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Sample records for alloimmune thrombocytopenia nait

  1. 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

  2. Alloimmune thrombocytopenia: state of the art 2006.

    PubMed

    Berkowitz, Richard L; Bussel, James B; McFarland, Janice G

    2006-10-01

    In alloimmune thrombocytopenia maternal immunoglobulin G anti-platelet alloantibodies cross the placenta and cause fetal thrombocytopenia. The diagnosis requires laboratory demonstration of incompatibility between a maternal and paternal platelet alloantigen, and detection of maternal antibody to the discordant paternal alloantigen. This disorder should be treated in utero because of its propensity to cause fetal intracranial bleeding. Administration of intravenous immunoglobulin 1 gm/kg/wk to the mother is successful in substantially raising the platelet count in many fetuses, but this is most successful if the count is >20,000/mL3 at the time that the therapy is initiated. The addition of prednisone administered daily to the mother and/or increasing the dose of intravenous immunoglobulin has a therapeutic benefit in cases that have failed to respond to initial therapy with intravenous immunoglobulin alone. The only reliable noninvasive indicator of the potential for severe fetal thrombocytopenia is a history of an antenatal intracranial hemorrhage in a prior affected sibling. Because fetal blood sampling to determine the fetal platelet count may be associated with significant fetal morbidity, attempts are being made to derive a rational, non-invasive, stratified approach to patient-specific therapy of this disorder in affected pregnancies.

  3. T-cell responses associated with neonatal alloimmune thrombocytopenia: isolation of HPA-1a-specific, HLA-DRB3*0101-restricted CD4+ T cells.

    PubMed

    Ahlen, Maria Therese; Husebekk, Anne; Killie, Mette Kjaer; Skogen, Bjørn; Stuge, Tor B

    2009-04-16

    T-cell responses have been implicated in the development of HPA-1a-induced neonatal alloimmune thrombocytopenia (NAIT). However, HPA-1a-specific T cells have neither been isolated nor characterized. Here, we aimed to determine whether HPA-1a-specific T cells could be isolated from HPA-1a-immunized women. In the present study, peripheral blood mononuclear cells (PBMCs) from an HPA-1a-alloimmunized woman were cultured for weeks in the presence of HPA-1a peptide, labeled with CFSE, and assayed for antigen-specific proliferation. Individual proliferating cells were isolated by fluorescence-activated cell sorting and expanded in culture. Antigen specificity and HLA restriction were determined by cytokine secretion (enzyme-linked immunospot [ELISPOT]) and proliferation assays. Several CD3(+)CD4(+) T-cell clones were isolated that proliferated and secreted cytokines in response to HPA-1a peptide. Two of these clones have been established in long-term culture in our laboratory. Both of these recognize synthetic as well as naturally processed HPA-1a antigen, and the recognition is restricted by the MHC molecule HLA-DRB3*0101 that is strongly associated with NAIT. These HPA-1a-specific T-cell clones represent unambiguous evidence for the association of T-cell responses with NAIT, and they will serve as unique tools to elucidate the cellular immune response that may result in NAIT.

  4. Fetal and neonatal alloimmune thrombocytopenia: progress and ongoing debates.

    PubMed

    Bussel, James B; Primiani, Andrea

    2008-01-01

    Fetal and neonatal alloimmune thrombocytopenia (AIT) is a result of a parental incompatibility of platelet-specific antigens and the transplacental passage of maternal alloantibodies against the platelet antigen shared by the father and the fetus. It occurs in approximately 1 in 1000 live births and is the most common cause of severe thrombocytopenia in fetuses and term neonates. As screening programs are not routinely performed, most affected fetuses are identified after birth when neonatal thrombocytopenia is recognized. In severe cases, the affected fetus is identified as a result of suffering from an in utero intracranial hemorrhage. Once diagnosed, AIT must be treated antenatally as the disease can be more severe in subsequent pregnancies. While there have been many advances regarding the diagnosis and treatment of AIT, it is still difficult to predict the severity of disease and which therapy will be effective.

  5. 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.

  6. Fatal alloimmune thrombocytopenia due to anti-HLA alloimmunization in a twin pregnancy: A very infrequent complication of assisted reproduction.

    PubMed

    Meler, Eva; Porta, Roser; Canals, Carme; Serra, Bernat; Lozano, Miguel

    2016-11-02

    The most frequently involved antigen in severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the human platelet antigen 1a. Platelets express the HLA-A and B antigens on their membrane and some studies report that maternal anti-HLA class I antibody can also cause FNAIT. We report here a very unusual case of a first twin pregnancy produced in vitro by oocyte and semen donation where the mother developed markedly elevated HLA antibodies, in the absence of anti-platelet or anti-neutrophil antibodies, that provoked in one of the twins a profound thrombocytopenia and intracranial hemorrhage and a mild thrombocytopenia and neutropenia in the second twin lasting until the fourth month of life. In addition, anti-D alloimmunization provoked hemolytic disease of the newborn with intrauterus anemia detected in the first twin and post-natal anemia in the second twin that required red blood cell transfusion and phototherapy. We hypothesize that the complete HLA-incompatible twin pregnancy due to the oocyte donation might have contributed to the severity of the clinical manifestations.

  7. Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

    PubMed

    Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula

    2016-06-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

  8. 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).

  9. 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.

  10. Antenatal management in fetal and neonatal alloimmune thrombocytopenia: a systematic review.

    PubMed

    Winkelhorst, Dian; Murphy, Michael F; Greinacher, Andreas; Shehata, Nadine; Bakchoul, Tamam; Massey, Edwin; Baker, Jillian; Lieberman, Lani; Tanael, Susano; Hume, Heather; Arnold, Donald M; Baidya, Shoma; Bertrand, Gerald; Bussel, James; Kjaer, Mette; Kaplan, Cécile; Kjeldsen-Kragh, Jens; Oepkes, Dick; Ryan, Greg

    2017-01-27

    Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), and weekly maternal intravenous immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy are common options, but the optimal management has not been determined. The aim of this systematic review was to assess antenatal treatment strategies for FNAIT. Four randomized controlled trials and twenty-two non-randomized studies were included. Pooling of results was not possible due to considerable heterogeneity. Most studies found comparable outcomes regarding the occurrence of intracranial hemorrhage, regardless of antenatal management strategy applied; FBS, IUPT or IVIG with/without corticosteroids. There is no consistent evidence for the value of adding steroids to IVIG. Fetal blood sampling or intrauterine platelet transfusion resulted in a relatively high complication rate, consisting mainly of preterm emergency cesarean section, 11% per treated pregnancy in all studies combined. Overall, non-invasive management in pregnant mothers who have had a previous neonate with FNAIT is effective without the relatively high rate of adverse outcomes seen with invasive strategies. This systematic review suggests that first line antenatal management in FNAIT is weekly IVIG administration, with or without the addition of corticosteroids.

  11. Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

    PubMed Central

    Vadasz, Brian; Chen, Pingguo; Yougbaré, Issaka; Zdravic, Darko; Li, June; Li, Conglei; Carrim, Naadiya; Ni, Heyu

    2017-01-01

    Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

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

    PubMed

    Ghevaert, Cedric; 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

    2013-07-18

    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.

