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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.

  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. Severe intracranial haemorrhage in neonatal alloimmune thrombocytopenia

    PubMed Central

    Silva, Francisco; Morais, Sofia; Sevivas, Teresa; Veiga, Ricardo; Salvado, Ramon; Taborda, Adelaide

    2011-01-01

    Neonatal alloimmune thrombocytopenia is a rare (1/1000–5000 births) life-threatening disorder, caused by fetomaternal incompatibility for a fetal human platelet alloantigen inherited from the father, with production of maternal alloantibodies against fetal platelets, leading to severe thrombocytopenia and potential bleeding. Intracranial haemorrhage is the most feared complication. This report presents the case of a term newborn infant, born from caesarean section after a normal pregnancy, presenting signs of skin bleeding with different ages. Obstetric history included a previous spontaneous abortion after amniocentesis. Severe thrombocytopenia (4×109/l platelets) was found and brain ultrasound showed multiple intracranial haemorrhages. Human platelet antigen (HPA) phenotyping showed maternal negative HPA-1a and paternal positive HPA-1a platelets. Strongly positive anti-HPA-1a and weakly positive anti-human leukocyte antigen class I alloantibodies were found in the mother. Multiple platelet transfusions, intravenous immunoglobulin and corticosteroid were given but favourable response was accomplished only after a compatible platelet transfusion. Brain MRI showed multiple subacute and chronic haemorrhages. PMID:22679192

  6. Prediction of neonatal alloimmune thrombocytopenia using PCR.

    PubMed

    Marshall, L R; Jones, C; Munro, T E

    1994-01-01

    Neonatal alloimmune thrombocytopenia (NAIT) is a potentially fatal condition and in the majority of cases is associated with maternal antibodies to the HPA-1a (PLA1) haplotype. Early diagnosis in utero can enhance survival rates. The application of DNA genomic analysis and PCR technology for the determination of the HPA-1a/HPA-1b (PLA1/PLA2) locus is described and applied in a family study where the fetus was diagnosed to have NAIT. This rapid technique differentiated between the 3 haplotypes HPA-1a/HPA-1a, HPA-1b/HPA-1b and HPA-1a/HPA-1b using the polymorphism at base 196 of the GPIIIa gene. This is the first Australian report on the establishment of this technology for platelet genotype typing and the application in the diagnosis of NAIT. This technique can be performed on DNA extracted from any nucleated cells and avoids the difficulty of requiring fetal platelets for serological typing when NAIT is suspected. The PCR technique of genomic DNA analysis has an important application in the prediction and management of this potentially severe condition.

  7. Neonatal alloimmune thrombocytopenia due to HLA-A2 antibody.

    PubMed

    Chow, M P; Sun, K J; Yung, C H; Hu, H Y; Tzeng, J L; Lee, T D

    1992-01-01

    A male, full-term baby with thrombocytopenia was born by a G3P2A1 mother who was not associated with autoimmune disease. Platelet antibody screening was positive by using lymphocytotoxicity test, platelet suspension immunofluorescence test and solid-phase red cell adherence test. The identified HLA antibody was of A2 specificity. It was confirmed by testing the mother's and the baby's sera against the lymphocytes and platelets of 10 HLA-A2-positive donors. The possibility of platelet-specific antibody as the cause of neonatal alloimmune thrombocytopenia was ruled out by testing against platelets of 10 HLA-A2-negative donors and the known platelet-specific antigens utilizing immobilized, purified platelet glycoprotein as targets. The mother's serum reacted strongly with both the father's and the baby's platelets and lymphocytes. This neonatal thrombocytopenia was most likely due to the maternal HLA antibody, which was induced by her antecedent gestations.

  8. 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

  9. 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

  10. Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

    PubMed

    Avent, Neil D

    2014-12-01

    Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

  11. 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

  12. 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).

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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

  18. Neonatal alloimmune thrombocytopenia in Taiwan due to an antibody against a labile component of HPA-3a (Baka).

    PubMed

    Lin, M; Shieh, S H; Liang, D C; Yang, T F; Shibata, Y

    1995-01-01

    We report on two siblings who developed severe neonatal alloimmune thrombocytopenia (NAIT) due to an alloantibody against a labile component or components of the HPA-3a (Baka) antigen. The antibody reacted only with fresh, unfixed platelets by the solid-phase red cell adherence test, immunofluorescence test and mixed passive haemagglutination test. In the latter method, weakly fixed platelets also gave a weak positive reaction. Monoclonal-antibody-specific immobilization of platelet antigens and immunoblotting tests gave negative results. Our findings may possibly help to explain why in some cases of NAIT no platelet-specific antibody is demonstrable in tests with fixed or solubilized platelets.

  19. Provision of HPA-1a (PlA1)-negative platelets for neonatal alloimmune thrombocytopenia: screening, testing, and transfusion protocol.

    PubMed

    Munizza, M; Nance, S; Keashen-Schnell, M A; Sherwood, W; Murphy, S

    1999-01-01

    HPA-1a-negative platelet products are not routinely available for newborns with alloimmune thrombocytopenia. In this article we describe a program established to identify normal pheresis donors who are HPA-1a-negative and to organize their future donations so that our regional blood center would always have an HPA-1a-negative platelet product available. The solid phase red cell adherence assay was used for initial screening of platelet pheresis products. HPA-1a-negative donors were confirmed with the platelet suspension immunofluorescence test using three anti-HPA-1a sera. Screening of 2600 plateletpheresis donor samples identified 40 HPA-1a-negative donors. Of these, 36 are active and are coded for recognition on the daily pheresis inventory sheet. Theoretically, assuming four donations per year and donors' cooperation with scheduling, these 36 donors would enable us to have at least one HPA-1a-negative product available every day. In addition, a decision tree for patient management using platelet serology and availability of HPA-1a-negative products was developed. The GTI-PAK trade mark 12 is the major technique used for serologic screening of mothers of patients thought to have neonatal alloimmune thrombocytopenia. By screening pheresis donors and developing a clinical decision tree, HPA-1a-negative products, a rare resource, can be fully utilized.

  20. 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

  1. [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

  2. 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

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

    PubMed Central

    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

  4. 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

  5. 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

  6. 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

  7. [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.

  8. [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

  9. Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia.

    PubMed

    Li, Conglei; Chen, Pingguo; Vadasz, Brian; Ma, Li; Zhou, Hui; Lang, Sean; Freedman, John; Ni, Heyu

    2013-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. IntegrinαIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

  10. 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

  11. 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

  12. A case of neonatal alloimmune thrombocytopenia in the presence of both anti-HPA-4b and anti-HPA-5b antibody: clinical and serological analysis of the subsequent pregnancy.

    PubMed

    Kiyokawa, Tomoko; Koh, Yangsook; Mimura, Kazuya; Nakayama, Kotarosumitomo; Hosokawa, Mika; Sakuragi, Mikiko; Morikawa, Tamayo; Nakao, Mayumi; Aochi, Hiroshi; Fukumori, Yasuo; Kanagawa, Takeshi; Nagamine, Keisuke; Kimura, Tadashi; Tomiyama, Yoshiaki

    2014-10-01

    Neonatal alloimmune thrombocytopenia (NAIT) is induced by maternal alloantibodies raised against fetal platelet antigens inherited from the paternal parent. In contrast to Caucasians, in Asians, predominantly in Japanese, most frequently detected antibodies in NAIT are anti-HPA-4b and anti-HPA-5b. In some NAIT cases multiple alloantibodies are detected. In such cases it is very difficult to determine which antibody is the dominant antibody in NAIT. In this case report, we describe a NAIT case (first sibling) with severe thrombocytopenia and cephalhematoma in the presence of both anti-HPA-4b and anti-HPA-5b antibodies in the maternal serum. We carefully examined titers of anti-HPA antibodies during the subsequent pregnancy with HPA-4b-positive and HPA-5b-negative fetus determined by amniocentesis at gestational week 16. We administered IVIG (1 g/kg/w) to the mother from gestational week 32 to 35. The mother subsequently delivered a second sibling with normal platelet count by cesarean section. Although we could not completely rule out the involvement of anti-HPA-4b, our findings suggested that anti-HPA-5b was implicated in the NAIT in the first sibling.

  13. 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

  14. Diagnosis and management of neonatal thrombocytopenia.

    PubMed

    Holzhauer, Susanne; Zieger, Barbara

    2011-12-01

    Thrombocytopenia is the most common haematological abnormality in newborns admitted to neonatal care units and serves as an important indicator of underlying pathological processes of mother or child. In most cases thrombocytopenia is mild to moderate and resolves within the first weeks of life without any intervention. However, in some neonates thrombocytopenia is severe or may reflect an inborn platelet disorder. As clinical course and outcome of thrombocytopenia depend on the aetiology of thrombocytopenia, an appropriate work-up is essential to guide therapy in neonates with thrombocytopenia and to avoid severe bleeding.

  15. [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

  16. [The new paradigm of neonatal hemochromatosis: fetal alloimmune hepatitis].

    PubMed

    Costaguta, Alejandro; Alvarez, Fernando

    2012-01-01

    The classical model of neonatal hemochromatosis was based on the analogy with hereditary hemochromatosis. Medical treatment consisted on the antioxidant-chelator cocktail. The new hypothesis of an alloimmune origin of the process by which the pregnant woman mounts an IgG-based destructive response against fetal hepatocytes offers a pathogenic explanation, allowing treatment to be focused on the immunological aspects, with excellent results, and opens the possibility of preventive treatment in future pregnancies. This new paradigm produces a deep impact in diagnosis, prognosis and treatment of the disease, that should be called "fetal alloimmune hepatitis".

  17. 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

  18. Neonatal Thrombocytopenia as a Consequence of Maternal Preeclampsia.

    PubMed

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

    2016-03-01

    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

  19. 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

  20. Factors predictive of neonatal thrombocytopenia in pregnant women with immune thrombocytopenia.

    PubMed

    Kawaguchi, Koji; Matsubara, Kousaku; Takafuta, Toshiro; Shinzato, Isaku; Tanaka, Yasuhiro; Iwata, Aya; Nigami, Hiroyuki; Takeuchi, Yasuhito; Fukaya, Takashi

    2014-01-01

    To determine predictive factors for neonatal thrombocytopenia in deliveries with immune thrombocytopenia (ITP), we conducted a retrospective study at a tertiary hospital between 1997 and 2013. During this period, 30 women with ITP delivered 44 children. Neonatal thrombocytopenia (<100 × 10(9)/L) at birth was observed in seven neonates; four of these cases were severe (<50 × 10(9)/L). No cases were complicated by intracranial hemorrhage, and there was no neonatal mortality. Platelet counts at birth of neonates born to mothers, who had first been diagnosed with ITP during pregnancy were significantly higher than those born to mothers diagnosed with ITP before pregnancy. There were significant correlations between neonatal platelet counts in the first and second siblings at birth (P = 0.015) and at nadir (P = 0.035). Platelet counts of neonates born vaginally were significantly more likely to decline after birth than those delivered by cesarean section (13/16 vs. 10/23, P = 0.024). In conclusion, diagnosis of ITP before pregnancy was significantly associated with neonatal thrombocytopenia, and the platelet count of an older sibling is a strong predictor for that of the next baby. The delivery mode may be an indicator of the timing of platelet count nadir after birth. PMID:24623263

  1. [A child with neonatal allo-immune neutropenia].

    PubMed

    Markhorst, D G; Hack, W W; de Waal, F C; Kuypers, R

    1990-10-01

    A newborn child with neonatal neutropenia as a result of the presence of maternal IgG isoantibodies against neutrophil granulocyte blood group antigens is reported. Mechanism, diagnostics and therapy of the disease are discussed. The diagnosis not only has consequences for the child, but also for the mother and following pregnancies. A review of the most important causes of neonatal neutropenia is given.

  2. 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

  3. 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

  4. 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

  5. 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 ...

  6. Congenital thrombocytopenia in a neonate with an interstitial microdeletion of 3q26.2q26.31.

    PubMed

    Bouman, Arjan; Knegt, Lia; Gröschel, Stefan; Erpelinck, Claudia; Sanders, Mathijs; Delwel, Ruud; Kuijpers, Taco; Cobben, Jan Maarten

    2016-02-01

    Interstitial deletions encompassing the 3q26.2 region are rare. Only one case-report was published this far describing a patient with an interstitial deletion of 3q26.2 (involving the MDS1-EVI1 complex (MECOM)) and congenital thrombocytopenia. In this report we describe a case of a neonate with congenital thrombocytopenia and a constitutional 4.52 Mb deletion of 3q26.2q26.31 including TERC and the first 2 exons of MECOM, involving MDS1 but not EVI1. The deletion was demonstrated by array-CGH on lymphocytes. Our report confirms that congenital thrombocytopenia can be due to a constitutional deletion of 3q26.2 involving MECOM. We suggest that in case of unexplained neonatal thrombocytopenia, with even just slight facial dysmorphism, DNA microarray on peripheral blood should be considered early in the diagnostic work-up.

  7. Current problems and future directions of transfusion-induced alloimmunization: summary of an NHLBI working group.

    PubMed

    Zimring, James C; Welniak, Lis; Semple, John W; Ness, Paul M; Slichter, Sherrill J; Spitalnik, Steven L

    2011-02-01

    In April 2010, a working group sponsored by the National Heart, Lung, and Blood Institute was assembled to identify research strategies to improve our understanding of alloimmunization caused by the transfusion of allogeneic blood components and to evaluate potential approaches to both reduce its occurrence and manage its effects. Significant sequelae of alloimmunization were discussed and identified, including difficulties in maintaining chronic transfusion of red blood cells and platelets, hemolytic disease of the newborn, neonatal alloimmune thrombocytopenia, and rejection of transplanted cells and tissues. The discussions resulted in a consensus that identified key areas of future research and developmental areas, including genetic and epigenetic recipient factors that regulate alloimmunization, biochemical specifics of transfused products that affect alloimmunization, and novel technologies for high-throughput genotyping to facilitate extensive and efficient antigen matching between donor and recipient. Additional areas of importance included analysis of unappreciated medical sequelae of alloimmunization, such as cellular immunity and its effect upon transplant and autoimmunity. In addition, support for research infrastructure was discussed, with an emphasis on encouraging collaboration and synergy of animal models biology and human clinical research. Finally, training future investigators was identified as an area of importance. In aggregate, this communication provides a synopsis of the opinions of the working group on the above issues and presents both a list of suggested priorities and the rationale for the topics of focus. The areas of research identified in this report represent potential fertile ground for the medical advancement of preventing and managing alloimmunization in its different forms and mitigating the clinical problems it presents to multiple patient populations. PMID:21251006

  8. Postnatal cytomegalovirus infection in an infant with congenital thrombocytopenia: how it can support or mislead the diagnosis of Wiskott-Aldrich syndrome.

    PubMed

    Poddighe, Dimitri; Virginia, Elena; Nedbal, Marco; Soresina, Annarosa; Bruni, Paola

    2016-09-01

    A male newborn developed a post-natal cytomegalovirus (CMV) infection, arising in the clinical setting of congenital thrombocytopenia, which was diagnosed as being alloimmune. The evidence of active CMV infection in an infant showing slow-resolution lower airways infection, persistent neonatal and low platelet volume thrombocytopenia, and diffuse eczema (associated to very high levels of serum immunoglobulin E) led to the diagnosis of Wiskott-Aldrich syndrome (WAS) before the third month of life, despite the presence of several confounding clinical factors. The correct interpretation of all clinical features supported the precocious diagnosis of WAS. PMID:27668906

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

    PubMed

    Ayadi, Imene Dahmane; Ben Hamida, Emira; 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 10(9)/L. Within the second day of life, platelet level dropped to 20 x 10(9)/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 10(9)/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10(th) of life platelets rate was stable around 60 x 10(9)/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up.

  10. 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

  11. 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

  12. 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.

  13. [Specificities of neonatal hemostasis and implications in pathologic situations].

    PubMed

    Gruel, Y

    2010-09-01

    The haemostasis of healthy newborn differs from those of normal adult but remains well balanced without bleeding or thrombosis. However, this equilibrium is unstable, and the neonate is exposed to acquired or inherited haemostasis disorders that necessitate to be early diagnosed in order to be appropriately treated. Several studies provided reference ranges for haemostatic components in the foetus, the newborn and throughout childhood. The particularities of neonatal haemostasis are therefore better defined and contribute to further understand the pathophysiology and characteristics of hemorrhagic and thrombotic disorders that occur in newborns. Some examples of the impact of age on haemostasis are: the risk of neonatal alloimmune thrombocytopenia is high in the first newborn of a woman at risk since the involved antigens are fully expressed by foetal platelets; the newborn is at risk for vitamin K deficiency with bleeding due to poor transport of vitamin K across the placenta and low levels of coagulation factors II, VII, IX, X; the diagnosis of some inherited coagulation deficiencies can be difficult in the newborn due to physiologically low levels of coagulation factors; thrombotic events are rare in the healthy neonate, despite physiologically very low levels of several coagulation inhibitors; the pharmacokinetic and effects of antithrombotic agents are influenced by the specificities of haemostasis in neonates. This review will discuss about the foetal development of haemostasis until birth, and some implications regarding the pathophysiology, the diagnosis and the treatment of bleeding disorders in the human neonate.

  14. 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

  15. Intrauterine transfusion for fetal anemia due to red blood cell alloimmunization: 14 years experience in Leuven

    PubMed Central

    Pasman, S.A.; Claes, L.; Lewi, L.; Van Schoubroeck, D.; Debeer, A.; Emonds, M.; Geuten, E.; De Catte, L.; Devlieger, R.

    2015-01-01

    Objective: The purpose of this study is to report on the pregnancy and neonatal outcome of intrauterine transfusion (IUT) for red blood cell (RBC-)alloimmunization. Material and Methods: Retrospective cohort study of all IUT for RBC-alloimmunization in the University Hospital of Leuven, between January 2000 and January 2014. The influence of hydrops, gestational age and technique of transfusion on procedure related adverse events were examined. Results: 135 IUTs were performed in 56 fetuses. In none of the cases fetal or neonatal death occurred. Mild adverse events were noted in 10% of IUTs, whereas severe adverse events occurred in 1.5%. Hydrops and transfusion in a free loop were associated with an increased risk of adverse events whereas gestational age (GA) at transfusion after 34 weeks was not. Median GA at birth was 35.6 weeks and 9% was born before 34 weeks. Besides phototherapy 65.4% required additional neonatal treatment for alloimmune anemia. Non-hematologic complications occurred in 23.6% and were mainly related to preterm birth. Conclusion: In experienced hands, IUT for RBC-alloimmunization is a safe procedure in this era. Patients should be referred to specialist centers prior to the development of hydrops. IUT in a free loop of cord and unnecessary preterm birth are best avoided. PMID:26175890

  16. Characterization of a human platelet antigen-1a-specific monoclonal antibody derived from a B cell from a woman alloimmunized in pregnancy.

    PubMed

    Eksteen, Mariana; Tiller, Heidi; Averina, Maria; Heide, Gøril; Kjaer, Mette; Ghevaert, Cedric; Michaelsen, Terje E; Ihle, Øistein; Husebekk, Anne; Skogen, Bjørn; Stuge, Tor B

    2015-06-15

    Human platelet Ag (HPA)-1a, located on integrin β3, is the main target for alloantibodies responsible for fetal and neonatal alloimmune thrombocytopenia (FNAIT) in the white population. There are ongoing efforts to develop an Ab prophylaxis and therapy to prevent or treat FNAIT. In this study, an mAb specific for HPA-1a, named 26.4, was derived from an immortalized B cell from an alloimmunized woman who had an infant affected by FNAIT. It is the only HPA-1a-specific human mAb with naturally paired H and L chains. Specific binding of mAb 26.4, both native and recombinant forms, to platelets and to purified integrins αIIbβ3 (from platelets) and αVβ3 (from trophoblasts) from HPA-1a(+) donors was demonstrated by flow cytometry and surface plasmon resonance technology, respectively. No binding to HPA-1a(-) platelets or integrins was detected. Moreover, the Ab binds with higher affinity to integrin αVβ3 compared with a second HPA-1a-specific human mAb, B2G1. Further in vitro experimentation demonstrated that mAb 26.4 can opsonize HPA-1a(+) platelets for enhanced phagocytosis by monocytes, inhibit binding of maternal polyclonal anti-HPA-1a Abs, and weakly inhibit aggregation of HPA-1a-heterozygous platelets, the latter with no predicted clinical relevance. Thus, mAb 26.4 is highly specific for HPA-1a and could potentially be explored for use as a prophylactic or therapeutic reagent for FNAIT intervention and as a phenotyping reagent to identify women at risk for immunization.

  17. 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.

  18. Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates.

    PubMed

    Dahl, J; Husebekk, A; Acharya, G; Flo, K; Stuge, T B; Skogen, B; Straume, B; Tiller, H

    2016-02-01

    In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti-HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected.

  19. [Heparin-induced thrombocytopenia].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-09-01

    Heparin-induced thrombocytopenia is a serious and underestimated adverse drug effect. We briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.

  20. [Autoimmune thrombocytopenia: diagnosis and treatment].

    PubMed

    Veneri, Dino; Franchini, Massimo

    2005-05-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by an isolated, persistent thrombocytopenia in absence of known causes. In this review, we briefly analyze the most important diagnostic criteria of this autoimmune disorder, with particular consideration to differential diagnosis (false thrombocytopenia, congenital thrombocytopenia, acquired thrombocytopenia, pregnancy-associated thrombocytopenia) and to therapeutic options.

  1. Neonatal Hemochromatosis

    PubMed Central

    Feldman, Amy G.; Whitington, Peter F.

    2013-01-01

    Neonatal hemochromatosis is a clinical condition in which severe liver disease in the newborn is accompanied by extrahepatic siderosis. Gestational alloimmune liver disease (GALD) has been established as the cause of fetal liver injury resulting in nearly all cases of NH. In GALD, a women is exposed to a fetal antigen that she does not recognize as “self” and subsequently begins to produce IgG antibodies that are directed against fetal hepatocytes. These antibodies bind to fetal liver antigen and activate the terminal complement cascade resulting in hepatocyte injury and death. GALD can cause congenital cirrhosis or acute liver failure with and without iron overload and siderosis. Practitioners should consider GALD in cases of fetal demise, stillbirth, and neonatal acute liver failure. Identification of infants with GALD is important as treatment is available and effective for subsequent pregnancies. PMID:25755519

  2. Neonatal haemochromatosis with reversible pituitary involvement.

    PubMed

    Indolfi, Giuseppe; Bèrczes, Rita; Pelliccioli, Isabella; Bosisio, Michela; Agostinis, Cristina; Resti, Massimo; Zambelli, Marco; Lucianetti, Alessandro; Colledan, Michele; D'Antiga, Lorenzo

    2014-08-01

    Neonatal haemochromatosis is a rare alloimmune gestational disease with a high mortality. The hallmark of neonatal haemochromatosis is severe neonatal liver failure associated with extrahepatic siderosis. Thus far, no pituitary dysfunction has been reported to result from the tissue damage associated with extrahepatic siderosis. The present report describes a neonate with neonatal haemochromatosis and secondary hypothyroidism associated with pituitary iron deposition. Both the conditions were successfully treated by ABO-incompatible liver transplantation. Pituitary gland dysfunction is another possible extrahepatic manifestation of neonatal haemochromatosis, and it is reversible after liver transplantation.

  3. Heparin-induced thrombocytopenia.

    PubMed

    2013-05-01

    Patients can develop thrombocytopenia during heparin therapy.The most frequent form, type I heparin-induced thrombocytopenia, does not require cessation of therapy. Type II heparin-induced thrombocytopenia is immune-mediated. It can cause venous or arterial thrombosis, which may be fatal or require amputation. Type II thrombocytopenia typically develops 5 to 10 days after initiation of treatment, sometimes earlier in patients previously exposed to heparins. The recommendations on platelet-count monitoring during heparin therapy are not based on high-level evidence. The main risk factors for type II thrombocytopenia must be taken into account: unfractionated heparin, previous heparin exposure, surgery, female patient. For patients considered at high risk for heparin-induced thrombocytopenia, platelet-count monitoring is usually recommended at least twice a week for at least 2 weeks. The treatment of immune-mediated heparin-induced thrombocytopenia is based on stopping heparin and replacing it with danaparoid or argatroban. In practice, the decision to initiate treatment with unfractionated or low-molecular-weight heparin is not a trivial one. In addition to the bleeding risk, the risk of type II thrombocytopenia in the short- term, or during subsequent heparin therapy, should be taken into account when assessing the harm-benefit balance. PMID:23819174

  4. Hemin controls T cell polarization in sickle cell alloimmunization

    PubMed Central

    Zhong, Hui; Bao, Weili; Friedman, David; Yazdanbakhsh, Karina

    2014-01-01

    Patients with sickle cell disease (SCD) often require transfusions to treat and prevent worsening anemia and other SCD complications. However, transfusions can trigger alloimmunization against transfused red blood cells (RBCs) with serious clinical sequelae. Risk factors for alloimmunization in SCD remain poorly understood. We recently reported altered regulatory T cell (Treg) and T helper (Th) responses with higher circulating Th1 (IFN-γ+) cytokines in chronically transfused SCD patients with alloantibodies as compared to those without alloantibodies. Since monocytes play a critical role in polarization of T cell subsets and participate in clearance of transfused RBCs, we tested the hypothesis that in response to RBC breakdown product, hemin, monocyte control of T cell polarization will differ between alloimmunized and non-alloimmunized SCD patients. Exogenous hemin induced Treg polarization in purified T-cell-monocyte cocultures from healthy volunteers through monocyte anti-inflammatory heme degrading enzyme HO-1. Importantly, hemin primarily through its effect on CD16+ monocytes induced an anti-inflammatory (higher Treg/lower Th1) polarization state in non-alloimmunized SCD group, whereas it had little effect in the alloimmunized group. Non-alloimmunized SCD CD16+ monocytes expressed higher basal levels of HO-1. Furthermore, IL-12, which contributed to a pro-inflammatory polarization state (low Treg/high Th1) in SCD, was dampened in hemin-treated stimulated monocytes from non-alloimmunized SCD patients, but not in alloimmunized group. These data suggest that unlike alloimmunized patients, non-alloimmunized SCD CD16+ monocytes in response to transfused RBC breakdown products promote an anti-inflammatory state that is less conductive to alloimmunization. PMID:24879794

  5. [Diagnosis of inherited thrombocytopenia].

    PubMed

    Baccini, V; Alessi, M C

    2016-02-01

    Inherited thrombocytopenias are rare, heterogenous and probably under-diagnosed because often classified as autoimmune thrombocytopenia. About 20 genes were described responsible for these thrombocytopenias. Precise diagnosis is necessary because the prognosis is different and some of them can evolve into hemopathies. First of all, it is important to gather a body of evidence to orientate towards an inherited cause: presence of the thrombocytopenia since childhood and of other family cases is a strong argument. Secondly, it is difficult to target the genetic investigations that settle the precise diagnosis. Genetic variants responsible for inherited thrombocytopenias affect different stage during megakaryocytopoiesis and cause thrombocytopenias with distinct characteristics. Presence of extra-hematological features, platelets' size measurement and evaluation of bone marrow megakaryocyte morphology when it is possible allow a primary orientation. We propose a diagnostic approach considering extra-hematological features, mode of inheritance, morphology, molecular and functional platelets' studies and bone marrow megakaryocyte morphology in order to better target genetic study. Nevertheless, despite this approach, some inherited thrombocytopenias remain still unexplained and could benefit from new methods of new generation sequencing in the future. PMID:26617290

  6. 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

  7. Sunitinib Induced Immune Thrombocytopenia.

    PubMed

    Shekarriz, Ramin; Koulaeinejad, Neda; Nosrati, Anahita; Salehifa, Ebrahim

    2015-01-01

    Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Grade 3 or 4 abnormalities following bone marrow suppression, in the rare cases, the immune mediated abnormality may drive the sunitinib-induced hematologic disorder. In this report, we present a case of immune-mediated thrombocytopenia induced by sunitinib. One month after first treatment cycle with sunitinib, leucopenia and thrombocytopenia were occurred. The patient had a normal bone marrow aspiration and biopsy, the thrombocytopenia was resistant to platelet transfusion which successfully was treated with prednisolone. PMID:26664400

  8. Sunitinib Induced Immune Thrombocytopenia

    PubMed Central

    Shekarriz, Ramin; Koulaeinejad, Neda; Nosrati, Anahita; Salehifa, Ebrahim

    2015-01-01

    Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Grade 3 or 4 abnormalities following bone marrow suppression, in the rare cases, the immune mediated abnormality may drive the sunitinib-induced hematologic disorder. In this report, we present a case of immune-mediated thrombocytopenia induced by sunitinib. One month after first treatment cycle with sunitinib, leucopenia and thrombocytopenia were occurred. The patient had a normal bone marrow aspiration and biopsy, the thrombocytopenia was resistant to platelet transfusion which successfully was treated with prednisolone. PMID:26664400

  9. 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 ...

  10. Antibody formation in pregnant women with maternal-neonatal human platelet antigen mismatch from a hospital in northern Taiwan.

    PubMed

    Yang, Wan-Hua; Cheng, Chuen-Sheng; Chang, Jin-Biou; Liu, Kuang-Ting; Chang, Junn-Liang

    2014-01-01

    Neonatal alloimmune thrombocytopenia (NAIT) is a clinical syndrome that resembles hemolytic disease of the newborn, affecting the platelets only. The thrombocytopenia results from the maternal alloantibodies reacting with specific human platelet antigens (HPAs) on the fetal platelets. Forty-four maternal plasma samples were screened for platelet alloantibodies using qualitative solid phase enzyme-linked immunosorbent assay (ELISA) commercial kit (LIFECODES Pakplus, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA), and both the maternal and the corresponding cord blood samples were genotyped (LIFECODES ThromboType, Hologic Gen-Probe GTI Diagnostics, Waukesha, WI, USA). HPA genotyping results correlated with the genetic frequencies in the Taiwan population. A total of 34 newborns (77.3%) had partial HPA genotyping mismatches with the corresponding mothers. The most common partial mismatches between mothers and neonates in HPA genotypes were 13 (29.5%) in both HPA-3b and HPA-15a, followed by 12 (27.3%) in HPA-15b, and 8 (18.2%) in HPA-3a. The frequencies of homozygotic mother with heterozygotic neonate were 15.9% in both HPA-3a and HPA-15b, 9.1% in HPA-15a, 6.8% in HPA-3b, and 2.3% in both HPA-2a and HPA-6a. In this study, maternal HPA antibodies were found in five samples, whereas HLA class I antibodies were found in seven maternal plasma samples from the antibody screen. The results from this study have demonstrated that HPA mismatch is not the main cause for the production of HPA alloantibodies.

  11. Thrombocytopenia in Experimental Trypanosomiasis

    PubMed Central

    Davis, Charles E.; Robbins, Robert S.; Weller, Richard D.; Braude, Abraham I.

    1974-01-01

    The effect of experimental trypanosomiasis on coagulation was studied because a patient in this hospital with Rhodesian trypanosomiasis developed thrombocytopenia with disseminated intravascular coagulation. Rats injected intraperitoneally with this strain of Trypanosoma rhodesiense consistently developed trypanosomiasis and severe thrombocytopenia without changes in hematocrit or concentration of fibrinogen or fibrin split products. At the time of 50% mortality (4-5 days) mean platelet counts per cubic millimeter of infected rats were 18,000±9,000 (±2 SEM) compared to 1,091,000±128,000 in uninfected controls. In vitro, concentrated trypanosomes and trypanosomefree supernates of disrupted organisms added to normal rat, rabbit, or human blood produced platelet aggregation within 30 min. This platelet aggregation was not blocked by inhibitors of ADP, kinins, or early or late components of complement. In vivo thrombocytopenia also occurred in infected rabbits congenitally deficient in C6 and in infected, splenectomized rats. Although the aggregating substance obtained from disrupted trypanosomes is heat-labile, it is active in the presence of complement inhibitors, suggesting that this trypanosomal product may be a protein enzyme or toxin. Since the phenomenon is independent of immune complexes, complement, ADP, and kinins, it appears to represent a new mechanism of microbial injury of platelets and the induction of thrombocytopenia. Images PMID:4207622

  12. Modulation of Alloimmunity by Heat Shock Proteins.

    PubMed

    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

  13. 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

  14. Modulation of Alloimmunity by Heat Shock Proteins.

    PubMed

    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.

