made after birth when most affected neonates have petechiae, purpura or overt bleeding. The degree of severity varies according to platelet count. Current methods allow detection of maternal platelet alloantibodies (usually HPA-1a). Clinical grounds and the exclusion of other causes of neonatal thrombocytopenia are required to establish an accurate diagnosis. Recurrence of this disease is very high and has prompted clinicians to develop antenatal prophylactic programs in subsequent pregnancies. However, the optimal treatment of at-risk pregnancies remains controversial. The early diagnosis of this process allows effective therapy based on the infusion of compatible platelets and IgG immunoglobulins when hemorrhage is not obvious. Antenatal management of subsequent pregnancies can prevent recurrence of thrombocytopenia and intracranial hemorrhage. The aim of this review is to draw pediatricians' attention to the importance of this probably under-diagnosed disease in which early diagnosis can prevent potentially severe complications. PMID:12781112

  4. Neonatal alloimmune thrombocytopenia: pathogenesis, diagnosis and management

    PubMed Central

    Peterson, Julie A.; McFarland, Janice G.; Curtis, Brian R.; Aster, Richard H.

    2014-01-01

    Summary Neonatal alloimmune thrombocytopenia, (NAIT) is caused by maternal antibodies raised against alloantigens carried on fetal platelets. Although many cases are mild, NAIT is a significant cause of morbidity and mortality in newborns and is the most common cause of intracranial haemorrhage in full-term infants. In this report, we review the pathogenesis, clinical presentation, laboratory diagnosis and prenatal and post-natal management of NAIT and highlight areas of controversy that deserve the attention of clinical and laboratory investigators. PMID:23384054

  5. Fetal and neonatal alloimmune thrombocytopenia: prenatal interventions.

    PubMed

    Kamphuis, Marije M; Oepkes, Dick

    2011-07-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating condition, which may lead to intracranial haemorrhage (ICH) in the fetus or neonate, often with death or major neurological damage as consequence. In the absence of screening, preventive measures are only possible in the next pregnancy of women with an affected child. Controversy exists on the best intervention to minimise the risk of ICH. Most centres have abandoned treatment with serial fetal blood sampling (FBS) and platelet transfusions, because of a high rate of complications and the availability of quite effective non-invasive alternatives. In pregnancies with FNAIT and a previous affected child without ICH, weekly intravenous administration of immunoglobulins to the mother appears close to 100% effective to prevent fetal or neonatal ICH. Some centres add prednisone; this combination leads to slightly higher platelet counts at birth. In pregnant women with a previous child with ICH, the recurrence risk seems particularly high, and more aggressive maternal medical treatment is recommended, starting earlier with immunoglobulins. Whether a higher intravenous immunoglobulin dose or the addition of prednisone is really necessary is unclear. What does seem to be clear is that the use of FBS should be minimised, possibly even abandoned completely. PMID:21618560

  6. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

    PubMed

    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway. PMID:26564154

  7. Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report

    PubMed Central

    Conti, Fabiana Mendes; Hibner, Sergio; Costa, Thiago Henrique; Dezan, Marcia Regina; Aravechia, Maria Giselda; Pereira, Ricardo Antonio D'Almeida; Kondo, Andrea Tiemi; D'Amico, Élbio Antônio; Mota, Mariza; Kutner, José Mauro

    2014-01-01

    ABSTRACT Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease. PMID:24728253

  8. Extreme Elevation of Alkaline Phosphatase in a Pregnancy Complicated by Gestational Diabetes and Infant with Neonatal Alloimmune Thrombocytopenia.

    PubMed

    Lozo, Svjetlana; Atabeygi, Amir; Healey, Michael

    2016-01-01

    There have been few case reports of isolated elevation of alkaline phosphatase beyond the normal physiologic amount with subsequent return to baseline after delivery. Here we present a similar case of extreme elevation of alkaline phosphatase in a pregnancy complicated by gestational diabetes and subsequently by neonatal alloimmune thrombocytopenia (NAIT). PMID:27610256

  9. Extreme Elevation of Alkaline Phosphatase in a Pregnancy Complicated by Gestational Diabetes and Infant with Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    Healey, Michael

    2016-01-01

    There have been few case reports of isolated elevation of alkaline phosphatase beyond the normal physiologic amount with subsequent return to baseline after delivery. Here we present a similar case of extreme elevation of alkaline phosphatase in a pregnancy complicated by gestational diabetes and subsequently by neonatal alloimmune thrombocytopenia (NAIT). PMID:27610256

  10. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia.

    PubMed

    Curtis, Brian R

    2015-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal-fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis. PMID:26344048

  11. Detection and effects on platelet function of anti-platelet antibody in mule foals with experimentally induced neonatal alloimmune thrombocytopenia.

    PubMed

    Ramirez, S; Gaunt, S D; McClure, J J; Oliver, J

    1999-01-01

    Horse mares carrying mule foals were immunized during the last trimester of pregnancy with whole acid-citrate-dextrose-anticoagulated donkey blood to experimentally induce neonatal alloimmune thrombocytopenia. Thrombocytopenia occurred in the neonatal mule foals born to immunized horse mares within 24 hours after ingestion of their dams' colostrum. Mule foals born to mares not immunized with donkey blood did not develop thrombocytopenia. These findings suggest that antibodies may have been directed against a donkey platelet antigen present in the mule foals but not present in their dams. The objectives of this study were to determine whether anti-platelet antibody could be detected in mule foals with experimentally induced neonatal alloimmune thrombocytopenia, to identify any platelet proteins recognized by serum antibody in these foals, and to determine if platelet function was altered by sera from these mule foals. An indirect enzyme-linked immunosorbent assay demonstrated significantly higher absorption at 1:200 of platelet-bindable immunoglobulin G in serum from thrombocytopenic mule foals, compared with nonthrombocytopenic mule foals. Sera from thrombocytopenic and nonthrombocytopenic mule foals produced similar binding patterns in western immunoblots with donkey platelet proteins separated on sodium dodecyl sulfate polyacrylamide gels. Maximal platelet aggregation and relative slope of aggregation in response to collagen were significantly inhibited after incubation with sera from thrombocytopenic mule foals. These results suggest that mule foals with induced alloimmune thrombocytopenia have serum antibodies that bind to platelets and may compete with collagen binding sites to impair platelet aggregation. PMID:10587252

  12. Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27 antibody.

    PubMed

    Thude, H; Schorner, U; Helfricht, C; Loth, M; Maak, B; Barz, D

    2006-04-01

    Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens presented on foetal platelets cause their immune destruction. Whether human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a patient was described who suffered from a NAIT caused by an HLA-B27 antibody. Sera from the mother and the newborn were tested for human platelet antigen antibodies and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies against cluster designation (CD)109 and platelet glycoproteins of the father were found in patient's and mother's serum. However, HLA ELISA was used to identify HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing results showed that the father descended HLA-B27 antigen on patient and his brother. The mother was HLA-B27 negative. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-B27 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented. PMID:16623921

  13. Neonatal alloimmune thrombocytopenia in the Irish population: a discrepancy between observed and expected cases

    PubMed Central

    Davoren, A; McParland, P; Barnes, C A; Murphy, W G

    2002-01-01

    Aims: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present. Methods: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus™), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers. Results: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed. Conclusions: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered. PMID:11919215

  14. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  15. [PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in Polish foetuses and newborns--the PREVFNAIT program].

    PubMed

    Uhrynowska, Małgorzata Ewa; Dębska, Marzena; Guz, Katarzyna; Orzińska, Agnieszka; Wróbel, Agnieszka; Maślanka, Krystyna; Dębski, Romuald; Brojer, Ewa

    2015-01-01

    The scientific goals related to the grant include 1) estimation of FNAIT prevalence in Poland and 2) search for biomarkers to predict the risk of the antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood platelets due to maternal antibodies. This condition, which most commonly results from incompatibility between the mother and the fetus for the Human Platelet Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central nervous system (CNS) and even death of the fetus or the newborn. It can be the cause of strokes in term newborns. FNAIT is usually attributed to the presence of anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000-2000 live births. In the absence of a screening program, it is usually diagnosed after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage. Monitoring of antibody production and thrombocytopenia treatment to effectively minimize the risk of stroke are therefore launched only at the next pregnancy. Testing indications are broader to include fetal ultrasound for symptoms of stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric failure. Diagnostic process is also recommended prior to the planned cordocentesis, in vitro fertilization and in sisters of mothers with children with FNAIT history. HPA-1a testing remains the best method for diagnosing pregnancies at risk. The detection frequency for FNAIT in Poland remains low. Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have performed such HPA-1a antigen testing in 30 000 Polish women within the framework of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the population) are a risk group for production of anti- HPA-1a antibodies responsible for FNAIT therefore all of them will be monitored for the presence and activity of anti-HPA-1a antibodies. Such testing will be

  16. Maternal alloimmunization against the rare platelet-specific antigen HPA-9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia

    PubMed Central

    Peterson, Julie A.; Balthazor, Stephanie M.; Curtis, Brian R.; McFarland, Janice G.; Aster, Richard H.

    2006-01-01

    BACKGROUND Neonatal alloimmune thrombocytopenia (NATP) is an important cause of morbidity and mortality in the newborn. Optimal management of subsequent pregnancies requires knowledge of the alloantigen that caused maternal immunization, but this is possible only in a minority of cases. This study investigated whether this can be explained in part by maternal immunization against the “rare” alloantigen HPA-9b (Maxa), implicated previously only in a single NATP case. STUDY DESIGN AND METHODS Archived paternal DNA from unresolved cases of NATP and normal individuals was typed for platelet (PLT)-specific antigens with real-time polymerase chain reaction and direct sequencing. PLT-specific alloantibodies were characterized by flow cytometry and solid-phase enzyme-linked immunosorbent assay. Recombinant GPIIb/IIIa was expressed in stably transfected Chinese hamster ovary cells. Clinical information was obtained directly from attending physicians. RESULTS Six of 217 fathers were positive for the presence of HPA-9b (Maxa), an incidence about seven times that in the general population. In each of five cases studied, maternal serum samples reacted with intact paternal PLTs and paternal GPIIb/IIIa. Only one of three serum samples tested recognized recombinant GPIIb/IIIa carrying the HPA-9b (Maxa) mutation. These seemingly discrepant reactions may reflect different requirements for oligosaccharides linked to residues close to the mutation in GPIIb that determines HPA-9b (Maxa). NATP in the affected children was severe and was associated with intracranial hemorrhage in three of six infants on whom information was obtained. CONCLUSIONS Maternal immunization against HPA-9b (Maxa) is an important cause of NATP and should be considered in cases of apparent NATP not resolved on the basis of maternal-fetal incompatibility for “common” PLT antigens. PMID:16131382

  17. Anti-Human Platelet Antigen-1a Immunoglobulin G Preparation Intended to Prevent Fetal and Neonatal Alloimmune Thrombocytopenia.

    PubMed

    Weng, Ying-Jan; Husebekk, Anne; Skogen, Björn; Kjaer, Mette; Lin, Liang-Tzung; Burnouf, Thierry

    2016-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a severe disease that is caused by maternal alloantibodies generated during pregnancy or at delivery as a result of incompatibility between maternal and fetal human platelet antigens (HPAs) inherited from the father. Antibody-mediated immune suppression using anti-HPA-1a immunoglobulins is thought to be able to prevent FNAIT caused by HPA-1a. A fractionation process to prepare anti-HPA-1a immunoglobulin (Ig) G (IgG) from human plasma was therefore developed. Anti-HPA-1a plasma was obtained from volunteer mothers who underwent alloimmunization against HPA-1a during a previous pregnancy. Plasma was cryoprecipitated and the supernatant treated with caprylic acid and solvent/detergent (S/D), purified by chromatography, nanofiltered, concentrated, and sterile-filtered. The anti-HPA-1a immunoglobulin fraction was characterized for purity and safety. PAK12 and quantitative monoclonal antibody immobilization of platelet antigen (MAIPA) assays were used to detect anti-HPA-1a IgG. Hepatitis C virus (HCV) removal during nanofiltration was assessed by spiking experiments, using cell culture-derived reporter HCV and luciferase analysis. The caprylic acid treatment precipitated non-Ig proteins yielding a 90% pure Ig supernatant. S-HyperCel chromatography of the S/D-treated supernatant followed by HyperCel STAR AX provided high IgG recovery (>80%) and purity (>99.5%), and efficient IgA and IgM removal. Concentrations of complement factors C3 and C4 were < 0.5 and < 0.4 mg/dL, respectively. The final IgG could be nanofiltered on Planova 20N under conditions removing more than 3 log HCV infectivity to baseline mock infection level, and concentrated to ca. 30 g/L. Proteolytic activity and thrombin generation were low in the final fraction. The Pak12 and MAIPA assays showed good recovery of anti-HPA-1a throughout the process. Clinical-grade HPA-1a IgG can be prepared using a process compliant with current quality requirements

  18. The Development of Severe Neonatal Alloimmune Thrombocytopenia due to Anti-HPA-1a Antibodies Is Correlated to Maternal ABO Genotypes

    PubMed Central

    Ahlen, Maria Therese; Husebekk, Anne; Killie, Mette Kjær; Kjeldsen-Kragh, Jens; Olsson, Martin L.; Skogen, Bjørn

    2012-01-01

    Background. Maternal alloantibodies against HPA-1a can cross placenta, opsonize foetal platelets, and induce neonatal alloimmune thrombocytopenia (NAIT). In a study of 100, 448 pregnant women in Norway during 1995–2004, 10.6% of HPA-1a negative women had detectable anti-HPA-1a antibodies. Design and Methods. A possible correlation between the maternal ABO blood group phenotype, or underlying genotype, and severe thrombocytopenia in the newborn was investigated. Results. We observed that immunized women with blood group O had a lower risk of having a child with severe NAIT than women with group A; 20% with blood group O gave birth to children with severe NAIT, compared to 47% among the blood group A mothers (relative risk 0.43; 95% CI 0.25–0.75). Conclusion. The risk of severe neonatal alloimmune thrombocytopenia due to anti-HPA-1a antibodies is correlated to maternal ABO types, and this study indicates that the observation is due to genetic properties on the maternal side. PMID:22110529

  19. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    PubMed

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b. PMID:24763012

  20. Fetal intracranial haemorrhages caused by fetal and neonatal alloimmune thrombocytopenia: an observational cohort study of 43 cases from an international multicentre registry

    PubMed Central

    Tiller, Heidi; Kamphuis, Marije M; Flodmark, Olof; Papadogiannakis, Nikos; David, Anna L; Sainio, Susanna; Koskinen, Sinikka; Javela, Kaija; Wikman, Agneta Taune; Kekomaki, Riitta; Kanhai, Humphrey H H; Oepkes, Dick; Husebekk, Anne; Westgren, Magnus

    2013-01-01

    Objective To characterise pregnancies where the fetus or neonate was diagnosed with fetal and neonatal alloimmune thrombocytopenia (FNAIT) and suffered from intracranial haemorrhage (ICH), with special focus on time of bleeding onset. Design Observational cohort study of all recorded cases of ICH caused by FNAIT from the international No IntraCranial Haemorrhage (NOICH) registry during the period 2001–2010. Setting 13 tertiary referral centres from nine countries across the world. Participants 37 mothers and 43 children of FNAIT pregnancies complicated by fetal or neonatal ICH identified from the NOICH registry was included if FNAIT diagnosis and ICH was confirmed. Primary and secondary outcome measures Gestational age at onset of ICH, type of ICH and clinical outcome of ICH were the primary outcome measures. General maternal and neonatal characteristics of pregnancies complicated by fetal/neonatal ICH were secondary outcome measures. Results From a total of 592 FNAIT cases in the registry, 43 confirmed cases of ICH due to FNAIT were included in the study. The majority of bleedings (23/43, 54%) occurred before 28 gestational weeks and often affected the first born child (27/43, 63%). One-third (35%) of the children died within 4 days after delivery. 23 (53%) children survived with severe neurological disabilities and only 5 (12%) were alive and well at time of discharge. Antenatal treatment was not given in most (91%) cases of fetal/neonatal ICH. Conclusions ICH caused by FNAIT often occurs during second trimester and the clinical outcome is poor. In order to prevent ICH caused by FNAIT, at-risk pregnancies must be identified and prevention and/or interventions should start early in the second trimester. PMID:23524102

  1. Foetal and neonatal alloimmune thrombocytopaenia

    PubMed Central

    Kaplan, Cecile

    2006-01-01

    Foetal/neonatal alloimmune thrombocytopaenia (NAIT) results from maternal alloimmunisation against foetal platelet antigens inherited from the father and different from those present in the mother, and usually presents as a severe isolated thrombocytopaenia in otherwise healthy newborns. The incidence has been estimated at 1/800 to 1/1 000 live births. NAIT has been considered to be the platelet counterpart of Rh Haemolytic Disease of the Newborn (RHD). Unlike RHD, NAIT can occur during a first pregnancy. The spectrum of the disease may range from sub-clinical moderate thrombocytopaenia to life-threatening bleeding in the neonatal period. Mildly affected infants may be asymptomatic. In those with severe thrombocytopaenia, the most common presentations are petechiae, purpura or cephalohaematoma at birth, associated with major risk of intracranial haemorrhage (up to 20% of reported cases), which leads to death or neurological sequelae. Alloimmune thrombocytopaenia is more often unexpected and is usually diagnosed after birth. Once suspected, the diagnosis is confirmed by demonstration of maternal antiplatelet alloantibodies directed against a paternal antigen inherited by the foetus/neonate. Post-natal management involves transfusion of platelets devoid of this antigen, and should not be delayed by biological confirmation of the diagnosis (once the diagnosis is suspected), especially in case of severe thrombocytopaenia. Prompt diagnosis and treatment are essential to reduce the chances of death and disability due to haemorrhage. Due to the high rate of recurrence and increased severity of the foetal thrombocytopaenia in successive pregnancies, antenatal therapy should be offered. However, management of high-risk pregnancies is still a matter of discussion. PMID:17032445

  2. A severe case of intracranial hemorrhage due to alloimmune thrombocytopenia.

    PubMed

    Cota, Francesco; Zuppa, Antonio Alberto; Luciano, Rita; Gallini, Francesca; Savarese, Immacolata; Alighieri, Giovanni; Orchi, Claudia; Romagnoli, Costantino

    2008-11-01

    Alloimmune thrombocytopenia (AIT) is an important cause of intrauterine hemorrhagic lesions that result from platelet-antigen incompatibility between mother and foetus. Foetal platelets are destroyed by cross-reactive maternal antibodies that cross the placenta. The most serious complication of AIT is foetal intracranial bleeding that may eventually result in intrauterine death or severe neurological impairments. PMID:19031280

  3. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping

    PubMed Central

    Hayashi, Tomoya; Hirayama, Fumiya

    2015-01-01

    Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia. PMID:26057488

  4. [Fetal and neonatal immune thrombocytopenias. Study group "Mother-child immune thrombopenias"].

    PubMed

    Kaplan, C; Morel-Kopp, M C; Verdy, E; Pron, B; Tchernia, G

    1992-10-31

    Neonatal thrombocytopenia has benefited from the advances achieved during the last few years in platelet immunology and foetal therapy. The major risk of the disease is cerebral haemorrhage resulting in death or neurological sequelae. Establishing the aetiological diagnosis of immune thrombocytopenia makes it possible nowadays to apply the appropriate treatment and eventually to take care of future pregnancies. Treatments in utero of foeto-maternal alloimmunization have radically altered the natural course of foetal thrombocytopenia, thereby permitting the management of pregnancies at risk. On the other hand, so far no prenatal treatment has proved to be effective against thrombocytopenia due to maternal autoimmunity. PMID:1480577

  5. A rare manifestation of neonatal alloimmune thrombocytopaenia

    PubMed Central

    Jerónimo, Monica; Azenha, Cátia; Mesquita, Joana; Pereira, Dolores Faria

    2014-01-01

    Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×109/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24–72 h of life. PMID:24891486

  6. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia.

    PubMed

    Sonneveld, Myrthe E; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A M; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-07-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable correlation with severity, making screening for FNAIT impractical and highly inefficient. We recently found IgG Fc-glycosylation towards platelet and red blood cell antigens to be skewed towards decreased fucosylation, increased galactosylation and sialylation. The lowered core-fucosylation increases the affinity of the pathogenic antibodies to FcγRIIIa and FcγRIIIb, and hence platelet destruction. Here we analysed the N-linked glycans of human platelet antigen (HPA)-1a specific IgG1 with mass spectrometry in large series of FNAIT cases (n = 166) including longitudinal samples (n = 26). Besides a significant decrease in Fc-fucosylation after the first pregnancy (P = 0·0124), Fc-glycosylation levels remained stable during and after pregnancy and in subsequent pregnancies. Multiple logistic regression analysis identified anti-HPA-1a -fucosylation (P = 0·006) combined with galactosylation (P = 0·021) and antibody level (P = 0·038) correlated with bleeding severity, making these parameters a feasible marker in screening for severe cases of FNAIT. PMID:27017954

  7. Feto-maternal alloimmune thrombocytopenia: a literature review and statistical analysis.

    PubMed

    Spencer, J A; Burrows, R F

    2001-02-01

    Exploring prognostic factors that determine outcomes in fetomaternal alloimmune thrombocytopenia (FMAIT), a search of Medline was performed covering the years 1966 to April 1998. 376 articles were collected and reviewed; 140 articles contained the case histories of 297 mothers and 433 pregnancies that fulfilled entry criteria. More than 30 data variables were sought from these cases. The data were analysed using SPSS and Arcus Quickstat Biomedical. Nineteen different antigen incompatibilities were documented, the majority being human platelet antigen (HPA)-1a (77.3%), HPA-3a (3.5%) and HPA-5b (3.5%). The relative risk reduction (RRR) in mortality with any intervention was 57% (0.19-0.77) p = 0.009. Treatment of HPA-1a (PlA1) pregnancies with intravenous immunoglobulin (IVIG) increased the likelihood of a neurologically normal outcome, relative risk (RR) 1.68, confidence interval (1.3-2.2) p = 0.0003. Treatment of HPA-1a (PlA1) pregnancies with only antenatal complementary platelet transfusions increased the likelihood of a neurologically normal outcome, RR 1.63 (1.1-2.1) p = 0.01. Despite reviews of more than 400 cases of FMAIT, few prognostic variables are identifiable. Although IVIG appears to reduce the risk of intracranial haemorrhage (ICH), the dosage and timing of IVIG treatment was varied. This study highlights the need for standardised and directed research. PMID:11284646

  8. Neonatal Thrombocytopenia as a Consequence of Maternal Preeclampsia

    PubMed Central

    Kalagiri, Ram R.; Choudhury, Saiara; Carder, Timothy; Govande, Vinayak; Beeram, Madhava R.; Uddin, M Nasir

    2015-01-01

    Introduction Preeclampsia (preE) is pregnancy-induced hypertension affecting a significant proportion of pregnant women worldwide and can cause detrimental effects in the mother and newborn. Some of the effects in the newborn include neonatal thrombocytopenia. Pertaining specifically to neonatal thrombocytopenia, several questions remain unanswered. Discussion According to the current literature, neonatal thrombocytopenia due to maternal preE is highly prevalent in the general population and the incidence is reported to be around 30% worldwide. This review gives an insight into the syndrome and summarizes the possible pathological mechanisms, the diagnostic approach, complications, and therapeutic interventions of neonatal thrombocytopenia. It also identifies the involvement of other cell lines, apart from platelets in the newborns. Furthermore, we suggest a future prospective study to investigate the pathogenesis of preE and plan a study involving animal models to come up with a possible therapeutic intervention to prevent preE and its various consequences in neonates. PMID:26929869

  9. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers

    PubMed Central

    Herbert, Nina; Hawkins, Louise; Grehan, Nicola; Cookson, Philip; Garner, Steve F.; Crisp-Hihn, Abigail; Lloyd-Evans, Paul; Evans, Amanda; Balan, Kottekkattu; Ouwehand, Willem H.; Armour, Kathryn L.; Clark, Mike R.; Williamson, Lorna M.

    2013-01-01

    Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcγ receptors. In vitro studies with a range of clinical anti–HPA-1a sera have shown that B2G1Δnab blocks monocyte chemiluminescence by >75%. In this first-in-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Δnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Δnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Δnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a–negative mothers. PMID:23656729

  10. Neonatal liver failure owing to gestational alloimmune liver disease without iron overload.

    PubMed

    Tsunoda, Tomoyuki; Inui, Ayano; Kawamoto, Manari; Sogo, Tsuyoshi; Komatsu, Haruki; Kasahara, Mureo; Nakazawa, Atsuko; Fujisawa, Tomoo

    2015-05-01

    Although neonatal hemochromatosis (NH) is a well-known cause of liver failure during the neonatal period and iron deposition in extrahepatic tissues is considered essential in the diagnosis of NH, there is no consensus regarding the pathology or diagnostic criteria of NH. Recent studies of immunohistochemical assays have shown that the C5b-9 complex (the terminal membrane attack complement complex) is strongly expressed in the liver of NH cases, suggesting that a gestational alloimmune mechanism is the cause of liver injury. The patient was a low birthweight primiparous male born at 37 weeks of gestation by vaginal delivery. Blood tests 3 h after birth showed signs of liver failure, including high transferrin saturation, resembling the clinical characteristics of NH. However, magnetic resonance imaging and a lip biopsy showed no obvious iron deposition outside the liver. The patient was refractory to exchange transfusion and immunoglobulin therapy but was successfully treated by liver transplantation. Histologically, the explanted liver showed established cirrhosis, with large amounts of human C5b-9 in the residual hepatocytes, suggesting the alloimmune mechanism of liver injury was the cause of his liver failure. Liver failure caused by a gestational alloimmune mechanism should be considered in patients with antenatal liver failure, even without obvious extrahepatic siderosis. PMID:24976253

  11. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study.

    PubMed

    Fustolo-Gunnink, S F; Vlug, R D; Smits-Wintjens, V E H J; Heckman, E J; Te Pas, A B; Fijnvandraat, K; Lopriore, E

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  12. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study

    PubMed Central

    Vlug, R. D.; Smits-Wintjens, V. E. H. J.; Heckman, E. J.; te Pas, A. B.; Fijnvandraat, K.; Lopriore, E.

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  13. Thrombocytopenia

    MedlinePlus

    ... NHLBI on Twitter. What Is Thrombocytopenia? Thrombocytopenia (THROM-bo-si-to-PE-ne-ah) is a condition ... is damaged. Platelets also are called thrombocytes (THROM-bo-sites) because a clot also is called a ...

  14. Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

    PubMed Central

    Ghevaert, Cedric; Wilcox, David A.; Fang, Juan; Armour, Kathryn L.; Clark, Mike R.; Ouwehand, Willem H.; Williamson, Lorna M.

    2008-01-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a–specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a–specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor–dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a+ platelets and substantially inhibited binding of clinical HPA-1a–specific sera to HPA-1a+ platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a–specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a–specific sera reduced circulating HPA-1a+ platelets, concomitant with transient thrombocytopenia. As the Δnab constant region is uninformative in mice, F(ab′)2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a–specific antibodies. These results provide rationale for human clinical studies. PMID:18654666

  15. [Autoimmune-alloimmune neonatal neutropenia. Serum reactive IgG and neutrophil-specific phenotype detected by flow cytometry].

    PubMed

    Riera, Norma E; Kantor, Gustavo L; Khoury, Marina; Nucci, Rodrigo Parias; Rapetti, Maria Cristina; Aixala, Monica; Goldsztein, Sofia; Flores, Gabriela; de Bracco, Maria M de E

    2006-01-01

    Auto or alloantibodies reactive with neutrophils define immune neutropenia. Alloimmune neonatal neutropenia is caused by maternal sensitization to paternal neutrophil antigens, resulting in IgG antibodies that are transferred to the fetus through the placenta. We present the studies in 4 children from 3 families with neutropenia of unknown origin (two of them were brothers). They were evaluated by flow cytometry in parallel with leukoagglutination. Reference values were established for serum reactive IgG in healthy volunteers for three dilutions (1/2, 1/5 and 1/20), both for the autologous reaction (serum and cells of the same individual) and for the heterologous reaction (serum and cells of different individuals). Results were expressed by an index defined by the quotient of the mean fluorescence intensity of the patient's serum divided by that of the reference serum. Serum reactive/agglutinant factors and circulating immune complexes were evaluated in patients and parents serum. Neutrophil specific phenotypes were determined for HNA-1a, HNA-1b and HNA-2a. Reactive IgG/agglutinant factors were found in 4 children. Two maternal sera were reactive against paternal and/or children neutrophils. Circulating immune complexes were detected in 2/4 children sera and were negative in 3/3 maternal sera. Maternal/children incompatibility was detected in the four cases. The three mothers had the same phenotype: homozygous NA1/NA1, NB1+. PMID:17137169

  16. Isolated anti-Ro/SSA thrombocytopenia: a rare feature of neonatal lupus

    PubMed Central

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Boukhris, Mohamed Riadh; Bezzine, Ahlem; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    We report a rare case of isolated thrombocytopenia related to anti-Ro/SSA antibodies. The mother was followed for unlabeled familial thrombocytopenia. The mother had positive anti-Ro/SSA antibodies. She was asymptomatic without skin lesions or other criteria neither of systemic lupus erythematosus nor other connective tissue disease. Pregnancy was uneventful. The postnatal examination was normal. On the first day of life, blood cells count showed thrombocytopenia at 40 x 109/L. Within the second day of life, platelet level dropped to 20 x 109/L. The management of thrombocytopenia included platelet transfusion and human immunoglobulin infusion. On the fifth day of life, there has been a drop in platelet count to 10 x 109/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10th of life platelets rate was stable around 60 x 109/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up. PMID:26977221

  17. Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis.

    PubMed

    Meberg, A; Johansen, K B

    1998-12-01

    In a population-based study including 2463 infants, serum bilirubin measurements were added to the neonatal screening programme for phenylketonuria and congenital hypothyreosis. This screening programme detected 11/17 (65%) of infants with serum bilirubin levels >350 micromol 1(-1), of whom 7 (3 per 1000) were readmitted from home (6 treated with phototherapy). A total of 139 infants (5.6%) received phototherapy. Maternal blood type O occurred significantly more often in term infants treated (30/54; 55.6%) compared with preterm infants treated (32/85; 37.6%) and with blood type O occurrence in the total population of mothers (906/2426; 37.3%) (p < 0.05). The blood type constellations mother O/infant A or B showed a sensitivity of 64%, specificity 65%, positive predictive value 12% and a negative predictive value of 96% for the requirement of phototherapy for the whole material. Exchange transfusion was not required in any of the infants. No infant developed bilirubin encephalopathy (kemicterus). Adding bilirubin to a neonatal screening programme detects some cases with unexpectedly high bilirubin levels in need of intervention. Routine ABO blood typing of pregnant women, ABO cord blood typing and Coombs' test in infants of mothers with blood type O cannot be recommended because of low positive predictive value for the requirement of intervention (phototherapy) by these tests. PMID:9894828

  18. Thrombocytopenia in pregnancy.

    PubMed

    Palta, A; Dhiman, P

    2016-01-01

    Thrombocytopenia during pregnancy is quite common. Evaluation of blood counts of pregnant women has shown that thrombocytopenia is the second most common haematological problem in pregnancy, after anaemia. While mostly thrombocytopenia has no consequences for either the mother or the foetus, in some cases it is associated with substantial maternal and/or neonatal morbidity and mortality. It may result from a number of diverse aetiologies. Adequate knowledge of these causes will help the clinicians in making proper diagnosis and management of thrombocytopenia in pregnancy. The evaluation of thrombocytopenia is essential to rule out any systemic disorders that may affect pregnancy management as thrombocytopenia can present as an isolated finding or in combination with underlying conditions. In this concise review, we have provided the overview of thrombocytopenia diagnosed during pregnancy. PMID:26431056

  19. A de novo T73I mutation in PTPN11 in a neonate with severe and prolonged congenital thrombocytopenia and Noonan syndrome.

    PubMed

    Christensen, Robert D; Yaish, Hassan M; Leon, Eyby L; Sola-Visner, Martha C; Agrawal, Pankaj B

    2013-01-01

    We observed a neonate with severe congenital thrombocytopenia and features of Noonan syndrome where evaluations were negative for immune-mediated thrombocytopenia, congenital infections, and Fanconi anemia. The marrow findings and a significantly elevated plasma thrombopoietin (Tpo) level were consistent with congenital amegakaryocytic thrombocytopenia; we sought a genetic mutation that could explain this phenotype. No mutations were identified in c-MPL (the Tpo receptor gene). Microarray analysis of peripheral blood did not reveal an abnormality. DNA sequencing of the PTPN11 gene showed a heterozygous C>T nucleotide substitution in exon 3 (c.218C>T) predicted to result in a threonine-to-isoleucine change at residue 73 (T73I). A 6-week trial of eltrombopag (an agonist of the Tpo receptor) failed to increase the platelet count. We propose this specific PTPN11 mutation results in abnormalities of the protein product SHP-2, which, because of its role in signal transduction, results in severe congenital thrombocytopenia refractory to c-MPL agonists. PMID:23446178

  20. ACOG Practice Bulletin No. 75: Management of alloimmunization during pregnancy.

    PubMed

    2006-08-01

    When any fetal blood group factor inherited from the father is not possessed by the mother, antepartum or intrapartum fetal-maternal bleeding may stimulate an immune reaction in the mother Maternal immune reactions also can occur from blood product transfusion. The formation of maternal antibodies, or"alloimmunization,' may lead to various degrees of transplacental passage of these antibodies into the fetal circulation. Depending on the degree of antigenicity and the amount and type of antibodies involved, this transplacental passage may lead to hemolytic disease in the fetus and neonate. Undiagnosed and untreated, alloimmunization can lead to significant perinatal morbidity and mortality. Advances in Doppler ultrasonography have led to the development of noninvasive methods of management of alloimmunization in pregnant women. Together with more established protocols, Doppler ultrasound evaluation may allow for a more thorough and less invasive workup with fewer risks to the mother and fetus. Prevention of alloimmunization is addressed in another Practice Bulletin (1). PMID:16880320

  1. Alloimmunization due to red cell antibodies in Rhesus positive Omani Pregnant Women: Maternal and Perinatal outcome

    PubMed Central

    Al-Dughaishi, Tamima; Al-Rubkhi, Ikhlass S.; Al-Duhli, Maymoona; Al-Harrasi, Yusra; Gowri, Vaidyanathan

    2015-01-01

    Objective: This study is aimed to determine the prevalence of alloimmunization due to antibodies to red blood cell (RBC) antigens (other than rhesus [Rh] antigen) and report the maternal, perinatal, and neonatal outcomes. Materials and Methods: A retrospective review of medical records of all patients with minor RBCs antibodies alloimmunization who were followed and delivered at Sultan Qaboos University Hospital, Oman from June 2011 to June 2013. Maternal characteristics, antibody type, antibody titer in addition to perinatal and neonatal outcomes were reviewed. Results: There were 1160 patients with Rh positive status in the study. The most common ABO blood group was O, followed by A, B, and AB. We found 33 out of 1160 Rh positive women alloimmunized with minor RBCs antibodies that gave a prevalence of minor RBCs alloimmunization of 2.7%. The most frequent antibody was anti-E 38%, followed by anti-c 17% and anti-kell 17%. 6 of these 33 patients were identified to have significant antibody titer, and two cases showed evidence of fetal anemia. Only one case required an intrauterine blood transfusion. The most common neonatal complication was jaundice in 53%, followed by respiratory distress syndrome in 28%. Two cases complicated by neonatal anemia required a postnatal blood transfusion. Conclusion: Alloimmunization with anti-E, anti-c, and anti-kell were the most common antibodies among the study group. Minor RBCs alloimmunization was an important cause of neonatal morbidity. PMID:26420934

  2. [Management of feto-maternal red cell allo-immunizations].

    PubMed

    Bricca, P; Guinchard, E; Guitton Bliem, C

    2011-04-01

    Feto-maternal red cell alloimmunization is defined by the presence in a pregnant woman of alloantibodies directed against blood group antigens present on the red blood cells of the fetus and inherited from the father. It arises from the immune response to a first contact to these same antigens during a prior transfusion, transplant or pregnancy. The placental transfer and the fixation of the antibodies on the fetal red cells antigenic targets lead to a haemolysis in the fetus and the newborn. The resulting haemolytic disease can show different clinical forms, from a mild anaemia with neonatal hyperbilirubinemia to a major fetal damage with stillbirth caused by hydrops fetalis. The objective of management strategies of feto-maternal alloimmunization is to detect and monitor maternal alloimmunization and to appreciate the effects on the fetus or the newborn. Since a few years, some new non-invasive techniques of surveillance are used, for instance fetal RHD genotyping on maternal plasma and evaluation of fetal anaemia through velocimetry measurement of the blood flow in the middle cerebral artery. The need for a careful postnatal surveillance has to be emphasized due to the neonatal anaemia, which can be prolonged, and to the resurgence of cases of severe neonatal icteruses recently reported by the Académie de Médecine. The policy of prevention of anti-RH1 alloimmunization should also benefit from the evolution of biological techniques by allowing an improved targeting of concerned women. PMID:21397546

  3. Immune Thrombocytopenia in Pregnancy

    PubMed Central

    Stavrou, Evi; McCrae, Keith R.

    2009-01-01

    SYNOPSIS Management of ITP in pregnancy can be a complex and challenging task, and may be complicated by fetal/neonatal thrombocytopenia. Though fetal intracranial hemorrhage is a rare complication of ITP in pregnancy, invasive studies designed to determine the fetal platelet count before delivery are associated with greater risk than that of fetal intracranial hemorrhage, and therefore are discouraged. Moreover, the risk of neonatal bleeding complications does not correlate with the mode of delivery, and thus cesarean section should be reserved for obstetric indications only. PMID:19932435

  4. [Thrombocytopenia and pregnancy].

    PubMed

    Khellaf, M; Loustau, V; Bierling, P; Michel, M; Godeau, B

    2012-08-01

    The occurrence of thrombocytopenia during pregnancy is frequent (about 10%). Etiologies of thrombocytopenia are dominated by the gestational thrombocytopenia (>75%), which requires no exploration and no specific treatment; it usually occurs during the last trimester of pregnancy and corrects itself spontaneously after delivery. Other etiologies are: (1) immune thrombocytopenia (ITP) either primary or associated with other pathologies; ITP may appear early in the first trimester of pregnancy, (2) thrombotic microangiopathy syndromes, and (3) obstetric thrombocytopenia: eclampsia and HELLP syndrome (hemolysis elevated liver enzymes, and low platelet count). Treatment of pre-eclampsia and HELLP syndrome is based on resuscitative measures and symptomatic fetal extraction that will be discussed according to the term and severity of the case. The treatment of microangiopathy is based on resuscitation and plasma exchange. For ITP, no specific action is needed during pregnancy and only symptomatic patients with a platelet count less than 30×10(9)/L must receive a treatment. It is important to prepare the childbirth that can be vaginally except if there is an obstetric contraindication. A platelet count of 50×10(9)/L is required for the delivery, and of 75×10(9)/L in case of spinal anesthesia. Treatment implies a short course of corticosteroids associated with infusion of immunoglobulins in the most severe forms or in case of steroids resistance. There is a risk of neonatal thrombocytopenia requiring a control of the blood count for the baby at birth and within 5 days, newborns have to be treated if the platelet count is less than 20×10(9)/L. PMID:22742709

  5. Immune thrombocytopenia and pregnancy

    PubMed Central

    Sankaran, Srividhya; Robinson, Susan E

    2011-01-01

    Immune thrombocytopenia (ITP) is not infrequently encountered during reproductive years with an estimated incidence of 0.1–1 per 1000 pregnancies. An international consensus group recently re-defined ITP and outlined standardized response criteria and up-to-date investigation and management. The pathogenesis encompasses autoantibody platelet destruction and immune-mediated decreased platelet production. Maternal antibodies may cross the placenta and have the potential to cause fetal and/or neonatal thrombocytopenia. The diagnosis and subsequent management of ITP in pregnancy requires a multidisciplinary approach involving the midwife, obstetrician, haematologist and anaesthetist. Women with ITP diagnosed prior to pregnancy should receive preconception counselling to outline potential treatments and provide information regarding expected maternal and neonatal outcome. Management prior to 36 weeks aims to avoid treatment in the absence of bleeding and ensure an acceptable platelet count for planned procedures. At 34–36 weeks, women are generally reviewed to consider whether a tailored course of treatment is required in preparation for delivery. Further research is required to determine a suitable platelet count for neuraxial anaesthesia. The mode of delivery should be guided by obstetric indication. It is pertinent to consider both the risk of maternal bleeding and thrombosis in maternal ITP. The risk of neonatal intracranial haemorrhage in association with ITP is less than 1%. Postpartum a cord blood platelet count should be checked. Additional management is dependent upon the neonatal platelet count. Data collection using the new standardized terminology should provide robust comparable epidemiological data regarding ITP in pregnancy.

  6. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    SciTech Connect

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  7. 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

  8. Immune thrombocytopenia.

    PubMed

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. 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. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

  9. Immune-mediated thrombocytopenias: basic and immunological aspects.

    PubMed

    Porcelijn, L; von dem Borne, A E

    1998-06-01

    Acute idiopathic or autoimmune thrombocytopenic purpura (AITP) is a disorder found mainly in children, usually preceded by a viral infection, with a higher incidence in the autumn and winter. The platelet-specific autoantibodies in acute childhood AITP are more often of the IgM class. Chronic AITP occurs mostly in adults. The platelet immunofluorescence test (PIFT) detects platelet-specific autoantibodies with a sensitivity of 65-75%. The autoantibodies in chronic AITP are classified as IgG in 95%, IgM in 26% and IgA in 4% of cases. The antibodies are usually bound to platelets and are detectable as free circulating antibodies in about 40%. AITP in pregnancy may cause neonatal AITP by autoantibodies of the IgG class which pass the placenta barrier. The rare neonatal alloimmune thrombocytopenic purpura (NAITP) are caused by IgG alloantibodies against HPA-1a in 75-90%, HPA1b in 3-5%, HPA 3a in 4-5%, HPA5b in 6-19% and against private platelet antigens in 3%. To confirm the diagnosis of NAITP requires extensive serological testing of the child, and the parents have to be typed for the important platelet-specific antigens by PIFT, monoclonal antibody immobilisation of platelet antigens (MAIPA) and/or enzyme-linked immunosorbent assay (ELISA) techniques. Three mechanisms of drug-induced thrombocytopenias are described. Platelets of both the donor and the patient are destroyed in post-transfusion thrombocytopenic purpura (PTP) but PTP does not occur again if incompatible platelets are re-administered. PMID:10097811

  10. Immune thrombocytopenia.

    PubMed

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  11. Delayed cord clamping in red blood cell alloimmunization: safe, effective, and free?

    PubMed Central

    2016-01-01

    Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization. PMID:27186530

  12. Delayed cord clamping in red blood cell alloimmunization: safe, effective, and free?

    PubMed

    McAdams, Ryan M

    2016-04-01

    Hemolytic disease of the newborn (HDN), an alloimmune disorder due to maternal and fetal blood type incompatibility, is associated with fetal and neonatal complications related to red blood cell (RBC) hemolysis. After delivery, without placental clearance, neonatal hyperbilirubinemia may develop from ongoing maternal antibody-mediated RBC hemolysis. In cases refractory to intensive phototherapy treatment, exchange transfusions (ET) may be performed to prevent central nervous system damage by reducing circulating bilirubin levels and to replace antibody-coated red blood cells with antigen-negative RBCs. The risks and costs of treating HDN are significant, but appear to be decreased by delayed umbilical cord clamping at birth, a strategy that promotes placental transfusion to the newborn. Compared to immediate cord clamping (ICC), safe and beneficial short-term outcomes have been demonstrated in preterm and term neonates receiving delayed cord clamping (DCC), a practice that may potentially be effective in cases RBC alloimmunization. PMID:27186530

  13. Sairei-to therapy on alloimmune recurrent spontaneous abortions and alloimmune-, autoimmune complicated recurrent spontaneous abortions.

    PubMed

    Kano, Takashi; Shimizu, Masahiko; Kanda, Takayoshi; Hijikata, Yasuyo

    2010-01-01

    Alloimmune recurrent spontaneous abortion (RSA) cases that could not be treated with lymphocyte transfusion due to medical and social reasons were treated with Sairei-to therapy as an emergency measure and all four cases resulted in live births. This may show that Sairei-to treatment is effective in preventing alloimmune RSA. The efficacy of Sojyutsu-Sairei-to and Byakujyutsu-Sairei-to on autoimmune RSA has already been proven. When they were used in the treatment of alloimmune-, autoimmune complicated RSA, the abortion prevention rates were 65.4% and 82.3% respectively. These results indicate that Sairei-to is effective in the treatment of alloimmune RSA and alloimmune-, autoimmune complicated RSA. PMID:20626056

  14. Red Cell Alloimmunization to Rhesus Antigen Among Pregnant Women Attending a Tertiary Care Hospital in Oman

    PubMed Central

    Al-Dughaishi, Tamima; Al Harrasi, Yusra; Al-Duhli, Maymoona; Al-Rubkhi, Ikhlass; Al-Riyami, Nihal; Al-Riyami, Arwa Z.; Pathare, Anil V.; Gowri, Vaidyanathan

    2016-01-01

    Objectives The detection of maternal alloimmunization against red cell antigens is vital in the management of hemolytic disease of the fetus and newborn. We sought to measure the presence of allosensitization to Rhesus D (RhD) antibodies in antenatal women attending a tertiary care hospital and assess the fetal outcome in sensitized women. 
Methods: We conducted a retrospective review of pregnant Omani women who registered at the Sultan Qaboos University Hospital between June 2011 and June 2013. Pregnant women were tested for ABO blood type and were screened for RhD antigen and antibodies at their first antenatal clinic visit. In women who tested positive for the RhD antibodies, an antibody titer was performed to evaluate the severity of their case. Results Data was available on 1,251 pregnant women who were managed and delivered at Sultan Qaboos University Hospital. The prevalence of RhD negative pregnant women was 7.3%. Blood group O was the most common followed by A, B, and AB. The rate of RhD negative alloimmunization was 10%, and anti-D was the most common antibody detected. There were no stillbirths or neonatal deaths. Postnatal transfusion was necessary for only one baby. Conclusions The prevalence of RhD negativity was comparable to other Asian countries. Previous RhD alloimmunization and history of miscarriages were the most common maternal medical history. PMID:26813962

  15. Hyperthyroidism and immune thrombocytopenia.

    PubMed Central

    Jacobs, P.; Majoos, F.; Perrotta, A.

    1984-01-01

    Hyperthyroidism and immune thrombocytopenia occurred concurrently in five patients; in a sixth, thyrotoxicosis developed after successful treatment of the thrombocytopenia. Correction of the hyperthyroidism was followed by a variable pattern of clinical response. In one case with mild asymptomatic thrombocytopenia spontaneous complete remission occurred. Two patients required adrenocorticosteroids to control severe thrombocytopenic purpura during the period of hyperthyroidism, after which complete remission occurred. Another patient with severe symptomatic thrombocytopenia remains with a partially compensated thrombocytolytic state but is without purpura and off all therapy. A fifth patient required splenectomy for drug-resistant thrombocytopenia and remains critically dependent on immunosuppressive therapy. The sixth patient had a relapse of immune thrombocytopenia with subsequent development of thyrotoxicosis but platelet count spontaneously returned to normal after correction of the hyperthyroidism. Pregnancy in two of these six patients was not associated with recurrence of either hyperthyroidism or thrombocytopenia. Management of symptomatic purpura in adults with co-existent hyperthyroidism may differ from that customarily employed since adrenocorticosteroid therapy may need to be extended until euthyroidism has been established before proceeding to splenectomy. When surgery is necessary, the risk of thyrotoxic storm should be anticipated, and the patient appropriately premedicated. PMID:6494085

  16. Management of thrombocytopenia

    PubMed Central

    Bussel, James B.

    2014-01-01

    Thrombocytopenia is one of the most common hematologic disorders, characterized by an abnormally low number of platelets from multiple causes. The normal count of thrombocytes (platelets) is between 150,000 and 450,000 per microliter. The clinical expression of thrombocytopenia has broad variation from asymptomatic to life-threatening bleeding. Various syndromes and diseases are associated with thrombocytopenia. Thrombocytopenia is sometimes a first sign of hematologic malignancies, infectious diseases, thrombotic microangiopathies, and autoimmune disorders, and is also a common side effect of many medications. There are more than 200 diseases that include low number of platelets among their symptoms. A brief discussion of the most common etiologies and management of them is provided in this review. PMID:24991422

  17. Living with Immune Thrombocytopenia

    MedlinePlus

    ... Trials Links Related Topics Blood Tests Blood Transfusion Bone Marrow Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link ... possible effects of the treatment on the unborn baby. Women who have mild cases of ITP usually can ...

  18. Thrombocytopenia - drug induced

    MedlinePlus

    ... and a seizure medicine called valproic acid may lead to this problem. Other medicines that cause drug-induced thrombocytopenia include: Furosemide Gold, used to treat arthritis Nonsteroidal anti-inflammatory drugs ( ...

  19. What Causes Thrombocytopenia?

    MedlinePlus

    ... Transfusion Disseminated Intravascular Coagulation Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... low platelet count. Two examples are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). TTP is ...

  20. Alloimmunity and Tolerance in Corneal Transplantation.

    PubMed

    Amouzegar, Afsaneh; Chauhan, Sunil K; Dana, Reza

    2016-05-15

    Corneal transplantation is one of the most prevalent and successful forms of solid tissue transplantation. Despite favorable outcomes, immune-mediated graft rejection remains the major cause of corneal allograft failure. Although low-risk graft recipients with uninflamed graft beds enjoy a success rate ∼90%, the rejection rates in inflamed graft beds or high-risk recipients often exceed 50%, despite maximal immune suppression. In this review, we discuss the critical facets of corneal alloimmunity, including immune and angiogenic privilege, mechanisms of allosensitization, cellular and molecular mediators of graft rejection, and allotolerance induction. PMID:27183635

  1. Modulation of Alloimmunity by Heat Shock Proteins

    PubMed Central

    Borges, Thiago J.; Lang, Benjamin J.; Lopes, Rafael L.; Bonorino, Cristina

    2016-01-01

    The immunological mechanisms that evolved for host defense against pathogens and injury are also responsible for transplant rejection. Host rejection of foreign tissue was originally thought to be mediated mainly by T cell recognition of foreign MHC alleles. Management of solid organ transplant rejection has thus focused mainly on inhibition of T cell function and matching MHC alleles between donor and host. Recently, however, it has been demonstrated that the magnitude of the initial innate immune responses upon transplantation has a decisive impact on rejection. The exact mechanisms underlying this phenomenon have yet to be characterized. Ischemic cell death and inflammation that occur upon transplantation are synonymous with extracellular release of various heat shock proteins (Hsps), many of which have been shown to have immune-modulatory properties. Here, we review the impact of Hsps upon alloimmunity and discuss the potential use of Hsps as accessory agents to improve solid organ transplant outcomes. PMID:27555846

  2. Responder individuality in red blood cell alloimmunization.

    PubMed

    Körmöczi, Günther F; Mayr, Wolfgang R

    2014-11-01

    Many different factors influence the propensity of transfusion recipients and pregnant women to form red blood cell alloantibodies (RBCA). RBCA may cause hemolytic transfusion reactions, hemolytic disease of the fetus and newborn and may be a complication in transplantation medicine. Antigenic differences between responder and foreign erythrocytes may lead to such an immune answer, in part with suspected specific HLA class II associations. Biochemical and conformational characteristics of red blood cell (RBC) antigens, their dose (number of transfusions and pregnancies, absolute number of antigens per RBC) and the mode of exposure impact on RBCA rates. In addition, individual circumstances determine the risk to form RBCA. Responder individuality in terms of age, sex, severity of underlying disease, disease- or therapy-induced immunosuppression and inflammation are discussed with respect to influencing RBC alloimmunization. For particular high-risk patients, extended phenotype matching of transfusion and recipient efficiently decreases RBCA induction and associated clinical risks. PMID:25670932

  3. Cyclosporin for treatment of life-threatening alloimmunization.

    PubMed

    Tilly, H; Azagury, M; Bastit, D; Lallemand, A; Piguet, H

    1990-05-01

    We describe a 16-year-old girl with aplastic anemia who, 1 year after initial diagnosis developed a refractory state to platelet transfusions due to alloimmunization and resulting in severe bleeding. Treatment with cyclosporin, initially prescribed as treatment of the bone marrow failure, resulted in prompt decrease in lymphocytotoxic antibodies, which paralleled a marked improvement in platelet recovery. To our knowledge, such a dramatic effect of cyclosporin on alloimmunization has not been previously reported and merits further attention. PMID:2327409

  4. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization. PMID:27605851

  5. Thrombocytopenia in Systemic Lupus Erythematosus

    PubMed Central

    Jung, Jin-Hee; Soh, Moon-Seung; Ahn, Young-Hwan; Um, Yoo-Jin; Jung, Ju-Yang; Suh, Chang-Hee; Kim, Hyoun-Ah

    2016-01-01

    Abstract The aim of the study was to examine the clinical characteristics and prognosis according to severity of thrombocytopenia and response to treatment for thrombocytopenia in patients with systemic lupus erythematosus (SLE). We retrospectively evaluated 230 SLE patients with thrombocytopenia, and reviewed their clinical data and laboratory findings. Thrombocytopenia was defined as platelet counts under 100,000/mm3, and patients were divided into 3 thrombocytopenia groups according to severity: mild (platelet counts >50,000/mm3), moderate (>20,000/mm3, ≤50,000/mm3), and severe (≤20,000/mm3). Clinical characteristics, treatments, and prognoses were compared among the groups. Furthermore, complete remission of thrombocytopenia was defined as platelet counts >100,000/mm3 after treatment. There was no significant difference in clinical or laboratory findings among the groups according to severity of thrombocytopenia. However, hemorrhagic complications were more frequent in severe thrombocytopenia (P < 0.001) and mortality was also higher (P = 0.001). Complete remission was achieved in 85.2% of patients. The clinical characteristics and modality of treatment did not differ between the patients with and without complete remission. Mortality in patients with complete remission (1.5%) was significantly lower than in those without complete remission (29.4%, P < 0.001). Survival was significantly higher in patients with complete remission from thrombocytopenia (odds ratio = 0.049, 95% confidence interval: 0.013–0.191, P < 0.001). The severity of thrombocytopenia in SLE patients can be a useful independent prognostic factor to predict survival. Moreover, complete remission of thrombocytopenia after treatment is an important prognostic factor. The severity of thrombocytopenia and response to treatment should be closely monitored to predict prognosis in SLE patients. PMID:26871854

  6. Neonatal hemochromatosis in monochorionic twins.

    PubMed

    Korkmaz, L; Baştuğ, O; Daar, G; Doğanay, S; Deniz, K; Kurtoğlu, S

    2015-01-01

    Neonatal hemochromatosis (NH) is a form of neonatal liver failure caused by maternal-fetal alloimmune injury to hepatocytes. The etiology of neonatal hemochromatosis is not exactly understood. However, according to one theory neonatal hemochromatosis is believed to be an alloimmune disorder causing liver injury in the fetus. In order to diagnose neonatal hemochromatosis there are some criteria that should be taken into account, such as positive family history, high serum ferritin levels, high serum alpha-fetoprotein levels and siderosis demonstrated by histology or with magnetic resonance.We present a case of a monochorionic newborn twin who applied to our hospital with sepsis clinical symptoms like clinics, was diagnosed with NH and immediately treated with antioxidant therapy while the other twin with same clinical symptoms did not respond to therapy and passed away. NH should be considered in the differential diagnosis of cases with sepsis-like clinical symptoms that do not respond to antibiotics; early antioxidant therapy in these cases is lifesaving. PMID:26836824

  7. Genetics Home Reference: immune thrombocytopenia

    MedlinePlus

    ... develop frequent bruising or red or purple spots (purpura) on the skin caused by bleeding just under ... of immune thrombocytopenia: Genetic Testing Registry: Idiopathic thrombocytopenic purpura Johns Hopkins Medicine MedlinePlus Encyclopedia: Idiopathic Thrombocytopenic Purpura ( ...