  13. 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

  14. Neonatal alloimmune thrombocytopenia associated with maternal-fetal incompatibility for blood group B

    PubMed Central

    Curtis, Brian R.; Fick, Andrea; Lochowicz, Andrew J.; McFarland, Janice G.; Ball, Robert H.; Peterson, Julie; Aster, Richard H.

    2013-01-01

    BACKGROUND Blood group A and B antigens are expressed only weakly on platelets (PLTs) of most individuals but are very strongly expressed on PLTs from approximately 1 percent of normal subjects (Type II high expressers). The implications of this trait for transfusion medicine are undefined. STUDY DESIGN AND METHODS A family was studied in which two Group B infants were born with neonatal thrombocytopenia, whereas a third infant whose blood group was A2 had a normal PLT count at birth. RESULTS Serologic studies demonstrated a maternal antibody that reacted strongly with PLTs from the father and the two group B children in flow cytometry and with GPIIb/IIIa from their PLTs in solid-phase assays. No PLT-specific antibodies were detected in maternal serum sample, but it contained a high-titer immunoglobulin G antibody specific for blood group B. All PLT-reactive antibody in the mother’s serum was removed by absorption with pooled, washed group A and B red cells (RBCs). Studies with monoclonal anti-B and measurement of serum B-glycosyltransferase activity showed that the father and both group B children were Type II high expressers of blood group B. CONCLUSIONS The findings indicate that high-titer blood group antibodies acquired from the mother can cause thrombocytopenia in infants possessing the Type II high-expresser phenotype despite competition for antibody binding by blood group antigens expressed on RBCs and other tissues. PMID:18028270

  15. [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.

  16. Perinatal Coxsackievirus B3 Infection with Transient Thrombocytopenia.

    PubMed

    Kaga, Akimune; Katata, Yu; Suzuki, Akira; Otani, Kanako; Watanabe, Hiroshi; Kitaoka, Setsuko; Kumaki, Satoru

    2016-01-01

    Coxsackievirus (Cox) B is the second common picornaviruses, after echovirus, detected from children younger than 2 months of age. Neonates who present with Cox B3 infection in the first week are known to have severe illness such as myocarditis or menigoencephalitis. Severity is commonly associated with perinatal vertical transmission. Here, we report a neonatal case of Cox B3 infection with severe thrombocytopenia through horizontal transmission. The patient was a preterm infant born without asphyxia by selective cesarean section. From his 6(th) day of life, the patient had recurrent episodes of apnea. At that time, the laboratory investigations revealed a profound thrombocytopenia without any evidence of inflammation. Thus, neonatal alloimmune thrombocytopenia (NAIT) was suspected, and the patient received transfusion of immunoglobulin and platelets. Thereafter, the patient had no further episodes of apnea, and platelet counts of the patient increased gradually. Later, the possibility of NAIT was ruled out by the result of the platelet antigen genotyping of the patient and his parents. Culture obtained from his nasopharynx was positive for Cox B3. We thus speculate that the patient was exposed to the virus from his mother because she had a febrile episode at her 5(th) day after delivery, and her Cox B3 infection was confirmed by serology. Assuming that the thrombocytopenia was a complication of Cox B3 infection, the immunoglobulin transfusion might have provided a neutralizing antibody against Cox B3. It is important to consider the possibility of enterovirus infection as a differential diagnosis whenever unexplained thrombocytopenia was observed in neonates.

  17. Thrombocytopenia

    MedlinePlus

    ... bleeding, you may need medicines or blood or platelet transfusions . Rarely, the spleen may need to be removed. Outlook Thrombocytopenia can be fatal, especially if the bleeding is severe or occurs in the brain. However, ... Rate This Content: ...

  18. Foetal and neonatal alloimmune thrombocytopaenia.

    PubMed

    Kaplan, Cecile

    2006-10-10

    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 1/1000 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.

  19. Inhibition of HPA-1a alloantibody-mediated platelet destruction by a deglycosylated anti-HPA-1a monoclonal antibody in mice: toward targeted treatment of fetal-alloimmune thrombocytopenia.

    PubMed

    Bakchoul, Tamam; Greinacher, Andreas; Sachs, Ulrich J; Krautwurst, Annika; Renz, Harald; Harb, Habi; Bein, Gregor; Newman, Peter J; Santoso, Sentot

    2013-07-18

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is often caused by maternal alloantibodies against the human platelet antigen (HPA)-1a, which opsonizes fetal platelets (PLTs). Subsequent PLT destruction is mediated via the Fc part of the alloantibodies. The monoclonal antibody (mAb) SZ21 binds to the HPA-1a epitope and inhibits the binding of maternal alloantibodies. However, it also promotes complement activation and phagocytosis. Deglycosylation of antibodies abrogates the Fc-related effector functions. We modified the N-glycan of SZ21 by endoglycosidase F. The in vivo transplacental transport of N-glycan-modified (NGM)-SZ21 was not impaired. When injected into pregnant mice, both native-SZ21 and NGM-SZ21 were transported equally into fetal circulation (8.9% vs 8.7%, respectively, P = .58). Neither the binding properties of NGM-SZ21 to HPA-1a in surface plasmon resonance, nor the inhibition of anti-HPA-1a-induced PLT phagocytosis, were affected by N-glycan modification. NGM-SZ21 prevented PLT destruction induced by maternal anti-HPA-1a antibodies in vivo in a mouse model (PLT clearance after 5 hours; 18% vs 62%, in the presence or absence of NGM-SZ21, respectively, P = .013). Deglycosylation of SZ21 abrogates Fc-effector functions without interfering with placental transport or the ability to block anti-HPA-1a binding. Humanized, deglycosylated anti-HPA-1a mAbs may represent a novel treatment strategy to prevent anti-HPA-1a-mediated PLT destruction in FNAIT.

  20. Gestational thrombocytopenia and immune thrombocytopenias in pregnancy.

    PubMed

    Schwartz, K A

    2000-10-01

    Appropriate management of thrombocytopenia in the pregnant patient is important for the well-being of both mother and fetus. The healthy-appearing mother with mild thrombocytopenia may have either gestational benign thrombocytopenia, which does not produce fetal thrombocytopenia, or immune-mediated thrombocytopenia, which can produce fetal thrombocytopenia. These two types of pregnancy-associated thrombocytopenias can be differentiated. Gestational benign thrombocytopenia is initially discovered during pregnancy, and in these patients a reliable test for antiplatelet antibody is usually negative. Conversely, patients with immune-mediated thrombocytopenia may have a history of thrombocytopenia before the pregnancy, and these patients usually have a detectable antiplatelet antibody. The pregnancy patient who presents with a normal platelet count and a history of neonatal alloimmune thrombocytopenia in a prior pregnancy or with a history of an infant of a close relative with NAT must be carefully monitored. Antiplatelet antibody assays performed on mother's and baby's blood will help determine if an antiplatelet antibody is present in maternal plasma, if the antibody reacts with the baby's platelets, and (with appropriate typing plasma) the antigenic specificity of the maternal and fetal platelets. In addition, antigenic typing of the father's platelets will help determine the risk of NAT in the current pregnancy. If a fetus is at risk for severe immune-mediated thrombocytopenia from either an autoantibody or an alloantibody, the fetal platelet count should be measured, if possible, from blood obtained by umbilical cord puncture. If the fetal platelet count is less than 50,000/microL or cannot be measured but is thought to have a high probability of being less than 50,000/microL, strong consideration should be given to a cesarean delivery.