  15. 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

  16. 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.

  17. Platelets, immune-mediated thrombocytopenias, and fetal hemorrhage.

    PubMed

    Xu, Xiaohong Ruby; Gallant, Reid C; Ni, Heyu

    2016-05-01

    Platelets are small versatile blood cells generated from megakaryocytes in the bone marrow and cleared in the reticuloendothelial system. Platelet accumulation (adhesion and aggregation) at the site of injury has been considered the first wave of hemostasis. Interestingly, although fibrinogen and von Willebrand factor (VWF) are documented to be essential for hemostasis, fibrinogen/VWF-independent platelet aggregation and thrombosis still occur. Following platelet activation and phosphatidylserine expression, platelets also contribute to cell-based thrombin generation and blood coagulation - the second wave of hemostasis. Most recently, deposition of fibronectin and other plasma proteins onto the injured vessel wall was identified as a "protein wave" of hemostasis, in which platelets may release their granule proteins and thus also contribute to this very early hemostatic event. Due to the central roles of platelets in hemostasis, excessive platelet clearance may lead to bleeding disorders as observed in auto- and alloimmune-mediated thrombocytopenias. In this review, we will introduce several new pathways of thrombosis and hemostasis as well as antibody Fc-independent platelet clearance, which may play an important role in immune-mediated thrombocytopenias. We will also discuss the roles of platelets in fetal hemostasis that may deserve further investigation. PMID:27207432

  18. 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

  19. 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

  20. Aging augments IL-17 T-cell alloimmune responses.

    PubMed

    Tesar, B M; Du, W; Shirali, A C; Walker, W E; Shen, H; Goldstein, D R

    2009-01-01

    As increasing numbers of elderly patients require solid organ transplantation, the need to better understand how aging modifies alloimmune responses increases. Here, we examined whether aged mice exhibit augmented, donor-specific memory responses prior to transplantation. We found that elevated donor-specific IL-17, but not IFN-gamma, responses were observed in aged mice compared to young mice prior to transplantation. Further characterization of the heightened IL-17 alloimmune response with aging demonstrated that memory CD4(+) T cells were required. Reduced IL-2 alloimmune responses with age contributed to the elevated IL-17 phenotype in vitro, and treatment with an anti-IL-17 antibody delayed the onset of acute allograft rejection. In conclusion, aging leads to augmented, donor-specific IL-17 immune responses that are important for the timing of acute allograft rejection in aged recipients. IL-17 targeting therapies may be useful for averting transplant rejection responses in older transplant recipients.

  1. [Use of Groupamatic in surveying fetomaternal alloimmunizations].

    PubMed

    Massaro, A L; Martinelli, A

    1978-03-01

    The A.V.I.S. Blood Transfusion Center of Turin performs the screening of foetomaternal allo-immunizations for the S. Anna Hospital of Turin. This hospital includes 3 hospital departments and 3 obstetrical and gynaecological university departments. The number of births in one year is roughly 13.000, i.e. 50 mother-baby couples, are tested every day. The identification system and the sampling process are described. The program used on the Groupamatic system includes: 1.) First run: Blood typing of mother blood with screening of alloantibodies. Second run: Blood typing control, screening of immune anti-A and anti-B antibodies, syphilis screening. 2.) Washing of cord blood red blood cells: First run: Washed red blood cells ABO and Rhesus typing, direct Coombs test. Second run: Blood typing control. Automatic screening of maternal irregular alloantibodies and automatic indirect Coombs test on washed cordblood red cells are simultaneously controlled with standard manual techniques. Sampling and testing are processed within 24 hours after birth. The set of results concerning mother-baby couples are grouped on one card and sent to the hospital department for a quick MHNN prophylaxy. Results of tests performed on 6.351 pregnancies studied until birth are presented. The automated direct Coombs test was positive with: 1--95% of new borns from mother who have a high immune allo antibody anti-A/B titer (IgG after treatment with two Mercapto etanol greater than I/64). 2--100% of new borns from mother who have irregular allo antibodies in Rh, Kell, Duffy or Kidd systems.

  2. Altered heme-mediated modulation of dendritic cell function in sickle cell alloimmunization

    PubMed Central

    Godefroy, Emmanuelle; Liu, Yunfeng; Shi, Patricia; Mitchell, W. Beau; Cohen, Devin; Chou, Stella T.; Manwani, Deepa; Yazdanbakhsh, Karina

    2016-01-01

    Transfusions are the main treatment for patients with sickle cell disease. However, alloimmunization remains a major life-threatening complication for these patients, but the mechanism underlying pathogenesis of alloimmunization is not known. Given the chronic hemolytic state characteristic of sickle cell disease, resulting in release of free heme and activation of inflammatory cascades, we tested the hypothesis that anti-inflammatory response to heme is compromised in alloimmunized sickle patients, increasing their risk of alloimmunization. Heme-exposed monocyte-derived dendritic cells from both non-alloimmunized sickle patients and healthy donors inhibited priming of pro-inflammatory CD4+ type 1 T cells, and exhibited significantly reduced levels of the maturation marker CD83. In contrast, in alloimmunized patients, heme did not reverse priming of pro-inflammatory CD4+ cells by monocyte-derived dendritic cells or their maturation. Furthermore, heme dampened NF-κB activation in non-alloimmunized, but not in alloimmunized monocyte-derived dendritic cells. Heme-mediated CD83 inhibition depended on Toll-like receptor 4 but not heme oxygenase 1. These data suggest that extracellular heme limits CD83 expression on dendritic cells in non-alloimmunized sickle patients through a Toll-like receptor 4-mediated pathway, involving NF-κB, resulting in dampening of pro-inflammatory responses, but that in alloimmunized patients this pathway is defective. This opens up the possibility of developing new therapeutic strategies to prevent sickle cell alloimmunization. PMID:27229712

  3. Altered heme-mediated modulation of dendritic cell function in sickle cell alloimmunization.

    PubMed

    Godefroy, Emmanuelle; Liu, Yunfeng; Shi, Patricia; Mitchell, W Beau; Cohen, Devin; Chou, Stella T; Manwani, Deepa; Yazdanbakhsh, Karina

    2016-09-01

    Transfusions are the main treatment for patients with sickle cell disease. However, alloimmunization remains a major life-threatening complication for these patients, but the mechanism underlying pathogenesis of alloimmunization is not known. Given the chronic hemolytic state characteristic of sickle cell disease, resulting in release of free heme and activation of inflammatory cascades, we tested the hypothesis that anti-inflammatory response to heme is compromised in alloimmunized sickle patients, increasing their risk of alloimmunization. Heme-exposed monocyte-derived dendritic cells from both non-alloimmunized sickle patients and healthy donors inhibited priming of pro-inflammatory CD4(+) type 1 T cells, and exhibited significantly reduced levels of the maturation marker CD83. In contrast, in alloimmunized patients, heme did not reverse priming of pro-inflammatory CD4(+) cells by monocyte-derived dendritic cells or their maturation. Furthermore, heme dampened NF-κB activation in non-alloimmunized, but not in alloimmunized monocyte-derived dendritic cells. Heme-mediated CD83 inhibition depended on Toll-like receptor 4 but not heme oxygenase 1. These data suggest that extracellular heme limits CD83 expression on dendritic cells in non-alloimmunized sickle patients through a Toll-like receptor 4-mediated pathway, involving NF-κB, resulting in dampening of pro-inflammatory responses, but that in alloimmunized patients this pathway is defective. This opens up the possibility of developing new therapeutic strategies to prevent sickle cell alloimmunization.

  4. Heparin induced thrombocytopenia: review.

    PubMed

    Dasararaju, Radhika; Singh, Nirupama; Mehta, Amitkumar

    2013-08-01

    Heparin induced thrombocytopenia (HIT) is a serious, potentially life and limb threatening immune adverse reaction to heparin. IgG antibodies against platelet factor 4 and heparin multimer complexes activate platelets to create a prothrombotic state. ELISA based immunoassay to detect these antibodies is sensitive while serotonin release assay is highly specific but is not widely available. 4T score is a simple score to calculate pre-test probability of HIT. Score < 3 is highly specific to exclude the diagnosis. Alternate anticoagulants like lepirudin, argatroban or danaparoid are recommended in therapeutic dose to treat or prevent thrombotic events in HIT. Increased awareness of this condition among clinicians is important to ensure its early recognition and treatment to avoid serious complications. PMID:23991928

  5. 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 ( ...

  6. 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 ...

  7. 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

  8. Severe gastrointestinal bleeding and thrombocytopenia in a child with an anti-GATA1 autoantibody.

    PubMed

    de Waele, Liesbeth; Freson, Kathleen; Louwette, Sophie; Thys, Chantal; Wittevrongel, Christine; de Vos, Rita; Debeer, Anne; van Geet, Chris

    2010-03-01

    We describe a patient, who developed during the first week of life petechiae and hematomas caused by severe thrombocytopenia and gastrointestinal bleeding due to multiple small gastric hemangiomata. Bone marrow examination showed hypermegakaryocytosis and dysmegakaryopoiesis. Alloimmune thrombocytopenia was excluded. Only 3 y later, platelet counts normalized and bleedings disappeared but small skin hemangiomata remained. Electron microscopy showed enlarged round platelets with a paucity of alpha granules similar as in GATA1-deficient patients but no GATA1 mutation was found. Immunoblot analysis showed a strong interaction between patient Igs and recombinant GATA1, GATA2, and the N finger (Nf) of GATA1. The lymphocyte transformation test with recombinant GATA1Nf was positive. In vitro culturing of normal CD34 cells with purified patient Igs showed a decreased number of megakaryocyte colonies but an increased overall size of the colonies compared with control Igs. Mice injected with patient Igs showed a reduced platelet count compared with mice injected with control Igs. Thrombopoiesis was also reduced after injection of patient Igs in transgenic zebrafish compared with control Igs. In conclusion, this study is the first report of an anti-GATA1 autoantibody leading to severe thrombocytopenia and gastrointestinal bleeding from multiple pinpoint hemangiomata.

  9. [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

  10. [Heparin-induced thrombocytopenia].

    PubMed

    Thiele, T; Althaus, K; Greinacher, A

    2010-09-01

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction that carries an increased risk of thromboembolic complications. HIT is caused by platelet-activating antibodies directed against a complex of platelet factor 4 (PF4) and heparin. HIT typically manifests in the second week after initiation of heparin therapy with a platelet count reduction of more than 50% of the highest level after the start of heparin administration as well as thromboembolic events. The clinical probability can be calculated by the 4 T's score. The laboratory diagnosis of HIT is based on confirmation of PF4/heparin antibodies or on functional tests that provide evidence of heparin-dependent platelet-activating antibodies. A low 4 T's score and negative HIT test virtually rule out the presence of HIT. Patients with acute HIT require anticoagulation with a compatible anticoagulant in a therapeutic dose. The drugs currently available for this include the direct thrombin inhibitors argatroban, lepirudin, bivalirudin, and desirudin and the indirect factor Xa inhibitors danaparoid and fondaparinux. PMID:20694716

  11. ALLOIMMUNIZATION IN SICKLE CELL DISEASE: CHANGING ANTIBODY SPECIFICITIES AND ASSOCIATION WITH CHRONIC PAIN AND DECREASED SURVIVAL

    PubMed Central

    Telen, Marilyn J.; Afenyi-Annan, Araba; Garrett, Melanie E.; Combs, Martha Rae; Orringer, Eugene P.; Ashley-Koch, Allison E.

    2014-01-01

    BACKGROUND: Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD. STUDY DESIGN AND METHODS Adult SCD patients were enrolled in a study of outcome modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical and laboratory findings, end organ damage, and overall disease severity were then compared between alloimmunized and non-alloimmunized patients. RESULTS Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vaso-occlusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short acting narcotics (p=0.006), long acting narcotics (p=0.013), or both (p=0.03). Additionally, alloimmunized patients had poorer survival (HR=1.92, p=0.01) and were more likely to have avascular necrosis (p=0.024), end-organ damage (p=0.049) and red cell autoantibodies (p<0.001), even after controlling for the effects of age, gender, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD related complications, such as acute chest syndrome or stroke. CONCLUSIONS Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain. PMID:25444611

  12. 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

  13. Influenza vaccination and humoral alloimmunity in solid organ transplant recipients.

    PubMed

    Vermeiren, Pieter; Aubert, Vincent; Sugamele, Rocco; Aubert, John-David; Venetz, Jean-Pierre; Meylan, Pascal; Pascual, Manuel; Manuel, Oriol

    2014-09-01

    Annual influenza vaccination is recommended in solid organ transplant (SOT) recipients. However, concerns have been raised about the impact of vaccination on antigraft alloimmunity. We evaluated the humoral alloimmune responses to influenza vaccination in a cohort of SOT recipients between October 2008 and December 2011. Anti-HLA antibodies were measured before and 4-8 weeks after influenza vaccination using a solid-phase assay. Overall, 169 SOT recipients were included (kidney = 136, lung = 26, liver = 3, and combined = 4). Five (2.9%) of 169 patients developed de novo anti-HLA antibodies after vaccination, including one patient who developed donor-specific antibodies (DSA) 8 months after vaccination. In patients with pre-existing anti-HLA antibodies, median MFI was not significantly different before and after vaccination (P = 0.73 for class I and P = 0.20 for class II anti-HLA antibodies) and no development of de novo DSA was observed. Five episodes of rejection (2.9%) were observed within 12 months after vaccination, and only one patient had de novo anti-HLA antibodies. The incidence of development of anti-HLA antibodies after influenza vaccination in our cohort of SOT recipients was very low. Our findings indicate that influenza vaccination is safe and does not trigger humoral alloimmune responses in SOT recipients.

  14. 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

  15. Thrombocytosis following thrombocytopenia in man

    PubMed Central

    Ogston, D.; Dawson, Audrey A.

    1969-01-01

    Observations are presented on the changes in the platelet count of patients during the treatment of Addisonian pernicious anaemia with vitamin B12, of thrombocytopenic purpura with prednisone, and of malignant disease with methotrexate. In each of these clinical situations, thrombocytopenia was succeeded, after a delay of a number of days, by a phase of thrombocytosis. PMID:5392350

  16. [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.

  17. [Epidemiology of anti-D allo-immunization during pregnancy].

    PubMed

    Branger, B; Winer, N

    2006-02-01

    The number of women exposed to a risk of anti-D allo-immunization who require care depends on the number of pregnancies, the distribution of blood groups in the Rhesus D system, and the number of allo-immunization risk situations as well as the chosen prevention protocol. In 2004, there were 790,000 pregnancies in metropolitan France. The total number of conceptions (adding abortions, voluntary interruptions, ectopic pregnancies and in utero fetal deaths) would be to the order of 1,100,000 to 1,200,000. Since 15% of the French population is RhD-negative, 15% of pregnant women or women who have delivered are RhD-negative, which would correspond to 160,000 to 180,000 women exposed to a risk of anti-D allo-immunization. Two strategies could be evaluated: prevention targeting risk factors and systematic prevention from 28 weeks gestation. Both strategies involve treatment with anti-D anti-globulins to RhD-negative women with an RhD-positive newborn. Targeted prevention would involve 160,000 to 190,000 doses for 130,000 to 150,000 women. The systematic approach would consist in 300,000 to 340,000 doses for 250,000 to 280,000 women. This number could be lowered by reserving treatment for women with a RhD-positive partner (210,000 to 230,000 doses for 260,000 to 290,000 women), but this would require a precise contract between the physician and the woman. Another way to reduce the number of doses would be to determine the Rh group of the fetus either by ovular samples or by genotyping on maternal blood. This would give about 200,000 to 220,000 doses for 240,000 to 270,000 women. In light of the literature, the systematic protocol would probably reduce the number of immunized women, the current estimation being 700 women still immunized in France and the goal being a reduction to a residual 200. The number of infants at risk of in utero maternal allo-immunization (fetal death, anasark, anemia) or after birth (jaundice, severe anemia) is not known in France and could be the

  18. Is exchange transfusion a possible treatment for neonatal hemochromatosis?

    PubMed

    Timpani, Giuseppina; Foti, Francesca; Nicolò, Antonino; Nicotina, Pier Antonio; Nicastro, Emanuele; Iorio, Raffaele

    2007-11-01

    Neonatal hemochromatosis is a rare congenital disorder of the liver associated to a poor prognosis. Liver transplantation is often required, since no effective medical treatment has been found. Despite mounting evidence of an alloimmune etiology of this condition, exchange transfusion has never been proposed as a specific treatment for neonatal hemochromatosis. Here we describe two siblings affected by neonatal hemochromatosis. The first, a female, died at 18 days of severe coagulopathy and acute renal failure, diagnosed as affected by neonatal hemochromatosis only when the second sibling was suspected as being affected by the same disease. The second child showed a rapidly worsening coagulopathy which was treated with two exchange transfusions, followed by rapid clinical and laboratory improvement, before reaching a definite diagnosis of neonatal hemochromatosis. He is healthy at present after a follow-up of 12 months. Although exchange transfusion has never been considered as treatment for neonatal hemochromatosis, this case suggests that it could be a feasible treatment option for children affected by this disease, as for other alloimmune conditions.

  19. 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.

  20. Gestational thrombocytopenia among pregnant Ghanaian women

    PubMed Central

    Olayemi, Edeghonghon; Akuffo, Frederick William

    2012-01-01

    Background Thrombocytopenia is a common problem during pregnancy that is not frequently detected and as a result is often inappropriately managed. The obvious concern with thrombocytopenia during pregnancy is the risk of significant bleeding at the time of delivery. This study was designed to determine the prevalence of gestational thrombocytopenia in pregnant women reporting for ante-natal care at a Ghanaian primary health care centre. Methods Platelet count was evaluated in 300 blood samples from pregnant women and 100 non pregnant female blood donors. The platelet counts were performed using Sysmex KX-21N automated hematology analyzer. The study design was cross sectional. Proportions were analyzed for statistical significance with the Chi square, Odds ratio was also calculated Results The prevalence of thrombocytopenia in pregnant women in this study was 15.3% compared with 4% in controls. This was statistically significant with a P value of 0.003. Odds ratio was 4.31 (95% CI: 1.52-12.04). Most cases of thrombocytopenia were mild (76%), only 4% of the women with thrombocytopenia had severe thrombocytopenia. Conclusion The frequency of thrombocytopenia in this study was higher than that reported from more developed parts of the world. This may be due to undetected malaria infection in our patients. Pregnant women should be routinely screened for thrombocytopenia. Those found to be thrombocytopenic should have both thick and thin blood films done to exclude the presence of malaria parasites. PMID:22891092

  1. 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

  2. Modification of solid phase red cell adherence assay for the detection of platelet antibodies in patients with thrombocytopenia.

    PubMed

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

    2008-09-01

    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%.

  3. Management of thrombocytopenia in advanced liver disease

    PubMed Central

    Gangireddy, VGR; Kanneganti, PC; Sridhar, S; Talla, S; Coleman, T

    2014-01-01

    Thrombocytopenia (defined as a platelet count <150×109/L) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×109/L to 75×109/L) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease. PMID:25222481

  4. Neonatal antiphospholipid syndrome.

    PubMed

    Soares Rolim, A M; Castro, M; Santiago, M B

    2006-01-01

    Antiphospholipid syndrome (APS) is a clinical entity characterized by arterial and venous thrombosis, adverse obstetric outcome and the presence of antibodies against phospholipids in serum or plasma. The objective of the present study is to describe a rare case of APS that occurred in a neonate born from a patient previously diagnosed as primary APS. A male, preterm born twin infant, whose mother had been diagnosed as primary APS, developed thrombocytopenia, livedo reticularis, pericardial effusion and thrombosis of the left subclavian and external jugular veins concomitantly with severe respiratory tract infection soon after his delivery, that culminated with his death two months after the birth, in spite of the large spectrum antibiotic therapy and all supportive measures. Laboratory findings included high titers of IgM anticardiolipin antibodies and moderate titers of IgG isotype and negative antinuclear antibody, configuring a case of neonatal APS. Neonatal APS is a rare clinical condition, with only a few cases described in the literature. Its occurrence may depend on the passage of antibodies through the placenta or, as it seems to have occurred in the present case, by the production of de novo antibodies by the fetus. The present case illustrates the necessity of a higher surveillance of the neonates born from mothers with primary APS or systemic lupus erythematosus (SLE) for the eventual development of such complication. PMID:16761506

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy.

    PubMed

    Sun, Dongmei; Shehata, Nadine; Ye, Xiang Y; Gregorovich, Sandra; De France, Bryon; Arnold, Donald M; Shah, Prakesh S; Malinowski, Ann Kinga

    2016-09-01

    Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 × 10(9)/L vs corticosteroids 77 × 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 × 10(9)/L and 18 (9%) had platelet counts <50 × 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 × 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP. PMID:27402971

  11. 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

  12. 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

  13. 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

  14. Novel treatments for immune thrombocytopenia.

    PubMed

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

    2014-04-01

    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

  15. Autoantibody formation after alloimmunization inducing bystander immune hemolysis.

    PubMed

    Mota, M; Bley, C; Aravechia, M G; Hamerschlak, N; Sakashita, A; Kutner, J M; Castiho, L

    2009-01-01

    The development of RBC autoantibodies resulting from or associated with allogeneic blood transfusions is not an easily determined complication of RBC transfusions. This report discusses one patient who developed RBC autoantibodies in association with an allogeneic blood transfusion and alloimmunization leading to a temporary bystander immune hemolysis. A 72-year-old woman was hospitalized as a result of severe anemia and received two units of ABO- and D-compatible RBCs. She had a history of two pregnancies 40 years before, but no history of RBC transfusion, and her antibody screen was negative. On the tenth day after transfusion her hemoglobin dropped, and alloanti-c was identified in her serum and eluate. At this time she received another two units of compatible blood according to her phenotype (group O, R1R1, K:-1). After 48 hours, she developed joint pain, pyrexia, and hemoglobinuria, and her Hb dropped from 9.2 g/dL to 5.3 g/ dL. The direct antiglobulin test was positive, an IgG autoantibody was present in the eluate, and the antibody investigation revealed the presence of anti-Jk(b) in addition to the previously identified alloanti-c. Her genotype was determined, and, based on the findings, two additional units were selected, found to be compatible, and transfused without incident. Transfusions were discontinued, and she was treated with IVIG and corticosteroids. Her Hb increased to 9.7 g/dL, and the patient made an uneventful recovery. It was concluded that transfusion of incompatible RBCs induced the formation of an autoantibody in this patient, resulting in lysis of bystander RBCs. The need for additional blood transfusion was successfully avoided by treatment with IVIG, steroid therapy, and rituximab.

  16. 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

  17. 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 ...

  18. Alloimmune Activation Promotes Anti-Cancer Cytotoxicity after Rat Liver Transplantation

    PubMed Central

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A.; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor. PMID:24651497

  19. Alloimmune activation promotes anti-cancer cytotoxicity after rat liver transplantation.

    PubMed

    Lacotte, Stéphanie; Oldani, Graziano; Slits, Florence; Orci, Lorenzo A; Rubbia-Brandt, Laura; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-01-01

    Liver transplantation for hepatocellular carcinoma (HCC) results in a specific condition where the immune response is potentially directed against both allogeneic and cancer antigens. We have investigated the level of anti-cancer immunity during allogeneic immune response. Dark Agouti-to-Lewis and Lewis-to-Lewis rat liver transplantations were performed and the recipients anti-cancer immunity was analysed at the time of alloimmune activation. The occurrence of rejection in the allogeneic recipients was confirmed by a shorter survival (p<0.01), increased liver function tests (p<0.01), the presence of signs of rejection on histology, and a donor-specific ex vivo mixed lymphocyte reaction. At the time of alloimmune activation, blood mononuclear cells of the allogeneic group demonstrated increased anti-cancer cytotoxicity (p<0.005), which was related to an increased natural killer (NK) cell frequency (p<0.05) and a higher monocyte/macrophage activation level (p<0.01). Similarly, liver NK cell anti-cancer cytotoxicity (p<0.005), and liver monocyte/macrophage activation levels (p<0.01) were also increased. The alloimmune-associated cytotoxicity was mediated through the NKG2D receptor, whose expression was increased in the rejected graft (p<0.05) and on NK cells and monocyte/macrophages. NKG2D ligands were expressed on rat HCC cells, and its inhibition prevented the alloimmune-associated cytotoxicity. Although waiting for in vivo validation, alloimmune-associated cytotoxicity after rat liver transplantation appears to be linked to increased frequencies and levels of activation of NK cells and monocyte/macrophages, and is at least in part mediated through the NKG2D receptor.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. Plasmapheresis and intravenous immune globulin for the treatment of D alloimmunization in pregnancy.

    PubMed

    Novak, Deborah J; Tyler, Lisa N; Reddy, Ramakrishna L; Barsoom, Michael J

    2008-01-01

    The alloimmunized pregnancy can result in fetal and newborn mortality due to fetal anemia. Control of fetal anemia has not been possible until recently, and management consists of following the degree of fetal anemia during gestation until intrauterine transfusion is feasible to support the fetus until delivery. Cordocentesis and intrauterine transfusion have potential complications that have been well documented. Control of fetal anemia via immune modulation utilizing plasmapheresis and intravenous immune globulin administration has been attempted alone and in combination with varying results. We present a case report of an Rh(D) alloimmunized pregnancy, in which successful management consisted of initial therapeutic plasmapheresis (TPE) followed by intravenous immunoglobulin (IVIG) administration until delivery at 37 weeks gestation without the need for intrauterine transfusion.

  9. 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.

  10. 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

  11. Thrombocytopenia and fever: not just another infection….

    PubMed

    Sriskandarajah, Priya; Davies, Rhys

    2016-01-01

    Diffuse large B-cell lymphoma (DLBCL) is a high-grade, aggressive disease that typically presents with widespread lymphadenopathy and active 'B' symptoms, making it easy to recognise and manage. However, a small proportion of patients can present with no evidence of lymphadenopathy or organomegaly, with the disease confined to the bone marrow; this presentation is also known as 'Primary Bone Marrow DLBCL'. Subsequently, diagnosis can be a challenge, resulting in delayed treatment and an overall poorer prognosis. Given the rarity of this disease, we wished to describe a patient who presented initially with fevers associated with isolated thrombocytopenia and was later diagnosed with this condition. Unfortunately, due to the aggressive nature of this disease, subsequent treatment was unsuccessful. Overall, we felt that in future cases of fevers with thrombocytopenia, clinicians should include this rare lymphoma subtype as part of the differential diagnosis, as early identification and treatment can be associated with a favourable outcome. PMID:27174453

  12. [Heparin-induced thrombocytopenia. New therapeutical options].

    PubMed

    Seculini Patiño, Carina E; Tabares, Aldo H

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment. PMID:27576282

  13. Current management of heparin-induced thrombocytopenia.

    PubMed

    Cosmi, Benilde

    2015-12-01

    Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients. PMID:26368591

  14. [Heparin-induced thrombocytopenia. New therapeutical options].

    PubMed

    Seculini Patiño, Carina E; Tabares, Aldo H

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

  15. 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

  16. Current management of heparin-induced thrombocytopenia.

    PubMed

    Cosmi, Benilde

    2015-12-01

    Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients.

  17. Risk estimation of HNA-3 incompatibility and alloimmunization in Thai populations.

    PubMed

    Nathalang, Oytip; Intharanut, Kamphon; Siriphanthong, Kanokpol; Nathalang, Siriporn; Leetrakool, Nipapan

    2015-01-01

    Severe transfusion-related acute lung injury (TRALI) is often due to antibodies in blood components directed against human neutrophil antigen (HNA)-3a. This study aimed to report the genotype frequencies of the HNA-3 system and to estimate the potential risk of HNA-3 incompatibility and alloimmunization in two Thai populations. Eight hundred DNA samples obtained from 500 unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok and 300 samples from the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand were included. HNA-3 genotyping was performed using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The observed frequencies of the HNA-3a/3a, HNA-3a/3b, and HNA-3b/3b genotypes were 0.528, 0.380, and 0.092 in central Thais and 0.600, 0.350, and 0.050 in northern Thais, respectively. The frequencies were used to estimate HNA-3 incompatibility and risk of HNA-3a alloimmunization. The HNA-3 incompatibility in central Thais (33.28%) was higher than northern Thais (28.75%), corresponding to a significantly higher probability of HNA-3a alloimmunization (P<0.05) similar to Japanese and Chinese populations. This study showed the high risk of HNA-3 incompatibility and alloimmunization, especially in central Thai blood donors. A molecular-based identification of the HNA-3 genotype of female donors is suggested to reduce the risk of TRALI following plasma and whole blood allogeneic transfusion.

  18. 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

  19. 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

  20. 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

  1. Current treatment options for primary immune thrombocytopenia.

    PubMed

    Salama, Abdulgabar

    2011-02-01

    Traditional treatment of primary (idiopathic) immune thrombocytopenia (ITP) predominantly consists of immune suppression and/or modulation. In addition, many treated patients develop severe adverse effects, and approximately a third of patients do not respond. Two of the newly developed thrombopoietin-receptor agonists, romiplostim and eltrombopag, are now available for the treatment of ITP. Both drugs have been shown to increase the production of platelets in a dose-dependent manner, and to compensate, at least partly, for thrombocytopenia in the majority of ITP patients. The reported adverse effects are predominantly mild, although serious and long-term side effects cannot be excluded. Nevertheless, these drugs are increasingly used in the treatment of patients with thrombocytopenias. Thrombopoietin-receptor agonists do not appear to stop either the production of autoantibodies or the accelerated platelet destruction observed in ITP. Thus, the need for a specific therapy is essential, and the ultimate solution is to clarify and halt the mechanism(s) that lead to the development of ITP.

  2. 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).

  3. Thrombocytopenia with Unilateral Dysplastic Radius- Is it Thrombocytopenia - Absent Radius (TAR) Syndrome?

    PubMed

    Kumar, Mani Kant; Chaudhary, Indradeo Prasad; Ranjan, Ram Bilas; Kumar, Prashant

    2015-03-01

    Thrombocytopenia - absent radii (TAR) syndrome is an autosomal recessive genetic rare disorder with hypomegakaryocytic thrombocytopenia and bilateral absent radius that may have additional anomalies. This disorder is characterized by thrombocytopenia resulting in potentially severe bleeding episodes primarily during infancy. We report the case of a 7-day-old term appropriate for gestational age (AGA) male baby, product of non consanguineous marriage presented with bloody loose stool, right sided upper limb deformity and paleness of the body, was diagnosed as TAR syndrome with some atypical presentation. Such type of atypical presentation has not been previously reported in a case with TAR Syndrome.Patient was managed in our hospital with packed cell transfusion and two units platelets concentrates transfusion, Intra-venous antimicrobials, and other supportive treatment. He gradually improved and was discharged after seven days of hospital stay with advice to consult orthopedic surgeon for opinion regarding limb reconstruction. PMID:25954675

  4. 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

  5. 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

  6. [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.

  7. Neonatal teeth.

    PubMed

    Kovac, J; Kovac, D

    2011-01-01

    Teeth that are present at birth are called natal teeth, and teeth that emerge through the gingiva during the first 4 weeks of life are called neonatal teeth. The incidence of the appearance of natal and neonatal teeth has been reported to be between once every 800 and once every 6000 births. Natal and neonatal teeth may be uncomfortable for a nursing mother and present a risk of aspiration and swallowing by the infant if they are loose. Also, they may cause irritation and trauma to the infant's soft tissues. Under these circumstances, natal and neonatal teeth need to be extracted. In this article, a case report of two neonatal teeth in a five week old girl is presented. The teeth were present in the mandibular incisor region and were excessively mobile and caused discomfort for the nursing mother. They were extracted because of the fear of aspiration (Fig. 4, Ref. 10).

  8. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates.