  8. How Is Immune Thrombocytopenia Treated?

    MedlinePlus

    ... Blood Transfusion Bone Marrow Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... who have bleeding symptoms, other than merely bruising (purpura), usually are treated. Children who have mild ITP ...

  9. [Etiology and treatment of thrombocytopenia].

    PubMed

    Bargetzi, M J

    2004-02-01

    Thrombocytopenia has many causes. History, clinical examination of the patient, and a careful analysis of the peripheral blood smear may already lead to the etiology of cytopenia. The aim of the treatment is the correction of the underlying disease. In the management of immune thrombocytopenic purpura, the most common form of thrombocytopenia in adults, the goal is to avoid hemorrhages and not to increase the platelet value to normal. PMID:15018402

  10. Juvenile Myelomonocytic Leukemia in a Premature Neonate Mimicking Neonatal Sepsis.

    PubMed

    Lee, Ming-Luen; Yen, Hsiu-Ju; Chen, Shu-Jen; Hung, Giun-Yi; Tsao, Pei-Chen; Soong, Wen-Jue

    2016-04-01

    Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in children. Its presentations include anemia, thrombocytopenia, monocytosis, skin rash, marked hepatomegaly, and/or splenomegaly. Fever and respiratory involvement are common. Here, we report a case of a premature neonate with initial symptoms of respiratory distress. She gradually developed clinical manifestations of JMML that mimicked neonatal sepsis. Three weeks after birth, JMML was diagnosed. This is the first reported case of JMML presenting in a premature infant in Taiwan. PMID:24269860

  11. Pathobiology of secondary immune thrombocytopenia

    PubMed Central

    Cines, Douglas B.; Liebman, Howard; Stasi, Roberto

    2009-01-01

    Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management. PMID:19245930

  12. Heparin-induced thrombocytopenia.

    PubMed

    Brieger, D B; Mak, K H; Kottke-Marchant, K; Topol, E J

    1998-06-01

    Heparin-induced thrombocytopenia (HIT) is a potentially serious complication of heparin therapy and is being encountered more frequently in patients with cardiovascular disease as use of anticoagulant therapy becomes more widespread. Our understanding of the pathophysiology of this immune-mediated condition has improved in recent years, with heparin-platelet factor 4 complex as the culprit antigen in most patients. New sensitive laboratory assays for the pathogenic antibody are now available and should permit an earlier, more reliable diagnosis, but their optimal application remains to be defined. For patients in whom HIT is diagnosed, immediate discontinuation of heparin infusions and elimination of heparin from all flushes and ports are mandatory. Further management of patients with HIT is problematic at present, as there are no readily available alternative anticoagulant agents in the United States with proven efficacy in acute coronary disease. The direct thrombin inhibitors appear to be the most promising alternatives to heparin, when continued use of heparin is contraindicated, and the results of several multicenter trials evaluating their application in patients with HIT are awaited. PMID:9626819

  13. [Consensus report on the management of immune thrombocytopenia in pregnancy].

    PubMed

    Miyakawa, Yoshitaka

    2015-10-01

    Primary immune thrombocytopenia (ITP) is a benign hematological disorder characterized by platelet counts under 100×10(9)/l. We updated the consensus report for the management of ITP in pregnancy after a 20-year lag. For this update, not only hematologists, but also obstetricians, pediatricians, and anesthesiologists joined our committee. We recommend that physicians maintain platelet counts above 20×10(6)/l in the first and second trimesters. We also agree that counts should be at least 50×10(9)/l and 80×10(9)/l for vaginal and C-section deliveries, respectively. There might be no obvious reasons to forbid lactation in ITP patients receiving treatment with corticosteroids. In this educational session, I will discuss the differential diagnosis of thrombocytopenia and the management of ITP in pregnant women and their neonates based on international and updated domestic guidelines. PMID:26458448

  14. Neonates born to mothers with immune thrombocytopenic purpura: a single-center experience of 20 years.

    PubMed

    Bayhan, Turan; Tavil, Betül; Korkmaz, Ayşe; Ünal, Şule; Hanalioğlu, Damla; Yiğit, Şule; Gümrük, Fatma; Çetin, Mualla; Yurdakök, Murat

    2016-01-01

    Neonates born to mothers with immune thrombocytopenic purpura (ITP) have an increased risk of having thrombocytopenia and bleeding. The aim of our study was to determine maternal and fetal factors that can predict bleeding risk in neonates born to mothers with ITP, and effective treatment strategies by retrospective analysis of our single-center data. We performed a retrospective data review of neonates that were recorded as 'neonates born to mothers with ITP' in the Neonatal ICU of Hacettepe University, Ihsan Dogramacı Children's Hospital, Ankara, Turkey. Medical records of 36 neonates born from 35 mothers were analyzed. Among the 36 neonates born to mothers with ITP, thrombocytopenia (platelet count of less than 150 × 10/l) was detected in 20 (56.0%) neonates on the first day of life. Twelve of the 20 neonates with thrombocytopenia (60.0%) required treatment to increase the platelet counts. Clinical findings related to thrombocytopenia occurred in three (15.0%) neonates, but none of them presented with severe bleeding. There was no statistically significant association between neonatal lowest platelet count and maternal lowest platelet count, maternal platelet count at the time of delivery, and duration of thrombocytopenia, respectively. Neonates born to mothers with ITP have an increased tendency to develop thrombocytopenia, but severe bleeding is very rare in these neonates. Clinicians should pay special attention to follow these neonates. According to our results, both intravenous immunoglobulin and methyl prednisolone were found to be in equivalent efficacy for the treatment of neonatal thrombocytopenia due to maternal ITP. PMID:26258676

  15. Prevention of HLA alloimmunization: role of leukocyte depletion and UV-B irradiation.

    PubMed Central

    Snyder, E. L.

    1990-01-01

    HLA alloimmunization is a major cause of the platelet refractory state. The stimulus for HLA alloimmunization is believed to derive from incompatibility between the recipient's lymphocytes and the passenger donor lymphocytes contained in transfused red cells or platelet concentrates. Two techniques to prevent post-transfusion HLA alloimmunization include filtration, which physically removes the donor lymphocytes, and UV-B irradiation, which renders the donor leukocytes biologically inactive. The role of these two techniques in the prevention of HLA alloimmunization is the focus of this review. PMID:2293501

  16. Prevention of HLA alloimmunization: Role of leukocyte depletion and UV-B irradiation

    SciTech Connect

    Snyder, E.L. )

    1990-09-01

    HLA alloimmunization is a major cause of the platelet refractory state. The stimulus for HLA alloimmunization is believed to derive from incompatibility between the recipient's lymphocytes and the passenger donor lymphocytes contained in transfused red cells or platelet concentrates. Two techniques to prevent post-transfusion HLA alloimmunization include filtration, which physically removes the donor lymphocytes, and UV-B irradiation, which renders the donor leukocytes biologically inactive. The role of these two techniques in the prevention of HLA alloimmunization is the focus of this review.42 references.

  17. Alloimmunization of patients by blood units harboring distinct DEL variants.

    PubMed

    St-Louis, Maryse; Lebrun, André; Goldman, Mindy; Lavoie, Marianne

    2013-01-01

    The alloimmunization potential of many RHD variants is unknown, and it can be explored by lookback and traceback studies. Hema-Quebec (HQ) investigated the RHD status of 3980 D- repeat blood donors. Thirteen were found to be RHD positive: 4 RHD*1p, and 1 RHD*487delACAG, which show a Dphenotype;and 1 RHD*885T and 7 RHD*(93-94insT) causing a DEL phenotype when C antigen is present. Look back studies were done to verify the alloimmunization potential of these eight DEL donors. Coincidentally, Canadian Blood Services (CBS)performed a trace back study by investigating the RHD status of donors after aD- recipient developed anti-Dafter transfusion of two D- red blood cell (RBC) units. Donor genotyping was done either manually (HQ) or using the Progenika Bloodchip platform(CBS). Donations were traced through computer records. Letters were sent to hospital blood bank physicians to verify the presence of anti-Din recipients and to donors to request repeat samples.A total of 118 RBC units were transfused, 82 to D- recipients.Anti-D was found in three patients transfused with RHD*(93-94insT) DEL red blood cells. One donor presenting the same DEL variant was involved in the trace back study. Even without strong evidence clearly demonstrating the alloimmunization potential of DEL variants, whenever HQ or CBS identifies a donor harboring a DEL phenotype, his or her D status will be changed from DtoD+ to protect against the potential alloimmunization risk. PMID:24689683

  18. Rosiglitazone-induced immune thrombocytopenia.

    PubMed

    Liu, Xiaojing; Huang, Tao; Sahud, Mervyn A

    2006-05-01

    Rosiglitazone is one of the members in the thiazolidinedione (TZD) class of anti-diabetic agents that have proven efficacy in the treatment of patients with type 2 diabetes. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to rosiglitazone maleate (Avandia) and proposed the mechanisms for rosiglitazone-induced thrombocytopenia. Tested by flow cytometry, the patient's serum was positive for rosiglitazone-induced antibody with the binding ratio of 5.93 (mean fluorescence intensity, MFI) in the presence of the patient's serum and rosiglitazone in a final concentration of 0.53 mmol/l. The antibody was found to bind both glycoprotein (GP) IIb-IIIa complex and GP Ib/IX complex by MAIPA assay using five different monoclonal antibodies (mAbs) against GP complexes Ib/IX, GPIIb/IIIa or GPIa/IIa. Immunoprecipitation studies showed that both GPIIb/IIIa and GP Ib/IX complex were precipitated by antibody in the presence, but not in the absence of rosiglitazone. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to the antidiabetic agent rosiglitazone maleate. This report documents the first case of rosiglitazone-induced immune thrombocytopenia. PMID:16702039

  19. Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion.

    PubMed

    Nickel, Robert S; Horan, John T; Fasano, Ross M; Meyer, Erin; Josephson, Cassandra D; Winkler, Anne M; Yee, Marianne E M; Kean, Leslie S; Hendrickson, Jeanne E

    2015-12-01

    Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non-responders), a cross-sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti-E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non-alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non-alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non-alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization. PMID:26361243

  20. [Difficulties of the care of public antigen alloimmunization].

    PubMed

    Ben Amor, I; Rekik, T; Louati, N; Lahiani, W; Rekik, H; Peyrard, T; Menif, H; Gargouri, J

    2016-05-01

    Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss. PMID:26826911

  1. How I treat thrombocytopenia in pregnancy.

    PubMed

    Gernsheimer, Terry; James, Andra H; Stasi, Roberto

    2013-01-01

    A mild thrombocytopenia is relatively frequent during pregnancy and has generally no consequences for either the mother or the fetus. Although representing no threat in the majority of patients, thrombocytopenia may result from a range of pathologic conditions requiring closer monitoring and possible therapy. Two clinical scenarios are particularly relevant for their prevalence and the issues relating to their management. The first is the presence of isolated thrombocytopenia and the differential diagnosis between primary immune thrombocytopenia and gestational thrombocytopenia. The second is thrombocytopenia associated with preeclampsia and its look-alikes and their distinction from thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. In this review, we describe a systematic approach to the diagnosis and treatment of these disease entities using a case presentation format. Our discussion includes the antenatal and perinatal management of both the mother and fetus. PMID:23149846

  2. Thrombocytopenia associated with environmental exposure to polyurethane

    SciTech Connect

    Michelson, A.D. )

    1991-10-01

    Few chemicals in the environment have been implicated as causes of isolated thrombocytopenia, and the evidence is usually less than convincing because the patients were not rechallenged with the chemical in vivo. In the present paper, a child is reported with the onset of thrombocytopenia in temporal association with environmental exposure to polyurethane. Five years after the initial thrombocytopenia had resolved, an inadvertent in vivo rechallenge with environmental polyurethane resulted in recurrence of the thrombocytopenia. This recurrence, together with the fact that only 1-4% of cases of idiopathic thrombocytopenic purpura in children recur, provided strong evidence for a causal role for the polyurethane exposure in this patient's thrombocytopenia. In summary, environmental exposure to polyurethane should be considered in the differential diagnosis of acquired thrombocytopenia in childhood.

  3. Notch signaling in hematopoietic cell transplantation and T cell alloimmunity

    PubMed Central

    Ebens, Christen; Maillard, Ivan

    2013-01-01

    Notch signaling can regulate both hematopoietic progenitors and alloimmune T cells in the setting of allogeneic bone marrow or hematopoietic cell transplantation (allo-HCT). Ex vivo culture of multipotent blood progenitors with immobilized Delta-like ligands induces supraphysiological Notch signals and can markedly enhance progenitor expansion. Infusion of Notch-expanded progenitors shortened myelosuppression in preclinical and early clinical studies, while accelerating T cell reconstitution in preclinical models. Notch also plays an essential role in vivo to regulate pathogenic alloimmune T cells that mediate graft-versus-host disease (GVHD), the most severe complication of allo-HCT. In mouse allo-HCT models, Notch inhibition in donor-derived T cells or transient blockade of Delta-like ligands after transplantation profoundly decreased GVHD incidence and severity, without causing global immunosuppression. These findings identify Notch in T cells as an attractive therapeutic target to control GVHD. In this review, we discuss these contrasting functions of Notch signaling with high translational significance in allo-HCT patients. PMID:24050990

  4. Antiplatelet antibodies in oxaliplatin-induced immune thrombocytopenia

    PubMed Central

    McNamara, Michael J; Curtis, Brian R; McCrae, Keith R

    2014-01-01

    Lesson Drug-induced immune thrombocytopenia may be potentially fatal; here we report the development of severe thrombocytopenia with strong oxaliplatin-dependent antiplatelet antibodies. PMID:25057402

  5. Thrombocytopenia

    MedlinePlus

    ... number. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: ... hemodilution. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: ...

  6. Modification of Solid Phase Red Cell Adherence Assay for the Detection of Platelet Antibodies in Patients With Thrombocytopenia

    PubMed Central

    Vongchan, Preeyanat; Nawarawong, Weerasak; Linhardt, Robert J.

    2009-01-01

    Platelet refractoriness is caused by HLA antibodies and platelet-specific antibodies. Current methods used to detect antiplatelet antibodies have limitations. Solid phase red cell adherence (SPRCA) lacks sensitivity and requires a second assay using chloroquine-treated intact platelets to specify the response due to anti-HLA. We modified SPRCA by using 2 types of antihuman platelet antibodies with different specificities toward platelet lysate and tested samples from 361 patients (69 with unexplained thrombocytopenia and 292 with poor response to platelet transfusions not explicable by alloimmunization or the clinical situation) and 50 from healthy volunteers. Our method compared favorably with platelet suspension direct immunofluorescence. All samples from healthy volunteers were negative; of the samples from the patient population, 240 were positive (147 samples had only antiplatelet and 3 samples had only anti-HLA antibodies). This modified technique had a sensitivity of 98% and a specificity of 91%. PMID:18701420

  7. Heparin induced thrombocytopenia management with bivalirudin.

    PubMed

    Meera, R; Rachel, D; Ramakrishnapillai, V; Vijayaraghavan, G

    2007-01-01

    We report a case of Heparin Induced Thrombocytopenia (HIT) following percutaneous coronary intervention. The case is unique in that thrombocytopenia occurred very early after heparin administration and responded well to a regime of bivalirudin-a direct thrombin inhibitor readily available in India. Heparin, Thrombocytopenia, Bivalirudin Acute HIT, occurring within few hours of heparin therapy have been reported in patients previously exposed to unfractionated heparin (UFH) or low molecular weight heparin (LMWH) 1. Prompt recognition of the condition and timely intervention with direct thrombin inhibitors, can result in salvaging patients from this potentially fatal complication. PMID:19126942

  8. Early occurrence of red blood cell alloimmunization in patients with sickle cell disease.

    PubMed

    Sins, Joep W R; Biemond, Bart J; van den Bersselaar, Sil M; Heijboer, H; Rijneveld, Anita W; Cnossen, Marjon H; Kerkhoffs, Jean-Louis H; van Meurs, Alfred H; von Ronnen, F B; Zalpuri, Saurabh; de Rijke, Yolanda B; Ellen van der Schoot, C; de Haas, Masja; van der Bom, Johanna G; Fijnvandraat, Karin

    2016-08-01

    Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization. Am. J. Hematol. 91:763-769, 2016. © 2016 Wiley Periodicals, Inc. PMID:27102719

  9. Predictors of Red Cell Alloimmunization in Kurdish Multi Transfused Patients with Hemoglobinopathies in Iraq.

    PubMed

    Al-Mousawi, Muqdad M N; Al-Allawi, Nasir A S; Alnaqshabandi, Rubad

    2015-01-01

    Hemoglobinopathies are significant health problems in Iraq, including its Northern Kurdistan region. One of the essential components of management of these disorders is regular lifelong blood transfusions. The latter is associated with several complications including red cell alloimmunization. No study has looked at the frequency of alloimmunization and its associations in the country. To address the latter issue, 401 multi transfused patients [311 with β-thalassemia (β-thal) syndrome and 90 with sickle cell disease], registered at a large thalassemia care center in Iraqi Kurdistan had their records reviewed, and their sera tested for atypical antibodies using screening and extended red cell panels. Red cell alloimmunization was detected in 18 patients (4.5%) with a total of 20 alloantibodies, while no autoantibodies were detected. The most frequent alloantibody was anti-E, followed by anti-D, anti-K, anti-C(w), anti-C, anti-c and anti-Le(a). Ethnicity was an important predictor of alloimmunization, while age at start of transfusion (>2 vs. ≤2 years) (p = 0.005), Rhesus D (RhD) negative status (p = 0.0017) and history of previous transfusion reactions (p = 0.007) showed a statistically significant higher rate of alloimmunization. However, patients' age, gender, number of units transfused, underlying diagnosis and splenectomy were not significantly associated with alloimmunization. Based on our observations, measures to reduce alloimmunization rates may include extended matching for Rhesus and Kell antigens and early initiation of blood transfusions. PMID:26327166

  10. Heparin-induced thrombocytopenia in essential thrombocytosis.

    PubMed

    Murawaki, Ayumi; Nakayasu, Hiroyuki; Doi, Mitsuru; Suzuki-Kinoshita, Kaori; Asai, Yasumasa; Omura, Hiromi; Nakashima, Kenji

    2012-11-01

    We report a 67-year-old woman with essential thrombocytosis who developed cerebral infarction and heparin-induced thrombocytopenia during treatment for the cerebral infarction. She developed additional cerebral infarcts, acute femoral artery occlusion, and thrombophlebitis of her lower extremities. She was successfully treated with argatroban. This is the first report of a patient with essential thrombocytosis who developed heparin-induced thrombocytopenia and serious conditions, which included multiple thromboembolisms and coagulation disorders mimicking disseminated intravascular coagulation. PMID:22425438

  11. Low incidence of anti-D alloimmunization following D+ platelet transfusion: The Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study

    PubMed Central

    Cid, Joan; Lozano, Miguel; Ziman, Alyssa; West, Kamille A.; O'Brien, Kerry L.; Murphy, Michael F.; Wendel, Silvano; Vázquez, Alejandro; Ortín, Xavier; Hervig, Tor A.; Delaney, Meghan; Flegel, Willy A.; Yazer, Mark H.

    2014-01-01

    Summary The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5%±2%. A primary anti-D immune response was defined as the detection of anti-D ≥28 days following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010-2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1.44%; 95%CI 0.58-2.97%) recipients had a primary anti-D response after a median serological follow-up of 77 days (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets. PMID:25283094

  12. Low frequency of anti-D alloimmunization following D+ platelet transfusion: the Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study.

    PubMed

    Cid, Joan; Lozano, Miguel; Ziman, Alyssa; West, Kamille A; O'Brien, Kerry L; Murphy, Michael F; Wendel, Silvano; Vázquez, Alejandro; Ortín, Xavier; Hervig, Tor A; Delaney, Meghan; Flegel, Willy A; Yazer, Mark H

    2015-02-01

    The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5 ± 2%. A primary anti-D immune response was defined as the detection of anti-D ≥ 28 d following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010 and 2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1·44%; 95% CI 0·58-2·97%) recipients had a primary anti-D response after a median serological follow-up of 77 d (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets. PMID:25283094

  13. Thrombocytopenia associated with neoplasia in dogs.

    PubMed

    Grindem, C B; Breitschwerdt, E B; Corbett, W T; Page, R L; Jans, H E

    1994-01-01

    Ten percent (214/2,059) of all dogs with cancer at North Carolina State University Veterinary Teaching Hospital had thrombocytopenia. The thrombocytopenia was associated with infectious/inflammatory etiologies in 4%, miscellaneous disorders (therapy, bone marrow failure, disseminated intravascular coagulation) in 35%, and neoplasia without identifiable secondary factors in 61% of cancer-bearing dogs. Classifying these dogs by tumor groups revealed the following proportionate ratios: lymphoid, 29%; carcinoma, 28%; sarcoma, 20%; hemic neoplasia, 7%; multiple, 5%; unclassified, 3%; benign, 3%; brain, 3%; and endocrine, 3%. Dogs with hemangiosarcoma, lymphoma, and melanoma were at increased risk of developing thrombocytopenia. Cytotoxic therapy was the major factor increasing the risk of thrombocytopenia in dogs with melanoma. Golden Retrievers were the only breed recognized with a predisposition to develop thrombocytopenia. If thrombocytopenia is identified in a dog with cancer, we recommend thorough evaluation of the coagulation system before surgery or therapy, and careful consideration of the risks and potential benefits of myelosuppressive or L-asparaginase therapy. PMID:7884725

  14. Practice Bulletin No. 166: Thrombocytopenia in Pregnancy.

    PubMed

    2016-09-01

    Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Système International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/µL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID:27548554

  15. Lupus thrombocytopenia: clinical implications and prognostic significance

    PubMed Central

    Ziakas, P; Giannouli, S; Zintzaras, E; Tzioufas, A; Voulgarelis, M

    2005-01-01

    Methods: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. Results: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0–11) compared with 1 (range 0–12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. Conclusions: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis. PMID:16100344

  16. Novel treatments for immune thrombocytopenia

    PubMed Central

    Shih, Andrew; Nazi, Ishac; Kelton, John G.; Arnold, Donald M.

    2016-01-01

    Summary Primary immune thrombocytopenia (ITP) is caused by platelet autoantibodies and T-cell dysregulation. Both platelets and their precursor megakaryocytes may be targeted leading to platelet destruction and underproduction. Current treatments for ITP are inadequate since they do not reverse the disease process and generally do not result in durable remissions. In addition, many treatments are limited by side effects including infection and potentially thrombosis. Novel agents that are currently in development target certain key steps in the disease process, including: (1) the interaction between T-cell and antigen presenting cells (CD40–CD154 interaction); (2) the binding of the Fc portion of platelet autoantibodies to Fc-receptors on macrophages (soluble Fc-RIIb); and (3) the signaling pathways leading to platelet phagocytosis by macrophages (Syk inhibition). Other strategies have been to augment platelet production by simulating thrombopoiesis or by neutralizing physiological inhibitors of megakaryopoiesis. Targeted therapies in ITP have the potential to improve disease morbidity and mortality while limiting systemic side effects. Before these agents can be used in practice, additional clinical studies are needed with rational study outcomes including platelet count, bleeding and quality of life. An individualized treatment strategy is needed for patients since ITP is a distinctly heterogeneous disease. PMID:24656294

  17. Amoxicillin/Clavulanic Acid-Induced Thrombocytopenia

    PubMed Central

    Saad, Aline; Azar, Marina; Khoueiry, Paul

    2014-01-01

    Introduction and Objective: Drug-induced thrombocytopenia is a common adverse effect reported in the literature. Typically patients present with a low platelet count with signs and symptoms ranging from bruising to bleeding, and major organ damage. Penicillin-induced thrombocytopenia previously reported in the literature is explained primarily through the hapten-dependent antibody process. The goal of this report is to present a case of an amoxicillin/clavulanic acid-induced thrombocytopenia. Case Presentation: A 23-year-old male presented to the emergency department with bruises on his arms and legs after completing a full course of amoxicillin/clavulanic acid of 625 mg twice a day for 5 days for tonsillitis. After several tests, the patient was diagnosed with thrombocytopenia induced by amoxicillin/clavulanic acid. The patient was treated with a corticosteroids taper regimen for 3 weeks. He was discharged after 3 days of inpatient treatment with instructions to avoid physical activity for 2 weeks. Two weeks post discharge, the follow-up showed that the platelet count had increased. Discussion: Penicillin-induced thrombocytopenia has been previously reported in the inpatient setting where bleeding was observed. However, the patient in this case report presented with bruises on his arms and legs. The diagnosis was made by the process of elimination; not all possible tests were conducted. The patient was prescribed corticosteroids that are not indicated for drug-induced thrombocytopenia. The Naranjo scale showed that this is a probable adverse event of amoxicillin/clavulanic acid. Conclusion: This is a unique case where amoxicillin/clavulanic acid was reported to be a probable cause of thrombocytopenia in an outpatient setting without signs of bleeding and without concomitant medications. PMID:25477568

  18. Study of alloimmunization and autoimmunization in Iranian β-thalassemia major patients

    PubMed Central

    Davari, Kambiz; Soltanpour, Mohammad Soleiman

    2016-01-01

    Background: Thalassemia is one of the most common monogenic disorders characterized by reduced production of globin chains. Although regular red blood cell (RBC) transfusion support is the main treatment for these patients, it may be associated with complications such as RBC alloimmunization. Aim: The study aimed to determine the incidence of alloimmunization and autoimmunization to RBC antigens in β-thalassemia major patients from Zanjan, Zanjan Province, Iran. Materials and Methods: A total of 49 β-thalassemia major patients comprising 24 females and 25 males (mean age: 18.59 ± 8.16 years; range: 2-40 years) from Northwest Iran were included in a cross-sectional study. Alloantibody screening and identification were done using 3-cell and 10-cell reagent red blood cells, respectively. Autoantibody detection was performed using direct Coomb's test. Results: The incidence of alloimmunization was 16.32% with 10 alloantibodies identified in 8 patients. The most common clinically significant alloantibody identified in alloimmunized patients was anti-Kell (K-antigen) (60%) followed by anti-Rhesus (Rh) (E, c-antigens). The rate of alloimmunization was significantly lower in patients transfused with leukoreduced RBCs compared with those transfused with nonleukoreduced RBCs (9.53% vs 57.14%, P = 0.001). There was no significant correlation between alloantibody formation and the age, gender, hemoglobin levels, number of transfused units, and splenectomy. Conclusion: Transfusion of leukoreduced and phenotypically matched red blood cells for Kell (K) and Rh (E, c) antigens may help reduce the alloimmunization rate in Iranian β-thalassemia major patients. Moreover, autoimmunization to RBC antigens was rare in our patients. PMID:27011679

  19. Pentoxifylline-Induced Thrombocytopenia: A Case Report.

    PubMed

    Tan, Michelle W; Sklar, Grant E

    2015-12-01

    Pentoxifylline-induced thrombocytopenia is rare, and information is lacking about its presentation. We describe a 72-year-old Chinese male who developed thrombocytopenia after initiation of pentoxifylline for the treatment of chronic lower limb ischemia due to peripheral artery disease. Venous thromboembolism had been ruled out with an ultrasound. Vascular surgeons had also determined there was no indication for surgical intervention. Four days after initiation of pentoxifylline, he developed thrombocytopenia, and his platelets were 68 × 10(3)/μL. He was not in overt disseminated intravascular coagulation (DIC), based on his International Society for Thrombosis and Hemostasis (ISTH) DIC score of 4. Dengue fever, which is endemic in Singapore, was ruled out. Pseudothrombocytopenia was also excluded with a peripheral blood film. When his platelets continued to fall, pentoxifylline was discontinued on the fifth day of treatment, and platelets normalized 48 hours after discontinuation. Pentoxifylline was a probable cause of thrombocytopenia using the Naranjo Adverse Drug Reaction Probability Scale (score = 7). The patient did not receive further doses of pentoxifylline. Prescribers should be aware of the risk of thrombocytopenia with pentoxifylline therapy and discontinue its use promptly if it is suspected. PMID:26429719

  20. Computer methodology for simulation and prediction of alloimmune responses: expected antibody specificities.

    PubMed

    Altarriba, J; Zarazaga, I; Amorena, B

    1983-01-01

    The methodology presented here was developed for simulating planned alloimmunization results, with regard to the type and number of expected antibody specificities. The computer program designed for this purpose was adapted to an immunogenetic model using Boolean algebra. It was written to help immunogeneticists avoid handling routine data preceding selection of donor-recipient pairs, specially concerning blood type alloimmunizations in animals: all of the donor-recipient combinations and the expected antibody specificities (their limit number being specified in each particular immunization program) are provided in the print-out. PMID:6661908

  1. Alleviating anemia and thrombocytopenia in myelofibrosis patients.

    PubMed

    Cervantes, Francisco; Correa, Juan-Gonzalo; Hernandez-Boluda, Juan Carlos

    2016-05-01

    Anemia and thrombocytopenia are frequent clinical manifestations of myelofibrosis as well as important prognostic factors of the disease. Concerning the treatment of anemia, the first step should be the correction of reversible contributing factors, such as possible iron, folate and vitamin B12 deficiency. Then, treatment options include erythropoiesis stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy. Anemia responses may also be observed in some patients treated with JAK inhibitors. However, most patients eventually fail to such therapies and become transfusion dependent. Some of the aforementioned therapies can also improve thrombocytopenia, but the responses are usually observed in patients with moderate platelet count decrease. Allogeneic hematopoietic stem cell transplantation, the only curative treatment of myelofibrosis, can be an alternative for selected patients with cytopenias who are refractory to conventional therapies. However, for the majority of patients, the management of anemia and severe thrombocytopenia remains an unmet need. PMID:26891375

  2. [Cerebellar hemangioblastoma and thrombocytopenia: Report of one case].

    PubMed

    Patiño G, Santiago

    2016-04-01

    The association between vascular tumors and thrombocytopenia is rare. Kasabach-Merritt Syndrome is seen in childhood and is characterized by hemangiomas and thrombocytopenia. A 42 years-old man with a cerebellar hemangioblastoma and thrombocytopenia, admitted with a subarachnoid hemorrhage is reported. The patient was operated and required a splenectomy to manage the thrombocytopenia. After the splenectomy the patient developed a subdural hematoma that was operated. Despite the surgical treatment, the patient died. PMID:27401386

  3. Frequency and Specificity of Red Blood Cell Alloimmunization in Chilean Transfused Patients

    PubMed Central

    Caamaño, José; Musante, Evangelina; Contreras, Margarita; Ulloa, Hernán; Reyes, Carolina; Inaipil, Verónica; Saavedra, Nicolás; Guzmán, Neftalí

    2015-01-01

    Summary Background Alloimmunization is an adverse effect of blood transfusions. In Chile, alloimmunization frequency is not established, and for this reason the aim of this study was to investigate the prevalence and specificity of red blood cell (RBC) alloantibodies in Chilean transfused subjects. Methods Records from 4,716 multi-transfused patients were analyzed. In these patients, antibody screening was carried out prior to cross-matching with a commercially available two-cell panel by the microcolum gel test, and samples with a positive screen were analyzed for the specificity of the alloantibody with a 16-cell identification panel. Results The incidence of RBC alloimmunization in transfused patients was 1.02% (48/4,716) with a higher prevalence in women (40/48). We detected 52 antibodies, the most frequent specificities identified were anti-E (30.8%), anti-K (26.9%), anti-D (7.7%), and anti-Fya (5.8%). The highest incidence of alloantibodies was observed in cancer and gastroenterology patients. Conclusion The data demonstrated a low alloimmunization frequency in Chilean transfused patients, principally associated with antibodies anti-E, anti-K, anti-D, and anti-Fya. PMID:25960709

  4. Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia Patients: A Report from Eastern India

    PubMed Central

    Datta, Suvro Sankha; Mukherjee, Somnath; Talukder, Biplabendu; Bhattacharya, Prasun; Mukherjee, Krishnendu

    2015-01-01

    Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice. PMID:26425124

  5. Clinical practice: immune thrombocytopenia in paediatrics.

    PubMed

    Labarque, Veerle; Van Geet, Chris

    2014-02-01

    Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A "watch and wait" strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents. PMID:24390128

  6. Wilson disease with thrombocytopenia (case report).

    PubMed

    Zhvania, M; Gogberashvili, K; Gagoshidze, M; Uberi, E

    2014-12-01

    We present an adolescent patient with WD accompanied with secondary amenorrhea, and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite having had regular menses for 2 years. An abdominal ultrasound scan revealed ascitis and some ovarian cysts. On physical examination: slight jaundice, edema of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no hepatomegaly and no splenomegaly. Breast and pubic hair development was concomitant with Tanner stage 4. There was performed laboratory and instrumental investigations. The patient was diagnosed as WD owing to the low level of ceruloplasmin, with increased level of copper in 24-hour urine excretion and in dry liver tissue. The needle biopsy of liver showed severe hepatocellular necrosis, inflammatory changes and fibrosis. The platelet count was found to be low with lack of increased number of megakaryocytes in the bone marrow aspiration suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The absence of antithrombocyte and other autoimmune and viral antibodies excluded respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune diseases and viral infections. Thus, we support the recommendation that adolescents with amenorrhea or children with thrombocytopenia without any obvious cause should be evaluated for WD, because the early detection and treatment of WD is capable of reversing described changes and restoring a normal liver function. PMID:25617103

  7. Refractory Thrombocytopenia and Neutropenia: a Diagnostic Challenge

    PubMed Central

    Gyan, Emmanuel; Dreyfus, François; Fenaux, Pierre

    2015-01-01

    The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD) as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT), and refractory neutropenia (RN), characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors. Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS). Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS), and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification) as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008) are quite rare. These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates. PMID:25745545

  8. Thrombocytopenia and vomiting due to difluoromethylornithine.

    PubMed

    Tietze, K J; Gaska, J A; Cosgrove, E M

    1987-01-01

    A 32-year-old Haitian male with acquired immunodeficiency syndrome presented with complications of Isospora belli enteritis. Therapy with the investigational drug difluoromethylornithine was initiated. Severe thrombocytopenia, nausea, and vomiting developed during intravenous drug therapy and recurred upon rechallenge with low-dose oral difluoromethylornithine. Therapy was discontinued because of these severe adverse effects. PMID:3111810

  9. Neonatal haemochromatosis associated with gastroschisis.

    PubMed

    Thornton, M P; Marven, S S; Tanner, M S; Gürtl-Lackner, B

    2008-05-01

    We describe, to our knowledge, the first case of progressive neonatal liver failure due to neonatal haemochromatosis (NH) occurring in an infant with a gastroschisis and review the literature regarding these two conditions. A 1,665 g male infant with antenatally diagnosed gastroschisis was born with a severe coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed progressive liver failure, complicated by necrotising enterocolitis. Serum ferritin was elevated at 1,459 microg/L. He died on day 40 and a limited post-mortem examination confirmed significant hepatic siderosis with fibrosis and cholestasis, and siderosis of the pancreas. Although no genetic aetiology for gastroschisis has been identified, an occasional inherited tendency has been observed. There is also evidence to support an autosomal recessive inheritance in NH. PMID:18338135

  10. Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

    PubMed Central

    Stasi, Roberto; Chia, Lian Wea; Kalkur, Pallavi; Lowe, Robert; Shannon, Muriel S.

    2009-01-01

    Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy. PMID:21415958

  11. Hemolytic disease of the newborn associated with anti-Jra alloimmunization in a twin pregnancy: the first case report in Korea.

    PubMed

    Kim, Hyungsuk; Park, Min-Jeong; Sung, Tae-Jung; Choi, Ji Seon; Hyun, Jungwon; Park, Kyoung Un; Han, Kyou-Sup

    2010-10-01

    Jr(a) is a high-frequency antigen found in all ethnic groups. However, the clinical significance of the anti-Jr(a) antibody has remained controversial. Most studies have reported mild hemolytic disease of the newborn and fetus (HDNF) in Jr(a)-positive patients. Recently, fatal cases of HDNF have also been reported. We report the first case of HDNF caused by anti-Jr(a) alloimmunization in twins in Korea. A 33-yr-old nulliparous woman with no history of transfusion or amniocentesis was admitted at the 32nd week of gestation because of vaginal bleeding caused by placenta previa. Anti-Jr(a) antibodies were detected in a routine laboratory examination. An emergency cesarean section was performed at the 34th week of gestation, and 2 premature infant twins were delivered. Laboratory examination showed positive direct antiglobulin test and Jr(a+) phenotype in the red blood cells and the presence of anti-Jr(a) antibodies in the serum in both neonates. The infants underwent phototherapy for neonatal jaundice; this was followed by conservative management. They showed no further complications and were discharged on the 19th postpartum day. Preparative management to ensure the availability of Jr(a-) blood, via autologous donation, and close fetal monitoring must be performed even in cases of first pregnancy in Jr(a-) women. PMID:20890084

  12. Emerging science, emerging ethical issues: who should fund innate alloimmunity-suppressing drugs?

    PubMed

    Land, W G; Gutmann, Th; Daar, A S

    2008-01-01

    An emerging body of evidence suggests that the innate immune system plays a critical role in allograft rejection. Any injury to the donor organ, e.g. the reperfusion injury, induces an inflammatory milieu in the allograft which appears to be the initial event for activation of the innate immune system. Injury-induced intragraft damage- associated molecular patterns (DAMPs) are recognized by donor-derived and recipient-derived, TLR4/2-bearing immature dendritic cells (iDCs). After recognition, these cells mature and initiate allorecognition/alloactivation in the lymphoid system of the recipient. Indeed, the key "innate" event, leading to activation of the adaptive alloimmune response, is the injury-induced, TLR4-triggered, and NFkappaB-mediated maturation of DCs ("innate alloimmunity"). Time-restricted treatment of innate immune events would include 1) treatment of the donor during organ removal, 2) in-situ/ex-vivo treatment of the donor organs alone, and 3) treatment of the recipient during allograft reperfusion and immediately postoperatively. Treatment modalities would include 1) minimization of the oxidative allograft injury with the use of antioxidants; 2) prevention of the TLR4-triggered maturation of DCs with the use of TLR4-antagonists; 3) inhibition of complement activation with the use of complement inhibiting agents. According to data from clinical and experimental studies it can be assumed that successful suppression of innate alloimmune events results in either subsequent significant reduction in, or even complete avoidance of the currently applied adaptive alloimmunity-suppressing drugs. However, in view of the time-restricted period of treatment, and the fear to potentially destroy its own business with currently applied alloimmunity-suppressing drugs, the pharmaceutical industry is still, but quite legitimately, reluctant to invest in the high cost of clinical development of those drugs for transplant patients because there are no marketing interests

  13. Neonatal sepsis

    MedlinePlus

    ... BE. Perinatal viral infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ... K. Postnatal bacterial infections. In Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal ...

  14. Study of red blood cell alloimmunization in multitransfused thalassemic children of Jammu region

    PubMed Central

    Dogra, Ashu; Sidhu, Meena; Kapoor, Raman; Kumar, Dinesh

    2015-01-01

    Introduction: Thalassemia is one of the most common genetic disorder of hemoglobin synthesis in Jammu region. Although RBC transfusion is life saving for these patients, it may be associated with some complications like RBC alloimmunization. Thus, the aim of this study was to determine the frequency of alloimmunization and the most common alloantibodies involved. Material and Methods: This was a descriptive study involving a total of 70 thalassemic patients in the age range of 2-17 years receiving regular blood transfusions, registered at SMGS Blood Bank, Jammu. Relevant clinical and laboratory data was collected with reference to age at the start of transfusions, total number of transfusions received and splenectomy status. Antibodies screening, antibody identification, and cross matching was done on allpatient samples included in the study, during the period between November 2009 and October 2010. Results: In this study, a total of six alloantibodies six patients (8.5%) and one autoantibody (1.42%) was detected. All identified alloantibodies belonged to Rh system (i.e. anti-E, in 3 patients (50%), anti D, in one patient (16.66%)) and Kell system (anti-K, in two patients (33.34%)). Higher frequency of alloimmunization was found, with increase in number of transfusions and in those who received transfusions after 1 year of age. Alloimmunization was not significantly associated with gender and splenectomy status (P-value > 0.05). Conclusion: Red cell alloantibodies developed in 8.5% of thalassemic patients and 1.42% had autoantibodies. The most common alloantibodies identified were anti Rh system antibodies (anti-E and anti-D) present in 50% and 16.66% of patients respectively. Alloimmunization is not an uncommon problem faced by blood banks and finding compatible units for regularly transfused thalassemic patients may become very difficult. In order to reduce alloimmunization, a policy for performing extended red cell phenotyping of these patients is essential and

  15. Miliary tuberculosis presenting with hyponatremia and thrombocytopenia.

    PubMed Central

    Cockcroft, D. W.; Donevan, R. E.; Copland, G. M.; Ibbott, J. W.

    1976-01-01

    A 74-year-old woman with miliary tuberculosis had moderately severe hyponatremia due to inappropriate secretion of antidiuretic hormone (SIADH) and very severe thrombocytopenia without other hematologic abnormalities. She was treated with isoniazid, rifampin, ethambutol, prednisone, vincristine and fluid restriction and recovered completely. The SIADH may have been a response by the posterior pituitary to a decrease in intravascular volume resulting from the extensive pulmonary disease or associated hypoxia, or the tuberculous lung may have released ADH or an ADH-like substance. The thrombocytopenia may have resulted from a direct or indirect toxic effect of infection or, less likely, the tuberculosis may have activated latent idiopathic thrombocytopenic purpura. Images FIG. 2 FIG. 3 PMID:991033

  16. Canine infectious cyclic thrombocytopenia found in Taiwan.

    PubMed

    Chang, A C; Chang, W L; Lin, C T; Pan, M J; Lee, S C

    1996-05-01

    Here were report the first canine infectious cyclic thrombocytopenia (CICT) found in Taiwan. Platelet-specific inclusions were detected in the blood smear of a military working dog. To identify the etiologic agent, the patient's blood was transmitted to three six-month-old German Shepherd dogs. The Ehrlichia platys-like inclusions were observed six to eight days after inoculation. Indirect fluorescent antibody test showed that the serum from the patient reacted specifically with the microorganisms within the platelets. Typical hematologic manifestations of E. platys infection, cyclic parasitemia and concomitant thrombocytopenia, were observed in these dogs. The prevalence of CICT in north Taiwan was also studied, and the incidence was 8.9% (4 out of 45) in civilian dogs and 97.1% (34 out of 35) in dogs from a heavily tick infested kennel. PMID:8741613

  17. Primary immune thrombocytopenia accompanied by pituitary apoplexy.

    PubMed

    Tsuji, Takahiro; Mochinaga, Hiromi; Yamasaki, Hiroshi; Tsuda, Hiroyuki

    2016-07-01

    An 83-year-old woman was admitted to our hospital with a severe headache and purpura. She had previously been diagnosed with idiopathic thrombocytopenia purpura (ITP) and achieved complete remission with steroid therapy. Steroid therapy had been completed one week prior to the current admission. The recurrence of severe thrombocytopenia (<1.0×10(4) platelets/μl) was detected and a CT scan revealed pituitary hemorrhage without pituitary adenoma. She received steroid therapy combined with intravenous immunoglobulin, which resulted in the amelioration of ITP and improvements in the pituitary hemorrhage. Intracranial hemorrhage, which is the most serious bleeding manifestation in ITP, is relatively uncommon. Pituitary apoplexy in ITP is extremely rare. PMID:27498733

  18. Childhood immune thrombocytopenia: Clinical presentation and management

    PubMed Central

    Faki Osman, Mohamed El

    2012-01-01

    Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1–6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2–0.9%) [7–12]. Childhood primary ITP usually runs a benign, self-limiting course, with or without treatment. Complete remission occurs within six months from diagnosis, commonly within 6–12 weeks, in the majority of children with the diagnosis of ITP. However, 20–30% of children will continue to have persistent low platelets count with bleeding symptoms beyond six months from diagnosis [4, 12–18]. The diagnosis of ITP in children is essentially one of exclusion. The child is usually one to seven years old, develops skin bruises, petechiae, or mucosal bleeding, who is otherwise healthy and having no lymphadenopathy or organomegally. Full blood count reveals isolated thrombocytopenia with normal hemoglobin (Hb) level, white blood count (WBC) and normal peripheral blood smear. Initial management options for newly diagnosed childhood ITP include; observation only, the use of intravenous immunoglobulin (IVIG), steroids, anti-D immunoglobulin, each alone or in combination [6, 19.] Children who develop chronic ITP may benefit from splenectomy [19, 20–24]. Rituximab, a chimeric monoclonal antibody (anti-CD20), may lead to complete remission, and defers the need for splenectomy [25–27]. Recently, the thrombopoietin (TPO) agonists (Romiplostim and Eltrombopag) produced very good response in adult and pediatric patients with severe chronic ITP [28–30].

  19. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

    Cyclophosphamide was given intermittently rather than daily to 14 patients with autoimmune thrombocytopenic purpura. Eight patients responded and six did not. In those who responded the rise in platelet count was rapid, and in all patients the lack of toxicity was striking. Intermittent cyclophosphamide seems effective in some cases of autoimmune thrombocytopenia and is safe, at least in the short term. Controlled trials would be required to prove that intermittent is better than daily administration. PMID:4473260

  20. Immune thrombocytopenia: No longer ‘idiopathic’

    PubMed Central

    McCRAE, KEITH

    2012-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

  1. Genetics of familial forms of thrombocytopenia.

    PubMed

    Balduini, Carlo L; Savoia, Anna

    2012-12-01

    The joint application of clinical and genetic investigation to patients with inherited thrombocytopenias, as well as the availability of new methods for studying megakaryopoiesis, has greatly expanded the knowledge of these disorders in the last few years with regard to their etiology, pathogenesis and clinical aspects. In particular, new diseases have been described, as deriving from mutations in the genes FLNA, TUBB1, ITGA2/ITGB3, ANKRD26, CYCS, and ABCG5 or ABCG8. Moreover, forms previously considered separate entities were found to be different clinical aspects of a single disease. For instance, identification of MYH9 as the gene whose mutations cause the May-Hegglin anomaly led to the recognition that Sebastian platelet syndrome, Epstein syndrome, and Fechtner syndrome derive from mutations of the same gene and describe overlapping disorders. Despite these advances, knowledge of hereditary thrombocytopenias is still far from satisfactory because for approximately half of the patients it is not possible to formulate a definite diagnosis in that their illnesses has not yet been described. In this review, we provide a systematic description of hereditary thrombocytopenias as we know them today, giving special attention to genetic aspects. PMID:22886561

  2. Thrombocytopenia in Plasmodium vivax Malaria: How Significant?

    PubMed Central

    Muley, Arti; Lakhani, Jitendra; Bhirud, Saurabh; Patel, Abhinam

    2014-01-01

    Introduction. Thrombocytopenia is frequently noticed with P. falciparum malaria but is less reported and studied with P. vivax. Materials and Methods. The study was conducted in the Department of Medicine, SBKS MI & RC, Pipariya. We included patients who were diagnosed with vivax malaria. The data regarding their clinical and hematological profile was collected and analysed. Result. A total of 66 patients were included. 42 (63%) had platelet count <100000/mm3. Mean platelet count was 1,18,650, range being 8000/mm3–6,10,000/mm3. Amongst those with thrombocytopenia, 16 (38.09%) had anemia, 14 (33.33%) had serum creatinine >1.2 gm/dL, 15 (35.71%) had jaundice (s. bilirubin > 1.2), 2 (4.76%) had altered sensorium, 6 (14.28%) had ARDS, 2 needed ventilator support, and 1 expired. Amongst those with normal platelet count, 5 (20.83%) had anemia and 1 had jaundice whereas none had elevated s. creatinine, altered sensorium, or lung involvement. Conclusion. Thrombocytopenia is now being seen more commonly with vivax malaria. Patients with platelet count <1 lac/cumm have more severe disease. PMID:25045358

  3. Thrombocytopenia in Plasmodium vivax Malaria: How Significant?

    PubMed

    Muley, Arti; Lakhani, Jitendra; Bhirud, Saurabh; Patel, Abhinam

    2014-01-01

    Introduction. Thrombocytopenia is frequently noticed with P. falciparum malaria but is less reported and studied with P. vivax. Materials and Methods. The study was conducted in the Department of Medicine, SBKS MI & RC, Pipariya. We included patients who were diagnosed with vivax malaria. The data regarding their clinical and hematological profile was collected and analysed. Result. A total of 66 patients were included. 42 (63%) had platelet count <100000/mm(3). Mean platelet count was 1,18,650, range being 8000/mm(3)-6,10,000/mm(3). Amongst those with thrombocytopenia, 16 (38.09%) had anemia, 14 (33.33%) had serum creatinine >1.2 gm/dL, 15 (35.71%) had jaundice (s. bilirubin > 1.2), 2 (4.76%) had altered sensorium, 6 (14.28%) had ARDS, 2 needed ventilator support, and 1 expired. Amongst those with normal platelet count, 5 (20.83%) had anemia and 1 had jaundice whereas none had elevated s. creatinine, altered sensorium, or lung involvement. Conclusion. Thrombocytopenia is now being seen more commonly with vivax malaria. Patients with platelet count <1 lac/cumm have more severe disease. PMID:25045358

  4. Treatment of D alloimmunization in pregnancy with plasmapheresis and intravenous immune globulin: case report.

    PubMed

    Fernández Alba, Juan J; León, Raquel; González-Macías, Carmen; Paz, Antonio; Prado, Fabiana; Moreno, Luis J; Torrejón, Rafael

    2014-08-01

    The prevalence of D alloimmunization occurs between 0.15% and 0.4%. The anti-D can cross the placenta and cause hemolysis and fetal anemia. At present, a Doppler study of the middle cerebral artery allows the monitoring of the degree of fetal anemia. The treatment in cases of moderate to severe anemia in fetuses of less than 34-35 weeks of gestation is intrauterine transfusion via cordocentesis. However, with high titers of anti-D, in the absence of fetal anemia it is possible to modulate the maternal immune response by plasmapheresis and intravenous immunoglobulin administration. We present a case report of an Rh(D) alloimmunized pregnancy treated with plasmapheresis followed by intravenous immunoglobulin administration. We performed a caesarean section at 31 weeks, 5 days of gestation. The hemoglobin at birth was 13.8 g/dl and hematocrit 40.8%. Intrauterine transfusion was not necessary. PMID:25312036

  5. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    PubMed

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP). PMID:26437745

  6. Alloimmunization is associated with older age of transfused red blood cells in sickle cell disease

    PubMed Central

    Desai, Payal C.; Deal, Allison M.; Pfaff, Emily R.; Qaqish, Bahjat; Hebden, Leyna M.; Park, Yara A.; Ataga, Kenneth I.

    2016-01-01

    Red blood cell (RBC) alloimmunization is a significant clinical complication of sickle cell disease (SCD). It can lead to difficulty with cross-matching for future transfusions and may sometimes trigger life-threatening delayed hemolytic transfusion reactions. We conducted a retrospective study to explore the association of clinical complications and age of RBC with alloimmunization in patients with SCD followed at a single institution from 2005 to 2012. One hundred and sixty six patients with a total of 488 RBC transfusions were evaluated. Nineteen patients (11%) developed new alloantibodies following blood transfusions during the period of review. The median age of RBC units was 20 days (interquartile range: 14–27 days). RBC antibody formation was significantly associated with the age of RBC units (P = 0.002), with a hazard ratio of 3.5 (95% CI: 1.71–7.11) for a RBC unit that was 7 days old and 9.8 (95% CI: 2.66–35.97) for a unit that was 35 days old, 28 days after the blood transfusion. No association was observed between RBC alloimmunization and acute vaso-occlusive complications. Although increased echocardiography-derived tricuspid regurgitant jet velocity (TRV) was associated with the presence of RBC alloantibodies (P = 0.02), TRV was not significantly associated with alloimmunization when adjusted for patient age and number of transfused RBC units. Our study suggests that RBC antibody formation is significantly associated with older age of RBCs at the time of transfusion. Prospective studies in patients with SCD are required to confirm this finding. PMID:25963831

  7. Red blood cell and leukocyte alloimmunization in patients awaiting kidney transplantation

    PubMed Central

    da Silva, Silvia Fernandes Ribeiro; Ferreira, Gláucia Maria; da Silva, Sonia Leite; Alves, Tânia Maria de Oliveira; Ribeiro, Ilana Farias; Ribeiro, Thyciana Rodrigues; Cavalcante, Maria do Carmo Serpa

    2013-01-01

    Objective To determine the rates of red blood cell and leukocyte alloimmunization in patients with chronic kidney disease awaiting kidney transplantation. Methods In this cross-sectional and prospective study, the serum of 393 chronic kidney disease patients on a transplant waiting list in Ceará, Northeastern Brazil were tested for red cell and leukocyte antibodies. In addition, demographic, clinical and laboratory data were collected. Results The average age in the sample of 393 patients was 34.1 ± 14 years. Slightly more than half (208; 52.9%) were male. The average numbers of transfusions and gestations were 3.1 ± 3.3 and 1.6 ± 6, respectively. One third (33.6%) were alloimmunized: 78% with leukocyte antibodies, 9.1% with red cell antibodies and 12.9% with both. Red cell antibodies were detected in 29 cases (7.4%), 17 of whom were women, who had received more transfusions than the males (p-value < 0.0001). The most frequently detected red cell antibodies belonged to the Rh (24.1%) and Kell (13.8%) blood group systems. Leukocyte antibodies were detected in 30.5% of cases, 83 of whom were women, who had received more transfusions than the males (p-value < 0.0001) and were more reactive to panel reactive antibodies (p-value < 0.0001). The mean alloreactivity to panel reactive antibodies was 47.7 ± 31.2%. Conclusion Chronic kidney disease patients on the transplant waiting list in Ceará, Brazil, display high rates of red cell (7.4%) and leukocyte (30.5%) alloimmunization. In this sample, alloimmunization was significantly associated with the number of transfusions and gender. PMID:23904808

  8. Genetics of Transfusion Recipient Alloimmunization: Can Clues from Susceptibility to Autoimmunity Pave the Way?

    PubMed Central

    Tatari-Calderone, Zohreh; Luban, Naomi L.C.; Vukmanovic, Stanislav

    2014-01-01

    Summary The search for genetic determinants of alloimmunization in sickle cell disease transfusion recipients was based on two premises: i) that polymorphisms responsible for stronger immune and/or inflammatory responses and hemoglobin βS mutation were co-selected by malaria; and ii) that stronger responder status contributes to development of lupus. We found a marker of alloimmunization in the gene encoding for Ro52 protein, also known as Sjögren syndrome antigen 1 (SSA1) and TRIM21. Surprisingly, the nature of the association was opposite of that with lupus; the same variant of a polymorphism (rs660) that was associated with lupus incidence was also associated with induction of tolerance to red blood cell antigens during early childhood. The dual function of Ro52 can explain this apparent contradiction. We propose that other lupus/autoimmunity susceptibility loci may reveal roles of additional molecules in various aspects of alloimmunization induced by transfusion as well as during pregnancy. PMID:25670931

  9. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

    PubMed Central

    Cordiano, I; Betterle, C; Spadaccino, C A; Soini, B; Girolami, A; Fabris, F

    1998-01-01

    The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations. PMID:9737665

  10. A case of oxaliplatin-induced immune-mediated thrombocytopenia

    PubMed Central

    Suh, Seong Eun; Jang, Moon Ju; Chong, So Young; Aster, Richard H.; Curtis, Brian R.