  1. [Platelet transfusion role in neonatal immune thrombocytopenia].

    PubMed

    Petermann, R

    2016-11-01

    Neonatal immune thrombocytopenia represent less than 5% of cases of early thrombocytopenia (early-onset<72hours post-delivery). As in adults, thrombocytopenia in neonates is defined as a platelet count less than 150G/L. They are either auto- or allo-immune. Thrombocytopenia resulting from transplacental passage of maternal antibodies directed to platelet membrane glycoproteins can be severe. The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial haemorrhage and neurologic sequelea following. However, auto- and allo-immune thrombocytopenia have very different characteristics including the treatment management. In fact, this treatment is based on platelet transfusion associated or not to intravenous immunoglobulin administration. The purpose of this article is to remind platelet transfusion's place in neonatal immune thrombocytopenia in terms of recently published French guidelines and international practices.

  2. A rare manifestation of neonatal alloimmune thrombocytopaenia.

    PubMed

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

    2014-06-02

    Neonatal alloimmune thrombocytopaenia (NAIT) results from a fetomaternal incompatibility with maternal sensitisation against a fetal human platelet antigen (HPA) and antibodies transfer to the fetal circulation, leading to platelet destruction. The clinical presentation is variable and isolated intraocular haemorrhage is rare. We present the case of a male newborn, with intrauterine growth restriction, born at 29 weeks due to pre-eclampsia. He presented proptosis of the left eye, hyphaema and elevated intraocular pressure, with no other signs of haemorrhage. Severe thrombocytopaenia was found (27×10(9)/L). Perinatal infection and maternal thrombocytopaenia were excluded. Positive anti-HPA-1a and antihuman leucocyte antigen class I alloantibodies were found in the mother. Platelet crossmatch between the father's platelets and mother's plasma was positive. Platelet transfusions and intravenous immunoglobulin were given with favourable response. This case highlights an unusual presentation of NAIT, which should be suspected in the presence of severe thrombocytopaenia in the first 24-72 h of life.

  3. Immune Thrombocytopenia

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Immune Thrombocytopenia? Immune thrombocytopenia (THROM-bo-si-toe-PE-ne- ... from one person to another. Types of Immune Thrombocytopenia The two types of ITP are acute (temporary ...

  4. Gamma-ray spectrometer experiment, Apollo 17: NaI(T1) detector crystal activation

    NASA Technical Reports Server (NTRS)

    Trombka, J. I.; Schmadebeck, R. L.; Bielefeld, M.; Okelley, G. D.; Eldridge, J. S.; Northcutt, K. J.; Metzger, A. E.; Schonfeld, E.; Peterson, L. E.; Arnold, J. R.

    1973-01-01

    An attempt was made to obtain experimental data on proton induced activity and its effect on gamma ray spectral measurements. A NaI(T1) crystal flown in Apollo 17 command module was used for the experiment.

  5. Detection of platelet alloimmunity with a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Bishop, J.; Baldini, M.G.

    1981-06-01

    A quantitative immunofluorescence PA-IgG assay was used to detect alloimmunity to platelets. The assay identified serum alloantibodies in 10 out of 14 multitransfused patients and for two of three infants with neonatal thrombocytopenia. The correct separation of all multitransfused patients into alloimmune and nonalloimmune groups by the PA-IgG assay was substantiated with chromium-51-labeled platelet survival studies. The allogeneic nature of the serum antibodies was demonstrated by progressive absorption of the antibody with increasing numbers of allogeneic platelets but not with autologous platelets. The sensitivity of the PA-IgG assay for detection of serum alloantibodies was superior to that of platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing. In dilution experiments with alloimmune serum, elevated levels of serum PA-IgG could still be detected on donor platelets when platelet aggregation and serotonin release tests became negative. Platelet survival studies with selected platelets performed in the 10 alloimmunized, multitransfused patients confirmed the results of the PA-IgG assays, predicting alloimmunity to the donor platelets. In contrast, platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing indicated alloimmunity for 50% or less of the patients. Reduced platelet survival times were also seen with HLA A- and HLA B-matched donor platelets when donor-recipient incompatibility was demonstrated by the PA-IgG assay. Thus the PA-IgG assay provides a sensitive method to detect serum platelet alloantibodies and may offer a technique in platelet crossmatching.

  6. Understanding red blood cell alloimmunization triggers.

    PubMed

    Hendrickson, Jeanne E; Tormey, Christopher A

    2016-12-02

    Blood group alloimmunization is "triggered" when a person lacking a particular antigen is exposed to this antigen during transfusion or pregnancy. Although exposure to an antigen is necessary for alloimmunization to occur, it is not alone sufficient. Blood group antigens are diverse in structure, function, and immunogenicity. In addition to red blood cells (RBCs), a recipient of an RBC transfusion is exposed to donor plasma, white blood cells, and platelets; the potential contribution of these elements to RBC alloimmunization remains unclear. Much attention in recent years has been placed on recipient factors that influence RBC alloantibody responses. Danger signals, identified in murine and human studies alike as being risk factors for alloimmunization, may be quite diverse in nature. In addition to exogenous or condition-associated inflammation, autoimmunity is also a risk factor for alloantibody formation. Triggers for alloimmunization in pregnancy are not well-understood beyond the presence of a fetal/maternal bleed. Studies using animal models of pregnancy-induced RBC alloimmunization may provide insight in this regard. A better understanding of alloimmunization triggers and signatures of "responders" and "nonresponders" is needed for prevention strategies to be optimized. A common goal of such strategies is increased transfusion safety and improved pregnancy outcomes.

  7. Alloimmune refractoriness to platelet transfusions.

    PubMed

    Sandler, S G

    1997-11-01

    Patients who are transfused on multiple occasions with red cells or platelets may develop platelet-reactive alloantibodies and experience decreased clinical responsiveness to platelet transfusion. This situation, conventionally described as "refractoriness to platelet transfusions," is defined by an unsatisfactory low post-transfusion platelet count increment. If antibodies to HLAs are detected, improved clinical outcomes may result from transfusions of HLA-matched or donor-recipient cross-matched platelets. Because refractoriness is an expected, frequently occurring phenomenon, prevention of HLA alloimmunization is an important management strategy. Prevention strategies include efforts to decrease the number of transfusions, filtration of cellular components to reduce the number of HLA-bearing leukocytes, or pretransfusion ultraviolet B irradiation of cellular components to decrease their immunogenicity. Other investigational approaches include reducing the expression of HLAs on transfused platelets, inducing a transient reticuloendothelial system blockade by infusions of specialized immunoglobulin products, or transfusing semisynthetic platelet substitutes (thromboerythrocytes, thrombospheres) or modified platelets (infusible platelet membranes, lyophilized platelets).

  8. Genotyping for human platelet alloantigen polymorphisms: applications in the diagnosis of alloimmune platelet disorders.