    PubMed

    Sola-Visner, Martha C; Christensen, Robert D; Hutson, Alan D; Rimsza, Lisa M

    2007-04-01

    Thrombocytopenia is frequent among sick neonates, but little is known about its underlying mechanisms. It is known, however, that neonatal megakaryocytes are smaller and of lower ploidy than their adult counterparts and that smaller megakaryocytes produce fewer platelets than larger, more polyploid, megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase their size in response to thrombocytopenia, thus limiting the ability of neonates to mount a response. To test this, we obtained marrow specimens from thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were immunohistochemically stained, quantified using an eyepiece reticle, and measured using an image analysis system with incorporated electronic micrometer. We found that, after adjusting for differences in cellularity, neonates and adults had similar megakaryocyte concentrations. When samples from the same sources were compared (tibial clot and vertebral body sections in neonates, iliac crest biopsies in adults), there were also no differences in megakaryocyte concentration between thrombocytopenic and nonthrombocytopenic subjects. The megakaryocyte diameter, however, was greater in adults than in neonates (19.4 +/- 3.0 versus 15.3 +/- 1.7 microm, p<0.0001). Thrombocytopenic adults also had a higher proportion of large megakaryocytes than nonthrombocytopenic adults (p<0.001). This was not observed among thrombocytopenic neonates, suggesting a developmental limitation in their ability to increase megakaryocyte size. PMID:17515875

  9. 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.

  10. 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

  11. 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

  12. Management of thrombocytopenia due to liver cirrhosis: A review

    PubMed Central

    Hayashi, Hiromitsu; Beppu, Toru; Shirabe, Ken; Maehara, Yoshihiko; Baba, Hideo

    2014-01-01

    Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis. PMID:24627595

  13. Management of thrombocytopenia in the ICU (pregnancy excluded).

    PubMed

    Van der Linden, Thierry; Souweine, Bertrand; Dupic, Laurent; Soufir, Lilia; Meyer, Pascal

    2012-08-28

    Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy.

  14. Management of thrombocytopenia in the ICU (pregnancy excluded)

    PubMed Central

    2012-01-01

    Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy. PMID:22929300

  15. 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 ...

  16. 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 ...

  17. Childhood immune thrombocytopenia: a changing therapeutic landscape.

    PubMed

    Breakey, Vicky R; Blanchette, Victor S

    2011-10-01

    Childhood immune thrombocytopenia (ITP) is generally a benign self-limiting disorder of young children with <10% of cases requiring regular platelet enhancing therapy at 1 year following diagnosis. Increasingly, children with newly diagnosed ITP, who have isolated thrombocytopenia and no atypical features in the history or physical examination, are managed with minimal investigation and observation alone. The role of up-front, short-course corticosteroid therapy without bone marrow aspiration in this subgroup of cases merits further investigation. For children with clinically significant chronic ITP, the timing of elective splenectomy and the role of splenectomy-sparing strategies such as rituximab continues to be debated. Management of children with combined autoimmune cytopenias secondary to systemic lupus erythematosus, common variable immunodeficiency, and the autoimmune lymphoproliferative syndrome is often a challenge. Splenectomy should be avoided in cases with documented immunodeficiencies because of the increased risk of overwhelming sepsis postsplenectomy. For these cases, as well as for children with resistant primary chronic ITP who have failed splenectomy, the role of therapies such as mycophenolate mofetil, sirolimus, and the thrombopoietins remains to be determined.

  18. Heparin-induced thrombocytopenia: an update.

    PubMed

    Prechel, Margaret; Walenga, Jeanine M

    2012-07-01

    Heparin-induced thrombocytopenia (HIT) is an immune response to heparin that can progress to severe thrombosis, amputation, and in some cases death. The diagnosis and treatment of HIT is complex, but needs to be considered in the clinical management of patients exposed to heparin due to its serious outcomes. Early diagnosis based on a comprehensive interpretation of clinical and laboratory information improves clinical outcomes. This begins with careful monitoring for thrombocytopenia and thrombosis during and for at least 5 to 10 days after heparin treatment of any dose and duration. Appropriate use and knowledgeable interpretation of laboratory tests for HIT are important, as these vary in sensitivity and specificity, with each type providing unique information. 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. Important drug-specific limitations, dosing, and monitoring guidelines must be respected for patient safety. There continues to be new developments in the field of HIT: laboratory testing, clinical scoring systems, and available new anticoagulants. Research and clinical studies will continue to address the unresolved issues and unmet clinical needs associated with HIT. This review summarizes the clinical management of HIT. PMID:22399304

  19. Severe Rh alloimmunization and hemolytic disease of the fetus managed with plasmapheresis, intravenous immunoglobulin and intrauterine transfusion: A case report.

    PubMed

    Houston, Brett L; Govia, Rachelle; Abou-Setta, Ahmed M; Reid, Gregory J; Hadfield, Marie; Menard, Chantalle; Noyd, Jocelyn; Main, Susan; Zarychanski, Ryan

    2015-12-01

    Rh alloimmunization remains a potentially devastating complication of pregnancy, with fetal anemia causing hydrops and intrauterine death. Intrauterine transfusion is the standard treatment, but is particularly dangerous before 20 weeks gestation. When the need for intrauterine transfusion is anticipated early in pregnancy, immune-modulating therapies such as plasmapheresis and IVIG have been used to delay transfusion to a later gestational age. We report a 35-year-old G5P1 Rh(D)-negative woman with severe Rh alloimmunization managed successfully with sequential plasmapheresis, intravenous immune globulin and intrauterine transfusion. The optimal plasmapheresis treatment protocol and incremental benefit of IVIG remains unknown.

  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. Neonatal pain.

    PubMed

    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.

  2. The Influence of Clinical and Biological Factors on Transfusion-Associated Non-ABO Antigen Alloimmunization: Responders, Hyper-Responders, and Non-Responders.

    PubMed

    Gehrie, Eric A; Tormey, Christopher A

    2014-11-01

    In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy, transfusion, or transplantation. The development of RBC alloantibodies can have important clinical consequences, particularly in patients who require chronic transfusions. It has been suggested that alloimmunization is more common in some clinical circumstances and patient populations than in others. As such, individuals that develop alloantibodies are frequently referred to as 'responders' in the medical literature. In contrast, individuals that do not develop alloantibodies despite repeated exposures to non-self blood group antigens have been referred to as 'non-responders'. The purpose of this article is to review the phenomenon of RBC alloimmunization in the context of responders and non-responders to: i) establish a basic framework for alloimmunization as reported across several diverse patient populations; ii) more fully explore literature reports which support the concept of responders/non-responders regarding blood group antigen alloimmunization; iii) summarize the mechanisms that have been shown to predispose an individual to alloimmunization to determine how these factors may differentiate 'responders' from 'non-responders'; and iv) briefly discuss some practical approaches to prevent alloimmunization in patients who may be prone to alloantibody development.

  3. 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

  4. 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.

  5. Receipt of older RBCs does not predispose D-negative recipients to anti-D alloimmunization.

    PubMed

    Yazer, Mark H; Triulzi, Darrell J

    2010-09-01

    The effect of the age of RBCs on anti-RBC alloimmunization has not been investigated in previous studies of the RBC storage lesion. D-negative recipients of at least 1 D-positive RBC unit were identified. Responders produced an anti-D, while nonresponders had not made anti-D when the database was searched. The 2 groups were matched for age, sex, length of serologic follow-up, and hospital location. There were 29 responders and 58 nonresponders. The median number of all RBCs transfused to the responders was 6, vs 10 for the nonresponders (P < .01); the median age of the RBCs was 15 vs 14 days, respectively (P = .70). Responders received a median of 3 D-positive RBC units vs 4 D-positive RBCs for nonresponders (P = .02); median ages of the D-positive RBCs were 16 vs 14 days, respectively (P = .21). There was no association between the age of transfused RBCs and the likelihood of anti-D alloimmunization.

  6. A case of thrombocytopenia caused by rifampicin and pyrazinamide

    PubMed Central

    Bansal, Rekha; Sharma, Parveen K.; Sharma, Aradhna

    2013-01-01

    A 32-year-old male patient was diagnosed as having pulmonary tuberculosis and put on category II antitubercular regime since he had a history of antituberculosis treatment 10 years ago. Within 3 weeks, patient presented with ulcers in mouth, and blood picture confirmed thrombocytopenia. Rifampicin-induced thrombocytopenia was suspected and antitubercular treatment stopped. Patient improved and was re-exposed to the drugs one by one. After re-exposure with pyrazinamide, the platelet count decreased drastically and oral mucosal ecchymoses reappeared, while with rifampicin, thrombocytopenia was accompanied with petechiae on legs and forearms. Isoniazid, ethambutol, and streptomycin were continued. PMID:24014922

  7. Severe Fever with Thrombocytopenia Syndrome, Shandong Province, China, 2011

    PubMed Central

    Wen, Hong-Ling; Zhao, Li; Zhai, Shenyong; Chi, Yuanyuan; Cui, Feng; Wang, Dongxu; Wang, Ling; Wang, Zhiyu; Wang, Qian; Zhang, Shoufeng; Liu, Yan; Yu, Hao

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China. The incidence and clinical and laboratory characteristics of SFTS are not clearly defined. During May 22–October 2, 2011, a total of 24 patients with fever, thrombocytopenia, and leukopenia were clinically diagnosed as having SFTS in Yiyuan County, Shandong Province, China. We conducted laboratory tests for these SFTS patients. SFTS virus (SFTSV) infection was confirmed in 22 patients by using reverse transcription PCR and ELISA by acute-phase and convalescent-phase serum samples. Clinical and laboratory manifestations included fever (100%), gastrointestinal symptoms (91%), myalgia (55%), chills (41%), thrombocytopenia (100%), and leukopenia (95%). PMID:24378074

  8. Pediatric heparin-induced thrombocytopenia: management with Danaparoid (orgaran).

    PubMed

    Saxon, B R; Black, M D; Edgell, D; Noel, D; Leaker, M T

    1999-09-01

    Heparin-induced thrombocytopenia is a rare and serious complication of anticoagulation therapy. There remains a paucity of information pertaining to alternative anticoagulation strategies for use during cardiopulmonary bypass concomitant with heparin-induced thrombocytopenia, especially in children. We report the successful treatment of heparin-induced thrombocytopenia and subsequent hemorrhagic complications postoperatively in a 2-year-old child with Danaparoid (orgaran). Emergent conduit revision with cardiopulmonary bypass was required for a thrombosed systemic-venous to pulmonary-arterial connection (completion modified Fontan procedure). Required doses of Danaparoid were consistently twofold that previously reported for adults. PMID:10510017

  9. [Current treatment of primary immune thrombocytopenia].

    PubMed

    Lozano, María L; Vicente, Vicente

    2014-05-01

    Primary immune thrombocytopenia, also termed immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction and impaired platelet production. Traditional treatment of ITP has predominantly consisted of immune suppression and/or modulation. However, the understanding of the immune mediated impairment of platelet production has led to the development of new treatments that target the thrombopoietin receptor, promoting formation of megakaryocytes and increasing platelet counts. Best practice for the management of ITP has not yet been established because data from comparative studies are lacking. While some disagreement might still remain among experts concerning therapy (when, who, and how should be treated), in recent years different evidence-based practice guidelines have been published to assist healthcare professionals in the diagnosis and treatment of ITP. This review describes the current treatment landscape of ITP.

  10. Heparin induced thrombocytopenia: diagnosis and management.

    PubMed

    Alaraj, Ali; Wallace, Adam; Tesoro, Eljim; Ruland, Sean; Amin-Hanjani, Sepideh; Charbel, Fady T; Aletich, Victor

    2010-12-01

    The incidence of heparin induced thrombocytopenia (HIT) in neurological patients continues to increase with expansion of indication for neurointerventional procedures. The pathophysiology of HIT is related to a hypersensitivity reaction against complex platelet factor 4. The diagnosis is mostly clinical and is often confirmed by laboratory testing. Patients with HIT have a higher rate of thromboembolic complications, both arterial and venous, and with worse neurological outcomes at the time of discharge. Early diagnosis and heparin cessation are essential in the management of those patients. Both immediate and prolonged alternative anticoagulation are necessary. Understanding of the mechanism of action, indication and drug interaction of the alternative anticoagulants (direct thrombin inhibitors, fondaparinux and danaparoid) and warfarin is essential during management of these patients. PMID:21990651

  11. Eltrombopag for the treatment of immune thrombocytopenia.

    PubMed

    Cheng, Gregory

    2011-06-01

    Chronic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count that has persisted for more than 12 months. Patients with severe, symptomatic disease may have significant morbidity and require treatment. Historically, the underlying cause of ITP was believed to be accelerated platelet destruction by antiplatelet antibodies. Treatment options were therefore focused on reducing platelet autoantibody production or inhibiting macrophage-mediated platelet destruction. These treatments are not always effective or, at best, only have a transient effect and treatment-related adverse events often preclude their long-term use. Recently, impaired platelet production was observed in many ITP patients. Therefore, growth factor or growth factor analogs that stimulate megakaryopoiesis may be useful in ITP treatment. This article presents data on the pharmacology, clinical efficacy, safety profile and future roles of eltrombopag, an orally bioavailable, low-molecular-weight, synthetic nonpeptide thrombopoietin receptor agonist, in the treatment of ITP.

  12. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. PMID:27312156

  13. Imbalanced immune homeostasis in immune thrombocytopenia.

    PubMed

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders.

  14. 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.

  15. Fetal and neonatal thyrotoxicosis

    PubMed Central

    Batra, Chandar Mohan

    2013-01-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20th week of pregnancy and reaches its maximum by 30th week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  16. Fetal and neonatal thyrotoxicosis.

    PubMed

    Batra, Chandar Mohan

    2013-10-01

    Fetal thyrotoxicosis is a rare disease occurring in 1 out of 70 pregnancies with Grave's disease or in 1 out of 4000-50,000 deliveries. The mortality is 12-20%, usually from heart failure, but other complications are tracheal compression, infections and thrombocytopenia. It results from transfer of thyroid stimulating immunoglobulins from mother to fetus through the placenta. This transplacental transfer begins around 20(th) week of pregnancy and reaches its maximum by 30(th) week. These autoantibodies bind to the fetal thyroid stimulating hormone (TSH) receptors and increase the secretion of the thyroid hormones. The mother has an active autoimmune thyroid disease or has been treated for it in the past. She may be absolutely euthyroid due to past treatment by drugs, surgery or radioiodine ablation, but still have active TSH receptor stimulating autoantibodies, which can cause fetal thyrotoxicosis. The other features of this disease are fetal tachycardia, fetal goiter and history of spontaneous abortions and findings of goiter, ascites, craniosyntosis, fetal growth retardation, maceration and hydrops at fetal autopsy. If untreated, this disease can result in intrauterine death. The treatment for this disease consists of giving carbimazole to the mother, which is transferred through the placenta to the fetus. The dose of carbimazole is titrated with the fetal heart rate. If the mother becomes hypothyroid due to carbimazole, thyroxine is added taking advantage of the fact that very little of thyroxine is transferred across the placenta. Neonatal thyrotoxicosis patients are very sick and require emergency treatment. The goal of the treatment is to normalize thyroid functions as quickly as possible, to avoid iatrogenic hypothyroidism while providing management and supportive therapy for the infant's specific signs and symptoms. PMID:24251220

  17. Acquired amegakaryocytic thrombocytopenia in a patient with occupational chemical exposure.

    PubMed

    Patel, Monaliben; Kalra, Ankur; Surapaneni, Rakesh; Schwarting, Roland; Devereux, Linda

    2014-01-01

    Acquired amegakaryocytic thrombocytopenia (AAT) is a hematologic disorder that presents as thrombocytopenia with absent megakaryocytes in the bone marrow. Causes of AAT include toxins, drugs, viral infections, systemic lupus erythematosus, and cytokine deficiencies. Patients with AAT should be followed for possible progression to aplastic anemia or myelodysplastic syndrome. We present a case of a 61-year-old woman with AAT due to occupational chemical exposure.

  18. 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

  19. 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

  20. 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

  1. 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

  2. Prevalence of Thrombocytopenia and Its Association with Serum Magnesium.

    PubMed

    Lu, Leihong; Zhan, Yiqiang; Yu, Jinming; Sui, Lihong

    2016-01-01

    The present study aimed to investigate the prevalence of thrombocytopenia and its association with serum magnesium in a nationally representative cohort. A total of 8478 participants aged 18 years and over were recruited in a cross-sectional survey. Thrombocytopenia was defined as platelet count less than 150 × 10(9)/L. Multivariable logistic regression models were applied to examine the association between serum magnesium and thrombocytopenia. The prevalence of thrombocytopenia in total was 16.5% with 18.8% for men and 14.4% for women (P < 0.0001), respectively. Compared with men in the first quartile of serum magnesium, the odds ratios (ORs) and 95% confidence intervals (CIs) for those in the second, third, and fourth quartiles of serum magnesium were 0.96 (0.75, 1.21), 0.78 (0.62, 0.98), and 0.82 (0.65, 1.04), respectively, after adjusting for multiple confounders. Likewise, the corresponding ORs (95% CIs) were 0.80 (0.63, 1.01), 0.79 (0.62, 0.99), and 0.65 (0.51, 0.84) in women. When serum magnesium was treated as a continuous variable, each one standard deviation increase of magnesium was associated with 12 and 8% lower risk of thrombocytopenia in men and women, respectively. Serum magnesium was inversely associated with thrombocytopenia, and the association was slightly different in men compared with that in women.

  3. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    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. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis.

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

    PubMed

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

    2015-05-17

    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.

  5. Alloimmune IgG binds and modulates cardiac beta-adrenoceptor activity.

    PubMed Central

    Sterin-Borda, L; Cremaschi, G; Pascual, J; Genaro, A; Borda, E

    1984-01-01

    Purified IgG from murine alloimmune sera directed against class I products from the major histocompatibility complex of the mouse, could bind to the beta-adrenoceptors and stimulate contractile activity of myocardium. Immune IgG inhibited the binding of (-) 3H-DHA to beta-adrenoceptors of mouse myocardial membranes behaving as a competitive inhibitor. Moreover, immune IgG induced positive inotropic and chronotropic effects on isolated mouse atria. These effects could be blocked by beta-adrenoceptors antagonists. Data prove that immune IgG directed against specific alloantigens are able to recognize the beta-adrenoceptors and mimic the stimulation of the beta-adrenoceptor agonist. PMID:6090043

  6. 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

  7. [Heparin-induced thrombocytopenia: recent data].

    PubMed

    Gruel, Y; Rollin, J; Leroux, D; Pouplard, C

    2014-03-01

    Despite less frequent, heparin-induced thrombocytopenia (HIT) remains a severe complication of treatment with heparin, and is important to diagnose and manage appropriately. HIT results from an atypical immune response to heparin, with the synthesis of IgG antibodies specific to heparin-modified platelet factor 4 (PF4) which activate platelets, leukocytes and the endothelium. This activation explains that low platelet count is associated with thrombotic events in 50% of patients. The diagnosis of HIT is sometimes evoked because of atypical manifestations (i.e. cutaneous necrosis, amnesia, hypotension or dyspnea following intravenous injection of heparin). Biological assays are always necessary to confirm HIT in case of clinical suspicion, and specific rapid tests are now available for detecting anti-PF4 antibodies. However, their specificity is poor and functional assays such as serotonin release assay or platelet aggregation test are often necessary. Argatroban that is a direct antithrombin drug can be used in patients with severe renal failure and will be preferred to danaparoid sodium in this situation. Fondaparinux is not licensed for treating confirmed HIT and can only be used in case of suspicion. The early detection of HIT is based on the monitoring of platelet count recommended in surgical patients receiving a low molecular weight heparin and in all patients treated with unfractionated heparin. PMID:24074968

  8. Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

    PubMed Central

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

    2015-01-01

    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

  9. 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.

  10. Neonatal tumours.

    PubMed

    Moore, S W

    2013-12-01

    Neonatal or perinatal tumours frequently relate to prenatal or developmental events and have a short exposure window which provides an opportunity to study tumours in a selective sensitive period of development. As a result, they display a number of host-specific features which include occasional spontaneous maturational changes with cells still responding to developmental influences. Neonatal tumours (NNT) are studied for a number of important reasons. Firstly, many of the benign tumours arising from soft tissue appear to result from disturbances in growth and development and some are associated with other congenital anomalies. Study of these aspects may open the door for investigation of genetic and epigenetic changes in genes controlling foetal development as well as environmental and drug effects during pregnancy. Secondly, the clinical behaviour of NNT differs from that of similar tumours occurring later in childhood. In addition, certain apparently malignant NNT can 'change course' in infancy leading to the maturation of apparently highly malignant tumours. Thirdly, NNT underline the genetic associations of most tumours but appear to differ in the effects of proto-oncogenes and other oncogenic factors. In this context, there are also connections between the foetal and neonatal period and some "adult" cancers. Fourthly, they appear to arise in a period in which minimal environmental interference has occurred, thus providing a unique potential window of opportunity to study the pathogenesis of tumour behaviour. This study will seek to review what is currently known in each of these areas of study as they apply to NNT. Further study of the provocative differences in tumour behaviour in neonates provides insights into the natural history of cancer in humans and promotes novel cancer therapies.

  11. [Thrombocytopenia induced by heparin. Diagnosis, treatment, physiopathology: current concepts].

    PubMed

    Gruel, Y; Drouet, L

    1986-01-01

    Iatrogenic thrombocytopenia is a rare, but severe complication of treatments with heparin and heparinoids. Mean temporary thrombocytopenia failing to show any complications are usually diagnosed as quite different from acute and delayed thrombocytopenia of which severity depends mainly on thrombotic symptoms demonstrated in 65 p. 100 of cases; the initial evolution of an average thrombocytopenia is not easy to diagnose; it may as well exist a connection between the two diseases, from a physiopathogenic point of view. The diagnosis of severe thrombocytopenia depends:--clinically, on the initial data, delayed as compared with the heparin treatment beginning and existence of arterial and/or venous thrombosis;--biologically, by demonstrating an aggregating activity for platelets in presence of heparin, in the patient plasma. Such an activity requires the suppression of standard heparinotherapy as well as the choice of substitutive anticoagulant treatment in case of evolutive thrombosis. Low molecular weight heparins are prescribed only if in vitro tests of platelet aggregation with the patient's plasma are negative. Antivitamins K are to be used as soon as possible alone or combined with heparin fractions. Antiaggregants are prescribed alone, above all in case of isolated thrombocytopenia and combined with AVK. Treatment of thrombotic complications depends on surgical disobstruction if arterial thrombosis, and use of fibrinolytics if pulmonary embolisms. The acute reaction of some thrombocytopenia to heparin as well as therapeutic difficulties demonstrate the efficiency of an early diagnosis performed thanks to systematic platelet numerations during the first 15 days of a treatment with heparin, as well as to the prevention along with systematic association with aspirin, especially if replaced with AVK.

  12. Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study.

    PubMed

    Noris, Patrizia; Klersy, Catherine; Gresele, Paolo; Giona, Fiorina; Giordano, Paola; Minuz, Pietro; Loffredo, Giuseppe; Pecci, Alessandro; Melazzini, Federica; Civaschi, Elisa; Mezzasoma, Annamaria; Piedimonte, Monica; Semeraro, Fabrizio; Veneri, Dino; Menna, Francesco; Ciardelli, Laura; Balduini, Carlo L

    2013-07-01

    The most frequent forms of inherited thrombocytopenia (IT) are characterized by platelet size abnormalities and it has been suggested that this parameter is useful for their differentiation from immune thrombocytopenia (ITP). Recently, a monocentric study identified cut-off values for mean platelet volume (MPV) and mean platelet diameter (MPD) with good diagnostic accuracy in this respect. To validate these cut-off values in a different and larger case series of patients, we enrolled 130 subjects with ITP and 113 with IT in six different centres. The platelet count and MPV was each measured by the instrument routinely used in each institution. In some centres, platelet count was also measured by optical microscopy. MPD was evaluated centrally by image analysis of peripheral blood films. The previously identified cut-off value for MPV had 91% specificity in distinguishing ITP from inherited macrothrombocytopenias (mono and biallelic Bernard-Soulier, MYH9-related disease), while its sensitivity was greatly variable depending on the instrument used. With an appropriate instrument, specificity was 83%. The diagnostic accuracy of MPD was lower than that obtained with MPV. We concluded that MPV is a useful parameter for differentiating ITP from IT provided that it is measured by appropriate cell counters.

  13. Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study

    PubMed Central

    Noris, Patrizia; Klersy, Catherine; Gresele, Paolo; Giona, Fiorina; Giordano, Paola; Minuz, Pietro; Loffredo, Giuseppe; Pecci, Alessandro; Melazzini, Federica; Civaschi, Elisa; Mezzasoma, Annamaria; Piedimonte, Monica; Semeraro, Fabrizio; Veneri, Dino; Menna, Francesco; Ciardelli, Laura; Balduini, Carlo L

    2013-01-01

    The most frequent forms of inherited thrombocytopenia (IT) are characterized by platelet size abnormalities and it has been suggested that this parameter is useful for their differentiation from immune thrombocytopenia (ITP). Recently, a monocentric study identified cut-off values for mean platelet volume (MPV) and mean platelet diameter (MPD) with good diagnostic accuracy in this respect. To validate these cut-off values in a different and larger case series of patients, we enrolled 130 subjects with ITP and 113 with IT in six different centres. The platelet count and MPV was each measured by the instrument routinely used in each institution. In some centres, platelet count was also measured by optical microscopy. MPD was evaluated centrally by image analysis of peripheral blood films. The previously identified cut-off value for MPV had 91% specificity in distinguishing ITP from inherited macrothrombocytopenias (mono and biallelic Bernard-Soulier, MYH9-related disease), while its sensitivity was greatly variable depending on the instrument used. With an appropriate instrument, specificity was 83%. The diagnostic accuracy of MPD was lower than that obtained with MPV. We concluded that MPV is a useful parameter for differentiating ITP from IT provided that it is measured by appropriate cell counters. PMID:23617394

  14. 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

  15. Rapid anticoagulation using ancrod for heparin-induced thrombocytopenia.

    PubMed

    Demers, C; Ginsberg, J S; Brill-Edwards, P; Panju, A; Warkentin, T E; Anderson, D R; Turner, C; Kelton, J G

    1991-11-01

    In order to determine the efficacy and safety of ancrod, a rapid acting defibrinogenating drug, for patients with heparin-induced thrombocytopenia, 11 consecutive patients who required anticoagulant therapy because of venous thromboembolism and who developed acute heparin-induced thrombocytopenia or had a history of heparin-induced thrombocytopenia were treated with ancrod. Heparin therapy was discontinued (in patients receiving heparin) and ancrod started at a dose of 1 to 2 U/kg every 24 hours with subsequent daily doses adjusted to maintain fibrinogen levels between 0.5 and 1.0 g/L. Ancrod was continued until warfarin had become effective. The platelet count increased to more than 150 x 10(9)/L within 2 to 10 days in all thrombocytopenic patients. Two patients with a history of heparin-induced thrombocytopenia maintained normal platelet counts while receiving ancrod. Two patients had recurrent venous thrombosis while receiving warfarin, 10 days after ancrod was discontinued: one of these patients had metastatic pancreatic carcinoma and developed phlegmasia cerulea dolens and the other patient developed a venographically proven extension of her deep venous thrombosis. One patient suffered a bleeding episode into the thigh with a 16-g/L decrease in her hemoglobin level while receiving ancrod therapy. No other side effects were noted. Our experience indicates that ancrod therapy is a reasonable approach for patients with heparin-induced thrombocytopenia who require anticoagulant therapy.

  16. Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

    PubMed

    Ohira, Masahiro; Ishifuro, Minoru; Ide, Kentaro; Irei, Toshimitsu; Tashiro, Hirotaka; Itamoto, Toshiyuki; Ito, Katsuhide; Chayama, Kazuaki; Asahara, Toshimasa; Ohdan, Hideki

    2009-02-01

    Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P < 0.001). Furthermore, the PLT count of patients with thrombocytopenia (PLT count thrombocytopenia coexist (PLT count or= 400), persistent thrombocytopenia is predictable after LTx.

  17. Heparin-induced thrombocytopenia after ICD-lead flushing.

    PubMed

    de Bree, L Charlotte J; Alings, A Marco W; van Wijngaarden, Peter

    2014-04-01

    Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening prothrombotic complication following heparin administration. We describe a patient, known with idiopathic dilating cardiomyopathy, presenting nine days after a biventricular ICD implantation with dyspnoea and thrombocytopenia. Thirteen days after administration of a single heparin flush during ICD implantation, the patient developed venous thrombosis in two extremities and pulmonary embolism caused by HIT. HIT is the development of thrombocytopenia, caused by IgG antibodies against complexes of platelet factor 4 and heparin, leading to platelet aggregation. HIT may be accompanied by thrombosis in 20-50% of patients and untreated mortality rates are high. Once HIT is suspected, heparin should be replaced by an alternative anti-factor Xa or anti-factor II therapy. Regardless of the low incidence of HIT, because of the widespread use of heparin and the potentially life-threatening course of HIT, all physicians should be aware of it. PMID:24783473

  18. 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.

  19. Tirofiban-Induced Thrombocytopenia Occurring with Crohn's Disease.

    PubMed

    Ibrahim, Toni; El Karak, Fady; Araji, Assem; El Rassy, Elie

    2016-01-01

    A 69-year-old man, with severe refractory Crohn's disease, presented with acute coronary syndrome that required angioplasty. He developed severe tirofiban-induced thrombocytopenia (TIT) heralded by type I allergic reaction that required steroids and a combination of antihistamine H1 and antihistamine H2 for symptomatic management. The thrombocytopenia spontaneously resolved uneventfully in 48 hours thereafter. This case report suggests a possible association between TIT and inflammatory bowel disease. Therefore, strict monitoring of the platelet count is required in patients who develop allergic reactions to tirofiban. PMID:27144035

  20. 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.

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

    PubMed

    Llovet, Valentina; Rada, Gabriel

    2016-09-05

    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.

  2. 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

  3. 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

  4. Neonatal lupus.

    PubMed

    Robles, David T; Jaramillo, Lorena; Hornung, Robin L

    2006-12-10

    An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active connective tissue disease in the mother does not have to be present and in fact is often absent. Although the cutaneous, hematologic and hepatic manifestations are transient, the potential for permanent heart block makes it necessary for this to be carefully ruled out. As in this case, the dermatologist may be the one to make the diagnosis and should be aware of the clinical presentation, work-up, and management of this important disease.

  5. 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

  6. 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

  7. Bleeding issues in neonates and infants - update 2015.

    PubMed

    Nowak-Göttl, Ulrike; Limperger, Verena; Bauer, Alexander; Kowalski, Dorothee; Kenet, Gili

    2015-02-01

    The presentation of a neonate with clinical bleeding symptoms commonly causes considerable anxiety to parents and treating physicians. Since inherited coagulation disorders are rare many children with persistently abnormal coagulation screens will have an underlying bleeding disorder. Apart from emergency cases a family history including a bleeding questionnaire is mandatory asking for the onset and/or severity symptoms of hemorrhage prior to laboratory assessment. The absolute values of reference ranges for coagulation assays in neonates and children vary with analyzer and reagent systems, but confirm the concept of developmental hemostasis, showing that physiologic concentrations of coagulation proteins gradually increase and are lower in premature infants as compared to full-term babies or healthy children. The evaluation should include global screening tests and a full blood cell count to rule out thrombocytopenia. As in adults a prolonged PT in neonates reflects decreased plasma concentrations of vitamin-K-dependent factors, whereas the prolonged PTT stems from decreased plasma levels of contact factors. When initial laboratory test results reveal abnormalities, as compared to age-related values, a stepwise diagnostic approach should be followed. In the bleeding neonate or infant that has no laboratory abnormality, FXIII and alpha2-antiplasmin activity should be assessed, and when primary hemostatic defects are suspected, platelet function should be further evaluated. Treatment options of a bleeding neonate vary according to the underlying medical condition.