    2014-01-01

    Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin. PMID:24724069

  11. Associations of Rhesus and non-Rhesus maternal red blood cell alloimmunization with stillbirth and preterm birth

    PubMed Central

    Fan, Jing; Lee, Brian K; Wikman, Agneta T; Johansson, Stefan; Reilly, Marie

    2014-01-01

    Background: Although the risks of adverse pregnancy outcomes associated with anti-D antibodies are well-recognized, much less is known concerning alloimmunization with other red blood cell antibodies detected during routine maternal screening. To date, most reports of adverse pregnancy outcomes associated with non-anti-D antibodies have been from small case studies. The aim of this study was to examine the associations of maternal alloimmunization with specific red blood cell antibodies and the risks of preterm birth and stillbirth in the Swedish population. Methods: All antibody screening, outcome and covariate data were obtained through linkages of Swedish national health and data registers. Follow-up in these population-based registers was available up to 31 December 2002. The final study sample consisted of 1 022 569 singleton births from 668 952 mothers during 1987–2002. Results: In total, 1.3% of the 1 022 569 study pregnancies were alloimmunized. In adjusted logistic regression models, compared with having no antibodies, alloimmunization with anti-D, anti-E, anti-C and anti-c was associated with increased risk of both stillbirth and preterm birth. In addition, anti-Kell was associated with increased risk of preterm birth and anti-Lea with increased risk of stillbirth. Compared with firstborn children, risk of preterm birth associated with alloimmunization was greater in subsequent births Conclusions: In the largest study to date, alloimmunization with Rhesus, K- and -Lea red blood cell antibodies increased the risk of preterm birth and/or stillbirth. The association of anti-Lea with stillbirth was an unexpected finding. Further study of the consequences of non-anti-D alloimmunization is warranted. PMID:24801308

  12. Heparin-induced thrombocytopenia: laboratory studies.

    PubMed

    Kelton, J G; Sheridan, D; Santos, A; Smith, J; Steeves, K; Smith, C; Brown, C; Murphy, W G

    1988-09-01

    This report describes studies into the pathophysiology of heparin-induced thrombocytopenia. The IgG fraction from each of nine patients with heparin-induced thrombocytopenia caused heparin-dependent platelet release of radiolabeled serotonin. Both the Fc and the Fab portions of the IgG molecule were required for the platelet reactivity. The platelet release reaction could be inhibited by the Fc portion of normal human or goat IgG, and patient F(ab')2, but not F(ab')2 from healthy controls. These results suggested that the Fab portion of IgG binds to heparin forming an immune complex and the immune complexes initiate the platelet release reaction by binding to the platelet Fc receptors. To directly challenge this hypothesis, we preincubated the serotonin-labeled platelets with the monoclonal antibody against the platelet Fc receptor (IV.3). This monoclonal antibody completely inhibited the release reaction caused by heparin and patient sera, as well as heat aggregated IgG, but did not block collagen or thrombin-induced platelet release. Heparin-dependent platelet release also could be inhibited in vitro by the addition of monocytes and neutrophils, but not by red cells, presumably because the Fc receptors on the phagocytic cells have a higher binding affinity for IgG complexes than do platelets. Platelets from patients with congenital deficiencies of specific glycoproteins Ib and IX (Bernard-Soulier syndrome) and IIb and IIIa (Glanzmann's thrombasthenia) displayed normal heparin-dependent release indicating that the release reaction did not require the participation of these glycoproteins. These studies indicate that heparin-induced thrombocytopenia is an IgG-heparin immune complex disorder involving both the Fab and Fc portion of the IgG molecule. PMID:3416077

  13. Predictive value of mean platelet volume in gold induced thrombocytopenia.

    PubMed Central

    Klimiuk, P S; Holt, P J; Clague, R B; Herod, E; Dyer, P A

    1987-01-01

    In rheumatoid arthritis the mean platelet volume does not alter with the institution of parenteral gold therapy and with long term gold therapy. It appears to have no value in predicting the onset of thrombocytopenia. It may, however, predict a haemorrhagic diathesis once gold induced thrombocytopenia is established. PMID:3813673

  14. [Neonatal hemochromatosis: Another entity that is no longer orphan. Advances in the diagnosis and management of the main cause of neonatal acute liver failure].

    PubMed

    Molera Busoms, C; Quintero Bernabeu, J; Martín de Carpi, J

    2015-09-01

    Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers. PMID:25801288

  15. Pathophysiology and management of primary immune thrombocytopenia.

    PubMed

    Kashiwagi, Hirokazu; Tomiyama, Yoshiaki

    2013-07-01

    Primary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins, such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production, although autoantibody-independent mechanisms, such as T cell-mediated cytotoxicity, may also be involved in its pathogenesis. Recent advances in the localization of autoantigenic epitopes and the characterization of T cell functional abnormalities in ITP patients have improved our understanding of the pathophysiology of this disease. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized. PMID:23702914

  16. Therapeutic Amenorrhea in Patients at Risk for Thrombocytopenia

    PubMed Central

    Martin-Johnston, Meredith K.; Okoji, Olanma Y.; Armstrong, Alicia

    2016-01-01

    To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive—extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy. PMID:18492296

  17. Presumptive bovine neonatal pancytopenia in a Holstein calf in Québec.

    PubMed

    Gosselin, Véronique Bernier; Fecteau, Gilles; Nichols, Sylvain

    2011-07-01

    An 18-day-old heifer was presented with fever, depression, tachycardia, tachypnea, and prolonged bleeding time. Blood tests revealed severe anemia, thrombocytopenia, and leucopenia. The animal was negative by PCR for bovine virus diarrhea virus antigen. The findings supported a diagnosis of bovine neonatal pancytopenia. Treatments included fresh whole blood transfusion and antibiotics. The animal recovered fully. PMID:22210946

  18. Wiskott-Aldrich Syndrome Presenting with JMML-Like Blood Picture and Normal Sized Platelets

    PubMed Central

    Patil, Rajesh B.; Shanmukhaiah, Chandrakala; Bamborde, Shailesh; Wasekar, Nilesh; Toshniwal, Manoj; Mohite, Aniket; Patil, Vinod

    2016-01-01

    Objective. The aim of this paper is to report the case of Wiskott-Aldrich syndrome (WAS) that presented with unusual laboratory features. Clinical Presentation and Intervention. Male neonate admitted with symptoms related to thrombocytopenia, whose initial diagnosis was considered as neonatal alloimmune thrombocytopenia and JMML (juvenile myelomonocytic leukemia) but subsequently diagnosis was confirmed as WAS. Conclusion. This case shows that a suspicion of WAS is warranted in the setting of neonatal thrombocytopenia with JMML-like blood picture and normal sized platelets. PMID:27340577

  19. Bovine neonatal pancytopenia in calves in Poland.

    PubMed

    Jaśkowski, J M; Polak, M P; Marszałek, A; Nowak, K; Frackowiak, H; Olechnowicz, J

    2012-01-01

    Bovine neonatal pancytopenia (BNP), a newly emerged syndrome of discussed etiology in calves, has been diagnosed since 2006. Here we describe first cases of BNP in Poland. Between September 2008 and April 2011, 62 cases of BNP were diagnosed in dairy calves. Bleeding skin lesions were mostly pronounced in summer and early autumn. Severe thrombocytopenia was observed in all sick animals. All calves came from herds vaccinated against BVDV infection with PregSure BVD vaccine (Pfizer). Substitution of colostrum from dams of BNP positive calves with colostrum from dams from herds free of BNP was the only effective measure to avoid new cases in affected herds. PMID:23214380

  20. Risk factors for ganciclovir-induced thrombocytopenia and leukopenia.

    PubMed

    Matsumoto, Kazuaki; Shigemi, Akari; Ikawa, Kazuro; Kanazawa, Naoko; Fujisaki, Yuko; Morikawa, Norifumi; Takeda, Yasuo

    2015-01-01

    Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR)=3.1), creatinine clearance (<20 mL/min) (OR=12.8), and the ganciclovir dose (≥12 mg/kg/d) (OR=15.1). Leukopenia occurred in 36 patients (28.6%), and white blood cell count (<6000 cells/mm(3)) (OR=3.7) and the ganciclovir dose (≥12 mg/kg/d) (OR=7.8) were identified as risk factors. These results demonstrated that several factors influenced the occurrence of ganciclovir-induced thrombocytopenia and leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia. PMID:25747982

  1. Intramuscular anti-D in chronic immune thrombocytopenia children with severe thrombocytopenia.

    PubMed

    Sirachainan, Nongnuch; Anurathapan, Usanarat; Chuansumrit, Ampaiwan; Songdej, Duantida; Wongwerawattanakoon, Pakawan; Hutspardol, Sakara; Kitpoka, Pimpun

    2013-12-01

    Nine patients with chronic immune thrombocytopenia and platelet counts <20 × 10(9) /L, with a median age of 7.8 (3.8-15.5) years, received three phases of 10 mcg/kg/dose of intramuscular anti-D. Phase 1 was anti-D daily for 5 days, followed by phase 2, anti-D weekly for 12 weeks and withheld when platelet counts ≥ 20 × 10(9) /L, and then phase 3 was anti-D once every 2 weeks for 24 weeks. According to the International Working Group criteria, in phase 1, 66.7% of patients responded to the treatment. In phases 2 and 3, 11.1% (0-41.7%) and 7.7% (0-33.3%) of total episodes of follow up, respectively, responded to the treatment. Therefore, intramuscular anti-D given at a dose of 10 mcg/kg for 5 days is an alternative method to raise platelet counts in chronic immune thrombocytopenia children with severe thrombocytopenia where the intravenous form of anti-D is not available. PMID:24330299

  2. Neonatal hypotonia.

    PubMed

    Sparks, Susan E

    2015-06-01

    Neonatal hypotonia is a common problem in the neonatal intensive care unit. The genetic differential diagnosis is broad, encompassing primary muscular dystrophies, chromosome abnormalities, neuropathies, and inborn errors of metabolism. Recognition of hypotonia is relatively straightforward, but determining the cause can be challenging. It is important for the neonatologist to have an organized approach to the assessment of neonatal hypotonia. Physical examination and history alongside basic laboratory testing and imaging aid in the differential diagnosis. Identification of the cause is essential for determining prognosis, associated morbidities, and recurrence risk. The prevailing therapeutic modality is physical, occupational, speech/feeding, and respiratory therapy. PMID:26042909

  3. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    PubMed Central

    Bernal-Macías, Santiago; Fino-Velásquez, Laura-Marcela; Vargas-Barato, Felipe E.; Guerra-Galue, Lucio; Reyes-Beltrán, Benjamín; Rojas-Villarraga, Adriana

    2015-01-01

    Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL). Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl. PMID:26798527

  4. Neonatal conjunctivitis

    MedlinePlus

    Newborn conjunctivitis; Conjunctivitis of the newborn; Ophthalmia neonatorum; Eye infection - neonatal conjunctivitis ... diseases spread through sexual contact to prevent newborn conjunctivitis caused by these infections. Putting eye drops into ...

  5. Neonatal Death

    MedlinePlus

    ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Neonatal death ... story First Candle Centering Corporation The Compassionate Friends Star Legacy Foundation Last reviewed: November, 2015 Complications & Loss ...

  6. Neonatal sepsis

    MedlinePlus

    ... and some strains of streptococcus. Group B streptococcus (GBS) has been a major cause of neonatal sepsis. ... an infant's risk of early-onset bacterial sepsis: GBS colonization during pregnancy Preterm delivery Water breaking (rupture ...

  7. Acute renal failure and severe thrombocytopenia associated with metamizole.

    PubMed

    Redondo-Pachon, Maria Dolores; Enriquez, Ricardo; Sirvent, Ana Esther; Millan, Isabel; Romero, Alberto; Amorós, Francisco

    2014-01-01

    Metamizole or dipyrone is a pyrazolone derivative that belongs to the non-steroidal anti-inflammatory drugs. Its main side-effect is hematological toxicity. Thrombocytopenia due to metamizole is rare and is usually associated with the involvement of the two other blood series. Drug-induced thrombocytopenia is more frequently related to immune mechanisms, and the diagnosis is still largely made by exclusion of other causes and by correlation of timing of thrombocytopenia with the administration of drug. Metamizole may cause acute renal failure due to hemodynamic renal failure/acute tubular necrosis and/or acute tubulointerstitial nephritis. We report a case of acute renal failure and severe thrombocytopenia after metamizole. As far as we know, this combination of adverse effects from this drug has not been reported previously. PMID:24434395

  8. Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD).

    PubMed

    Anderson, B; Shad, A T; Gootenberg, J E; Sandler, S G

    1999-03-01

    Alloimmunization to the D blood group antigen following the transfusion of D-positive red blood cells to a D-negative recipient may be prevented in most persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until recently, the only RhIG approved by the US Food and Drug Administration (FDA) for this indication required intramuscular injection, an inconvenient and painful route for the relatively large volume that may be required. We describe the successful prevention of Rh alloimmunization following the unintentional transfusion of D-positive red blood cells to a D-negative infant by the intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention of post-transfusion Rh alloimmunization by intravenous administration. We believe that this more convenient and less painful approach should be the treatment of choice for preventing Rh alloimmunization following the transfusion of D-positive red cells to a D-negative recipient. PMID:10072121

  9. Thrombopoietin: a potential diagnostic indicator of immune thrombocytopenia in pregnancy

    PubMed Central

    Zhang, Xu; Zhao, Yajing; Li, Xiaoqing; Han, Panpan; Jing, Fangmiao; Kong, Zhangyuan; Zhou, Hai; Qiu, Jihua; Li, Lizhen; Peng, Jun; Hou, Ming

    2016-01-01

    To evaluate whether the serum thrombopoietin levels in pregnancy-associated immune thrombocytopenia (ITP) differ from those in gestational thrombocytopenia, and reveal the possibility of thrombopoietin serving as a marker for differential diagnosis. Serum thrombopoietin concentration was determined in ITP in pregnancy (n = 35), gestational thrombocytopenia (n = 31), healthy pregnancy (n = 32), age-matched nonpregnant ITP (n = 32) and nonpregnant healthy controls (n = 35) by ELISA. The serum thrombopoietin level of ITP in pregnancy (1283 ± 646 pg/mL) was significantly higher than gestational thrombocytopenia (187 ± 64 pg/mL) (P < 0.01), although the platelet counts of these two disorders may overlap. Twenty-nine of 35 patients with ITP in pregnancy had thrombopoietin values >500 pg/mL, whereas none of the gestational thrombocytopenia patients' thrombopoietin levels exceeded 500 pg/mL. In addition, ITP in pregnancy presented a markedly higher thrombopoietin level than nonpregnant ITP (88 ± 41 pg/mL) (P < 0.01), indicating that the pathogenesis of pregnant and nonpregnant ITP was different. Our findings suggest that measurement of serum thrombopoietin concentration provides valuable diagnostic information for differentiating ITP in pregnancy from gestational thrombocytopenia. Thrombopoietin represents a reliable marker for ITP in pregnancy. PMID:26840092

  10. The pathophysiology of thrombocytopenia in chronic liver disease

    PubMed Central

    Mitchell, Oscar; Feldman, David M; Diakow, Marla; Sigal, Samuel H

    2016-01-01

    Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD). In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex pathophysiology of the thrombocytopenia of CLD is crucial when considering treatment strategies. This review outlines the recent advances in our understanding of thrombocytopenia in cirrhosis and CLD. PMID:27186144

  11. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

    PubMed Central

    de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave’s disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy. PMID:26484334

  12. The pathophysiology of thrombocytopenia in chronic liver disease.

    PubMed

    Mitchell, Oscar; Feldman, David M; Diakow, Marla; Sigal, Samuel H

    2016-01-01

    Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD). In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex pathophysiology of the thrombocytopenia of CLD is crucial when considering treatment strategies. This review outlines the recent advances in our understanding of thrombocytopenia in cirrhosis and CLD. PMID:27186144

  13. Practice Bulletin No 166 Summary : Thrombocytopenia in Pregnancy.

    PubMed

    2016-09-01

    Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (1). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Système International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/μL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (2, 3). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID:27548548

  14. Seasonal Association of Immune Thrombocytopenia in Adults

    PubMed Central

    Tombak, Anıl; Boztepe, Burcu; Tiftik, Naci; Cömert, Melda; Salim, Ozan; Aydın, Kaniye; Gürkan, Emel; Yücel, Orhan Kemal; Saydam, Güray; Sungur, Mehmet Ali

    2015-01-01

    Background: Immune thrombocytopenia (ITP) is an autoimmune disorder. It is characterized by thrombocytopenia due to thrombocyte destruction mediated by autoantibodies; however, cytotoxic and defective regulatory T-lymphocytes play an important role in its pathogenesis. While childhood ITP is usually acute, self-limiting and generally seasonal in nature, ITP in adults is usually chronic; its relation with seasons has not been studied. Aims: We investigated whether months and/or seasons have triggering roles in adults with ITP. Study Design: Descriptive study. Methods: A retrospective case review of adult patients with primary ITP diagnosed at various University Hospitals in cities where Mediterranean climate is seen was performed. Demographic data, date of referral and treatments were recorded. Corticosteroid-resistant, chronic and refractory cases were determined. Relation between sex, corticosteroid-resistant, chronic and refractory ITP with the seasons was also investigated. Results: The study included 165 patients (124 female, mean age=42.8±16.6). Most cases of primary ITP were diagnosed in the spring (p=0.015). Rates of patients diagnosed according to the seasons were as follows: 35.8% in spring, 23% in summer, 20.6% in fall, and 20.6% in winter. With respect to months, the majority of cases occurred in May (18.2%). Time of diagnosis according to the seasons did not differ between genders (p=0.699). First-line treatment was corticosteroids in 97.3%, but 35% of the cases were corticosteroid-resistant. Steroid-resistant patients were mostly diagnosed in the spring (52.1%) (p=0.001). ITP was chronic in 52.7% of the patients and they were also diagnosed mostly in the spring (62.7%) (p=0.149). Conclusion: This is the first study showing seasonal association of ITP in adults and we have observed that ITP in adults is mostly diagnosed in the spring. The reason why more patients are diagnosed in the spring may be due to the existence of atmospheric pollens reaching

  15. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  16. Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia.

    PubMed

    Hillgruber, Carina; Pöppelmann, Birgit; Weishaupt, Carsten; Steingräber, Annika Kathrin; Wessel, Florian; Berdel, Wolfgang E; Gessner, J Engelbert; Ho-Tin-Noé, Benoît; Vestweber, Dietmar; Goerge, Tobias

    2015-07-27

    Spontaneous organ hemorrhage is the major complication in thrombocytopenia with a potential fatal outcome. However, the exact mechanisms regulating vascular integrity are still unknown. Here, we demonstrate that neutrophils recruited to inflammatory sites are the cellular culprits inducing thrombocytopenic tissue hemorrhage. Exposure of thrombocytopenic mice to UVB light provokes cutaneous petechial bleeding. This phenomenon is also observed in immune-thrombocytopenic patients when tested for UVB tolerance. Mechanistically, we show, analyzing several inflammatory models, that it is neutrophil diapedesis through the endothelial barrier that is responsible for the bleeding defect. First, bleeding is triggered by neutrophil-mediated mechanisms, which act downstream of capturing, adhesion, and crawling on the blood vessel wall and require Gαi signaling in neutrophils. Second, mutating Y731 in the cytoplasmic tail of VE-cadherin, known to selectively affect leukocyte diapedesis, but not the induction of vascular permeability, attenuates bleeding. Third, and in line with this, simply destabilizing endothelial junctions by histamine did not trigger bleeding. We conclude that specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients. PMID:26169941

  17. Neonatal transfusion.

    PubMed

    Kelly, Anne M; Williamson, Lorna M

    2013-11-01

    Neonates and particularly preterm neonates are frequent recipients of large volumes of blood products relative to their size. Good quality evidence for transfusion practice in this patient group has been lacking but is now increasing. Triggers for red cell transfusion are now better defined, with on-going trials of platelet transfusions likely to yield similar evidence. Transfusion is now extremely safe, but complications such as transfusion associated acute lung injury (TRALI) and transfusion associated circulatory overload (TACO) are likely to be under recognised, particularly in the sick extremely preterm neonate with respiratory symptoms. This review summarises the rationale and current practice with regard to blood component therapy. Background data on component specifications and hazards of transfusion are provided. Indications for transfusion of specific products including red cells, platelets, and plasma are discussed, and their use is illustrated by case examples. PMID:24095206

  18. Neonatal Stridor

    PubMed Central

    Daniel, Matija; Cheng, Alan

    2012-01-01

    Neonatal stridor is an important condition, in many cases implying an impending disaster with a very compromised airway. It is a sign that has to be considered with the rest of the history and examination findings, and appropriate investigations should then be undertaken to confirm the source of the noise. Neonates with stridor should be managed in a multidisciplinary setting, by clinicians familiar with the intricate physiology of these children, and with access to the multitude of medical and surgical investigative and therapeutic options required to provide first-rate care. PMID:22235209

  19. Mouse model of alloimmune-induced vascular rejection and transplant arteriosclerosis.

    PubMed

    Enns, Winnie; von Rossum, Anna; Choy, Jonathan

    2015-01-01

    Vascular rejection that leads to transplant arteriosclerosis (TA) is the leading representation of chronic heart transplant failure. In TA, the immune system of the recipient causes damage of the arterial wall and dysfunction of endothelial cells and smooth muscle cells. This triggers a pathological repair response that is characterized by intimal thickening and luminal occlusion. Understanding the mechanisms by which the immune system causes vasculature rejection and TA may inform the development of novel ways to manage graft failure. Here, we describe a mouse aortic interposition model that can be used to study the pathogenic mechanisms of vascular rejection and TA. The model involves grafting of an aortic segment from a donor animal into an allogeneic recipient. Rejection of the artery segment involves alloimmune reactions and results in arterial changes that resemble vascular rejection. The basic technical approach we describe can be used with different mouse strains and targeted interventions to answer specific questions related to vascular rejection and TA. PMID:26066300

  20. Micromanaging alloimmunity.

    PubMed

    Ford, Mandy L

    2016-07-01

    Increasing evidence indicates that microbes have a large influence on immune function. Previous studies have linked pathogenic microorganisms with decreased allograft tolerance and subsequent rejection. In this issue of the JCI, Lei and colleagues demonstrate that commensal organisms also influence the host response to allograft transplantation. Using murine skin and cardiac transplant models, the authors demonstrate that allograft rejection is accelerated in mice with a normal microbiome compared with germ-free animals and antibiotic-treated mice. The increased graft rejection observed in conventional animals was due to enhanced T cell priming and was mediated through type I IFN. Together, these results suggest that altering a patient's microbial community prior to transplant could improve allograft acceptance. PMID:27322057

  1. Alloimmunization screening after transfusion of red blood cells in a prospective study

    PubMed Central

    Alves, Vitor Mendonça; Martins, Paulo Roberto Juliano; Soares, Sheila; Araújo, Gislene; Schmidt, Luciana Cayres; Costa, Sidneia Sanches de Menezes; Langhi, Dante Mário; Moraes-Souza, Helio

    2012-01-01

    Background Several irregular red blood cell alloantibodies, produced by alloimmunization of antigens in transfusions or pregnancies, have clinical importance because they cause hemolysis in the fetus and newborn and in transfused patients. Objective a prospective analysis of patients treated by the surgical and clinical emergency services of Hospital de Clínicas of the Universidade Federal do Triângulo Mineiro (HC/UFTM), Brazil was performed to correlate alloimmunization to clinical and epidemiological data. Methods Blood samples of 143 patients with initial negative antibody screening were collected at intervals for up to 15 months after the transfusion of packed red blood cells. Samples were submitted to irregular antibody testing and, when positive, to the identification and serial titration of alloantibodies. The Fisher Exact test and Odds Ratio were employed to compare proportions. Results Fifteen (10.49%) patients produced antibodies within six months of transfusion. However, for 60% of these individuals, the titers decreased and disappeared by 15 months after transfusion. Anti-K antibodies and alloantibodies against antigens of the Rh system were the most common; the highest titer was 1:32 (anti-K). There was an evident correlation with the number of transfusions. Conclusions Given the high incidence of clinically important red blood cell alloantibodies in patients transfused in surgical and clinical emergency services, we suggest that phenotyping and pre-transfusion compatibilization for C, c, E, e (Rh system) and K (Kell system) antigens should be extended to all patients with programmed surgeries or acute clinical events that do not need emergency transfusions. PMID:23049421

  2. Neonatal meningitis.

    PubMed

    Heath, P T; Nik Yusoff, N K; Baker, C J

    2003-05-01

    Twelve years ago an annotation was published in Archives of Disease in Childhood regarding the antibiotic treatment of suspected neonatal meningitis. The authors recommended the use of cephalosporins rather than chloramphenicol and advocated intraventricular aminoglycoside treatment in selected cases. They noted the absence of clinical trials with third generation cephalosporins that showed an improvement in mortality or neurological outcome. PMID:12719388

  3. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation and early initiation of therapy are required to prevent adverse outcomes. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  4. Thrombocytopenia in Malaria with Immunoglobulin (IgM) Changes

    PubMed Central

    Beale, P. J.; Cormack, J. D.; Oldrey, T. B. N.

    1972-01-01

    Of 33 cases of naturally occurring human malaria 32 were found to have significant thrombocytopenia. Only one patient showed signs of bleeding. The lowest platelet levels were found between the day of diagnosis and the fourth day of treatment. Thereafter they returned to normal values. No other factors could be found to correlate with the presence or depth of thrombocytopenia, and no evidence of intravascular coagulation was found in any case. A rise in the immunoglobulin IgM was found in all 13 cases in which it was estimated. Since thrombocytopenia can occur independently of intravascular coagulation the latter should be diagnosed and heparin given only after clotting factors have been shown to be depleted. ImagesFIG. 3 PMID:5008661

  5. Intravenous Immunoglobulin Responsive Persistent Thrombocytopenia after Dengue Haemorrhagic Fever

    PubMed Central

    Charaniya, Riyaz; Ghosh, Anindya; Sahoo, Ratnakar

    2016-01-01

    Dengue outbreak is common in Indian subcontinent and causes significant morbidity and mortality. Year 2015 has witnessed yet another Dengue epidemic in northern India and the number of cases this year is maximum in a decade. Dengue infection is a viral disease and there are 4 different serotypes DENV1, DENV2, DENV3 and DENV4. This year DENV2 and DENV4 have been isolated from most of the patients. Thrombocytopenia is hallmark of dengue infection and generally recovers within ten days of onset of symptoms. We report a case of dengue haemorrhagic fever in which thrombocytopenia persisted for almost a month and improved after Intravenous immunoglobulin (IVIG) administration. This is the first case where IVIG has been successfully used for treating persisting thrombocytopenia after dengue infection. PMID:27190868

  6. Drug-induced thrombocytopenia secondary to natalizumab treatment

    PubMed Central

    Cachia, David; Izzy, Saef; Berriosmorales, Idanis; Ionete, Carolina

    2014-01-01

    Summary A 52-year-old woman with a 10-year history of relapsing-remitting multiple sclerosis (RRMS) was started on natalizumab after she developed side effects for interferon β-1a and glatiramer acetate. The patient presented with acute severe infusion reaction after the third treatment with natalizumab, developing whole-body purpura. Laboratory testing revealed progressive worsening thrombocytopenia up to 3 weeks following natalizumab discontinuation. Platelet antibodies to platelet-specific antigen as well as antibodies against natalizumab were positive. Bone marrow biopsy was negative. The patient was diagnosed with drug-induced immune thrombocytopenia (DITP) as a rare case of natalizumab side effect which was treated with intravenous methylprednisolone followed by rituximab with successful resolution of thrombocytopenia. The patient had a stable course of RRMS with no relapses and no brain MRI changes at 2 years after initiation of rituximab. PMID:24879724

  7. Immune thrombocytopenia (ITP): a rare association of lymph node tuberculosis.

    PubMed

    Surana, Anuj P; Shelgikar, Kishor M; Melinkeri, Sameer; Phadke, Arvind

    2014-01-01

    Although various haematologic abnormalities are known to occur with tuberculosis, association of immune thrombocytopenia with tuberculosis is uncommon. We report a case of retroperitoneal lymph node tuberculosis who presented with ITP. A 76 year old female was admitted to our hospital with oral mucosal bleed and petechial lesions over extremities and abdomen. A diagnosis of immune thrombocytopenia (ITP) was established. Intravenous Anti-D immunoglobulin and Dexamethasone therapy was started, but failed to elicit any sustained platelet response. CT abdomen revealed multiple retroperitoneal lymph nodes with central necrosis. Histopathology (HPE) of these revealed caseating lymphadenitis suggestive of tuberculosis. After 2 months of anti-tuberculous therapy, the platelet counts returned to normal and patient was off all therapy for ITP thereby suggesting likely association between tuberculosis and immune thrombocytopenia. PMID:25327103

  8. Intravenous Immunoglobulin Responsive Persistent Thrombocytopenia after Dengue Haemorrhagic Fever.

    PubMed

    Kumar, Prabhat; Charaniya, Riyaz; Ghosh, Anindya; Sahoo, Ratnakar

    2016-04-01

    Dengue outbreak is common in Indian subcontinent and causes significant morbidity and mortality. Year 2015 has witnessed yet another Dengue epidemic in northern India and the number of cases this year is maximum in a decade. Dengue infection is a viral disease and there are 4 different serotypes DENV1, DENV2, DENV3 and DENV4. This year DENV2 and DENV4 have been isolated from most of the patients. Thrombocytopenia is hallmark of dengue infection and generally recovers within ten days of onset of symptoms. We report a case of dengue haemorrhagic fever in which thrombocytopenia persisted for almost a month and improved after Intravenous immunoglobulin (IVIG) administration. This is the first case where IVIG has been successfully used for treating persisting thrombocytopenia after dengue infection. PMID:27190868

  9. Quinine-induced thrombocytopenia following intravenous use of heroin

    SciTech Connect

    Christie, D.J.; Walker, R.H.; Kolins, M.D.; Wilner, F.M.; Aster, R.H.

    1983-06-01

    Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin.

  10. A rare case of idiopathic thrombocytopenia in association with an ovarian teratoma in pregnancy

    PubMed Central

    Soma-Pillay, P; Macdonald, A P; Mnisi, E

    2009-01-01

    Thrombocytopenia complicates 6–7% of pregnancies. We present the case of a 26-year-old patient who presented with severe thrombocytopenia associated with an ovarian teratoma in the second trimester of pregnancy.

  11. Anti-TJa alloimmunization (anti-PP1Pk): two consecutive pregnancies of an anti-TJa-carrying patient.

    PubMed

    Haentjens-Verbeke, K; Dufour, P h; Vinatier, D; Tordjeman, N; Monnier, J C; Manessier, L

    1996-01-01

    Anti-TJa alloimmunization is an extremely rare condition which can cause miscarriages during the first and second terms of pregnancy. At 20-year-old female patient, an anti-TJa carrier, was given plasma transfusions in the course of her first two pregnancies. The cordocentesis, which was the main follow-up test during the first pregnancy, could not be carried out during the second pregnancy due to the presence of a huge subchorionic hematoma. Both pregnancies were characterized by fetal growth retardation, which was particularly considerable in one. Due to chronic fetal distress, both infants were delivered prematurely by cesarean section. The immunohematological data concerning anti-TJa alloimmunization and the different palliative treatments available to date are reviewed. PMID:8838768

  12. Rapid-Onset Thrombocytopenia Following Piperacillin-Tazobactam Reexposure.

    PubMed

    Nguyen, Van Dong; Tourigny, Jean-François; Roy, Renaud; Brouillette, Denis

    2015-12-01

    Drug-induced thrombocytopenia is a rare but serious adverse event that has been associated with multiple drugs including β-lactams. Although it mostly occurs with prolonged medication use, some cases of rapid-onset thrombocytopenia have been reported. We describe the case of a 69-year-old man who developed severe and immediate thrombocytopenia following reexposure to piperacillin-tazobactam in the critical care setting. He received a 6-day course of piperacillin-tazobactam for a possible pneumonia immediately after cardiac surgery. During this course of therapy, his platelet count decreased (fluctuating between 69 × 10(3) /mm(3) and 104 × 10(3) /mm(3) ) and then progressively increased after completion of the antibiotic to 340 × 10(3) /mm(3) on postoperative day 15. Ten days after the antibiotic course was completed (postoperative day 16), the patient developed new signs of infection (fever and neutrophilia), and piperacillin-tazobactam was restarted. Eight hours after reintroducing the antibiotic, his platelet count dropped from 317 × 10(3) /mm(3) to 7 × 10(3) /mm(3) . After reviewing all the medications administered to the patient as well as other potential causes of thrombocytopenia, and given the chronology of events, piperacillin-tazobactam was suspected as the most likely offending agent and was therefore replaced by meropenem on postoperative day 17. The patient's platelet count began to rise 2 days after discontinuation of piperacillin-tazobactam and reached 245 × 10(3) /mm(3) by postoperative day 30. No spontaneous bleeding or thrombosis occurred while the patient was thrombocytopenic. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of thrombocytopenia and piperacillin-tazobactam therapy. This case highlights the severity and swiftness in which drug-induced thrombocytopenia may present in the context of cardiac surgery. PMID:26684560

  13. Myelodysplastic Syndrome Presenting as Amegakaryocytic Thrombocytopenia in a Collodion Baby

    PubMed Central

    Al Pakra, Mohammed; Al Jabri, Abdullah; Hanafy, Ehab

    2015-01-01

    We report a rare case of myelodysplastic syndrome that presented early as amegakaryocytic thrombocytopenia in a collodion baby, which is a rare congenital disorder characterized by thick, taut membrane resembling oiled parchment or collodion, which is subsequently shed. To our knowledge, this is the first reported case of a collodion baby who presented with amegakaryocytic thrombocytopenia and who has a significant family history of the same condition. We document the rarity of this possible association and also the need for further study to establish whether a causal relationship exists. PMID:26904703

  14. Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review.

    PubMed

    Salter, Benjamin S; Weiner, Menachem M; Trinh, Muoi A; Heller, Joshua; Evans, Adam S; Adams, David H; Fischer, Gregory W

    2016-05-31

    Heparin-induced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. In this comprehensive review, the authors highlight heparin-induced thrombocytopenia's risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment. The authors place special emphasis on the management of patients requiring procedures using cardiopulmonary bypass or interventions in the catheterization laboratory. Clinical vigilance of this disease process is important to ensure its recognition, diagnosis, and treatment. Misdiagnosis of the syndrome, as well as misunderstanding of the disease process, continues to contribute to its morbidity and mortality. PMID:27230048

  15. Immune thrombocytopenia following successful treatment of cancer in children.

    PubMed

    Price, Victoria; Barnes, Chris; Canning, Patricia; Blanchette, Victor; Greenberg, Mark

    2006-03-01

    A predisposition to developing immune thrombocytopenia (ITP) has not been reported in survivors of childhood cancer. We report a case series of childhood cancer survivors who developed an isolated thrombocytopenia in the presence of a normocellular bone marrow. Five children, two with endodermal sinus tumors and three with acute lymphoblastic leukemia, developed ITP at a median of 4 years (range: 0.2-8 years) after completion of therapy. We suggest the association of ITP in survivors of childhood malignancy may not be co-incidental as chemotherapy may cause persistent immune dysfunction. PMID:15700256

  16. Does Helicobacter pylori eradication play a role in immune thrombocytopenia?

    PubMed

    Llovet, Valentina; Rada, Gabriel

    2016-01-01

    Helicobacter pylori infection has been implicated as trigger or disease modifier in immune thrombocytopenia (ITP). So, eradication treatment for this agent could have clinical benefits. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified four systematic reviews comprising 40 studies addressing the question of this article overall, including one randomized controlled trial. We combined the evidence using meta-analysis and generated a summary of findings following the GRADE approach. We concluded Helicobacter eradication might decrease risk of bleeding in patients with immune thrombocytopenia but the certainty of the evidence is low. PMID:27603101

  17. Selective Plasma Exchange for Critically Ill Patients Accompanied With Thrombocytopenia.

    PubMed

    Nakae, Hajime; Fukuda, Hirokazu; Okuyama, Manabu; Igarashi, Toshiko

    2016-08-01

    Selective plasma exchange is a blood purification therapy in which simple plasma exchange is performed using a selective membrane plasma separator (pore size of 0.03 µm). Seven critically ill patients accompanied with thrombocytopenia were treated with selective plasma exchange using fresh frozen plasma. The total bilirubin levels and prothrombin time international normalized ratios decreased significantly after treatment. The total protein, albumin, and fibrinogen levels increased significantly after treatment. Selective plasma exchange may be a useful blood purification therapy for removing causal substances and retaining coagulation factors in patients accompanied with thrombocytopenia. PMID:27523072

  18. Neonatal circumcision.

    PubMed

    Lerman, S E; Liao, J C

    2001-12-01

    The merits of neonatal circumcision continue to be debated hotly. Some argue that circumcision is a "uniquely American medical enigma." Most of the world's male population remains uncircumcised; however, most boys born in the United States continue to undergo neonatal circumcision. Review of existing literature supports that most children who are uncircumcised do well from a medical standpoint and, thus, the question of whether US health care practitioners are subjecting neonates to an unnecessary surgical procedure remains. The medical benefits of circumcision are multiple, but most are small. The clearest medical benefit of circumcision is the relative reduction in the risk for a UTI, especially in early infancy. Although this risk [figure: see text] is real, the absolute numbers are small (risk ranges from 1 in 100 to 1 in 1000), and one investigator has estimated that it may take approximately 80 neonatal circumcisions to prevent one UTI. In the case of a patient with known urologic abnormalities that predispose to UTI, neonatal circumcision has a clearer role in terms of medical benefit to the patient. Most of the other medical benefits of circumcision probably can be realized without circumcision as long as access to clean water and proper penile hygiene are achieved. Proper penile hygiene should all but eliminate the risk for foreskin-related medical problems that will require circumcision. Moreover, proper hygiene and access to clean water has been shown to reduce the rate of development of squamous cell carcinoma of the penis in the uncircumcised population. Proper techniques on the care of the foreskin are illustrated in the American Academy of Pediatrics pamphlet titled "How to care for the uncircumcised penis." Regarding the relationship between STDs and circumcision, patient education and the practice of low-risk sexual behavior make a far greater impact than does routine circumcision in hopes of reducing the spread of HIV and other STDs. Nevertheless

  19. Linkage between the mechanisms of thrombocytopenia and thrombopoiesis

    PubMed Central

    Kunishima, Shinji

    2016-01-01

    Thrombocytopenia is defined as a status in which platelet numbers are reduced. Imbalance between the homeostatic regulation of platelet generation and destruction is 1 potential cause of thrombocytopenia. In adults, platelet generation is a 2-stage process entailing the differentiation of hematopoietic stem cells into mature megakaryocytes (MKs; known as megakaryopoiesis) and release of platelets from MKs (known as thrombopoiesis or platelet biogenesis). Until recently, information about the genetic defects responsible for congenital thrombocytopenia was only available for a few forms of the disease. However, investigations over the past 15 years have identified mutations in genes encoding >20 different proteins that are responsible for these disorders, which has advanced our understanding of megakaryopoiesis and thrombopoiesis. The underlying pathogenic mechanisms can be categorized as (1) defects in MK lineage commitment and differentiation, (2) defects in MK maturation, and (3) defect in platelet release. Using these developmental stage categories, we here update recently described mechanisms underlying megakaryopoiesis and thrombopoiesis and discuss the association between platelet generation systems and thrombocytopenia. PMID:26787737

  20. Intracerebral hemorrhage caused by varicella-induced thrombocytopenia.

    PubMed

    Lizarazo, Jairo; Castellanos, María Fernanda; Omaña, Claudia Rosa; Chaín, Miguel; Villamizar, Sergio

    2016-01-01

    We present the case of a previously healthy 44-years-old man with chickenpox, severe thrombocytopenia, mucosal hemorrhage, and intracerebral hemorrhage in the right hemisphere. The patient was treated with platelets and high doses of steroids. He recovered although with persistent left homonymous hemianopsia and epilepsy, which were controlled with medication. PMID:27622799

  1. Linkage between the mechanisms of thrombocytopenia and thrombopoiesis.

    PubMed

    Eto, Koji; Kunishima, Shinji

    2016-03-10

    Thrombocytopenia is defined as a status in which platelet numbers are reduced. Imbalance between the homeostatic regulation of platelet generation and destruction is 1 potential cause of thrombocytopenia. In adults, platelet generation is a 2-stage process entailing the differentiation of hematopoietic stem cells into mature megakaryocytes (MKs; known as megakaryopoiesis) and release of platelets from MKs (known as thrombopoiesis or platelet biogenesis). Until recently, information about the genetic defects responsible for congenital thrombocytopenia was only available for a few forms of the disease. However, investigations over the past 15 years have identified mutations in genes encoding >20 different proteins that are responsible for these disorders, which has advanced our understanding of megakaryopoiesis and thrombopoiesis. The underlying pathogenic mechanisms can be categorized as (1) defects in MK lineage commitment and differentiation, (2) defects in MK maturation, and (3) defect in platelet release. Using these developmental stage categories, we here update recently described mechanisms underlying megakaryopoiesis and thrombopoiesis and discuss the association between platelet generation systems and thrombocytopenia. PMID:26787737

  2. [A neonate with pustules].

    PubMed

    Groot, Dominique T; van den Broek, Annique J M

    2016-01-01

    We describe a female neonate with non-grouped pustules directly postpartum without clinical signs of illness. There were no red maculae. At follow-up some pustules had turned to pigmented maculae, which confirmed the diagnosis of neonatal pustular melanosis. This benign transient condition occurs in 4-8% of dark-coloured neonates and in <1% of white neonates. PMID:26840934

  3. Neonatal resuscitation: Current issues

    PubMed Central

    Chadha, Indu A

    2010-01-01

    The following guidelines are intended for practitioners responsible for resuscitating neonates. They apply primarily to neonates undergoing transition from intrauterine to extrauterine life. The updated guidelines on Neonatal Resuscitation have assimilated the latest evidence in neonatal resuscitation. Important changes with regard to the old guidelines and recommendations for daily practice are provided. Current controversial issues concerning neonatal resuscitation are reviewed and argued in the context of the ILCOR 2005 consensus. PMID:21189881

  4. [Neonatal cholestasis].

    PubMed

    Lacaille, F

    2016-03-01

    "Cholestasis" means abnormal synthesis or secretion of bile. The main symptom in a neonate or infant is jaundice. Urine is dark, staining diapers, and stools are variably pale or white. Vitamin K should be injected (to prevent coagulation disorders due to malabsorption). The two diagnoses requiring urgent treatment are urinary tract infection and biliary atresia. If stools are permanently white, biliary atresia is highly probable. A few genetic causes of intrahepatic cholestasis should be screened and corrective surgery organized. The diseases responsible for cholestasis in this age group are described as well as the investigations and treatments, including the management of non-specific complications of cholestasis. A delay in the diagnosis of biliary atresia can have such severe consequences that consultation with a hepatology unit or transfer should be easy and rapid. PMID:26850153

  5. Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

    PubMed Central

    Elayeb, Rahma; Tamagne, Marie; Bierling, Philippe; Noizat-Pirenne, France; Vingert, Benoît

    2016-01-01

    Murine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization. In vaccination studies, the intensity of antigen-specific responses depends on the delay between antigen and adjuvant administration, with a short delay limiting immune responses. In mouse models of alloimmunization, the delay between the injection of Toll-like receptor agonists and transfusion is usually short. In this study, we hypothesized that the timing of Toll-like receptor 3 agonist administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like receptor 3 agonist, was administered to B10BR mice at various time points before the transfusion of HEL-expressing red blood cells. For each time point, we measured the activation of splenic HEL-presenting dendritic cells, HEL-specific CD4+ T cells and anti-HEL antibodies in serum. The phenotype of activated immune cells depended on the delay between transfusion and Toll-like receptor-dependent inflammation. The production of anti-HEL antibodies was highest when transfusion occurred 7 days after agonist injection. The proportion of HEL-presenting CD8α+ dendritic cells producing interleukin-12 was highest in mice injected with poly(I:C) 3 days before transfusion. Although the number of early-induced HEL-specific CD4+ T cells was similar between groups, a high proportion of these cells expressed CD134, CD40 and CD44 in mice injected with poly(I:C) 7 days before transfusion. This study clearly shows that the delay between transfusion and Toll-like receptor-induced inflammation influences the immune response to transfused red blood cells. PMID:26430173

  6. Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

    PubMed Central

    Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

    1978-01-01

    Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

  7. Immune Thrombocytopenia (ITP) Secondary to Subclinical Hashimoto’s Thyroiditis

    PubMed Central

    Tahir, Hassan; Sheraz, Faizan; Sagi, Jahnavi; Daruwalla, Vistasp

    2016-01-01

    Immune thrombocytopenia (ITP) is the most common cause of isolated thrombocytopenia in healthy people. ITP may rarely coexist with autoimmune thyroid disorders, which may indicate more complex defect in immune system. Primary ITP usually responds well to steroids and intravenous immunoglobulins. However, ITP may be difficult to treat when associated with thyroid autoimmune disorders. In such cases, treating the underlying thyroid disorder may significantly improve platelet count and can either cause remission of disease or improve response to standard ITP therapy. We report a case of 47-year-old male who was diagnosed with ITP and was also found to have subclinical Hashimoto’s thyroiditis. Treatment of subclinical hypothyroidism with levothyroxine in our patient significantly improved the platelets, thus successfully bringing the disease in remission. PMID:27200380

  8. Platelet destruction in immune thrombocytopenia. Understanding the mechanisms.

    PubMed

    Bakchoul, Tamam; Sachs, Ulrich J

    2016-08-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia. A dysfunctional proliferation of autoreactive T cells is suggested to be responsible for the loss of tolerance to self-platelet antigens in ITP patients. Autoreactive T cells induce uncontrolled proliferation of autoantibody producing B cells leading to persistent anti-platelet autoimmunity in some ITP patients. The autoimmune response causes an increased destruction of platelets by antibody-mediated phagocytosis, complement activation but also by T cell mediated cytotoxicity. In addition, abnormalities in thrombopoiesis and insufficient platelet production due to antibody or T cell mediated megakaryocyte inhibition and destruction contribute to the pathophysiology of ITP. These various effector cell responses may account for the heterogeneity in the clinical manifestation of ITP and also, to success or failure of different treatment strategies. A better understanding of the mechanisms behind ITP will hopefully allow for better diagnostic and, particularly, therapeutic strategies in the future. PMID:25982994

  9. [Cerebrovascular complications of immunologically mediated heparin-induced thrombocytopenia].

    PubMed

    Macha, K; Kloska, S; Dörfler, A; Raaz-Schrauder, D; Schwab, S; Köhrmann, M; Seifert, F

    2014-03-01

    Immunologically mediated heparin-induced thrombocytopenia (HIT) is a thrombotic disease caused by antibodies occurring after heparin exposure. Thrombocytopenia occurs within a few days after heparin exposure, about half of HIT-patients develop venous or arterial thrombotic complications. Neurological complications of HIT are mainly ischaemic stroke and sinus vein thrombosis. To ensure the primary clinical diagnosis functional and immunological assays for antibody detection are available. The probability for the occurrence of HIT depends on the nature of heparin employed (LMWH vs. UFH) and individual patient characteristics such as gender and primary disease (medical vs. surgical patients). In the case of suspected HIT heparin administration should be discontinued immediately and replaced by an alternative anticoagulation to prevent the expansion or development of further thrombotic complications. Herein we report a case of a patient suffering from HIT-associated embolic cerebral ischaemic stroke. PMID:24615586

  10. Heparin-induced thrombocytopenia: pathophysiology and new treatment options.

    PubMed

    Harenberg, J; Jörg, I; Fenyvesi, T

    2002-01-01

    Heparin induced thrombocytopenia (HIT) is a severe complication of heparin therapy. It is generally accompanied by a paradoxical decrease in platelets leading to activation of platelets and of the coagulation system. HIT type I is a mild, transient, non-immune disorder. HIT type II is an immune-mediated reaction towards neo-antigen on PF4, which is platelet factor 4 (PF4) that is exposed upon binding to heparins. A low sulfated octasaccharide is required for binding to PF4. The generated immunoglobulines bridge platelets by binding to the FcgRIIa-receptor. In patients with HIT type II heparin/LMW-heparin has to be discontinued immediately upon clinical suspicion. Diagnosis can be confirmed by laboratory tests. As patients are at high risk for or because they have developed thromboembolism, anticoagulation is mandatory, despite thrombocytopenia. Treatment options are danaparoid, r-hirudin, bivalirudin, argatroban, dextransulfate, and dermatansulfate. In future, fondaparinux and ximelagatran may be considered for treatment. PMID:13679659

  11. Immune-mediated mechanism for thrombocytopenia after Loxosceles spider bite.

    PubMed

    Levin, Carina; Bonstein, Lilach; Lauterbach, Roy; Mader, Rivka; Rozemman, Dganit; Koren, Ariel

    2014-08-01

    Loxoscelism, characterized by high fever, vomiting, malaise, a dermonecrotic lesion, and thrombocytopenia, was diagnosed in a 3-year-old female. Clinical laboratory and dermatological signs are described. Blood test showed a transient hypercoagulable state and the presence of IgG antibodies against platelets, suggesting an immune-mediated mechanism for platelet destruction, in addition to the direct toxic effect of the spider venom. The finding of platelet antibodies after a Loxosceles spider bite has not been previously reported. PMID:24497468

  12. Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP).

    PubMed

    Kumar, Manjusha; Lambert, Michele P; Breakey, Vicky; Buchanan, George R; Neier, Michelle; Neufeld, Ellis J; Kempert, Pamela; Neunert, Cindy E; Nottage, Kerri; Klaassen, Robert J

    2015-12-01

    We surveyed 278 pediatric hematologists/oncologists regarding how children with immune thrombocytopenia (ITP) are counseled for participation in sports. Results show substantial variation in physician perception of contact risk for different sports, and the advice offered about restriction of sport activities of affected children. Many physicians recommend restriction of sports when platelet counts are under 50 × 10(9) /L. Such restriction may affect the child's quality of life despite their having an overall benign disease. PMID:26174203

  13. Thrombocytopenia with absent radius in a boy and his uncle.

    PubMed

    Schnur, R E; Eunpu, D L; Zackai, E H

    1987-09-01

    We report a boy and his maternal uncle who have Thrombocytopenia-Absent Radius (TAR) syndrome. The mother of the propositus is normal. A maternal aunt has mild radial hypoplasia, possibly representing partial expression of the syndrome. A review of the literature shows several pedigrees in which relatives other than sibs were affected with TAR. Thus, autosomal recessive inheritance may not account for all cases and alternate modes of transmission should be considered. PMID:3314504

  14. Congenital hemophagocytic lymphohistiocytosis presenting as thrombocytopenia in a newborn.

    PubMed

    Hinson, Ashley; Owen, William; Prose, Neil; Parikh, Suhag; Thornburg, Courtney

    2015-05-01

    Hemophagocytic lymphohistiocytosis (HLH) is a disease caused by dysregulation and hyperactivation of the immune system, and can be familial or acquired. HLH presenting in infancy can be rapidly fatal if not promptly recognized and treated. Congenital HLH can be caused by various genetic mutations or part of immunodeficiency syndromes. We present an infant with Griscelli syndrome and familial HLH with atypical genetic mutations, presenting as thrombocytopenia on the first day of life, cured with chemotherapy and unrelated cord blood transplant. PMID:25121636

  15. A Rare Case of Myelodysplastic Syndrome with Refractory Thrombocytopenia

    PubMed Central

    Jehangir, Waqas; Webb, John; Singh, Shilpi; Arshed, Sabrina; Sen, Shuvendu; Yousif, Abdalla

    2015-01-01

    Myelodysplastic syndromes (MDS) represent a variety of clonal abnormalities, possibly preleukemic and display numerous phenotypic manifestations. Specific mutations carry high morbidity and mortality rates due to cell line dysplasia. MDS commonly presents with symptoms related to anemia, and approximately two-thirds will develop thrombocytopenia, a rare, but potentially lethal complication that increases complexity in treatment and morbidity, and may be due to unique genetic mutations leading to refractory thrombocytopenia, ultimately leading to an overall reduction in survival. Careful identification and monitoring of this patient subdivision can significantly reduce morbidity and mortality, and potential identification of specific gene mutations and advances in treatment options will hopefully provide guidance on detecting at-risk patients in the future. We present a case of a man with MDS-U (karyotype 46, XY, del (20) (q11.2q13.3) (20) with no detected JAK2 V617F mutation), who in despite of appropriate evidenced based treatment, continued to exhibit refractory thrombocytopenia. PMID:26487931

  16. A Rare Case of Myelodysplastic Syndrome with Refractory Thrombocytopenia.

    PubMed

    Jehangir, Waqas; Webb, John; Singh, Shilpi; Arshed, Sabrina; Sen, Shuvendu; Yousif, Abdalla

    2015-09-23

    Myelodysplastic syndromes (MDS) represent a variety of clonal abnormalities, possibly preleukemic and display numerous phenotypic manifestations. Specific mutations carry high morbidity and mortality rates due to cell line dysplasia. MDS commonly presents with symptoms related to anemia, and approximately two-thirds will develop thrombocytopenia, a rare, but potentially lethal complication that increases complexity in treatment and morbidity, and may be due to unique genetic mutations leading to refractory thrombocytopenia, ultimately leading to an overall reduction in survival. Careful identification and monitoring of this patient subdivision can significantly reduce morbidity and mortality, and potential identification of specific gene mutations and advances in treatment options will hopefully provide guidance on detecting at-risk patients in the future. We present a case of a man with MDS-U (karyotype 46, XY, del (20) (q11.2q13.3) (20) with no detected JAK2 V617F mutation), who in despite of appropriate evidenced based treatment, continued to exhibit refractory thrombocytopenia. PMID:26487931

  17. Flow cytometry for the diagnosis of autoimmune thrombocytopenia.

    PubMed

    Tomer, Aaron

    2006-03-01

    Autoimmune thrombocytopenia is a disorder characterized by antibody-mediated accelerated platelet destruction. Despite its clinical importance, the diagnosis of autoimmune thrombocytopenia is one of exclusion, thus inevitably associated with potential difficulties. Current clinically applicable methods used to determine antigen-specific antibodies, primarily directed to GPIIb/IIIa (CD41a) and GPIb (CD42b), include the monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay and the radioactive immunobead assay. Neither of these assays is commonly used by clinical laboratories, however, because of methodologic and practical limitations. As a result, diagnoses are generally based on clinical impression despite patient presentations that are sometimes complex. To overcome some of these difficulties, flow cytometric techniques have been developed, employing standard methods and equipment suitable for testing a single sample or multiple samples, as may occur in cases of autoimmune thrombocytopenia. The availability of a feasible technique such as flow cytometry, with improved sensitivity and specificity, should facilitate the routine use of a diagnostic method in the evaluation of thrombo-cytopenic patients suspected of having an autoimmune disorder and permit follow-up to determine immune remission. PMID:16537048

  18. Suspects in the tale of lupus-associated thrombocytopenia

    PubMed Central

    Ziakas, P D; Routsias, J G; Giannouli, S; Tasidou, A; Tzioufas, A G; Voulgarelis, M

    2006-01-01

    Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren’s syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues. PMID:16792676

  19. Novel oral anticoagulants for heparin-induced thrombocytopenia.

    PubMed

    Skelley, Jessica W; Kyle, Jeffrey A; Roberts, Rachel A

    2016-08-01

    To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians. PMID:27102287

  20. Noninvasive low-level laser therapy for thrombocytopenia.

    PubMed

    Zhang, Qi; Dong, Tingting; Li, Peiyu; Wu, Mei X

    2016-07-27

    Thrombocytopenia is a common hematologic disorder that is managed primarily by platelet transfusions. We report here that noninvasive whole-body illumination with a special near-infrared laser cures acute thrombocytopenia triggered by γ-irradiation within 2 weeks in mice, as opposed to a 5-week recovery time required in controls. The low-level laser (LLL) also greatly accelerated platelet regeneration in the presence of anti-CD41 antibody that binds and depletes platelets, and prevented a severe drop in platelet count caused by a common chemotherapeutic drug. Mechanistically, LLL stimulated mitochondrial biogenesis specifically in megakaryocytes owing to polyploidy of the cells. LLL also protected megakaryocytes from mitochondrial injury and apoptosis under stress. The multifaceted effects of LLL on mitochondria bolstered megakaryocyte maturation; facilitated elongation, branching, and formation of proplatelets; and doubled the number of platelets generated from individual megakaryocytes in mice. LLL-mediated platelet biogenesis depended on megakaryopoiesis and was inversely correlated with platelet counts, which kept platelet biogenesis in check and effectively averted thrombosis even after repeated uses, in sharp contrast to all current agents that stimulate the differentiation of megakaryocyte progenitors from hematopoietic stem cells independently of platelet counts. This safe, drug-free, donor-independent modality represents a paradigm shift in the prophylaxis and treatment of thrombocytopenia. PMID:27464749

  1. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

    Sugiura, K.; Steiner, M.; Baldini, M.G.