    PubMed

    Curtis, Brian R

    2008-09-01

    Molecular typing for platelet allelic polymorphisms was first made possible by discovery of the HPA-1a/1b single nucleotide polymorphism in 1989. Since then, six other biallelic human platelet antigen (HPA) systems have been determined and can be typed using genomic DNA. The introduction of polymerase chain reaction enabled development of several different assays including polymerase chain reaction-sequence-specific primer, melting curve analysis by LightCycler, and 5'-nuclease assays. More recently, multiplex polymerase chain reaction has allowed for the development of high-throughput assays for genotyping large numbers of patients and blood donors for not only platelet gene polymorphisms but also for those of other blood cell genes. Platelet genotyping is a valuable tool in confirming platelet antigen specificities of alloantibodies detected in patient sera to complement the clinical history in the diagnosis of alloimmune platelet disorders such as fetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura, and multiplatelet transfusion refractoriness. In addition, it has made possible prenatal platelet typing of the fetus in suspected cases of FNAIT and large-scale blood donor typing for provision of antigen-negative platelets to transfuse highly alloimmunized patients. Platelet genotyping may also someday prove important as an aid in determining the relative risk of patients for various thrombotic disorders.

  9. 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.

  10. Hospital-acquired thrombocytopenia.

    PubMed

    McMahon, Christine M; Cuker, Adam

    2014-10-01

    The development of thrombocytopenia is common in hospitalized patients and is associated with increased mortality. Frequent and important causes of thrombocytopenia in hospitalized patients include etiologies related to the underlying illness for which the patient is admitted, such as infection and disseminated intravascular coagulation, and iatrogenic etiologies such as drug-induced immune thrombocytopenia, heparin-induced thrombocytopenia, posttransfusion purpura, hemodilution, major surgery, and extracorporeal circuitry. This review presents a brief discussion of the pathophysiology, distinguishing clinical features, and management of these etiologies, and provides a diagnostic approach to hospital-acquired thrombocytopenia that considers the timing and severity of the platelet count fall, the presence of hemorrhage or thrombosis, the clinical context, and the peripheral blood smear. This approach may offer guidance to clinicians in distinguishing among the various causes of hospital-acquired thrombocytopenia and providing management appropriate to the etiology.

  11. Challenges of alloimmunization in patients with haemoglobinopathies.

    PubMed

    Chou, Stella T; Liem, Robert I; Thompson, Alexis A

    2012-11-01

    Red blood cell (RBC) transfusions can be life-sustaining in chronic inherited anaemias, such as thalassaemia, and the indications for blood transfusions in patients with sickle cell disease continue to expand. Complications of transfusions, such as allosensitization, can create significant medical challenges in the management of patients with haemoglobinopathies. This review summarizes key findings from the medical literature related to alloimmunization in haemoglobinopathies and examines potential measures to mitigate these risks. Areas where future studies are needed are also addressed.

  12. Hyperthyroidism and immune thrombocytopenia.

    PubMed Central

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

    1984-01-01

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

  13. How Is Thrombocytopenia Treated?

    MedlinePlus

    ... be used if treatment with medicines doesn't work. This surgery mostly is used for adults who have immune thrombocytopenia (ITP). However, medicines often are ... National Institutes of Health Department of Health and Human Services USA.gov

  14. What Causes Thrombocytopenia?

    MedlinePlus

    ... some conditions that cause too much blood clotting. Autoimmune Diseases Autoimmune diseases occur if the body's immune system mistakenly attacks healthy cells in the body. If an autoimmune disease destroys the body's platelets, thrombocytopenia can occur. One ...

  15. [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".

  16. Babesiosis-associated immune thrombocytopenia

    PubMed Central

    Narurkar, Roshni; Mamorska-Dyga, Aleksandra; Agarwal, Anup; Nelson, John C.

    2017-01-01

    Thrombocytopenia is a common feature of babesiosis. The mechanism for thrombocytopenia in babesiosis remains elusive. We report a case of babesiosis with severe new onset immune thrombocytopenia (ITP). In addition to antibiotics treatment for babesiosis, ITP therapy was administered. ITP in the present case was most likely triggered by the babesia infection. The severity of ITP in this case was not proportional to the severity of parasitemia. The neoantigen triggering the autoimmune response in babesiosis requires further characterization. PMID:28217703

  17. 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

  18. Guidance on platelet transfusion for patients with hypoproliferative thrombocytopenia.

    PubMed

    Nahirniak, Susan; Slichter, Sherrill J; Tanael, Susano; Rebulla, Paolo; Pavenski, Katerina; Vassallo, Ralph; Fung, Mark; Duquesnoy, Rene; Saw, Chee-Loong; Stanworth, Simon; Tinmouth, Alan; Hume, Heather; Ponnampalam, Arjuna; Moltzan, Catherine; Berry, Brian; Shehata, Nadine

    2015-01-01

    Patients with hypoproliferative thrombocytopenia are at an increased risk for hemorrhage and alloimmunization to platelets. Updated guidance for optimizing platelet transfusion therapy is needed as data from recent pivotal trials have the potential to change practice. This guideline, developed by a large international panel using a systematic search strategy and standardized methods to develop recommendations, incorporates recent trials not available when previous guidelines were developed. We found that prophylactic platelet transfusion for platelet counts less than or equal to 10 × 10(9)/L is the optimal approach to decrease the risk of hemorrhage for patients requiring chemotherapy or undergoing allogeneic or autologous transplantation. A low dose of platelets (1.41 × 10(11)/m2) is hemostatically as effective as higher dose of platelets but requires more frequent platelet transfusions suggesting that low-dose platelets may be used in hospitalized patients. For outpatients, a median dose (2.4 × 10(11)/m2) may be more cost-effective to prevent clinic visits only to receive a transfusion. In terms of platelet products, whole blood-derived platelet concentrates can be used interchangeably with apheresis platelets, and ABO-compatible platelet should be given to improve platelet increments and decrease the rate of refractoriness to platelet transfusion. For RhD-negative female children or women of child-bearing potential who have received RhD-positive platelets, Rh immunoglobulin should probably be given to prevent immunization to the RhD antigen. Providing platelet support for the alloimmunized refractory patients with ABO-matched and HLA-selected or crossmatched products is of some benefit, yet the degree of benefit needs to be assessed in the era of leukoreduction.

  19. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity.

    PubMed

    Parry, Christian S; Gorski, Jack; Stern, Lawrence J

    2007-08-10

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin alphaII(B)betaIII 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 alphaII(B)betaIII 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 A. There are two alphabeta heterodimers to the asymmetric unit in space group P4(1)2(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 beta57 Asp-->Val substitution abrogates the salt-bridge to alpha76 Arg and along with a hydrophobic beta37 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.

  20. 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.

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

    SciTech Connect

    Snyder, E.L. )

    1990-09-01

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

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

    PubMed Central

    Snyder, E. L.

    1990-01-01

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

  3. [Cellular mechanisms implicated in anti-erythrocyte alloimmunization].