  8. A case of severe Rh (D) alloimmunization pregnant woman delivery an infant with limited treatment.

    PubMed

    Xu, Wenhao

    2013-10-01

    A 35-year-old woman with histories of frequent failed pregnancies was pregnant after having five plasma exchange procedures during which she was given Rh (D) positive plasma as replacement and her anti-D antibody titer went from 512 to 1024. Antenatal surveillance of the fetus showed no abnormality. At 36 weeks gestation she delivered an infant who initially had no significant clinical problems but was severely anemic on the following days. Using exchange transfusion and blood transfusions the infant's hemoglobin was normal at 4 months of age. Thus, the Rh (D) status of donor plasma should be considered when used as the replacement in plasma exchange for Rh (D) negative women. Severe Rh (D) alloimmunization pregnant woman may delivery an infant who seem in good condition at birth. If severe Rhesus isoimmunisation of the infant is confirmed, whole blood exchange should be done as early as possible and the infant must be considered to be at risk for late anemia. Clinical judgment plays a vital role in the decision to transfuse red cells or not.

  9. Case report: solid-phase platelet crossmatching to support the alloimmunized patient.

    PubMed

    O'Connell, B A

    1995-01-01

    Platelet crossmatching by a solid-phase red cell adherence assay was used to provide compatible platelets for two alloimmunized patients with leukemia. In this study, a successful platelet transfusion was defined as giving a corrected count increment (CCI) of >7,500 in a posttransfusion sample. For patient A, a total of 205 random platelet concentrates (PCs) were crossmatched. Eleven were considered compatible. These 11 PCs were transfused during five transfusion episodes. Four of the five transfusions produced CCIs of >7,500 and were considered successful. Individually, eight of the eleven units were considered in vivo compatible, and five of the eight donors of these units agreed to become apheresis donors. Platelets from three of these five apheresis donors gave CCIs of >7,500. For patient B, 1,074 random PCs were crossmatched, and 332 were considered compatible. These units were administered during 78 different transfusions. Seventy-one of these transfusion episodes resulted in CCIs of >7,500. In addition, 19 apheresis donors were identified by platelet crossmatching, and they provided platelets for 38 of 39 successful transfusions for Patient B. Platelet crossmatching should therefore be considered when a blood bank is called upon to support a refractory thrombocytopenic patient.

  10. Clinical and blood bank factors in the management of platelet refractoriness and alloimmunization.

    PubMed

    Friedberg, R C; Donnelly, S F; Boyd, J C; Gray, L S; Mintz, P D

    1993-06-15

    Numerous independent and interdependent factors are involved in the posttransfusion platelet response. Factors such as ABO match and platelet age are related to circumstances potentially under the control of the blood bank physician and therefore may permit circumvention by an active transfusion service. On the other hand, factors such as fever or sepsis may be unavoidable, being related more to the individual patient or clinical condition. To evaluate which factors could be circumvented, we prospectively followed the 1-hour corrected count increments (CCIs) for 962 single-donor apheresis platelet transfusions to 71 refractory hematologic oncology inpatients, with concomitant recording of implicated factors. Stepwise regression analysis allowed for determination of which concurrent and confounding clinical-, patient-, and blood bank-related factors significantly affected the CCIs. Although many implicated factors proved to be independently associated with an increased or decreased CCI, we found that no single variable consistently explained the CCI variation across the patient population. Each patient appeared sensitive to one or a few particular factors, but because of marked intraindividual variation, it was not possible to identify a priori which factors were important for a given patient. The single exception was a solid-phase red blood cell adherence assay used to cross-match platelets, but only for alloimmunized patients. We also evaluated the utility of requesting HLA-matched platelets from the local suppliers and maintained a clear distinction between platelets simply ordered as HLA matched and actually HLA-identical platelets. Accounting for the confounding clinical-, patient-, and blood bank-related factors, the cross-match assay was a better predictor of an adequate CCI than ordering platelets as HLA matched.

  11. [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.

  12. [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

  13. Neonatal lupus.

    PubMed

    Brucato, Antonio; Cimaz, Rolando; Stramba-Badiale, Marco

    2002-12-01

    Congenital heart block (CHB), defined as an atrioventricular block diagnosed in utero, at birth, or within the neonatal period (0-27 d after birth), is a rare disorder closely linked to transplacental transport of maternal antibodies anti-Ro/SSA and anti-La/SSB. These antibodies may induce a myocarditis, or interact directly with calcium channel proteins with disturbance of transmembrane signaling at the level of the conduction tissue, or interfere with apoptosis. Depending on the severity of the process, the fetus may die in utero or a few days after birth or survive to the perinatal period and have a near-normal life; in most survivors a pace-maker must be implanted. Skin lesions, haematological disorders, and hepatic cholestasis are other transient clinical features of the syndrome. Sinus bradycardia and QT interval prolongation may be observed as well in babies born from anti-Ro/SSA positive mothers. The risk of recurrence of complete block ranges from 10-17%. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long-term outcome generally is more reassuring than previously assumed and arthralgias and dry eyes are the most common symptoms. A standard therapy for blocks detected in utero still does not exist. The prevalence of complete CHB in newborns of anti-Ro/SSA positive women and with known connective-tissue disease was 2%. Serial echocardiograms and obstetric sonograms, performed at least every 2 wk starting from the 16 wk gestation, are recommended in anti-Ro/SSA positive pregnant women.

  14. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma.

    PubMed

    Tokeji, Kayo; Sakaguchi, Sachi; Kurimoto, Tomoko; Fujimura, Junya; Shimizu, Toshiaki

    2016-01-01

    We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP) after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case. PMID:27668103

  15. Severe fever with thrombocytopenia syndrome presenting as acute hepatic failure

    PubMed Central

    Park, Jung Gil

    2015-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is characterized by fever, thrombocytopenia, leukopenia, and altered consciousness, which may also involve multi-organ failure. Initially SFTS mortality was as high as 30%, when diagnosis remained unclear. We present a case of a 53-year- old man with SFTS presenting with acute hepatic failure. On admission, he presented with confusion, elevated serum liver enzyme and ammonia levels, whose serum markers were negative for acute viral hepatitis. He was diagnosed with SFTS based on reverse transcription-polymerase chain reaction identification of the SFTS virus M segment. Percutaneous liver biopsy was performed to identify the degree and extent of necroinflammation and patient prognosis. After recovery, he was followed-up for 12 months with no SFTS-related sequelae. A discordance in severity between biopsy findings and clinical course could explain the rapid clinical improvement. Atypical presentations with multi-organ failure can delay timely diagnosis and management of infected patients. PMID:27752587

  16. [Danaparoid sodium for dialysis in heparin-associated thrombocytopenia].

    PubMed

    Ben Ami, R; Rachmimov, R; Berliner, S

    1999-03-01

    Danaparoid sodium is an antithrombin composed of 3 glycosaminoglycans: heparan sulfate, dermatan sulfate and chondroitin sulfate. Similar to heparin, danaparoid operates by activating antithrombin 3, but does not contain heparin or heparin fragments, and is therefore antigenically distinct. Danaparoid has been advocated as a safe and effective anticoagulant for heparin-associated thrombocytopenia. However, there is little experience in its use as a substitute for heparin in hemodialysis. We report 2 men, aged 82 and 73 years, respectively, who developed thrombocytopenia while undergoing hemodialysis with heparin, and who subsequently underwent successful dialysis with danaparoid. There was a rise in platelet levels in both while receiving danaparoid, and dialysis was completed without hemorrhagic or thrombotic complications. Danaparoid is a safe and effective substitute for heparin, and may be used as an anticoagulant in hemodialysis. PMID:10914239

  17. 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

  18. 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

  19. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    PubMed Central

    Kurimoto, Tomoko; Fujimura, Junya; Shimizu, Toshiaki

    2016-01-01

    We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP) after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case. PMID:27668103

  20. Rivaroxaban in treatment refractory heparin-induced thrombocytopenia.

    PubMed

    Casan, Joshua Misha Lewis; Grigoriadis, George; Chan, Noel; Chunilal, Sanjeev

    2016-01-01

    Following orthopaedic surgery, a 56-year-old woman developed heparin-induced thrombocytopenia (HIT), complicated by extensive proximal deep vein thrombosis. The patient did not respond to multiple conventional therapies; however, a prompt treatment response occurred after starting rivaroxaban at standard dosing. This case represents the first documentation of efficacy for rivaroxaban in the setting of treatment refractory HIT and strengthens the limited existing evidence for this agent in HIT. PMID:27520997

  1. [Guideline for diagnosis and treatment of immune thrombocytopenia].

    PubMed

    2010-04-01

    Management, outcome, diagnosis, prognosis and treatment of immune thrombocytopenia are controversial. Several guidelines stating different experts' opinions have been published; however, no worldwide consensus regarding the management of the disease has been reached yet. This guideline defines diagnostic criteria, states initial laboratory tests, establishes differential diagnosis, develops topics concerning outcome and prognosis, and enumerates available treatments for acute and chronic disease, as well as for management of life-threatening bleeding.

  2. 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.

  3. Heparin-induced thrombocytopenia: the role of platelets genetic polymorphisms.

    PubMed

    Pamela, Scarparo; Anna Maria, Lombardi; Elena, Duner; Giovanni, Malerba; Emanuele, Allemand; Silvia, Vettore; Carmen, Blumentritt; Andreas, Greinacher; Fabrizio, Fabris

    2013-01-01

    Heparin-induced thrombocytopenia (HIT) is a severe complication of heparin therapy, characterized by thrombocytopenia and an increased risk for thrombotic complications secondary to the formation of IgG antibodies (Ab), recognizing a complex of heparin (H) and PF4. Using the 4T clinical score for HIT and the presence of heparin-associated Ab assayed by enzyme-linked immunosorbent assay and heparin-induced platelet aggregation, we define the phenotype of three groups of patients: 51 H/PF4/Ab patients with antibodies and without thrombocytopenia; 50 patients with thrombocytopenia (HIT) and 53 patients with thrombosis (HITT). In these patients we studied four polymorphisms: FcγRIIA-H131R, GpIIb/IIIa-HP-1, PECAM1-L125V (in linkage-disequilibrium with S563N and R670G), and FcγRIIIA-F158V, to understand if these variations may influence the different phenotypes of the patients. There were no difference in genotype or allele frequencies between controls and the three groups of patients. Afterward, we created a genotype score for multiple risk alleles for thrombosis considering as risk genotype FcγRIIA R/R131, HPA-1a/b, and PECAM1-V/V125. These polymorphisms were overrepresented in HITT patients, ascertained by a permutation test (10 000 replicates) p = 0.0198 for the two-single-nucleotide polymorphism (SNP) model and p = 0.0119 for the three-SNP model. The calculated odds ratio for thrombosis was 4.01[CI: 2.30-6.96] in the case of the presence of two at risk genotypes and 8.002 [CI: 4.59-13.93] if all the three at risk genotypes were present. In conclusion these polymorphisms could contribute to the risk of thrombotic complications in HIT.

  4. Dengue Fever: A Rare Cause Of Immune Thrombocytopenia.

    PubMed

    Ramírez-Fonseca, Tania; Segarra-Torres, Amaury; Jaume-Anselmi, Francisco; Ramírez-Rivera, José

    2015-01-01

    Immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet count and skin-mucosal bleeding. In adults it is usually idiopathic and may have a chronic onset, while in children it is usually acute following a viral illness. Dengue has been rarely reported as a cause of ITP. We report a case of a young adult woman that presented with acute ITP following a dengue virus infection.

  5. Thrombocytopenia-absent radius syndrome: a clinical genetic study

    PubMed Central

    Greenhalgh, K; Howell, R; Bottani, A; Ancliff, P; Brunner, H; Verschuuren-Bemel..., C; Vernon, E; Brown, K; Newbury-Ecob, R

    2002-01-01

    The thrombocytopenia-absent radius (TAR) syndrome is a congenital malformation syndrome characterised by bilateral absence of the radii and a thrombocytopenia. The lower limbs, gastrointestinal, cardiovascular, and other systems may also be involved. Shaw and Oliver in 1959 were the first to describe this condition, but it was Hall et al in 1969 who reported the first major series of patients. Since then most reports have been based on single or small numbers of cases. We report the results of a clinical study looking at the phenotype of 34 patients with TAR syndrome. All cases had a documented thrombocytopenia and bilateral radial aplasia, 47% had lower limb anomalies, 47% cow's milk intolerance, 23% renal anomalies, and 15% cardiac anomalies. Congenital anomalies not previously described in association with TAR syndrome included facial capillary haemangiomata, intracranial vascular malformation, sensorineural hearing loss, and scoliosis. Karyotype analysis, chromosome breakage studies including premature centromeric separation and fluorescence in situ hybridisation studies looking for a deletion of chromosome 22q11 were undertaken. Two abnormal karyotypes were identified. PMID:12471199

  6. Orthotopic liver transplant for multifocal lymphangioendotheliomatosis with thrombocytopenia.

    PubMed

    Yang, Christine H; Zhou, Shengmei; Alexopoulos, Sophoclis; Wang, Larry; Baron, Howard I; Genyk, Yuri; Kerkar, Nanda

    2016-05-01

    An eight-yr-old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach-Merritt-like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d-dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan to manage her GI lesions with APC post-transplant. Post-transplant, her liver function and coagulopathy normalized, and GI tract lesions disappeared upon screening with capsule endoscopy. The patient is doing well, without recurrence of either GI lesions or thrombocytopenia, at 18 months after transplantation. PMID:26917412

  7. 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

  8. 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

  9. [Thrombocytopenia induced by rifampicin not previously sensitized: a case presentation].

    PubMed

    Neino Mourtala Mohamed, A; Tummino, C; Gouitaa, M; Chanez, P

    2013-11-01

    Thrombocytopenia induced by rifampicin in the absence of prior sensitization is exceptional, especially when it occurs in a patient without risk factors. We report the case of a patient aged 25 years with no past history of medical, surgical or knowledge of having taken rifampicin previously, who was hospitalized for treatment of thrombocytopenic purpura occurring after the initiation of fixed combination quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for pulmonary tuberculosis. The biological pretreatment and therapeutic education had not been made. The patient presented with thrombocytopenic purpura 30000/mm(3) on day 9 after the initiation of treatment. The platelet count returned to normal 10 days after discontinuation of treatment. We elected not to reintroduce rifampicin given the strong likelihood that it was responsible for this complication. We conducted a phased reintroduction of isoniazid, ethambutol and pyrazinamide. No recurrence of the thrombocytopenia occurred. Thus, the diagnosis of rifampicin-induced thrombocytopenia appears to have been confirmed and the patient tolerated the remainder of their treatment well.

  10. 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.

  11. 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

  12. 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

  13. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

    PubMed Central

    Nakajima, Shihoko; Ando, Taiki; Oda, Keisuke; Sugita, Manabu; Maeda, Kunimi; Nakiri, Yutaka

    2016-01-01

    A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT. PMID:27699076

  14. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

    PubMed Central

    Nakajima, Shihoko; Ando, Taiki; Oda, Keisuke; Sugita, Manabu; Maeda, Kunimi; Nakiri, Yutaka

    2016-01-01

    A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT). By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT.

  15. 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

  16. Prevalence of Alloimmunization to Human Platelet Antigen Glycoproteins and Human Leucocyte Antigen Class I in β Thalassemia Major Patients in Western India.

    PubMed

    Philip, Joseph; Kumar, Sudeep; Chatterjee, T; Mallhi, R S

    2014-12-01

    Present management of β thalassemia major by regular packed red blood cell (PRBC) transfusions poses risk of alloimmunization not only to red blood cell antigens, but also to human platelet antigens (HPA) and Human leucocyte antigens class I (HLA I). However data in this context is very limited in Indian population. The aim of the study was to determine the prevalence of alloimmunization to HPA and HLA I in β thalassemia major patients who have received multiple PRBC transfusions over the years. A cross sectional study was performed at our tertiary care blood bank. β thalassemia major patients of more than 6 years of age were included who were receiving fresh, leucoreduced and irradiated PRBC units regularly with annual requirement of more than ten PRBC transfusions. A total of 9 out of 80 (11.25 %) patients were found to be alloimmunized for HPA antigens of various specificity and 24 out of 80 (30 %) developed antibodies to HLA I. The awareness of development of alloimmunization to HPA and HLA antigens in multi PRBC transfused thalassemics, despite use of leucofilters will prompt us, to look for improvement in our current PRBC preparations to minimise platelet alloimmunisation. Further studies are required to validate the findings and build the base line data in this regard. This is of importance, especially in view of providing suitable cross-matched platelets when required in future especially when considering future haematopoietic stem cell transplantation (HSCT).

  17. Delayed profound thrombocytopenia presenting 7 days after use of abciximab (ReoPro).

    PubMed

    Sharma, Sanjiv; Bhambi, Brijesh; Nyitray, William; Sharma, Geetanjali; Shambaugh, Shawn; Antonescu, Adrian; Shukla, Pankaj; Denny, Eileen

    2002-01-01

    A case of a 65-year-old woman presenting with delayed profound thrombocytopenia 7 days after the use of abciximab (ReoPro) in the setting of percutaneous coronary intervention is described. The patient had normal platelet counts for the first 24 hours after the use of abciximab (ReoPro). She presented with petechiae and profound thrombocytopenia 1 week later. The patient was treated successfully with a platelet transfusion and recovered uneventfully. Profound thrombocytopenia occurs acutely within the first few hours after abciximab (ReoPro) use, so this case was unique in that the profound thrombocytopenia presented 1 week after use of abciximab (ReoPro).

  18. 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

  19. 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.

  20. 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

  1. Contemporary management of primary immune thrombocytopenia in adults.

    PubMed

    Lakshmanan, S; Cuker, A

    2012-10-01

    Immune thrombocytopenia (ITP) comprises a syndrome of diverse disorders that have in common immune-mediated thrombocytopenia, but that differ with respect to pathogenesis, natural history and response to therapy. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or as a sequela of a growing list of associated conditions (secondary ITP). Primary ITP remains a diagnosis of exclusion and must be differentiated from non-autoimmune etiologies of thrombocytopenia and secondary causes of ITP. The traditional objective of management is to provide a hemostatic platelet count (> 20-30 × 10(9) L(-1) in most cases) while minimizing treatment-related toxicity, although treatment goals should be tailored to the individual patient and clinical setting. Corticosteroids, supplemented with either intravenous immune globulin G or anti-Rh(D) as needed, are used as upfront therapy to stop bleeding and raise the platelet count acutely in patients with newly diagnosed or newly relapsed disease. Although most adults with primary ITP respond to first-line therapy, the majority relapse after treatment is tapered and require a second-line approach to maintain a hemostatic platelet count. Standard second-line options include splenectomy, rituximab and the thrombopoietin receptor agonists, romiplostim and eltrombopag. Studies that directly compare the efficacy, safety and cost-effectiveness of these approaches are lacking. In the absence of such data, we do not favor a single second-line approach for all patients. Rather, we consider the pros and cons of each option with our patients and engage them in the decision-making process.

  2. 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

  3. Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism

    PubMed Central

    Bowles, K M; Turner, G E; Wimperis, J Z

    2004-01-01

    The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later. PMID:15333667

  4. [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

  5. 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

  6. Immunity to Polyomavirus BK Infection: Immune Monitoring to Regulate the Balance between Risk of BKV Nephropathy and Induction of Alloimmunity

    PubMed Central

    Cioni, Michela; Basso, Sabrina; Gagliardone, Chiara; Potenza, Leonardo; Verrina, Enrico; Luppi, Mario; Zecca, Marco; Ghiggeri, Gian Marco; Ginevri, Fabrizio

    2013-01-01

    Polyomavirus BK-associated nephropathy (PyVAN) is the main infectious cause of allograft damage after kidney transplantation. A number of studies revealed an association between the presence of BKV-specific cellular immunity and BK viral clearance, with patients failing to recover specific T cells progressing to PyVAN. Evolution to allograft dysfunction can be prevented by restoration of BKV-specific immunity through a stepwise reduction of maintenance immunosuppressive drugs. Prospective monitoring of BK viral load and specific immunity, together with B-cell alloimmune surveillance, may allow a targeted modification/reduction of immunosuppression, with the aim of obtaining viral clearance while preventing graft injury due to deposition of de novo donor-specific HLA antibodies and late/chronic antibody-mediated allograft injury. Innovative, immune-based therapies may further contribute to BKV infection prevention and control. PMID:24000288

  7. High level increase in liver enzymes and severe thrombocytopenia in a male case of anorexia nervosa*

    PubMed Central

    Karahmadi, Mojgan; Layegh, Elmira; Layegh, Samira; Keypour, Maryam

    2011-01-01

    BACKGROUND: Anorexia nervosa (AN) is a difficult-to-treat psychosomatic disease. Very few cases of acute liver failure associated with AN have been described. We describe one patient who was affected by AN and presented high level increase of serum liver enzymes, along with sever thrombocytopenia. Then, we discuss the possible etiopathogenic factors. METHODS: A 14-year-old boy with AN was admitted in the pediatric psychiatric emergency department of Alzahra Hospital with impaired electrolyte levels, bradycardia, hypotension, liver dysfunction, and thrombocytopenia. RESULTS: A ten-time increase in liver enzymes and thrombocytopenia were observed on admission. After two months of treatment, the levels were within the normal range. CONCLUSIONS: Improvement of initial clinical symptoms and recovery of liver enzymes and thrombocytopenia after the treatment suggested that liver dysfunction and thrombocytopenia may be observed in AN patients and should be taken care of by physicians. PMID:22973335

  8. 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

  9. Elevated Plasma P-Selectin Autoantibodies in Primary Sjögren Syndrome Patients with Thrombocytopenia.

    PubMed

    Hu, Ya-Hui; Zhou, Peng-Fei; Long, Guang-Feng; Tian, Xin; Guo, Yu-Fan; Pang, Ai-Ming; Di, Ran; Shen, Yan-Na; Liu, Yun-De; Cui, Yu-Jie

    2015-11-28

    BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.

  10. Heparin-induced thrombocytopenia screening and management in pediatric patients.

    PubMed

    Takemoto, Clifford M; Streiff, Michael B

    2011-01-01

    The diagnosis and management of heparin-induced thrombocytopenia (HIT) in pediatric patients poses significant challenges. The cardinal findings in HIT, thrombocytopenia and thrombosis with heparin exposure, are seen commonly in critically ill children, but are most often secondary to etiologies other than HIT. However, without prompt diagnosis, discontinuation of heparin, and treatment with an alternative anticoagulant such as a direct thrombin inhibitor (DTI), HIT can result in life- and limb-threatening thrombotic complications. Conversely, DTIs are associated with higher bleeding risks than heparin in adults and their anticoagulant effects are not rapidly reversible; furthermore, the experience with their use in pediatrics is limited. Whereas immunoassays are widely available to aid in diagnosis, they carry a significant false positive rate. Age-dependent differences in the coagulation and immune system may potentially affect manifestations of HIT in children, but have not been extensively examined. In this chapter, diagnostic approaches and management strategies based on a synthesis of the available pediatric studies and adult literature on HIT are discussed.

  11. 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

  12. Neonatal leukaemia cutis.

    PubMed

    Handler, M Z; Schwartz, R A

    2015-10-01

    Neonatal leukaemia cutis is a significant neoplasm that may represent a cutaneous manifestation of systemic leukaemia, usually of myeloblastic type. Rarely, it may be or appear to be limited to skin, in which case it is called neonatal aleukaemic leukaemia cutis. By definition, it presents within the first 4 weeks of life and often has a 'blueberry muffin baby' appearance of magenta coloured nodules affecting almost any area of the skin, usually sparing mucous membranes, palms and soles. This clinical pattern is more commonly associated with neonatal infections such rubella and toxoplasmosis, and may be evident with other neonatal neoplasms such as neuroblastoma. Due to the morbidity associated with chemotherapy and reported cases of spontaneous remission without systemic progression in those with neonatal aleukaemic leukaemia cutis without 11q23 translocation, the authors not treating the child with chemotherapy, but to simply monitor for fading of the violaceous nodules, and watch for possible signs of systemic leukaemia.

  13. 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

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

    PubMed

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

    2016-06-01

    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.

  15. 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

  16. TIGIT-positive circulating follicular helper T cells display robust B-cell help functions: potential role in sickle cell alloimmunization.

    PubMed

    Godefroy, Emmanuelle; Zhong, Hui; Pham, Petra; Friedman, David; Yazdanbakhsh, Karina

    2015-11-01

    T follicular helper cells are the main CD4(+) T cells specialized in supporting B-cell responses, but their role in driving transfusion-associated alloimmunization is not fully characterized. Reports of T follicular helper subsets displaying various markers and functional activities underscore the need for better characterization/identification of markers with defined functions. Here we show that a previously unidentified subset of human circulating T follicular helper cells expressing TIGIT, the T-cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains, exhibit strong B-cell help functions. Compared to the subset lacking the receptor, T follicular helper cells expressing this receptor up-regulated co-stimulatory molecules and produced higher levels of interleukins (IL-21 and IL-4) critical for promoting B-cell activation/differentiation. Furthermore, this subset was more efficient at inducing the differentiation of B cells into plasmablasts and promoting immunoglobulin G production. Blocking antibodies abrogated the B-cell help properties of receptor-expressing T follicular helper cells, consistent with the key role of this molecule in T follicular helper-associated responses. Importantly, in chronically transfused patients with sickle cell anemia, we identified functional differences of this subset between alloimmunized and non-alloimmunized patients. Altogether, these studies suggest that expression of the T-cell immunoreceptor with Ig and immunoreceptor tyro-sine-based inhibitory domains not only represents a novel circulating T follicular helper biomarker, but is also functional and promotes strong B-cell help and ensuing immunoglobulin G production. These findings open the way to defining new diagnostic and therapeutic strategies in modulating humoral responses in alloimmunization, and possibly vaccination, autoimmunity and immune deficiencies.

  17. 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

  18. [Heparin induced thrombocytopenia and anticoagulation in renal replacemant therapy].

    PubMed

    Steinfeldt, Thorsten; Rolfes, Caroline

    2008-04-01

    The decision for an anticoagulant for renal replacement therapy (RRT) in patients with acute renal failure and heparin-induced thrombocytopenia (HIT) has to be made carefully. Based on results from the literature argatroban is favoured in patients without hepatic dysfunction, referring to its short halftime and easy feasable monitoring. In the case of coexsisting hepatic disorder, danaparoid provides a safe alternative therapy. However, long halftime and the difficult elimination of the substance are unfavourable. Lepirudin represents another possible anticoagulant therapy. Bleeding complications and monitoring of the ecarin clotting time imposes limitations. Experiences with bivalirudin, fondaparinux and prostaglandines are limited and future trials will have to determine the significance of their application in RRT in HIT patients. Furthermore it has to be proven whether the combination of alternative anticoagulants with citrate prolongates circuit halftime of CVVH.

  19. 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

  20. Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC).

    PubMed

    Kitchens, Craig S

    2009-01-01

    Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.

  1. Agents for the treatment of heparin-induced thrombocytopenia.

    PubMed

    Warkentin, Theodore E

    2010-08-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect characterized by platelet activation, hypercoagulability, and increased risk of thrombosis, both venous and arterial. A diagnosis of HIT usually signifies that heparin products, including unfractionated and low-molecular-weight heparin, are contraindicated. Although it is uncertain whether heparin continuation really worsens clinical outcomes, it is clear that vitamin K antagonists such as warfarin do worsen outcomes, as they promote microvascular thrombosis, with the potential for limb amputation (venous limb gangrene). Thus, alternative nonheparin anticoagulants are at the forefront of HIT therapy. This review proposes that alternative anticoagulants (danaparoid, fondaparinux) that share certain properties of heparin-namely its irreversible antithrombin-mediated inhibition of factor Xa-and that have relatively long half-lives, have several advantages in the therapy for HIT over short-acting agents that inhibit thrombin directly (recombinant hirudin, argatroban, and bivalirudin). PMID:20659659

  2. 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

  3. Neonatal hearing screening.

    PubMed

    Kenna, Margaret A

    2003-04-01

    Neonatal hearing screening can be performed using reliable and reproducible methods. Intervention before the age of 6 months with hearing aids and appropriate educational support services will give the infant the best possible opportunity to develop language. Potential barriers to efficient implementation of a neonatal hearing screening program include access to appropriate and timely diagnostic and support services and insurance to cover the services. Without universal neonatal hearing screening, many children with hearing loss will be missed, which will have a direct negative impact on their speech, language, educational, and social development. PMID:12809324

  4. Immunomodulation and immune thrombocytopenia: some unmet needs, questions, and outlook.

    PubMed

    Godeau, Bertrand

    2016-04-01

    During the last two decades, new therapeutic strategies have been developed, particularly anti-CD20 agents and thrombopoietin-receptor (TPO-r) mimetics, for immune thrombocytopenia (ITP). However, although the new efficient drugs have deeply modified the therapeutic strategy and the disease prognosis, there are still unmet needs and challenges. Concerning rituximab, reassuring data concerning its safety have recently been reported. The main limitation of the treatment is its modest long-term efficacy, with frequent disease relapse. Maintenance treatment or association with other immunomodulatory drugs such as dexamethasone may achieve better long-term response. With failure of one of the available TPO-r agonists (ie, romiplostim and eltrombopag), another can be used. Switching may be beneficial, with more than 50% chance of response, and could limit the risk of platelet fluctuation occasionally observed with these treatments. According to the mechanism of action of TPO-r agonists, a rapid relapse of thrombocytopenia should be observed after they are stopped. Several recent observational studies suggested sustained responses in patients achieving complete response with TPO-r agonists and who stopped the treatments. Prospective studies to confirm these unexpected data are needed. Thrombosis in ITP is a concern, particularly with TPO-r agonists, even though the pivotal studies of eltrombopag and romiplostim did not report a higher incidence of thrombosis events with TPO-r agonists than placebo. Despite these reassuring data, the risk of thrombosis with TPO-r agonists remains unanswered, particularly with secondary ITP or in older adults. PMID:27312163

  5. [Neonatal herpes simplex infection].

    PubMed

    van Ham-Borawitz, Veronique E J; Stam, Edo D; Welborn, Kathleen M; Sas, Theo 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.

  6. Drug Screening in Neonates.

    PubMed

    Bell, Susan Givens

    2016-01-01

    Gestational substance exposure continues to be a significant problem. Neonates may be exposed to various substances including illicit drugs, prescription drugs, and other legal substances that are best not used during pregnancy because of their potential deleterious effects as possible teratogens or their potential to create dependence and thus withdrawal in the neonate. Screening the newborn for gestational substance exposure is important for both acute care and early intervention to promote the best possible long-term outcomes. This column provides insight into what is known about the extent of substance use by pregnant women, an overview of neonatal biologic matrices for drug testing, and a discussion of the legal implications of neonatal substance screening. PMID:27636697

  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. 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

  9. Telemedicine for neonatal resuscitation.

    PubMed

    Scheans, Patricia

    2014-01-01

    Maintaining high levels of readiness for neonatal resuscitation in low-risk maternity settings is challenging. The neonatal resuscitation program (NRP) algorithm is a community standard in the United States; yet training is biannual, and exposure to enough critical events to be proficient at timely implementation of the algorithm and the advanced procedures is rare. Evidence supports hands-free leadership to help prevent task saturation and communication to promote patient safety. Telemedicine for neonatal resuscitation involves the addition of remote, expert NRP leadership (a NICU-based neonatal nurse practitioner) via camera link to augment effectiveness of the low-risk birth center team. Unanticipated outcomes to report include faster times to transfer initiation and neuroprotective cooling. The positive impact of remote NRP leadership could lead to use of telemedicine to support teams at birthing centers throughout the United States as well as around the world.

  10. Erythropoietin and Neonatal Neuroprotection.

    PubMed

    Juul, Sandra E; Pet, Gillian C

    2015-09-01

    Certain groups of neonates are at high risk of developing long-term neurodevelopmental impairment and might be considered candidates for neuroprotective interventions. This article explores some of these high-risk groups, relevant mechanisms of brain injury, and specific mechanisms of cellular injury and death. The potential of erythropoietin (Epo) to act as a neuroprotective agent for neonatal brain injury is discussed. Clinical trials of Epo neuroprotection in preterm and term infants are updated. PMID:26250911

  11. [Acute-onset thrombocytopenia following single inhalation xylene exposure--a case report].