    1980-10-01

    Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/..mu..l had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

  2. Neonatal lupus with atypical cardiac and cutaneous manifestation

    PubMed Central

    Morais, Sofia; Santos, Isabel Cristina; Pereira, Dolores Faria; Mimoso, Gabriela

    2013-01-01

    Neonatal lupus erythematosus is a rare, passively acquired autoimmune disease, caused by maternal autoantibodies. The most common manifestations are skin rash and congenital heart block. Cutaneous manifestations may be present at birth, but often develop within a few weeks after delivery. Congenital heart block may present as bradycardia in utero or during physical examination at birth. Approximately 40–60% of mothers are asymptomatic when the infants are diagnosed. We present a case of a child, born with erythematosus lesions in the face, scalp, trunk, limbs and nodules/papules on the palmar and plantar surfaces. He also had hepatosplenomegaly and thrombocytopenia. Echocardiography showed hyperechoic lesions on the anterior papilar muscle of the left ventricle and on the lateral cusp of the tricuspid valve. The mother had unexplained fever and vasculitic lesions in her hands and feet. Antinuclear antibodies, anti-SSa/Ro and anti-SSb/La were positive in the mother and child, making the diagnosis of neonatal lupus. PMID:23839605

  3. Clinical analysis of kasabach-merritt syndrome in 17 neonates

    PubMed Central

    2014-01-01

    Background Kasabach-Merritt syndrome (KMS) is characterized by giant hemangiomas and severe thrombocytopenia, which may result in life-threatening multi-organ hemorrhage. This study evaluated the clinical characteristics, treatments, and outcomes in neonates with KMS, in order to find out the optimal therapy. Methods The clinical data of 17 patients treated for KMS in the Department of Neonates, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, China from January 2007 to January 2012 were retrospectively analyzed. Results The patients were 13 males and 4 females, aged 17 hours to 28 days at admission. Four patients had visceral hemangiomas and 13 had cutaneous hemangiomas. All had thrombocytopenia and coagulation disorders. Intravenous steroid therapy was initially effective in 6 patients (of which 3 relapsed) and ineffective in 11. The 11 patients with a poor response to steroids and the 3 who relapsed underwent arterial embolization therapy, which was effective in 9 patients (of which 1 relapsed), ineffective in 4, and discontinued before completion in 1. Subsequently, four patients in whom arterial embolization therapy was ineffective and one with relapse were treated with vincristine. This was effective in four patients, and the other died of disseminated intravascular coagulation. Steroid therapy was effective in 35.3% of patients, but the relapse rate was 50%. Arterial embolization was effective in 64.3% of patients and vincristine was effective in 80%. Conclusions In patients with neonatal KMS, steroid therapy has a low rate of effectiveness and high rate of relapse. Arterial embolization has a good rate of effectiveness. Combined steroid and embolization therapy should be considered for first-line treatment of neonatal KMS. If this approach is ineffective, vincristine may be useful. PMID:24920221

  4. Neonatal euthanasia.

    PubMed

    Kon, Alexander A

    2009-12-01

    Despite advances in the care of infants, there remain many newborns whose medical conditions are incompatible with sustained life. At times, healthcare providers and parents may agree that prolonging life is not an appropriate goal of care, and they may redirect treatment to alleviate suffering. While pediatric palliative treatment protocols are gaining greater acceptance, there remain some children whose suffering is unrelenting despite maximal efforts. Due to the realization that some infants suffer unbearably (ie, the burdens of suffering outweigh the benefits of life), the Dutch have developed a protocol for euthanizing these newborns. In this review, I examine the ethical aspects of 6 forms of end of life care, explain the ethical arguments in support of euthanasia, review the history and verbiage of the United States regulations governing limiting and withdrawing life-prolonging interventions in infants, describe the 3 categories of neonates for whom the Dutch provide euthanasia, review the published analyses of the Dutch protocol, and finally present some practical considerations should some form of euthanasia ever be deemed appropriate. PMID:19914522

  5. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    PubMed Central

    ATTAYA, SHARIFF; KANTHI, YOGENDRA; ASTER, RICHARD; MCCRAE, KEITH

    2015-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies. PMID:19172524

  6. [Severe thrombocytopenia associated with simultaneous cytomegalovirus and Epstein-barr virus infection in an immunocompetence patient].

    PubMed

    Bober, Grazyna; Krawczyk-Kuliś, Małgorzata; Kopera, Małgorzata; Hołowiecki, Jerzy

    2003-06-01

    A 22 year old woman, without preceeding immunological and hematological disorders was hospitalized because of severe thrombocytopenia. The results of extended workup revealed simultaneous cytomegalovirus and Epstein-Barr virus infection as the most probable causative factor. Both, thrombocytopenia and the symptoms of viral infections resolved after consequent treatment with acyclovir, corticosteroids and intravenous immunoglobulines. Based on this original case report authors suggest the need of virological tests in newly diagnosed idiopatic thrombocytopenia. PMID:14567095

  7. Interaction between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmune responses in vivo.

    PubMed

    Salama, Alan D; Yuan, Xueli; Nayer, Ali; Chandraker, Anil; Inobe, Manabu; Uede, Toshimutsu; Sayegh, Mohamed H

    2003-04-01

    The B7-CD28 pathway is one of the foremost costimulatory pathways involved in T-cell activation. Recently, a number of additional costimulatory pathways have been described and preliminary data suggest that they play important roles in alloimmunity. However, the interactions between these different pathways are not well understood. We studied the effect of targeting ICOS ligand, B7RP1, in a rat cardiac transplant model, with and without concomitant blockade of the B7 pathway using CTLA4Ig. In a fully mismatched WF to LEW vascularized cardiac allograft model, without therapy, grafts were acutely rejected (MST 10.8 +/- 1.6 days). Early (day of transplant) B7RP1 blockade with ICOSIg alone had little effect on graft survival and rather than being additive with B7 blockade, ICOSIg abrogated the prolonged graft survival induced by CTLA4Ig treatment. By contrast, delayed (day 2 post-transplant) blockade of B7RP1 did not have such an effect. These findings were not related to cytokine deviation but may be in part related to the pattern of down-regulation of B7.2 expression following early B7RP1 blockade. This is the first report describing the complex interactions between ICOS-B7RP1 and B7-CD28 costimulatory pathways in alloimmunity in vivo. PMID:12694060

  8. Constitutional aplastic anaemia: a family with a new X linked variety of amegakaryocytic thrombocytopenia.

    PubMed Central

    Griffiths, A D

    1983-01-01

    A family is described in which three male members died in early infancy with severe thrombocytopenia and a fourth in adolescence with aplastic anaemia. One child was investigated in detail and shown to have amegakaryocytic thrombocytopenia, progressing to pancytopenia as a result of bone marrow hypoplasia. His associated congenital abnormalities differed from those described in Fanconi's aplastic anaemia, his chromosomes were normal, and the fetal haemoglobin level was 48%. Amegakaryocytic thrombocytopenia is itself rare and the index case appears unique. It is suggested that this family has a previously undescribed X linked variety of amegakaryocytic thrombocytopenia. PMID:6196483

  9. Baseline thrombocytopenia complicated by recurrent episodes of transient severe thrombocytopenia following infections in an adult woman with a non involuting congenital hemangioma – a case report

    PubMed Central

    2013-01-01

    Background Congenital hemangiomas are benign abnormal proliferation of blood vessels. Noninvoluting congenital hemangiomas are a rare variant which persist, and may become bigger. Hemangiomas are known to be associated with thrombocytopenia, microangiopathic hemolytic anemia and Kasabach-Merritt phenomenon. Kasabach-Merritt phenomenon is characterized by consumptive coagulopathy with microangiopathic haemolyic anemia and thrombocytopenia. Platelet sequestration in the hemangioma or increased destruction which may either be immune or non immune are also further contributors to thrombocytopenia. Case presentation A 45 year old female with a non involuting hemangioma and baseline thrombocytopenia was observed to develop repeated episodes of transient severe thrombocytopenia associated with a variety of infectious conditions. Laboratory investigations suggested a peripheral mechanism. Platelet counts always returned to baseline levels on resolution of the precipitating infection. Conclusion The authors report this phenomenon as the first reported case of baseline thrombocytopenia complicated by recurrent episodes of transient severe thrombocytopenia following infections associated with a non involuting congenital hemangioma. The observations made in this patient were unique and hitherto unreported in medical literature. Both peripheral sequestration and destructive consumption were considered likely. Consumptive mechanisms were likely to encompass either or both immune and non immune causes. Further studies are needed to establish the precise pathogenesis. PMID:23758712

  10. [Neonatal Dengue. Presentation of clinical cases].

    PubMed

    Romero-Santacruz, Edith; Lira-Canul, Janeth Jaqueline; Pacheco-Tugores, Fredy; Palma-Chan, Adolfo Gonzalo

    2015-05-01

    Dengue is an infectious disease caused by a flavivirus, with four serotypes, transmitted by the mosquito Aedes aegypti. In Mexico it is a public health problem, especially in the region of central and southeast of the country. The disease can be asymptomatic or present serious forms and even death. It is confirmed by detection of the NS1 Antigen; IgM antibodies, polymerase chain reaction and virus isolation. The vertical transmission to de newborn has been little studied. 7 cases in neonates from November to December 2011 are reported. All patients were male, obtained by caesarean section between 34 and 40 weeks of gestation, whose mothers were enrolled with fever and symptoms associated with dengue disease and serology positive for dengue. Six with positive AgNS1 and one positive IgM; one mother died. All the newborns had positive serology for dengue, 4 with positive AgNS1 and 3 positive IgM. The clinical features of the newborn ranged from asymptomatic to one serious dengue fever, shock and hemorrhage. The symptomatic 6 attended with thrombocytopenia, changes in temperature and unspecific disturbance. The severity of mothers conditioned disrepair product at birth, but not with subsequent gravity of the new born. Vertical trasmission of dengue should be suspected in risk areas, to maintain vigilance and to give early treatment. Also is neccesary promote the realization of specific diagnostic and therapeutic guidelines to the neonatal period. PMID:26233977

  11. Routine neonatal circumcision?

    PubMed Central

    Tran, P. T.; Giacomantonio, M.

    1996-01-01

    Routine neonatal circumcision is still a controversial procedure. This article attempts to clarify some of the advantages and disadvantages of neonatal circumcision. The increased rate of penile cancer among uncircumcised men appears to justify the procedure, but that alone is not sufficient justification. The final decision on neonatal circumcision should be made by parents with balanced counsel from attending physicians. PMID:8939321

  12. Interferon-β therapy and risk of thrombocytopenia in multiple sclerosis patients.

    PubMed

    Koudriavtseva, Tatiana; Plantone, Domenico; Renna, Rosaria; Mandoj, Chiara; Giannarelli, Diana; Mainero, Caterina

    2015-12-01

    Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (±SD) 44.5 ± 10.7 years] and 200 controls (56 males, mean age 45.5 ± 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 × 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-β therapy compared with those on low-dose interferon-β therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-β therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-β therapy is the variable most strongly associated with thrombocytopenia. PMID:26209931

  13. Rituximab-associated acute thrombocytopenia: an under-diagnosed phenomenon.

    PubMed

    Ram, Ron; Bonstein, Lilach; Gafter-Gvili, Anat; Ben-Bassat, Isaac; Shpilberg, Ofer; Raanani, Pia

    2009-04-01

    Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines--TNF-alpha, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. PMID:19260124

  14. Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

    PubMed Central

    Domínguez, A; Gamallo, G; Garcia, R; Lopez-Pastor, A; Peña, J M; Vazquez, J J

    1994-01-01

    AIM--To analyse the pathogenic mechanism of HIV related thrombocytopenia. METHODS--Forty one patients with thrombocytopenia and HIV-1 infection were investigated over two years. Anticardiolipin antibodies were measured using an enzyme linked immunosorbent assay and antiplatelet antibodies were measured using an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and rheumatoid factor were also carried out in all patients and 80 control subjects (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were transfused in 13 patients. P24 antigen were also measured in 12 bone marrow aspirates. RESULTS--Antiplatelet antibodies and circulating immune complexes were found exclusively in the thrombocytopenic group; values for antiplatelet antibodies and circulating immune complexes were both higher in homosexual and bisexual patients. Three kinds of pattern were observed using 111 In-labelled platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in just one case. The two most influential factors in the sequestration pattern were antiplatelet antibodies in the splenic uptake and circulating immune complexes in the hepatic and marrow sequestration. All patients, except three, had decreased platelet recovery. In those patients with a CD4 lymphocyte count of less than 200 x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were chosen for immunohistochemical study, p24 antigen was detected in the megakaryocytes, verifying that HIV-1 infects such cells. CONCLUSIONS--The pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted. Antiplatelet antibodies and circulating immune complexes would cause peripheral destruction in the spleen, liver, and bone marrow, in that order; and, on the other hand, there would be an ineffective immune thrombopoiesis and direct infection of the megakaryocytes which

  15. Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer.

    PubMed

    Morton, Jordan M; George, James N

    2016-06-01

    The unexpected occurrence of thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia and thrombocytopenia, in a patient with cancer requires urgent diagnosis and appropriate management. TMA is a term used to describe multiple syndromes caused by microvascular thrombosis, including thrombotic thrombocytopenic purpura (TTP), Shiga toxin-mediated hemolytic uremic syndrome, and complement-mediated TMA. In patients with cancer, systemic microvascular metastases and bone marrow involvement can cause microangiopathic hemolytic anemia and thrombocytopenia. This occurs most often in patients with known metastatic cancer, but microangiopathic hemolytic anemia and thrombocytopenia may occur unexpectedly in patients without known metastatic disease or be the presenting features of undiagnosed cancer. TMA may also be caused by commonly used chemotherapy agents, either through dose-dependent toxicity or an acute immune-mediated reaction. These causes of TMA must be distinguished from TTP, which results from a severe deficiency of ADAMTS13 and is the most common cause of TMA among adults without cancer. The importance of this distinction is to avoid inappropriate use of plasma exchange, which is associated with major complications. Plasma exchange is the essential treatment for TTP, but it has no known benefit for patients with cancer-induced or drug-induced TMA. We will describe cancer-induced and drug-induced TMA using the experience of the Oklahoma TTP-Hemolytic Uremic Syndrome Registry and data from a systematic review of all published reports of drug-induced TMA. We will illustrate the principles of evaluation and management of these disorders with patients' stories. PMID:27288467

  16. Banking of pluripotent adult stem cells as an unlimited source for red blood cell production: potential applications for alloimmunized patients and rare blood challenges.

    PubMed

    Peyrard, Thierry; Bardiaux, Laurent; Krause, Claire; Kobari, Ladan; Lapillonne, Hélène; Andreu, Georges; Douay, Luc

    2011-07-01

    The transfusion of red blood cells (RBCs) is now considered a well-settled and essential therapy. However, some difficulties and constraints still occur, such as long-term blood product shortage, blood donor population aging, known and yet unknown transfusion-transmitted infectious agents, growing cost of the transfusion supply chain management, and the inescapable blood group polymorphism barrier. Red blood cells can be now cultured in vitro from human hematopoietic, human embryonic, or human-induced pluripotent stem cells (hiPSCs). The highly promising hiPSC technology represents a potentially unlimited source of RBCs and opens the door to the revolutionary development of a new generation of allogeneic transfusion products. Assuming that in vitro large-scale cultured RBC production efficiently operates in the near future, we draw here some futuristic but realistic scenarios regarding potential applications for alloimmunized patients and those with a rare blood group. We retrospectively studied a cohort of 16,486 consecutive alloimmunized patients (10-year period), showing 1 to 7 alloantibodies with 361 different antibody combinations. We showed that only 3 hiPSC clones would be sufficient to match more than 99% of the 16,486 patients in need of RBC transfusions. The study of the French National Registry of People with a Rare Blood Phenotype/Genotype (10-year period) shows that 15 hiPSC clones would cover 100% of the needs in patients of white ancestry. In addition, one single hiPSC clone would meet 73% of the needs in alloimmunized patients with sickle cell disease for whom rare cryopreserved RBC units were required. As a result, we consider that a very limited number of RBC clones would be able to not only provide for the need for most alloimmunized patients and those with a rare blood group but also efficiently allow for a policy for alloimmunization prevention in multiply transfused patients. PMID:21377319

  17. Pregnancy boosts vaccine-induced Bovine Neonatal Pancytopenia-associated alloantibodies.

    PubMed

    Benedictus, Lindert; Rutten, Victor P M G; Koets, Ad P

    2016-02-17

    Although maternal vaccination is generally considered to be safe, the occurrence of Bovine Neonatal Pancytopenia (BNP) in cattle shows that maternal vaccination may pose a risk to the offspring. Pregsure BVD-induced maternal alloantibodies cause BNP in newborn calves. The occurrence of BNP years after last Pregsure BVD vaccination indicates that alloantibody levels may remain high in dams. Since pregnancy induces alloantibodies we hypothesized that pregnancy boosts the vaccine-induced alloantibody response. Alloantibody levels in Pregsure BVD-vaccinated dams increased from conception towards the end of gestation and declined after parturition. In parallel, BVDV-antibody levels remained constant, indicating that there is specific boosting of alloantibodies. Since the rise in alloantibodies coincides with pregnancy and other alloantigen sources were excluded, we concluded that fetal alloantigens expressed during pregnancy boost the alloimmune response in the dam. These results help explain why BNP cases occur even years after Pregsure BVD has been taken off the market. PMID:26796141

  18. How we manage patients with heparin induced thrombocytopenia.

    PubMed

    Scully, Marie; Gates, Carolyn; Neave, Lucy

    2016-07-01

    Heparin induced thrombocytopenia (HIT) remains a rare, but significant, condition related to mortality and morbidity. The incidence has decreased with reduced use of unfractionated heparin, with the exception of cardiac surgery. Due to the high risk of thrombosis, a switch to a non-heparin anticoagulant is required, until platelet counts normalize. Within the acute setting, argatroban, fondaparinux and direct acting oral anticoagulants (DOACS) are therapeutic options. In patients with HIT-associated thrombosis or who require long-term anticoagulation, warfarin remains the preference, but DOACs are attractive alternatives. PMID:27097741

  19. Fatal anaphylactoid reaction associated with heparin-induced thrombocytopenia.

    PubMed

    Singla, Atul; Amini, Mohammad R; Alpert, Martin A; Gornik, Heather L

    2013-06-01

    Acute systemic (anaphylaxis and anaphylactoid) reactions have been well described in patients with heparin-induced thrombocytopenia (HIT). Both necrotizing and non-necrotizing skin lesions at heparin injection sites have been reported and may occur in 10-20% of patients with HIT. We report herein a patient treated with subcutaneous enoxaparin sodium who developed non-necrotizing erythematous skin lesions at enoxaparin sodium injection sites. A subsequent intravenous bolus of unfractionated heparin produced a fatal anaphylactoid reaction. This suggests that caution should be exercised in the administration of intravenous heparin to patients with non-necrotizing erythematous skin lesions at prior heparin injection sites. PMID:23579400

  20. Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection.

    PubMed

    Di Mario, A; Sica, S; Zini, G; Salutari, P; Leone, G

    1995-01-01

    A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported. A hemogram showed severe thrombocytopenia, anemia, and leukopenia. Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis. After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities. PMID:7827209

  1. [Latest Advance of Study on Pathogenesis of Immune Thrombocytopenia].

    PubMed

    Yang, Min; Liu, Wen-Jun

    2016-06-01

    Immune thrombocytopenia (ITP) is recognized as a multifactorial cell-specific autoimmune disorder, and its pathogenesis is still not very clear. Traditional concept suggests that the platelet destruction mediated by autoantibodies is the pathophysiology mechanism of ITP, while many studies in recent years have shown that the abnormities of T lymphocyte, dendritic cell (DC), natural killer cell (NK), cytokine, programmed cell death (PCD), oxidative stress (OS), infection, pregnancy and drugs etc play an important role in the pathogenesis of ITP. Since the study of ITP has made a series of important achievements in recent years, this review focuses on the latest advance of studies on pathogenesis of ITP. PMID:27342542

  2. Expansion of the neonatal platelet mass is achieved via an extension of platelet lifespan

    PubMed Central

    Liu, Zhi-Jian; Hoffmeister, Karin M.; Hu, Zhongbo; Mager, Donald E.; Ait-Oudhia, Sihem; Debrincat, Marlyse A.; Pleines, Irina; Josefsson, Emma C.; Kile, Benjamin T.; Italiano, Joseph; Ramsey, Haley; Grozovsky, Renata; Veng-Pedersen, Peter; Chavda, Chaitanya

    2014-01-01

    The fetal/neonatal hematopoietic system must generate enough blood cells to meet the demands of rapid growth. This unique challenge might underlie the high incidence of thrombocytopenia among preterm neonates. In this study, neonatal platelet production and turnover were investigated in newborn mice. Based on a combination of blood volume expansion and increasing platelet counts, the platelet mass increased sevenfold during the first 2 weeks of murine life, a time during which thrombopoiesis shifted from liver to bone marrow. Studies applying in vivo biotinylation and mathematical modeling showed that newborn and adult mice had similar platelet production rates, but neonatal platelets survived 1 day longer in circulation. This prolonged lifespan fully accounted for the rise in platelet counts observed during the second week of murine postnatal life. A study of pro-apoptotic and anti-apoptotic Bcl-2 family proteins showed that neonatal platelets had higher levels of the anti-apoptotic protein Bcl-2 and were more resistant to apoptosis induced by the Bcl-2/Bcl-xL inhibitor ABT-737 than adult platelets. However, genetic ablation or pharmacologic inhibition of Bcl-2 alone did not shorten neonatal platelet survival or reduce platelet counts in newborn mice, indicating the existence of redundant or alternative mechanisms mediating the prolonged lifespan of neonatal platelets. PMID:24599546

  3. Immune Responses in Neonates

    PubMed Central

    Basha, Saleem; Surendran, Naveen; Pichichero, Michael

    2015-01-01

    Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. PMID:25088080

  4. Probable Levofloxacin-Induced Thrombocytopenia in a Patient Previously on Ciprofloxacin: A Case Report and Literature Review

    PubMed Central

    Landi, A. Justine; Burkes, Robert

    2016-01-01

    Drug-induced thrombocytopenia is a poorly understood, yet common phenomenon widely encountered in clinical practice. We present a case of suspected levofloxacin-induced thrombocytopenia, a rare side effect of a ubiquitous antibiotic, in a patient without similar effect to ciprofloxacin. This report builds upon other isolated case reports of fluoroquinolone-induced thrombocytopenia and demonstrates our algorithmic approach to the issue as well as a literature review pertaining to fluoroquinolone-induced thrombocytopenia. PMID:26884767

  5. Intraoperative management of patients with heparin-induced thrombocytopenia.

    PubMed

    Kappa, J R; Fisher, C A; Todd, B; Stenach, N; Bell, P; Campbell, F; Ellison, N; Addonizio, V P

    1990-05-01

    For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation. PMID:1692679

  6. Newly diagnosed immune thrombocytopenia: update on diagnosis and management.

    PubMed

    Bansal, Deepak; Rajendran, Aruna; Singhi, Sunit

    2014-10-01

    Immune thrombocytopenia (ITP) continues to intrigue pediatricians and hematologists alike. Patients can have a dramatic presentation with wide-spread bleeds over a few days. There is an aura and fear of intra-cranial hemorrhage that drives the physician to recommend and the patient's family to accept drug treatment. Difference of opinion among physicians in the recommendations for treatment is not uncommon, even though recent evidence-based guidelines recommend a conservative, observation-based approach for the majority of patients with newly diagnosed childhood ITP. It is important to note that a specific 'platelet cut-off count', is no longer suggested as an indication by itself to recommend drug therapy. The manuscript is an update on newly diagnosed ITP in children. Recent changes in definitions and recommendations for treatment are highlighted. Pros and cons of 1st line drugs, including corticosteroids, intravenous immunoglobulin and anti-D are listed. Adjunctive therapies for the management of epistaxis and menorrhagia are described. Role of splenic artery embolization and emergency splenectomy in the backdrop of severe thrombocytopenia is discussed. Realistic case scenarios, common errors and frequently asked questions are included for a practical and easy reading. PMID:24091868

  7. NxStage dialysis system-associated thrombocytopenia: a report of two cases.

    PubMed

    Sekkarie, Mohamed; Waldron, Michelle; Reynolds, Texas

    2016-01-01

    Thrombocytopenia in hemodialysis patients has recently been reported to be commonly caused by electron-beam sterilization of dialysis filters. We report the occurrence of thrombocytopenia in the first two patients of a newly established home hemodialysis program. The 2 patients switched from conventional hemodialysis using polysulfone electron-beam sterilized dialyzers to a NxStage system, which uses gamma sterilized polyehersulfone dialyzers incorporated into a drop-in cartridge. The thrombocytopenia resolved after return to conventional dialysis in both patients and recurred upon rechallenge in the patient who opted to retry NxStage. This is the first report of thrombocytopenia with the NxStage system according to the authors’ knowledge. Dialysis-associated thrombocytopenia pathophysiology and clinical significance are not well understood and warrant additional investigations. PMID:26521886

  8. A child with split-hand/foot associated with tibial hemimelia (SHFLD syndrome) and thrombocytopenia maps to chromosome region 17p13.3.

    PubMed

    Al Kaissi, Ali; Ganger, Rudolf; Rötzer, Katharina M; Klaushofer, Klaus; Grill, Franz

    2014-09-01

    We describe a-2-year-old boy who presented with a neonatal history of thrombocytopenia associated with a constellation of limb malformations mimicking split hand/foot malformation with long bone deficiency (SHFLD) syndrome. Limb malformations consisted of unilateral monodactyly with radial aplasia, unilateral split foot and bilateral club foot. Tibial aplasia of one limb and tibial hypoplasia of the other limb were notable. Partial agenesis of the sacrum was additional skeletal malformation. Craniofacial features included dense thick scalp hair, narrow frontal area, thick eye-brows, deep-set eyes, depressed nasal bridge, and small overhanging nasal tip, full-cheeks, and large ears. Array-CGH showed duplication of the short arm of chromosome 17p13.3 in the boy and his father, respectively. The father was free from any skeletal abnormalities, though he shares similar craniofacial dysmorphic features like his son. In addition, a paternal sib (uncle of the proband) manifested a phenotype similar to that of the proband. To the best of our knowledge the overall phenotypic and genotypic characterizations were consistent but not completely compatible with the traditional type of TAR syndrome or with SHFLD syndrome. We report on what might be a novel variant of SHFLD associated with transient thrombocytopenia, dysmorphic facial features, and a constellation of bone malformations. PMID:24838992

  9. A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia

    PubMed Central

    Flint, Shaun M.; Gibson, Adele; Lucas, Geoff; Nandigam, Raghava; Taylor, Louise; Provan, Drew; Newland, Adrian C.; Savage, Caroline O.; Henderson, Robert B.

    2016-01-01

    Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B- and T-cell dysregulation. Flow cytometry was used to further characterize the B- and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4+ T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95+ naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naïve B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia. PMID:26969086

  10. Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates.

    PubMed

    Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A; Veng-Pedersen, Peter; Mager, Donald E

    2015-01-01

    Neonatal thrombocytopenia affects 22-35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates. PMID:25362135

  11. Dabigatran approaching the realm of heparin-induced thrombocytopenia.

    PubMed

    Ho, Patricia J; Siordia, Juan A

    2016-06-01

    Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options. PMID:27382551

  12. Use of Thrombopoietin Receptor Agonists in Childhood Immune Thrombocytopenia

    PubMed Central

    Garzon, Angelica Maria; Mitchell, William Beau

    2015-01-01

    Most children with immune thrombocytopenia (ITP) will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long-term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA) have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data are emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long-term safety issues that need to be considered when using these agents. PMID:26322297

  13. Dabigatran approaching the realm of heparin-induced thrombocytopenia

    PubMed Central

    Ho, Patricia J

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is a serious, immune mediated complication of exposure to unfractionated or low-molecular-weight heparin. Though rare, it is a condition associated with high morbidity and mortality that requires immediate change to alternative anticoagulants for the prevention of life-threatening thrombosis. The direct thrombin inhibitors lepirudin and argatroban are currently licensed for the treatment of HIT. Dabigatran, a novel oral anticoagulant (NOAC) with a similar mechanism of action and effective use in other indications, has recently been proposed as another therapeutic option in cases of HIT. This review serves as an introduction to using dabigatran for this purpose, detailing the clinical aspects of its administration, evidence of its performance compared to other anticoagulants, and the preliminary reports of HIT successfully treated with dabigatran. As the literature on this develops, it will need to include clinical trials that directly evaluate dabigatran against the other NOACs and current treatment options. PMID:27382551

  14. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    PubMed Central

    Alva, Ajjai; Davis, Elizabeth; Chinnaiyan, Arul M.; Dhanasekaran, Saravana; Mehra, Rohit

    2015-01-01

    Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery. PMID:26793516

  15. Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency

    PubMed Central

    Palandri, Francesca; Polverelli, Nicola; Lifrieri, Francesca; Catani, Lucia; Giannini, Maria Benedetta; Baccarani, Michele; Vianelli, Nicola

    2012-01-01

    Immunosuppressive agents are the standard therapeutic approach for immune thrombocy-topenia (ITP). Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs), may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second-line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections. PMID:22826792

  16. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study

    PubMed Central

    Wu, Qin; Ren, Jianan; Wang, Gefei; Li, Guanwei; Gu, Guosheng; Wu, Xiuwen; Li, Yuan; Chen, Jun; Zhao, Yunzhao; Li, Jieshou

    2016-01-01

    Background Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies. Methods We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors. Results Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors. Conclusions This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients. PMID:26808492

  17. Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry

    PubMed Central

    Nunez, Rafael; Gomes-Keller, M Alice; Schwarzwald, Colin; Feige, Karsten

    2001-01-01

    Rationale Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i) decreased production; ii) increased utilization; iii) increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. Objectives This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. Findings The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i) increased number of platelets with high FSC and high SSC, ii) a significant number of those gigantic platelets had strong fluorescent signal (IgG bound), iii) very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv) significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. Conclusions This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses. PMID:11313001

  18. Over-testing for heparin induced thrombocytopenia in hospitalized patients.

    PubMed

    Chaturvedi, Shruti; Kohli, Ruhail; McCrae, Keith

    2015-07-01

    Heparin induced thrombocytopenia (HIT) is a pro-thrombotic and potentially fatal complication of heparin therapy. Its diagnosis rests on high clinical probability and the laboratory demonstration of anti-PF4/heparin antibodies. The high prevalence of thrombocytopenia in hospitalized patients and the high sensitivity but low specificity of immunoassays for HIT antibodies can lead to over-testing and over-diagnosis. We conducted a study to review HIT screening practices in a tertiary care setting. We reviewed 63 consecutive patients undergoing testing for anti-PF4/heparin antibodies over 3 months. Pre-test probability for HIT was calculated using the 4T score. Sixty three patients underwent testing for anti-PF4/heparin antibodies. Twenty one had been admitted for cardiovascular surgery, 5 for other surgery and 35 for non-surgical indications. Twenty nine patients (46 %) had low pre- test probability, twenty three (36.5 %) had intermediate probability, and eleven (17.4 %) had high pre-test probability of having HIT. Anti-PF4/heparin ELISA was positive in 8 of 63 patients. SRA was ordered for 16 patients and was positive in 5. Only five patients were diagnosed and treated for HIT. Over-testing for HIT is highly prevalent in a tertiary care setting. This increases cost and exposes patients to expensive anti-coagulation with its attendant risk of hemorrhage. The 4Ts score has been shown to have high sensitivity and may be used to rule out HIT in most situations, although its utility depends on subjective analysis. Consistently applying this in practice could minimize over-testing and facilitate safer, cost-effective care. PMID:25127902

  19. A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

    PubMed

    Lum, S H; How, S J; Ariffin, H; Krishnan, S

    2016-02-01

    Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage. PMID:27130741

  20. Autoimmune thrombocytopenia: a complication of fludarabine therapy in the treatment of Waldenstrom’s macroglobulinemia

    PubMed Central

    Jiang, Yujie; Peng, Hongjuan; Cui, Xin; Zhou, Ying; Yuan, Dai; Sui, Xiaohui; Zhang, Lingyan; Xu, Hongzhi

    2014-01-01

    Fludarabine is an effective purine analogue which has become extensive used in lymph proliferative malignancies. However, an increased incidence of autoimmune disorders including autoimmune hemolytic anemia (AHIA) and idiopathic thrombocytopenia (ITP) is reported with the use of fludarabine. The exact mechanism for fludarabine to exacerbate thrombocytopenia is not distinct. In our report, we describe a patient with WM developed a refractory, life-threatening and fludarabine-associated thrombocytopenia which could not be explained by the cytotoxic effects of fludarabine. Possible mechanisms of fludarabine on autoimmune disorders are discussed. PMID:25664138

  1. Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid

    PubMed Central

    Kaltenbach, Tonya; Martin, Beth; Rouse, Robert V.; Soetikno, Roy

    2014-01-01

    Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia. PMID:26157896

  2. Acute intracranial hemorrhage secondary to thrombocytopenia: CT appearances unaffected by absence of clot retraction

    SciTech Connect

    Pierce, J.N.; Taber, K.H.; Hayman, L.A. )

    1994-02-01

    To describe the in vivo CT appearance of acute intracerebral blood clots formed from anemic platelet-depleted blood. Three patients with intracerebral hemorrhage secondary only to thrombocytopenia were examined with CT within 2 1/2 hours after the onset of clinical symptoms. There were no unusual CT features found in the intracerebral hemorrhages of patients with only thrombocytopenia. Specifically, a hyperdense zone(s) surrounded by areas of decreased density was identified. Clot retraction (which cannot occur in patients with severe thrombocytopenia) is not necessary for the CT appearance of acute intracerebral hemorrhage. 22 refs., 3 figs., 1 tab.

  3. [Management of complex thrombocytopenia with thrombelastometry : a case of simultaneous posttransfusion purpura and heparin-induced thrombocytopenia].

    PubMed

    Haeberle, H A; Menzel, D; Unertl, K; Nohé, B

    2011-12-01

    The case presented describes the combined onset of heparin-induced thrombocytopenia II (HIT) and post-transfusion purpura (PTP) 5-10 days following exposure to heparin and blood transfusion during aortic dissection repair. On day 4 the platelet count decreased by 40% and D-dimers started to increase again. Despite a low clinical probability for HIT-II at this time (4T score of 3) serological testing was done the next day and yielded a negative test result. Following a transient rise after platelet transfusion another 40% decrease in platelet count occurred on day 8. To increase precision of the 4T score, screening ultrasonography was performed and identified a clinically unapparent jugular vein thrombosis. As this increased the 4T score to 6 points, serological testing was repeated and now showed the presence of HIT-II antibodies. Despite switching from heparin to argatroban the platelet count continued to decrease to <5×10(3)/µl. Conventional clotting tests showed a prolonged prothrombin time and severe hypofibrinogenemia. Because of the female sex, age >50 years, history of pregnancy and transfusion 8 days before, PTP was suspected. The alteration of the plasmatic coagulation, however, could not be explained by PTP. Therefore, disseminated intravascular coagulation (DIC) and interference of argatroban with conventional clotting tests were considered as alternative diagnoses. In order to differentiate between the two alternatives rotational thrombelastometry (ROTEM®) was performed and revealed an increased functional fibrinogen level without signs of hyperfibrinolysis. This argued for an interference of argatroban with the Clauss method of fibrinogen measurement and rendered DIC unlikely. Under suspicion of PTP, treatment with immunoglobulin was initiated and blood transfusions were avoided. Detection of PTP antibodies 1 day later confirmed the combined presence of PTP and HIT-II. As hyperfibrinogenemia compensated for the effects of thrombocytopenia on clot

  4. Primary Neonatal Diaphragmatic Abscess

    PubMed Central

    Zouari, Mohamed; Jallouli, Mohamed; Ben Thabet, Afef; Ben Dhaou, Mahdi; Gargouri, Abdellatif; Mhiri, Riadh

    2015-01-01

    Neonatal diaphragmatic abscesses are extremely rare and they usually develop by direct extension from a liver abscess. The first case of primary diaphragmatic abscess in a neonate is reported and the difficulties of diagnosing this rare entity are discussed. PMID:26023529

  5. Oral Exposure to Phytomonas serpens Attenuates Thrombocytopenia and Leukopenia during Acute Infection with Trypanosoma cruzi

    PubMed Central

    da Silva, Rosiane V.; Malvezi, Aparecida D.; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H.; Yamauchi, Lucy M.; Yamada-Ogatta, Sueli F.; Rizzo, Luiz V.; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  6. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    PubMed

    da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  7. Autoimmune thrombocytopenia following autologous hematopoietic cell transplantation: review of literature and treatment options.

    PubMed

    Jillella, A P; Kallab, A M; Kutlar, A

    2000-10-01

    Autoimmune thrombocytopenia after high-dose chemotherapy and autologous bone marrow/peripheral blood stem cell transplantation occurs infrequently and only six cases meeting the criteria have been reported in the literature. All six of these patients had either acute myelogenous leukemia (AML) or lymphoblastic lymphoma (LBL). Immune thrombocytopenia following autologous transplantation in solid tumors has not been reported. We report the first case of autoimmune thrombocytopenia after high-dose chemotherapy and peripheral blood stem cell transplantation in a patient with breast cancer. A review of the literature has been conducted and treatment options are discussed. In two patients the condition resolved with treatment and in a third patient it improved. Immune-mediated thrombocytopenia in the post-transplant period is one of the causes of a low platelet count. It should be recognized promptly and treated. PMID:11081398

  8. A case report of sudden thrombocytopenia detected only by in vitro analysis.

    PubMed

    Noguchi, Satoko; Kitayama, Masato; Niwa, Hidetomo; Tamai, Yoshiko; Hirota, Kazuyoshi

    2016-08-01

    We experienced an unexpected thrombocytopenia detected only in vitro during radical prostatectomy for a 66-year-old patient. Thrombocytopenia with platelet aggregation was observed in a blood sample obtained using a heparinized syringe (not by ethylene diamine tetra-acetic acid tube). Although we could not exclude platelet agglutination in vivo, no thrombosis or coagulation disorder was observed. We changed the anti-coagulant in the arterial catheter carrier fluid (saline) from heparin to argatroban, and continued with the operation. No embolic complications were observed during the perioperative period. Although pseudothrombocytopenia or heparin-induced thrombocytopenia was highly suspected in the present case, we were not able to confirm which of the two developed. Multi-directional attention and care may be required for perioperative unexpected thrombocytopenia. PMID:27142615

  9. [Syncumar-induced necrosis following heparin-induced thrombocytopenia and thrombosis].

    PubMed

    Pósán, E; Adi, S; Szücs, G; Rigó, J; Boda, Z

    1995-04-30

    The authors describe the combined occurrence of heparin-induced thrombocytopenia and cumarin-induced skin necrosis, a rare condition that has not yet been reported in Hungary. The 69-year-old woman had received prophylactic heparin treatment prior to total hip arthroplasty. The first complication that the anticoagulant therapy brought about was serious thrombocytopenia paradoxically associated not with bleeding but with deep vein thrombosis. The latter necessitated coumarin therapy which resulted in severe skin necrosis. PMID:7739854

  10. Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function.

    PubMed

    Tiedemann Skipper, Mette; Rubak, Peter; Halfdan Larsen, Ole; Hvas, Anne-Mette

    2016-06-01

    In vitro models of thrombocytopenia are useful research tools. Previously published models have shortcomings altering properties of platelets and other blood components. The aim of the present study was to develop a whole blood method to induce thrombocytopenia with minimal manipulation, and to describe platelet function in induced thrombocytopenia in individuals with healthy platelets. Hirudin anticoagulated blood was obtained from 20 healthy volunteers. One part of the blood was gently centrifuged at 130g for 15 minutes. The platelet-rich plasma was replaced with phosphate-buffered saline to establish thrombocytopenia. Various levels of thrombocytopenia were achieved by combining different volumes of baseline whole blood and thrombocytopenic blood. Platelet counts were measured by flow cytometry (Navios, Beckman Coulter) and routine haematological analyser (Sysmex XE-5000). Platelet function was analysed by impedance aggregometry (Multiplate® Analyzer, Roche) and by flow cytometry (Navios, Beckman Coulter) using collagen, adenosine diphosphate, thrombin receptor activating peptide-6 and ristocetin as agonists. Median baseline platelet count was 227×10(9)/l. The in vitro model yielded median platelet counts at 51×10(9)/l (range 26-93×10(9)/l). We observed minor, yet significant, changes in platelet size and maturity from baseline to modelled thrombocytopenia. In the thrombocytopenic samples, significant and positive linear associations were found between platelet count and platelet aggregation across all agonists (all p-values<0.001). Platelet function assessed by flow cytometry showed minimal alterations in the thrombocytopenic samples. A new whole blood-based model of thrombocytopenia was established and validated. This new model serves as a useful future tool, particularly to explore platelet function in patients with thrombocytopenia. PMID:26555800

  11. Pathogenesis and management of inherited thrombocytopenias: rationale for the use of thrombopoietin-receptor agonists.

    PubMed

    Pecci, Alessandro

    2013-07-01

    Knowledge in the field of inherited thrombocytopenias (ITs) has considerably improved over the recent years. In the last 5 years, nine new genes whose mutations are responsible for thrombocytopenia have been identified, and this also led to the recognition of several novel nosographic entities, such as thrombocytopenias deriving from mutations in CYCS, TUBB1, FLNA, ITGA2B/ITGB3, ANKRD26 and ACTN1. The identification of novel molecular alterations causing thrombocytopenia together with improvement of methodologies to study megakaryopoiesis led to considerable advances in understanding pathophysiology of ITs, thus providing the background for proposing new treatments. Thrombopoietin-receptor agonists (TPO-RAs) represent an appealing therapeutic hypothesis for ITs and have been tested in a limited number of patients. In this review, we provide an updated description of pathogenetic mechanisms of thrombocytopenia in the different forms of ITs and recapitulate the current management of these disorders. Moreover, we report the available clinical and preclinical data about the role of TPO-RAs in ITs and discuss the rationale for the use of these molecules in view of pathogenesis of the different forms of thrombocytopenia of genetic origin. PMID:23636669

  12. GNE myopathy associated with congenital thrombocytopenia: a report of two siblings.

    PubMed

    Izumi, Rumiko; Niihori, Tetsuya; Suzuki, Naoki; Sasahara, Yoji; Rikiishi, Takeshi; Nishiyama, Ayumi; Nishiyama, Shuhei; Endo, Kaoru; Kato, Masaaki; Warita, Hitoshi; Konno, Hidehiko; Takahashi, Toshiaki; Tateyama, Maki; Nagashima, Takeshi; Funayama, Ryo; Nakayama, Keiko; Kure, Shigeo; Matsubara, Yoichi; Aoki, Yoko; Aoki, Masashi

    2014-12-01

    GNE myopathy is an autosomal recessive muscular disorder caused by mutations in the gene encoding the key enzyme in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE/MNK). Here, we report two siblings with myopathy with rimmed vacuoles and congenital thrombocytopenia who harbored two compound heterozygous GNE mutations, p.V603L and p.G739S. Thrombocytopenia, which is characterized by shortened platelet lifetime rather than ineffective thrombopoiesis, has been observed since infancy. We performed exome sequencing and array CGH to identify the underlying genetic etiology of thrombocytopenia. No pathogenic variants were detected among the known causative genes of recessively inherited thrombocytopenia; yet, candidate variants in two genes that followed an autosomal recessive mode of inheritance, including previously identified GNE mutations, were detected. Alternatively, it is possible that the decreased activity of GNE/MNK itself, which would lead to decreased sialic content in platelets, is associated with thrombocytopenia in these patients. Further investigations are required to clarify the association between GNE myopathy and the pathogenesis of thrombocytopenia. PMID:25257349

  13. The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

    SciTech Connect

    Castle, V.P.; Shulkin, B.L.; Coates, G.; Andrew, M. )

    1989-11-01

    We have utilized {sup 111}In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, {sup 111}In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma.

  14. Heparin induced thrombocytopenia in critically ill: Diagnostic dilemmas and management conundrums

    PubMed Central

    Gupta, Sachin; Tiruvoipati, Ravindranath; Green, Cameron; Botha, John; Tran, Huy

    2015-01-01

    Thrombocytopenia is often noted in critically ill patients. While there are many reasons for thrombocytopenia, the use of heparin and its derivatives is increasingly noted to be associated with thrombocytopenia. Heparin induced thrombocytopenia syndrome (HITS) is a distinct entity that is characterised by the occurrence of thrombocytopenia in conjunction with thrombotic manifestations after exposure to unfractionated heparin or low molecular weight heparin. HITS is an immunologic disorder mediated by antibodies to heparin-platelet factor 4 (PF4) complex. HITS is an uncommon cause of thrombocytopenia. Reported incidence of HITS in patients exposed to heparin varies from 0.2% to up to 5%. HITS is rare in ICU populations, with estimates varying from 0.39%-0.48%. It is a complex problem which may cause diagnostic dilemmas and management conundrum. The diagnosis of HITS centers around detection of antibodies against PF4-heparin complexes. Immunoassays performed by most pathology laboratories detect the presence of antibodies, but do not reveal whether the antibodies are pathological. Platelet activation assays demonstrate the presence of clinically relevant antibodies, but only a minority of laboratories conduct them. Several anticoagulants are used in management of HITS. In this review we discuss the incidence, pathogenesis, diagnosis and management of HITS. PMID:26261772

  15. Reverse Genetics System for Severe Fever with Thrombocytopenia Syndrome Virus

    PubMed Central

    Brennan, Benjamin; Li, Ping; Zhang, Shuo; Li, Aqian; Liang, Mifang; Li, Dexin

    2014-01-01

    ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that was first reported in China in 2009. Phylogenetic analysis of the viral genome showed that SFTS virus represents a new lineage within the Phlebovirus genus, distinct from the existing sandfly fever and Uukuniemi virus groups, in the family Bunyaviridae. SFTS disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic manifestations with a case fatality rate of about 2 to 15%. Here we report the development of reverse genetics systems to study STFSV replication and pathogenesis. We developed and optimized functional T7 polymerase-based M- and S-segment minigenome assays, which revealed errors in the published terminal sequences of the S segment of the Hubei 29 strain of SFTSV. We then generated recombinant viruses from cloned cDNAs prepared to the antigenomic RNAs both of the minimally passaged virus (HB29) and of a cell culture-adapted strain designated HB29pp. The growth properties, pattern of viral protein synthesis, and subcellular localization of viral N and NSs proteins of wild-type HB29pp (wtHB29pp) and recombinant HB29pp viruses were indistinguishable. We also show that the viruses fail to shut off host cell polypeptide production. The robust reverse genetics system described will be a valuable tool for the design of therapeutics and the development of killed and attenuated vaccines against this important emerging pathogen. IMPORTANCE SFTSV and related tick-borne phleboviruses such as Heartland virus are emerging viruses shown to cause severe disease in humans in the Far East and the United States, respectively. Study of these novel pathogens would be facilitated by technology to manipulate these viruses in a laboratory setting using reverse genetics. Here, we report the generation of infectious SFTSV from cDNA clones and demonstrate that the behavior of recombinant viruses

  16. Oral Lesions in Neonates

    PubMed Central

    Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    ABSTRACT Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  17. Oral Lesions in Neonates.

    PubMed

    Patil, Shankargouda; Rao, Roopa S; Majumdar, Barnali; Jafer, Mohammed; Maralingannavar, Mahesh; Sukumaran, Anil

    2016-01-01

    Oral lesions in neonates represent a wide range of diseases often creating apprehension and anxiety among parents. Early examination and prompt diagnosis can aid in prudent management and serve as baseline against the future course of the disease. The present review aims to enlist and describe the diagnostic features of commonly encountered oral lesions in neonates. How to cite this article: Patil S, Rao RS, Majumdar B, Jafer M, Maralingannavar M, Sukumaran A. Oral Lesions in Neonates. Int J Clin Pediatr Dent 2016;9(2):131-138. PMID:27365934

  18. Regulatory T cells sequentially migrate from the site of tissue inflammation to the draining LN to suppress the alloimmune response

    PubMed Central

    Zhang, Nan; Schröppel, Bernd; Lal, Girdhari; Jakubzick, Claudia; Mao, Xia; Chen, Dan; Yin, Na; Jessberger, Rolf; Ochando, Jordi C.; Ding, Yaozhong; Bromberg, Jonathan S.