    PubMed

    Ansart-Pirenne, H; Rouger, P; Noizat-Pirenne, F

    2005-06-01

    In many clinical situations patients are dependent on blood transfusions. Occurrence of alloimmunization to blood group antigens (BGA) complicates the transfusion strategy and may be involved in clinical transfusion stalemate situations. B cell differentiation into antibody-secreting plasma cells is triggered by antigen and requires helper T cells which produce cytokines. Although antibodies implicated in BGA alloimmunization have been studied for many years, little is known about helper T cell responses that drive their production. Few studies on BGA specific T cell responses have been published today. This review summarizes the new developments in the field of cellular mechanisms implicated into antibody production. The definition of immunodominant peptides derived from RhD and Jk(a) BGAs, the cytokine patterns induced and the HLA class II molecules implicated in their presentation are analyzed. A tolerogenic route for RhD immunodominant peptides is experimented. Identification of such immunodominant peptides, the cytokine patterns induced and the HLA class II molecules implicated in their presentation, would facilitate the design of new therapeutic strategies including the specific control of alloimmunization with peptide antigen tolerogens or the ex-vivo induction of regulatory T cells.

  4. The natural history of fetomaternal alloimmunization to the platelet-specific antigen HPA-1a (PlA1, Zwa) as determined by antenatal screening.

    PubMed

    Williamson, L M; Hackett, G; Rennie, J; Palmer, C R; Maciver, C; Hadfield, R; Hughes, D; Jobson, S; Ouwehand, W H

    1998-10-01

    Immunization against the human platelet antigen (HPA)-1 alloantigen is the most common cause of severe fetal and neonatal thrombocytopenia. Fetal therapy has substantial risks and its indications need better definition. Of 24,417 consecutive pregnant women, 618 (2.5%) were HPA-1a negative of whom 385 entered an observational study. All were HLA-DRB3*0101 genotyped and screened for anti-HPA-1a. Their partners and neonates were HPA-1 genotyped and the latter were assessed by cord blood platelet counts and cerebral ultrasound scans. Anti-HPA-1a was detected in 46 of 387 pregnancies (12.0%; 95% CI 8.7%-15.2%). All but one were HLA-DRB3*0101 positive (odds ratio 140; 95% CI 19-1035; P< .00001). One baby died in utero, and of 26 HPA-1a-positive babies born to women with persistent antenatal antibodies, 9 were severely thrombocytopenic (8 with a count <10 x 10(9)/L, 1 with a large porencephalic cyst), 10 were mildly thrombocytopenic, whereas 7 had normal platelet counts. Severe thrombocytopenia was significantly associated with a third trimester anti-HPA-1a titer >/= 1:32 (P = . 004), but was not observed in babies of women with either transient or postnatal-only antibodies. HPA-1a alloimmunization complicates 1 in 350 unselected pregnancies, resulting in severe thrombocytopenia in 1:1,200. HPA-1a and HLA-DRB3*0101 typing combined with anti-HPA-1a titration allows selection of the majority of pregnancies at risk of severe thrombocytopenia.

  5. Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1981-09-01

    A quantitative immunofluorescence platelet-associated immunoglobulin-G (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only Pa-IgG incompatible donor platelets were found. Survival studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. Pa-IgG compatible donor platelets survived 3.5 to 8.7 days, while Pa-IgG incompatible platelets showed survival times of 0.1 to 2.4 days.

  6. 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

  7. Alloimmunization prevents the migration of transfused indium-111-labeled granulocytes to sites of infection

    SciTech Connect

    Dutcher, J.P.; Schiffer, C.A.; Johnston, G.S.; Papenburg, D.; Daly, P.A.; Aisner, J.; Wiernik, P.H.

    1983-08-01

    111In-labeled granulocytes were used to study the effects of histocompatibility factors on the migration of transfused granulocytes to infected sites. Fourteen alloimmunized and 20 nonalloimmunized patients received approximately 10(8) 111In-labeled granulocytes from ABO-compatible, non-HLA-matched donors, and scans were performed over known infected sites. All 14 alloimmunized patients had lymphocytotoxic antibody (LCTAb) and required HLA-matched platelet transfusions. Of the nonalloimmunized patients, 20/20 had positive scans at sites of infection. None of the 20 had LCTAb, 0/17 had a positive lymphocytotoxic crossmatch (LCTXM) with the donor, and 3/18 had a positive leukoagglutinin crossmatch (LAXM). Thus, histocompatibility testing was not found to be important in nonalloimmunized patients. In contrast, only 3/14 alloimmunized patients had positive scans at sites of infection (p . 0.00001 compared to nonalloimmunized patients). One of 3 had a positive LCTXM and 2/3 had a positive LAXM. Of the alloimmunized patients, 10/11 with negative scans had a positive LCTXM and 8/11 had a positive LAXM. Labeled granulocytes failed to reach sites of infection in 11/14 (78%) alloimmunized patients, demonstrating that histocompatibility factors can be of major importance in affecting the outcome of granulocyte transfusions. Granulocytes from random donors are unlikely to be effective in alloimmunized patients. The lack of an adequate crossmatching technique is a major problem limiting the ability to provide granulocyte transfusions for alloimmunized patients.

  8. Varicella infection complicated by marked thrombocytopenia.

    PubMed

    Shibusawa, Motoharu; Motomura, Sayuri; Hidai, Hiroko; Tsutsumi, Hisasi; Fujita, Akira

    2014-01-01

    We report a rare case of adult varicella complicated by marked thrombocytopenia. A 49-year-old woman presented with fever and rash for 3 days. Blood examination revealed marked thrombocytopenia (2.7 × 10(4)/μL). Varicella infection was diagnosed after elevated levels of varicella zoster virus IgM and IgG antibodies were observed 2 weeks later. In this case, thrombocytopenia was due to varicella infection, and the mechanism was estimated to be non-immunological. Because varicella infection complicated by thrombocytopenia may result in fatal bleeding, thrombocytopenia in patients with varicella warrants close attention.

  9. Safety and Efficacy Study of Romiplostim to Treat Immune Thrombocytopenia (ITP) in Pediatric Patients

    ClinicalTrials.gov

    2017-02-07

    Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura; Immune Thrombocytopenia

  10. Blood transfusion and alloimmunization in patients with thalassemia: multicenter study.

    PubMed

    Azarkeivan, Azita; Ansari, Shahla; Ahmadi, Mohammad Hossein; Hajibeigy, Bashir; Maghsudlu, Mahtab; Nasizadeh, Soheila; Shaigan, Mojgan; Toolabi, Abdolmajid; Salahmand, Mitra