    PubMed

    Siwek-Iwanicka, Jolanta; Chwaluk, Agnieszka

    2013-01-01

    Bone marrow damage is a well known consequence of chronic exposure to benzene and its homologues, which include xylene. Anemia dominates in the clinical picture and isolated thrombocytopenia is a rare symptom. We have not found reports of isolated thrombocytopenia in the course of acute xylene poisoning. A 56-years old man with thrombocytopenia, was admitted, after two days of work with concrete floor paint containing up to 17% xylene. The thrombocytes' nadir (29 x 10(9)/L) occurred on the fourth day from the exposure. After treatment with dexamethasone the platelet count normalized. There were no signs of hemorrhagic diathesis. Clinicians should be aware of the possibility of thrombocytopenia in patients acutely exposed to xylene.

  12. Neonatal renal vein thrombosis.

    PubMed

    Brandão, Leonardo R; Simpson, Ewurabena A; Lau, Keith K

    2011-12-01

    Neonatal renal vein thrombosis (RVT) continues to pose significant challenges for pediatric hematologists and nephrologists. The precise mechanism for the onset and propagation of renal thrombosis within the neonatal population is unclear, but there is suggestion that acquired and/or inherited thrombophilia traits may increase the risk for renal thromboembolic disease during the newborn period. This review summarizes the most recent studies of neonatal RVT, examining its most common features, the prevalence of acquired and inherited prothrombotic risk factors among these patients, and evaluates their short and long term renal and thrombotic outcomes as they may relate to these risk factors. Although there is some consensus regarding the management of neonatal RVT, the most recent antithrombotic therapy guidelines for the management of childhood thrombosis do not provide a risk-based algorithm for the acute management of RVT among newborns with hereditary prothrombotic disorders. Whereas neonatal RVT is not a condition associated with a high mortality rate, it is associated with significant morbidity due to renal impairment. Recent evidence to evaluate the effects of heparin-based anticoagulation and thrombolytic therapy on the long term renal function of these patients has yielded conflicting results. Long term cohort studies and randomized trials may be helpful to clarify the impact of acute versus prolonged antithrombotic therapy for reducing the morbidity that is associated with neonatal RVT.

  13. 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.

  14. 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

  15. 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.

  16. Evaluation of Thrombocytopenia in Systemic Lupus Erythematosus and Correlation with Different Organs Damages

    PubMed Central

    Ktona, Ergeta; Barbullushi, Myftar; Backa, Teuta; Idrizi, Alma; Shpata, Vjolica; Roshi, Enver

    2014-01-01

    Introduction: Thrombocytopenia is highly prevalent among patients with Systemic Lupus Erythematous(SLE) and at the same time it has been reported that a correlation exists between Thrombocytopenia and organ damage. The aim of this study is to highlight the correlation between Thrombocytopenia and the clinical manifestations of SLE. Objectives: The objective is to show the clinical manifestations and organ damage of Systemic Lupus Erythematous (SLE) patients who have been found to have Thrombocytopenia. Methods: A retrospective study was conducted examining all patient charts diagnosed and treated for SLE at the Rheumatology Service of Mother Teresa Hospital Centre. All the data were collected from discharged patient charts. The data included were Anti DNA,AAN,C3 , thrombocytopenia, leucopenia, and organ damage. Data were taken from 2009 to 2013. The classification criteria of the American College of Rheumatology was used for all patients regarding the diagnosis. Results: Out of 330 patients, 12 (3.64%) are men and 318 (96.3%) women. 73 of all patients have thrombocytopenia as cases and 257 patients had SLE without thrombocytopenia, which was considered as the control group. AAN 68(93.1%), Anti DNA 50 (64.3%) , low value of C3 46 (63%), and leucopenia were higher in thrombocytopenic patients compared with control group (p<0.05) 48 (65.7%) of thrombocytopenic patients develop lupus nephritis, 10 (13.6%) were with pulmonary involvement, and 42 (57.5%) had leukopenia. Conclusion: Thrombocytopenia is not directly associated with any disease activity, organ damage and mortality, but it should be considered as a prognostic factor which may help identifying a category of patients whose disease course can be aggravated. PMID:24944538

  17. Heparin-induced thrombocytopenia following coronary artery bypass grafting: a diagnostic dilemma

    PubMed Central

    Khanal, Raju; Karmacharya, Paras; Forman, Daniel A.

    2015-01-01

    The diagnosis of heparin-induced thrombocytopenia (HIT) is a challenge in post-cardiac surgery patients because of the high incidence of non-immune thrombocytopenia and heparin–platelet factor 4 antibodies in these groups. We present a case of HIT in a post coronary artery bypass surgery patient, which was successfully treated with prompt recognition and discontinuation of heparin products. PMID:26486110

  18. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    PubMed

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to <20,000 platelets/pL). Diagnosis of DIIT is complicated by its similarity to other non-drug-induced immune thrombocytopenias, including autoimmune thrombocytopenia, posttransfusion purpura, and platelet transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal

  19. 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.

  20. 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.

  1. 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

  2. Entecavir-Associated Thrombocytopenia in a Decompensated Cirrhotic Patient: A Case Report and Literature Review

    PubMed Central

    Fan, Xiaoli; Chen, Liyu; Yang, Jingyu; Feng, Ping

    2016-01-01

    Abstract Drug-associated thrombocytopenia is common and curable, but there were few reports about entecavir-associated thrombocytopenia. We report here a case of a 65-year-old female patient with decompensated cirrhosis. The patient developed a fatal thrombocytopenia while under entecavir treatment. After she received entecavir treatment for 4 days, the patient's platelet count dropped significantly to 1 × 109/L, accompanied with a manifestation of mild sclera bleeding. All diagnostic data suggested an entecavir-induced immunological thrombocytopenia. The patient eventually fully recovered after treated with daily intravenous immunoglobulin infusions. Actually, there were only a handful of reports that children or adults with chronic hepatitis B developed a thrombocytopenia due to nucleoside analogue medication. Timeliness of intravenous immunoglobulin infusion could stop the fatal bleeding for patients with entecavir-associated immunological thrombocytopenia. Hence, early diagnosis and treatment are recommended. Our case suggested that the platelet count should be monitored regularly in patients with decompensated cirrhosis with underline immunological disease while treated with ETV. PMID:27015182

  3. Expanded Non-human Primate Tregs Exhibit A Unique Gene Expression Signature and Potently Downregulate Allo-immune Responses

    PubMed Central

    Anderson, Alan; Martens, Christine; Hendrix, Rose; Stempora, Linda; Miller, Wes; Hamby, Kelly; Russell, Maria; Strobert, Elizabeth; Blazar, Bruce R.; Pearson, Thomas C.; Larsen, Christian P.; Kean, Leslie S.

    2009-01-01

    We have established two complementary strategies for purifying naturally occurring regulatory T cells (Tregs) from rhesus macaques in quantities which would be sufficient for use as an in vivo cellular therapeutic. The first identified Tregs based on their being CD4+/CD25bright. The second incorporated CD127, and purified Tregs based on their expression of CD4 and CD25 and their low expression of CD127. Using these purification strategies, we were able to purify as many as 1×106 Tregs from 120cc of peripheral blood. Culture of these cells with anti-CD3, anti-CD28 and IL-2 over 21 days yielded as much as 450-fold expansion, ultimately producing as many as 4.7×108 Tregs. Expanded Treg cultures potently inhibited alloimmune proliferation as measured by a CFSE-MLR assay even at a 1:100 ratio with responder T cells. Furthermore, both responder-specific and third-party Tregs downregulated alloproliferation similarly. Both freshly isolated and cultured Tregs had gene expression signatures distinguishable from concurrently isolated bulk CD4+ T cell populations, as measured by single-plex RT-PCR and gene array. Moreover, an overlapping yet distinct gene expression signature seen in freshly isolated compared to expanded Tregs identifies a subset of Treg genes likely to be functionally significant. PMID:18801023

  4. 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

  5. Laparoscopic splenectomy for primary immune thrombocytopenia: Current status and challenges

    PubMed Central

    Zheng, Dong; Huang, Chen-Song; Huang, Shao-Bin; Zheng, Chao-Xu

    2016-01-01

    Primary immune thrombocytopenia (ITP) is an immune-mediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20%-40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy (LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting long-term outcome of splenectomy which can help make the decision of operation. PMID:27668071

  6. [Guidelines for diagnosis, treatment and monitoring of primary immune thrombocytopenia].

    PubMed

    Sanz, Miguel Ángel; Vicente García, Vicente; Fernández, Antonio; López, M Fernanda; Grande, Carlos; Jarque, Isidro; Martínez, Rafael; Mingot, María Eva; Monteagudo, Emilio; Ribera, Josep M A; Valcárcel, David

    2012-03-17

    The consensus document on the diagnosis, treatment and monitoring of primary immune thrombocytopenia was developed in 2010 by specialists with recognized expertise in this disease under the auspices of the Spanish Society of Hematology and Hemotherapy and the Spanish Society of Pediatric Hematology and Oncology, with the aim to adapt to Spain the recommendations of the recently published international consensus documents. The decision to start treatment is based on bleeding manifestations and platelet count (<20×10(9)/L). The first-line treatment is corticosteroids, albeit for a limited period of 4-6 weeks. The addition of intravenous immunoglobulin is reserved to patients with severe bleeding. Splenectomy is the most effective second-line treatment. For patients refractory to splenectomy and those with contraindications or patient refusal, the new thrombopoietic agents are the drugs of choice due to their efficacy and excellent safety profile. The other treatment options have highly variable response rates, and the absence of controlled studies does not allow to establish clear recommendations. Monitoring should be individualized. In patients without active treatment, blood counts are recommended every 3-6 months, and the patient should be instructed to consult in case of bleeding, surgery or invasive procedure and pregnancy. In most of the pediatric population, the disease tends to spontaneous remission. High-dose corticosteroids in short course and intravenous immunoglobulin are the treatment of choice. Second- and further-line treatments should be monitored in specialized centers.

  7. Decreased IL-35 levels in patients with immune thrombocytopenia.

    PubMed

    Yang, Yanhui; Xuan, Min; Zhang, Xian; Zhang, Donglei; Fu, Rongfeng; Zhou, Fangfang; Ma, Li; Li, Huiyuan; Xue, Feng; Zhang, Lei; Yang, Renchi

    2014-08-01

    IL-35 is a novel heterodimeric anti-inflammatory cytokine consisting of Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. IL-35 has been shown to possess the potency of inhibiting the CD4+ effector T cells and alleviating autoimmune diseases. In the study we investigated the levels of IL-35 as well as its prospective role in immune thrombocytopenia (ITP).ELISA was adopted to measure plasma IL-35, TGF-β and IL-10 levels. The mRNA expression levels of P35 and EBI3 in peripheral blood mononuclear cells (PBMCs) were studied based on real-time quantitative PCR. The correlation between plasma cytokine levels and clinical parameters was analyzed. Significantly lower plasma IL-35 levels were found in active ITP patients compared with those in remission (p = 0.017) and the healthy controls (p < 0.001). In active ITP patients, the plasma IL-35 levels displayed a significantly positive correlation with platelet counts (r = 0.5335, p < 0.0008). Further, P35 mRNA expression levels were lower in patients with active ITP than patients in remission (p = 0.033) and normal controls (p = 0.016).Thus, for the first time, this research reported a dramatically decreased IL-35 levels in ITP patients, suggesting that IL-35 may be involved in the pathogenesis of ITP.

  8. Heparin-induced thrombocytopenia: real-world issues.

    PubMed

    Linkins, Lori-Ann; Warkentin, Theodore E

    2011-09-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. PMID:22102268

  9. Emerging therapy options in heparin-induced thrombocytopenia.

    PubMed

    Chaudhary, Ranjit K; Khanal, Nabin; Giri, Smith; Pathak, Ranjan; Bhatt, Vijaya R

    2014-01-01

    Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening thrombotic complication of heparin, which is the result of platelet activation by anti-PF4/heparin antibodies. With lepirudin and danaparoid no longer available in the US, treatment options are limited to argatroban, fondaparinux (off-label use) and bivalirudin (for patients undergoing percutaneous coronary intervention). Both argatroban and bivalirudin are parenteral drugs and require close monitoring and hospitalization. Fondaparinux is contraindicated in patients with significant renal impairment and is associated with a small risk of HIT. Anticoagulants approved for thromboprophylaxis and management of thromboembolic conditions such as rivaroxaban, dabigatran, and apixaban have fixed oral dose, rapid onset of action and does not require monitoring. These novel agents do not interact with anti-PF4/heparin antibody and offer attractive therapy options for HIT. Their utility in HIT has been supported by a few clinical reports, however, larger studies are needed before they can be utilized in clinical practice. Therapeutic plasma exchange has been utilized with some success in patients with HIT, who need heparin reexposure for cardiac surgery but their safety and efficacy needs further exploration. 2-O, 3-O desulfated heparin, which lacks any anticoagulant effect, has been shown to reduce the development of HIT in murine models. Finally, novel targets based on the molecular pathogenesis of HIT are being studied for therapeutic drug development. We hope that the availability of novel therapies in the future will expand the options available for the management of HIT. PMID:25374012

  10. Laparoscopic splenectomy for primary immune thrombocytopenia: Current status and challenges.

    PubMed

    Zheng, Dong; Huang, Chen-Song; Huang, Shao-Bin; Zheng, Chao-Xu

    2016-09-16

    Primary immune thrombocytopenia (ITP) is an immune-mediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20%-40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy (LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting long-term outcome of splenectomy which can help make the decision of operation. PMID:27668071

  11. Ischemic stroke associated with immune thrombocytopenia: lesion patterns and characteristics.

    PubMed

    Park, Hong-Kyun; Lee, Seung-Hoon

    2014-11-01

    Although the patients with immune thrombocytopenia (ITP) have a very low platelet count, which usually causes hemorrhagic complications, they occasionally experience ischemic stroke. However, the mechanism underlying ITP-related ischemic stroke (ITP-IS) has not been fully clarified. We aim to elucidate the ITP-IS mechanism by analyzing the ischemic lesion patterns and clinical characteristics. We assessed consecutive first-ever acute ischemic stroke (AIS) patients with ITP admitted to Seoul National University Hospital between October 2002 and October 2011. The stroke lesion pattern and clinical characteristics of ITP-IS patients were analyzed. Of the 2,185 patients with first-ever AIS, seven patients (4 women) with ITP-IS were identified. Of these seven patients, 3 (43 %) who were classified as undetermined stroke etiology indicated an embolic stroke pattern, and had no remarkable atherosclerotic risk factors, no steno-occlusive lesions in their relevant artery, and no cardioembolic etiologies or conditions causing secondary ITP. Moreover, compared with the patients without ITP, the patients with ITP were younger and had lower platelet counts. Thus, we noted that ITP is a rare cause of ischemic stroke, which primarily occurs due to the development of a thromboembolism in the brain. We believe that this paradoxical mechanism of ITP-associated thrombus formation requires further investigation.

  12. Role of CD61+ cells in thrombocytopenia of dengue patients.

    PubMed

    Noisakran, Sansanee; Onlamoon, Nattawat; Pattanapanyasat, Kovit; Hsiao, Hui-Mien; Songprakhon, Pucharee; Angkasekwinai, Nasikarn; Chokephaibulkit, Kulkanya; Villinger, Francois; Ansari, Aftab A; Perng, Guey Chuen

    2012-11-01

    Although hematological disorders with salient features of thrombocytopenia have been well documented in dengue patients, the role of CD61-expressing platelets and the megakaryocytic cell lineage in the pathogenesis of dengue virus (DENV) infection remains largely unexplored. A prospective observational study was performed using blood samples and PBMCs from dengue-confirmed patients, as well as from rhesus monkeys (RM) experimentally infected with DENV. Immunohistochemical staining and FACS techniques were applied to evaluate the frequencies of CD61(+) cells that contained DENV antigen. Highly enriched population of CD61(+) cells was also isolated from acute DENV-infected RM and assayed for DENV RNA by quantitative RT-PCR. Results revealed that DENV antigen was found in small vesicles of varying size, and more frequently in anucleated cells associated with platelets in dengue patients. The DENV antigen-containing cells were CD61(+) and appeared to share characteristics of megakaryocytes. Kinetic profiles of CD61(+) cells from DENV-infected RM revealed a transient increase in CD61(+)CD62P(+) cells early after DENV infection. DENV RNA in a highly enriched population of CD61(+) cells from the infected RM was observed during acute stage. Our results indicate that virus containing CD61(+) cells may be directly linked to the platelet dysfunction and low platelet count characteristics of dengue patients.

  13. 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

  14. Laparoscopic splenectomy for primary immune thrombocytopenia: Current status and challenges

    PubMed Central

    Zheng, Dong; Huang, Chen-Song; Huang, Shao-Bin; Zheng, Chao-Xu

    2016-01-01

    Primary immune thrombocytopenia (ITP) is an immune-mediated disorder affecting both adults and children, characterised by bleeding complications and low platelet counts. Corticosteroids are the first-line therapy for ITP, but only 20%-40% of cases achieve a stable response. Splenectomy is the main therapy for patients failing to respond to corticosteroids for decades, and about two-thirds of patients achieve a long-lasting response. Although some new drugs are developed to treat ITP as second-line therapies in recent years, splenectomy is still the better choice with less cost and more efficiency. Laparoscopic splenectomy (LS) for ITP proves to be a safe technique associated with lower morbidity and faster recovery and similar hematological response when compared to traditional open splenectomy. Based on the unified hematological outcome criteria by current international consensus, the response rate of splenectomy should be reassessed. So far, there are not widely accepted preoperative clinical indicators predicting favorable response to LS. Since the patients undergoing surgery take the risk of complications and poor hematological outcome, the great challenge facing the doctors is to identify a reliable biomarker for predicting long-term outcome of splenectomy which can help make the decision of operation.

  15. 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

  16. 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

  17. Illuminance of neonatal units.

    PubMed

    Robinson, J; Moseley, M J; Fielder, A R

    1990-07-01

    We have measured the illuminance (brightness) of seven neonatal units during both the day and the night. When the units were lit solely by fluorescent tubes the mean illuminance was 348 lux (range 192-690). During the day the mean illuminance was 470 lux (range 236-905). The high dependency regions in four of the seven units were significantly brighter than the corresponding low dependency nurseries at all times. In two of these units there is a policy of reducing the amount of artificial light in the low dependency areas at night, and in these the normal mean illuminance was 50 lux. We have measured the general levels of illumination to which a neonate might be exposed; the ocular exposure to light of a neonate depends, however, on both physical and biological factors and more research is required before an accurate estimate can be made.

  18. 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

  19. 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

  20. Large Bladder Clot-An Unusual Presentation of Neonatal Bilateral Renal Vein Thrombosis-Case Report and Review of Literature.

    PubMed

    Bandari, Jathin; Dangle, Pankaj P; Tennyson, Lauren E; Correa, Andres F; Cannon, Glenn M

    2015-10-01

    A 1-day-old boy born at 37 weeks gestation presented with hematuria, thrombocytopenia, and palpable irregular right flank mass. Renal ultrasound demonstrated large clot within the bladder, bilateral kidney masses with loss of corticomedullary differentiation, and reversal of diastolic flow. The patient was diagnosed with bilateral renal vein thrombosis and was managed conservatively. There was complete resolution of the bladder clot with restoration of corticomedullary differentiation bilaterally. We report the first case of renal vein thrombosis associated with a large bladder clot in a neonate.

  1. A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation.

    PubMed

    Arai, Keisuke; Kuramitsu, Kaori; Fukumoto, Takumi; Kido, Masahiro; Takebe, Atsushi; Tanaka, Motofumi; Kinoshita, Hisoka; Ajiki, Tetsuo; Toyama, Hirochika; Asari, Sadaki; Goto, Tadahiro; Ku, Yonson

    2016-06-16

    There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated.

  2. 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

  3. 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

  4. Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

    PubMed

    Maan, Raoel; de Knegt, Robert J; Veldt, Bart J

    2015-11-01

    Thrombocytopenia (platelet count <150 × 10(9)/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

  5. 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

  6. Moving towards a new era in the management of chronic immune thrombocytopenia.

    PubMed

    Wadenvik, Hans; Olsson, Bob

    2010-07-01

    Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease in which a low concentration of plasma thrombopoietin (TPO) contributes to the thrombocytopenia. Functional thrombopoietin deficiency in response to thrombocytopenia is central to the pathophysiology of chronic ITP. Decreased platelet production in ITP patients has been described only in recent years, however. Following the development of TPO-mimetics, it has become clear that the augmentation of thrombopoiesis is a key therapeutic target. TPO mimetics are novel effective treatments providing durable platelet responses in ITP. Two agents have reached clinical practice, the 'peptibody' romiplostim (Nplate(R)) approved for treatment of thrombocytopenia in patients with chronic ITP in Europe, Canada, Australia and the USA and the non-peptide TPO mimetic, eltrombopag (Promacta(R)), approved in the USA. This review summarises the background to the development of these agents and presents an update on data from randomised phase III trials and open-label studies. These novel drugs provide a noteworthy treatment option for patients with chronic ITP, in whom thrombocytopenia and bleeding risk have not been controlled by standard treatments. The first candidates for treatment in clinical practice are undoubtedly refractory patients with lack of response to other therapies or at continued risk for bleeding despite treatment. Appropriate inclusion of TPO mimetics into the treatment paradigm will most likely have a positive impact on the long-term outcome of ITP and allow carefully monitored patients to remain well controlled, with good tolerability for prolonged periods. PMID:20339846

  7. A difficult diagnosis case of prolonged thrombocytopenia with sepsis and disseminated intravascular coagulation.

    PubMed

    Yoshika, Masamichi; Komiyama, Yutaka; Hirakawa, Akihiko; Nakatani, Toshio; Takahashi, Hakuo

    2011-08-01

    A 19-year-old male was admitted because of the trauma due to sepsis-induced disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). We treated with antibiotics, danaparoid, and continuous hemodiafiltration (CHDF). Once he recovered, but after several days, he had septic shock and MOF again. With treatment, the inflammation and MOF improved but the platelet count was less than 1.0 × 10( 4)/μL. Because of the usage of heparin, we suspected heparin-induced thrombocytopenia (HIT) and measured the HIT antibody and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Heparin-induced thrombocytopenia antibody was positive in the second sepsis but negative in the first sepsis. ADAMTS13 activity was low in both sepses. After stopping CHDF and the usage of heparin, his platelet count improved. Thrombocytopenia is the common and occasional condition for DIC. Heparin-induced thrombocytopenia and thrombotic thrombocytopenic purpura is rare but they must be ruled out in thrombocytopenia with nontypical clinical course, and the assays for HIT antibody and ADAMTS13 activity are useful tools. PMID:20530051

  8. 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

  9. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

    PubMed Central

    Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

    2016-01-01

    Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

  10. 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

  11. Persistent neonatal hyperinsulinism.

    PubMed

    Mathew, P M; Young, J M; Abu-Osba, Y K; Mulhern, B D; Hammoudi, S; Hamdan, J A; Sa'di, A R

    1988-03-01

    Over a 3-year period, the diagnosis of persistent neonatal hyperinsulinism (PNH) was made in seven infants, from an unselected cohort of 18,726 births, all of Saudi Arabian origin. Thus the incidence of PNH was one in 2,675 births. The high incidence, associated consanguinity, and occurrence in siblings suggest that PNH may be inherited as an autosomal recessive disorder.

  12. [Neonatal medicine, past and present].

    PubMed

    Salle, Bernard L; Vert, Paul

    2013-06-01

    This review deals with early neonatal medicine and its rapid development as a medical specialty, starting with the birth of neonatology in the early 19th century. Shaffer first used the term neonatology in 1963 to cover neonatal disorders and their treatment. Between the early 19th century and the 1950s, neonatal care was ensured by obstetricians, whose main goal was to reduce neonatal mortality. After the second world war, and especially the 1960s, the development of neonatal physiology and pathophysiology provided insights into neonatal diseases and their treatment, including respiratory distress, jaundice, malnutrition, and prevention of respiratory distress and brain complications, etc. Currently, neonatal mortality, regardless of birth weight, is below 2/1000, and the survival rate of premature infants, regardless of gestational age and birth weight, exceeds 85%. This represents a resounding success, despite the associated costs, ethical issues, and inevitable morbidity.

  13. 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

  14. An improbable and unusual case of thrombotic thrombocytopenia purpura

    PubMed Central

    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

  15. [Significance of regulatory B cells in nosogenesis of immune thrombocytopenia].

    PubMed

    Li, Xin; Wang, Fang; Ding, Kai Yang; Dai, Lan

    2014-04-01

    This study was aimed to investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia (ITP) and its clinical significance. A total of 35 ITP patients and 20 normal controls were enrolled in this study. The expression of CD19(+)CD24(hi)CD38(hi) B cells was detected by flow cytometry and the expression of IL-10 mRNA and TGF-β1 mRNA was assayed by RT-PCR. The results indicated that the expression level of CD19(+)CD24(hi)CD38(hi) B cells in peripheral blood of newly diagnosed ITP patients was obviously lower than that in normal controls (P < 0.05); the expression level of CD19(+)CD24(hi)CD38(hi) B cells in ITP patients with increased platelet count after treatment was higher than that before treatment (P < 0.05); the expression level of IL-10 mRNA in newly diagnosed ITP patients was significantly lower than that the in normal controls (P < 0.05), the expression level of TGF-β1 mRNA in newly diagnosed ITP patients increases as compared with normal controls (P < 0.05), after treatment with DXM the expression of IL-10 mRNA was enhanced, the expression of TGF-β1 mRNA was reduced as compared with expression level before treatment (P < 0.05). It is concluded that the Breg cells may play an important role in the pathogenesis of ITP via humoral immunity and its regulation of T lymphocytes.

  16. Consequences of treating false positive heparin-induced thrombocytopenia.

    PubMed

    Marler, Jacob; Unzaga, Jessica; Stelts, Sundae; Oliphant, Carrie S

    2015-11-01

    Identification of patients with heparin-induced thrombocytopenia is encumbered by false positive enzyme-linked immuno assay (ELISA) antibody results, therefore a serotonin release assay (SRA) is used for confirmation. Recently, several studies have demonstrated that increasing the optical density (OD) threshold (currently at 0.4) of the antibody test enhances the positive predictive value. The purpose of this study was to determine the frequency of patients who were ELISA antibody positive but SRA negative, and the costs and bleeding events associated with alternative anticoagulant treatment. We hypothesized that treating patients with a positive ELISA antibody OD value of <1.0 would result in increased cost and bleeding risk. This retrospective chart review was conducted on adult hospitalized patients from 2011 to 2013. Patients with positive ELISA antibodies (OD of 0.4-1.0) and an SRA result were included. Eighty-five patients were identified with positive antibodies (average OD of 0.66), 100 % of which were found to be SRA negative. A total of 59 patients (69 %) received alternative anticoagulants. The average duration of treatment was 3.1 days, and 4 patients (4.7 %) experienced a bleeding event. The cost of testing and laboratory monitoring was $36,346 and the cost of the alternative anticoagulants totaled $47,179. The total cost was $83,525, with an average total cost per patient of $982. This study adds to the body of literature suggesting treatment should only be initiated if the OD is one or greater. The high false positive rate caused increased cost and some bleeding events.

  17. Advances in Diagnosis and Treatments for Immune Thrombocytopenia.

    PubMed

    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 × 10(9)/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

  18. [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.

  19. Ebstein's anomaly in neonates.

    PubMed

    Moura, C; Guimarães, H; Areias, J C; Moreira, J

    2001-09-01

    Ebstein's anomaly is a rare congenital heart disease abnormality in which the tricuspid valve leaflets do not attach normally to the tricuspid valve annulus. The effective tricuspid valve orifice is displaced apically into the right ventricle (RV), near the junction of the inlet and the trabecular parts of the RV. The authors present a retrospective study of the patients with Ebstein's anomaly admitted to a neonatal intensive care unit, in the period between January 1993 and March 2000. There were ten patients, representing 0.24% of total neonates and 1.99% of total congenital heart disease admitted to the institution in the same period. Fifty per cent were male and only one case had prenatal diagnosis. Holosystolic murmur (100%) from tricuspid regurgitation and cyanosis (80%) were the most frequent clinical findings. Chest X-ray was abnormal in 90% of the neonates, with a "balloon-shaped" enlarged heart. The main electrocardiographic findings were right atrial enlargement (70%) and arrhythmias (40%). Apical displacement of the septal leaflet of the tricuspid valve, to a maximum of 20 mm, and leaflets tethering to underlying RV myocardium were found in all patients. Tricuspid valve regurgitation was found in 90% (severe form in four cases). An atrial intracardiac shunt, mostly right-to-left, was also found in 50%. Digoxin was used (40%) to restore sinus rhythm. Fifty per cent of the neonates received intravenous prostaglandins. Two patients required a surgical procedure. Two patients died in the neonatal period. During the follow-up period (range 0.3-74.6 months), only one episode of supraventricular tachycardia was recorded. At present seven patients are clinically stable, three of them on medication.

  20. [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

  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.

  2. Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin.

    PubMed

    Kharya, Gaurav; Yadav, Satya Prakash; Katewa, Satyendra; Sachdeva, Anupam

    2011-11-01

    Dengue hemorrhagic fever (DHF) is a potentially lethal complication of dengue fever due to shock and/or bleeding. Bleeding in DHF is due to thrombocytopenia and/or coagulopathy. The authors present their experience of usage of intravenous anti-D in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm(3)). It was administered in a dose of 50 to 75 μg/kg. Mean platelet count was 6800/mm(3) before and 33,600, 44,600, and 79,000/mm(3) after intravenous anti-D administration at 24, 48, and 72 hours, respectively. Average drop in hemoglobin after administration of anti-D was 2.28 g/dL. Intravenous anti-D can possibly be a treatment option for refractory thrombocytopenia in DHF.

  3. [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

  4. Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome

    PubMed Central

    Grimaldi-Bensouda, Lamiae; Nordon, Clémentine; Michel, Marc; Viallard, Jean-François; Adoue, Daniel; Magy-Bertrand, Nadine; Durand, Jean-Marc; Quittet, Philippe; Fain, Olivier; Bonnotte, Bernard; Morin, Anne-Sophie; Morel, Nathalie; Costedoat-Chalumeau, Nathalie; Pan-Petesch, Brigitte; Khellaf, Mehdi; Perlat, Antoinette; Sacre, Karim; Lefrere, François; Abenhaim, Lucien; Godeau, Bertrand

    2016-01-01

    This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×109/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome. PMID:27229715

  5. Mothers at risk of alloimmunization to the Rh (D) antigen and availability of gamma-globulin at the Mexican Institute of Social Security.

    PubMed

    Zavala, C; Salamanca, F

    1996-01-01

    Hemolytic disease of the newborn develops mainly when an Rh negative (D-) mother becomes sensitized and produces anti-Rh positive (anti-D) antibodies capable of hemolysing D+ fetal erythrocytes. Maternal alloimmunization can be prevented by the administration of anti-D gamma-globulin immediately after the birth of each Rh positive child. In order to identify the frequency of prevention of alloimmunization at the Instituto Mexicano del Seguro Social (IMSS), the amount of mothers at risk of sensitization from 1985 to 1995 was estimated from Rh and ABO blood group frequencies and with the number of deliveries and abortions at the Medical Institutions. Also, information in regard to the dose of gamma-globulin units purchased by the Institute of Social Security from 1985 to 1993 was obtained. The number of mothers at risk steadily increased from 16,616 in 1985 to 21,071 in 1995, amounting to a total of 203,203 in the 10-year period, while only 120,800 gamma-globulin units were purchased in that same period. The findings in this study suggest the need to define reasonable policies for the acquisition of gamma-globulin lots to prevent alloisoimmunization of mothers at risk.

  6. Neonatal thyroid storm accompanied with severe anaemia.

    PubMed

    Cao, Lu-Ying; Wei, Hong; Wang, Zheng-Li

    2015-07-01

    Neonatal thyroid storm is rare; the diagnostic criteria and management of neonatal thyroid storm have not been well established. In this paper, we report a preterm infant diagnosed with neonatal hyperthyroidism secondary to maternal Graves' disease who was discharged after therapy. Unfortunately, he was rehospitalised for neonatal thyroid storm. We will discuss the diagnosis and general therapy of neonatal thyroid storm.

  7. Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated intravascular coagulation immediately after left main coronary artery percutaneous coronary angioplasty.