    2009-01-01

    To determine site and mechanism of suppression, regulatory T cell (Treg) migration and function were investigated in an islet allograft model. Treg first migrated from blood to the inflammed allografts, this depended on CCR2, CCR4, CCR5, and P- and E-selectin ligands, and was essential for suppression of alloimmunity. In the allograft, Treg were activated, upregulated effector molecules, migrated to the draining lymph nodes (dLN) in a CCR2, CCR5, and CCR7 fashion, and this movement was essential for optimal suppression. Treg inhibited dendritic cell migration in a TGFβ and IL-10 dependent fashion; and suppressed antigen specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and then to dLNs were required for nTreg to differentiate and execute fully their suppressive function, by inhibiting DC in the peripheral tissue, and T effector cell responses in dLN and allografts. PMID:19303390

  19. Common variable immunodeficiency, immune thrombocytopenia, rituximab and splenectomy: important considerations.

    PubMed

    Arays, Ruta; Goyal, Sahil; Jordan, Kim M

    2016-08-01

    Common variable immunodeficiency (CVID) is readily considered in patients presenting with recurrent sino-pulmonary infections, however this disease has a broad range of clinical manifestations and diagnosis can be delayed by several years. We present the case of a 44-year-old postpartum female who presented with nausea, vomiting and abdominal distension. Four years prior, she was hospitalized for treatment of immune thrombocytopenia (ITP) with splenectomy and rituximab followed by two episodes of bacterial meningitis despite immunizations. The recurrent meningitis had been attributed to splenectomy and immunotherapy. During this hospitalization, extensive workup for gastrointestinal pathology was negative and she was diagnosed with intestinal pseudo-obstruction. Her hospital course was complicated by development of severe pseudomonas pneumonia, and subsequent immunoglobulin testing and impaired antibody response to vaccines were consistent with CVID. We review the clinical presentation of CVID, its association with autoimmune disease, and treatment implications, specifically the impact of rituximab therapy and splenectomy on immunoglobulin function and risk of serious infection. Intestinal pseudo-obstruction has been reported in children with CVID, but literature search failed to reveal similar presentation in adults. Physicians must consider the heterogeneous clinical manifestations of CVID to avoid delay in diagnosis and treatment. Institution of appropriate therapy with immunoglobulin replacement is important to decrease risk of serious infection. PMID:27276370

  20. Heparin-induced thrombocytopenia associated with acute liver graft failure.

    PubMed

    Pannicke, Nadine; Pollok, Joerg-Matthias; Kluge, Stefan; Petzoldt, Martin

    2012-01-01

    An orthotopic liver transplantation (OLT) is of a proven benefit in an acute liver failure (ALF). Heparin-induced thrombocytopenia (HIT) is strongly associated with thromboembolic complications. We present the case of a 56-year-old patient who underwent an OLT owing to an ALF of unknown aetiology. HIT type II with consecutive hepatic and portal vein thrombosis caused progressive graft failure. Total hepatectomy and porto-caval shunt were performed to reduce the toxic effects of liver cell necrosis such as multiorgan failure involving the respiratory, renal and cardiovascular systems. A suitable liver graft was allocated after an anhepatic bridging period of 56 h. Specific complications due to end-stage liver failure-such as acidosis, coagulopathy, decrease of vascular resistance, cerebral oedema, myocardial infarction and right heart failure-were treated. Following a re-OLT, the patient made a complete recovery. We present a rare case of HIT-associated early liver graft failure followed by a prolonged anhepatic phase and finally a successful re-OLT. PMID:23188860

  1. Advances in Diagnosis and Treatments for Immune Thrombocytopenia

    PubMed Central

    Nomura, Shosaku

    2016-01-01

    Immune thrombocytopenia (ITP) is an acquired hemorrhagic condition characterized by the accelerated clearance of platelets caused by antiplatelet autoantibodies. A platelet count in peripheral blood <100 × 109/L is the most important criterion for the diagnosis of ITP. However, the platelet count is not the sole diagnostic criterion, and the diagnosis of ITP is dependent on additional findings. ITP can be classified into three types, namely, acute, subchronic, and persistent, based on disease duration. Conventional therapy includes corticosteroids, intravenous immunoglobulin, splenectomy, and watch-and-wait. Second-line treatments for ITP include immunosuppressive therapy [eg, anti-CD20 (rituximab)], with international guidelines, including rituximab as a second-line option. The most recently licensed drugs for ITP are the thrombopoietin receptor agonists (TRAs), such as romiplostim and eltrombopag. TRAs are associated with increased platelet counts and reductions in the number of bleeding events. TRAs are usually considered safe, effective treatments for patients with chronic ITP at risk of bleeding after failure of first-line therapies. Due to the high costs of TRAs, however, it is unclear if patients prefer these agents. In addition, some new agents are under development now. This manuscript summarizes the pathophysiology, diagnosis, and treatment of ITP. The goal of all treatment strategies for ITP is to achieve a platelet count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should be based on the bleeding severity, bleeding risk, activity level, likely side effects of treatment, and patient preferences. PMID:27441004

  2. Increased RUNX1 expression in patients with immune thrombocytopenia.

    PubMed

    Zhong, Xiaomin; Wu, Yulu; Liu, Yun; Zhu, Feng; Li, Xiaoqian; Li, Depeng; Li, Zhenyu; Zeng, Lingyu; Qiao, Jianlin; Chen, Xiaofei; Xu, Kailin

    2016-08-01

    Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, characterized by dysregulation of cellular immunity. Th17 and associated IL-17 were involved in the pathogenesis of ITP. Runt-related transcription factor 1 (RUNX1), a member of the runt domain-containing family of transcription factors, is required for Th17 differentiation. Whether RUNX1 was involved in the pathogenesis of ITP remains poorly understood. In this study, 30 active ITP patients, 20 ITP in remission and 20 age and gender matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated to measure mRNA level of RUNX1 and retinoic acid receptor-related orphan receptor-γt (RORγt) by quantitative real-time PCR and Th17 cells by flow cytometry. Meanwhile, plasma was extracted for measurement of IL-17 level by ELISA. Our results showed a significantly higher expression of RUNX1, RORγt, Th17 cells and plasma level of IL-17 in active ITP patients than that in healthy controls. No differences of expression of RUNX1, RORγt and Th17 cells were observed between remission patients and controls. Furthermore, a significantly positive correlation of RUNX1 with RORγt was found in active ITP patients. In conclusion, RUNX1 was associated with the pathogenesis of ITP possibly through regulation of Th17 cell differentiation and therapeutically targeting it might be a novel approach in ITP treatment. PMID:27288310

  3. How we manage immune thrombocytopenia in the elderly.

    PubMed

    Mahévas, Matthieu; Michel, Marc; Godeau, Bertrand

    2016-06-01

    With prolonged life expectancy, immune thrombocytopenia (ITP) is frequent in elderly people. In this setting, ITP diagnosis is challenging because of the concern about an underlying myelodysplastic syndrome. Studies of older adults are lacking, and recommendations for treatment are based mainly on expert opinion. The therapeutic strategy differs from that for younger patients and must take into account the greater risk of bleeding and thrombosis, presence of comorbidities, possible impaired cognitive performance or poor life expectancy and concomitant medications, such as anticoagulant and antiplatelet therapy. Steroids and intravenous immunoglobulin (IVIg) therapy remain the first-line treatments in elderly patients, but prolonged treatment with steroids should be avoided and IVIg treatment may lead to renal failure. Splenectomy is less effective than in young patients and risk of thrombosis is increased. Severe co-morbidities can also contraindicate surgery. Therefore, other second-line treatments are frequently preferred. Danazol and dapsone can be an option for the less severe ITP form. Rituximab is a good option except in patients with a history of infection or with hypogammaglobulinaemia. Thrombopoietin agonists are attractive, especially for patients with severe comorbidities or with limited life expectancy but the risk of thrombosis is a concern. PMID:27062054

  4. Aberrant expression of RUNX3 in patients with immune thrombocytopenia.

    PubMed

    Qiao, Jianlin; Liu, Yun; Wu, Yulu; Li, Xiaoqian; Zhu, Feng; Xia, Yuan; Yao, Haina; Chu, Peipei; Li, Hongchun; Ma, Ping; Li, Depeng; Li, Zhenyu; Xu, Kailin; Zeng, Lingyu

    2015-09-01

    Immune thrombocytopenia (ITP) is an autoimmune disease, characterized by dysregulation of cellular immunity. Previous studies demonstrated that immune imbalance between Th1 and Th2 was associated with the pathogenesis of ITP. Runt-related transcription factor 3 (RUNX3) is a member of the runt domain-containing family of transcription factors and plays an important role in the regulation of T cell differentiation into Th1 cells. Whether RUNX3 was involved in the pathogenesis of ITP remains unclear. In this study, 47 active ITP patients, 18 ITP with remission and 26 age and gender matched healthy control were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma which were used to measure mRNA level of RUNX3 and T-box transcription factor (T-bet) by quantitative real-time PCR and interferon γ (IFN-γ) plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of RUNX3 expression. Our results showed a significantly higher expression of RUNX3, T-bet and plasma level of IFN-γ in active ITP patients compared to control. No differences were observed between ITP with remission and control. Furthermore, a positive correlation of RUNX3 with T-bet was found in active ITP patients. In conclusion, aberrant expression of RUNX3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a novel approach in ITP treatment. PMID:26093269

  5. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, V E J; Stam, E D; Welborn, K M; Sas, T C J

    2016-01-01

    Neonatal encephalitis caused by herpes simplex virus (HSV) is a familiar disease with a high mortality and morbidity rate. Isolated skin-eye-mouth infection is less familiar among professionals. In this article we present two neonates with an isolated skin lesion caused by an HSV infection. Of the neonates infected with HSV, 40-45% show isolated skin-eye-mouth disease. With correct treatment, the risk of spread to the central nervous system will decrease from 50-60% to 5-10%. Typical HSV skin lesions may present at a late stage of the disease or may be masked by a secondary bacterial infection. When a neonate presents with atypical skin lesions starting 7-12 days after the birth, immediate testing for HSV and immediate treatment are required, to decrease the risk of further progression of the disease. PMID:27122069

  6. Neonatal pain management

    PubMed Central

    Bhalla, Tarun; Shepherd, Ed; Tobias, Joseph D.

    2014-01-01

    The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions. PMID:25538531

  7. Neonatal respiratory distress syndrome

    MedlinePlus

    Hyaline membrane disease (HMD); Infant respiratory distress syndrome; Respiratory distress syndrome in infants; RDS - infants ... Neonatal RDS occurs in infants whose lungs have not yet fully ... disease is mainly caused by a lack of a slippery substance in ...

  8. Neonatal abstinence syndrome

    MedlinePlus

    NAS; Neonatal abstinence symptoms ... may contribute to the severity of a baby's NAS symptoms. ... symptoms of withdrawal. Even after medical treatment for NAS is over and babies leave the hospital, they ...

  9. Maternal and neonatal tetanus.

    PubMed

    Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

    2015-01-24

    Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58,000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

  10. Neonatal polycystic kidney disease.

    PubMed

    Verghese, Priya; Miyashita, Yosuke

    2014-09-01

    This article provides an up-to-date comprehensive review and summary on neonatal polycystic kidney disease (PKD) with emphasis on the differential diagnosis, clinical manifestations, diagnostic techniques, and potential therapeutic approaches for the major causes of neonatal PKD, namely hereditary disease, including autosomal recessive and autosomal dominant PKD and nonhereditary PKD, with particular emphasis on multicystic dysplastic kidney. A brief overview of obstructive cystic dysplasia and simple and complex cysts is also included. PMID:25155726

  11. Neonatal clinical pharmacology

    PubMed Central

    Allegaert, Karel; van de Velde, Marc; van den Anker, John

    2013-01-01

    Effective and safe drug administration in neonates should be based on integrated knowledge on the evolving physiological characteristics of the infant who will receive the drug, and the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. Consequently, clinical pharmacology in neonates is as dynamic and diverse as the neonates we admit to our units while covariates explaining the variability are at least as relevant as median estimates. The unique setting of neonatal clinical pharmacology will be highlighted based on the hazards of simple extrapolation of maturational drug clearance when only based on ‘adult’ metabolism (propofol, paracetamol). Secondly, maturational trends are not at the same pace for all maturational processes. This will be illustrated based on the differences between hepatic and renal maturation (tramadol, morphine, midazolam). Finally, pharmacogenetics should be tailored to neonates, not just mirror adult concepts. Because of this diversity, clinical research in the field of neonatal clinical pharmacology is urgently needed, and facilitated through PK/PD modeling. In addition, irrespective of already available data to guide pharmacotherapy, pharmacovigilance is needed to recognize specific side effects. Consequently, paediatric anesthesiologists should consider to contribute to improved pharmacotherapy through clinical trial design and collaboration, as well as reporting on adverse effects of specific drugs. PMID:23617305

  12. Neonatal surgery in Africa.

    PubMed

    Chirdan, Lohfa B; Ngiloi, Petronilla J; Elhalaby, Essam A

    2012-05-01

    The management of neonatal surgical problems continues to pose considerable challenges, particularly in low-resource settings. The burden of neonatal surgical diseases in Africa is not well documented. The characteristics of some neonatal surgical problems are highlighted. Late presentation coupled with poor understanding of the milieu interior of the neonates by incompetent health care providers and poorly equipped hospitals combine to give rise to the unacceptable high morbidity and mortality in most parts of Africa. Proper training of all staff involved in neonatal health care coupled with community awareness must be vigorously pursued by all stakeholders. Various governments throughout the continent of Africa, in conjunction with international donor agencies, must not only provide an adequate budget for health care services and improve infrastructures, but must also deliberately encourage and provide funding for neonatal surgical care and research across the continent. The well-established pediatric surgical training programs, particularly in North and South Africa, should hold the moral responsibility of training all possible numbers of young surgeons from other African countries that do not have any existing pediatric surgical training programs or those countries suffering from remarkable shortage of trained pediatric surgeons. PMID:22475121

  13. Prevalence of HIV-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda

    PubMed Central

    Taremwa, Ivan M; Muyindike, Winnie R; Muwanguzi, Enoch; Boum, Yap; Natukunda, Bernard

    2015-01-01

    Aims/objectives We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda. Materials and methods This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS) Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique. Results We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42) years, and there were 63.2% (n=9,500) females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%). The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4%) among antiretroviral therapy (ART)-naïve clients (n=2,675) and was 13.0% (95% CI: 0.3%–21.9%) for clients who were on ART (n=6). The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05). Two of the 40 participants (5.0%) had antiplatelet antibodies. Conclusion This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of thrombocytopenia burden in a high-HIV study population (Southwest Uganda); therefore, there is need to monitor platelet counts and initiate platelet transfusion in our blood banking practices, to avert possible risks of bleeding. PMID:25926763

  14. Evaluation of reticulated platelets in dogs with breed-related thrombocytopenia.

    PubMed

    Zmigrodzka, M; Guzera, M; Winnicka, A

    2014-01-01

    The aim of this study was to evaluate the percentage of reticulated platelets in healthy dogs with breed-related thrombocytopenia. Seventy two dogs, clinically healthy, were enrolled in the study. Blood was collected from the patients and anticoagulated with tripotassium ethylenediaminetetraacetic acid (K3-EDTA) and sodium citrate. Platelet count was obtained by an impedance haematology analyser and platelet morphology was evaluated by examination of blood smears. Patients were allocated into two groups. Group 1 consisted of 30 dogs with normal platelet count, whereas group 2 was composed of 42 dogs with thrombocytopenia. Thrombocytopenia was present in both K3-EDTA and citrate blood samples. Patients with thrombocytopenia were divided into two subgroups: the first subgroup included dogs with platelet count in K3-EDTA anticoagulated blood from 100 to 200 x10(9)/L, patients in the second subgroup had a platelet count of less than 100 x10(9)/L. The percentage of young reticulated platelets (RPs) labelled with thiazole orange, and the percentage of platelets coated with platelet surface-associated IgG, were determined in platelet-rich plasma (PRP) by a flow cytometer. The mean percentage of RPs in K3-EDTA and citrate PRP was significantly higher in dogs with thrombocytopenia than in dogs with normal platelet count. The mean percentage of RPs was significantly higher in citrate PRP than in K3-EDTA PRP in all groups. The results suggest that idiopathic, asymptomatic thrombocytopenia is not caused by platelet surface-associated IgG. Dogs with breed-related thrombocytopenia have a competent bone marrow. PMID:24724481

  15. Interleukin-23R gene polymorphism in pediatric Egyptian patients with primary immune thrombocytopenia.

    PubMed

    Farawela, Hala M; Botros, Shahira K A; El-Ghamrawy, Mona; Ebrahim, Eman O

    2016-06-01

    Primary immune thrombocytopenia is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case-control study aimed at detecting the frequency of interleukin-23 receptor rs1884444 single nucleotide polymorphism in Egyptian children with primary immune thrombocytopenia and its possible role as a genetic marker for disease risk. Interleukin-23 receptor rs1884444 single nucleotide polymorphism was studied in 50 patients with primary immune thrombocytopenia and 100 healthy age and sex-matched controls by polymerase chain reaction amplification of the target gene followed by allele-specific restriction enzyme digestion. Regarding the distribution of the genotypes of the interleukin-23 receptor rs1884444 polymorphism, no statistically significant difference was found between cases and control groups. The variant genotypes (GT/TT) frequency was 10% in primary immune thrombocytopenia cases versus 7% in the control groups [P value = 0.755, odds ratio (OR): 0.326, 95% confidence interval (CI): 0.099-1.076]. Similarly, no difference was found between acute and chronic cases. The variant genotypes GT/TT frequency was 10.7% in acute versus 9.1% in chronic primary immune thrombocytopenia (P value = 0.849). The variant genotypes GT/TT were not found to be a risk factor for acute primary (P value = 0.807, OR: 0.641, 95% CI: 0.16-2.563) or chronic primary immune thrombocytopenia (P value = 0.914, OR: 0.762, 95% CI: 0.153-3.797). Our study suggests the possibility that interleukin-23 receptor gene polymorphism may not contribute to the susceptibility of development of primary immune thrombocytopenia in Egyptian children. PMID:26859125

  16. A retrospective study of the risk factors for linezolid-induced thrombocytopenia and anemia.

    PubMed

    Hanai, Yuki; Matsuo, Kazuhiro; Ogawa, Miki; Higashi, Ayaka; Kimura, Itsuki; Hirayama, Shinobu; Kosugi, Takayoshi; Nishizawa, Kenji; Yoshio, Takashi

    2016-08-01

    Myelosuppression is major treatment-related adverse events of linezolid therapy and result in treatment termination in some cases. We aimed to identify the risk factors for linezolid-induced thrombocytopenia and anemia. We retrospectively retrieved demographic and laboratory data from the medical records of 221 Japanese patients who were undergoing linezolid therapy. Thrombocytopenia and anemia were defined as an unexplained reduction of >30% in the patient's platelet count and hemoglobin level, respectively, from the baseline. Thrombocytopenia developed in 48.4% of patients, and anemia developed in 10.4% of patients during linezolid therapy. In multivariate analysis, creatinine clearance (adjusted odds ratio = 0.94 [0.92-0.95], P < 0.001), hemodialysis (3.32 [1.14-9.67], P = 0.011), and the duration of linezolid therapy (1.14 [1.07-1.21], P < 0.001) were found to be significant risk factors for linezolid-induced thrombocytopenia. Patients with creatinine clearance rates of <60 mL/min and those on hemodialysis were found to be at high risk of linezolid-induced thrombocytopenia. In addition, a high incidence of linezolid-induced thrombocytopenia was even detected among the patients that had received linezolid therapy for <7 days. As for anemia, the duration of linezolid therapy (1.04 [1.01-1.07], P = 0.011) was shown to be a risk factor for anemia, and a high incidence of anemia was seen among the patients who received linezolid for >15 days. In conclusion, we recommend that among patients receiving linezolid therapy the platelet counts of those with risk factors for linezolid-induced thrombocytopenia should be monitored closely throughout treatment, and the hemoglobin levels of patients that receive linezolid for >15 days should be carefully monitored on a weekly basis to detect anemia. PMID:27321773

  17. Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease.

    PubMed

    Buchbinder, David; Hsieh, Loan; Krance, Robert; Nugent, Diane J

    2014-11-01

    Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three-yr-old male with X-linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids. PMID:25118016

  18. Platelet transfusion in the neonatal intensive care unit: benefits, risks, alternatives.

    PubMed

    Christensen, Robert D

    2011-01-01

    Platelet transfusions were introduced into clinical medicine about 60 years ago when they were shown to reduce the mortality rate of patients with leukemia who were bleeding secondary to hyporegenerative thrombocytopenia. In modern neonatology units, platelet transfusions are integral and indeed lifesaving for some neonates. However, the great majority of platelet transfusions currently administered in neonatal intensive care units (NICUs) are not given in the original paradigm to treat thrombocytopenic hemorrhage, but instead are administered prophylactically with the hope that they will reduce the risk of spontaneous bleeding. Weighing the risks and benefits of platelet transfusion, although imprecise, should be attempted each time a platelet transfusion is ordered. Adopting guidelines specific for platelet transfusion will improve consistency of care and will also generally reduce transfusion usage, thereby reducing costs and conserving valuable blood bank resources. Initiating specific programs to improve compliance with transfusion guidelines can further improve NICU transfusion practice. PMID:21986337

  19. Newly diagnosed immune thrombocytopenia in children and adults: a comparative prospective observational registry of the Intercontinental Cooperative Immune Thrombocytopenia Study Group

    PubMed Central

    Kühne, Thomas; Berchtold, Willi; Michaels, Lisa A.; Wu, Runhui; Donato, Hugo; Espina, Bibiana; Tamary, Hannah; Rodeghiero, Francesco; Chitlur, Meera; Rischewski, Johannes; Imbach, Paul

    2011-01-01

    Background Primary immune thrombocytopenia is a bleeding diathesis with an unknown etiology in predisposed individuals with immune disturbances. Although it is claimed that children and adults differ in clinical and laboratory aspects, few data exist to corroborate this observation. Our objective was to assess comparative data from children and adults with newly diagnosed immune thrombocytopenia. Design and Methods Clinical and laboratory data of 1,784 children and 340 adults were extracted from the Pediatric and Adult Registry on Chronic Immune Thrombocytopenia. The registry represents a prospective cohort of children and adults with newly diagnosed immune thrombocytopenia. Participating investigators registered their patients immediately after the diagnosis using a web based data transfer. Children aged under 16 years were compared with adults aged 16 years and over with descriptive statistical analyses. Results The presenting mean platelet count of children and adults was 18.1 and 25.4×109/L. Signs of bleeding were reported in 24% of children and in 23% of adults, and intracranial hemorrhage in 10 of 1,784 children and in 6 of 340 adults. Co-morbidity was observed in 3.9% of children and in 30% of adults. Bone marrow aspiration and laboratory tests (antinuclear antibodies, human immunodeficiency and hepatitis C virus) were performed more frequently in adults. Children and adults were followed with a ‘watch and wait’ strategy in 20% and in 29%, respectively. Immunoglobulins were used more frequently in children and corticosteroids in adults. Conclusions Comparative data of children and adults with newly diagnosed immune thrombocytopenia revealed similarities in presenting platelet counts and in bleeding, whereas differences occurred in co-morbidity, diagnostic procedures and therapy. PMID:21880634

  20. Novel diagnostic assays for heparin-induced thrombocytopenia

    PubMed Central

    Rux, Ann H.; Hinds, Jillian L.; Dela Cruz, May; Yarovoi, Serge V.; Brown, Isola A. M.; Yang, Wei; Konkle, Barbara A.; Arepally, Gowthami M.; Watson, Stephen P.; Cines, Douglas B.; Sachais, Bruce S.

    2013-01-01

    Laboratory testing for heparin-induced thrombocytopenia (HIT) has important shortcomings. Immunoassays fail to discriminate platelet-activating from nonpathogenic antibodies. Specific functional assays are impracticable due to the need for platelets and radioisotope. We describe 2 assays that may overcome these limitations. The KKO-inhibition test (KKO-I) measures the effect of plasma on binding of the HIT-like monoclonal antibody KKO to platelet factor 4 (PF4)/heparin. DT40-luciferase (DT40-luc) is a functional test comprised of a B-cell line expressing FcγRIIa coupled to a luciferase reporter. We compared these assays to polyspecific and immunoglobulin (Ig)G-specific PF4/heparin enzyme-linked immunosorbent assays (ELISAs) in samples from 58 patients with suspected HIT and circulating anti-PF4/heparin antibodies. HIT was defined as a 4Ts score ≥ 4 and positive 14C-serotonin release assay. HIT-positive plasma demonstrated greater mean inhibition of KKO binding than HIT-negative plasma (78.9% vs 26.0%; P < .0001) and induced greater luciferase activity (3.14-fold basal vs 0.96-fold basal; P < .0001). The area under the receiver-operating characteristic curve was greater for KKO-I (0.93) than for the polyspecific (0.82; P = .020) and IgG-specific ELISA (0.76; P = .0044) and for DT40-luc (0.89) than for the IgG-specific ELISA (P = .046). KKO-I and DT40-luc showed better discrimination than 2 commercially available immunoassays, are simple to perform, and hold promise for improving the specificity and feasibility of HIT laboratory testing. PMID:23446735

  1. An improbable and unusual case of thrombotic thrombocytopenia purpura.

    PubMed

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  2. Eltrombopag: A Review in Paediatric Chronic Immune Thrombocytopenia.

    PubMed

    Burness, Celeste B; Keating, Gillian M; Garnock-Jones, Karly P

    2016-05-01

    Eltrombopag (Promacta(®); Revolade(®)) is an orally active thrombopoietin receptor agonist recently approved in the USA and the EU for use in paediatric patients aged ≥1 year with chronic immune thrombocytopenia (ITP) who have had an insufficient response or are refractory to other ITP treatments (e.g. corticosteroids, immunoglobulins or splenectomy). The efficacy of 7 or 13 weeks' therapy with oral eltrombopag (up to 75 mg/day) was compared with that of placebo in patients aged 1-17 years with previously treated chronic ITP in randomized, double-blind, multicentre phase II and III trials (PETIT and PETIT-2). In these trials, the platelet response rate (primary endpoint of PETIT) and the sustained platelet response rate (primary endpoint of PETIT-2) were significantly higher with eltrombopag than with placebo. A clinical benefit was shown by a reduction in the need for rescue therapy with eltrombopag versus placebo in both trials and a reduction of clinically significant bleeding in PETIT. During longer-term therapy (open-label treatment period for ≥24 weeks), eltrombopag maintained platelet counts above 50 × 10(9)/L in the majority of patients and approximately one-half of patients were able to reduce or discontinue concurrent ITP drugs. Eltrombopag was generally well tolerated. Current evidence suggests that eltrombopag is a valuable addition to the limited treatment options available for the management of chronic ITP in paediatric patients with an inadequate response to first-line therapies. PMID:27151255

  3. Elevated expression of NLRP3 in patients with immune thrombocytopenia.

    PubMed

    Qiao, Jianlin; Liu, Yun; Li, Xiaoqian; Xia, Yuan; Wu, Yulu; Li, Depeng; Li, Hongchun; Ma, Ping; Zhu, Feng; Li, Zhenyu; Xu, Kailin; Zeng, Lingyu

    2016-04-01

    Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, which is characterized by dysregulation of T cell-mediated autoimmunity. NLRP3, a largest and mostly well-studied inflammasome, has been shown to be important in the regulation of adaptive immune response, especially in T cell response. Given the closely association of imbalance of T cell response with ITP, whether NLRP3 is involved in the pathogenesis of ITP remains poorly understood. In this study, 69 active ITP patients, 21 ITP in remission and 24 age- and gender-matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma, which were used to measure mRNA level of NLRP3 and adaptor protein ASC by quantitative real-time PCR and IL-18 plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of NLRP3 expression. Our results showed a significantly higher expression of NLRP3, ASC and plasma IL-18 level in patients with active ITP when compared to control. The expression of NLRP3, ASC and plasma IL-18 level was significantly lower in patients in remission than that in active ITP, and no difference was observed when compared to control. Furthermore, a significantly positive correlation of NLRP3 with ASC was observed in patients with active ITP. In conclusion, increased expression of NLRP3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a new strategy in the treatment of ITP. PMID:26306997

  4. Antiplatelet antibodies contribute to thrombocytopenia associated with chronic hepatitis C virus infection.

    PubMed

    Aref, Salah; Sleem, Tarek; El Menshawy, Nadia; Ebrahiem, Lamiaa; Abdella, Dooa; Fouda, Manal; Samara, Nashwa Abou; Menessy, Aymen; Abdel-Ghaffar, Hassen; Bassam, Ansaf; Abdel Wahaab, Mohamed

    2009-10-01

    Thrombocytopenia is one of the most frequent hematological manifestations of hepatitis C virus (HCV) infection; which typically worsens with progression of the liver disease and can become a major clinical complication. Several mechanisms have been postulated to explain thrombocytopenia in HCV hepatic patients, including immune mechanisms. The aim of the present work is to investigate the role of immune mechanisms as a causative agent of thrombocytopenia in HCV hepatic patients. The study included 50 hepatic patients with HCV infection (30 with thrombocytopenia and 20 with normal platelets counts). Platelets associated glycoprotein specific antibodies were evaluated by flow cytometry and confirmed by quantitative monoclonal immobilization of platelet antibodies (MAIPA). The frequency of platelet associated immunoglobulin (PAIg) in thrombocytopenic HCV positive hepatic patients by FCM was 86.7, 83.3, 46.7 and 33.3% for total PAIg, PAIgG, PAIgM and PAIgA respectively. MAIPA found platelet specific antibodies in 26/30 (86.7%) of patients. The most likely target antigen for platelets antibodies were glycoprotein (GP) IIb/IIIa (30%), followed by GP IIIa (20.5), GP IIb (13.3%), GPIb (13.3%), then GPIa (10%). The platelets count was inversely correlated to the levels of platelets GP specific antibodies (r=-0.42, p=0.024), and significantly parallel to spleen size (p=0.024). Platelet associated glycoprotein specific antibodies represent a common mechanism inducing thrombocytopenia in patients with chronic HCV infections. PMID:19843383

  5. Immune thrombocytopenia: antiplatelet autoantibodies inhibit proplatelet formation by megakaryocytes and impair platelet production in vitro

    PubMed Central

    Iraqi, Muna; Perdomo, Jose; Yan, Feng; Choi, Philip Y-I; Chong, Beng H.

    2015-01-01

    Primary immune thrombocytopenia is an autoimmune disease mediated by antiplatelet autoantibodies that cause platelet destruction and suppression of platelet production. In vitro effects of autoantibodies on megakaryocyte production and maturation have been reported recently. However, the impact of these autoantibodies on crucial megakaryocyte functions, proplatelet formation and subsequent platelet release, has not been evaluated. We examined the effects of serum and IgG from 19 patients with immune thrombocytopenia using day 8 or 9 megakaryocytes (66.3 ± 10.6% CD41+), derived from cord blood hematopoietic stem cells (CD34+). The number of proplatelet-bearing megakaryocytes, the number of platelets released in the culture, total megakaryocyte numbers, ploidy pattern and caspase activation were measured at various times after treatment. After 5 days of treatment the number of proplatelet-bearing megakaryocytes was significantly decreased by 13 immune thrombocytopenia autoantibodies relative to the control group (P<0.0001) and this decrease was accompanied by a corresponding reduction of platelet release. Other features, including total megakaryocyte numbers, maturation and apoptosis, were not affected by immune thrombocytopenia antibodies. Treating the megakaryocytes with the thrombopoietin receptor agonists romiplostim and eltrombopag reversed the effect of the autoantibodies on megakaryocytes by restoring their capacity to form proplatelets. We conclude that antiplatelet antibodies in immune thrombocytopenia inhibit proplatelet formation by megakaryocytes and hence the ability of the megakaryocytes to release platelets. Treatment with either romiplostim or eltrombopag regenerates proplatelet formation from the megakaryocytes. PMID:25682608

  6. The contribution of mouse models to the understanding of constitutional thrombocytopenia

    PubMed Central

    Léon, Catherine; Dupuis, Arnaud; Gachet, Christian; Lanza, François

    2016-01-01

    Constitutional thrombocytopenias result from platelet production abnormalities of hereditary origin. Long misdiagnosed and poorly studied, knowledge about these rare diseases has increased considerably over the last twenty years due to improved technology for the identification of mutations, as well as an improvement in obtaining megakaryocyte culture from patient hematopoietic stem cells. Simultaneously, the manipulation of mouse genes (transgenesis, total or conditional inactivation, introduction of point mutations, random chemical mutagenesis) have helped to generate disease models that have contributed greatly to deciphering patient clinical and laboratory features. Most of the thrombocytopenias for which the mutated genes have been identified now have a murine model counterpart. This review focuses on the contribution that these mouse models have brought to the understanding of hereditary thrombocytopenias with respect to what was known in humans. Animal models have either i) provided novel information on the molecular and cellular pathways that were missing from the patient studies; ii) improved our understanding of the mechanisms of thrombocytopoiesis; iii) been instrumental in structure-function studies of the mutated gene products; and iv) been an invaluable tool as preclinical models to test new drugs or develop gene therapies. At present, the genetic determinants of thrombocytopenia remain unknown in almost half of all cases. Currently available high-speed sequencing techniques will identify new candidate genes, which will in turn allow the generation of murine models to confirm and further study the abnormal phenotype. In a complementary manner, programs of random mutagenesis in mice should also identify new candidate genes involved in thrombocytopenia. PMID:27478199

  7. Corticosteroid in the Treatment of Moderate to Severe Thrombocytopenia Due to Leptospirosis

    PubMed Central

    Alian, Shahriar; Asghari, Hasan; Najafi, Narges; Davoudi, Alireza; Yazdani, Jamshid

    2014-01-01

    Background: Thrombocytopenia is associated with a bad prognosis in Leptospirosis. Objectives: We investigated the effect of corticosteroids to improve thrombocytopenia due to leptospirosis. Patients and Methods: In a clinical trial, all patients admitted with leptospirosis in Razi Hospital of Ghaemshahr, north of Iran were enrolled in a 2-year study. Totally, 56 patients with moderate to severe thrombocytopenia were randomized to control and treatment groups. The treatment group received corticosteroid (prednisolone 1 mg/kg/day for maximum one week) in addition to the standard antibiotic therapy. Results: There was no significant difference regarding age and gender between the two groups (P = 0.254, P = 0.789, respectively). The mean duration to improve thrombocytopenia was 4.41 ± 0.197 days in the treatment group and 5.72 ± 0.318 days in the control group, which was significantly different (P = 0.003). Duration of hospitalization in the treatment group was 5.24 ± 0.244 days and 6.23 ± 0.329 days in the control group, which was significantly different (P = 0.028). The two groups had no significant difference regarding mortality, intubation, level of platelet, duration of ICU admission and pulmonary, renal or hepatic involvement. Conclusions: Corticosteroid therapy decreased the length of hospitalization only in severe subgroup thrombocytopenia, but not in the moderate subgroup. PMID:25763200

  8. The contribution of mouse models to the understanding of constitutional thrombocytopenia.

    PubMed

    Léon, Catherine; Dupuis, Arnaud; Gachet, Christian; Lanza, François

    2016-08-01

    Constitutional thrombocytopenias result from platelet production abnormalities of hereditary origin. Long misdiagnosed and poorly studied, knowledge about these rare diseases has increased considerably over the last twenty years due to improved technology for the identification of mutations, as well as an improvement in obtaining megakaryocyte culture from patient hematopoietic stem cells. Simultaneously, the manipulation of mouse genes (transgenesis, total or conditional inactivation, introduction of point mutations, random chemical mutagenesis) have helped to generate disease models that have contributed greatly to deciphering patient clinical and laboratory features. Most of the thrombocytopenias for which the mutated genes have been identified now have a murine model counterpart. This review focuses on the contribution that these mouse models have brought to the understanding of hereditary thrombocytopenias with respect to what was known in humans. Animal models have either i) provided novel information on the molecular and cellular pathways that were missing from the patient studies; ii) improved our understanding of the mechanisms of thrombocytopoiesis; iii) been instrumental in structure-function studies of the mutated gene products; and iv) been an invaluable tool as preclinical models to test new drugs or develop gene therapies. At present, the genetic determinants of thrombocytopenia remain unknown in almost half of all cases. Currently available high-speed sequencing techniques will identify new candidate genes, which will in turn allow the generation of murine models to confirm and further study the abnormal phenotype. In a complementary manner, programs of random mutagenesis in mice should also identify new candidate genes involved in thrombocytopenia. PMID:27478199

  9. The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

    PubMed Central

    Danish, Fazal-i-Akbar; Yasmin, Saeeda

    2013-01-01

    Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective), there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity). In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV)-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012) using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.” PMID:24696622

  10. Re-evaluation of Need for Bone Marrow Examination in Patients with Isolated Thrombocytopenia Contributors.

    PubMed

    Purohit, Abhishek; Aggarwal, Mukul; Singh, Pawan Kumar; Mahapatra, Manoranjan; Seth, Tulika; Tyagi, Seema; Saxena, Renu; Pati, Hara P; Mishra, Pravas

    2016-06-01

    Diagnosis of immune thrombocytopenia (ITP) is based on clinical suspicion and normal peripheral smear except for thrombocytopenia. Bone marrow examination is carried out to rule out leukemia, myelodysplastic syndrome or aplastic anemia. However, in most cases, clinical diagnosis is not altered after the bone marrow reports. Hence, this present study was carried out to evaluate the justification for bone marrow examination in the setting of isolated thrombocytopenia. All patients presenting to the hematology OPD with isolated thrombocytopenia and suspected diagnosis of ITP, between October 2011 and April 2013, were included in the study. Data was collected from bone marrow reports and outpatient records. A total of 353 cases were found. 319 cases had features of typical ITP and the rest had some form of organomegaly and/or lymphadenopathy. Bone marrow examination in all cases revealed normal hematopoietic elements and prominence of megakaryocytes including juvenile forms with no novel diagnosis in any patient. Routine use of bone marrow examination in the diagnostic workup of isolated thrombocytopenia is not required in our center even if steroids are planned as a first line therapy. However, a detailed history, thorough examination with complete hemogram and peripheral smear examination are essential. PMID:27065582

  11. Mechanisms and etiologies of thrombocytopenia in the intensive care unit: impact of extensive investigations

    PubMed Central

    2014-01-01

    Background Thrombocytopenia is common in the intensive care unit. Potential mechanisms and etiologies behind this phenomenon are multiple and often entangled. We assessed the effect of a systematic approach, using routinely available tests, on the proportion of patients in whom the mechanism (primary objective) and etiology (secondary objective) of thrombocytopenia in a mixed intensive care unit (ICU) could be identified. Methods Before-and-after study of all patients with thrombocytopenia was used. ‘Before’ group had no intervention. New standard operating procedures for thrombocytopenia management were introduced. In the ‘After’ group, bone marrow aspiration; determination of fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes, haptoglobin, and bilirubin were performed. Results In the Before group (n = 20), the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83% in After group (n = 23) (p < 0.001) (48% peripheral, 35% mixed). Before intervention, ≥1 etiology was identified in 15% versus 95.7% in the After group (p < 0.001). Conclusions Systematic and extensive investigation using routine tests highlights the mechanisms and etiology of thrombocytopenia in most cases. PMID:25593741

  12. NEONATAL DESTRUCTION OF DOPAMINERGIC NEURONS

    EPA Science Inventory

    Rats treated as neonates with 6-hydroxydopamine are proposed to model the dopamine deficiency associated with Lesch-Nyhan syndrome (LNS). o understand the neurobiological basis of specific behaviors in LNS, investigations were undertaken in these neonatally lesioned rats. everal ...

  13. Changes in bone marrow morphology in adults receiving romiplostim for the treatment of thrombocytopenia associated with primary immune thrombocytopenia.

    PubMed

    Janssens, Ann; Rodeghiero, Francesco; Anderson, David; Chong, Beng H; Boda, Zoltán; Pabinger, Ingrid; Červinek, Libor; Terrell, Deirdra R; Wang, Xuena; Franklin, Janet

    2016-06-01

    The effects of romiplostim on bone marrow morphology were evaluated in adults with immune thrombocytopenia (ITP). Patients with platelet counts <50 × 10(9)/L, ≥1 prior ITP therapies, and no collagen at baseline received weekly subcutaneous romiplostim starting at 1 μg/kg, adjusted to maintain platelet counts between 50 and 200 × 10(9)/L. Biopsies were scheduled after 1, 2, or 3 years of romiplostim (cohorts 1, 2, and 3, respectively). Irrespective of scheduled time, biopsies were performed earlier if patients discontinued or failed to achieve/maintain a response to romiplostim. Reticulin (silver stain) and collagen (trichrome stain) were graded by two hematopathologists using the modified Bauermeister scale (0-4). Of 169 patients, 131 had evaluable biopsies; 9/131 (6.9 %) had increases of ≥2 grades on the modified Bauermeister scale (cohort 1: 0/34; cohort 2: 2/39; cohort 3: 7/58), including two with collagen. Three of the nine patients had follow-up biopsies, including one patient with collagen; changes were reversible after romiplostim discontinuation. Of the nine patients, one had neutropenia detected by laboratory test and two had adverse events of anemia, both non-serious and not treatment-related. By actual exposure (as some biopsies did not occur as scheduled), the number of patients with grade increases ≥2 were year 1: 3/41, year 2: 1/38, year 3: 5/52. Twenty-four patients sustained platelet counts ≥50 × 10(9)/L for ≥6 months with no ITP medications after discontinuing romiplostim, i.e., they entered clinical remission of their ITP. In conclusion, in patients with ITP receiving romiplostim, bone marrow changes were observed in a small proportion of patients.ClinicalTrials.gov identifier: NCT#00907478. PMID:27130310

  14. Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

    PubMed

    Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

    2015-09-01

    Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively. PMID:25173503

  15. Acute disseminated encephalomyelitis and thrombocytopenia following Epstein-Barr virus infection.

    PubMed

    Saeed, Muhammad; Dabbagh, Omar; Al-Muhaizae, Muhammad; Dhalaan, Hesham; Chedrawi, Aziza

    2014-11-01

    Epstein-Barr Virus (EBV) causes a broad spectrum of disease in humans with several clinical syndromes and is ubiquitous, infecting more than 95% of the world's population. Central Nervous System (CNS) disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. Systemic viral illness in children and complications are rare, but may occur. In few cases, it is associated with a variety of CNS and hematological complications like acute disseminated encephalomyelitis, transverse myelitis, neuropsychiatric syndrome, GBS, autoimmune thrombocytopenia and hemolytic anemia and they usually respond to immunotherapy. We report previously healthy boy, who presented with left sided weakness, headache and thrombocytopenia following EBV infection. The thrombocytopenia was resistant to intravenous immunoglobulin and methylprednisolone but responded well to Rituximab. PMID:25518779

  16. [A Case of Drug-Induced Thrombocytopenia Resulting from Sensitivity to Oxaliplatin].

    PubMed

    Masuda, Taiki; Nagai, Kagami; Sanada, Katsuya

    2015-11-01

    A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature. PMID:26805296

  17. Successful intravenous thrombolysis in a patient with antiphospholipid syndrome, acute ischemic stroke and severe thrombocytopenia.

    PubMed

    Camara-Lemarroy, Carlos R; Infante-Valenzuela, Adrian; Andrade-Vazquez, Catalina J; Enriquez-Noyola, Raul V; Garcia-Valadez, Erick A; Gongora-Rivera, Fernando

    2016-04-01

    Alteplase is the only approved drug for the treatment of acute ischemic stroke, but it is offered to a minority of patients, not only because of the short therapeutic window but also because of the numerous contraindications associated with thrombolysis, such as thrombocytopenia. There is some controversy on the true risk associated with thrombolysis in patients with thrombocytopenia. Here we report the case of a young patient, who developed an in-hospital acute ischemic stroke involving a large territory of the right middle cerebral artery, who was successfully treated with intravenous alteplase, despite having thrombocytopenia and prolonged prothrombin times due to systemic lupus erythematosus and antiphospholipid syndrome. This case exemplifies the need to reassess contraindications for thrombolysis, many based on expert opinion and not clinical evidence, especially in complex clinical situations. PMID:26575492

  18. [Treatment of neonatal hyperbilirubinemia

    PubMed

    Carvalho, M D

    2001-07-01

    OBJECTIVE: To review the recent medical literature on the treatment of neonatal jaundice, focusing on practical aspects that are relevant to pediatricians and neonatologists. SOURCES: An extensive review of the related literature was performed, also including the authors clinical experience in this field of investigation. SUMMARY OF THE FINDINGS: Jaundice is very common among infants during the first days of life. Several factors such as maternal and neonatal history have to be considered before implementing treatment. Significant advances have been made in the past few years concerning the treatment of jaundiced newborn infants. This review focuses on three forms of treatment of neonatal hyperbilirubinemia: phototherapy, exchange transfusion and the use of drugs to reduce serum bilirubin concentration. CONCLUSIONS: Nowadays, the in-depth knowledge about the mechanism of action of phototherapy, the development of intensified phototherapy units and the use of drugs to reduce bilirubin formation, have contributed to significantly decrease the need for exchange transfusion. PMID:14676895

  19. The Impact of Thrombocytopenia on Outcome in Patients with Acute Coronary Syndromes: A Single Center Retrospective Study

    PubMed Central

    Sinkovič, Andreja; Majal, Maja

    2015-01-01

    Background. In acute coronary syndromes (ACS), treated by combined antithrombotic therapy and percutaneous coronary interventions (PCI), thrombocytopenia may occur. Our aim was to evaluate predictors and the impact of thrombocytopenia on mortality in high-risk ACS patients. Methods. We retrospectively evaluated high-risk ACS patients. Thrombocytopenia was defined as platelet count <140.000/mL or a drop in platelet count of >50% during in-hospital stay. We compared demographic, laboratory, clinical, and mortality data between nonthrombocytopenic and thrombocytopenic ACS patients and evaluated independent predictors of thrombocytopenia. Results. In 371 ACS patients, thrombocytopenia was observed in 21.3%. Thrombocytopenic patients were significantly older and, less likely treated by PCIs (72.1% versus 89.7%, p < 0.001) and combined antithrombotic therapy, with increased incidence of in-hospital complications and the use of additional treatments, but with increased mortality at 30 days (27.8% versus 10.2%, p < 0.001) and 6 months (35.4% versus 13.6%, p < 0.001) when compared to nonthrombocytopenic patients. The use of antibiotics, transfusions, insertion of intra-aortic balloon pump (IABP), and prior stroke independently predicted thrombocytopenia. Conclusions. Thrombocytopenia, observed in about 20% of high-risk ACS patients, was associated significantly with in-hospital complications and mortality. Predictors of thrombocytopenia were the use of antibiotics, transfusions, insertion of IABP, and prior stroke. PMID:26504845

  20. Neonatal herpes simplex virus.

    PubMed

    Berardi, Alberto; Lugli, Licia; Rossi, Cecilia; Maria, Chiara Laguardia; Guidotti, Isotta; Gallo, Claudio; Ferrari, Fabrizio

    2011-10-01

    Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment. PMID:21942600

  1. [Severe hemolytic disease of the newborn as a result of late and undiagnosed alloimmunization--case report].

    PubMed

    Drozdowska-Szymczak, Agnieszka; Czaplińska, Natalia; Borek-Dziecioł, Beata; Kociszewska-Najman, Bozena; Bartkowiak, Robert; Wielgoś, Mirosław

    2014-03-01

    We report a case of a hemolytic disease in a newborn from the first pregnancy due to anti-D antibodies. The maternal blood group was A Rhesus negative. She had an antibody screening test twice during the pregnancy (in the second trimester) and it was negative. The pregnancy was uneventful, without any invasive procedures and bleeding. The infant was born at 39 weeks of gestation in good overall condition. After the delivery the blood group of the neonate was indicated - A Rhesus positive, BOC positive. Anti-D antibodies were detected in maternal blood. Neonatal blood tests revealed severe anemia (hemoglobin level: 6.0g/dl, hematocrit: 22.2%, erythrocytes: 2.01T/L). During the first day of neonatal life, the newborn received two transfusions of red blood cells. Bilirubin level and rate of rise were not recommendation enough for exchange transfusion. The newborn was treated with continuous phototherapy since the delivery The perinatal period was complicated with intrauterine infection and respiratory failure. Hematopoietic vitamins and iron supplementation was initiated in the second week of neonatal life due to persistent anemia. The child remained under medical care of a hematologic clinic and received human recombinant erythropoietin treatment. PMID:24783436

  2. Autoimmune thrombocytopenia: determination of platelet-specific autoantibodies by flow cytometry.

    PubMed

    Tomer, Aaron

    2006-10-15

    Autoimmune thrombocytopenia is a disorder characterized by antibody-mediated accelerated platelet destruction. Despite its clinical importance, the diagnosis of which is one of exclusion, thus inevitably associated with potential difficulties. Current methods used to determine antigen-specific antibodies including MAIPA and the radioactive immunobead assay, are not routinely used due to methodological and practical limitations. To facilitate diagnosis, flow cytometric methods have been developed, suitable for testing a single or multiple samples. The feasible flow cytometric methods with their high sensitivity and specificity should facilitate the routine use of diagnostic methods for autoimmune thrombocytopenia and permit follow-up to determine immune remission. PMID:16933272

  3. Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization

    PubMed Central

    Comstock, Ioanna A.; Longmire, Michelle; Aster, Richard H.; Milki, Amin A.

    2015-01-01

    Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically. PMID:25810935

  4. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report*

    PubMed Central

    Blais, Anne-Sophie; Deschênes Rompré, Marie-Pier; Lacombe, Louis

    2014-01-01

    Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy. PMID:26954936

  5. Acute profound abciximab induced thrombocytopenia: a correct management of a methodological error.

    PubMed

    Tanzilli, Gaetano; Sordi, Martina; Arrivi, Alessio; Mangieri, Enrico; Scappaticci, Massimiliano

    2009-01-01

    Thrombocytopenia is a rare complication of glycoprotein IIb/IIIa treatment. We report a case of an acute profound abciximab induced thrombocytopenia and its successful management. The patient, presenting with unstable angina, underwent percutaneous coronary intervention with implantation of three drug eluting stents without receiving a clopidogrel loading dose according to guidelines. The rapid drop in the platelet count after abciximab elastomeric pump infusion was treated with drug discontinuation and platelet transfusion. The high risk of stent thrombosis was avoided by a timely readministration of the dual antiplatelet treatment. PMID:21977060

  6. Risk Factors for Thrombocytopenia in Adult Chinese Patients Receiving Linezolid Therapy

    PubMed Central

    Chen, Chao; Guo, Dai-Hong; Cao, Xiutang; Cai, Yun; Xu, Yuanjie; Zhu, Man; Ma, Liang

    2012-01-01

    Background Linezolid (LZD), an oxazolidinone antibiotic agent, has excellent activity and bioavailability against most methicillin-sensitive and methicillin-resistant gram-positive bacteria. Although LZD is generally well tolerated, several studies have found adverse hematologic effects, of which thrombocytopenia is of most concern. Objective To investigate the risk factors for thrombocytopenia in patients who received oral or parenteral LZD therapy between February 1 and November 30, 2010. Methods Data were extracted retrospectively from the electronic medical records in our hospital information system. Thrombocytopenia was defined as either a final platelet count of <100 × 109/L (criterion 1) or a 25% reduction from the baseline platelet count (criterion 2). Risk factors were determined using logistic regression analysis, and clinical features were predicted using receiver operating characteristic curves. Results The study included 254 patients, with mean (SD) age of 59 (17.66) years. The duration of LZD therapy was 9.43 (5.63) days. Thrombocytopenia developed in 69 patients (27.2%), as defined by criterion 1, and in 127 patients (50%), as defined by criterion 2. At univariate analysis, age, weight, creatinine clearance, serum albumin concentration, baseline platelet count, daily dosage, and concomitant use of caspofungin, levofloxacin, and meropenem were significant risk factors for thrombocytopenia. At multivariate analysis and using ROC curves, daily dose ≥18.75 mg/kg, baseline platelet count ≤181 × 109/L, duration of LZD therapy ≥10 days, and concomitant use of caspofungin and levofloxacin were independent risk factors for thrombocytopenia as defined by criterion 1, whereas creatinine clearance ≤88.39 mL/min/1.73 m2, serum albumin concentration ≤33.5 g/L, daily dose ≥18.46 mg/kg, and caspofungin were independent risk factors for thrombocytopenia as defined by criterion 2. Conclusions The incidence of LZD-related thrombocytopenia in the Chinese

  7. Severe thrombocytopenia soon after drug-eluting stent implantation in ST-elevation myocardial infarction

    PubMed Central

    Pośnik-Kisło, Anna; Błaszak-Ciećwierska, Wiesława; Dąbrowski, Marek

    2015-01-01

    Thrombocytopenia is among the most frequent haematological issues in patients hospitalised with myocardial infarction. We discuss the case of a 77-year-old male who was admitted to hospital on the 4th hour of ST-elevation myocardial infarction of the anterior wall. A percutaneous coronary intervention to critically stenoted initial segment of the anterior descending branch was performed. A few days later he started developing symptomatic thrombocytopenia. On the course of his long hospitalization we faced many important problems, concerning both diagnosis and treatment of these co-existing conditions. PMID:26677393

  8. Scrotal Swelling in the Neonate

    PubMed Central

    Basta, Amaya M.; Courtier, Jesse; Phelps, Andrew; Copp, Hillary L.; MacKenzie, John D.

    2016-01-01

    Discovery of scrotal swelling in a neonate can be a source of anxiety for parents, clinicians, and sonologists alike. This pictorial essay provides a focused review of commonly encountered scrotal masses and mimics specific to the neonatal setting. Although malignancy is a concern, it is very uncommon, as most neonatal scrotal masses are benign. Key discriminating features and management options are highlighted to improve the radiologist’s ability to diagnose neonatal scrotal conditions and guide treatment decisions. Neonatal scrotal processes ranging from common to uncommon will be discussed. PMID:25715370

  9. Phase Contrast Imaging in Neonates

    PubMed Central

    Zhong, Kai; Ernst, Thomas; Buchthal, Steve; Speck, Oliver; Anderson, Lynn; Chang, Linda

    2011-01-01

    Magnetic resonance phase images can yield superior gray and white matter contrast compared to conventional magnitude images. However, the underlying contrast mechanisms are not yet fully understood. Previous studies have been limited to high field acquisitions in adult volunteers and patients. In this study, phase imaging in the neonatal brain is demonstrated for the first time. Compared to adults, phase differences between gray and white matter are significantly reduced but not inverted in neonates with little myelination and iron deposits in their brains. The remaining phase difference between the neonatal and adult brains may be due to different macromolecule concentration in the unmyelinated brain of the neonates and thus different frequency due to water macromolecule exchange. Additionally, the susceptibility contrast from brain myelination can be separately studied in neonates during brain development. Therefore, magnetic resonance phase imaging is suggested as a novel tool to study neonatal brain development and pathologies in neonates. PMID:21232619

  10. [Recommendations for neonatal transport].

    PubMed

    Moreno Hernando, J; Thió Lluch, M; Salguero García, E; Rite Gracia, S; Fernández Lorenzo, J R; Echaniz Urcelay, I; Botet Mussons, F; Herranz Carrillo, G; Sánchez Luna, M

    2013-08-01

    During pregnancy, it is not always possible to identify maternal or foetal risk factors. Infants requiring specialised medical care are not always born in centres providing intensive care and will need to be transferred to a referral centre where intensive care can be provided. Therefore Neonatal Transport needs to be considered as part of the organisation of perinatal health care. The aim of Neonatal Transport is to transfer a newborn infant requiring intensive care to a centre where specialised resources and experience can be provided for the appropriate assessment and continuing treatment of a sick newborn infant. Intrauterine transfer is the ideal mode of transport when the birth of an infant with risk factors is diagnosed. Unfortunately, not all problems can be detected in advance with enough time to safely transfer a pregnant woman. Around 30- 50% of risk factors will be diagnosed during labour or soon after birth. Therefore, it is important to have the knowledge and resources to resuscitate and stabilise a newborn infant, as well as a specialised neonatal transport system. With this specialised transport it is possible to transfer newly born infants with the same level of care that they would receive if they had been born in a referral hospital, without increasing their risks or affecting the wellbeing of the newborn. The Standards Committee of the Spanish Society of Neonatology reviewed and updated recommendations for intrauterine transport and indications for neonatal transfer. They also reviewed organisational and logistic factors involved with performing neonatal transport. The Committee review included the type of personnel who should be involved; communication between referral and receiving hospitals; documentation; mode of transport; equipment to stabilise newly born infants; management during transfer, and admission at the referral hospital. PMID:23434016

  11. Maternal, neonatal and community factors influencing neonatal mortality in Brazil.

    PubMed

    Machado, Carla Jorge; Hill, Kenneth

    2005-03-01

    Child mortality (the mortality of children less than five years old) declined considerably in the developing world in the 1990s, but infant mortality declined less. The reductions in neonatal mortality were not impressive and, as a consequence, there is an increasing percentage of infant deaths in the neonatal period. Any further reduction in child mortality, therefore, requires an understanding of the determinants of neonatal mortality. 209,628 birth and 2581 neonatal death records for the 1998 birth cohort from the city of São Paulo, Brazil, were probabilistically matched. Data were from SINASC and SIM, Information Systems on Live Births and Deaths of Brazil. Logistic regression was used to find the association between neonatal mortality and the following risk factors: birth weight, gestational age, Apgar scores at 1 and 5 minutes, delivery mode, plurality, sex, maternal education, maternal age, number of prior losses, prenatal care, race, parity and community development. Infants of older mothers were less likely to die in the neonatal period. Caesarean delivery was not found to be associated with neonatal mortality. Low birth weight, pre-term birth and low Apgar scores were associated with neonatal death. Having a mother who lives in the highest developed community decreased the odds of neonatal death, suggesting that factors not measured in this study are behind such association. This result may also indicate that other factors over and above biological and more proximate factors could affect neonatal death. PMID:15768774

  12. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators

    PubMed Central

    de Azeredo, Elzinandes Leal; Monteiro, Robson Q.; de-Oliveira Pinto, Luzia Maria

    2015-01-01

    Dengue is an infectious disease caused by dengue virus (DENV). In general, dengue is a self-limiting acute febrile illness followed by a phase of critical defervescence, in which patients may improve or progress to a severe form. Severe illness is characterized by hemodynamic disturbances, increased vascular permeability, hypovolemia, hypotension, and shock. Thrombocytopenia and platelet dysfunction are common in both cases and are related to the clinical outcome. Different mechanisms have been hypothesized to explain DENV-associated thrombocytopenia, including the suppression of bone marrow and the peripheral destruction of platelets. Studies have shown DENV-infected hematopoietic progenitors or bone marrow stromal cells. Moreover, anti-platelet antibodies would be involved in peripheral platelet destruction as platelets interact with endothelial cells, immune cells, and/or DENV. It is not yet clear whether platelets play a role in the viral spread. Here, we focus on the mechanisms of thrombocytopenia and platelet dysfunction in DENV infection. Because platelets participate in the inflammatory and immune response by promoting cytokine, chemokine, and inflammatory mediator secretion, their relevance as “immune-like effector cells” will be discussed. Finally, an implication for platelets in plasma leakage will be also regarded, as thrombocytopenia is associated with clinical outcome and higher mortality. PMID:25999666

  13. [Rifampicin-induced severe thrombocytopenia in a patient with miliary tuberculosis].