    2011-09-01

    One of transfusion's side effects is alloimmunization against red blood cell (RBC) antigens. Early diagnosis by antibody screening is an important step in the detection of these alloantibodies. The authors studied the frequency of alloimmunization in thalassemic patients of 4 centers (2 adult and 2 pediatric centers) and compared the rates in children (up to 15 years) and adults. Antibody screening tests were performed by gel method according to its standard pattern and respective program. In positive cases, antibody identification test by gel method was performed. Eight hundred thirty-five patients were studied; 548 (65.6%) were adults (mean age = 24.5), and 287 (34.4%) cases were pediatrics (mean age = 10.05). Of these patients, 74.1% had no history of transfusion reaction, whereas 21 (2.5%) had hemolytic complications. Seventy-eight (9.3%) exhibited allergic symptoms, and 117 (14%) cases experienced febrile reactions during transfusion. Antibody screening showed positive results in 22 pediatric cases (7.7%) and 79 adults (14.4%); 72 (71.3%), 19 (18.8%), 3 (3%), and 1 (1%) cases exhibited single, double, triple, and autoantibodies, respectively. Anti-Kell antibody was seen in 34 (33.7%) cases, anti-D was seen in 11 (10.9%) cases, and anti-E in was seen in 10 (9.9%) cases. The authors observed 8 anti-D+C (7.9%) cases, 1 anti-D+E (1%), 3 anti-Kell+E, 3 anti-Kell+Kpa (3%), and 1 anti-Kell+D double antibodies. These antibodies were also a combination of Rh subgroups or Rh and Kell subgroups. The authors observed meaningful relations between history of transfusion reactions and age with antibody screening results (P = .005). Based on alloantibodies types, more than two thirds of them were Rh subgroups and Kell groups. Phenotype determination of RBCs before beginning chronic blood transfusion and careful cross-matching with Kell and Rh subgroups in addition to ABO may help reduce alloimmunization in chronic transfusion patients.

  11. Current management of immune thrombocytopenia.

    PubMed

    Neunert, Cindy E

    2013-01-01

    Immune thrombocytopenia (ITP) is an autoimmune-mediated condition that results from antibody-mediated destruction of platelets and impaired megakaryocyte platelet production. ITP patients exhibit severe thrombocytopenia and are at risk for significant hemorrhage. Few randomized trials exist to guide management of patients with ITP. Ultimately, each patient requires an individualized treatment plan that takes into consideration the platelet count, bleeding symptoms, health-related quality of life, and medication side effects. This article provides an up-to-date review of management strategies drawing on links between the expanding amounts of clinical trial data and associated biology studies to enhance understanding of the disease heterogeneity with regard to the complex pathogenesis and response to treatment.

  12. 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.

  13. Why does my patient have thrombocytopenia?

    PubMed

    Wong, Ellice Y; Rose, Michal G

    2012-04-01

    Thrombocytopenia, usually defined as a platelet count of less than 150,000/μL, is a common reason for a hematology consult in both the inpatient and outpatient setting. In most patients, the cause of the thrombocytopenia can be identified and treated. This article reviews the clinical approach to the patient with thrombocytopenia, the mechanisms that underlie it, and the laboratory tests available to investigate it. A practical approach to the investigation and management of thrombocytopenia in the clinical settings commonly encountered by the hematology consultant is then described.

  14. ANKRD26 normocytic thrombocytopenia: a family report.

    PubMed

    Vincenot, Anne; Hurtaud-Roux, Marie-Françoise; René, Olivier; Binard, Sylvie; Fenneteau, Odile; Schlegel, Nicole

    2016-06-01

    We report the identification of a new case of familial non syndromic severe thrombocytopenia. Bleeding was mild and no extra-haematological symptoms were found. Platelet morphology was normal as well as the quantitative expression of platelet membrane glycoproteins. Platelet functions could not be studied due to the intensity of the thrombocytopenia. Molecular analysis identified a mutation located in the promoter of the ankyrin repeat domain 26 (ANKRD26) gene, c.-127A>T, recently reported to be responsible of normocytic thrombocytopenia, but also of a possible increased risk of leukemia/myelodysplasia. Actual knowledge on this new type of inherited thrombocytopenia is also presented.

  15. Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease.

    PubMed

    Fasano, Ross M; Booth, Garrett S; Miles, Megan; Du, Liping; Koyama, Tatsuki; Meier, Emily Riehm; Luban, Naomi L C

    2015-01-01

    Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro-inflammatory SCD-related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro-inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion-associated pro-inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty-two patients received 3166 pre-storage leuco-reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso-occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate-phosphate-dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro-inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

  16. 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.

  17. 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

  18. Managing thrombocytopenia associated with cancer chemotherapy.

    PubMed

    Kuter, David J

    2015-04-01

    Thrombocytopenia is a common problem in cancer patients. Aside from bleeding risk, thrombocytopenia limits chemotherapy dose and frequency. In evaluating thrombocytopenic cancer patients, it is important to assess for other causes of thrombocytopenia, including immune thrombocytopenia, coagulopathy, infection, drug reaction, post-transfusion purpura, and thrombotic microangiopathy. The incidence of chemotherapy-induced thrombocytopenia varies greatly depending on the treatment used; the highest rates of this condition are associated with gemcitabine- and platinum-based regimens. Each chemotherapy agent differs in how it causes thrombocytopenia: alkylating agents affect stem cells, cyclophosphamide affects later megakaryocyte progenitors, bortezomib prevents platelet release from megakaryocytes, and some treatments promote platelet apoptosis. Thrombopoietin is the main regulator of platelet production. In numerous studies, recombinant thrombopoietin raised the platelet count nadir, reduced the need for platelet transfusions, reduced the duration of thrombocytopenia, and allowed maintenance of chemotherapy dose intensity. Two thrombopoietin receptor agonists now available, romiplostim and eltrombopag, are potent stimulators of platelet production. Although few studies have been completed to demonstrate their ability to treat chemotherapy-induced thrombocytopenia, these agents may be useful in treating this condition in some situations. Chemotherapy dose reduction and platelet transfusions remain the major treatments for affected patients.

  19. Zika Virus Infection Associated With Severe Thrombocytopenia.

    PubMed

    Sharp, Tyler M; Muñoz-Jordán, Jorge; Perez-Padilla, Janice; Bello-Pagán, Melissa I; Rivera, Aidsa; Pastula, Daniel M; Salinas, Jorge L; Martínez Mendez, Jose H; Méndez, Mónica; Powers, Ann M; Waterman, Stephen; Rivera-García, Brenda

    2016-11-01

    We report two patients that developed severe thrombocytopenia after Zika virus (ZIKV) infection. The first patient had 1000 platelets/μL and died after multiple hemorrhages. The second patient had 2000 platelets/μL, had melena and ecchymoses, and recovered after receiving intravenous immunoglobulin. ZIKV may be associated with immune-mediated severe thrombocytopenia.

  20. Management of thrombocytopenia in advanced liver disease.

    PubMed

    Gangireddy, V G R; Kanneganti, P C; Sridhar, S; Talla, S; Coleman, T

    2014-11-01

    Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) 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.

  1. Thrombocytopenia and platelet transfusion in the neonate.

    PubMed

    Cremer, Malte; Sallmon, Hannes; Kling, Pamela J; Bührer, Christoph; Dame, Christof

    2016-02-01

    Neonatal thrombocytopenia is widespread in preterm and term neonates admitted to neonatal intensive care units, with up to one-third of infants demonstrating platelet counts <150 × 10(9)/L. Thrombocytopenia may arise from maternal, placental or fetal/neonatal origins featuring decreased platelet production, increased consumption, or both mechanisms. Over the past years, innovations in managing neonatal thrombocytopenia were achieved from prospectively obtained clinical data on thrombocytopenia and bleeding events, animal studies on platelet life span and production rate and clinical use of fully automated measurement of reticulated platelets (immature platelet fraction). This review summarizes the pathophysiology of neonatal thrombocytopenia, current management including platelet transfusion thresholds and recent developments in megakaryopoietic agents. Furthermore, we propose a novel index score for bleeding risk in thrombocytopenic neonates to facilitate clinician's decision-making when to transfuse platelets.