    PubMed

    Tempelhof, Michael W; Benzuly, Keith H; Fintel, Dan; Krichavsky, Marc Z

    2012-01-01

    Early clinical trials of eptifibatide did not show a significant association between eptifibatide and the development of thrombocytopenia, thrombosis, or disseminated intravascular coagulation. However, more recent literature has suggested a significant association between eptifibatide and the development of thrombocytopenia and thrombosis. Although the true incidence and the pathophysiology of these associations are unknown, the development of these events can be life-threatening. Herein, we describe the case of a patient who experienced acute onset of profound thrombocytopenia, developing thrombosis, pulmonary emboli, and disseminated intravascular coagulation. This paper adds to the few previous reports of cases that suggested an association between thrombocytopenia, thrombosis, and the administration of eptifibatide. To the best of our knowledge, this is the first case report in the medical literature that associates the new onset of thrombocytopenia, thrombosis, and disseminated intravascular coagulation with the administration of eptifibatide. We also provide a subject review.

  8. Dermatomyositis associated with autoimmune idiopathic thrombocytopenia and anti-Ku antibody.

    PubMed

    Okamoto, Hiroshi; Soejima, Makoto; Takeuchi, Megumi; Tateishi, Mutsuto; Terai, Chihiro; Hara, Masako; Saito, Terunobu; Kamatani, Naoyuki

    2004-01-01

    We describe a case of dermatomyositis with concurrent clinical and laboratory features of idiopathic thrombocytopenia associated with anti-Ku antibody. A diagnosis of dermatomyositis was established by the characteristic skin changes together with a muscle biopsy. Scintigraphic studies indicated cardiac involvement. Autoimmune idiopathic thrombocytopenia (AITP) has been described in association with both systemic lupus erythematosus (SLE) and scleroderma, but there are few reports describing AITP associated with myositis. To our knowledge, this is the first report of a case of dermatomyositis associated with AITP and anti-Ku antibody.

  9. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    SciTech Connect

    Poggi, Guido; Quaretti, Pietro; Montagna, Benedetta Sottotetti, Federico Tagliaferri, Barbara Pozzi, Emma Amatu, Alessio Pagella, Chiara; Bernardo, Giovanni

    2011-02-15

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  10. 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

  11. Cardiopulmonary bypass with bivalirudin in type II heparin-induced thrombocytopenia.

    PubMed

    Clayton, Stephanie B; Acsell, Jeffrey R; Crumbley, Arthur J; Uber, Walter E

    2004-12-01

    Cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia poses significant challenges. Inadequate pharmacokinetic profiles, monitoring, reversibility, and availability often limit alternative anticoagulation strategies. Bivalirudin, a semisynthetic direct thrombin inhibitor, was recently approved for use in patients undergoing percutaneous coronary interventions. Its unique properties, including a relatively short half-life, an anticoagulation effect that closely correlates with activated clotting time, and an alternate metabolic pathway for elimination, make bivalirudin an attractive agent for cardiopulmonary bypass in patients with type II heparin induced-thrombocytopenia. We report our experience using bivalirudin in 2 patients undergoing coronary artery bypass grafting.

  12. Heparin-induced thrombocytopenia with abdominal aortic stent-graft acute thrombosis.

    PubMed

    Canaud, Ludovic; Hireche, Kheira; Marty-Ané, Charles; Alric, Pierre

    2013-08-01

    We report a case of heparin-induced thrombocytopenia in a patient on low molecular weight heparin bridge therapy who developed acute abdominal aortic stent-graft thrombosis 1 week after uncomplicated endovascular abdominal aortic aneurysm repair. The diagnosis was confirmed by a computed tomographic scan of the abdomen. The patient was successfully treated by conversion to open repair. The postoperative course was marked by subacute left limb ischemia related to an in vivo cross-reactivity of danaparoid with the heparin immune complex. To our knowledge, this is the first case report of heparin-induced thrombocytopenia with acute abdominal aortic stent-graft thrombosis. PMID:23711968

  13. 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

  14. Severe thrombocytopenia after hepatitis B vaccine in an infant from Turkey.

    PubMed

    Polat, Aziz; Akca, Halise; Dagdeviren, Erol

    2008-12-01

    Recombinant hepatitis B vaccine has been used widely in the world since 1991. The side effects of hepatitis B vaccine are seen rarely. In this paper, we present clinical and laboratory progress of an infant who gets severe thrombocytopenia after the second dosage hepatitis B vaccine. Our case is different from other cases because our patient is very young, the number of platelet is the lowest in the literature, and intravenous immunoglobulin (IVIG) are immunoglobulin (IVIG) are used in the treatment. Although it is a severe thrombocytopenia, the patient has recovered without any bleeding. PMID:18926870

  15. Induction of acute thrombocytopenia and infection of megakaryocytes by Rauscher murine leukemia virus reflect the genetic susceptibility to leukemogenesis

    PubMed Central

    1983-01-01

    Acute thrombocytopenia and megakaryocyte infection have been investigated during the preleukemic phase of the disease induced by the Rauscher murine leukemia virus (RMuLV) in mice. Injection of RMuLV, either intravenously or intraperitoneally, rapidly induced thrombocytopenia, possibly as a result of direct interaction between platelets and viral particles. The susceptibility to this acute thrombocytopenia was genetically controlled and was inherited as a dominant trait. Murine strains with H-2d or H-2k haplotype, which are susceptible to the induction of leukemia by RMuLV, developed thrombocytopenia, whereas leukemia-resistant H-2b and H-2q strains of mice failed to develop thrombocytopenia. Using B10 H-2-congenic and intra-H-2-recombinant mice, it was shown that the susceptibility to RMuLV-induced thrombocytopenia was controlled by gene(s) in or closely linked to the D region of the H-2 complex. Megakaryocytes may be one of the first sites for the replication of RMuLV. Indeed, among bone marrow cells, only megakaryocytes expressed viral antigens gp70 and p30 during the initial phase of RMuLV infection. In addition, megakaryocytes from infected mice were able to transfer preleukemic thrombocytopenia as well as leukemia in syngeneic mice. The infection of megakaryocytes by RMuLV appears to be genetically controlled in a manner similar to the induction of thrombocytopenia, since only the megakaryocytes from mice developing thrombocytopenia were infected by RMuLV. These results indicate that the gene(s) governing the induction of thrombocytopenia by RMuLV may be the same gene(s) (or closely linked to the gene) that controls the susceptibility to leukemogenesis, and would be consistent with the expression of the gene product, presumably a receptor-like molecule for RMuLV, on platelet and megakaryocyte membranes. PMID:6833948

  16. [Neonatal hearing screening].

    PubMed

    Oudesluys-Murphy, A M; van Straaten, H L; Ens-Dokkum, M H; Kauffman-de Boer, M A

    2000-03-25

    Approximately 1 to 2 per thousand live-born infants suffer from a serious perceptive hearing loss. Normal hearing from birth is essential for optimal human development (language and speech, social and emotional development, communicative skills and learning). The earlier the hearing loss is diagnosed the better the prognosis for the infant with a hearing impairment. Suitable methods are now available for neonatal hearing screening: automated measurement of auditory brain stem response and measurement of oto-acoustic emissions. Screening must be viewed as only the first step in a program of diagnosis, treatment and habilitation of these children. The ultimate goal of the implementation of neonatal hearing screening is: identification of bilateral hearing losses before the age of 3 months and start of therapy and counselling before the age of 6 months.

  17. 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

  18. [Neonatal conventional ventilation guidelines].

    PubMed

    2001-09-01

    Respiratory pathology is a frequent problem in Neonatal Intensive Care Units; the last few years, our knowledge about its management has improved enormously. Conventional Ventilatory support is a high-specialized technique that maintains a correct alveolar gas exchange while the primary aetiology is to present some clinical guidelines for every professional working with newborns who have respiratory failure improves. The aim of this document is to present some clinical guidelines for every professional working with newborns who have respiratory pathology

  19. Humane Neonatal Care Initiative.

    PubMed

    Levin, A

    1999-04-01

    The author has worked for many years in experimental departments in the former Soviet health system. Now, with integration into the western health system, many questions are being asked about high-technology neonatal medicine and whether it is sufficiently humane. The Baby Friendly Hospital Initiative (BFHI) movement is well known all over the world, but unfortunately it is only used for healthy children in maternity hospitals. A paradoxical situation has been created: the routines of maternity wards comply with the BFHI, whereas a neonatal intensive care unit in the same hospital may not meet the requirements of the BFHI. BFHI mainly cover breastfeeding in maternity hospitals. Humane Neonatal Care Initiatives include minimum aggressive therapy, minimum contact between sick newborns and medical staff, and maximum contact with mothers; the number of tests and examinations should be reduced to a minimum. Eleven steps towards the improvement of psychosocial and medical care in units for sick newborns are presented. This article is intended to provoke serious discussion. PMID:10342526

  20. Pasteurella gallinarum neonatal meningitis.

    PubMed

    Ahmed, K; Sein, P P; Shahnawaz, M; Hoosen, A A

    2002-01-01

    A 4-day-old baby weighing 1.7 kg was admitted to the neonatal intensive care unit of Ga-Rankuwa Hospital, Pretoria, with a history of apneic attacks. On examination there was an umbilical sepsis and the neonate was septicemic. The baby had been delivered at home and the umbilical cord had been cut by the grandmother using unclean scissors and chimney soot applied to the umbilical stump. On admission, a septic screen was done and antibiotic treatment was started with penicillin and amikacin. The investigations showed that the baby was slightly anemic, with hemoglobin levels of 10.0 g/dL (14.9-23.7 g/dL), and a pure growth of a Gram-negative bacillus was obtained from the cerebrospinal fluid, blood culture and suprapubic aspirate urine specimens. The Gram-negative bacillus was catalase and oxidase positive and it was identified as Pasteurella gallinarum. Antimicrobial profiling showed the organism to be susceptible to penicillin, cefotaxime, gentamicin and amikacin. Despite having received antimicrobial agents to which the etiological agent was susceptible, the neonate died within 5 days of admission. The cause of death was postulated to be due to overwhelming sepsis which resulted in septic shock. PMID:11906503

  1. Neonatal cardiovascular physiology.

    PubMed

    Hines, Michael H

    2013-11-01

    The pediatric surgeon deals with a large number and variety of congenital defects in neonates that frequently involve early surgical intervention and care. Because the neonatal cardiac physiology is unique, starting with the transition from fetal circulation and including differences in calcium metabolism and myocardial microscopic structure and function, it serves the pediatric surgeon well to have a sound understanding of these principles and how they directly and indirectly affect their plans and treatments. In addition, many patients will have associated congenital heart disease that can also dramatically influence not only the surgical and anesthetic care but also the timing and planning of procedures. Finally, the pediatric surgeon is often called upon to treat conditions and complications associated with complex congenital heart disease such as feeding difficulties, bowel perforations, and malrotation in heterotaxy syndromes. In this article, we will review several unique aspects of neonatal cardiac physiology along with the basic physiology of the major groups of congenital heart disease to better prepare the training and practicing pediatric surgeon for care of these complex and often fragile patients.

  2. Platelet Dysfunction: Status of Thrombopoietin in Thrombocytopenia Associated with Chronic Liver Failure.

    PubMed

    Giannini, Edoardo G; Peck-Radosavljevic, Markus

    2015-07-01

    Thrombocytopenia is a common hematological abnormality in patients with chronic liver disease, and its prevalence is higher in patients with liver failure. Although the presence of thrombocytopenia has historically been associated with portal hypertension, the characterization of thrombopoietin has improved our understanding of the determinants of platelet count in patients with liver disease. In particular, the association between thrombopoietin levels and residual liver function helped disclose the multifaceted pathophysiology of thrombocytopenia in patients with chronic liver failure. In this regard, important results were provided by studies performed in patients with chronic viral hepatitis that assessed the complex interplay between thrombocytopenia induced by the myelosuppressive effect of interferon-based treatment and thrombopoietin pathophysiology. These studies showed that successful antiviral therapy is accompanied by improved hepatic thrombopoietin production. Moreover, studies that evaluated thrombopoietin and platelet count dynamics before and after liver transplantation were instrumental in describing how restoration of liver function determines a normalization of the thrombopoietin-platelet count feedback that is deranged in patients with end-stage liver disease. PMID:26049067

  3. [A severe course of autoimmune thrombocytopenia and the procedure for its treatment in systemic lupus erythematosus].

    PubMed

    Mendeleev, I M; Miasnikov, A A; Polezhaev, Iu N; Berliner, G B

    1991-01-01

    The authors describe three comparatively rare cases of extremely severe symptomatic autoimmune thrombocytopenia associated with systemic lupus erythematosus. The use of glucocorticoids in large doses and in two cases of splenectomy turned out ineffective. The next therapeutic measures are suggested in the following succession: glucocorticoids----cytostatic drugs (vincristine)----splenectomy to be performed only in special cases.

  4. 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

  5. Multiple major cerebral artery thromboses with profound thrombocytopenia in acute leukaemia.

    PubMed

    Sims, D G; Scott, D J; Noble, T C

    1976-01-01

    A child with acute lymphoblastic leukaemia complicated by prolonged gastrointestinal and skin haemorrhages due to profound thrombocytopenia finally died of thrombotic occlusions of major cerebral arteries due to mucormycosis. Biopsy of any suspect lesion is needed urgently before prolonged therapy with amphotericin B is started. So far there have been no cures in childhood.

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

    PubMed

    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

    2014-08-01

    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 × 10(9)/L.

  7. 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

  8. Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome.

    PubMed

    Oh, Won Sup; Heo, Sang Taek; Kim, Sun Hyung; Choi, Won Jun; Han, Myung Guk; Kim, Ji Young

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a novel bunyavirus. Although the increasing numbers of cases and deaths is of great concern, an effective treatment strategy for SFTS has not been established. We present the cases of two patients with rapidly progressing SFTS who were successfully treated with plasma exchange and ribavirin.

  9. 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

  10. 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

  11. 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

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

    PubMed

    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.

  13. 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

  14. 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

  15. Neonatal haemostasis and the management of neonatal thrombosis.

    PubMed

    Will, Andrew

    2015-05-01

    Two detailed reviews of the management of neonatal thrombosis were published in 2012; one was an up-dated version of guidance first issued in 2004 and the other was a comprehensive review. Both of these publications gave very similar advice regarding the practical aspects of the indications, dosage and management of antithrombotic therapy. The authors stated that the evidence supporting most of their recommendations for anti-thrombotic therapy in neonates remained weak and so the therapy for a neonate with a thrombosis has to be based on an individualized assessment of estimated risk versus potential benefit. The aim of this present review is to give the treating physician an outline of the unique physiology of neonatal coagulation and how this affects the monitoring, dosing and even the choice of therapeutic strategy for the management of thrombosis in the neonate.

  16. Heparin-induced thrombocytopenia: when a low platelet count is a mandate for anticoagulation.

    PubMed

    Ortel, Thomas L

    2009-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT. PMID:20008202

  17. 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

  18. Neonatal lupus syndromes.

    PubMed

    Buyon, Jill P; Clancy, Robert M

    2003-09-01

    The neonatal lupus syndromes, although quite rare, provide an excellent opportunity to examine disease from bench to bedside. During the past year numerous publications have reported basic and clinical research. Although anti-SSA/Ro-SSB/La antibodies are detected in more than 85% of mothers whose fetuses are identified with conduction abnormalities in a structurally normal heart, when clinicians applied this testing to their pregnant patients, the risk for a woman with the candidate antibodies to have a child with congenital heart block was at or below one in 50. Although the precise pathogenic mechanism of antibody-mediated injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease, and fetal factors are likely contributory. In vivo and in vitro evidence supports a pathologic cascade involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors from the scavenging macrophages, and transdifferentiation of cardiac fibroblasts to a myofibroblast scarring phenotype. Cross-reactivity of anti-52-kD SSA/Ro antibodies with a serotoninergic cardiac receptor, 5-hydroxytryptamine (HT)4, has been suggested but remains unconfirmed. The spectrum of cardiac abnormalities continues to grow, with varying degrees of block identified in utero and reports of late-onset cardiomyopathy (some of which display endocardial fibroelastosis). Moreover, there is now clear documentation that incomplete blocks (including those improving in utero with dexamethasone) can progress postnatally, despite the clearance of the maternal antibodies from the neonatal circulation. Better echocardiographic measurements that identify first-degree block in utero may be the optimal means of approaching pregnant women at risk. Prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials. Reassuringly, most children with neonatal lupus syndromes do not

  19. [Natal and neonatal teeth].

    PubMed

    Baumgart, Manuela; Lussi, Adrian

    2006-01-01

    Natal teeth have been defined as teeth which are present at birth, while neonatal teeth erupt during the first 30 days. Their occurrence is rare, the prevalence ranges from 1:2000 to 1:3000 with a higher frequency in the lip and palate clefts and syndroms. In about 85% natal or neonatal teeth are lower central incisors (60% in pairs), rare are upper teeth, molars and multiple teeth. In almost 90% they are part of the deciduous dentition. A lot of possible causes of early eruption are discussed, but only the relation to hereditary factors seems to be evident. An autosomal dominant trait is often described. The appearance of these teeth is dependent on the degree of maturity, but most of the time it is loose, small, discoloured and hypoplastic. Histologically, enamel hypoplasia with normal prism structure is apparent. No significant disturbances of the dentin structures are observed, only cervically dentin becomes atubular with spaces and enclosed cells. A large vascular pulp and failure of root formation are further investigations. Our microhardness measurements showed values from 24.3-32.4 KHN for enamel and 48.3-62.2 KHN for dentin, while normal deciduous teeth have an enamel hardness of 322.0 +/- 17.5 KHN. The thickness of enamel was never more than 280 microm compared to up to 1200 microm in normal teeth. This shows the retarded development of natal and neonatal teeth, because mineralization has not finished at the time of birth. In accordance with developmental age tooth structure and appearence are normal. In consideration of complications as Riga-Fede-disease, feeding problems, possibility of infection and hypermobility most of the time extraction is the treatment of choice, but in the interest of protecting the child this decision should be made carefully. PMID:17051960

  20. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions.

    PubMed

    Kanagasegar, Sivalingam; Cimaz, Rolando; Kurien, Biji T; Brucato, Antonio; Scofield, R Hal

    2002-01-01

    Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia.

  1. Thrombocytopenia caused by albendazole in a patient with Sjögren’s syndrome: A case report

    PubMed Central

    Açıkgöz, Pınar; Türkbeyler, İbrahim Halil; Pehlivan, Yavuz

    2014-01-01

    Sjögren’s syndrome (SS) is an autoimmune disease characterised by a chronic inflammatory response mainly localised to the lachrymal and salivary glands. Haematological abnormalities are common, although they rarely have clinical significance. Here, we report a patient with SS and thrombocytopenia caused by albendazole. Haematological abnormalities such as thrombocytopenia are seen in approximately 5–15% of SS patients; however, this disease is usually asymptomatic and can often be recovered to normal levels with corticosteroids. If it is not, we should keep in mind other reasons for the thrombocytopenia, such as drug use.

  2. Neonatal congenital microvillus atrophy

    PubMed Central

    Pecache, N; Patole, S; Hagan, R; Hill, D; Charles, A; Papadimitriou, J

    2004-01-01

    Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory diarrhoea with onset either in the first 72 hours of life (early onset) or at 6–8 weeks after birth (late onset). To date over 30 cases have been reported worldwide. The prognosis for this life threatening condition continues to be poor. Therapeutic agents like somatostatin and epidermal growth factor are either ineffective or of marginal benefit. Overall five year survival after small bowel transplantation is currently ∼50%. The following brief review is aimed towards helping neonatologists/perinatologists in the early diagnosis, and management of CMVA and in counselling the parents appropriately. PMID:14970294

  3. Neonatal opioid withdrawal syndrome.

    PubMed

    Sutter, Mary Beth; Leeman, Lawrence; Hsi, Andrew

    2014-06-01

    Neonatal opioid withdrawal syndrome is common due to the current opioid addiction epidemic. Infants born to women covertly abusing prescription opioids may not be identified as at risk until withdrawal signs present. Buprenorphine is a newer treatment for maternal opioid addiction and appears to result in a milder withdrawal syndrome than methadone. Initial treatment is with nonpharmacological measures including decreasing stimuli, however pharmacological treatment is commonly required. Opioid monotherapy is preferred, with phenobarbital or clonidine uncommonly needed as adjunctive therapy. Rooming-in and breastfeeding may decease the severity of withdrawal. Limited evidence is available regarding long-term effects of perinatal opioid exposure.

  4. Transient neonatal tyrosinaemia.

    PubMed

    Rice, D N; Houston, I B; Lyon, I C; Macarthur, B A; Mullins, P R; Veale, A M; Guthrie, R

    1989-01-01

    Children who had presented with transient neonatal tyrosinaemia (TNT) were compared with a group of unaffected controls at 7-9 years of age. A comprehensive psychometric assessment revealed significant differences between the groups in adaptive behaviour, psycholinguistic abilities, and speed of learning. In nearly all components of the tests used, higher levels of TNT were associated with lower levels of performance. This study demonstrates that TNT, a condition commonly regarded as benign in the short term, has long-term effects which may be detrimental to the child in school.

  5. 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

  6. Neonatal hygroscopic condenser humidifier.

    PubMed

    Gedeon, A; Mebius, C; Palmer, K

    1987-01-01

    A hygroscopic condenser humidifier was developed for neonates on mechanical ventilation and was evaluated by laboratory tests and clinically. Humidification provided by the unit was measured in the 10- to 50-ml tidal-volume range at ambient temperatures of 24 degrees C and 38 degrees C. The effect of a leaking patient connection on device performance was investigated. Leakage rates were measured routinely in a neonatal ICU and surgery to determine the clinical significance. In the entire tidal volume and temperature range, the unit provided an inspiratory water content in excess of 30 g/m3 when the leak fraction (volume leaked/volume delivered at Y-piece) was less than 15%. This was found in three out of four cases. In about one out of ten cases, the leak exceeded 30%, which invariably led to corrective action, such as repositioning or changing the endotracheal tube. However, even at a 30% leak, a water content of about 26 g/m3 was still available for humidifying the inspired gas, which corresponds to normal physiologic conditions found in the trachea for nasal breathing of room air.

  7. Neonatal Conjunctivitis Leading to Neonatal Sepsis--A Case Report.

    PubMed

    Dey, A C; Hossain, M I; Dey, S K; Mannan, M A; Shahidullah, M

    2016-01-01

    Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day. PMID:26931268

  8. Neonatal Conjunctivitis Leading to Neonatal Sepsis--A Case Report.

    PubMed

    Dey, A C; Hossain, M I; Dey, S K; Mannan, M A; Shahidullah, M

    2016-01-01

    Neonatal conjunctivitis is the most common occular disease in neonates. Most infections are acquired during vaginal delivery. In spite most of these cases are benign; some of them may progress to systemic complications like loss of vision if left untreated. The authors present a case of a newborn who developed late onset neonatal sepsis from E. coli positive conjunctivitis. The baby was treated with Injection Meropenem and Injection Amikacin for 10 days. The course was uneventful, after that baby responded well and discharged home on 24th day.

  9. [How I explore and treat a neonatal renal vein thrombosis: a case report].

    PubMed

    Tribolet, S; Dresse, M F; Lombet, J; Rigo, V; Pieltain, C; Kalenga, M

    2014-04-01

    Neonatal renal vein thrombosis is a rare condition. The present case is rather unfrequent and particularly educative since it shows the complete diagnostic triad including hematuria, flank mass and thrombocytopenia. The diagnosis relies on the demonstration, by Doppler ultrasound, of an obstructed renal venous bed. The investigation is completed by a platelet count and the determination of the prothrombin time, of the activated partial thromboplastin time as well as of the concentration of fibrinogen. The screening also includes the search for a possible etiology, such as a deficiency in coagulation proteins, the presence of antiphospholipid antibodies or of a genetic mutation of one of the coagulation factors. Since there exist no evidence based guidelines for the management of the disease, we will discuss the diagnosis and treatment in relation with the published literature.

  10. Control of massive bleeding in dengue hemorrhagic fever with severe thrombocytopenia by use of intravenous anti-D globulin.

    PubMed

    Yadav, Satya P; Sachdeva, Anupam; Gupta, Dhiren; Sharma, Sunil D; Kharya, Gaurav

    2008-12-01

    Dengue hemorrhagic fever (DHF) is a potentially lethal complication of mosquito borne viral disease, Dengue Fever. Thrombocytopenia is a constant finding in DHF/Dengue Shock Syndrome (DSS). We report two cases that fulfilled the WHO criteria of DSS: high fever, positive tourniquet test, severe thrombocytopenia (<10,000/mm(3)), hemo-concentration (Hematocrit increase >20%), hypotension and bleeding refractory to routine therapeutic measures, who showed dramatic improvement after receiving Intravenous Anti-D globulin (IV anti-D).

  11. 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

  12. Neonatal iron nutrition.

    PubMed

    Rao, R; Georgieff, M K

    2001-10-01

    Preterm infants are prone to iron deficiency. Their total body iron content at birth is low and gets further depleted by clinical practices such as uncompensated phlebotomy losses and exogenous erythropoietin administration during the neonatal period. Early iron deficiency appears to adversely affect cognitive development in human infants. To maintain iron sufficiency and meet the iron demands of catch-up postnatal growth, iron supplementation is prudent in preterm infants. A dose of 2-4 mg/kg/day is recommended for preterm infants who are fed exclusively human milk. A dose of 6 mg/kg/day or more is needed with the use of exogenous erythropoietin or to correct preexisting iron deficiency. However, due to the poor antioxidant capabilities of preterm infants and the potential role of iron in several oxidant-related perinatal disorders, indiscriminate iron supplementation should be avoided.

  13. Selective Spleen Embolization of Splenomegaly to Improve Thrombocytopenia Facilitating Open Aortic Aneurysm Repair: A Staged Approach.

    PubMed

    Maras, Dimitrios; Kontopodis, Nikolaos; Dedes, Athansios; Tsanis, Antonios; Mazarakis, Ioannis; Gekas, Christos; Ioannou, Christos V

    2016-08-01

    We present an 82-year-old man with a history of hairy cell leukemia, having an 11-cm abdominal aortic aneurysm, who also had severe thrombocytopenia (about 20 000 platelets/μL) and splenomegaly at presentation. The patient had unfavorable anatomy for endovascular aneurysm repair, and therefore, an open procedure was planned. To reduce risk for perioperative bleeding and optimize patient preoperative status, a staged approach was employed. Initially, several sessions of embolization of 2 splenic artery branches were performed with the intent to decrease spleen size and to increase platelet count thus decreasing the perioperative bleeding risk. Then, after successfully increasing platelet count (280 000 PLT/μL), open repair of the aneurysm was conducted. This case demonstrates that selective splenic embolization in patients with hypersplenism and subsequent thrombocytopenia who are in need for major surgery may achieve a significant rise in platelet count and optimize patient's preoperative status in order to avoid bleeding complications. PMID:27581226

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

    PubMed

    Topka, Sabine; Vijai, Joseph; Walsh, Michael F; 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

    2015-06-01

    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.

  15. Heparin-induced thrombocytopenia with iliacofemoropopliteal thrombosis in a patient operated for colorectal carcinoma liver metastases.

    PubMed

    Vucelić, Dragica; Antonijević, Nebojsa; Galun, Danijel; Bulajić, Predrag; Basarić, Dragan; Milićević, Miroslav

    2011-01-01

    We report a case of heparin-induced thrombocytopenia thrombosis (HITT) syndrome in a patient prophylactically treated with low molecular weight heparin. A 66-year-old men underwent radiofrequency-assisted partial liver resection for colorectal carcinoma liver metastases a year-and-a-half after he had been operated for rectal cancer. In the postoperative period, patient was prophilactically treated with reviparin sodium. On the 8th postoperative day, the platelet count decreased by more than 50% without clinical signs of thrombosis. HITT syndrome was suspected on the 19th postoperative day, after iliacofemoropopliteal thrombosis had developed, and related diagnosis was supported by the strongly positive particle gel agglutination technique immunoassay. Heparin was withdrawn and alternative anticoagulant, danaparoid sodium, was introduced in therapeutic doses. Despite delayed recognition, favorable clinical outcome was achieved. HITT syndrome should be considered with priority among the possible causes of thrombocytopenia in a surgical patient on heparin. PMID:22519199

  16. Cerebral venous thrombosis due to essential thrombocythemia and worsened by heparin-induced thrombocytopenia and thrombosis.

    PubMed

    Richard, Sebastien; Perrin, Julien; Lavandier, Karine; Lacour, Jean-Christophe; Ducrocq, Xavier

    2011-01-01

    This case describes the medical history of a 61-year-old woman treated for cerebral venous thrombosis (CVT) leading to diagnosis of essential thrombocythemia (ET). During treatment with unfractionated heparin, after initial improvement of clinical state, signs of cerebral hypertension reappeared. Although the platelet count decreased, heparin-induced thrombocytopenia (HIT) was only suspected 2 days later when it dropped below the standard 150 × 10(9) L(-1) threshold. HIT diagnosis was confirmed by the presence of anti-PF4/heparin IgG. This late finding was the cause of the extension of CVT with worsening of cerebral hypertension necessitating decompressive craniectomy. Elevated basal platelet count due to ET can delay diagnosis and treatment of HIT. In this case, physicians should be more attentive to platelet count variations rather than thrombocytopenia threshold. PMID:21142409

  17. Mild Clinical Course of Severe Fever with Thrombocytopenia Syndrome Virus Infection in an Elderly Japanese Patient

    PubMed Central

    Ohagi, Yuko; Nakamoto, Chiaki; Nakamoto, Hiromichi; Saijo, Masayuki; Shimojima, Masayuki; Nakano, Yoshio; Fujimoto, Tokuzo

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient's blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail. PMID:25574405

  18. 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

  19. 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

  20. [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

  1. Neonatal lupus syndromes.

    PubMed

    Buyon, J P; Rupel, A; Clancy, R M

    2004-01-01

    The neonatal lupus syndromes (NLS), while quite rare, carry significant mortality and morbidity in cases of cardiac manifestations. Although anti-SSA/Ro-SSB/La antibodies are detected in > 85% of mothers whose fetuses are identified with congenital heart block (CHB) in a structurally normal heart, when clinicians applied this testing to their pregnant patients, the risk for a woman with the candidate antibodies to have a child with CHB was at or below 1 in 50. While the precise pathogenic mechanism of antibody-mediated injury remains unknown, it is clear that the antibodies alone are insufficient to cause disease and fetal factors are likely contributory. In vivo and in vitro evidence supports a pathologic cascade involving apoptosis of cardiocytes, surface translocation of Ro and La antigens, binding of maternal autoantibodies, secretion of profibrosing factors (e.g., TGFbeta) from the scavenging macrophages and modulation of cardiac fibroblasts to a myofibroflast scarring phenotype. The spectrum of cardiac abnormalities continues to expand, with varying degrees of block identified in utero and reports of late onset cardiomyopathy (some of which display endocardial fibroelastosis). Moreover, there is now clear documentation that incomplete blocks (including those improving in utero with dexamethasone) can progress postnatally, despite the clearance of the maternal antibodies from the neonatal circulation. Better echocardiographic measurements which identify first degree block in utero may be the optimal means of approaching pregnant women at risk. Prophylactic therapies, including treatment with intravenous immunoglobulin, await larger trials. In order to achieve advances at both the bench and bedside, national research registries established in the US and Canada are critical.

  2. 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

  3. Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia.

    PubMed

    Bakchoul, Tamam; Greinacher, Andreas

    2012-08-01

    Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options. PMID:23606934

  4. [Extracorporeal circulation with danaparoid sodium for valve replacement in thrombocytopenia induced by type II heparin].