    PubMed

    Onoda, Tetsuya; Murakami, Kazuo; Eda, Ryousuke; Hiraki, Akio; Makihata, Kiyoshi; Takao, Kazushi; Aoe, Keisuke; Maeda, Tadashi; Takeyama, Hiroyasu

    2003-07-01

    A 74-year-old female visited a local clinic complaining of fever on January 21, 2002. A chest X-ray and a chest computed tomography (CT) showed diffuse micronodules in all lung fields, which strongly suggested miliary tuberculosis. On January 23, she was referred to our hospital for further examinations. Though sputum was negative on smear, culture, and polymerase chain reaction (PCR) for M. tuberculosis, bone marrow aspirate examined on admission revealed epithelioid granuloma. Therefore we diagnosed her as a miliary tuberculosis, and she was treated with 300 mg of Isoniazid (INH), 450 mg of Rifampicin, and 750 mg of Streptomycin (SM) daily. Five days later, severe thrombocytopenia (platelet count 0.3 x 10(4)/microliter) was observed. We immediately discontinued all antituberculous drugs and administered concentrated platelets and immune globulin. Platelet-associated IgG was detected, and megakaryocytes were slightly increased in moderately hypocellular marrow on the bone marrow aspirate examined again after the appearance of thrombocytopenia. Eleven days after discontinuing all antituberculous drugs, platelet count recovered to 10.2 x 10(4)/microliter. INH, SM, Levofloxacin (LV) were administered afterward, and these drugs did not induce thrombocytopenia. Though challenge administration of RFP was not performed, we concluded that the thrombocytopenia was immunologically induced by RFP. We should keep in mind that RFP-induced thromobocytopenia could appear in the first week after the initiation of therapy. PMID:12931647

  14. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia

    PubMed Central

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

    2015-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). PMID:26814707

  15. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

    PubMed Central

    Noris, Patrizia; Schlegel, Nicole; Klersy, Catherine; Heller, Paula G.; Civaschi, Elisa; Pujol-Moix, Nuria; Fabris, Fabrizio; Favier, Remi; Gresele, Paolo; Latger-Cannard, Véronique; Cuker, Adam; Nurden, Paquita; Greinacher, Andreas; Cattaneo, Marco; De Candia, Erica; Pecci, Alessandro; Hurtaud-Roux, Marie-Françoise; Glembotsky, Ana C.; Muñiz-Diaz, Eduardo; Randi, Maria Luigia; Trillot, Nathalie; Bury, Loredana; Lecompte, Thomas; Marconi, Caterina; Savoia, Anna; Balduini, Carlo L.; Bayart, Sophie; Bauters, Anne; Benabdallah-Guedira, Schéhérazade; Boehlen, Françoise; Borg, Jeanne-Yvonne; Bottega, Roberta; Bussel, James; De Rocco, Daniela; de Maistre, Emmanuel; Faleschini, Michela; Falcinelli, Emanuela; Ferrari, Silvia; Ferster, Alina; Fierro, Tiziana; Fleury, Dominique; Fontana, Pierre; James, Chloé; Lanza, Francois; Le Cam Duchez, Véronique; Loffredo, Giuseppe; Magini, Pamela; Martin-Coignard, Dominique; Menard, Fanny; Mercier, Sandra; Mezzasoma, Annamaria; Minuz, Pietro; Nichele, Ilaria; Notarangelo, Lucia D.; Pippucci, Tommaso; Podda, Gian Marco; Pouymayou, Catherine; Rigouzzo, Agnes; Royer, Bruno; Sie, Pierre; Siguret, Virginie; Trichet, Catherine; Tucci, Alessandra; Saposnik, Béatrice; Veneri, Dino

    2014-01-01

    Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 109/L. PMID:24763399

  16. Saddle Pulmonary Embolism in a Cancer Patient with Thrombocytopenia: A Treatment Dilemma

    PubMed Central

    Zalpour, Ali; Hanzelka, Katy; Patlan, John T.; Rozner, Marc A.; Yusuf, Syed Wamique

    2011-01-01

    The association between cancer and venous thromboembolism (VTE) is well established. Saddle pulmonary embolism is not uncommon in hospitalized cancer patients and confers a higher mortality. We report a case of saddle pulmonary embolism in a cancer patient with thrombocytopenia, discuss the bleeding risks, complexity of managing such patients and review current guidelines. PMID:21234423

  17. Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

    PubMed Central

    Lonial, Sagar; Waller, Edmund K.; Richardson, Paul G.; Jagannath, Sundar; Orlowski, Robert Z.; Giver, Cynthia R.; Jaye, David L.; Francis, Dixil; Giusti, Sara; Torre, Claire; Barlogie, Bart; Berenson, James R.; Singhal, Seema; Schenkein, David P.; Esseltine, Dixie-Lee W.; Anderson, Jessica; Xiao, Hugh; Heffner, Leonard T.; Anderson, Kenneth C.

    2005-01-01

    Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production. PMID:16099887

  18. Inherited thrombocytopenia: novel insights into megakaryocyte maturation, proplatelet formation and platelet lifespan

    PubMed Central

    Johnson, Ben; Fletcher, Sarah J.; Morgan, Neil V.

    2016-01-01

    Abstract The study of patients with inherited bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets and their precursor, the megakaryocyte. The normal range of platelet counts in the bloodstream ranges from 150 000 to 400 000 platelets per microliter and is normally maintained within a narrow range for each individual. This requires a constant balance between thrombopoiesis, which is primarily controlled by the cytokine thrombopoietin (TPO), and platelet senescence and consumption. Thrombocytopenia can be defined as a platelet count of less than 150 000 per microliter and can be acquired or inherited. Heritable forms of thrombocytopenia are caused by mutations in genes involved in megakaryocyte differentiation, platelet production and platelet removal. In this review, we will discuss the main causative genes known for inherited thrombocytopenia and highlight their diverse functions and whether these give clues on the processes of platelet production, platelet function and platelet lifespan. Additionally, we will highlight the recent advances in novel genes identified for inherited thrombocytopenia and their suggested function. PMID:27025194

  19. Pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia in Japanese patients with renal cell carcinoma.

    PubMed

    Nagata, Masashi; Ishiwata, Yasuyoshi; Takahashi, Yutaka; Takahashi, Hiromitsu; Saito, Kazutaka; Fujii, Yasuhisa; Kihara, Kazunori; Yasuhara, Masato

    2015-01-01

    The aim of the present study was to clarify the therapeutic range and adequate dose of sunitinib in Japanese renal cell carcinoma patients by means of a pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia. Six patients with renal cell carcinoma were enrolled in this study. After starting the sunitinib treatment, between three and seven blood samples were obtained from each patient just before the administration of sunitinib. Serum concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were fit to the 1-compartment model with first-order absorption. Changes in platelet counts were fit to the pharmacokinetic-pharmacodynamic model, in which the proliferation of platelet progenitor cells was assumed to be linearly inhibited by sunitinib and its metabolite. All patients using 50 mg as an initial dose of sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic-pharmacodynamic model created successfully described the time course of sunitinib-induced thrombocytopenia and could predict changes in platelet counts after alterations to the dosage of sunitinib administered. The simulation results indicated that the total trough level of sunitinib to avoid severe thrombocytopenia should be <100 ng/mL, and also that the initial daily dose of sunitinib could be reduced to 37.5 mg or 25 mg in most Japanese patients. In addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring of platelet counts is required for the safe use of sunitinib. PMID:25757921

  20. A case of IgA deficiency with anti-IgA antibodies and autoimmune thrombocytopenia.

    PubMed

    Pierre, P G; Ferrant, A; Michaux, J L; Vaerman, J P; Van den Bosshe, L

    1994-01-01

    The case of a young woman with autoimmune thrombocytopenia, complete IgA deficiency and anti-IgA antibodies is presented and the role of the AH 8-1 supratype (HLA B8, DR3) is discussed. Such an association necessitates use of IgA-free blood products in order to avoid anaphylactic reactions. PMID:8152904

  1. Diabetes Mellitus Increases Severity of Thrombocytopenia in Dengue-Infected Patients

    PubMed Central

    Chen, Chung-Yuan; Lee, Mei-Yueh; Lin, Kun-Der; Hsu, Wei-Hao; Lee, Yaun-Jinn; Hsiao, Pi-Jung; Shin, Shyi-Jang

    2015-01-01

    Background: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54 ± 51.69 vs. 86.58 ± 63.4 (p ≤ 0.001), 43.98 ± 44.09 vs. 64.52 ± 45.06 (p = 0.002), 43.86 ± 35.75 vs. 62.72 ± 51.2 (p = 0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression β of −13.981 (95% confidence interval (CI) −27.587, −0.374), −26.847 (95% CI −37.562, −16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of −2.947 (p = 0.004), 2.801 (p = 0.005), and −3.568 (p ≤ 0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in

  2. An Elevated Fetal IL-6 Concentration Can Be Observed In Fetuses with Anemia Due To Rh Alloimmunization: Implications for the Understanding of the Fetal Inflammatory Response Syndrome

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Gomez, Ricardo; Kusanovic, Juan Pedro; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

    2010-01-01

    Objective The fetal inflammatory response syndrome (FIRS) has been described in the context of preterm labor and preterm PROM and is often associated with intra-amniotic infection/inflammation. This syndrome is characterized by systemic fetal inflammation and operationally-defined by an elevated fetal plasma interleukin (IL)-6. The objective of this study was to determine if FIRS can be found in fetuses with activation of their immune system, such as the one observed in Rh alloimmune-mediated fetal anemia. Methods Fetal blood sampling was performed in sensitized Rh-D negative women with suspected fetal anemia (n=16). Fetal anemia was diagnosed according to reference range nomograms established for the assessment of fetal hematologic parameters. An elevated fetal plasma IL-6 concentration was defined using a cutoff of >11 pg/mL. Concentrations of IL-6 were determined by immunoassay. Non-parametric statistics were used for analysis. Results 1) The prevalence of an elevated fetal plasma IL-6 was 25% (4/16); 2) there was an inverse relationship between the fetal hematocrit and IL-6 concentration - the lower the hematocrit, the higher the fetal IL-6 (r= −0.68, p=0.004); 3) fetuses with anemia had a significantly higher plasma IL-6 concentration than those without anemia (3.74 pg/ml, interquartile range (IQR) 1.18–2.63 vs. 1.46 pg/ml, IQR 1.76–14.7; p=0.02); 4) interestingly, all fetuses with an elevated plasma IL-6 concentration had anemia (prevalence 40%, 4/10), while in the group without anemia, none had an elevated fetal plasma IL-6. Conclusions An elevation in fetal plasma IL-6 can be observed in a subset of fetuses with anemia due to Rh alloimmunization. This observation suggests that the hallmark of FIRS can be caused by non-infection-related insults. Further studies are required to determine whether the prognosis of FIRS caused by intra-amniotic infection/inflammation is different from that induced by alloimmunization. PMID:20701435

  3. Neonatal iliopsoas abscess.

    PubMed

    Horiuchi, Atsushi; Kameoka, Kazuhiro; Kuwabara, Jun; Watanabe, Yuji; Kawakami, Sanae; Tauchi, Hisamichi; Ishii, Eiichi

    2012-10-01

    Iliopsoas abscess (IPA) is rare in children, particularly in neonates. A male neonate was born at 38 weeks of gestation with a weight of 2915 g. On day 22 after birth, his family noticed that his right thigh was swollen. Abdominal computed tomography showed a mass extending to the right iliopsoas from the right thigh with thick septa. Puncture to the right groin yielded purulent fluid, and so a diagnosis of abscess was made. The puncture was followed by surgical drainage through a small inguinal incision, and the abscess cavity was irrigated thoroughly using normal saline. Culture of abscess fluid was positive for Streptococcus pneumoniae, so intravenous ABPC infusion was continued. The postoperative magnetic resonance imaging indicate that the IPA was derived from arthritis of the hip, and the patients received Riemenbügel for the incomplete hip dislocation. He is doing well at 2 years of age. PMID:23005905

  4. Remifentanil: applications in neonates.

    PubMed

    Kamata, Mineto; Tobias, Joseph D

    2016-06-01

    Remifentanil is a synthetic opioid derivative that was introduced into clinical practice in the United States in 1996. The unique modification of its chemical structure to include a methyl-ester ring allows its hydrolysis by non-specific plasma and tissue esterases. This molecular configuration results in its rapid metabolism thereby providing a rapid onset, easy titration by continuous infusion, and a short context-sensitive half-life with rapid elimination. These principles are stable and consistent across all age groups regardless of the infusion characteristics. Owing to these pharmacokinetic characteristics, it is an effective agent in the neonatal population allowing the provision of intense analgesia and anesthesia with a rapid recovery profile in various clinical scenarios. Here, we review the pharmacokinetics of remifentanil in neonates, discuss its clinical applications including intraoperative administration for anesthetic care, unique applications for procedural sedation including endotracheal intubation, and its potential use for sedation in the Intensive Care Unit setting during mechanical ventilation. PMID:26758072

  5. Neonatal mortality in Meerut district.

    PubMed

    Garg, S K; Mishra, V N; Singh, J V; Bhatnagar, M; Chopra, H; Singh, R B

    1993-09-01

    A study of neonatal mortality in Meerut district revealed an infant mortality rate of 50.1 per 1000 live births. Neonatal mortality accounted for 37.8% of infant mortality with a neonatal mortality rate of 19.0 per 1000 live births. 90.5% of these neonates were delivered at home largely by untrained personnel (57.2%). Only 28.6% of these neonates were treated by qualified doctors and only 30.9% of their mothers were fully immunized against tetanus. At least 2/3rd of neonatal mortality was due to exogenous factors with tetanus neonatorum and septicaemia being the principal causes of mortality each accounting for a mortality rate of 4.7 per 1000 live births. PMID:8112786

  6. Late onset autoimmune thrombocytopenia associated with pegylated interferon-alpha-2b plus ribavirin treatment for chronic hepatitis C.

    PubMed

    Elefsiniotis, Ioannis S; Pantazis, Konstantinos D; Fotos, Nikolaos V; Moulakakis, Antonios; Mavrogiannis, Christos

    2006-03-01

    Interferon-induced, immune-mediated, thrombocytopenia is a rare event. In this report the case is described of development of severe, reversible, autoimmune thrombocytopenia in a patient with chronic hepatitis C virus infection, 6 months after the discontinuation of pegylated interferon-alpha-2b plus ribavirin treatment. Physicians must be aware that autoimmune thrombocytopenia can occur even after the end of treatment, as a late onset complication, especially when using the pegylated forms of interferons, which have longer half-lives and prolonged activity. PMID:16638114

  7. [Physiopathology of neonatal hyperbilirubinemia].

    PubMed

    Vert, P

    1998-09-01

    The most important steps of bilirubin metabolism involved in the pathophysiology of neonatal hyperbilirubinemia are: 1) hemoglobin degradation by heme oxygenase; 2) bilirubin binding to serum albumin; 3) bilirubin conjugation to acid glucoronic by glucoronyl transferase. Progress in the knowledge of these metabolic steps allows to understanding of why massive hemolysis, infections, hypoxia and prematurity increase the risk of kernicterus and therefore justify adapted preventive and therapeutic measures. PMID:9789638

  8. Anti-KEL7 (anti-Js(b)) alloimmunization diagnostic supported by molecular KEL*6,7 typing in a pregnant woman with previous intrauterine deaths.

    PubMed

    Boturão-Neto, Edmir; Chiba, Akemi Kuroda; Oliveira Barros, Melca Maria; Barretto de Mello, Adriana; Fabron, Antonio; Orlando Bordin, José

    2006-12-01

    Anti-KEL7 (anti-Js(b)) is a rare antibody that has been related to haemolytic transfusion reactions and HDN. We report a case of anti-KEL7 alloimmunization detected in a pregnant woman who had an obstetric previous history of four miscarriages and one stillborn. Employing classical immunohematological techniques, we studied the propositus and her available relatives. Due to the unavailability of commercial anti-KEL6 and anti-KEL7 reagents, we used a KEL*6,7 genotyping method as an alternative tool to contribute with the identification of the alloantibody origin. The results of KEL genotyping showed that the propositus was KEL*6/6 homozygous, while her second partner was KEL*7/7 homozygous. PMID:17097348

  9. Clinical and microbiological profile of persistent coagulase-negative staphylococcal bacteraemia in neonates.

    PubMed

    Dimitriou, G; Fouzas, S; Giormezis, N; Giannakopoulos, I; Tzifas, S; Foka, A; Anastassiou, D E; Spiliopoulou, I; Mantagos, S

    2011-11-01

    An atypical pattern of coagulase-negative staphylococcal (CoNS) sepsis, characterized by persistence despite aggressive antibiotic therapy, has been described in neonates cared for in neonatal intensive-care units. Our aim was to analyse the clinical, microbiological and molecular determinants of this persistent CoNS bacteraemia. Neonates with late-onset CoNS bacteraemia were studied for a 2-year period. Demographic, clinical, laboratory, microbiological and molecular data were compared between neonates with persistent (≥3 consecutive positive blood cultures) and non-persistent CoNS bacteraemia. Twenty-nine infants with persistent and 43 with non-persistent bacteraemia were identified, with no significant differences regarding demographic and clinical characteristics between the two groups. Of a total of 170 CoNS isolates, 80 showed biofilm production (54 persistent and 26 non-persistent; p 0.013), whereas 127 were positive for the icaA and icaD genes (74 persistent and 53 non-persistent; p 0.598). Sixty ica-positive isolates did not produce slime, whereas 13 ica-negative isolates showed biofilm production. Endotracheal intubation and the presence of central vascular catheters were significant risk factors for persistent bacteraemia, but, in a logistic regression model, only biofilm production was significantly related to the persistent form of the disease (p 0.005). In this study, persistent CoNS sepsis in neonates requiring intensive care was not related to most of the known clinical risk factors, and it was associated with severe thrombocytopenia. Isolates associated with persistent bacteraemia were more likely to produce biofilm, independently of the presence of the ica operon. PMID:21463392

  10. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia

    PubMed Central

    Jacobs, Lauren; Maria, Ann; Villano, Danylo; Gaddam, Pragna; Wu, Gang; McGee, Rose B.; Quinn, Emily; Inaba, Hiroto; Hartford, Christine; Pui, Ching-hon; Pappo, Alberto; Edmonson, Michael; Zhang, Michael Y.; Stepensky, Polina; Steinherz, Peter; Schrader, Kasmintan; Lincoln, Anne; Bussel, James; Lipkin, Steve M.; Goldgur, Yehuda; Harit, Mira; Stadler, Zsofia K.; Mullighan, Charles; Weintraub, Michael; Shimamura, Akiko; Zhang, Jinghui; Downing, James R.; Nichols, Kim E.; Offit, Kenneth

    2015-01-01

    Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition. PMID:26102509

  11. Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia.

    PubMed

    Elalfy, Mohsen S; Nugent, Diane

    2016-04-01

    Immune thrombocytopenia (ITP) might be preceded by silent or overt viral infections. Similarly, anti-viral drugs and viral vaccines could also trigger ITP and might play a central role in its pathogenesis. The seasonal nature of childhood ITP suggests that viral infections might initiate immune responses that increase the predisposition and occurrence of ITP. Active cytomegalovirus or Epstein-Barr virus should be considered in differential diagnosis when thrombocytopenia is associated with lymphadenopathy, especially with splenomegaly. This review will focus on the specific association of ITP in association with viral disease and vaccinations, and will discuss the effectiveness of current therapies in light of our current understanding of viral-associated ITP. PMID:27312173

  12. [Effect of the evaluation parameter on sensitivity of resonance thrombography of thrombocytopenia in dogs].

    PubMed

    Adamik, A; Mischke, R

    1998-11-01

    Based on 109 blood samples taken from 36 dogs suffering from thrombocytopenia resonance thrombography with the resonance thrombograph RTG 801 (von Hoerner und Sulger Electronic GmbH, Schwetzingen; manufacturer: Fresenius AG, Bad Homburg) was distinctly more sensitive and more closely correlated to the platelet count using an optimized parameter of the resonance thrombogramm (RTG) in comparison to usual parameters. Nevertheless, clinical requirements regarding samples with platelet counts > 25,000/microliter were not fulfilled. Out of 13 samples with reduced platelet count and simultanous extended capillary bleeding time, depending on the used parameter a maximum of 9 samples could be detected as pathological by the RTG. The normal RTG in part of the cases with clearly altered primary haemostasis contrasts to the exclusive use of RTG in the screening of thrombocytopenia in dogs. PMID:9857562

  13. Aplastic anaemia in pregnancy with severe thrombocytopenia refractory to platelet transfusion: a case and management plan

    PubMed Central

    Smolinsky, Adi; Carson, Michael P; Guzman, Edwin R; Ranzini, Angela; Toscano, Joanne; Bukhari, Amar

    2009-01-01

    Aplastic anaemia is a rare haematological disorder during pregnancy, which when complicated by severe thrombocytopenia poses a significant maternal risk. A woman with aplastic anaemia and a platelet (PLT) count of 11 × 109/L refractory to PLT transfusion required caesarean delivery. Proactive planning by a multidisciplinary team, large volume PLT transfusion prior to surgery and postoperative uterine artery embolization resulted in avoidance of mortality. Maternal preferences should be discussed in detail due to the high risk of maternal morbidity and mortality associated with severe aplastic anaemia. This report outlines a management plan to address the medical and ethical issues faced when caring for a pregnant patient with severe aplastic anaemia and severe thrombocytopenia. We credit the good outcome to our proactive multidisciplinary approach.

  14. Drug Induced Lupus Erythematosus Due to Capecitabine and Bevacizumab Treatment Presenting with Prolonged Thrombocytopenia.

    PubMed

    Ozaslan, Ersin; Eroglu, Eray; Gok, Kevser; Senel, Soner; Baldane, Suleyman; Akyol, Lutfi; Ozkan, Metin

    2015-01-01

    Drug induced lupus erythematosus (DLE) is a syndrome that is formed by lupus-like symptoms and laboratory characteristics. Capecitabine is an orally administered tumor-selective fluoropyrimidine that acts as a prodrug of 5-Fluorouracil and bevacizumab is an antivascular endothelial growth factor (anti-VEGF) antibody, both are used for the treatment of patients with colorectal cancer. Herein we report the first case of DILE in a 68-year-old woman who presented with arthralgia, myalgia and prolonged thrombocytopenia after receiving capecitabine and bevacizumab combination treatment as palliative treatment for metastatic colon cancer. Platelet-levels were increased and joint complaints disappeared in the first week of hydroxychloroquine and methylprednisolone treatment after chemotherapy had been discontinued. In conclusion, physicians should be alert to the possibility of DILE in patients presenting with thrombocytopenia under a capecitabine and bevacizumab chemotherapy regimen. PMID:26710505

  15. Is there still a place for "old therapies" in the management of immune thrombocytopenia?

    PubMed

    Audia, S; Godeau, B; Bonnotte, B

    2016-01-01

    New molecules such as rituximab or thrombopoietin receptor agonists (romiplostim and eltrombopag) have changed the management of immune thrombocytopenia. Therefore, old drugs which are less expensive and with a well-known benefit/risk ratio are being underused. We aim to define the place of dapsone, danazol, hydroxychloroquine and vinca-alkaloids at the era of targeted therapy in immune thrombocytopenia. With a response rate around 30% to 50%, dapsone is an interesting second-line therapy to be used just after corticosteroids. Patients with positive antinuclear antibodies can benefit from hydroxychloroquine with a 50% response rate. Because of its side effects, mostly virilization, danazol will be preferentially used in the elderly. Vinca-alkaloids could be temporarily used in patients that do not respond to intravenous immunoglobulins or to limit their use to avoid shortage periods. PMID:26422785

  16. [Anesthetic management of a patient with thrombocytopenia induced by methotrexate undergoing emergent clipping surgery].

    PubMed

    Morishima, Kuniko; Nakatani, Keiji; Nishi, Yuichi; Doi, Akiko; Yamama, Yoshihiro; Nakanishi, Mika; Yagi, Masami; Kurita, Satoshi; Nagata, Noboru

    2012-10-01

    A 70-year-old woman underwent emergent clipping surgery for subarachnoid hemorrhage under general anesthesia. Her laboratory data showed thrombocytopenia (4.0 x 10(4) microl(-1)). She had taken prednisolone (3 mg x day(-1)) and methotrexate (MTX) (10 mg x week(-1)) for rheumatoid arthritis for the last 10 years. Anesthesia was induced with remifentanil as well as propofol, maintained with remifentanil and sevoflurane in oxygen. The operation was performed uneventfully without platelet transfusion. Since the cause of thrombocytopenia was suspected to be MTX, we started rescue therapy by calcium folinate postoperatively. Platelet count was normalized two days later (11.6 x 10(4) microl(-1)). One month after the operation, she was discharged uneventfully. PMID:23157096

  17. [A review on the epidemiologic features of severe fever with thrombocytopenia syndrome].

    PubMed

    Wang, J Y; Wu, H; Tong, Z D; Yan, J B; Li, K F; Tang, A

    2016-02-01

    Severe fever with Thrombocytopenia Syndrome (SFTS) is an emerging hemorrhagic fever disease in the rural areas of east-central China, which is caused by SFTSV-a newly discovered bunyavirus. SFTSV is most likely transmitted by tick bites but can also be transmitted within human beings. The onset of SFTS is sudden and with rapid progress, with main clinical manifestations as fever, thrombocytopenia, leucopenia and gastrointestinal and hepatorenal dysfunctions. Some patients may die from multiple organ failure, and the case fatality rate is approximately 10%. In this paper, we use the method of literature review to summarize the recent research progress of SFTS which includes the epidemic distribution characteristics, medium of transmission, host animals, transmission routes and susceptibility in the general population. PMID:26917534

  18. Neonatal neurosonography: A pictorial essay

    PubMed Central

    Bhat, Venkatraman; Bhat, Varun

    2014-01-01

    Neurosonography is a simple, established non-invasive technique for the intracranial assessment of preterm neonate. Apart from established indication in the evaluation of periventricular haemorrhage, it provides clue to wide range of pathology. This presentation provides a quick roadmap to the technique, imaging anatomy and spectrum of pathological imaging appearances encountered in neonates. PMID:25489132

  19. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice.

    PubMed

    Meyer, Todd; Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L; Amirkhosravi, Ali

    2015-11-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

  20. Successful Percutaneous Nephrolithotomy in Patients with Immune-Mediated Thrombocytopenia Treated with Romiplostim

    PubMed Central

    McCall, Andrew N.; Ingimarsson, Johann P.; Morrisson, Griffin T.; Hook, Christopher C.

    2016-01-01

    Abstract Background: Percutaneous nephrolithotomy (PCNL) for large stone burden can be problematic in patients with significant risk of bleeding complications, specifically thrombocytopenia. This report demonstrates effective correction of two patients' thrombocytopenia, subsequently leading to removal of large stone burden through PCNL. Case Presentation: We present two Middle Eastern patients who presented with medical histories significant for thrombocytopenia, secondary to splenomegaly and hepatic vein thrombosis, and large volume nephrolithiasis. Patient 1 is a 65-year-old female with a right 5 cm stone and a platelet count of 34,000. Patient 2 is a 45-year-old female with a 3 cm left staghorn stone and a platelet count of 44,000. After consultation with hematology, both underwent therapy with prednisone and intravenous immunoglobulin without improvement in their platelet count. They then received 3 μg/kg/dose of romiplostim weekly that improved their platelet counts to 133,000 and 195,000 in 2 weeks, respectively. Patient 1's PCNL was completed in a single-stage procedure with stone-free status shown on CT postoperative day 1. Patient 2 underwent PCNL and a secondary ureteroscopy for residual stone fragments on postoperative day 2. Both patients experienced no complication during the procedure, hospital stay, or postoperative course. Both continued romiplostim for 20 days postoperatively with platelet levels returning to their baseline range after 1 month. Conclusion: In the appropriately selected patient, romiplostim can correct thrombocytopenia enough to safely and effectively perform PCNL in patients with underlying hematologic disorders. Close coordination between urology and hematology is imperative to ensure an effective outcome in this challenging patient population.

  1. Preoperative platelet transfusions and perioperative red blood cell requirements in patients with thrombocytopenia undergoing noncardiac surgery

    PubMed Central

    Warner, Matthew A.; Jia, Qing; Clifford, Leanne; Wilson, Gregory; Brown, Michael J.; Hanson, Andrew C.; Schroeder, Darrell R.; Kor, Daryl J.

    2016-01-01

    BACKGROUND Perioperative hemorrhage impacts patient outcomes and health care resource utilization, yet the risks of transfusion therapies are significant. In patients with preoperative thrombocytopenia, the effects of prophylactic preoperative platelet (PLT) transfusion on perioperative bleeding complications remain uncertain. STUDY DESIGN AND METHODS This is a retrospective cohort study of noncardiac surgical patients between January 1, 2008, and December 31, 2011. Propensity-adjusted analyses were used to evaluate associations between preoperative thrombocytopenia, preoperative PLT transfusion, and the outcomes of interest, with a primary outcome of perioperative red blood cell (RBC) transfusion. RESULTS A total of 13,978 study participants were included; 860 (6.2%) had a PLT count of not more than 100 × 109/L with 71 (8.3%) receiving PLTs preoperatively. Administration of PLTs was associated with higher rates of perioperative RBC transfusion (66.2% vs. 49.1%, p 0.0065); however, in propensity-adjusted analysis there was no significant difference between groups (odds ratio [OR] [95% confidence interval {95% CI}], 1.68 [0.95–2.99]; p =0.0764]. Patients receiving PLTs had higher rates of intensive care unit (ICU) admission (OR [95% CI], 1.95 [1.10–3.46]; p =0.0224) and longer hospital lengths of stay (estimate [95% bootstrap CI], 7.2 [0.8–13.9] days; p =0.0006) in propensity-adjusted analyses. CONCLUSION Preoperative PLT transfusion did not attenuate RBC requirements in patients with thrombocytopenia undergoing noncardiac surgery. Moreover, preoperative PLT transfusion was associated with increased ICU admission rates and hospital duration. These findings suggest that more conservative management of preoperative thrombocytopenia may be warranted. PMID:26559936

  2. Thrombocytopenia-associated multi-organ failure caused by diabetic ketoacidosis.

    PubMed

    Alsaied, Tarek; Goldstein, Stuart L; Kaddourah, Ahmad; Poynter, Sue E

    2016-03-01

    Thrombocytopenia-associated multi-organ failure (TAMOF) is an increasingly reported entity in the pediatric intensive care unit. The clinical presentation is similar to thrombotic thrombocytopenic purpura, but with no evidence of hemolysis and no schistocytes on peripheral smear. We report a case of TAMOF induced by diabetic ketoacidosis and treated with therapeutic plasma exchange (TPE). Early diagnosis and initiation of TPE significantly decrease the morbidity associated with TAMOF. PMID:26712331

  3. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice

    PubMed Central

    Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L.; Amirkhosravi, Ali

    2015-01-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised “3KO” mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic “FCGR2A” mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG “Fc” effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

  4. ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers

    PubMed Central

    Sofi, Fayaz; Altaf, Sheikh Shoaib; Raina, Adnan; Raina, Ab. Hameed

    2016-01-01

    SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneously taking care of the patient as a whole. PMID:27006850

  5. Fetal and Neonatal Arrhythmias.

    PubMed

    Jaeggi, Edgar; Öhman, Annika

    2016-03-01

    Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID:26876124

  6. Hyperbilirubinemia in Preterm Neonates.

    PubMed

    Bhutani, Vinod K; Wong, Ronald J; Stevenson, David K

    2016-06-01

    Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity. PMID:27235203

  7. Hemolysis in Preterm Neonates.

    PubMed

    Christensen, Robert D; Yaish, Hassan M

    2016-06-01

    Hemolysis can be an important cause of hyperbilirubinemia in premature and term neonates. It can result from genetic abnormalities intrinsic to or factors exogenous to normal to red blood cells (RBCs). Hemolysis can lead to a relatively rapid increase in total serum/plasma bilirubin, hyperbilirubinemia that is somewhat slow to fall with phototherapy, or hyperbilirubinemia that is likely to rebound after phototherapy. Laboratory methods for diagnosing hemolysis are more difficult to apply, or less conclusive, in preterm infants. Transfusion of donor RBCs can present a bilirubin load that must be metabolized. Genetic causes can be identified by next-generation sequencing panels. PMID:27235204

  8. Treatment of patients with immune thrombocytopenia admitted to the emergency room.

    PubMed

    Bavunoğlu, Işıl; Eşkazan, Ahmet Emre; Ar, Muhlis Cem; Cengiz, Mahir; Yavuzer, Serap; Salihoğlu, Ayşe; Öngören, Şeniz; Tunçkale, Aydın; Soysal, Teoman

    2016-08-01

    Immune thrombocytopenia (ITP) is the most frequent cause of acquired thrombocytopenia. In adult ITP patients, corticosteroids and intravenous immunoglobulin (IVIg) are used as first-line treatment. The aim of the present study was to investigate retrospectively the demographic and etiologic characteristics of patients with ITP admitted to the emergency room at our hospital. Seventy-five adult patients with ITP were included, and demographic data, bleeding characteristics, etiologic features and responses to treatments were evaluated retrospectively. Fifty-six patients (75 %) were female, and the median age was 43 years. Eighteen patients had a history of ITP, whereas in 57, thrombocytopenia was identified for the first time. During admission, the median platelet count was 5 × 10(9)/L. Cutaneous and/or mucosal bleeding was the most common clinical feature. High-dose dexamethasone was administered in 60 episodes, whereas IVIg and conventional-dose methylprednisolone were used in nine and six episodes, respectively. The overall response rate of the entire cohort following first-line treatments was 67 %, and complete remission was achieved in 31 patients, 19 patients achieved partial remission, and 25 patients were non-responders. In cases with life-threatening bleeding, concomitant infection, post-traumatic bleeding and need for emergency surgery, IVIg can be used as the first line of treatment option in addition to platelet transfusions. PMID:27129318

  9. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia

    PubMed Central

    ARNOLD, D. M.; KUKASWADIA, S.; NAZI, I.; ESMAIL, A.; DEWAR, L.; SMITH, J. W.; WARKENTIN, T. E.; KELTON, J. G.

    2016-01-01

    Summary Background Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. Objective To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. Patients/Methods We developed a grading system to evaluate the quality of DITP laboratory testing. The ‘DITP criteria’ were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. Results Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. Conclusions We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient. PMID:23121994

  10. Evaluation of thrombocytopenia in patients treated with rhenium-186-HEDP: Guidelines for individual dosage recommendations

    SciTech Connect

    Klerk, J.M.H. de; Schip, A.D. van het; Zonnenberg, B.A

    1994-09-01

    A potential limitation of rhenium-186-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP) therapy in patients with painful bone metastases is thrombocytopenia. Given the palliative character of this therapy, it is essential to be able to predict the degree of thrombocytopenia before therapy. Thus far, 39 prostatic cancer patients with multiple painful bone metastases were treated. Twenty-one patients underwent the therapy twice, resulting in 60 therapies. From the pre-therapy {sup 99m}Tc-HDP scintigram, the bone scan index (BSI) was determined as an index of the extent of bone involvement. The administered activity ranged from 1104 to 3479 MBq {sup 186}Re-HEDP. The platelet count was lowest 4 wk following therapy. From this value and the pretreatment level, the percentage decrease in the platelet count was determined (47%{+-}19%, range 14%-89%). The BSI ranged from 8 to 93. Regression analysis showed a functional relation (R = 0.78; p < 0.001) of the percentage of platelet decrease with BSI and administered activity normalized to standard body surface area. Using this relation, it is possible to predict thrombocytopenia by pretreatment bone scintigraphy and to adjust the dosage to each patient to avoid unacceptable toxicity. 27 refs., 4 figs., 1 tab.

  11. Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia.

    PubMed

    McElroy, Patricia L; Wei, Ping; Buck, Keri; Sinclair, Angus M; Eschenberg, Michael; Sasu, Barbra; Molineux, Graham

    2015-06-01

    Chemotherapy-induced thrombocytopenia can lead to chemotherapy treatment delays or dose reductions. The ability of romiplostim, a thrombopoietin (TPO) mimetic, to promote platelet recovery in a mouse model of multicycle chemotherapy/radiation therapy (CRT)-induced thrombocytopenia was examined. In humans, an inverse relationship between platelet counts and endogenous TPO (eTPO) concentration exists. In a CRT mouse model, eTPO was not elevated during the first 5 days after CRT treatment (the "eTPO gap"), then increased to a peak 10 days after each CRT treatment in an inverse relationship to platelet counts seen in humans. To bridge the eTPO gap, mice were treated with 10-1,000 μg/kg of romiplostim on day 0, 1, or 2 after CRT. In some mice, the romiplostim dose was approximately divided over 3 days. Platelet recovery occurred faster with romiplostim in most conditions tested. Romiplostim doses of ≥100 μg/kg given on day 0 significantly lessened the platelet nadir. Fractionating the dose over 3 days did not appear to confer a large advantage. These data may provide a rationale for clinical studies of romiplostim in chemotherapy-induced thrombocytopenia. PMID:25754671

  12. Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia

    PubMed Central

    Antony-Debré, Iléana; Manchev, Vladimir T.; Balayn, Nathalie; Bluteau, Dominique; Tomowiak, Cécile; Legrand, Céline; Langlois, Thierry; Bawa, Olivia; Tosca, Lucie; Tachdjian, Gérard; Leheup, Bruno; Debili, Najet; Plo, Isabelle; Mills, Jason A.; French, Deborah L.; Weiss, Mitchell J.; Solary, Eric; Favier, Remi; Vainchenker, William

    2015-01-01

    To explore how RUNX1 mutations predispose to leukemia, we generated induced pluripotent stem cells (iPSCs) from 2 pedigrees with germline RUNX1 mutations. The first, carrying a missense R174Q mutation, which acts as a dominant-negative mutant, is associated with thrombocytopenia and leukemia, and the second, carrying a monoallelic gene deletion inducing a haploinsufficiency, presents only as thrombocytopenia. Hematopoietic differentiation of these iPSC clones demonstrated profound defects in erythropoiesis and megakaryopoiesis and deregulated expression of RUNX1 targets. iPSC clones from patients with the R174Q mutation specifically generated an increased amount of granulomonocytes, a phenotype reproduced by an 80% RUNX1 knockdown in the H9 human embryonic stem cell line, and a genomic instability. This phenotype, found only with a lower dosage of RUNX1, may account for development of leukemia in patients. Altogether, RUNX1 dosage could explain the differential phenotype according to RUNX1 mutations, with a haploinsufficiency leading to thrombocytopenia alone in a majority of cases whereas a more complete gene deletion predisposes to leukemia. PMID:25490895

  13. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia.

    PubMed

    Kapur, Rick; Heitink-Pollé, Katja M J; Porcelijn, Leendert; Bentlage, Arthur E H; Bruin, Marrie C A; Visser, Remco; Roos, Dirk; Schasfoort, Richard B M; de Haas, Masja; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-12

    Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients. PMID:25548320

  14. Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia

    PubMed Central

    Hirsch, Jessica D.; Greene, Teshell K.; Zhai, Li; Hayes, Vincent M.; Kowalska, M. Anna; Cines, Douglas B.; Poncz, Mortimer

    2010-01-01

    Heparin-induced thrombocytopenia (HIT) is a life- and limb-threatening thrombotic disorder that develops after exposure to heparin, often in the setting of inflammation. We have shown previously that HIT is associated with antibodies to complexes that form between platelet factor 4 and glycosaminoglycan (GAG) side chains on the surface of platelets. However, thrombosis can occur in the absence of thrombocytopenia. We now show that platelet factor 4 binds to monocytes and forms antigenic complexes with their surface GAG side chains more efficiently than on platelets likely due to differences in GAG composition. Binding to monocytes is enhanced when the cells are activated by endotoxin. Monocyte accumulation within developing arteriolar thrombi was visualized by situ microscopy. Monocyte depletion or inactivation in vivo attenuates thrombus formation induced by photochemical injury of the carotid artery in a modified murine model of HIT while paradoxically exacerbating thrombocytopenia. These studies demonstrate a previously unappreciated role for monocytes in the pathogenesis of arterial thrombosis in HIT and suggest that therapies targeting these cells might provide an alternative approach to help limit thrombosis in this and possibly other thrombotic disorders that occur in the setting of inflammation. PMID:20724543

  15. Heparin-Induced Thrombocytopenia in the Pediatric Population: A Review of Current Literature

    PubMed Central

    Vakil, Niyati H.; Kanaan, Abir O.; Donovan, Jennifer L.

    2012-01-01

    Heparin-induced thrombocytopenia is a rare and serious reaction to unfractionated heparin and low-molecular-weight heparins in children. Quick recognition, discontinuation of heparin, and subsequent treatment with an alternative anticoagulant are essential steps to prevent serious complications such as thrombus and limb amputation. The purpose of this review is to describe the clinical features of heparin-induced thrombocytopenia in children and to summarize the data available for its management. This paper summarizes data and relates the use of direct thrombin inhibitors with clinical outcomes. A literature search was conducted with Ovid, using the key terms argatroban, bivalirudin, hirulog, danaparoid, lepirudin, direct thrombin inhibitor, heparin-induced thrombocytopenia, thrombosis, warfarin, and fondaparinux. Articles were excluded if they were classified as editorials, review articles, or conference abstracts or if they involved patients 18 years of age or older or described disease states not related to thrombosis. Nineteen articles containing 33 case reports were identified and evaluated for this review. Of the 33 cases, 14, 10, 4, and 2 cases described the use of lepirudin, danaparoid, argatroban, and bivalirudin, respectively. Two cases did not report the type of anticoagulant used, and 1 case used aspirin. The most commonly reported complication was bleeding. PMID:23118656

  16. Low incidence of thrombocytopenia with porcine mucosal heparin. A prospective multicenter study.

    PubMed

    Rao, A K; White, G C; Sherman, L; Colman, R; Lan, G; Ball, A P

    1989-06-01

    We treated 193 patients either intravenously (94) or subcutaneously (99) for at least 5 days with porcine intestinal mucosal heparin and followed them up prospectively with frequent platelet counts to determine the incidence of heparin-related thrombocytopenia and arterial thrombosis. None of the patients in the study developed severe thrombocytopenia (platelet count, less than 100 x 10(9)/L) or arterial thrombosis. Eight patients had a platelet count of 100 to 140 X 10(9)/L on one occasion, with a count of greater than 140 x 10(9)/L on the subsequent measurement. The mean (+/- SD) values of the initial and lowest platelet counts during therapy in all patients were 288 +/- 100 x 10(9)/L and 253 +/- 88 x 10(9)/L, respectively, with the lowest counts occurring on day 4.1 +/- 4.2. A least-squares line was computed for each patient to fit the day and counts; the slopes were significantly different from zero and negative in 7.8% of patients and positive in 14.5%. This multicenter study confirms the reports that the incidence of heparin-related severe thrombocytopenia and arterial thrombosis is distinctly low in patients treated with porcine-mucosal heparin. PMID:2658898

  17. Update on Neonatal Hypoglycemia

    PubMed Central

    Rozance, Paul J.

    2014-01-01

    Purpose of Review Neonatal hypoglycemia is one of the most common biochemical abnormalities encountered in the newborn. However, controversy remains surrounding its definition and management especially in asymptomatic patients. Recent Findings New information has been published that describes the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia. Furthermore, one large prospective study failed to find an association between repetitive low glucose concentrations and poor neurodevelopmental outcomes in preterm infants. But hypoglycemia due to hyperinsulinism, especially genetic causes, continued to be associated with brain injury. New advances were made in the diagnosis and management of hyperinsulinism, including acquired hyperinsulinism in small for gestational age infants and others. Continuous glucose monitoring remains an attractive strategy for future research in this area. Summary The fundamental question of how best to manage asymptomatic newborns with low glucose concentrations remains unanswered. Balancing the risks of over treating newborns with low glucose concentrations who are undergoing a normal transition following birth against the risks of under treating those in whom low glucose concentrations are pathological, dangerous, and/or a harbinger of serious metabolic disease remains a challenge. PMID:24275620

  18. Neonatal Subventricular Zone Electroporation

    PubMed Central

    Feliciano, David M.; Lafourcade, Carlos A.; Bordey, Angélique

    2013-01-01

    Neural stem cells (NSCs) line the postnatal lateral ventricles and give rise to multiple cell types which include neurons, astrocytes, and ependymal cells1. Understanding the molecular pathways responsible for NSC self-renewal, commitment, and differentiation is critical for harnessing their unique potential to repair the brain and better understand central nervous system disorders. Previous methods for the manipulation of mammalian systems required the time consuming and expensive endeavor of genetic engineering at the whole animal level2. Thus, the vast majority of studies have explored the functions of NSC molecules in vitro or in invertebrates. Here, we demonstrate the simple and rapid technique to manipulate neonatal NPCs that is referred to as neonatal subventricular zone (SVZ) electroporation. Similar techniques were developed a decade ago to study embryonic NSCs and have aided studies on cortical development3,4 . More recently this was applied to study the postnatal rodent forebrain5-7. This technique results in robust labeling of SVZ NSCs and their progeny. Thus, postnatal SVZ electroporation provides a cost and time effective alternative for mammalian NSC genetic engineering. PMID:23426329

  19. Pseudotyping Serotype 5 Adenovirus with the Fiber from Other Serotypes Uncovers a Key Role of the Fiber Protein in Adenovirus 5-Induced Thrombocytopenia.

    PubMed

    Raddi, Najat; Vigant, Frédéric; Wagner-Ballon, Oriane; Giraudier, Stéphane; Custers, Jerome; Hemmi, Silvio; Benihoud, Karim

    2016-02-01

    Adenovirus (Ad) infection in humans is associated with inflammatory responses and thrombocytopenia. Although several studies were conducted in mice models to understand molecular and cellular mechanisms of Ad-induced inflammatory responses, only few of them turned their interest toward the mechanisms of Ad-induced thrombocytopenia. Using different depletion methods, the present study ruled out any significant role of spleen, macrophages, and vitamin K-dependent factor in Ad-induced thrombocytopenia. Interestingly, mice displaying thrombocytopenia expressed high levels of cytokines/chemokines after Ad administration. Most importantly, pseudotyping adenovirus with the fiber protein from other serotypes was associated with reduction of both cytokine/chemokine production and thrombocytopenia. Altogether, our results suggest that capsid fiber protein (and more precisely its shaft) of Ad serotype 5 triggers the cytokine production that leads to Ad-induced thrombocytopenia. PMID:26757054

  20. Neonates need tailored drug formulations

    PubMed Central

    Allegaert, Karel

    2013-01-01

    Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety. PMID:25254168

  1. Bacillus species infections in neonates.

    PubMed

    Patrick, C C; Langston, C; Baker, C J

    1989-01-01

    A case of neonatal meningitis due to Bacillus cereus is presented. Postmortem histopathologic examination revealed an invasive disease involving the brain parenchyma, with a cellular composition consistent with an indolent process indicative of possible perinatally acquired infection. One other neonate from our institution with systemic disease due to a nonanthrax bacillus is described, and a review of the English-language literature since 1900 reveals four additional neonates infected with these unusual pathogens. Such Bacillus species infections are rare but should be suspected when gram-positive bacilli are noted on gram stain, especially in an immunocompromised host. PMID:2505353

  2. Transient neonatal zinc deficiency.

    PubMed

    Krieger, I; Alpern, B E; Cunnane, S C

    1986-06-01

    We report an infant who developed clinical manifestations of zinc deficiency during the first month of life although the diet was adequate for zinc and no other causes could be ascertained. The diagnosis was confirmed by low plasma-zinc concentrations and a positive response to zinc treatment. The fatty acid profile of plasma phospholipids was typical of zinc deficiency (ie, arachidonic acid was markedly decreased). The transient nature of this disorder was evident when no relapse occurred after cessation of zinc therapy and plasma-zinc and arachidonic acid concentrations remained normal. Several explanations for the development of transient neonatal zinc deficiency are offered. The observation demonstrates that occasional infants may have requirements for zinc that are beyond the intakes of the conventional RDA. PMID:3717070

  3. Neonatal sensitization to latex.

    PubMed

    Worth, J

    2000-05-01

    Babies born in delivery rooms of hospitals are exposed to latex through skin and mucous membrane contact with prepowdered latex gloves worn by midwives and doctors, and through the inhalation of latex-bound starch powder in the air of the delivery room. This paper examines the hypothesis that they are at risk for latex sensitization, and that part of the sharp increase of childhood asthma, eczema and anaphylaxis in the past 30-40 years may be linked. These possibilities seem hitherto unsuspected. In over 700 papers on latex allergy no mention of neonatal exposure to latex has been found. Even obstetric papers discussing the risks for an atopic mother (atopy - a tendency to develop allergies) do not seem to anticipate any risk for the baby, who might also be atopic. Latex allergy is primarily regarded as an occupational hazard. This paper suggests that it is a hazard for every baby handled by latex gloves at birth. PMID:10859678

  4. Neonatal pulmonary hemosiderosis.

    PubMed

    Limme, Boris; Nicolescu, Ramona; Misson, Jean-Paul

    2014-01-01

    Idiopathic pulmonary hemosiderosis (IPH) is a rare complex entity characterized clinically by acute or recurrent episodes of hemoptysis secondary to diffuse alveolar hemorrhage. The radiographic features are variable, including diffuse alveolar-type infiltrates, and interstitial reticular and micronodular patterns. We describe a 3-week-old infant presenting with hemoptysis and moderate respiratory distress. Idiopathic pulmonary hemosiderosis was the first working diagnosis at the Emergency Department and was confirmed, 2 weeks later, by histological studies (bronchoalveolar lavage). The immunosuppressive therapy by 1 mg/kg/d prednisone was immediately started, the baby returned home on steroid therapy at a dose of 0,5 mg/kg/d. The diagnosis of idiopathic pulmonary hemosiderosis should be evocated at any age, even in the neonate, when the clinical presentation (hemoptysis and abnormal radiological chest images) is strongly suggestive. PMID:25389504

  5. First Isolation of Severe Fever with Thrombocytopenia Syndrome Virus from Haemaphysalis longicornis Ticks Collected in Severe Fever with Thrombocytopenia Syndrome Outbreak Areas in the Republic of Korea

    PubMed Central

    Yun, Seok-Min; Song, Bong Gu; Choi, WooYoung; Roh, Jong Yul; Lee, Ye-Ji; Park, Won Il; Han, Myung Guk; Ju, Young Ran

    2016-01-01

    Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease that is endemic to China, Japan, and the Republic of Korea (ROK). In this study, 8313 ticks collected from SFTS outbreak areas in the ROK in 2013 were used to detect the SFTS virus (SFTSV). A single SFTSV was isolated in cell culture from one pool of Haemaphysalis longicornis ticks collected from Samcheok-si, Gangwon Province, in the ROK. Phylogenetic analysis showed that the SFTSV isolate was clustered with the SFTSV strain from Japan, which was isolated from humans. To the best of our knowledge, this is the first isolation in the world of SFTSV in ticks collected from vegetation. PMID:26745758

  6. Therapeutic drug monitoring in neonates.

    PubMed

    Pauwels, Steven; Allegaert, Karel

    2016-04-01

    Therapeutic drug monitoring (TDM) aims to integrate drug measurement results into clinical decision making. The basic rules apply when using TDM in neonates (aminoglycosides, vancomycin, phenobarbital, digoxin), but additional factors should also be taken into account. First, due to both pharmacokinetic variability and non-pharmacokinetic factors, the correlation between dosage and concentration is poor in neonates, but can be overcome with the use of more complex, validated dosing regimens. Second, the time to reach steady state is prolonged, especially when no loading dose is used. Consequently, the timing of TDM sampling is important in this population. Third, the target concentration may be uncertain (vancomycin) or depend on specific factors (phenobarbital during whole body cooling). Finally, because of differences in matrix composition (eg, protein, bilirubin), assay-related inaccuracies may be different in neonates. We anticipate that complex validated dosing regimens, with subsequent TDM sampling and Bayesian forecasting, are the next step in tailoring pharmacotherapy to individual neonates. PMID:26803050

  7. Mastitis in a neonatal filly

    PubMed Central

    Gilday, Rebecca; Lewis, Danyse; Lohmann, Katharina L.

    2015-01-01

    Neonatal mastitis is a rare occurrence in the horse. This report documents a case of mastitis caused by an organism within the Streptococcus dysgalactiae group in a 1-week-old Paint filly. PMID:25565717

  8. Neonatal and pediatric respiratory care

    SciTech Connect

    Koff, P.B. ); Eitzman, D.V.; Nev, J. )

    1988-01-01

    This book contains 23 chapters. Some of the titles are: Radiographic evaluations; Neonatal parenchymal diseases: physiologic development; Oxygen therapy; Pediatric parenchymal diseases; and Care of the neurologically injured child.

  9. Neonatal euthanasia: The Groningen Protocol*

    PubMed Central

    Vizcarrondo, Felipe E.

    2014-01-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  10. Therapeutic hypothermia in neonatal asphyxia

    PubMed Central

    Cornette, L.

    2012-01-01

    Hypoxic ischemic encephalopathy is a serious condition affecting newborn infants which can result in death and disability. There is now strong clinical evidence that moderate post-asphyxial total body cooling or hypothermia in full term neonates results in long-term neuroprotection, allowing us to proclaim this innovative therapy as “standard of care.” The treatment is a time-critical emergency and should be started within 6 hours after the insult. Such requires optimal collaboration among local hospitals, transport teams and the closest neonatal intensive care unit. The technique is only safe when applied according to published clinical trial protocols, and with admission of these patients to a neonatal intensive care unit. Future studies should be aimed at optimizing the onset, duration, and depth of hypothermia. Combination of hypothermia and drugs may further improve neuroprotection in asphyxiated full term neonates. PMID:24753900

  11. Neonatal euthanasia: The Groningen Protocol.

    PubMed

    Vizcarrondo, Felipe E

    2014-11-01

    For the past thirty years, voluntary euthanasia and physician-assisted suicide of adult patients have been common practice in the Netherlands. Neonatal euthanasia was recently legalized in the Netherlands and the Groningen Protocol (GP) was developed to regulate the practice. Supporters claim compliance with the GP criteria makes neonatal euthanasia ethically permissible. An examination of the criteria used by the Protocol to justify the euthanasia of seriously ill neonates reveals the criteria are not based on firm moral principles. The taking of the life of a seriously ill person is not the solution to the pain and suffering of the dying process. It is the role of the medical professional to care for the ailing patient with love and compassion, always preserving the person's dignity. Neonatal euthanasia is not ethically permissible. PMID:25473136

  12. Combination therapy with pegylated interferon plus ribavirin in the treatment of hepatitis C virus-related thrombocytopenia

    PubMed Central

    Karakan, Tarkan; Cindoruk, Mehmet; Degertekin, Bulent; Dogan, Ibrahim; Sancak, Alper; Dumlu, Sukru; Gorgul, Ahmet; Unal, Selahattin

    2005-01-01

    Background: Isolated thrombocytopenia is a common manifestation of hepatitis C virus (HCV) infection. There is no established treatment modality for this condition. The efficacy of standard interferon (IFN) monotherapy has been reported in some studies. The major disadvantage of this treatment is the high rate of recurrence due to viral breakthrough during the first 12 weeks of treatment. Pegylated IFNs are now the standard regimen for chronic hepatic disease due to HCV infection. However, due to a lack of evidence, pegylated IFNs are not widely used for HCV-related isolated thrombocytopenia. Objective: The aim of this report was to present the case of a male patientwith severe symptomatic thrombocytopenia due to HCV infection. Methods: Thrombocytopenia was treated with pegylated IFN plus ribavirin. Results: Although standard IFN monotherapy failed to achieve virologic and hematologic improvement, therapy with pegylated IFN alfa-2a plus ribavirin was associated with both virologic and hematologic improvement without any significant adverse effects. Conclusions: Pegylated IFN plus ribavirin was effective in this patient for thetreatment of HCV-related thrombocytopenia. However, further research is needed to define the response rate in different patient populations. PMID:24764593

  13. Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

    PubMed Central

    Arnold, Donald M.; Nazi, Ishac; Warkentin, Theodore E.; Smith, James W.; Toltl, Lisa J.; George, James N.; Kelton, John G.