  2. Red cell alloimmunization in RhD positive pregnant women and neonatal outcome.

    PubMed

    Sankaralingam, Prabakaran; Jain, Ashish; Bagga, Rashmi; Kumar, Praveen; Marwaha, Neelam

    2016-08-01

    The frequency of red blood cell (RBC) alloimmunization in RhD positive pregnant women is not known in our population. We planned to determine its frequency and correlation with neonatal outcome. We included 1000 RhD positive pregnant women: 500 had 'normal pregnancy' (Group I) and another 500 had 'high risk pregnancy' (Group II). ABO and extended Rh phenotyping were done by tube technique, antibody screening and identification by gel technique. For alloimmunized women, the paternal and neonatal ABO and extended Rh typing were done. Neonatal direct antiglobulin test (DAT) was also done and their clinical outcome observed. The frequency of RBC alloimmunization was 0.7% (7/1000) and all these women were from group II (p = 0.015). The alloantibodies were anti-E (85.7%), anti-c (71.4%), anti-Cw (14.3%) and anti-S (14.3%). Also, 6 women had history of transfusion (p < 0.01). Of the 7 neonates born to alloimmunized mothers, 4 (57.14%) had a positive DAT. The mean duration of phototherapy was higher in the DAT positive neonates (p < 0.01) and 2 (50%) required exchange transfusion. Thus, the frequency of alloimmunization was 0.7% in RhD positive pregnant women. High risk pregnancies and antenatal patients having a history of blood transfusion should be considered for regular antibody screening.

  3. T-cell alloimmunity and chronic allograft dysfunction.

    PubMed

    Safinia, Niloufar; Afzali, Behdad; Atalar, Kerem; Lombardi, Giovanna; Lechler, Robert I

    2010-12-01

    Solid organ transplantation is the standard treatment to improve both the quality of life and survival in patients with various end-stage organ diseases. The primary barrier against successful transplantation is recipient alloimmunity and the need to be maintained on immunosuppressive therapies with associated side effects. Despite such treatments in renal transplantation, after death with a functioning graft, chronic allograft dysfunction (CAD) is the most common cause of late allograft loss. Recipient recognition of donor histocompatibility antigens, via direct, indirect, and semidirect pathways, is critically dependent on the antigen-presenting cell (APC) and elicits effector responses dominated by recipient T cells. In allograft rejection, the engagement of recipient and donor cells results in recruitment of T-helper (Th) cells of the Th1 and Th17 lineage to the graft. In cases in which the alloresponse is dominated by regulatory T cells (Tregs), rejection can be prevented and the allograft tolerated with minimum or no immunosuppression. Here, we review the pathways of allorecognition that underlie CAD and the T-cell effector phenotypes elicited as part of the alloresponse. Future therapies including depletion of donor-reactive lymphocytes, costimulation blockade, negative vaccination using dendritic cell subtypes, and Treg therapy are inferred from an understanding of these mechanisms of allograft rejection.

  4. Thrombocytopenia

    MedlinePlus

    ... J, Kelton J. Diseases of platelet number. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ... caused by platelet destruction, hypersplenism, or hemodilution. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop HE, ...

  5. Thrombocytopenia in pregnancy - pathogenesis and diagnostic approach.

    PubMed

    Jodkowska, Anna; Martynowicz, Helena; Kaczmarek-Wdowiak, Beata; Mazur, Grzegorz

    2015-11-12

    Thrombocytopenia (TP) affects 7-10% of pregnant women. It occurs 4 times more frequently in pregnancy than in the non-pregnant women population. Women with thrombocytopenia in pregnancy are a heterogeneous and poorly known group. There are several possible causes of thrombocytopenia in pregnancy. The most common are: gestational thrombocytopenia (GE) (60-75%), preeclampsia (PE) and HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome associated TP (21%), and idiopathic immune thrombocytopenia (ITP) (3-10%). Although thrombocytopenia diagnosed in pregnancy in most cases has a mild course, it has also been reported to be associated with a higher rate of preterm birth and premature detachment of the placenta. Some cases of severe thrombocytopenia with systemic involvement are associated with high risk of serious perinatal complications and require early diagnosis, careful clinical monitoring and medical treatment. The differential diagnosis and proper assessment of clinical risk of TP during pregnancy may be of great concern. The article discusses these issues, focusing on pathophysiology of TP in pregnancy.

  6. An unusual presentation of gestational thrombocytopenia.

    PubMed

    Lim, Calvin C Y; Patel, D K; Bakhtiari, Azam; Subrayan, Visvaraja

    2013-01-01

    Thrombocytopenia is classically defined as a platelet count of less than 150 000/µl. Counts from 100 000 to 150 000/µl are considered mildly depressed, 50 000 to 100 000/µl moderately depressed, and less than 50 000/µl severely depressed. Thrombocytopenia occurs in about 10% of pregnant women. Gestational thrombocytopenia (GT) is a diagnosis of exclusion and considered the most prevalent cause of thrombocytopenia in pregnancy. GT accounts for almost 75% of cases of thrombocytopenia in pregnancy. The cause of GT is unclear, although existing studies denote the possibility of accelerated platelet consumption and the increased plasma volume during pregnancy. The presence of antiplatelet antibodies is not specific to GT. The degree of thrombocytopenia in GT is usually mild to moderate, usually remaining greater than 70 000/µl. Patients are asymptomatic with no evidence of bleeding and rarely preconception history of thrombocytopenia. The platelet count returns to normal within 2-12 weeks post partum. We wish to report a unique case of GT presenting as blurred vision due to retinal hemorrhages.

  7. Autoantibody formation in the alloimmunized red blood cell recipient: clinical and laboratory implications.

    PubMed

    Zumberg, M S; Procter, J L; Lottenberg, R; Kitchens, C S; Klein, H G

    2001-01-22

    Alloimmunization to erythrocyte antigens is a well-characterized complication in heavily transfused patients. Less well recognized, however, is the frequency of autoantibody formation in these previously alloimmunized patients. The autoantibodies are heterogeneous and of variable clinical significance. We describe the clinical history, laboratory evaluation, diagnosis, and treatment in 4 patients who developed autoantibodies in temporal association with alloantibody formation. In one case, the autoantibody found on routine screening had no clinical significance. In another case, the autoantibody made accurate blood typing and subsequent transfusion exceedingly difficult. Two patients experienced hemolysis as a consequence of the autoantibody. The management of both patients included supportive measures, while one patient required glucocorticosteroids and red blood cell transfusion. We review the published literature concerning autoimmunization in the transfused alloimmunized host. The spectrum of clinical consequences is important for the general practitioner to recognize, as these complications may occur during routine blood transfusions.