    PubMed

    Salmi, L; Leroy-Matheron, C; LeBesnerais, P; Rosanval, O; Duvaldestin, P; Gouault-Heilmann, M

    2001-11-01

    A type II heparin-induced thrombocytopenia (HIT) was diagnosed in a 64-year-old woman at day 20 of intravenous unfractionated heparin (UFH) therapy, given after myocardial infarction treated by angioplasty and intracoronary stent. The infarction was complicated by a mitral insufficiency that led to a mitral valve replacement. Cardiopulmonary bypass was successfully performed with sodium danaparoid (Orgaran), as an alternative to UFH, without thrombotic or haemorrhagic complications and the follow-up was uneventful. PMID:11759322

  5. Usefulness of Danaparoid sodium in patients with Heparin-induced thrombocytopenia after cardiac surgery

    PubMed Central

    Foroughinia, Farzaneh; Farsad, Fariborz; Gholami, Kheirollah; Ahmadi, Somayeh

    2015-01-01

    Objective: Thrombocytopenia is a common problem in cardiovascular surgery patients. However, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of prophylaxis or treatment with heparin. Prompt management of HIT with an alternative anticoagulant is necessary due to the extreme risk of thrombotic complications. Therefore, we evaluated the effects of danaparoid in the treatment of HIT in patients with cardiac surgery who are at moderate to high risk of HIT. Methods: A prospective observational study involving 418 postcardiac surgery patients who received unfractionated heparin and low-molecular weight heparin was conducted in an educational tertiary cardiac care hospital in Iran. All patients were assessed for HIT type II based on thrombocytopenia and pretest clinical scoring system, the “4T's” score. HIT patients were treated with 1500–2500 units intravenous bolus danaparoid sodium followed by 200–400 units/h for a mean of 5 days. Successful response to danaparoid therapy, defined as augmentation in platelet count and improvement of thrombotic events was assessed in all patients treated with danaparoid. Findings: According to pretest clinical score (4T's), the probability of HIT was high in 14 (3.3%) patients and intermediate in three ones (0.7%). 15 patients with HIT were treated with danaparoid. One death occurred in danaparoid-treated group due to persistent thrombocytopenia. The rest of patients were treated successfully with danaparoid without any major thrombotic complication. Conclusion: According to our data and the previous studies’, HIT can be managed prosperously with danaparoid in postcardiac surgery patients. However, with the absence of any increase in platelet count after 3–5 days of danaparoid therapy and/or the occurrence of a new thrombotic event, danaparoid cross-reactivity with heparin should be suspected. PMID:25984544

  6. Glucocorticoid-dependent hypoadrenocorticism with thrombocytopenia and neutropenia mimicking sepsis in a Labrador retriever dog

    PubMed Central

    Snead, Elisabeth; Vargo, Cheryl; Myers, Sherry

    2011-01-01

    Glucocorticoid-deficient hypoadrenocorticism (GDH) with immune-mediated-neutropenia (IMN) and -thrombocytopenia (IMT) were diagnosed in a 3-year-old Labrador retriever dog. Glucocorticoid-deficient hypoadrenocorticism is rare and diagnostically challenging as clinical signs and laboratory abnormalities are often nonspecific. Immune-mediated cytopenias and other autoimmune disorders, as part of an autoimmune polyglandular syndrome have been reported with hypoadrenocorticism in humans. This is the first reported case of hypoadrenocorticism and bicytopenia in a dog. PMID:22467971

  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 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

  9. Barrier mechanisms in neonatal stroke

    PubMed Central

    Kratzer, Ingrid; Chip, Sophorn; Vexler, Zinaida S.

    2014-01-01

    Clinical data continue to reveal that the incidence of perinatal stroke is high, similar to that in the elderly. Perinatal stroke leads to significant morbidity and severe long-term neurological and cognitive deficits, including cerebral palsy. Experimental models of cerebral ischemia in neonatal rodents have shown that the pathophysiology of perinatal brain damage is multifactorial. Cerebral vasculature undergoes substantial structural and functional changes during early postnatal brain development. Thus, the state of the vasculature could affect susceptibility of the neonatal brain to cerebral ischemia. In this review, we discuss some of the most recent findings regarding the neurovascular responses of the immature brain to focal arterial stroke in relation to neuroinflammation. We also discuss a possible role of the neonatal blood-CSF barrier in modulating inflammation and the long-term effects of early neurovascular integrity after neonatal stroke on angiogenesis and neurogenesis. PMID:25426016

  10. 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

  11. Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia.

    PubMed

    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; Raslova, Hana

    2015-02-01

    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.

  12. Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

    PubMed Central

    Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

    2015-01-01

    Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

  13. 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

  14. A novel canine model of immune thrombocytopenia: Has ITP gone to the dogs?

    PubMed Central

    LeVine, Dana N; Birkenheuer, Adam J; Brooks, Marjory B; Nordone, Shila K; Bellinger, Dwight A; Jones, Sam L; Fischer, Thomas H; Oglesbee, Stephen E; Frey, Kahlina; Brinson, Nicole S; Peters, Allison Pazandak; Marr, Henry S; Motsinger-Reif, Alison; Gudbrandsdottir, Sif; Bussel, James B; Key, Nigel S

    2014-01-01

    Summary Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody-mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose-dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin-8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet-neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP. PMID:25039744

  15. T-cell-dependent immunity and thrombocytopenia in rats infected with Plasmodium chabaudi.

    PubMed Central

    Watier, H; Verwaerde, C; Landau, I; Werner, E; Fontaine, J; Capron, A; Auriault, C

    1992-01-01

    Normal, splenectomized, and athymic Fischer rats were infected with Plasmodium chabaudi. In normal rat infections, acute-phase infection resolved rapidly and completely. In splenectomized rats, infection resulted in high parasitemia and ultimately death. In nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. Complete resolution of the infection was achieved after adoptive transfer of T lymphocytes, even when transfer occurred during the course of infection. These results indicated that an acquired, T-lymphocyte-dependent immunity was necessary for the complete recovery observed in normal rats. In normal rats, thrombocytopenia and splenomegaly occurred during infection. By contrast, in nude rats, both of these pathological manifestations were only observed after thymus grafting. Thrombocytopenia was also absent in the splenectomized animals. Despite an increase in platelet-associated immunoglobulin levels during the infection, thrombocytopenia was not transferred by injection of infected rat serum to normal recipients. It has been concluded that the nude rat infection can be regarded as a novel and useful model for studying the T-cell-dependent effector and pathological mechanisms and to investigate the anti-P. chabaudi immune response. PMID:1729178

  16. Heparin-induced thrombocytopenia in the pediatric population: a review of current literature.

    PubMed

    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

  17. 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

  18. A case of neonatal tetanus.

    PubMed

    Kumar, S; Malecki, J M

    1991-03-01

    The morbidity and mortality from neonatal tetanus are preventable. It is largely a disease of developing countries. This single case of neonatal tetanus in southern Florida must serve as an indicator for the need for health care professionals to evaluate the degree of utilization of maternal health services and the impact of immunization programs for those women at risk, in this case, women who have migrated from developing countries. PMID:2000534

  19. Risk estimates for neonatal myotonic dystrophy.

    PubMed Central

    Glånz, A; Fråser, F C

    1984-01-01

    Children who inherit the autosomal dominant gene for myotonic dystrophy from their mother rather than their father may develop the severe neonatal type rather than the late onset type. The families of 22 neonatal type probands and 59 late onset type probands were studied to determine the risk of occurrence and recurrence of the neonatal type. The frequency of the neonatal type in sibs of neonatal type probands was 29%, or 37% if cases of neonatal deaths are counted as affected. This is significantly higher than the 6% of the neonatal type found in the offspring of affected women not ascertained through a child with the neonatal type. These data suggest that certain women carrying the gene for myotonic dystrophy are predisposed to have children affected with the neonatal type rather than the late onset type. The female near relatives of these women do not seem to share this predisposition. The data should be useful for genetic counseling. PMID:6748014

  20. Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia.

    PubMed

    Adly, Amira Abdel Moneam; Ragab, Iman Ahmed; Ismail, Eman Abdel Rahman; Farahat, Mona Mohammed

    2015-01-01

    Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥ 1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p < 0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p < 0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p < 0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p < 0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients

  1. 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.

  2. Neonatal infrared axillary thermometry.

    PubMed

    Seguin, J; Terry, K

    1999-01-01

    The authors compared axillary skin temperatures (AT) measured with an infrared (IR) thermometer (Lightouch Neonate, Exergen Corp) with rectal temperatures (RT) in 16 newly born term infants under radiant warmers (RW) and in cribs. Twelve stable, growing premature infants in incubators were also studied. This new device may be useful because of safety and rapid results (1 second), but clinical accuracy is unknown. For term infants, mean (SD) RT-AT difference was 0.1 (0.48) degree C under RW and 0.25 (0.17) degree C 2 hours later in cribs. For premature infants in incubators the mean RT-AT difference was 0.09 (0.16) degree C. Axillary temperatures measured by IR thermometer approximate RT for newly born term infants in cribs and stable premature infants in incubators. For newly born term infants under RW, RT-AT differences vary more widely, limiting clinical usefulness in this setting. The device, the unique age of this population, and the RW environment may play a role. PMID:9924640

  3. The Potential of Antimicrobials to Induce Thrombocytopenia in Critically Ill Patients: Data from a Randomized Controlled Trial

    PubMed Central

    Johansen, Maria Egede; Jensen, Jens-Ulrik; Bestle, Morten Heiberg; Hein, Lars; Lauritsen, Anne Øberg; Tousi, Hamid; Larsen, Kim Michael; Løken, Jesper; Mohr, Thomas; Thormar, Katrin; Johansson, Pär I.; Cozzi-Lepri, Alessandro; Lundgren, Jens D.

    2013-01-01

    Background Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia. Methods Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group) or drug-escalation in case of procalcitonin increases (high-exposure group). Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤100x109/L) or relative (≥20% decrease in platelet count). Analyses were performed in the two randomized groups and as a merged cohort. Results Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively). Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05). Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively), as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14) was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively), however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0.0005). Conclusion

  4. 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

  5. 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

  6. Neonatal and infantile acne vulgaris: an update.

    PubMed

    Serna-Tamayo, Cristian; Janniger, Camila K; Micali, Giuseppe; Schwartz, Robert A

    2014-07-01

    Acne may present in neonates, infants, and small children. Neonatal and infantile acne vulgaris are not considered to be rare. The presentation of acne in this patient population sometimes represents virilization and may portend later development of severe adolescent acne. Neonatal and infantile acne vulgaris must be distinguished from other cutaneous disorders seen in newborns and infants. Infantile acne tends to be more pleomorphic and inflammatory, thus requiring more vigorous therapy than neonatal acne.

  7. 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

  8. Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells

    PubMed Central

    Sagoo, Pervinder; Ali, Niwa; Garg, Garima; Nestle, Frank O.; Lechler, Robert I.; Lombardi, Giovanna

    2013-01-01

    Graft rejection by the immune system is a major cause of transplant failure. Lifelong immunosuppression decreases the incidence of graft rejection; however, nonspecific immunosuppression results in increased susceptibly to infection and cancer. Regulatory T cells (Tregs), which suppress the activation of the immune system and induce tolerance, are currently under evaluation for use in clinical transplantation. Ex vivo expanded polyclonal Tregs that are introduced into transplant recipients alter the balance of T effector cells to Tregs; however, experimental data suggest that alloantigen-specific Tregs would be more effective at preventing graft rejection. We have developed a method to enrich alloantigen-specific human Tregs based on the coexpression of activation markers, CD69 and CD71. These Tregs could be readily expanded in vitro and demonstrated potent antigen-specific suppression. In a humanized mouse model of alloimmune-mediated injury of human skin grafts, alloantigen-specific Tregs resulted in a significant reduction in clinically relevant indicators of dermal tissue injury when compared with polyclonal Tregs, restoring a histology comparable to healthy skin. This method of human allospecific Treg selection should be scalable to the clinic. The improved in vivo efficacy of alloantigen-specific Tregs over polyclonal Tregs shown here suggests that generating “customized” Tregs with defined anti-donor allospecificities may improve current practice in clinical immunotherapy. PMID:21593402

  9. Nonpolio enterovirus infections in neonates.

    PubMed

    Haston, Julia C; Dixon, Terry C

    2015-05-01

    There are currently 12 species and over 100 serotypes that have been identified in the enterovirus genus, including the coxsackieviruses, echoviruses, and polioviruses. Since their discovery 65 years ago, much has been discovered and continues to be researched regarding the pathogenicity and scope of disease of nonpolio enteroviruses. Like many infections, enteroviruses have been found to affect neonates much differently, and often more severely, than older children and adults. Neonatal infections often cause mild illnesses with nonspecific symptoms, but they may also have severe presentations involving the cardiovascular, gastrointestinal, hematologic, or central nervous systems. This article provides an overview of what is known about nonpolio enteroviruses in neonates including epidemiology, transmission, clinical presentation, diagnosis, and treatment.

  10. Neonatal Hemophilia: A Rare Presentation

    PubMed Central

    Proença, Elisa; Godinho, Cristina; Oliveira, Dulce; Guedes, Ana; Morais, Sara; Carvalho, Carmen

    2015-01-01

    Hemophilia A is a X-linked hereditary condition that lead to decreased factor VIII activity, occurs mainly in males. Decreased factor VIII activity leads to increased risk of bleeding events. During neonatal period, diagnosis is made after post-partum bleeding complication or unexpected bleeding after medical procedures. Subgaleal hemorrhage during neonatal period is a rare, severe extracranial bleeding with high mortality and usually related to traumatic labor or coagulation disorders. Subgaleal hemorrhage complications result from massive bleeding. We present a neonate with unremarkable family history and uneventful pregnancy with a vaginal delivery with no instrumentation, presenting with severe subgaleal bleeding at 52 hours of life. Aggressive support measures were implemented and bleeding managed. The unexpected bleeding lead to a coagulation study and the diagnosis of severe hemophilia A. There were no known sequelae. This case shows a rare hemophilia presentation reflecting the importance of coagulation studies when faced with unexplained severe bleeding. PMID:26734126

  11. 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... § 880.5400 Neonatal incubator. (a) Identification. A neonatal incubator is a device consisting of a... humidity, a control valve through which oxygen may be added, and access ports for nursing care....

  12. 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.

  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. Approach to the diagnosis and management of drug-induced immune thrombocytopenia.

    PubMed

    Arnold, Donald M; Nazi, Ishac; Warkentin, Theodore E; Smith, James W; Toltl, Lisa J; George, James N; Kelton, John G

    2013-07-01

    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 <20×10(9)/L); bleeding complications; onset 5 to 10days 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

  15. Utility of consecutive repeat HIT ELISA testing for heparin-induced thrombocytopenia.

    PubMed

    Chan, Maren; Malynn, Elizabeth; Shaz, Beth; Uhl, Lynne

    2008-03-01

    Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy. Limited data are available regarding repeat HIT antibody testing after an initial negative test. We conducted a retrospective study to determine the utility of repeat testing. Heparin antibodies were detected using the GTI-PF4 enzyme-linked immunoabsorbent assay, ELISA (GTI Diagnostics, Waukesha, WI). Patients (n = 137) were assigned to one of three groups based upon the initial negative test optical density (OD) range of low = 0-0.132, medium = 0.133-0.267, and high = 0.268-0.399. A pretest clinical score was retrospectively determined using the "4T's" (Thrombocytopenia, Timing of platelet fall, Thrombosis, and the absence of oTher causes of thrombocytopenia). A subsequent positive ELISA was found in 16% (22/137) of patients who underwent repeat testing. Most of these patients had a low pretest clinical score (62%). Four patients had an interval change in the pretest score between the initial negative and subsequent positive tests. Only these four patients developed HIT with thrombosis (HITT). Eighty percent of patients with a high initial negative test OD value had a positive ELISA on repeat testing; however, the initial negative test OD value could not predict whether a patient developed HITT. In contrast, an increase in the pretest clinical probability between initial and repeat testing better predicted HITT. Consecutive repeat ELISA testing for heparin antibodies may be warranted in patients with an increase in their pretest clinical score after an initial negative test as an adjunct to confirm the diagnosis of HIT.

  16. 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

  17. Neonatal meningitis complicating with pneumocephalus.

    PubMed

    Kumari, Anita; Agrawal, Satish C

    2014-01-01

    Pneumocephalus is a rare condition characterized by the presence of gas within the cranial cavity. This gas may arise either from a trauma, a tumor, a surgical, or a diagnostic procedure or occasionally from an infection. Pneumocephalus as a complication of bacterial meningitis, in absence of trauma or a procedure, is extremely rare, particularly in a newborn. A case of pneumocephalus occurring in a baby, suffering from neonatal meningitis, acquired probably through unsafe cutting and tying of the cord, is reported here. Cutting, tying, and care of the umbilical cord is of utmost importance to prevent neonatal infection as the same is a potential cause of serious anaerobic infections, besides tetanus. PMID:24741257

  18. 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

  19. Severe preeclampsia with persistent postpartum hemolysis and thrombocytopenia treated by plasmapheresis.

    PubMed

    Schwartz, M L; Brenner, W

    1985-03-01

    A case of severe preeclampsia in which hemolysis and rapid platelet consumption persisted after delivery, but in which the blood urea nitrogen and serum glutamic oxaloacetic acid transaminase levels returned to normal is presented. Antiplatelet aggregating medications and exchange plasmapheresis with fresh frozen plasma were begun on the eighth postpartum day, but the hemolysis and rapid platelet consumption did not begin to improve until the 12th postpartum day. The use of plasmapheresis in highly selected cases of severe preeclampsia with hemolysis and thrombocytopenia that do not resolve after delivery is discussed. PMID:3974976

  20. 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

  1. 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

  2. [Cerebral venous thrombosis and immune thrombocytopenia in a 7-year-old girl: a fortuitous association?].

    PubMed

    Cotillon, M; Lebas, A; Blanc, T; Schneider, P; Vannier, J-P; Buchbinder, N

    2014-12-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by autoantibody-mediated peripheral platelet destruction. It is rarely accompanied by thrombosis. Here, we describe a wide cerebral venous thrombosis that occurred at the onset of a primary ITP in a 7-year-old girl. ITP was confirmed by the presence of anti-platelet antibodies. Whether ITP is a risk factor for venous thrombosis is a matter of debate. The platelet microparticles released during the platelet destruction and the interaction between the autoantibodies and the platelet glycoproteins may contribute to platelet activation. Increased risk of thromboembolic events should be considered in all patients with ITP, including children. PMID:25445130

  3. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome.

    PubMed

    Pachtman, Sarah L; 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

  4. Successful pregnancy after pulmonary embolism and heparin-induced thrombocytopenia--case report.

    PubMed

    Plesinac, S; Babović, I; Karapandzić, V Plesinac

    2013-01-01

    The authors present the case of a nulliparous 34-year-old patient. At the tenth week of gestation, she developed phlebothrombosis of veins of the right leg and massive pulmonary embolism. After thrombolytic and heparin therapy she developed rethrombosis and heparin-induced thrombocytopenia type II. Lepirudin was introduced in therapy and in the 12th week of gestation acenocumarol was added. After the 34th week, she received danaparoid sodium. After a week, by cesarean section, a healthy and mature female was delivered. PMID:23971268

  5. 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

  6. Unexpected platelets elevation in a patient with idiopathic thrombocytopenia treated with oseltamivir for influenza infection.

    PubMed

    Bigot, Pierre; Auffret, Marine; Gautier, Sophie; Weinborn, Marie; Ettahar, Nicolas-Kader; Coupé, Patrick

    2016-10-01

    Oseltamivir is a neuraminidase inhibitor approved for the prevention and treatment of influenza. Few haematological side effects have been reported with oseltamivir. We report herein the case of an unexpected platelet increase in a 46-year-old woman with idiopathic thrombocytopenia (ITP) treated with oseltamivir for influenza. The mechanism may involve the neuraminidase inhibition which decrease platelet surface sialic acid content and reduce their removal by the reticuloendothelial system. Oseltamivir may be responsible for platelet increase especially in patients with ITP. PMID:27343486

  7. Thrombopoietin receptor agonists: a new immune modulatory strategy in immune thrombocytopenia?

    PubMed

    Schifferli, Alexandra; Kühne, Thomas

    2016-04-01

    In 2008, new drugs that mimic the effects of thrombopoietin became available for the treatment of primary immune thrombocytopenia, eg, romiplostim and eltrombopag. These drugs activate the thrombopoietin receptor, stimulate the production of megakaryocytes, and increase the production of platelets. Important clinical observation has been gained, such as unexpected long-term remission after stopping thrombopoietin receptor agonists. The pathophysiology of this unforeseen cure is currently the subject of discussion and is investigated in clinical trials and laboratory research projects. Here we evaluate the different hypotheses on how thrombopoietin receptor agonists can affect the immune system, particularly the induction of tolerance, and by which mechanisms this may be achieved. PMID:27312161

  8. 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

  9. Multicentric warfarin-induced skin necrosis complicating heparin-induced thrombocytopenia.

    PubMed

    Warkentin, T E; Sikov, W M; Lillicrap, D P

    1999-09-01

    Two patients developed catastrophic multicentric skin necrosis while receiving warfarin to treat venous thromboembolism complicated by immune-mediated heparin-induced thrombocytopenia (HIT). Patient 1 developed skin necrosis involving the breasts, thighs, and face, as well as venous limb gangrene and bilateral hemorrhagic necrosis of the adrenal glands, resulting in death. The second patient developed bilateral mammary necrosis necessitating mastectomies, as well as skin necrosis involving the thigh. Neither patient had an identifiable hypercoagulable syndrome, other than HIT. HIT may represent a risk factor for the development of multicentric warfarin-induced skin necrosis (WISN).

  10. 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

  11. Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice.

    PubMed

    Sridharan, Aishwarya; Chen, Qingfeng; Tang, Kin Fai; Ooi, Eng Eong; Hibberd, Martin L; Chen, Jianzhu

    2013-11-01

    A characteristic clinical feature of dengue virus infection is thrombocytopenia, though its underlying mechanism is not definitively determined. By adoptive transfer of human CD34(+) fetal liver cells into immunodeficient mice, we have constructed humanized mice with significant levels of human platelets, monocytes/macrophages, and hepatocytes. Infection of these mice with both lab-adapted and clinical strains of dengue virus induces characteristic human hematological changes, including transient leukopenia and thrombocytopenia. We show that the specific depletion of human platelets is not mediated by antibodies in the periphery or reduced production of human thrombopoietin in the liver but reduction of human megakaryocytes and megakaryocyte progenitors in the bone marrow of the infected mice. These findings identify inhibition of platelet production in the bone marrow as a key mechanism underlying dengue-induced thrombocytopenia and suggest the utility of the improved humanized mouse model in studying dengue virus infection and pathogenesis in a human cell context.

  12. 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

  13. Novel optical system for neonatal brain imaging

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Zhou, Shuoming; Nioka, Shoko; Chance, Britton; Anday, Endla; Ravishankar, Sudha; Delivoria-Papadopoulos, Maria

    1999-03-01

    A highly portable, fast, safe and affordable imaging system that provides interpretable images of brain function in full- and pre-term neonates within a few seconds has been applied to neonates with normal and pathological states. We have used a uniquely sensitive optical tomography system, termed phased array, which has revealed significant functional responses, particularly to parietal stimulation in neonate brain. This system can indicate the blood concentration and oxygenation change during the parietal brain activation in full- and pre-term neonates. The preliminary clinical results, especially a longitudinal study of a cardiac arrest neonate, suggest a variety of future applications.

  14. [Fondaparinux as an alternative anticoagulant in heparin-induced thrombocytopenia in the patient with a ventricular assist device].

    PubMed

    Cegarra-Sanmartín, V; Paniagua, P; Galán, J; Muñoz, C; Moral, M V

    2013-11-01

    Heparin-induced thrombocytopenia is a reaction associated with the use of this drug. It occurs in up to 3% of patients treated for at least 5 days. Its treatment is to stop the heparin, and according to patient needs, replace it with another anticoagulant. We present a patient who, after a heart transplant, and the need for a ventricular assist device, required anticoagulation. The patient developed heparin-induced thrombocytopenia. Heparin was stopped and anticoagulation was replaced by fondaparinux. The peri-operative complications and the management of the coagulation are described.

  15. Neonatal posterior fossa subdural hematoma.

    PubMed

    Coker, S; Beltran, R; Fine, M

    1987-07-01

    Hemorrhage into the posterior fossa is a rare neurosurgical emergency in neonates. CT scanning is diagnostic. Blood layering under the apex of the tentorium cerebelli, however, may resemble a dilated vascular structure, and the rigidity of the pressured tentorium may prevent upward transmission of increased intracranial pressure, resulting in a soft fontanelle.

  16. Standardisation of neonatal clinical practice.

    PubMed

    Bhutta, Z A; Giuliani, F; Haroon, A; Knight, H E; Albernaz, E; Batra, M; Bhat, B; Bertino, E; McCormick, K; Ochieng, R; Rajan, V; Ruyan, P; Cheikh Ismail, L; Paul, V

    2013-09-01

    The International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ) is a large-scale, population-based, multicentre project involving health institutions from eight geographically diverse countries, which aims to assess fetal, newborn and preterm growth under optimal conditions. Given the multicentre nature of the project and the expected number of preterm births, it is vital that all centres follow the same standardised clinical care protocols to assess and manage preterm infants, so as to ensure maximum validity of the resulting standards as indicators of growth and nutrition with minimal confounding. Moreover, it is well known that evidence-based clinical practice guidelines can reduce the delivery of inappropriate care and support the introduction of new knowledge into clinical practice. The INTERGROWTH-21(st) Neonatal Group produced an operations manual, which reflects the consensus reached by members of the group regarding standardised definitions of neonatal morbidities and the minimum standards of care to be provided by all centres taking part in the project. The operational definitions and summary management protocols were developed by consensus through a Delphi process based on systematic reviews of relevant guidelines and management protocols by authoritative bodies. This paper describes the process of developing the Basic Neonatal Care Manual, as well as the morbidity definitions and standardised neonatal care protocols applied across all the INTERGROWTH-21(st) participating centres. Finally, thoughts about implementation strategies are presented.

  17. 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...

  18. 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.

  19. 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

  20. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage.

    PubMed

    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

    2015-04-01

    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.

  1. 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.

  2. 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

  3. 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

  4. Successful laparoscopic splenectomy after living-donor liver transplantation for thrombocytopenia caused by antiviral therapy

    PubMed Central

    Kato, Hiroyuki; Usui, Masanobu; Azumi, Yoshinori; Ohsawa, Ichiro; Kishiwada, Masashi; Sakurai, Hiroyuki; Tabata, Masami; Isaji, Shuji

    2008-01-01

    Although interferon (IFN) based therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has been widely accepted, it induces various adverse effects such as thrombocytopenia, resulting in its interruption. Recently, concomitant splenectomy at the time of living donor liver transplantation (LDLT) has been tried to overcome this problem, but this procedure leads to several complications such as excessive intraoperative bleeding and serious infection. A 60-year-old female received LDLT using a left lobe graft from her second son for liver failure caused by hepatitis C-related cirrhosis. Six months after LDLT, she was diagnosed as recurrent HCV infection by liver biopsy. IFN monotherapy was started from 7 mo after LDLT and her platelet count decreased to less than 50 000/μL, which thus made it necessary to discontinue the treatment. We decided to attempt laparoscopic splenectomy (LS) under general anesthesia. Since intra-abdominal findings did not show any adhesion formations around the spleen, LS could be successfully performed. After LS, since her platelet count immediately increased to 225 000/μL 14 d after operation, IFN therapy was restarted and we could convert the combination therapy of IFN and ribavirin, resulting in no detectable viral marker. In conclusion, LS can be performed safely even after LDLT, and LS after LDLT is a feasible and less invasive modality for thrombocytopenia caused by antiviral therapy. PMID:18636675

  5. Severe Acquired Idiopathic Thrombocytopenia in a Female Cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Parrula, Cecilia M; Mysore, Jagannatha; Burr, Holly; Freebern, Wendy; Neef, Natasha

    2015-06-01

    A 4-y-old female cynomolgus macaque presented for veterinary evaluation prior to placement in a preclinical study showed markedly low platelet counts that continued to decrease over time. Physical examination over the next several days showed areas of pale red discoloration in forelimbs, anterior thorax, and inguinal area and multifocal pinpoint areas of erythema or scabs. An area of dark red discoloration approximately 2 cm in diameter on the dorsal surface of the tongue was discovered on day 9. The macaque was euthanized, and histopathologic evaluation showed multifocal, ulcerative or erosive, hemorrhagic, lymphohistiocytic and neutrophilic glossitis and tonsillitis. The lesions on the tongue were associated with opportunistic fungi consistent with Candida albicans. The bone marrow showed megakaryocytic hyperplasia. There was no evidence of increased consumption of platelets, sequestration of platelets, or bone marrow suppression. The monkey was serologically negative for simian retrovirus, SIV, and simian T-lymphotropic virus. In light of cases reported in humans, immune-mediated destruction of platelets due to autoantibodies secondary to Candida albicans infection was considered. However, we were unable to detect antiplatelet antibodies on the platelet surface or in serum to support this etiology; therefore idiopathic thrombocytopenia was diagnosed. To our knowledge, this case represents the second reported observation of acquired thrombocytopenia in a nonhuman primate and the first reported observation in a cynomolgus macaque.

  6. Severe reversible autoimmune haemolytic anaemia and thrombocytopenia associated with diclofenac therapy.

    PubMed

    Kramer, M R; Levene, C; Hershko, C

    1986-01-01

    Severe immune haemolytic anaemia and thrombocytopenia developed in a 71-year-old female within 10 d of starting diclofenac (Voltarol) therapy. These complications resolved within 3 weeks of discontinuation of the drug and corticosteroid therapy. A warm autoantibody of the IgG type together with C3 was found in the direct antiglobulin test of the patient's RBC. The patient's serum and RBC eluate contained a warm autoantibody which reacted with all commercial panel cells without the addition of diclofenac, and gave a negative reaction with Rh null and -D- RBC. This pattern of interactions is similar to haemolysis associated with alpha-methyldopa, indicating the presence of autoantibodies directed against structural components common to all Rh antigens. The coexistence of immune thrombocytopenia and immune haemolytic anaemia is suggestive of an autoimmune disease caused by modified T-cell regulation. Although immune haemolytic anaemia is a rare complication of diclofenac therapy, our observations illustrate the severity of haemolytic anaemia in the occasional patient and stress the need for increased awareness of such a development.

  7. Thrombocytopenia induced by the histone deacetylase inhibitor abexinostat involves p53-dependent and -independent mechanisms

    PubMed Central

    Ali, A; Bluteau, O; Messaoudi, K; Palazzo, A; Boukour, S; Lordier, L; Lecluse, Y; Rameau, P; Kraus-Berthier, L; Jacquet-Bescond, A; Lelièvre, H; Depil, S; Dessen, P; Solary, E; Raslova, H; Vainchenker, W; Plo, I; Debili, N

    2013-01-01

    Abexinostat is a pan histone deacetylase inhibitor (HDACi) that demonstrates efficacy in malignancy treatment. Like other HDACi, this drug induces a profound thrombocytopenia whose mechanism is only partially understood. We have analyzed its effect at doses reached in patient plasma on in vitro megakaryopoiesis derived from human CD34+ cells. When added at day 0 in culture, abexinostat inhibited CFU-MK growth, megakaryocyte (MK) proliferation and differentiation. These effects required only a short incubation period. Decreased proliferation was due to induction of apoptosis and was not related to a defect in TPO/MPL/JAK2/STAT signaling. When added later (day 8), the compound induced a dose-dependent decrease (up to 10-fold) in proplatelet (PPT) formation. Gene profiling from MK revealed a silencing in the expression of DNA repair genes with a marked RAD51 decrease at protein level. DNA double-strand breaks were increased as attested by elevated γH2AX phosphorylation level. Moreover, ATM was phosphorylated leading to p53 stabilization and increased BAX and p21 expression. The use of a p53 shRNA rescued apoptosis, and only partially the defect in PPT formation. These results suggest that HDACi induces a thrombocytopenia by a p53-dependent mechanism along MK differentiation and a p53-dependent and -independent mechanism for PPT formation. PMID:23887629

  8. 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.