    2013-01-01

    Drug-induced immune thrombocytopenia (DITP) is a challenging clinical problem that is under-recognized, difficult to diagnose and associated with severe bleeding complications. DITP may be caused by classic drug-dependent platelet antibodies (eg, quinine); haptens (eg, penicillin); fiban-dependent antibodies (eg, tirofiban); monoclonal antibodies (eg, abciximab); autoantibody formation (eg, gold); and immune complex formation (eg, heparin). A thorough clinical history is essential in establishing the diagnosis of DITP and should include exposures to prescription medications, herbal preparations and even certain foods and beverages. Clinical and laboratory criteria have been established to determine the likelihood of a drug being the cause of thrombocytopenia, but these criteria can only be applied retrospectively. The most commonly implicated drugs include quinine, quinidine, trimethoprim/sulfamethoxazole and vancomycin. We propose a practical approach to the diagnosis of the patient with suspected DITP. Key features are: the presence of severe thrombocytopenia (platelet nadir <20 × 109/L); bleeding complications; onset 5 to 10 days after first drug exposure, or within hours of subsequent exposures or after first exposure to fibans or abciximab; and exposure to drugs that have been previously implicated in DITP reactions. Treatment involves stopping the drug(s), administering platelet transfusions or other therapies if bleeding is present and counselling on future drug avoidance. The diagnosis can be confirmed by a positive drug re-challenge, which is often impractical, or by demonstrating drug-dependent platelet reactive antibodies in vitro. Current test methods, which are mostly flow cytometry-based, must show drug-dependence, immunoglobulin binding, platelet specificity and ideally should be reproducible across laboratories. Improved standardization and accessibility of laboratory testing should be a focus of future research. PMID:23845922

  14. Heparin-induced thrombocytopenia (HIT II) - a drug-associated autoimmune disease.

    PubMed

    Nowak, Götz

    2009-11-01

    Autoimmune thrombocytopenia (ITP) is an acquired autoimmune disease characterised by isolated persistent thrombocytopenia and normal megakaryopoiesis. This definition also applies to heparin-induced thrombocytopenia (HIT II), a frequent side effect of heparin treatment. In HIT II, the immunogen is a coagulation active complex of heparin and platelet factor 4 (PF4). By now, diagnostics of HIT II is often material and time consuming. Three groups of patients were investigated for HIT II antibodies (HIT II-AB): 54 hospitalised stroke patients, 87 hospitalised cardiac patients, and 71 patients on chronic haemodialysis, all treated with heparin. Furthermore, 100 healthy volunteers were investigated. For detection of HIT II-AB the innovative whole blood test PADA-HIT (PADA: platelet adhesion assay) was used. PADA-HIT quantifies the interaction of IgG antibodies with FcgammaIIA receptors by comparing the activation state of platelets in citrated and heparinised whole blood. The occurrence of HIT II-AB in blood was very high with 44 % of stroke patients, 69% of cardiac patients and 38% of haemodialysis patients compared to only 15% of healthy volunteers. This demonstrates a high incidence and a rapid onset of HIT II-AB in patients being acutely treated with heparin. HIT II is one of the most frequent and severe autoimmune diseases bearing a great thrombosis risk. PADA-HIT represents an innovative diagnostic method for detection of autoimmune antibodies of IgG type that are directed against platelet factor 4 (PF4)-heparin-complex. By early and fast diagnostics and appropriate treatment severe complications of HIT II can be prevented. PMID:19888524

  15. A primary production deficit in the thrombocytopenia of equine infectious anemia.

    PubMed Central

    Crawford, T B; Wardrop, K J; Tornquist, S J; Reilich, E; Meyers, K M; McGuire, T C

    1996-01-01

    The purpose of this study was to identify the mechanisms responsible for the thrombocytopenia that develops following infection of horses by the lentivirus equine infectious anemia virus (EIAV). Immunocompetent Arabian foals and Arabian foals with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were experimentally infected with EIAV. Levels of viremia and a number of clinical and hematologic parameters were examined prior to and following infection. Thrombocytopenia was not dependent on the immune response: SCID foals were affected as severely as immunocompetent foals. Production of platelets, measured by metabolic incorporation of radioactive label, was significantly reduced. The decrease ranged from 35 to 89% in three SCID and two immunocompetent foals examined. Platelet survival, measured by 51Cr labeling, also declined following infection in both SCID and immunocompetent foals: 51 and 68%, respectively, relative to the preinfection life spans. The difference between immunocompetent and immunodeficient foals was not statistically significant. The number of megakaryocytes (MK) per square millimeter of bone marrow, determined by digitizing morphometry, was not significantly altered in either SCID or immunocompetent thrombocytopenic foals. Numbers of denuded MK nuclei per unit area increased, but the elevation was not statistically significant. No evidence for viral replication in MK was found. Three different parameters of intravascular coagulation (activated prothombin time, fibrin degradation products, and one-step prothombin time) remained normal until after platelet numbers had declined significantly, arguing against an important role for disseminated intravascular coagulation. The findings indicate that EIAV induces thrombocytopenia principally through an indirect, noncytocidal suppressive effect on platelet production, the mechanism of which is unknown. A shortening of platelet life span apparently contributes moderately

  16. The Role of Platelet Factor 4 in Radiation-Induced Thrombocytopenia

    SciTech Connect

    Lambert, Michele P.; Xiao Liqing; Nguyen, Yvonne; Kowalska, M. Anna; Poncz, Mortimer

    2011-08-01

    Purpose: Factors affecting the severity of radiation-induced thrombocytopenia (RIT) are not well described. We address whether platelet factor 4 (PF4; a negative paracrine for megakaryopoiesis) affects platelet recovery postradiation. Methods and Materials: Using conditioned media from irradiated bone marrow (BM) cells from transgenic mice overexpressing human (h) PF4 (hPF4+), megakaryocyte colony formation was assessed in the presence of this conditioned media and PF4 blocking agents. In a model of radiation-induced thrombocytopenia, irradiated mice with varying PF4 expression levels were treated with anti-hPF4 and/or thrombopoietin (TPO), and platelet count recovery and survival were examined. Results: Conditioned media from irradiated BM from hPF4+ mice inhibited megakaryocyte colony formation, suggesting that PF4 is a negative paracrine released in RIT. Blocking with an anti-hPF4 antibody restored colony formation of BM grown in the presence of hPF4+ irradiated media, as did antibodies that block the megakaryocyte receptor for PF4, low-density lipoprotein receptor-related protein 1 (LRP1). Irradiated PF4 knockout mice had higher nadir platelet counts than irradiated hPF4+/knockout litter mates (651 vs. 328 x 106/mcL, p = 0.02) and recovered earlier (15 days vs. 22 days, respectively, p <0.02). When irradiated hPF4+ mice were treated with anti-hPF4 antibody and/or TPO, they showed less severe thrombocytopenia than untreated mice, with improved survival and time to platelet recovery, but no additive effect was seen. Conclusions: Our studies show that in RIT, damaged megakaryocytes release PF4 locally, inhibiting platelet recovery. Blocking PF4 enhances recovery while released PF4 from megakaryocytes limits TPO efficacy, potentially because of increased release of PF4 stimulated by TPO. The clinical value of blocking this negative paracrine pathway post-RIT remains to be determined.

  17. The Safety of Acupuncture in Patients with Cancer Therapy–Related Thrombocytopenia

    PubMed Central

    Cybularz, Paul A.; Brothers, Karen; Singh, Gurneet M.; Feingold, Jennifer L.; Niesley, Michelle L.

    2015-01-01

    Abstract Background: Acceptance of acupuncture as an efficacious integrative modality for oncology-related side-effect management is rapidly expanding. It is imperative that guidelines regarding safe treatment supported by clinical experience are established. Oncology patients frequently experience thrombocytopenia as a side-effect of chemotherapy or radiation. However, safety data for acupuncture in adult patients with cancer who are thrombocytopenic is lacking. Materials and Methods: The medical records of 684 patients who received acupuncture treatments in an established acupuncture program at a private cancer treatment hospital were reviewed for adverse events occurring within the context of thrombocytopenia. Results: Of 2135 visits eligible for evaluation, 98 individual acupuncture visits occurred in patients with platelet counts <100,000/μL, including nine visits in which platelet counts were <50,000/μL. No adverse events of increased bruising or bleeding were noted. Medications and nutritional supplements or botanicals that may influence coagulation were also tabulated, with no apparent adverse events in this patient population. Conclusions: Discrepancies in the literature highlight the need to create cohesive safety guidelines backed by clinical research, specifically for groups at higher risk for adverse events. The preliminary evidence put forth in this study lays the foundation that supports the notion that acupuncture can be used safely with a high-need oncology population within an integrated model of care. In this descriptive retrospective case series of adult oncology patients with thrombocytopenia, no adverse events of increased bruising or bleeding were documented. Prospective trials are needed to confirm these initial observations. PMID:26401193

  18. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    PubMed Central

    Deng, Kathy; Nanda, Deepak

    2016-01-01

    Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia. PMID:27366335

  19. Are Serotonin Alterations the Link between Thrombocytopenia and Poor Immune Status among HIV Infected Individuals?

    PubMed Central

    Míguez-Burbano, María José; Rodriguez, Allan; Vargas, Mayra; Tantalean, Gabriella; Valiathan, Ranjini; Chan, Wenyaw

    2014-01-01

    Objective Thrombocytopenia (TCP<150 × 103 cells/mm3) has emerged as a relevant factor in the clinical course of HIV. However, the mechanisms mediating such observations have not been well characterized, limiting the possibility of creating targeted interventions. Notably, platelets are the storage and transporter system for serotonin and Brain derived neurotrophic factor (BDNF), which recent laboratory studies associated with viral replication and lymphocyte survival. Thus, we posit that (1) TCP will be associated with reduced levels of BDNF and serotonin (2) That these alterations will lead to poor viro-immune responses to antiretroviral therapy. Methods To achieve this goal, a total of 400 people living with HIV were consecutively enrolled to characterize the frequency of thrombocytopenia in hazardous and non-hazardous alcohol user populations in the HAART era. Then, participants underwent immune and laboratory assessments, to determine if TCP was associated with alterations in serotonin (5-HT) and brain derived neurotrophic factor (BDNF). Results The prevalence of thrombocytopenia in this antiretroviral treated cohort was 14%. Rates were significantly higher in the heavy alcohol users, HAU versus the non HAU group (Heavy: 25% versus HAU: 15% versusnon-HAU: 10%). Multivariate model analyses indicated that having TCP, low BDNF levels (<5000 pg/ml), and number of drinks per day were predictors of serotonin levels. PLWH with TCP had about 2-fold lower PPP-BDNFlevels (5037.4 ± 381 vs. 9137.5 ± 7062 pg/ml p=0.0001). Other significant predictors of BDNF levels at the last visit included receiving selective serotonin reuptake inhibitors and PPP serotonin levels. Multivariate analyses also confirmed that altered serotonin levels were associated withhigh viral loadsboth low CD4 cell counts. Conclusions Thrombocytopenia is a relatively frequent complication of HIV, andis particularly prevalent among hazardous alcohol users (HAU). These findings suggest that TCP is

  20. A Word of Caution Is Needed Before Uttering a Word of Caution: Thrombocytopenia and Sutureless Valves.

    PubMed

    Santarpino, Giuseppe; Fischlein, Theodor; Pfeiffer, Steffen

    2016-01-01

    Thrombocytopenia occurring after surgical bioprosthetic valve implantation is a phenomenon that has been long investigated, and various explanations have been provided [Santarpino 2012a]. Our group has been addressing this topic over several years, extending back to the original description of this phenomenon in Freedom Solo (Sorin Group, Saluggia, Italy). However, we observed that this was a transitory and self-limited phenomenon without clinical consequence [Santarpino 2011; Santarpino 2012a]. Our center began implanting the Perceval aortic valve (Sorin Group, Saluggia, Italy) in 2010, and we have gained a vast experience in sutureless aortic valve replacement with Perceval, with more than 300 implants performed to date [Fischlein 2015]. PMID:27585194

  1. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients.

    PubMed

    Claushuis, Theodora A M; van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Klein Klouwenberg, Peter M C; Hoogendijk, Arie J; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Zwinderman, Aeilko H; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom

    2016-06-16

    Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal

  2. Celiac disease with Evans syndrome and isolated immune thrombocytopenia in monozygotic twins: a rare association.

    PubMed

    Roganovic, Jelena

    2016-04-01

    Celiac disease is a multisystem immune-mediated disorder caused by exposure to dietary gluten in genetically predisposed individuals. The clinical presentation is characterized by a multitude and diversity of symptoms and complications. The coexistence of celiac disease with other autoimmune disorders has been established, most frequently with type 1 diabetes mellitus and autoimmune thyroiditis. The association of celiac disease with immune-mediated hematologic conditions has been rarely reported. This case study describes a pair of identical twin sisters with celiac disease associated with Evans syndrome in one sibling, and with isolated immune thrombocytopenia in the other. PMID:27312169

  3. Development of myelofibrosis during eltrombopag treatment in a patient with immune thrombocytopenia.

    PubMed

    Horikoshi, Akira; Tsukuda, Jumpei; Abe, Ryouhei; Fujiwara, Naoki; Ito, Eisaku; Takaku, Tomoo

    2016-05-01

    Eltrombopag, a thrombopoietin (TPO) receptor agonist, is effective for treating refractory immune thrombocytopenia (ITP). However, the development of bone marrow fibrosis is a concern. A 78-year-old man was diagnosed with ITP in 2004. His platelet count did not increase after eltrombopag treatment initiation in 2014. However, anemia progressed, along with the presence of immature myelocytes, erythroblasts, and tear drop cells. At 8 months after initiating eltrombopag treatment, the patient underwent a bone marrow biopsy that showed grade 2 myelofibrosis. Hence, eltrombopag was discontinued. In our experience with this case indicates that careful observation is required while using TPO receptor agonists. PMID:27263792

  4. [Single-donor protocol: Transfusion practices and multiple transfusion risk factors in neonatal intensive care unit].

    PubMed

    Dollat, C; Pierron, C; Keslick, A; Billoir, E; François, A; Jarreau, P-H

    2016-09-01

    In France since 2002, the single-donor transfusion protocol, using four pediatric units from the same adult donor's packed red blood cells (PRBCs) in multiply transfused newborns, is recommended in preterm neonates to reduce the risks of infection and alloimmunization. This protocol is controversial, however, because it causes the transfusion of stored blood, which could have adverse consequences. Before the new recommendations of the French Haute Autorité de santé (National authority for health) in 2015, we conducted a national practice survey in 63 neonatal intensive care units (NICU) and a retrospective study of the characteristics of 103 children transfused within our unit, to better target beneficiaries. The practice survey showed that 30 % of French NICUs no longer used the protocol in 2014, due to logistical or financial problems, or concerns about the transfusion of stored blood. The practices were heterogeneous. Few NICUs used a written protocol. In our NICU, the use of single-donor protocol involved the use of units stored for more than 20 days in half of the cases beginning with the third unit used. Six-term newborns were mainly transfused once, which does not seem to warrant the single-donor transfusion protocol. The use of this protocol caused the loss of 50 % of the manufactured units, which go unused. In multivariate analysis, two factors were predictive of multiple transfusion within our population of 95 premature neonates undergoing transfusion: low-term and a high Clinical Risk Index for Babies (CRIB) score. The risk of multiple transfusions would be reduced by about 15 % for each additional week of gestation and approximately 16 % per point within the CRIB score. These variables integrated into a statistical model predict the risk of multiplying transfusions. According to the ROC curve, a calculated risk higher than 50 % is the appropriate cut-off value to transfuse with the single-donor transfusion protocol. This would limit its

  5. Efficacy of linezolid on gram-positive bacterial infection in elderly patients and the risk factors associated with thrombocytopenia

    PubMed Central

    Bi, Li-qing; Zhou, Jing; Huang, Ming; Zhou, Su-ming

    2013-01-01

    Objective : Linezolid is active against drug-resistant gram-positive bacteria. However, the efficacy and safety of linezolid in the treatment of the elderly have not been well characterized. The purpose of this study was to evaluate the efficacy of linezolid in the treatment of the elderly with gram-positive bacterial infection and to investigate the risk factors associated with the development of thrombocytopenia in these patients. Methodology: This was a retrospective analysis of 50 elderly patients who were treated with intravenous linezolid for gram-positive bacterial infection. Clinical data and bacteriological responses were assessed. Risk factors associated with thrombocytopenia in elderly patients were analyzed. Results: The overall clinical cure rate of linezolid was 74%, and the bacteriological eradication rate was 69%. Thrombocytopenia occurred in 24 patients, and thrombocytopenia was associated with both the duration of treatment (P = 0.005) and the baseline platelet count (P = 0.042). Based on a logistic regression analysis, the baseline platelet count <200×109/L (OR = 0.244; 95% CI = 0.068- 0.874; P = 0.030) was identified as the only significant risk factor for linezolid-associated thrombocytopenia in elderly patients. The mean platelet count decreased significantly from the 7th day of treatment, and decreased to the lowest value 1-2 days after the end of therapy. Conclusions : Linezolid is effective and safe for the elderly with gram-positive bacterial infections. Adverse effects such as thrombocytopenia are of greater concern. Platelet counts should be monitored in patients who are treated with linezolid and that measures should be taken in advance to avoid hemorrhagic tendencies. PMID:24353639

  6. Functional Neonatal Echocardiography: Indian Experience

    PubMed Central

    Suryawanshi, Pradeep B.; Maheshwari, Rajesh; Patnaik, Suprabha; Malshe, Nandini; Kalrao, Vijay; Lalwani, Sanjay; Surwade, Jitendra

    2015-01-01

    Introduction Functional echocardiography, as opposed to echocardiography as performed by the cardiologist, is the bedside utilization of cardiac ultrasound to take after functional and haemodynamic changes longitudinally. Information reflecting cardiovascular capacity and systemic and pulmonary blood flow in sick preterm and term neonates can be observed utilizing this strategy. Information is lacking on its use in neonatal units in India. Aim To characterize the impact of Functional neonatal echocardiography (FnECHO) programme on decision making in a tertiary care centre in India by evaluating its frequency of use, patient characteristics, and indications. Materials and Methods Prospective observational study of neonates in a tertiary Neonatal Intensive Care Unit (NICU) in Pune (India) from February 2014 to January 2015. All the neonates undergoing FnECHO during this 12 month period based on clinical findings were included in the study. Data extracted from the review of the clinical notes included gestational age, birth-weight, mode of delivery, Apgar scores, details of respiratory and cardiovascular support, timing of FnECHO and any other clinical diagnosis. The findings of echocardiography were recorded and correlated with the clinical and other laboratory or X-ray findings. If these findings indicated a change in management, it was instituted. Results A total of 348 echocardiographic studies were performed in 187 neonates (mean 1.86; SD 2.02). The most frequent indication was Patent Ductus Arteriosus (PDA) assessment (n= 174, 50%), followed by haemodynamic instability (n=43, 12.36%). The results of FnECHO modified treatment in 148 cases (42.50%) in the form of addition and/or change in the treatment or avoidance of unnecessary intervention. Conclusion FnECHO is frequently used in the NICU setting and may be a useful tool to guide treatment. PDA assessment and haemodynamic instability are the most frequent indications. To validate its usefulness, well co

  7. Overview of neonatal lupus.

    PubMed

    Johnson, Benay

    2014-01-01

    Neonatal lupus (NL) is defined by the presentation of the fetus and the newborn who possess autoantibodies received from the mother. It is the dysfunction of the maternal immune system that leads to the production of autoantibodies to anti-Sjögren syndrome-A, anti-Sjögren syndrome-B, and anti-ribonuclear protein antigens. These antibodies are shared through the placenta and produce bodily changes in the fetal skin and heart, as well as potential changes in other body systems. Congenital complete heart block is the most dangerous manifestation of NL that can occur in utero or after birth. This article will provide an overview the presentation of NL and current therapies. Prenatal steroids have been the mainstay of therapy to try to reverse first- and second-degree congenital heart block and to prevent progression to a more advanced stage. New therapies are combining steroids with intravenous immunoglobulin and plasmapheresis. This article will provide guidelines for practitioners so they can consider NL as a differential diagnosis when presented with cutaneous lesions, congenital heart block, or abnormal findings in the hematologic, hepatobiliary, neurologic, and musculoskeletal systems. PMID:24100008

  8. [Neonatal mucolipidosis type II].

    PubMed

    Hmami, F; Oulmaati, A; Bouharrou, A

    2016-01-01

    Mucolipidosis type II (ML II, OMIM 252,500) is an autosomal recessive disorder clinically characterized by facial dysmorphia similar to Hurler syndrome and pronounced gingival hypertrophy. The disorder is caused by a defect in targeting acid hydrolases on the surface of lysosomes, which impede their entry and lead to accumulation of undigested substrates in lysosomes. The onset of the symptoms is usually in infancy, beginning in the 6th month of life. Early onset, at birth or even in utero, is a sign of severity and involves the specific dysmorphia as well as skeletal dysplasia related to hyperparathyroidism. We report on a severe neonatal form of this disorder revealed by respiratory distress with severe chest deformity. The dysmorphic syndrome, combining coarse features, pronounced gingival hypertrophy, with diffuse bone demineralization and secondary hyperparathyroidism associating significant elevation of parathyroid hormone and alkaline phosphatase with normal levels of vitamin D and calcium were characteristics of mucolipidosis type II. Recognizing this specific association of anomalies helps eliminate the differential diagnosis and establish appropriate diagnosis and care. PMID:26552632

  9. Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia.

    PubMed

    Silvestri, F; Virgolini, L; Savignano, C; Zaja, F; Velisig, M; Baccarani, M

    1995-01-01

    Among 111 patients referred to our outpatient clinic for isolated thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the second most frequent cause of thrombocytopenia in this population. The diagnosis was confirmed by the following findings: (a) normal platelet numbers immediately after blood withdrawal; (b) progressive fall of platelet counts and evident platelet clumping over time, only in EDTA-anticoagulated blood. A simple, inexpensive and quick diagnostic method was devised, that consists in evaluating the platelet number in a blood sample anticoagulated with EDTA immediately after blood withdrawal and 4 h later. PMID:7725669

  10. Use of peptide thrombopoietin receptor agonist romiplostim (Nplate) in a case of primary HIV-associated thrombocytopenia.

    PubMed

    Aslam, M Imran; Cardile, Anthony P; Crawford, George E

    2014-01-01

    Thrombocytopenia is frequently encountered in HIV-infected patients, and the predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard treatment regimens include optimization of antiretroviral therapy, intravenous immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to sustain remission or inferior responses is common, and investigation into the safety and efficacy of alternative therapies is warranted. We describe novel and effective treatment of PHAT with the peptide thrombopoietin receptor agonist romiplostim in a patient with a minimal response to conventional therapy. PMID:24036490

  11. Neonatal Screening Part 2: Neonatal Screening in Canada

    PubMed Central

    Morris, Brian A.P.

    1990-01-01

    Neonatal screening is a widely accepted, cost-effective method for early detection of various inborn errors of metabolism. This series of three articles examines different aspects of neonatal screening. In the first article, the author discussed general principles of screening and its function in the spectrum of diagnostic techniques for genetic disease. In this, the second article, the author reviews the history and current practices of neonatal screening in Canada. The individual diseases for which screening is used and particular points of interest for each of these diseases are briefly described. The author also outlines the benefits of screening and treatment. In the final article of this series, the author will examine controversial topics that represent the possible future of screening. PMID:21234041

  12. Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins

    PubMed Central

    Sahud, Mervyn A.; Caulfield, Michael; Clarke, Nigel; Koch, Robert; Bougie, Daniel; Aster, Richard

    2013-01-01

    Summary Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet gly coproteins (GP)Ia/IIa (integrin α2β1) in each patient and a second antibody specific for GPIIb/IIIa (αIIbβ3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2–30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug. PMID:23952260

  13. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia.

    PubMed

    Niihori, Tetsuya; Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kaneko, Takashi; Hashii, Yoshiko; Irie, Masahiro; Sato, Atsushi; Saito-Nanjo, Yuka; Funayama, Ryo; Nagashima, Takeshi; Inoue, Shin-Ichi; Nakayama, Keiko; Ozono, Keiichi; Kure, Shigeo; Matsubara, Yoichi; Imaizumi, Masue; Aoki, Yoko

    2015-12-01

    Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8(th) zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-β-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans. PMID:26581901

  14. Chronic immune thrombocytopenia in a child responding only to thrombopoietin receptor agonist

    PubMed Central

    2012-01-01

    Immune thrombocytopenia (ITP) is an acquired hematological disease in which the body produces antibodies against its own platelets leading to platelet destruction resulting in isolated thrombocytopenia. Childhood ITP may enter complete remission in the majority of cases within six months from diagnosis. However, 20-30% of affected children may develop chronic ITP (lasting for more than 12 months). First line treatment includes intravenous immunoglobulin (IVIG), corticosteroids or anti-D immunoglobulin. Second line treatment includes splenectomy, immunosuppressive therapy or Rituximab. Recently two thrombopoietin (TPO) receptor agonists (Romiplostim and Eltrombopag) are used to increase platelet count in refractory chronic ITP by increasing platelet production in bone marrow. Here is a case report on an 8 ½ -year-old boy with refractory chronic ITP who failed therapy with IVIG, corticosteroids, splenectomy and Rituximab. He showed excellent response to treatment with TPO receptor agonist (Romiplostim). His platelet count increased from less than 10 x103/dl and maintained between 100x103/dl to 200x103/dl after few weeks of starting Romiplostim therapy.

  15. Factors associated with Severe Fever with Thrombocytopenia Syndrome infection and fatal outcome

    PubMed Central

    Sun, Jimin; Gong, Zhenyu; Ling, Feng; Zhang, Rong; Tong, Zhendong; Chang, Yue; Chen, Enfu; Liu, Qiyong; Lin, Junfen; Chen, Zhiping; Jiang, Jianmin

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is emerging in China and the incidence increased year by year. In this study, we conducted case control study to explore factors associated with SFTS virus (SFTSV) infection and fatal outcome. In the study of factors associated with SFTSV infection, a total of 216 individuals participated the study, including 72 cases and 144 matched controls. There were significant differences in proportion of history of tick bite and breeding domestic animals between cases and controls. Of note, individuals who were unclear whether they had been bitten by ticks had the highest risk of SFTSV infection and odds ratio (OR) was 10.222. In the study of factors associated with SFTS fatal outcome, a total of 129 cases participated the study including 16 deaths and 113 survivors. Significant differences were observed in body mass index (BMI), intervals from illness onset to confirmation, and proportion of gingival hemorrhage between deaths and survivors, whose ORs of these factors were 3.903, 1.996, and 3.826, respectively. Our results suggest that all patients with fever, thrombocytopenia and leukocytopenia in SFTS endemic areas should be suspected of SFTS, even they don’t have history of tick bite, and more intense treatment should be administered to patients with abnormal BMI before laboratory parameters are detected. PMID:27605309

  16. ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization

    PubMed Central

    Bottega, Roberta; Marconi, Caterina; Faleschini, Michela; Baj, Gabriele; Cagioni, Claudia; Pecci, Alessandro; Pippucci, Tommaso; Ramenghi, Ugo; Pardini, Simonetta; Ngu, Loretta; Baronci, Carlo; Kunishima, Shinji; Balduini, Carlo L.; Seri, Marco; Noris, Patrizia

    2015-01-01

    Inherited thrombocytopenias (ITs) are a heterogeneous group of syndromic and nonsyndromic diseases caused by mutations affecting different genes. Alterations of ACTN1, the gene encoding for α-actinin 1, have recently been identified in a few families as being responsible for a mild form of IT (ACTN1-related thrombocytopenia; ACTN1-RT). To better characterize this disease, we screened ACTN1 in 128 probands and found 10 (8 novel) missense heterozygous variants in 11 families. Combining bioinformatics, segregation, and functional studies, we demonstrated that all but 1 amino acid substitution had deleterious effects. The clinical and laboratory findings of 31 affected individuals confirmed that ACTN1-RT is a mild macrothrombocytopenia with low risk for bleeding. Low reticulated platelet counts and only slightly increased serum thrombopoietin levels indicated that the latest phases of megakaryopoiesis were affected. Given its relatively high frequency in our cohort (4.2%), ACTN1-RT has to be taken into consideration in the differential diagnosis of ITs. PMID:25361813

  17. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

    PubMed Central

    Vishnu, Prakash; Aboulafia, David M

    2016-01-01

    Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim’s efficacy and safety in other primary and secondary thrombocytopenic states. PMID:27307776

  18. Factors associated with Severe Fever with Thrombocytopenia Syndrome infection and fatal outcome.

    PubMed

    Sun, Jimin; Gong, Zhenyu; Ling, Feng; Zhang, Rong; Tong, Zhendong; Chang, Yue; Chen, Enfu; Liu, Qiyong; Lin, Junfen; Chen, Zhiping; Jiang, Jianmin

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is emerging in China and the incidence increased year by year. In this study, we conducted case control study to explore factors associated with SFTS virus (SFTSV) infection and fatal outcome. In the study of factors associated with SFTSV infection, a total of 216 individuals participated the study, including 72 cases and 144 matched controls. There were significant differences in proportion of history of tick bite and breeding domestic animals between cases and controls. Of note, individuals who were unclear whether they had been bitten by ticks had the highest risk of SFTSV infection and odds ratio (OR) was 10.222. In the study of factors associated with SFTS fatal outcome, a total of 129 cases participated the study including 16 deaths and 113 survivors. Significant differences were observed in body mass index (BMI), intervals from illness onset to confirmation, and proportion of gingival hemorrhage between deaths and survivors, whose ORs of these factors were 3.903, 1.996, and 3.826, respectively. Our results suggest that all patients with fever, thrombocytopenia and leukocytopenia in SFTS endemic areas should be suspected of SFTS, even they don't have history of tick bite, and more intense treatment should be administered to patients with abnormal BMI before laboratory parameters are detected. PMID:27605309

  19. Massive Pulmonary Embolism in a Patient with Heparin Induced Thrombocytopenia: Successful Treatment with Dabigatran

    PubMed Central

    Bircan, Haci Ahmet; Alanoglu, Emine Guchan

    2016-01-01

    Heparin induced thrombocytopenia (HIT) is a rare, potentially fatal, immune-mediated complication of heparin therapy, associated with thrombosis and thrombocytopenia. In this study, a successful dabigatran administration in a case with massive pulmonary thromboembolism (mPTE) and HIT is presented. 57 years-old female, who was receiving low molecular weight heparin (LMWH) (0.4 mL once a daily, S.C. for 11 days) due to total knee replacement, was referred to our clinic with the hypotension and syncope attacks. Her echocardiography and pulmonary CT angiography findings were consistent with mPTE. We detected a serious decrease in her platelet count highly suggestive for HIT (plt: 54×103/µL). LMWH was discontinued and dabigatran was started (150 mg twice daily). After platelet count increased over 150×103/μL, dabigatran was switched to warfarin. Since heparin is widely used in medicine, all physicians need to be aware of this life threatening complication of heparin. Replacing heparin with an alternative anticoagulant such as dabigatran may become a life-saving strategy especially in case of HIT complicated with mPTE. PMID:27026768

  20. High Remission Rate of Chronic Immune Thrombocytopenia in Children: Result of 20-Year Follow-Up

    PubMed Central

    Kim, Chae Young; Lee, Eun Hye

    2016-01-01

    Purpose This study examined the outcomes of children with chronic immune thrombocytopenia (ITP). Materials and Methods We retrospectively analyzed the medical records of all patients diagnosed with ITP from January 1992 to December 2011 at our institution. Results A total of 128 patients (64%) satisfied the criteria for newly diagnosed ITP, 31 (15%) for persistent ITP, and 41 (21%) for chronic ITP. The median age at diagnosis was 4.5 years (range, 1 month to 18 years). The median platelet count at diagnosis was 32×109/L. A comparison of the initial treatment data from 2001 to 2011 with those from 1992 to 2000 showed that the number of bone marrow examinations decreased, whereas observation increased. Chronic ITP presented at an older age than newly diagnosed and persistent ITP (6.6 years vs. 3.8 years vs. 4.1 years, respectively); however, the difference did not reach statistical significance (p=0.17). The probability of complete remission of chronic ITP was 50% and 76% at 2 and 5 years after diagnosis, respectively. Patients aged <1 year at diagnosis had a significantly better prognosis than did older patients (hazard ratio, 3.86; p=0.02). Conclusion Children with chronic ITP showed a high remission rate after long-term follow-up. This study suggests that invasive treatments such as splenectomy in children with chronic ITP can be delayed for 4 to 5 years if thrombocytopenia and therapeutic medication do not affect the quality of life. PMID:26632392

  1. Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling

    PubMed Central

    Hirata, Shinji; Takayama, Naoya; Jono-Ohnishi, Ryoko; Endo, Hiroshi; Nakamura, Sou; Dohda, Takeaki; Nishi, Masanori; Hamazaki, Yuhei; Ishii, Ei-ichi; Kaneko, Shin; Otsu, Makoto; Nakauchi, Hiromitsu; Kunishima, Shinji; Eto, Koji

    2013-01-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor–mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl–/– mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC–derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT. PMID:23908116

  2. Non-surgical contraindication for acute appendicitis with secondary thrombocytopenia: a case report.

    PubMed

    Zhang, Hai-Hong; Gu, Guo-Li; Zhang, Xiang-Yang; Fan, Qin; Wang, Xin-Yan; Wei, Xue-Ming

    2015-03-01

    A 26-year-old man presented with migrated right lower abdominal pain and without any history of hematological systemic diseases. Blood routine test showed a leukocyte count of 22.74 × 10(9)/L, with 91.4% neutrophils, and a platelet count of 4 × 10(9)/L before admission. The case question was whether the team should proceed with surgery. Obviously, a differential diagnosis is essential before making such a decision. Acute appendicitis was easily diagnosed based on clinical findings, including migrating abdominal pain, a leukocyte count of 22.74 × 10(9)/L and the result of abdominal computed tomography scan. However, it was not clear whether the severe thrombocytopenia was primary or secondary. So smear of peripheral blood and aspiration of bone marrow were ordered to exclude hematological diseases. Neither of the tests indicated obvious pathological hematological changes. There was no hepatosplenomegaly found by ultrasound examination of the liver and spleen. Therefore, operative intervention may be a unique clinical scenario in acute severe appendicitis patients with secondary thrombocytopenia. PMID:25759558

  3. Antibody binding to megakaryocytes in vivo in patients with immune thrombocytopenia

    PubMed Central

    Arnold, Donald M; Nazi, Ishac; Toltl, Lisa J; Ross, Catherine; Ivetic, Nikola; Smith, James W; Liu, Yang; Kelton, John G

    2015-01-01

    Objectives Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production. Antibody binding to megakaryocytes may occur in ITP, but in vivo evidence of this phenomenon is lacking. Methods We determined the proportion of megakaryocytes bound with immunoglobulin G (IgG) in bone marrow samples from primary patients with ITP (n = 17), normal controls (n = 13) and thrombocytopenic patients with myelodysplastic syndrome (MDS; n = 10). Serial histological sections from archived bone marrow biopsies were stained for CD61 and IgG. IgG binding and the number of bone marrow megakaryocytes were determined morphologically by a hematopathologist with four assessors after a calibration exercise to ensure consistency. Results The proportion of ITP patients with high IgG binding (>50% of bone marrow megakaryocytes) was increased compared with normal controls [12/17 (71%) vs. 3/13 (23%), P = 0.03]. However, the proportion of ITP patients with high IgG binding was no different than thrombocytopenic patients with MDS [12/17 (71%) vs. 7/10 (70%), P = 1.00]. IgG binding was associated with increased megakaryocyte numbers. Like platelet-associated IgG, megakaryocyte-associated IgG is related to thrombocytopenia but may not be specific for ITP. Conclusion Mechanistic studies in ITP should focus on antibody specificity and include thrombocytopenic control patients. PMID:25684257

  4. Vitrectomy for Proliferative Diabetic Retinopathy in a Patient with Heparin-Induced Thrombocytopenia

    PubMed Central

    Fujii, Tomoko; Akashi, Mari; Morishita, Seita; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Kagitani, Maki; Morino, Ichiro; Ikeda, Tsunehiko

    2016-01-01

    Introduction In this study, we report a case of proliferative diabetic retinopathy in a patient with heparin-induced thrombocytopenia (HIT) in whom vitrectomy was performed with good results. Case A 57-year-old man presented with a chief complaint of decreased visual acuity (VA) in the left eye. Corrected VA of the left eye was 0.03, and ophthalmic examination showed fibrovascular membranes along the vascular arcade and a combined rhegmatogenous-traction retinal detachment with a macular hole. The patient began hemodialysis for diabetic nephropathy in March 2014; thrombocytopenia developed after dialysis was started, and HIT was diagnosed after further evaluation. Argatroban hydrate was being used during dialysis. Treatment was switched from warfarin to argatroban hydrate 6 days prior to vitrectomy being performed on the patient's left eye. Although there was bleeding with somewhat difficult hemostasis during the intraoperative treatment of the fibrovascular membranes, surgery was completed without complications and the postoperative course was good. Discussion Vitrectomy was performed with good results in this patient with HIT. Treatment with argatroban hydrate during surgery enabled surgery without the danger of intraoperative clotting. PMID:26933432

  5. Massive Pulmonary Embolism in a Patient with Heparin Induced Thrombocytopenia: Successful Treatment with Dabigatran.

    PubMed

    Bircan, Haci Ahmet; Alanoglu, Emine Guchan

    2016-02-01

    Heparin induced thrombocytopenia (HIT) is a rare, potentially fatal, immune-mediated complication of heparin therapy, associated with thrombosis and thrombocytopenia. In this study, a successful dabigatran administration in a case with massive pulmonary thromboembolism (mPTE) and HIT is presented. 57 years-old female, who was receiving low molecular weight heparin (LMWH) (0.4 mL once a daily, S.C. for 11 days) due to total knee replacement, was referred to our clinic with the hypotension and syncope attacks. Her echocardiography and pulmonary CT angiography findings were consistent with mPTE. We detected a serious decrease in her platelet count highly suggestive for HIT (plt: 54×10(3)/µL). LMWH was discontinued and dabigatran was started (150 mg twice daily). After platelet count increased over 150×10(3)/μL, dabigatran was switched to warfarin. Since heparin is widely used in medicine, all physicians need to be aware of this life threatening complication of heparin. Replacing heparin with an alternative anticoagulant such as dabigatran may become a life-saving strategy especially in case of HIT complicated with mPTE. PMID:27026768

  6. Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopenia.

    PubMed

    Tutwiler, Valerie; Madeeva, Daria; Ahn, Hyun Sook; Andrianova, Izabella; Hayes, Vincent; Zheng, X Long; Cines, Douglas B; McKenzie, Steven E; Poncz, Mortimer; Rauova, Lubica

    2016-01-28

    Heparin-induced thrombocytopenia (HIT) is characterized by a high incidence of thrombosis, unlike other antibody-mediated causes of thrombocytopenia. We have shown that monocytes complexed with surface-bound platelet factor 4 (PF4) activated by HIT antibodies contribute to the prothrombotic state in vivo, but the mechanism by which this occurs and the relationship to the requirement for platelet activation via fragment crystallizable (Fc)γRIIA is uncertain. Using a microfluidic model and human or murine blood, we confirmed that activation of monocytes contributes to the prothrombotic state in HIT and showed that HIT antibodies bind to monocyte FcγRIIA, which activates spleen tyrosine kinase and leads to the generation of tissue factor (TF) and thrombin. The combination of direct platelet activation by HIT immune complexes through FcγRIIA and transactivation by monocyte-derived thrombin markedly increases Annexin V and factor Xa binding to platelets, consistent with the formation of procoagulant coated platelets. These data provide a model of HIT wherein a combination of direct FcγRIIA-mediated platelet activation and monocyte-derived thrombin contributes to thrombosis in HIT and identifies potential new targets for lessening this risk. PMID:26518435

  7. The Effects of Increased Maternal Visual Regard of Neonate Upon the Neonate-Mother Interaction.

    ERIC Educational Resources Information Center

    Belcastro, Christina M.; And Others

    This study attempts to investigate the effects of increased maternal visual regard on neonatal social visual behavior and upon patterns of mother-neonate interaction within the context of a learning theory paradigm. Subjects were 3-day-old neonates and their mothers; with 10 of the 15 mother-neonate pairs as the experimental group, and 5 as the…

  8. Neonatal meningoencephalitis caused by Bacillus cereus.

    PubMed

    Manickam, Nisha; Knorr, Aimee; Muldrew, Kenneth L

    2008-09-01

    The classic organisms associated with central nervous system infection in the neonate are herpes simplex, Listeria monocytogenes, Escherichia coli, and Streptococcus agalactiae; we describe an unusual case of neonatal meningoencephalitis caused by Bacillus cereus. PMID:18679155

  9. Comparison of different platelet transfusion thresholds prior to insertion of central lines in patients with thrombocytopenia

    PubMed Central

    Estcourt, Lise J; Desborough, Michael; Hopewell, Sally; Doree, Carolyn; Stanworth, Simon J

    2016-01-01

    Background Patients with a low platelet count (thrombocytopenia) often require the insertion of central lines (central venous catheters (CVCs)). CVCs have a number of uses; these include: administration of chemotherapy; intensive monitoring and treatment of critically-ill patients; administration of total parenteral nutrition; and long-term intermittent intravenous access for patients requiring repeated treatments. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to CVC insertion, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to CVC insertion varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding after a central line insertion appears to be low if an ultrasound-guided technique is used. Patients may therefore be exposed to the risks of a platelet transfusion without any obvious clinical benefit. Objectives To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). Search methods We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2015, Issue 2), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 February 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 patients of any age with thrombocytopenia requiring insertion of a CVC. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results One RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver

  10. Immune Thrombocytopenia

    MedlinePlus

    ... Petechiae may look like a rash. Petechiae and Purpura The photograph shows purpura (bruises) and petechiae (red and purple dots) on ... the purple, brown, and red color of the purpura and petechiae. People who have ITP also may ...

  11. Clinical and laboratory characteristics of neonatal hypocalcemia

    PubMed Central

    Cho, Won Im; Yu, Hyeoh Won; Shin, Choong Ho; Yang, Sei Won; Choi, Chang Won; Kim, Beyong Il

    2015-01-01

    Purpose To describe the clinical characteristics of full-term neonates with hypocalcemia and to suggest factors associated with neonatal hypocalcemia Methods The medical records of full-term neonates with hypocalcemia were reviewed. Hypocalcemia was defined as an ionized calcium (iCa) concentration of <4 mg/dL. Parathyroid hormone (PTH) insufficiency was defined as a serum PTH level of <60 pg/mL or a serum phosphorus level higher than the serum calcium level in the presence of hypocalcemia. Results Fifty-three neonates were enrolled. The median age at diagnosis of hypocalcemia was 3 days. In all the neonates, formula feeding predominance was observed. Thirty-eight neonates (69.8%) were compatible with PTH insufficiency. The number of formula-fed neonates was significantly higher than that of breast-fed patients among neonates with PTH insufficiency (P=0.017). Intact PTH was negatively correlated with serum phosphorus levels. Twelve out of 14 neonates (85.7%) had 25-hydroxy vitamin D (25OHD) levels <20 ng/mL and 9 neonates (64.3%) had 25OHD levels <10 ng/mL. Twenty-one neonates had hypocalcemic tetany. The serum calcium and iCa concentrations of neonates with tetany were 4.2-8.3 mg/dL and 1.85-3.88 mg/dL, respectively. Three neonates showed symptomatic hypocalcemia with calcium levels over 7.5 mg/dL. Among the 16 neonates who underwent electroencephalography (EEG), 12 had abnormalities, which normalized after 1-2 months. Conclusion Formula milk feeding, PTH insufficiency and low serum vitamin D concentration are associated with the development of neonatal hypocalcemia. Symptoms such as tetany and QT interval prolongation can develop in relatively mild hypocalcemia. Moreover, transient neonatal hypocalcemia can cause transient EEG abnormalities. PMID:26191512

  12. Biliary atresia and neonatal hepatobiliary scintigraphy

    SciTech Connect

    Wynchank, S.; Guillet, J.; Leccia, F.; Soubiran, G.; Blanquet, P.

    1984-03-01

    Hepatobiliary scintigraphy using Tc-99m diethyl IDA was performed on 14 jaundiced neonates. It aided greatly the differential diagnosis between neonatal hepatitis and biliary atresia. Limitations in the interpretation of the results are described, as neonatal hepatitis may be accompanied by biliary excretion ranging from zero to normal. Also both biliary atresia (intra- and extrahepatic) and neonatal hepatitis may show no biliary excretion within 24 hours.

  13. Neonatal Jaundice Detection System.

    PubMed

    Aydın, Mustafa; Hardalaç, Fırat; Ural, Berkan; Karap, Serhat

    2016-07-01

    Neonatal jaundice is a common condition that occurs in newborn infants in the first week of life. Today, techniques used for detection are required blood samples and other clinical testing with special equipment. The aim of this study is creating a non-invasive system to control and to detect the jaundice periodically and helping doctors for early diagnosis. In this work, first, a patient group which is consisted from jaundiced babies and a control group which is consisted from healthy babies are prepared, then between 24 and 48 h after birth, 40 jaundiced and 40 healthy newborns are chosen. Second, advanced image processing techniques are used on the images which are taken with a standard smartphone and the color calibration card. Segmentation, pixel similarity and white balancing methods are used as image processing techniques and RGB values and pixels' important information are obtained exactly. Third, during feature extraction stage, with using colormap transformations and feature calculation, comparisons are done in RGB plane between color change values and the 8-color calibration card which is specially designed. Finally, in the bilirubin level estimation stage, kNN and SVR machine learning regressions are used on the dataset which are obtained from feature extraction. At the end of the process, when the control group is based on for comparisons, jaundice is succesfully detected for 40 jaundiced infants and the success rate is 85 %. Obtained bilirubin estimation results are consisted with bilirubin results which are obtained from the standard blood test and the compliance rate is 85 %. PMID:27229489

  14. Cardiogenic shock in a neonate

    PubMed Central

    Viveiros, Eulália; Aveiro, Ana Cristina; Costa, Edite; Nunes, José Luis

    2013-01-01

    We describe a case of a healthy male full-term neonate, 21 days old, admitted to the emergency room, presenting a severe cardiovascular collapse with an initial sinus rhythm. The first diagnostic hypothesis was of septic shock, having antibiotics, fluid resuscitation, inotropic drugs and ventilatory support started immediately. After achieving haemodynamic stability, a new cardiovascular collapse occurred with supraventricular tachycardia (SVT). The latter was successfully treated and the neonate did not suffer any organ damage. Cardiogenic shock should be considered despite being a much rarer cause of shock in neonates. SVT is promptly diagnosed when a cardiorespiratory monitor is available; however, the intermittent occurrence of the tachycardia episodes makes this diagnosis more difficult to recognise and manage. PMID:23737567

  15. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  16. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  17. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  18. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  19. 21 CFR 880.5400 - Neonatal incubator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Neonatal incubator. 880.5400 Section 880.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of...

  20. Regulation of muscle growth in neonates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review reports recent findings on the multiple factors that regulate skeletal muscle growth in neonates. Skeletal muscle is the fastest growing protein mass in neonates. The high rate of neonatal muscle growth is due to accelerated rates of protein synthesis accompanied by the rapid accumulatio...

  1. Amino acids and insulin in neonatal growth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rate of growth during the neonatal period is greater than at any other stage of postnatal life, and a majority of the mass increase is skeletal muscle. The rapid growth of skeletal muscle in the neonate is driven by an elevated rate of protein synthesis. Neonates are very efficient at utilizin...

  2. Neonatal records and the computer.

    PubMed Central

    Walker, C H

    1977-01-01

    To use a combined single document clinical case sheet/computer record which can form the basic document for a life medical record is a practical proposition. With adequate briefing doctors and nurses soon become familiar with the record and appreciate its value. Secretarial and clerical requirements are reduced to a minimum as transcription of medical data is eliminated, so greatly speeding up processing and feed back to the medical services. A few illustrations of trends in neonatal statistics and of computer linked maternal/neonatal data are presented. PMID:879830

  3. Interprofessional Education in Neonatal Care.

    PubMed

    Kenner, Carole

    2016-01-01

    Interprofessional education is not a new concept. Yet, the operationalization of interprofessional education with related competencies for collaborative team-based practice in neonatal units is often difficult. Changes in healthcare with an emphasis on patient-focused care and the concern for patient safety and quality care are accelerating the need for more interprofessional education. This article briefly outlines the evolution of interprofessional education to support collaborative team-based practice and how that facilitates safety and quality care in neonatal units. PMID:27465448

  4. [Treated with Artemether-Lumefantrine Five Evaluation of P. Falciparum Malaria Cases in Terms of Hyponatremia and Thrombocytopenia].

    PubMed

    Yalçın, Murat; Sevim, Erol; Duran, Arzu

    2015-06-01

    The most severe type of malaria, P. falciparum may progress with several complications. We have detected hyponatremia and thrombocytopenia in the cases with falciparum malaria. We have launched coartemether which is used in resistant falciparum and supportive care with our four cases. We found out hyponatremia in the cases because serum concentrations were between 117-134 mEq/L. Clinical conditions of the case were highly heavy, in which blood sodium level was pretty low. While the other three cases responded to the treatment in three days, this case responded after the fifth day. Owing to this situation, we thought that there was a relationship between the severity of hyponatremia and clinical course. We measured the number of blood platelet of three cases as 11000-65000-80000/mm3. There was no thrombocytopenia in other two cases. The patient with lowest blood sodium level had the lowest number of blood platelet, as well. With the help of coartemether and supportive care, thrombocytopenia recovered within three-five days in general, but in the patient with severe thrombocytopenia, it got better after the fifth day. PMID:26081891

  5. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  6. Two Cases of Refractory Thrombocytopenia in Systemic Lupus Erythematosus that Responded to Intravenous Low-Dose Cyclophosphamide

    PubMed Central

    Park, Hee-Jin; Kang, Mi-il; Kang, Yoon; Chung, Soo-jin; Park, Yong-Beom; Lee, Soo-Kon

    2013-01-01

    Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/µL. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/µL after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF. PMID:23487584

  7. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin.

    PubMed

    de Castro, Reynaldo Angelo C; de Castro, Jo-Anne A; Barez, Marie Yvette C; Frias, Melchor V; Dixit, Jitendra; Genereux, Maurice

    2007-04-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets < or = 50,000/mm(3)) reveal that the increase in platelet count with anti-D immune globulin (WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option. PMID:17426181

  8. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    SciTech Connect

    Murphy, Kenneth D.; McCrohan, Gerard; DeMarta, Deborah A.; Shirodkar, Nitin B.; Kwon, Oun J.; Chopra, Paramjit S.

    1996-03-15

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin.

  9. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    PubMed

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole. PMID:25614519

  10. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia

    PubMed Central

    Estcourt, Lise J; Ingram, Callum; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Stanworth, Simon J

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). PMID:27057148

  11. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy.

    PubMed

    Hanafy, A S; El Hawary, A T; Hamed, E F; Hassaneen, A M

    2016-07-01

    The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/μl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/μl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/μl to 104.2 ± 15.2 × 10(3)/μl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy. PMID:27180243

  12. Effect of High Dose of Steroid on Plateletcount in Acute Stage of Dengue Fever with Thrombocytopenia

    PubMed Central

    Shashidhara, K.C.; Murthy, K.A. Sudharshan; Gowdappa, H. Basavana; Bhograj, Abhijith

    2013-01-01

    Background: Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. Aim and Objectives: The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. Methods: During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (<50000/cumm) and 61patients were randomly allocated, 30 to the study group and 31 to the control group, in an open labeled study. The study group received intravenous dexamethasone 8mg initially followed by 4 mg every 8 h thereafter for 4 days and IV fluids whenever required. The control Group received only IV fluids and antipyretics whenever it was indicated. The daily measurement of platelet count was carried out in all patients from the day of enrolment to the fourth day of post treatment. Results: The baseline data (age, sex, and the mean duration of the illness, Hb%, haematocrit, and platelets) were similar in both the groups. The analysis of variance (ANOVA) statistics showed a significant linear association of the mean platelet counts with the days in either group. The mean platelet counts increased steadily in both the groups from days 1 to 4: day1 (0.687), day2 (0.34), day3 (0.530) and day4 (0.844). There was

  13. [Patient who developed heparin-induced thrombocytopenia type II after 24 years on hemodialysis].

    PubMed

    Gavranić, Bruna Brunetta; Basić-Jukić, Nikolina; Kes, Petar

    2012-10-01

    Heparin-induced thrombocytopenia type II (HIT) is a clinicopathologic syndrome in which one or more clinical events are temporally related to heparin administration and caused by HIT antibodies. There are at least five different types of clinical events that are associated with HIT: thrombocytopenia; thrombosis; skin necrosis at heparin injection site, venous limb gangrene; and an acute systemic reaction that occurs 5-30 min after intravenous bolus of heparin. HIT typically presents 5-14 days after initiation of heparin therapy, later onset is unusual. Heparin is a routine anticoagulant in hemodialysis but administration is different than in surgical and other medical population. Doses are lower and administered every other day, yet hemodialysis patients receive heparin for years. Relationship between dialysis vintage and HIT-antibody positivity has been analyzed in two studies. In national survey of HIT in hemodialysis population of the United Kingdom mean time between starting hemodialysis and development of HIT was 61 days (5-390 days). Japanese authors also found greatest incidence of HIT antibody positivity in patients who were on hemodialysis for less than 1 year, none of patients on hemodialysis for more than 10 years was HIT-antibody positive. We present a case of 70-years old female who developed HIT after 24 years of hemodialysis and exposure to heparin. First 22 years she was receiving unfractionated heparin for anticoagulation during hemodialysis sessions. Afterwards her therapy was changed to low molecular weight heparin. Last 12 years she has tunneled cuffed catheter which was also filled with unfractionated heparin. She had a history of severe renal osteodistrophy and severe aortal valve stenosis, hypothyreosis, thrombosis of both subclavian veins and partial colon resection due to mesenterial artery thrombosis. Her thrombocyte count was low, but despite extensive work-up which included HIT antibody detection, no cause could be identified. She

  14. Congenital thrombotic thrombocytopenic purpura: Upshaw-Schulman syndrome: a cause of neonatal death and review of literature.