  9. 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

  10. Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013–2014

    PubMed Central

    Shimada, Tomoe; Matsui, Tamano; Shimojima, Masayuki; Saijo, Masayuki; Oishi, Kazunori

    2016-01-01

    Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients. PMID:27776187

  11. 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

  12. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    PubMed

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson

    2013-01-01

    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  13. Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

    PubMed

    Liu, Shelan; Chai, Chengliang; Wang, Chengmin; Amer, Said; Lv, Huakun; He, Hongxuan; Sun, Jimin; Lin, Junfen

    2014-03-01

    Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10~15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector-animal-human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Coupled regulation of interleukin-12 receptor beta-1 of CD8+ central memory and CCR7-negative memory T cells in an early alloimmunity in liver transplant recipients

    PubMed Central

    Egawa, H; Ozawa, K; Takada, Y; Teramukai, S; Mori, A; Ogawa, K; Kaido, T; Fujimoto, Y; Kawaguchi, Y; Hatano, E; Sato, H; Ono, M; Takai, K; Tanaka, K; Uemoto, S

    2010-01-01

    This study investigated how CD8+ T cell subsets respond to allo- and infectious immunity after living donor liver transplantation (LDLT). Early alloimmunity: 56 recipients were classified into three types according to the post-transplant course; type I demonstrated uneventful post-transplant course, type II developed severe sepsis leading to multiple organ dysfunction syndrome or retransplantation and type III with acute rejection. In 23 type I recipients, the interleukin (IL)-12 receptor beta-1 (Rβ1)+ cells of central memory T cells (Il-12Rβ1+ TCM) were increased above the pretransplant level. In 16 type II recipients, IL-12Rβ1+ TCM was decreased markedly below the pretransplant level on postoperative day (POD) 5. In 17 type III recipients, IL-12Rβ1+ TCM was decreased for a more prolonged period until POD 10. Along with down-regulation of IL-12Rβ1+ TCM, the IL-12Rβ1+ cells of CCR7-negative subsets (CNS) as well as perforin, interferon (IFN)-γ and tumour necrosis factor (TNF)-α decreased gradually, resulting in the down-regulation of effectors and cytotoxicity. The down-regulation of IL-12Rβ1+ TCM was suggested to be due to the recruitment of alloantigen-primed T cells into the graft, and then their entry into the secondary lymphoid organ, resulting in graft destruction. Infectious immunity: immunocompetent memory T cells with the capacity to enhance effectors and cytotoxicity were generated in response to post-transplant infection along with both up-regulation of the IL-12Rβ1+ TCM and an increase in the CNS showing the highest level of IL-12Rβ1+ cells. In conclusion, this work demonstrated that the IL-12Rβ1+ cells of TCM and CNS are regulated in a tightly coupled manner and that expression levels of IL-12Rβ1+ TCM play a crucial role in controlling allo- and infectious immunity. PMID:20345976

  19. Neonatal Informatics: Information Technology to Support Handoffs in Neonatal Care.

    PubMed

    Palma, Jonathan P; Van Eaton, Erik G; Longhurst, Christopher A

    2011-01-01

    Communication failures during physician handoffs represent a significant source of preventable adverse events. Computerized sign-out tools linked to hospital electronic medical record systems and customized for neonatal care can facilitate standardization of the handoff process and access to clinical information, thereby improving communication and reducing adverse events. It is important to note, however, that adoption of technological tools alone is not sufficient to remedy flawed communication processes. OBJECTIVES: After completing this article, readers should be able to: Identify key elements of a computerized sign-out tool.Describe how an electronic tool might be customized for neonatal care.Appreciate that technological tools are only one component of the handoff process they are designed to facilitate.

  20. 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 ...

  1. 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

  2. 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.

  3. 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.

  4. Epidemiology of early neonatal mortality.

    PubMed

    Tyagi, N K; Bharambe, M S; Garg, B S; Mathur, J S; Goswami, K

    1994-01-01

    During 1981-1991 at a rural teaching hospital (Kasturba Hospital) of Mahatma Gandhi Institute of Medical Sciences in Sevagram, Wardha, India, 454 of 13,939 newborns died during the early neonatal period for an early neonatal mortality rate (ENMR) of 33.7/1000 live births. The ENMR for boys was not significantly different from that for girls (36.1 vs. 28.6). Community medicine specialists analyzed data on these early neonatal deaths to examine distribution of early neonatal mortality, especially its relationship with prematurity, low birth weight, birth order, and by sex. They calculated average percent deaths (APD) per hour to examine the dynamics in early neonatal mortality. The mean age at death was lower among newborns of birth order greater than 2 than those of birth order less than 2 (23.47 vs. 26.85 hours; p 0.001). ENMR was higher for newborns of birth order greater than 2 than those of birth order less than 2 (41.74% vs. 27.35%; P 0.001). The mean age at death increased as gestation increased (10.34 for 28 weeks; 24.27 for 28-33 weeks, 31.53 for 33-37 weeks, and 34.43 for 37 weeks; p 0.001). ENMR decreased as gestation increased (850 for 28 weeks; 375 for 28-33 weeks, 147.02 for 33-37 weeks, and 8.77 for 37 weeks; p 0.001). The mean age at death increased as birth weight increased for newborns weighing less than 1500 gms through 2000-2500 gms (23.36-37.13 hours; p 0.001). It was lowest among those weighing more 3000 gms (11.55 gms). ENMR fell as birth weight increased (614.33 for 1500 gms, 116.19 for 1500-2000 gms, 19.38 for 2000-2500 gms, 10.99 for 2500-3000 gms, and 5.41 for 3000 gms; p 0.001). The APD/hour for the first hour of life was 3.74% for a relative risk of 12.9. It decreased steadily as the hours of life increased (3.08% for 1-6 hours, 1.19% for 6-24 hours, 0.67% for 24-72 hours, and 0.29% for 72-168 hours). Knowledge of time of likely death can help providers know where they need to focus their attention to prevent early neonatal deaths.

  5. [Heart surgery in neonates (experience with surgery in 420 neonates)].

    PubMed

    Hucín, B; Tláskal, T; Horváth, P; Kostelka, M; Kucera, V; Tax, P; Reich, O; Chaloupecký, V; Skovránek, J; Kopecká, L

    1994-03-01

    In the child cardiocentre in Prague 5-Motol in 1977-1993 a total of 420 neonates with critical inborn heart disease were operated. Obstructive defects of the left heart were found in 178 children, obstructive defects of the right heart in 87, defects with a left-right shunt with pulmonary hypertension in 75, conotruncal malformations in 73 and various operations were made in 7 children. Complete repair of the defect was achieved in 281 neonates, incl. 104 where extracorporeal circulation was used. Palliative operations were made in 139 children. Early mortality during the entire period was 26%, whereby a decrease from 40% to 16% was recorded during the last three years. At present it is possible to repair permanently critical inborn heart disease in the majority of neonates. This is made possible in particular by early non-invasive diagnosis, treatment with prostaglandins E in duct-dependent critical heart disease, optimal time for and selection of most suitable surgery, microsurgical technique, miniaturization of extracorporeal circulation and the method of deep hypothermia. PMID:8184369

  6. 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

  7. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation.

    PubMed

    Soundravally, R; Sankar, P; Bobby, Z; Hoti, S L

    2008-09-01

    Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P < 0.05). Using one way ANOVA, high PCOs levels were found in DSS in comparison to DF and DHF cases on all the three days tested (P < 0.001). TAS levels were found to be low among DSS on days 5 and 7 and day 7 in DHF when compared with DF cases. Correlation analysis between MDA and hematocrit revealed a significant positive association between them in DHF and DSS on day 5 (DHF r = 0.372; p = 0.024 and DSS r = 0.535; p = 0.0-01) and day 7 (DHF r = 0.412; p = 0.003 and DSS r = 0.765; p < 0.0001). There was an important negative correlation between platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p < 0.001 and DSS r = -0.581; p < 0.001) and day 7 (DHF r = -0.418; p = 0.001 and DSS r = -0.515; p = 0.002)]. This study concludes that an increase in oxidative stress was found in dengue viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was

  8. DEA based neonatal lung simulator

    NASA Astrophysics Data System (ADS)

    Schlatter, Samuel; Haemmerle, Enrico; Chang, Robin; O'Brien, Benjamin M.; Gisby, Todd; Anderson, Iain

    2011-04-01

    To reduce the likelihood of ventilator induced lung injury a neonatal lung simulator is developed based on Dielectric Elastomer Actuators (DEAs). DEAs are particularly suited for this application due to their natural like response as well as their self-sensing ability. By actively controlling the DEA, the pressure and volume inside the lung simulator can be controlled giving rise to active compliance control. Additionally the capacitance of the DEA can be used as a measurement of volume eliminating the integration errors that plague flow sensors. Based on simulations conducted with the FEA package ABAQUS and experimental data, the characteristics of the lung simulator were explored. A relationship between volume and capacitance was derived based on the self sensing of a bubble actuator. This was then used to calculate the compliance of the experimental bubble actuator. The current results are promising and show that mimicking a neonatal lung with DEAs may be possible.

  9. EEG in the neonatal unit.

    PubMed

    Lamblin, M D; de Villepin-Touzery, A

    2015-03-01

    The execution and interpretation of neonatal EEG adheres to strict and specific criteria related to this very early age. In preterm newborns, the dedicated healthcare staff needs to respect EEG indications and chronology of EEG recordings in order to diagnose and manage various pathologies, and use EEG in addition to cerebral imaging. EEG analysis focuses on a global vision of the recording according to the neonate's state of alertness and various age-related patterns. Monitoring of continuous conventional EEG and simplified EEG signal processing can help screen for seizures and monitor the effect of antiepileptic treatment, as well as appreciating changes in EEG background activity, for diagnostic and prognostic purposes. EEG reports should be highly explanatory to meet the expectations of the physician's clinical request.

  10. Neonatal jaundice: the surgical viewpoint.

    PubMed

    Kling, S

    1980-12-20

    There is good evidence that neonatal hepatitis, biliary hypoplasia, biliary atresia and choledochal cyst are different stages of one disease process for which the term infantile obstructive cholangiopathy has been suggested. Thanks to the work of Kasai and the operation of hepatic portoenterostomy the surgical outlook has greatly improved, although in North America it still leaves much to be desired. One cannot procrastinate too long in the hope that the patient's condition will improve spontaneously, because the surgical results are much better when the operation is performed before the patient is 10 weeks old. This article outlines the steps that should be followed in investigating neonatal jaundice, the nonsurgical measures that can be taken in an attempt to reverse or alleviate the underlying condition, and the specific role of the pediatric surgeon in the management of choledochal cyst and biliary atresia.

  11. Pleural effusion in a neonate

    PubMed Central

    Shetty, Sandeep Krishnanand; Butler, Mark

    2011-01-01

    A premature neonate who developed respiratory distress in the first few days of life was found to have a pleural effusion, which reaccumulated following drainage. The effusion was demonstrated to be a chylothorax. He required multiple chest drains and was started on a medium chain triglyceride formula feed. This brought about a full resolution of the effusions and he made a complete recovery. PMID:22688472

  12. [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

  13. 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

  14. 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

  15. Early-onset neonatal sepsis.

    PubMed

    Simonsen, Kari A; Anderson-Berry, Ann L; Delair, Shirley F; Davies, H Dele

    2014-01-01

    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.

  16. Neonatal necrotizing enterocolitis: a focus on.

    PubMed

    Pellegrini, M; Lagrasta, N; Garcìa Garcìa, C; Campos Serna, J; Zicari, E; Marzocca, G

    2002-01-01

    Necrotizing enterocolitis (NEC) is a multifactorial worldwide problem, representing the most frequent gastrointestinal emergency in neonates. Extremely common in preterm infants, it is also registered in fullterm low birth weight neonates. Despite extensive research, its etiopathogenesis is not completely understood and this neonatal disease remains associated with high morbidity and mortality rates. This review proposes an interdisciplinary focus on recent developments in NEC etiopathogenesis, diagnosis and management. PMID:12608653

  17. 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

  18. Serum Thrombopoietin Levels and Its Relationship With Thrombocytopenia in Patients With Cirrhosis

    PubMed Central

    Temel, Tuncer; Cansu, Dondu Uskudar; Temel, Halide Edip; Ozakyol, Aysegul Harmanc

    2014-01-01

    Background: Patients with cirrhosis usually have thrombocytopenia in discrete levels. The mechanism of thrombocytopenia is thought as splenic sequestration and destruction of platelets, impaired bone marrow generation and diminished hepatic thrombopoietin synthesis. Objectives: The aim of this study was to evaluate serum thrombopoietin levels and its relationship with thrombocytopenia at patients with cirrhosis. Patients and Methods: Ninety–two cirrhotic patients and 45 healthy controls without history or findings of pathologies that can effect thrombopoietin levels were enrolled by simple random sampling to patient and control groups of this case control study performed at Eskisehir-Turkey. Thrombopoietin was measured in serum samples with a solid phase enzyme-linked immune absorbent assay. Additionally, spleen size and volume index were determined. Results: Platelet counts were lower in patients with cirrhosis (97000 ± 8000/mm3) than in healthy subjects (240000 ± 51000/mm3, P < 0.001). Significant difference was determined for platelet counts among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). Serum TPO concentration was higher (69 ± 12 pg/mL) in cirrhotic group than healthy controls (49 ± 9 pg/ml) (P < 0.05). No significant difference in TPO levels were found among the Child A, B and C stages (64 ± 11 pg/mL, 75 ± 13 pg/mL and 68 ± 10 pg/mL, respectively). Spleen size and SVI was significantly higher in the cirrhotic patients than healthy controls (148 ± 14 mm vs. 98 ± 11 mm, P < 0.001-9167 ± 287 cm2 vs. 4118 ± 123 cm2). Significant difference was determined for spleen size and spleen index among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). TPO levels were significantly different between cirrhotic patients with platelet levels below 50.000/mm3 (n = 16, plt-count: 41000 ± 8300/mm3, TPO levels: 73 ± 7 pg

  19. The use of argatroban for carotid endarterectomy in heparin-induced thrombocytopenia.

    PubMed

    Hallman, Sarah E; Hebbar, Latha; Robison, Jay; Uber, Walter E

    2005-04-01

    Heparin-induced thrombocytopenia (HIT) is a major obstacle in cardiovascular surgeries. In this case report, we used argatroban, a direct thrombin inhibitor, to achieve and maintain anticoagulation for carotid endarterectomy. Unlike heparin, the direct thrombin inhibitors bind directly to thrombin, bypassing antithrombin III and the potential to precipitate HIT. A bolus of argatroban 150 microg/kg followed by an infusion of 5 microg . kg(-1) . min(-1) was used, and adequate anticoagulation was demonstrated with multiple laboratory tests (at 28 min, prothrombin time = 29.8 s, partial thromboplastin time = 69.1 s, international normalized ratio = 3.52 s, and activated clotting time = 220 s). The surgery was successful, and the patient was discharged the next day with no postoperative neurologic sequelae or other complications. We conclude that argatroban can be used safely and successfully for carotid endarterectomy in a patient with a history of HIT.

  20. Thymoma complicated by acquired amegakaryocytic thrombocytopenia and pure red cell aplasia.

    PubMed

    Gay, Carl M; William, William N; Wang, Sa A; Oo, Thein Hlaing

    2014-11-01

    Although the association of pure red cell aplasia (PRCA) and aplastic anemia with thymoma is well-known, acquired amegakaryocytic thrombocytopenia (AAMT) is not a recognized paraneoplastic manifestation of thymoma. This report discusses a patient with recurrent thymoma complicated by myasthenia gravis, PRCA, and AAMT. Both PRCA and AAMT are diagnosed after a thymoma recurrence, 11 years after complete resection of the initial tumor and 9 months after chemotherapy for the relapsed disease. Both PRCA and AAMT responded to immunosuppression with cyclosporine, corticosteroid, and an abbreviated course of antithymocyte globulin, achieving a very good erythroid response and a complete remission for AAMT, suggesting that AAMT, although extremely rare, can be an immune-mediated paraneoplastic manifestation of thymoma.

  1. No detection of severe Fever with thrombocytopenia syndrome virus from ixodid ticks collected in seoul.

    PubMed

    Ham, Heejin; Jo, Sukju; Jang, Jungim; Choi, Sungmin

    2014-04-01

    Larvae, nymphs, and adult stages of 3 species of ixodid ticks were collected by tick drag methods in Seoul during June-October 2013, and their infection status with severe fever with thrombocytopenia syndrome (SFTS) virus was examined using RT-PCR. During the period, 732 Haemaphysalis longicornis, 62 Haemaphysalis flava, and 2 Ixodes nipponensis specimens were collected. Among the specimens of H. longicornis, the number of female adults, male adults, nymphs, and larvae were 53, 11, 240, and 446, respectively. Ticks were grouped into 63 pools according to the collection site, species, and developmental stage, and assayed for SFTS virus. None of the pools of ticks were found to be positive for SFTS virus gene.

  2. 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

  3. 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

  4. What do we learn from immunomodulation in patients with immune thrombocytopenia?

    PubMed

    Kuwana, Masataka

    2016-04-01

    Current therapeutic strategies for autoimmune diseases primarily rely on immunosuppression, but global immune suppression results in an increased risk for severe infection and malignancy. In contrast, immuomodulation is another therapeutic approach employing intrinsic or environmental regulators that exert modulatory effects by intervening multiple checkpoints of the immune system, leading to correction of dysregulated immune responses. We have learned that immunomodulation by intravenous immunoglobulin is highly efficacious and safe in patients with immune thrombocytopenia (ITP), an autoimmune disease mediated by IgG antiplatelet autoantibodies. Recently, another types of immunomodulatory treatment are also effective for ITP. These include eradication of Helicobacter pylori and thrombopoietic agents, such as thrombopoietin receptor agonists. These treatment modalities are shown to exert immunomodulatory action by suppressing multiple checkpoints of the pathogenic loop of ITP, although only certain subsets of the patients show robust responses. Understanding mechanisms underlying immunomodulation is highly useful in clarifying pathogenesis of immune-mediated diseases and developing novel therapeutic approaches. PMID:27312160

  5. 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

  6. The Centenary of Immune Thrombocytopenia – Part 1: Revising Nomenclature and Pathogenesis

    PubMed Central

    Consolini, Rita; Legitimo, Annalisa; Caparello, Maria Costanza

    2016-01-01

    The natural history of the immune thrombocytopenia (ITP) is interesting and intriguing because it traces different steps underlying autoimmune diseases. The review points out the main steps that have accompanied the stages of its history and the consequential changes related to its terminology. ITP is an autoimmune disease resulting from platelet antibody-mediated destruction and impaired megakaryocyte and platelet production. However, research advances highlight that a complex dysregulation of the immune system is involved in the pathogenesis of this condition. The review examines the role of the multiple immune components involved in the autoimmunity process, focusing on the more recent mechanisms, which could be new promising therapeutic targets for ITP patients. PMID:27807534

  7. Diagnosis and management of neonatal leukaemia.

    PubMed

    van der Linden, Marieke H; Creemers, Sara; Pieters, Rob

    2012-08-01

    Leukaemia in neonates (infants <1 month) is rare, whereby neonatal acute myeloid leukaemia (AML) is more frequent than neonatal acute lymphoblastic leukaemia (ALL). High mortality rates are observed, though AML has a better prognosis than ALL. Neonatal leukaemia is typically presented with hepatosplenomegaly, leukaemia cutis and/or hyperleucocytosis. Congenital infections should be ruled out before diagnosis. Rearrangement of the MLL gene is the most frequently occurring genetic aberration. Treatment includes intensive multi-agent chemotherapy, usually with age-related dose adjustments next to supportive care. Treatment intensification for ALL could be indicated in the future as the dismal prognosis is subject to high relapse rates in ALL.

  8. Neonatal sepsis: progress towards improved outcomes.

    PubMed

    Shane, Andi L; Stoll, Barbara J

    2014-01-01

    Neonates are predisposed to infections during the perinatal period due to multiple exposures and a relatively compromised immune system. The burden of disease attributed to neonatal infections varies by geographic region and maternal and neonatal risk factors. Worldwide, it is estimated that more than 1.4 million neonatal deaths annually are the consequence of invasive infections. Risk factors for early-onset neonatal sepsis (EOS) include prematurity, immunologic immaturity, maternal Group B streptococcal colonization, prolonged rupture of membranes, and maternal intra-amniotic infection. Intrapartum antimicrobial prophylaxis administered to GBS-colonized women has reduced the burden of disease associated with early onset GBS invasive infections. Active surveillance has identified Gram-negative pathogens as an emerging etiology of early-onset invasive infections. Late-onset neonatal sepsis (LOS) attributable to Gram-positive organisms, including coagulase negative Staphylococci and Staphylococcus aureus, is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of late-onset sepsis, especially among infants who receive broad spectrum antimicrobial agents. Prophylactic fluconazole administration to very low birthweight (VLBW) neonates during the first 6 weeks of life reduces invasive candidiasis in neonatal intensive care units with high rates of fungal infection. Prevention of healthcare associated infections through antimicrobial stewardship, limited steroid use, early enteral feeding, limited use of invasive devices and standardization of catheter care practices, and meticulous hand hygiene are important and cost-effective strategies for reducing the burden of late-onset neonatal sepsis.

  9. 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

  10. Autoimmune thrombocytopenia in response to splenectomy in cirrhotic patients with accompanying hepatitis C

    PubMed Central

    Sekiguchi, Tetsuro; Nagamine, Takeaki; Takagi, Hitoshi; Mori, Masatomo

    2006-01-01

    AIM: To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers. METHODS: PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen. RESULTS: Thrombocytopenia (PLT<15×104/μL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107cells were detected in all cirrhotic patients except for one splenectomized patient. PAIgG titers (ng/107cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9 ± 197.0) compared with the splenectomized patients (125.6±87.8) or non-C cirrhosis (152.4 ± 127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis. CONCLUSION: Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition, splenectomy may impair T cells function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production. PMID:16534872

  11. Interleukin-18 gene promoter--607 A/C polymorphism and the risk of immune thrombocytopenia.

    PubMed

    Zhao, Haifeng; Zhang, Yizhuo; Xiao, Gangfeng; Wu, Ningning; Xu, Jianfen; Fang, Zhi

    2014-11-01

    Interleukin-18 (IL-18) is a T helper 1 cytokine, which is postulated to play a role in immune thrombocytopenia (ITP). The aim of this study was to determine whether IL-18 promoter gene -607 A/C polymorphism was associated with ITP. Three-hundred and fifty-four Chinese ITP patients and 300 Chinese healthy individuals were enrolled. Genomic DNA was extracted from the peripheral blood. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) was used to genotype the DNA samples for single nucleotide polymorphism (SNP)-607. Allelic and genotypic frequencies were compared between the case-control groups by the chi-square test. The results showed that the frequencies of the CC, CA and AA genotypes and C and A allele were 32.4, 47.8, 19.8, 56.4 and 43.6% in ITP patients and 32.3, 50.4, 17.3, 57.5 and 42.5% in the controls, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. Furthermore, stratified analysis by the platelet count, age and disease course including ITP with severe thrombocytopenia (sITP), non-sITP, acute adult, chronic adult, acute childhood and chronic childhood revealed no significant difference in genotype and alleles distribution. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These data showed that this SNP may not be used as a stratification marker to predict the susceptibility to Chinese ITP.

  12. Practical viewpoints on the diagnosis and management of heparin-induced thrombocytopenia.

    PubMed

    Lassila, Riitta; Antovic, Jovan P; Armstrong, Elina; Baghaei, Fariba; Dalsgaard-Nielsen, Joern; Hillarp, Andreas; Holme, Paul A; Holmström, Margareta; Johnsson, Hans; Joutsi-Korhonen, Lotta; Sandset, Per Morten

    2011-04-01

    Heparin-induced thrombocytopenia (HIT, type II) is an immune-mediated disorder due to antibodies formed against heparin-platelet factor 4 complexes, usually appearing at days 5 to 14 after initiation of heparin. It is important to recognize HIT because heparin prophylaxis or treatment paradoxically associates with new venous and/or arterial thrombosis. Early clinical suspicion and diagnosis together with proper pharmacotherapy and close laboratory monitoring are the cornerstones for successful management. This includes monitoring of Thrombocytopenia, its Timing to heparin administration, appearance of new Thrombosis or resistance to treatment, and differential diagnosis by exclusion of o Ther causes (the 4T's). Specific attention should be paid to the absence or presence of thrombosis and to tailoring thromboprophylaxis or anticoagulant therapy with a nonheparin alternative. Even in the absence of HIT-associated thrombosis, an active policy for prolonged thromboprophylaxis is demanded. Rapid and reliable assays should be developed for diagnosis and anticoagulation monitoring to secure safe management with nonheparins. Semiquantitative testing for on-call hours should be available and later confirmed as clinically needed. Alternative therapeutic options are available, but because their use is infrequent, experienced coagulation treatment centers should provide guidance in the treatment and in laboratory monitoring. Most of the evidence in HIT is grade IC, and thus the best evidence is provided by clinical experience. New anticoagulants and platelet inhibitors may offer future alternatives in the management of HIT, but the current treatment options provide the best experience and benefit. The joint clinical and laboratory guidelines provided in this article along with two practical case scenarios were prepared by a Nordic expert panel. They will be valuable for hematologists and colleagues who do not routinely encounter HIT. PMID:21455867

  13. Drug-Antibody-Platelet Interaction in Quinine- and Quinidine-induced Thrombocytopenia

    PubMed Central

    Christie, Douglas J.; Aster, Richard H.

    1982-01-01

    Binding of quinine- and quinidine-dependent antibodies to platelets was studied using an electroimmunoassay to measure platelet-bound IgG. Antibodies from four patients with drug-induced thrombocytopenia differed significantly in their interaction with platelets: association constants for binding to platelets at high drug concentrations ranged from 0.29 to 2.6 × 107 M−1, the maximum number of antibody molecules bound ranged from 36,000 to 161,000/platelet, the amount of drug necessary to achieve half-maximum binding of antibodies to platelets ranged from 2 to 60 μM, and only one of the antibodies cross-reacted with the stereoisomer of the drug to which the patient was sensitized. Binding of the antibodies to platelets was enhanced at the highest achievable molar ratio of drug:antibody, 10,000:1, rather than being inhibited, as would be expected in a conventional, hapten-dependent reaction. The drug-antibody-platelet reaction was unaffected by Factor VIII/von Willebrand protein, nonspecifically aggregated IgG, or heat-labile complement components. After pretreatment with tritiated quinine, platelets retained several hundred thousand molecules of drug each, but failed to bind detectable amounts of antibody. However, platelets treated simultaneously with quinine-dependent antibody and tritiated quinine retained significantly more drug after repeated washes than platelets treated with drug and normal serum. These findings support the proposition that in quinine- and quinidine-induced thrombocytopenia, drug and antibody combine first in the soluble phase to form a complex, which then binds with high affinity to a receptor on the platelet surface (innocent bystander reaction), and demonstrate that these antibodies are heterogeneous in respect to the amount of drug required to promote their binding to platelets, the number of platelet receptors they recognize, and their binding affinities. PMID:6215430

  14. Ingestion of colostrum from specific cows induces Bovine Neonatal Pancytopenia (BNP) in some calves

    PubMed Central

    2011-01-01

    Background Since 2006, cases of haemorrhagic diathesis in young calves have been observed with a much higher incidence than previously known. The syndrome, now uniformly called Bovine Neonatal Pancytopenia (BNP), is characterized by multiple (external and internal) haemorrhages, thrombocytopenia, leukocytopenia, and bone marrow depletion. Although various infectious and toxicological causes of bleeding disorders in calves have been ruled out, the aetiology of BNP remains unknown. However, field observations have led to the hypothesis that the aetiological principle may be transmitted to calves via colostrum. The objective of the present study was to verify whether ingestion of colostrum from dams of known BNP calves can elicit signs of BNP and typical haematological findings in conveniently selected neonatal calves. Six such calves received one feeding of colostrum (or a mixture of colostrum batches) from dams of known BNP calves. As controls, another six conveniently selected calves from herds which had never had a BNP case received one feeding of colostrum from their own dams. Haematological and clinical parameters were monitored. Results One of the six experimental calves never showed any haematological, clinical or pathological evidence of BNP. In the other five calves, thrombocyte and leukocyte counts dropped within a few hours following ingestion of colostrum. Of those, three calves developed clinical signs of BNP, their post-mortem examination revealed bone marrow depletion. Of the remaining two calves, a pair of mixed twins, marked thrombocytopenia and recurrent leukocytopenia was evident in one, in which only slight changes in the bone marrow were detected, while in the other thrombocyte counts dropped, but rebounded later, and no bone marrow changes were noted. Thrombocyte counts of the experimental calves were statistically significantly lower than those of the control calves at 2 hours post ingestion of colostrum and at every sampling point between 9

  15. 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

  16. 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

    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.

  17. Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class I expression

    PubMed Central

    Benedictus, Lindert; Luteijn, Rutger D.; Otten, Henny; Jan Lebbink, Robert; van Kooten, Peter J. S.; Wiertz, Emmanuel J. H. J.; Rutten, Victor P. M. G.; Koets, Ad P.

    2015-01-01

    Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome of neonatal calves, is caused by maternal alloantibodies absorbed from colostrum and is characterized by lymphocytopenia, thrombocytopenia and bone marrow hypoplasia. An inactivated viral vaccine is the likely source of alloantigens inducing BNP-associated alloantibodies in the dam. In this study the specificity of BNP alloantibodies was assessed and was linked to the pathology of BNP. We demonstrated that Major Histocompatibility Complex class I (MHC I) and Very Late Antigen-3, an integrin α3/β1 heterodimer, were the major targets of BNP alloantibodies. However, alloantibody binding to various bovine cell types correlated with MHC I expression, rather than integrin β1 or α3 expression. Likewise, alloantibody-dependent complement-mediated cell lysis correlated strongly with MHC I expression. Examination of several tissues of third trimester bovine foetuses revealed that cells, shown to be affected in calves with BNP, were characterized by high MHC class I expression and high levels of alloantibody binding. We conclude that in spite of the heterogeneous specificity of BNP associated maternal alloantibodies, MHC I-specific antibodies mediate the pathogenicity of BNP in the calf and that cells with high MHC I expression were preferentially affected in BNP. PMID:26235972

  18. Pathogenicity of Bovine Neonatal Pancytopenia-associated vaccine-induced alloantibodies correlates with Major Histocompatibility Complex class I expression.

    PubMed

    Benedictus, Lindert; Luteijn, Rutger D; Otten, Henny; Lebbink, Robert Jan; van Kooten, Peter J S; Wiertz, Emmanuel J H J; Rutten, Victor P M G; Koets, Ad P

    2015-01-01

    Bovine Neonatal Pancytopenia (BNP), a fatal bleeding syndrome of neonatal calves, is caused by maternal alloantibodies absorbed from colostrum and is characterized by lymphocytopenia, thrombocytopenia and bone marrow hypoplasia. An inactivated viral vaccine is the likely source of alloantigens inducing BNP-associated alloantibodies in the dam. In this study the specificity of BNP alloantibodies was assessed and was linked to the pathology of BNP. We demonstrated that Major Histocompatibility Complex class I (MHC I) and Very Late Antigen-3, an integrin α3/β1 heterodimer, were the major targets of BNP alloantibodies. However, alloantibody binding to various bovine cell types correlated with MHC I expression, rather than integrin β1 or α3 expression. Likewise, alloantibody-dependent complement-mediated cell lysis correlated strongly with MHC I expression. Examination of several tissues of third trimester bovine foetuses revealed that cells, shown to be affected in calves with BNP, were characterized by high MHC class I expression and high levels of alloantibody binding. We conclude that in spite of the heterogeneous specificity of BNP associated maternal alloantibodies, MHC I-specific antibodies mediate the pathogenicity of BNP in the calf and that cells with high MHC I expression were preferentially affected in BNP. PMID:26235972

  19. Individual Differences and Auditory Conditioning in Neonates.

    ERIC Educational Resources Information Center

    Franz, W. K.; And Others

    The purposes of this study are (1) to analyze learning ability in newborns using heart rate responses to auditory temporal conditioning and (2) to correlate these with measures on the Brazelton Neonatal Behavioral Assessment Scale. Twenty normal neonates were tested using the Brazelton Scale on the third day of life. They were also given a…

  20. Teamwork in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Barbosa, Vanessa Maziero

    2013-01-01

    Medical and technological advances in neonatology have prompted the initiation and expansion of developmentally supportive services for newborns and have incorporated rehabilitation professionals into the neonatal intensive care unit (NICU) multidisciplinary team. Availability of therapists specialized in the care of neonates, the roles of…