    PubMed

    Sharma, Deepak; Shastri, Sweta; Pandita, Aakash; Sharma, Pradeep

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare disorder in children characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. The classic Moschcowitz Pentads of TTP include hemolytic anemia, with fragmentation of erythrocytes, thrombocytopenia, diffuse and non-focal neurologic findings, decrease renal function and fever. We report a newborn who was diagnosed with congenital TTP. The newborn was admitted at age of 40 h, in our hospital, in view of respiratory distress with impending respiratory failure and red colored urine. On examination, the newborn was febrile, tachypneic, had deep icterus, pallor and no hepatosplenomegaly. Family history was significant with one unexplained neonatal death at age of 24 with symptoms of red colored urine. Examination of peripheral smear was diagnostic with the presence of fragmented RBCS, giant but fewer platelets consistent with a diagnosis of MAHA. The diagnosis of TTP was confirmed with low ADAMTS activity and gene analysis showed c 2203 G > T-p.Glu735X (domain TSP1-2) mutation in exon 18 of ADAMTS 13 gene. The newborn had rapid deterioration, with respiratory distress and refractory shock leading to death. Post-mortem bone marrow done showed marrow hyperplasia. PMID:26365135

  15. Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count

    PubMed Central

    Saad, W. E.; Bleibel, W.; Adenaw, N.; Wagner, C. E.; Anderson, C.; Angle, J. F.; Al-Osaimi, A. M.; Davies, M. G.; Caldwell, S.

    2014-01-01

    Objectives: Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO) have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included), and to assess the effect of BRTO on platelet count over a 1-year period. Materials and Methods: This is a retrospective review of 35 patients who underwent BRTO (March 2008–August 2011). Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma) were analyzed (multivariate analysis). A total of 91% (n = 32/35) of patients had thrombocytopenia (<150,000 platelet/cm3) pre-BRTO. Platelet counts at within 48-h, within 2 weeks and at 30-60 days intervals (up to 6 months) after BRTO were compared with the baseline pre-BRTO values. Results: 35 Patients with adequate platelet follow-up were found. A total of 92% and 17% of patients had a platelet count of <150,000/cm3 and <50,000/cm3, respectively. There was a trend for transient worsening of thrombocytopenia immediately (<48 h) after BRTO, however, this was not statistically significant. Platelet count was not a predictor of post-BRTO rebleeding or patient survival. However, MELD-score, albumin, international normalized ratio (INR), and etiology were predictors of rebleeding. Conclusion: Thrombocytopenia is very common (>90% of patients) in patients

  16. Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

    PubMed Central

    2013-01-01

    Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects

  17. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage

    PubMed Central

    Yougbaré, Issaka; Lang, Sean; Yang, Hong; Chen, Pingguo; Zhao, Xu; Tai, Wei-She; Zdravic, Darko; Vadasz, Brian; Li, Conglei; Piran, Siavash; Marshall, Alexandra; Zhu, Guangheng; Tiller, Heidi; Killie, Mette Kjaer; Boyd, Shelley; Leong-Poi, Howard; Wen, Xiao-Yan; Skogen, Bjorn; Adamson, S. Lee; Freedman, John; Ni, Heyu

    2015-01-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening disease in which intracranial hemorrhage (ICH) is the major risk. Although thrombocytopenia, which is caused by maternal antibodies against β3 integrin and occasionally by maternal antibodies against other platelet antigens, such as glycoprotein GPIbα, has long been assumed to be the cause of bleeding, the mechanism of ICH has not been adequately explored. Utilizing murine models of FNAIT and a high-frequency ultrasound imaging system, we found that ICH only occurred in fetuses and neonates with anti–β3 integrin–mediated, but not anti-GPIbα–mediated, FNAIT, despite similar thrombocytopenia in both groups. Only anti–β3 integrin–mediated FNAIT reduced brain and retina vessel density, impaired angiogenic signaling, and increased endothelial cell apoptosis, all of which were abrogated by maternal administration of intravenous immunoglobulin (IVIG). ICH and impairment of retinal angiogenesis were further reproduced in neonates by injection of anti–β3 integrin, but not anti-GPIbα antisera. Utilizing cultured human endothelial cells, we found that cell proliferation, network formation, and AKT phosphorylation were inhibited only by murine anti–β3 integrin antisera and human anti–HPA-1a IgG purified from mothers with FNAIT children. Our data suggest that fetal hemostasis is distinct and that impairment of angiogenesis rather than thrombocytopenia likely causes FNAIT-associated ICH. Additionally, our results indicate that maternal IVIG therapy can effectively prevent this devastating disorder. PMID:25774504

  18. Microbiome Development in Neonatal Calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The initial colonization of eukaryotic hosts by microbial populations is poorly understood, yet this remains a critical time for growth and development. The goals of this study were to characterize the microbiome of neonatal calves. Terminal restriction fragment length polymorphism (T-RFLP) analysis...

  19. Eruption cysts in the neonate.

    PubMed

    Ricci, Hérica Adad; Parisotto, Thaís Manzano; Giro, Elisa Maria Aparecida; de Souza Costa, Carlos Alberto; Hebling, Josimeri

    2008-01-01

    Disturbances of the dental development may result in anomalies, which may be apparent as soon as the child is born. Eruption cysts are rarely observed in neonates considering that at this stage of the child's life teeth eruption is uncommon. Thus, the aim of this report is to describe a case of eruption cysts in a neonate. A male neonate was brought to the emergency service with the chief complaint of an elevated area on the anterior region of the inferior alveolar ridge. The lesion was clinically characterized as a compressive and floating swelling. Through a radiographic exam two mandibular primary incisors could be seen superficially located. Due to the patient's age and the initial diagnosis of eruption cysts the conduct adopted was clinical surveillance. Forty-five days after the first visit the lesions had significantly decreased in size, and completely disappeared after 4 months. At that age, both mandibular central incisors were already in the oral cavity exhibiting small hypoplastic areas in the incisal edges. The clinical and radiographic follow-up of eruption cysts in neonates appears to be an adequate conduct without differing from that recommended for older children. PMID:18524277

  20. [Top five neonatal articles 2015].

    PubMed

    Flamant, C; Fischer Fumeaux, C J

    2016-09-01

    This review includes five randomized controlled trials, published in the Medline database in 2015, which were selected by the Scientific commission of the French society of neonatology, taking into account their influence in perinatology. This selection was presented during the specific "Top five" session in the French congress of neonatal research. PMID:27431853

  1. Arginine production in the neonate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Endogenous arginine synthesis in adults is a complex multiorgan process, in which citrulline is synthesized in the gut, enters the general circulation, and is converted into arginine in the kidney, by what is known as the intestinal-renal axis. In neonates, the enzymes required to convert citrulline...

  2. Photodegradation of riboflavin in neonates

    SciTech Connect

    Sisson, T.R.

    1987-04-01

    The biologically most important flavins are riboflavin and its related nucleotides, all highly sensitive to light. It is because of its photoreactivity and its presence in almost all body fluids and tissues that riboflavin assumes importance in phototherapy of neonatal jaundice. The absorption maxima of both bilirubin and riboflavin in the body are nearly identical: 445-450 (447) nm. In consequence, blue visible light will cause photoisomerization of bilirubin accompanied by photodegradation of riboflavin. This results in diminished erythrocyte glutathione reductase, which indicates generalized tissue riboflavin deficiency and red cell lysis. Single- and double-strand breaks in intracellular DNA have occurred with phototherapy. This light exposure of neonates may result also in alterations of bilirubin-albumin binding in the presence of both riboflavin and theophylline (the latter frequently given to prevent neonatal apnea). Many newborns, especially if premature, have low stores of riboflavin at birth. The absorptive capacity of premature infants for enteral riboflavin is likewise reduced. Consequently, inherently low stores and low intake of riboflavin plus phototherapy for neonatal jaundice will cause a deficiency of riboflavin at a critical period for the newborn. Supplementation to those infants most likely to develop riboflavin deficiency is useful, but dosage, time, and mode of administration to infants undergoing phototherapy must be carefully adjusted to avoid unwanted side effects.

  3. Autoimmune Thrombocytopenia Complicated by EDTA- and/or Citrate-Dependent Pseudothrombocytopenia

    PubMed Central

    Salama, Abdulgabar

    2015-01-01

    Summary Background Pseudothrombocytopenia (PTCP) is a well-known phenomenon. However, confusion may occur due to unusual characteristics. Case Reports Two patients with autoimmune thrombocytopenia (ITP) and long-lasting PTCP are described. Initially, only the diagnosis of ITP was confirmed. During observation, discrepancies were recognized between clinical findings and platelet counts. Re-examination resulted in the additional diagnosis of EDTA-dependent PTCP. Subsequently, the latter diagnosis was changed to citrate-dependent PTCP in both cases. Interestingly, PTCP was observed to change again and became recognizable in citrate or heparin, and only during the first 20-30 min following phlebotomy in EDTA specimens. Conclusion The incidence of concomitant ITP with PTCP might be higher than previously reported, and PTCP may have variable dynamics and characteristics. PMID:26696805

  4. [Research Progress on role of Abnormal Tryptophan Metabolism in Immune Thrombocytopenia].

    PubMed

    Li, Zhao-Jian; Liu, Xiao-Qian; Xu, Jun-Qing; Chu, Xiao-Xia

    2015-12-01

    Immune thrombocytopenia (ITP) is a common acquired autoimmune hematological disorders. Platelet autoantibodies lead to the decrease of platelet production and (or) increase of its destruction. The latest researches showed that the abnormal tryptophan metabolism mediated by indoleamine-2, 3-dioxygenase(IDO) is related with the pathogenesis of ITP. The patients with ITP show less expression of IDO, reduction of Treg cells and increase of autoreactive T cells and autoantibodies. CTLA-4-Ig can improve the expression of IDO in the patients with ITP, which also can inhibit the proliferation and activation of self-reactive T cells. Thus, clarifying the abnormal tryptophan metabolism mediated by IDO may provide a new idea for improving the understand of the pathogenesis and treatment of ITP. This review focuses on reasearch progress of the tryptophan metabolism mediated by IDO and ITP. PMID:26708916

  5. Seroprevalence of severe fever with thrombocytopenia syndrome virus in southeastern China and analysis of risk factors.

    PubMed

    Sun, J M; Zhang, Y J; Gong, Z Y; Zhang, L; Lv, H K; Lin, J F; Chai, C L; Ling, F; Liu, S L; Gu, S P; Zhu, Z H; Zheng, X H; Lan, Y Q; Ding, F; Huang, W Z; Xu, J R; Chen, E F; Jiang, J M

    2015-03-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) has been prevalent for some time in China and it was first identified in 2010. However, the seroprevalence of SFTSV in the general population in southeastern China and risk factors associated with the infection are currently unclear. Blood samples were collected from seven counties across Zhejiang province and tested for the presence of SFTSV-specific IgG antibodies by ELISA. A total of 1380 blood samples were collected of which 5·51% were seropositive for SFTSV with seroprevalence varying significantly between sites. Seroprevalence of SFTSV in people who were family members of the patient, lived in the same village as the patient, or lived in a different village than the patient varied significantly. There was significant difference in seroprevalence between participants who bred domestic animals and participants who did not. Domestic animals are probably potential reservoir hosts and contact with domestic animals may be a transmission route of SFTSV. PMID:24866248

  6. Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy.

    PubMed

    Shan, Ning-Ning; Dong, Li-Li; Zhang, Xiao-Mei; Liu, Xin; Li, Ying

    2016-04-01

    Autophagy involves the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy is not only an essential cell-intrinsic mechanism for protecting against internal and external stress conditions but is also key in the cellular response against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. In recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Immune thrombocytopenia (ITP) is a multifactorial disease characterized by autoimmune responses to self-platelet membrane proteins. Recently, our unpublished original data demonstrated aberrant expression of molecules in the autophagy pathway in ITP patients compared with controls, and we found a close correlation between the pathogenesis of ITP and the autophagy pathway. The potential of targeting the autophagy pathway in ITP as a novel therapeutic approach has been discussed. PMID:26830007

  7. Role of romiplostim in splenectomized and nonsplenectomized patients with immune thrombocytopenia

    PubMed Central

    Perdomo, Jose

    2016-01-01

    Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used for the treatment of adult primary immune thrombocytopenia (ITP). ITP is an autoimmune condition characterized by low platelet counts due to increased destruction and reduced platelet production. First-line interventions include corticosteroids, anti-D, and intravenous immunoglobulins, while second-line therapies comprise splenectomy, rituximab, cyclosporine A, and TPO-RAs. The recognition that compromised platelet production is a critical part of the pathogenesis of ITP prompted the development of therapeutic strategies based on the stimulation of the TPO receptor. TPO-RAs enhance megakaryocyte proliferation, increase platelet production, and lead to a reduction in bleeding episodes in ITP patients. This review will summarize current data on the TPO-RA romiplostim, with a particular focus on its relation to splenectomy. PMID:27529057

  8. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    PubMed Central

    Arslan, Deniz; Tatlı, Ali Murat; Goksu, Sema Sezgin; Başsorgun, Cumhur İbrahim; Coskun, Hasan Senol; Bozcuk, Hakan; Savaş, Burhan

    2014-01-01

    Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone metastases. PMID:25045559

  9. Role of romiplostim in splenectomized and nonsplenectomized patients with immune thrombocytopenia.

    PubMed

    Perdomo, Jose

    2016-01-01

    Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used for the treatment of adult primary immune thrombocytopenia (ITP). ITP is an autoimmune condition characterized by low platelet counts due to increased destruction and reduced platelet production. First-line interventions include corticosteroids, anti-D, and intravenous immunoglobulins, while second-line therapies comprise splenectomy, rituximab, cyclosporine A, and TPO-RAs. The recognition that compromised platelet production is a critical part of the pathogenesis of ITP prompted the development of therapeutic strategies based on the stimulation of the TPO receptor. TPO-RAs enhance megakaryocyte proliferation, increase platelet production, and lead to a reduction in bleeding episodes in ITP patients. This review will summarize current data on the TPO-RA romiplostim, with a particular focus on its relation to splenectomy. PMID:27529057

  10. Relationship between total thiol status and thrombocytopenia in patients with Crimean-Congo hemorrhagic fever.

    PubMed

    Guner, Rahmet; Tasyaran, Mehmet A; Keske, Siran; Hasanoglu, Imran; Kalem, Ayse Kaya; Yapar, Derya; Gulen, Tugba Arslan; Neselioglu, Salim; Isikoglu, Semra; Erel, Ozcan

    2012-11-01

    The objective of this study was to investigate the relationship between serum total thiol level and total oxidant status (TOS) and thrombocytopenia among patients with Crimean-Congo hemorrhagic fever (CCHF). Eighty-three subjects and 56 controls were enrolled in the study. Thiol levels were measured with the DTNB method and TOS was measured with the Erel's method among subjects and controls. Thiol levels were lower in subjects than controls and TOS levels were higher in subjects than controls. There was a significant correlation between total thiol levels and platelet counts (r = 0.84, p < 0.0001) among subjects. Further investigations are needed into the link between total thiol level and TOS and the pathogenesis of hemorrhage in CCHF. PMID:23413704

  11. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia

    PubMed Central

    Niihori, Tetsuya; Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kaneko, Takashi; Hashii, Yoshiko; Irie, Masahiro; Sato, Atsushi; Saito-Nanjo, Yuka; Funayama, Ryo; Nagashima, Takeshi; Inoue, Shin-ichi; Nakayama, Keiko; Ozono, Keiichi; Kure, Shigeo; Matsubara, Yoichi; Imaizumi, Masue; Aoki, Yoko

    2015-01-01

    Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8th zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-β-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans. PMID:26581901

  12. Severe fever with thrombocytopenia syndrome with myocardial dysfunction and encephalopathy: A case report.

    PubMed

    Kawaguchi, Takeshi; Matsuda, Motohiro; Takajo, Ichiro; Kawano, Ayako; Kariya, Yumi; Kubo, Kazuyoshi; Miyauchi, Syunichi; Umekita, Kunihiko; Nagatomo, Yasuhiro; Yano, Takao; Yano, Kouji; Okayama, Akihiko

    2016-09-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China, Korea and Japan caused by a novel bunyavirus, SFTS virus (SFTSV). Although central nervous system manifestations are common in SFTS patients, the pathogenesis has not been elucidated; and there are few reports of myocardial dysfunction. Here we report an elderly Japanese patient with reversible myocardial dysfunction and encephalopathy. A previously healthy 65-year-old male engaged in forestry got a tick bite and developed fever and fatigue in 3 days. Three days after onset, he presented to a local hospital where the diagnosis of SFTS with hemophagocytotic syndrome was made. The blood test showed leukopenia and thrombocytopenia as well as elevated levels of alanine aminotransferase and aspartate aminotransferase. Marked hemophagocytosis was found on bone marrow smear. Peripheral blood was positive for SFTSV gene by reverse-transcription polymerase chain reaction. On day 7, the patient was transferred to our hospital. We observed disturbance of consciousness, Kernig sign and myoclonus to face and limbs. Decreased blood flow of whole cerebral cortex was detected by single photon emission computed tomography (SPECT). Chest X-ray revealed cardiomegaly and electrocardiography (ECG) showed abnormal T waves. These data suggested acute encephalopathy and myocardial dysfunction. We treated him with corticosteroid and blood transfusion, which resulted in the complete recovery of the above abnormal symptoms and laboratory data including the findings in SPECT and ECG in about a month. This case demonstrated transient myocardial dysfunction and encephalopathy can occur in addition to typical clinical manifestation of SFTS. PMID:26943978

  13. Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

    PubMed

    Yildiz, Inci; Ozdemir, Nihal; Celkan, Tiraje; Soylu, Selen; Karaman, Serap; Canbolat, Aylin; Dogru, Omer; Erginoz, Ethem; Apak, Hilmi

    2015-01-01

    Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. PMID:26154620

  14. Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia

    PubMed Central

    Cheung, Eric; Liebman, Howard A

    2009-01-01

    Immune thrombocytopenia (ITP) is an acquired bleeding autoimmune disorder characterized by a markedly decreased blood platelet count. The disorder is variable, frequently having an acute onset of limited duration in children and a more chronic course in adults. A number of therapeutic agents have demonstrated efficacy in increasing the platelet counts in both children and adults. Anti-RhD immunoglobulin (anti-D) is one such agent, and has been successfully used in the setting of both acute and chronic immune thrombocytopenia. In this report we review the use of anti-D in the management of ITP. While the FDA-approved dose of 50 mg/kg has documented efficacy in increasing platelet counts in approximately 80% of children and 70% of adults, a higher dose of 75 μg/kg has been shown to result in a more rapid increase in platelet count without a greater reduction in hemoglobin. Anti-D is generally ineffective in patients who have failed splenectomy. Anti-RhD therapy has been shown capable of delaying splenectomy in adult patients, but does not significantly increase the total number of patients in whom the procedure can be avoided. Anti-D therapy appears to inhibit macrophage phagocytosis by a combination of both FcR blockade and inflammatory cytokine inhibition of platelet phagocytosis within the spleen. Anti-RhD treatment is associated with mild to moderate infusion toxicities. Rare life-threatening toxicities such as hemoglobinuria, acute renal failure and disseminated intravascular coagulation have been reported. Recommendations have been proposed to reduce the risk of these complications. Anti-D immunoglobulin can be an effective option for rapidly increasing platelet counts in patients with symptomatic ITP. PMID:19707396

  15. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico

    PubMed Central

    Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown. PMID:26576310

  16. Neonatal Hyperglycemia due to Transient Neonatal Diabetes Mellitus in Puerto Rico.

    PubMed

    Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M

    2015-01-01

    Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown. PMID:26576310

  17. Neonatal Pustular Dermatosis: An Overview

    PubMed Central

    Ghosh, Sangita

    2015-01-01

    Neonatal pustular eruption is a group of disorders characterized by various forms of pustulosis seen in first 4 weeks of life. Its presentation is often similar with some subtle differences, which can be further established by few simple laboratory aids, to arrive at a definite diagnosis. Given their ubiquitous presentation, it is sometimes difficult to differentiate among self-limiting, noninfectious, pustular dermatosis such as erythema toxicum neonatorum, transient neonatal pustular melanosis, miliaria pustulosa, etc., and potentially life threatening infections such as herpes simplex virus and varicella zoster virus infections. This review article tries to address the chronological, clinical, morphological, and histological differences among the various pustular eruptions in a newborn, in order to make it easier for a practicing dermatologist to diagnose and treat these similar looking but different entities of pustulation with a clear demarcation between the physiological benign pustular rashes and the infectious pustular lesions. PMID:25814724

  18. Pain Perception in the Neonate

    PubMed Central

    Midmer, Deana K.

    1989-01-01

    Pain expression in both pre-term and term infants is a little understood phenomenon. Recent research has generated data documenting that the newborn can feel pain, can act to avoid the pain, and may form memory traces of the experience. ”Nociceptive activity” or ”noxious stimuli” are better terms to use when addressing aversive stimulation of the neonate because they encourage scrutiny of the behavioural and physiologic responses of the newborn without placing emphasis on the emotional and subjective associations of the word ”pain”. Many invasive procedures are performed on infants with little or no provision for adequate pain management. The general and specific responses of the neonate to pain must be recognized. Analgesia and anesthesia should be made available to all infants, pre-term or term, sick or well, on the same basis on which they are made available to older children and adults. PMID:21248938

  19. Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test

    PubMed Central

    Hron, Gregor; Knutson, Folke; Thiele, Thomas; Althaus, Karina; Busemann, Christoph; Friesecke, Sigrun; Greinacher, Andreas

    2013-01-01

    Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT. PMID:24102149

  20. Rapid Response of Advanced Squamous Non-Small Cell Lung Cancer with Thrombocytopenia after First-Line Treatment with Pembrolizumab Plus Autologous Cytokine-Induced Killer Cells

    PubMed Central

    Hui, Zhenzhen; Zhang, Xinwei; Ren, Baozhu; Li, Runmei; Ren, Xiubao

    2015-01-01

    We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells. PMID:26734004

  1. Neuroimaging in Neonatal Hypoxic Ischemic Encephalopathy.

    PubMed

    Krishnan, Pradeep; Shroff, Manohar

    2016-09-01

    Magnetic resonance (MR) imaging is emerging as one of the most important tools in identifying the etiology of neonatal encephalopathy as well as in predicting long-term outcomes. This makes it imperative to have a broader understanding of normal myelination of the neonatal brain on MR imaging and to be familiar with the spectrum of imaging features in ischemic and non-ischemic neonatal encephalopathy. Hypoxic ischemic injury (HIE) is one of the most common causes of neonatal encephalopathy and imaging appearances are influenced by factors such as the stage of maturation of the neonatal brain and severity as well as duration of ischemic insult. Other common causes of neonatal encephalopathy include infectious diseases, congenital disorders and inborn errors of metabolism. PMID:26909496

  2. [A neonate with ambiguous genitalia].

    PubMed

    Jansen, Burgo J; van Rijn, Rick R; van Trotsenburg, A S P Paul

    2015-01-01

    In a neonate with ambiguous genitalia, physical examination revealed a phallus. Ultrasonography showed a vagina and uterus, but no gonads. Because of severe undervirilisation in the presence of a uterus, probably due to 46,XY gonadal dysgenesis, parents were advised female sex assignment. When after a few weeks the phallus had increased in size, abdominal laparoscopy showed an underdeveloped uterus. Gonadal biopsy confirmed gonadal dysgenesis. Sex assignment was reconsidered and changed into the male gender. PMID:26200425

  3. Neonatal resuscitation: improving the outcome.

    PubMed

    Davidson, Autumn P

    2014-03-01

    Prudent veterinary intervention in the prenatal, parturient, and postpartum periods can increase neonatal survival by controlling or eliminating factors contributing to puppy morbidity and mortality. Postresuscitation or within the first 24 hours of a natural delivery, a complete physical examination should be performed by a veterinarian, technician, or knowledgeable breeder. Adequate ingestion of colostrum must occur promptly (within 24 hours) postpartum for puppies and kittens to acquire passive immunity. PMID:24580986

  4. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  5. Strategies to reduce neonatal mortality.

    PubMed

    Singh, M

    1990-01-01

    In India, 60% of deaths in infants under 1 year of age occur in the 1st 4 weeks after birth. The neonatal mortality rate is currently 76/1000 live births in rural areas and 39/1000 in urban areas. The Government if India has launched a plan of action of address the cycle of poorly spaced pregnancies, inadequate maternal health care and nutrition, and high incidence of low birthweight babies that contributes to this high neonatal mortality phenomenon. Crucial to such a plan is the expansion, strengthening, and improved organization of maternal-child health services. At the level of maternal health services, efforts will be made to identify pregnant women early, arrange a minimum of 4 prenatal visits, provide dietary supplementation and immunization against tetanus toxoid, create more sterile conditions for home deliveries, identify and refer high-risk pregnancies and deliveries, and provide postnatal follow-up care. Child health service staff are motivating mothers to breastfeed and screening newborns for jaundice and bacterial infection. A risk approach, in which there is a minimum necessary level of care for all pregnant women but more intensive management and follow-up of those at high risk, is most cost-efficient given the lack of human and financial resources. Attention must also be given to the determinants of low birthweight (maternal undernutrition, closely spaced pregnancies, severe anemia, adolescent childbearing, prenatal infections, strenuous work responsibilities, and maternal hypertension), which is a co-factor in neonatal mortality. PMID:12316586

  6. Neonatal asphyxia and forensic medicine.

    PubMed

    d'Aloja, E; Müller, M; Paribello, F; Demontis, R; Faa, A

    2009-01-01

    In the last decades, the scientific literature addressing neonatal encephalopathy has grown in a logarithmic way and malpractice claims in obstetrics and neonatology have become a major threat to the health service. At the moment, scientific evidence are insufficient to clearly identify in each single case whether the hypoxic insult has developed in the course of labor or in the first few hours after the birth or, otherwise, whether the damage has to recognize a remote and long-lasting cause acting during pregnancy. Several authors feel that this scientific uncertainty leads to a higher percentage of civil suit decisions prone to recognizing a guilty medical behavior, and they wish a more in-depth analysis of all these cases to clearly identify all the data either in favor or in contrary to the assumption of the existence of a causal correlation between neonatal encephalopathy and medical misbehavior. This article will focus on the medico-legal approach to a hypoxic-ischemic event in the perinatal period, addressing the relevant data to be collected in order to establish the medical and juridical cause of the neonatal damage. PMID:19757333

  7. Bone Marrow Suppression and Hemophagocytic Histiocytes Are Common Findings in Korean Severe Fever with Thrombocytopenia Syndrome Patients.

    PubMed

    Shin, Sang Yong; Cho, Oh Hyun; Bae, In Gyu

    2016-09-01

    The causes of cytopenia in patients with severe fever with thrombocytopenia syndrome (SFTS) are not fully understood until now. We reviewed the bone marrow (BM) findings of patients with SFTS to unravel the cause of the cytopenia. Three Korean SFTS were enrolled in this study. Thrombocytopenia, neutropenia, and anemia were detected in all three patients. Severe hypocellular marrow (overall cellularity <5%) and a decreased number of megakaryocytes were noted in one patient, and hypo-/normocellular marrow and an increased number of hemophagocytic histiocytes were observed in two patients. Megakaryocytes were relatively preserved in two patients. Although a limited number of cases are available, our observations suggest that both BM suppression and peripheral destruction or sequestration are causes of cytopenia of patients with SFTS. To the best of our knowledge, this is the first well documented pathologic evaluation of Korean SFTS. PMID:27401664

  8. Seroprevalence and risk factors for severe fever with thrombocytopenia syndrome virus infection in Jiangsu Province, China, 2011.

    PubMed

    Liang, Shuyi; Bao, Changjun; Zhou, Minghao; Hu, Jianli; Tang, Fenyang; Guo, Xiling; Jiao, Yongjun; Zhang, Wenshuai; Luo, Peilin; Li, Luxun; Zhu, Kuanyuan; Tan, Wenwen; Lu, Qimei; Ge, Hengming; Chen, Abao

    2014-02-01

    Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel bunyavirus, is an emerging infectious disease in China. In 2011, this new virus was designated as severe fever with thrombocytopenia syndrome virus (SFTSV). The aim of the present study was to determine the seroprevalence and risk factors of SFTSV infection. The investigation was conducted among the general population in Jiangsu Province, China in 2011. A total of 2,510 serum samples were collected. Testing by enzyme-linked immunosorbent assay was conducted to determine the seroprevalence of SFTSV infection. Result showed that the overall seroprevalence of SFTSV infection was 0.44% (11 of 2,510) in seven counties in Jiangsu Province. Multiple variable logistic regression analysis showed that raising goats, farming, and grazing were risk factors for SFTSV infection. Raising goats, farming, and grazing might be important risk factors for virus exposure, and appropriate health education could be useful in preventing infections. PMID:24343883

  9. Immune Thrombocytopenia (ITP) Secondary to Subclinical Hashimoto's Thyroiditis: Role of Levothyroxine in Improving the Clinical Outcome of ITP.

    PubMed

    Tahir, Hassan; Sheraz, Faizan; Sagi, Jahnavi; Daruwalla, Vistasp

    2016-01-01

    Immune thrombocytopenia (ITP) is the most common cause of isolated thrombocytopenia in healthy people. ITP may rarely coexist with autoimmune thyroid disorders, which may indicate more complex defect in immune system. Primary ITP usually responds well to steroids and intravenous immunoglobulins. However, ITP may be difficult to treat when associated with thyroid autoimmune disorders. In such cases, treating the underlying thyroid disorder may significantly improve platelet count and can either cause remission of disease or improve response to standard ITP therapy. We report a case of 47-year-old male who was diagnosed with ITP and was also found to have subclinical Hashimoto's thyroiditis. Treatment of subclinical hypothyroidism with levothyroxine in our patient significantly improved the platelets, thus successfully bringing the disease in remission. PMID:27200380

  10. Clinical Manifestations and Predictors of Thrombocytopenia in Hospitalized Adults with Dengue Fever

    PubMed Central

    Aroor, Akshatha Rao; Saya, Rama Prakasha; Sharma, Ajitha; Venkatesh, Anuroop; Alva, Rhea

    2015-01-01

    Background: India is one of the seven identified Southeast Asian countries reporting frequent outbreaks of dengue fever (DF). Aims: This study was to analyze clinical and laboratory profile and predictive markers of thrombocytopenia and length of hospital stay in DF. Materials and Methods: This record-based retrospective study conducted in a coastal district of Karnataka, South India, included all dengue cases in adults aged >18 years, admitted during period of January 2011 to December 2014. Multivariate logistic regression analysis was carried out to compute odds ratio (OR) and 95% confidence interval (CI) to assess independent associations of variables with low platelet count and longer duration of hospital stay. Results: Among 207 dengue immunoglobulin M (IgM) antibody confirmed cases (mean age of 36.94 ± 14.61 years), 143 (69.1%) were males and 64 were females. The mean duration of illness and hospital stay were 4.94 ± 3.58 days and 5.98 ± 2.58 days, respectively. Abdominal symptoms included nausea and vomiting (53.6%), abdominal pain (25.1%), and diarrhea (13.5%). Bleeding manifestations were seen in 24 (11.6%) cases and fluid accumulation was revealed in 18 (8.7%) cases. The mean platelet count was 110,159.42 ± 68,397.32 (cells/mm3). Low platelet count on admission was associated with the presence of rash (OR = 0.43, 95% CI 0.23-0.81), high aspartate aminotransferase (AST) levels (OR = 3.14, 95% CI 1.58-6.23), high alanine aminotransferase (ALT) levels (OR = 2.91, 95% CI 1.55-5.47), and low albumin levels (OR = 4.48, 95% CI 1.02-19.75). The duration of hospital stay was associated with diarrhea (OR = 0.4, 95% CI 0.18-0.9), abdominal pain (OR = 0.52, 95% CI 0.27-1.00), ascites (OR = 0.26, 95% CI 0.09-0.69), and low hemoglobin (OR = 0.46, 95% CI 0.25-0.86) level on admission. Conclusions: Though thrombocytopenia on admission was associated with the presence of rash, high AST and ALT levels, and low albumin levels, it was not predictive of length of

  11. Malsoor Virus, a Novel Bat Phlebovirus, Is Closely Related to Severe Fever with Thrombocytopenia Syndrome Virus and Heartland Virus

    PubMed Central

    Yadav, P. D.; Basu, A.; Shete, A.; Patil, D. Y.; Zawar, D.; Majumdar, T. D.; Kokate, P.; Sarkale, P.; Raut, C. G.; Jadhav, S. M.

    2014-01-01

    During a survey in the year 2010, a novel phlebovirus was isolated from the Rousettus leschenaultii species of bats in western India. The virus was identified by electron microscopy from infected Vero E6 cells. Phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (SFTS) and Heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus. PMID:24390329

  12. Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin β minor chain

    PubMed Central

    Kauppi, Maria; Hilton, Adrienne A.; Metcalf, Donald; Ng, Ashley P.; Hyland, Craig D.; Collinge, Janelle E.; Kile, Benjamin T.; Hilton, Douglas J.; Alexander, Warren S.

    2012-01-01

    Diverse mutations in the genes encoding hemoglobin (Hb) have been characterized in human disease. We describe here a mutation in the mouse Hbb-b2 gene, denoted Plt12, that precisely mimics the human hemoglobin Hotel Dieu variant. The mutation results in increased affinity of Hb for oxygen and Plt12 mutant mice exhibited reduced partial pressure of O2 in the blood, accompanied by erythrocytosis characterized by elevated erythropoietin levels and splenomegaly with excess erythropoiesis. Most homozygous Hbb-b2Plt12/Plt12 mice succumbed to early lethality associated with emphysema, cardiac abnormalities, and liver degeneration. Survivors displayed a marked thrombocytopenia without significant deficiencies in the numbers of megakaryocytes or megakaryocyte progenitor cells. The lifespan of platelets in the circulation of Hbb-b2Plt12/Plt12 mice was normal, and splenectomy did not correct the thrombocytopenia, suggesting that increased sequestration was unlikely to be a major contributor. These data, together with the observation that megakaryocytes in Hbb-b2Plt12/Plt12 mice appeared smaller and deficient in cytoplasm, support a model in which hypoxia causes thrombocytopenia as a consequence of an inability of megakaryocytes, once formed, to properly mature and produce sufficient platelets. The Plt12 mouse is a model of high O2-affinity hemoglobinopathy and provides insights into hematopoiesis under conditions of chronic hypoxia. PMID:22203977

  13. Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin β minor chain.

    PubMed

    Kauppi, Maria; Hilton, Adrienne A; Metcalf, Donald; Ng, Ashley P; Hyland, Craig D; Collinge, Janelle E; Kile, Benjamin T; Hilton, Douglas J; Alexander, Warren S

    2012-01-10

    Diverse mutations in the genes encoding hemoglobin (Hb) have been characterized in human disease. We describe here a mutation in the mouse Hbb-b2 gene, denoted Plt12, that precisely mimics the human hemoglobin Hotel Dieu variant. The mutation results in increased affinity of Hb for oxygen and Plt12 mutant mice exhibited reduced partial pressure of O(2) in the blood, accompanied by erythrocytosis characterized by elevated erythropoietin levels and splenomegaly with excess erythropoiesis. Most homozygous Hbb-b2(Plt12/Plt12) mice succumbed to early lethality associated with emphysema, cardiac abnormalities, and liver degeneration. Survivors displayed a marked thrombocytopenia without significant deficiencies in the numbers of megakaryocytes or megakaryocyte progenitor cells. The lifespan of platelets in the circulation of Hbb-b2(Plt12/Plt12) mice was normal, and splenectomy did not correct the thrombocytopenia, suggesting that increased sequestration was unlikely to be a major contributor. These data, together with the observation that megakaryocytes in Hbb-b2(Plt12/Plt12) mice appeared smaller and deficient in cytoplasm, support a model in which hypoxia causes thrombocytopenia as a consequence of an inability of megakaryocytes, once formed, to properly mature and produce sufficient platelets. The Plt12 mouse is a model of high O(2)-affinity hemoglobinopathy and provides insights into hematopoiesis under conditions of chronic hypoxia. PMID:22203977

  14. Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites.

    PubMed

    Santhosh, M Sebastin; Thushara, R M; Hemshekhar, M; Sunitha, K; Devaraja, S; Kemparaju, K; Girish, K S

    2013-11-01

    Viper envenomations are characterized by prominent local and systemic manifestations including hematological alterations. Snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2) plays crucial role in the pathophysiology of hemorrhage by targeting/altering the platelets function which may result in thrombocytopenia. Platelets undergo the classic events of mitochondria-mediated apoptotic pathway due to augmented endogenous reactive oxygen species (ROS) levels. The observed anticoagulant effects during viper envenomations could be due to exacerbated platelet apoptosis and thrombocytopenia. Moreover, antivenin treatments are ineffective against the venom-induced oxidative stress; therefore, it necessitates an auxiliary therapy involving antioxidants which can effectively scavenge the endothelium-generated/endogenous ROS and protect the platelets. The present study explored the effects of viper venom on platelet apoptosis and its amelioration by a phytochemical crocin. The study evaluated the Vipera russelli venom-induced apoptotic events including endogenous ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation and phosphatidylserine externalization which were effectively mitigated when the venom was pre-treated with crocin. The study highlights one of the less studied features of venom-induced secondary complications i.e. platelet apoptosis and sheds light on the underlying basis for venom-induced thrombocytopenia, systemic hemorrhage and in vivo anticoagulant effect. PMID:23412973

  15. Vitamin B12 and vitamin d deficiencies: an unusual cause of Fever, severe hemolytic anemia and thrombocytopenia.

    PubMed

    Mishra, Vikas A; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  16. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    PubMed Central

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  17. Spleen enlargement is a common finding in acute Puumala hantavirus infection and it does not associate with thrombocytopenia.

    PubMed

    Koskela, Sirpa M; Laine, Outi K; Paakkala, Antti S; Mäkelä, Satu M; Mustonen, Jukka T

    2014-10-01

    The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury. PMID:25119440

  18. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived. PMID:26945262

  19. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    PubMed Central

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  20. Expression of CD11a in lymphocyte subpopulation in immune thrombocytopenia

    PubMed Central

    Liu, Yan-Xia; Zhang, Feng; Yao, Qing-Min; Yuan, Ting; Xu, Jian; Zhu, Xiao-Juan

    2015-01-01

    Recent research demonstrates that the underlying mechanism in immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important roles in autoimmune diseases. The purpose of this study was to investigate the expression of CD11a on lymphocytes and explore its possible role in ITP. The expression of CD11a on lymphocyte subpopulations (CD3+ T cells, CD3+CD4+ T cells, CD3+CD4- T cells, CD4+Foxp3+ T regulatory cells and CD19+ B cells) were analyzed by flow cytometry. Specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). The mean fluorescence intensity of CD11a on CD3+ T, CD3+CD4- T and CD19+ B lymphocytes were increased in ITP patients compared to healthy controls. No significant difference of CD11a expression on CD3+CD4+ T cells or CD4+Foxp3+ T regulatory cells was found between ITP patients and controls. Our data indicates the possible role of CD11a in the pathogenesis of ITP. PMID:26884833

  1. Expression of CD11a in lymphocyte subpopulation in immune thrombocytopenia.

    PubMed

    Liu, Yan-Xia; Zhang, Feng; Yao, Qing-Min; Yuan, Ting; Xu, Jian; Zhu, Xiao-Juan

    2015-01-01

    Recent research demonstrates that the underlying mechanism in immune thrombocytopenia (ITP) is very complex. Lymphocyte function associated antigen-1 (LFA-1) plays important roles in autoimmune diseases. The purpose of this study was to investigate the expression of CD11a on lymphocytes and explore its possible role in ITP. The expression of CD11a on lymphocyte subpopulations (CD3(+) T cells, CD3(+)CD4(+) T cells, CD3(+)CD4(-) T cells, CD4(+)Foxp3(+) T regulatory cells and CD19(+) B cells) were analyzed by flow cytometry. Specific anti-platelet GPIIb/IIIa and/or GPIb/IX autoantibodies were assayed by modified monoclonal antibody specific immobilization of platelet antigens (MAIPA). The mean fluorescence intensity of CD11a on CD3(+) T, CD3(+)CD4(-) T and CD19(+) B lymphocytes were increased in ITP patients compared to healthy controls. No significant difference of CD11a expression on CD3(+)CD4(+) T cells or CD4(+)Foxp3(+) T regulatory cells was found between ITP patients and controls. Our data indicates the possible role of CD11a in the pathogenesis of ITP. PMID:26884833

  2. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

    PubMed Central

    Audia, Sylvain; Samson, Maxime; Guy, Julien; Janikashvili, Nona; Fraszczak, Jennifer; Trad, Malika; Ciudad, Marion; Leguy, Vanessa; Berthier, Sabine; Petrella, Tony; Aho-Glélé, Serge; Martin, Laurent; Maynadié, Marc; Lorcerie, Bernard; Rat, Patrick; Cheynel, Nicolas; Katsanis, Emmanuel; Larmonier, Nicolas

    2011-01-01

    Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug. PMID:21876120

  3. Systemic neosporosis in a dog treated for immune-mediated thrombocytopenia and hemolytic anemia.

    PubMed

    Magaña, Angie; Sánchez, Félix; Villa, Karina; Rivera, Liliana; Morales, Elizabeth

    2015-12-01

    A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case. PMID:26345698

  4. Thrombocytopenia resulting from mutations in filamin A can be expressed as an isolated syndrome.

    PubMed

    Nurden, Paquita; Debili, Najet; Coupry, Isabelle; Bryckaert, Marijke; Youlyouz-Marfak, Ibtissam; Solé, Guilhem; Pons, Anne-Cécile; Berrou, Eliane; Adam, Frédéric; Kauskot, Alexandre; Lamazière, Jean-Marie Daniel; Rameau, Philippe; Fergelot, Patricia; Rooryck, Caroline; Cailley, Dorothée; Arveiler, Benoît; Lacombe, Didier; Vainchenker, William; Nurden, Alan; Goizet, Cyril

    2011-11-24

    Filaminopathies A caused by mutations in the X-linked FLNA gene are responsible for a wide spectrum of rare diseases including 2 main phenotypes, the X-linked dominant form of periventricular nodular heterotopia (FLNA-PVNH) and the otopalatodigital syndrome spectrum of disorders. In platelets, filamin A (FLNa) tethers the principal receptors ensuring the platelet-vessel wall interaction, glycoprotein Ibα and integrin αIIbβ3, to the underlying cytoskeleton. Hemorrhage, coagulopathy, and thrombocytopenia are mentioned in several reports on patients with FLNA-PVNH. Abnormal platelet morphology in 2 patients with FLNA-PVNH prompted us to examine a third patient with similar platelet morphology previously diagnosed with immunologic thrombocytopenic purpura. Her enlarged platelets showed signs of FLNa degradation in Western blotting, and a heterozygous missense mutation in FLNA was detected. An irregular distribution of FLNa within the total platelet population was shown by confocal microscopy for all 3 patients. In vitro megakaryocyte cultures showed an abnormal differentiation, including an irregular distribution of FLNa with a frayed aspect, the presence of enlarged α-granules, and an abnormal fragmentation of the cytoplasm. Mutations in FLNA may represent an unrecognized cause of macrothrombocytopenia with an altered platelet production and a modified platelet-vessel wall interaction. PMID:21960593

  5. The Effect of Rituximab on Vaccine Responses in Patients with Immune Thrombocytopenia

    PubMed Central

    Nazi, Ishac; Kelton, John G.; Larché, Mark; Snider, Denis P.; Heddle, Nancy M.; Crowther, Mark A.; Cook, Richard J.; Tinmouth, Alan T.; Mangel, Joy; Arnold, Donald M.

    2013-01-01

    B-cell depletion therapy may impair vaccine responses and increase infection risk in patients with immune thrombocytopenia (ITP). Capitalizing on a multicenter randomized placebo-controlled trial, we investigated the effects of rituximab on the antibody and cellular responses to Streptococcus pneumoniae polysaccharide vaccine and Haemophilus influenzae type b (Hib) conjugate vaccine in ITP patients. Of 60 patients in the main trial, 24 patients received both vaccines 6 months after rituximab (n=17) or placebo (n=7). Among 20 evaluable patients, 3/14 (21%) in the rituximab group and 4/6 (67%) in the placebo group achieved a 4-fold increase in anti-pneumococcal antibodies (p=0.12). For anti-Hib antibodies, 4/14 (29%) and 5/6 (83%), respectively, achieved a 4-fold increase (p<0.05). Fewer patients in the rituximab group demonstrated functional Hib killing (2/14 [14%] versus 5/6 [83%], p<0.05). Three of 14 rituximab-treated patients failed to respond to vaccines by any criteria. After vaccinations, pre-plasma cell blasts and interferon-γ secreting T-cells were reduced in rituximab-treated patients. We found that antibody responses were impaired for at least 6 months after rituximab. Cellular immunity was reduced in parallel with the depleted B-cell pool. These findings have implications for the timing of vaccinations and the mechanism of infection after rituximab in patients with ITP. PMID:23851398

  6. [Primary immune thrombocytopenia in adults in Mexico: national characteristics and the relation to international literature].

    PubMed

    Meillón-García, Luis Antonio; García-Chávez, Jaime; Gómez-Almaguer, David; Gutiérrez-Espíndola, Guillermo R; Martínez-Murillo, Carlos

    2014-01-01

    In order to identify the clinical approach of a sample of Mexican hematologists for primary immune thrombocytopenia (ITP) in adults in Mexico, we applied an electronic survey via the internet to identify common practices for the diagnosis and treatment of ITP and draw a comparison between the information from these hematologists with international guidelines or the international literature. The results were analyzed using measures of central tendency. The sample was 21 medical hematologists, predominantly from Mexico City (average age: 51.4 years). A total of 66.7% of the surveyed physicians use international guidelines to make therapeutic decisions, and 43% defined ITP including the numerical concept (< 100 x 10(9)/l). We found some differences between requested clinical exams and tests indicated by the guidelines. In first-line treatment (except emergency), 91% of the participants start with prednisone and 24% use dexamethasone. Danazol is used in persistent ITP by most (41%) of the specialists. In second-line treatment, 67% would indicate splenectomy. Some differences were found between clinical practice of the hematologists in Mexico versus guidelines recommendations. PMID:25098212

  7. Atomic description of the immune complex involved in heparin-induced thrombocytopenia

    DOE PAGESBeta

    Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; Rauova, Lubica; Hayes, Vincent; Lebedeva, Tatiana; Liu, Qun; Poncz, Mortimer; Arepally, Gowthami; Cines, Douglas B.; et al

    2015-09-22

    Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

  8. Atomic description of the immune complex involved in heparin-induced thrombocytopenia

    PubMed Central

    Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; Rauova, Lubica; Hayes, Vincent; Lebedeva, Tatiana; Liu, Qun; Poncz, Mortimer; Arepally, Gowthami; Cines, Douglas B.; Greene, Mark I.

    2015-01-01

    Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed' end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open' end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize' the ternary pathogenic immune complex. Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. The atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT. PMID:26391892

  9. Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies.

    PubMed

    Langeberg, Wendy J; Schoonen, W Marieke; Eisen, Melissa; Gamelin, Laurence; Stryker, Scott

    2016-06-01

    This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists. PMID:27084254

  10. Thrombocytopenia in common variable immunodeficiency patients – clinical course, management, and effect of immunoglobulins

    PubMed Central

    Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2015-01-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose. PMID:26155188

  11. Shared decision making in the management of children with newly diagnosed immune thrombocytopenia.

    PubMed

    Beck, Carolyn E; Boydell, Katherine M; Stasiulis, Elaine; Blanchette, Victor S; Llewellyn-Thomas, Hilary; Birken, Catherine S; Breakey, Vicky R; Parkin, Patricia C

    2014-10-01

    This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP. PMID:24577546

  12. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    PubMed

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar

    2016-02-01

    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration. PMID:26628061

  13. Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment.

    PubMed

    Burenbatu; Borjigin, Mandula; Eerdunduleng; Huo, Wenyan; Gong, Cuiqin; Hasengaowa; Zhang, Guiping; Longmei; Li, Ming; Zhang, Xuemei; Sun, Xiaohui; Yang, Jie; Wang, Shuanglian; Narisu, Narisu; Liu, Yangjian; Bai, Haihua

    2015-10-01

    Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy. PMID:26297543

  14. The laboratory diagnosis and clinical management of patients with heparin-induced thrombocytopenia: an update.

    PubMed

    Prechel, Margaret; Walenga, Jeanine M

    2008-02-01

    Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin exposure that can progress to severe thrombosis, amputation, or death. HIT is an immune response in which antibodies cause platelet activation, platelet aggregation, the generation of procoagulant platelet microparticles, and activation of leukocytes and endothelial cells. Early diagnosis based on a comprehensive interpretation of clinical and laboratory information is important to improve clinical outcomes. However, limitations of the laboratory assays and atypical clinical presentations can make the diagnosis difficult. Clinical management of patients with HIT is with a non-heparin anticoagulant such as a direct thrombin inhibitor or danaparoid followed by a vitamin K antagonist for long-term treatment. The new anti-factor Xa drugs (fondaparinux, rivaroxaban, apixaban) and other non-heparin antithrombotic agents can potentially be used for the treatment of HIT if clinically validated. Important drug-specific limitations and dosing and monitoring guidelines must be respected for patient safety. Issues still exist regarding the optimal clinical management of HIT. PMID:18393145

  15. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.

    PubMed

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  16. Thrombocytopenia with reticulin fibrosis accompanied by fever, anasarca and hepatosplenomegaly : a clinical report of five cases.

    PubMed

    Takai, Kazue; Nikkuni, Koji; Momoi, Akihito; Nagai, Koichi; Igarashi, Natsue; Saeki, Takako

    2013-01-01

    We report five cases that presented with high fever, anasarca, hepatosplenomegaly and severe thrombocytopenia with reticulin fibrosis of the bone marrow. The constellation of symptoms is not compatible with any known disease, and we had difficulty in diagnosis and treatment. The age distribution was from 47 to 56 years, and two men and three women were affected. Two patients needed hemodialysis because of renal dysfunction and oliguria with massive pleural effusion. Laboratory examinations showed normal immunoglobulin levels and no monoclonal protein. None of them showed diagnostic autoantibodies for any autoimmune diseases. Histological examination of the liver in three patients and spleen in two showed non-specific findings. Lymphadenopathy was tiny and lymph node biopsy was carried out in only one case. Histologically, paracortical hyperplasia with vascular proliferation and atrophic germinal centers resembling hyaline-vascular-type Castleman's disease or POEMS syndrome were detected. Without a definitive diagnosis, treatment was started with cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP) regimen in one patient, semi-pulse therapy with methyl-predonisolone in three and cyclosporin A in three. Two patients achieved complete remission, two were steroid-dependent and the remaining one died of multiple organ failure. These findings suggest that this disease may be a novel clinical entity belonging to systemic inflammatory disorder with a background of immunological abnormality or a unique variant of multicentric Castleman's disease. [J Clin Exp Hematop 53(1): 63-68, 2013]. PMID:23801136

  17. A National Assessment of the Epidemiology of Severe Fever with Thrombocytopenia Syndrome, China

    PubMed Central

    Liu, Kun; Zhou, Hang; Sun, Ruo-Xi; Yao, Hong-Wu; Li, Yu; Wang, Li-Ping; Di Mu; Li, Xin-Lou; Yang, Yang; Gray, Gregory C.; Cui, Ning; Yin, Wen-Wu; Fang, Li-Qun; Yu, Hong-Jie; Cao, Wu-Chun

    2015-01-01

    First discovered in rural areas of middle-eastern China in 2009, severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis affecting hundreds of cases reported in China each year. Using the national surveillance data from 2010 to 2013, we conducted this retrospective epidemiological study and risk assessment of SFTS in China. We found that the incidence of SFTS and its epidemic areas are continuing to grow, but the case fatality rate (CFR) has steadily decreased. SFTS most commonly affected elderly farmers who acquired infection between May and July in middle-eastern China. However, other epidemiological characteristics such as incidence, sex ratio, CFR, and seasonality differ substantially across the affected provinces, which seem to be consistent with local agricultural activities and the seasonal abundance of ticks. Spatial scan statistics detected three hot spots of SFTS that accounted for 69.1% of SFTS cases in China. There was a strong association of SFTS incidence with temporal changes in the climate within the clusters. Multivariate modeling identified climate conditions, elevation, forest coverage, cattle density, and the presence of Haemaphysalis longicornis ticks as independent risk factors in the distribution of SFTS, based on which a predicted risk map of the disease was derived. PMID:25902910

  18. Detection and evaluation of immunofunction of patients with severe fever with thrombocytopenia syndrome.

    PubMed

    Sun, Liping; Hu, Yanjie; Niyonsaba, Aime; Tong, Qiaoxia; Lu, Li; Li, Huiyu; Jie, Shenghua

    2014-11-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection. PMID:24068614

  19. Anti-D treatment for pediatric immune thrombocytopenia: Is the bad reputation justified?

    PubMed

    Yacobovich, Joanne; Abu-Ahmed, Sabreen; Steinberg-Shemer, Orna; Goldberg, Tracie; Cohen, Miriam; Tamary, Hannah

    2016-04-01

    The purpose of this study was to assess the efficacy and side effect profile of the repeated use of anti-D for the treatment of pediatric immune thrombocytopenia (ITP) in a large pediatric hematology center. We performed a retrospective analysis of patient records for children (aged 4 months-18 years) treated for ITP at Schneider Children's Medical Center of Israel from 1995-2015. Demographic and clinical data, reported adverse events, and therapy response were extracted from written and electronic files for all patients having received anti-D. Therapy response was defined as time to platelet count >30 x 10(9)/L. Thirty-six patients received 170 treatments of anti-D at a dose of 75 μg/kg. The majority were previously treated with corticosteroids and/or intravenous immunoglobulin (IVIG). Minimal adverse events were recorded including fever (3.5%), vomiting (2.9%), and headaches (1.7%). Notably only 1/170 treatments required blood transfusion and no life-threatening events occurred. The average time to platelets >30 x 10(9)/L was 2.3 days, with a median of 1 day, range 1-12 days. Despite the reported severe adverse events in mainly elderly patients, the use of anti-D can be safe and effective in carefully chosen, low-risk pediatric patients with ITP. PMID:27312170

  20. Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience

    PubMed Central

    Özdemirkıran, Füsun; Payzın, Bahriye; Kiper, H. Demet; Kabukçu, Sibel; Akgün Çağlıyan, Gülsüm; Kahraman, Selda; Sevindik, Ömür Gökmen; Ceylan, Cengiz; Kadıköylü, Gürhan; Şahin, Fahri; Keskin, Ali; Arslan, Öykü; Özcan, Mehmet Ali; Görgün, Gülnur; Bolaman, Zahit; Büyükkeçeçi, Filiz; Bilgir, Oktay; Alacacıoğlu, İnci; Vural, Filiz; Tombuloğlu, Murat; Gökgöz, Zafer; Saydam, Güray

    2015-01-01

    Objective: Immune thrombocytopenia (ITP) is an immune-mediated disease characterized by transient or persistent decrease of the platelet count to less than 100x109/L. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists, which came into use in recent years, seem to be an effective option in the treatment of resistant cases. This study aimed to retrospectively assess the efficacy, long-term safety, and tolerability of eltrombopag in Turkish patients with chronic ITP in the Aegean region of Turkey. Materials and Methods: Retrospective data of 40 patients with refractory ITP who were treated with eltrombopag in the Aegean region were examined and evaluated. Results: The total rate of response was 87%, and the median duration of response defined as the number of the platelets being over 50x109/L was 19.5 (interquartile range: 5-60) days. In one patient, venous sinus thrombosis was observed with no other additional risk factors due to or related to thrombosis. Another patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of probable acute myocardial infarction. Conclusion: Although the responses to eltrombopag were satisfactory, patients need to be monitored closely for overshooting platelet counts as well as thromboembolic events. PMID:25914025