  8. Protective Effect of HLA-DQB1 Alleles Against Alloimmunization in Patients with Sickle Cell Disease

    PubMed Central

    Tatari-Calderone, Zohreh; Gordish-Dressman, Heather; Fasano, Ross; Riggs, Michael; Fortier, Catherine; Andrew; Campbell, D.; Charron, Dominique; Gordeuk, Victor R.; Luban, Naomi L.C.; Vukmanovic, Stanislav; Tamouza, Ryad

    2015-01-01

    Background Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. Results While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p=0.01) and HLA-DQ5/5 (p=0.03) combinations constitute additional predictor of protective status. Conclusion Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies. PMID:26476208

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

    PubMed Central

    Davari, Kambiz; Soltanpour, Mohammad Soleiman

    2016-01-01

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

  10. Alloimmunization and erythrocyte autoimmunization in transfusion-dependent thalassemia patients of predominantly asian descent.

    PubMed

    Singer, S T; Wu, V; Mignacca, R; Kuypers, F A; Morel, P; Vichinsky, E P

    2000-11-15

    The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P =.06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P =.0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

  11. Red Blood Cell Alloimmunization in Sickle Cell Disease: Listen to Your Ancestors

    PubMed Central

    Campbell-Lee, Sally A.; Kittles, Rick A.

    2014-01-01

    Summary Red blood cell (RBC) alloimmunization occurs in approximately 30% of transfused sickle cell disease patients compared to 2–5% of all transfusion recipients. Because RBC transfusion is an important part of therapy in sickle cell disease, the need for additional antigen matching once alloimmunization occurs is problematic and leads to therapeutic limitations. Thus, identification of risk factors would benefit this patient population. Genome-wide analyses, in particular, methods which take into account genetic ancestry such as admixture mapping, could identify molecular markers which could be used to identify immune responders to transfusion. PMID:25670930

  12. Profound thrombocytopenia after primary exposure to eptifibatide.

    PubMed

    Norgard, Nicholas B; Badgley, Brian T

    2010-01-01

    Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist used to reduce the incidence of ischemic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention. A minority of patients given eptifibatide develop acute, profound thrombocytopenia (<20,000 cells/mm(3)) within a few hours of receiving the drug. This case report discusses a patient who developed profound thrombocytopenia within hours of receiving eptifibatide for the first time. The Naranjo algorithm classified the likelihood that this patient's thrombocytopenia was related to eptifibatide as probable. Profound thrombocytopenia is an uncommon but clinically important complication of eptifibatide. This case report emphasizes the importance of monitoring platelet counts routinely at baseline and within 2-6 hours of eptifibatide administration.

  13. 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

  14. Can the Interval Between Antibody Identifications be Increased for Alloimmunized Patients?

    PubMed Central

    Goss, Cheryl; Avecilla, Scott T.; Garbaini, Jennifer; Degtyaryova, Diana; Lo, Dian; Chang, Dustin Y.M.; Cushing, Melissa

    2016-01-01

    Background New alloantibody formation is unpredictable in patients who have been previously alloimmunized. Pretransfusion testing is designed to detect these antibodies while antibody identification (ABI) techniques are designed to identify the specificity of the antibody. Pretransfusion testing intervals are prescribed by regulatory and accrediting agencies, intervals for ABI in alloimmunized patients are not. Our institution evaluated the safety of increasing the interval from every 72-hours to 14-days. The current 72-hour interval was chosen at our institution to align with AABB standard 5.14.3.2 which requires a pretransfusion specimen drawn within 3-days of the scheduled transfusion for potentially immunized patients. Study Design and Methods Over 2 years, all ABI entries in the laboratory information system were screened. All cases of alloimmunized patients with an additional antibody specificity that developed within 14-days of a previous ABI were reviewed and confirmed by four transfusion medicine physicians. Results Initially, 8948 entries were screened. Thirty patients were identified to have formed 33 newly identified clinically significant alloantibodies within 14-days. After further categorization, only 13 antibodies (0.15% of all ABI, 0.47% of alloimmunized patients examined) were deemed to be newly formed clinically significant antibodies that would have led to a change in transfusion practice. Discussion Retrospective analysis of ABI results over a 2-year period revealed that 0.47% of previously alloimmunized patients that have samples for pretransfusion testing develop a new clinically significant alloantibody in 14-days or less. While there would be significant resource advantages to increasing the duration between repeat ABI, it does not outweigh the risk of a potential hemolytic transfusion reaction. PMID:26456540

  15. Alloimmunization in Patients with Sickle Cell Disease and Thalassemia: Experience of a Single Centre in Oman

    PubMed Central

    Alkindi, Salam; AlMahrooqi, Saba; AlHinai, Sumaiya; AlMarhoobi, Ali; Al-Hosni, Saif; Daar, Shahina; Fawaz, Naglaa; Pathare, Anil

    2017-01-01

    Background Blood transfusion is an integral part of the supportive care for patients with sickle cell disease (SCD) and thalassaemia. The hazard of red cell alloimmunization, however, is one of the main complications of this therapy. Objectives The aim of this study was to evaluate the prevalence of red cell alloimmunization in Omani patients with sickle cell anaemia and thalassemia. Methods This study included 262 patients whose historical transfusion records were available. One hundred and twenty-nine patients with thalassaemia who were attending the day care unit for regular transfusions, and 133 SCD patients admitted at our hospital were included in this study. The Diamed® gel system was used for the screening and identification of atypical antibodies. Results The rate of alloimmunization in SCD patients was 31.6% (n=42, 95%CI, 24.87–40.66), whereas in patients with thalassaemia it was 20% (n=26; 95%CI, 13.9–27.6). Antibodies to E, e, C, c, D, K, S, Fyª, Kpª, Jkª and Cw were observed; 85% of the patients were also immunised with Rh and Kell antigens. Considering the two groups together, 8 developed nonspecific antibodies and 12 developed more than one antibody. Conclusions Red cell transfusions were associated with a significant risk of alloimmunization. It is, therefore, imperative to perform an initial extended red cell phenotyping for both donors and recipients, and carefully select ABO, Rh and Kell matched donors. The higher incidence of alloimmunization in SCD patients is related to the inherent SCD-specific inflammatory state. PMID:28293401

  16. 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

  17. Prevalence and characterization of thrombocytopenia in pregnancy in Indian women.

    PubMed

    Nisha, Singh; Amita, Dhakad; Uma, Singh; Tripathi, A K; Pushplata, Sankhwar

    2012-06-01

    To find the prevalence and causes of thrombocytopenia during pregnancy. An analytical prospective observational study was conducted in Department of Obstetrics & Gynecology, CSMMU, Lucknow. 1079 antenatal women screened for thrombocytopenia and investigated for cause and management strategies and fetomaternal outcome were recorded. Prevalence of thrombocytopenia was 8.8%. Gestational thrombocytopenia was seen in 64.2%, obstetric in 22.1% and medical in 13.68% cases. Mean platelet count in controls was lower with a significant fall (P < 0.001) in the platelet count as pregnancy advanced. Hypertensive and hepatic disorders were the most common obstetric causes of thrombocytopenia. Mode of delivery was not affected by thrombocytopenia. Maternal morbidity and mortality was seen only in medical and obstetric thrombocytopenia. The low platelet counts and declining trend with increasing gestational age predispose Indian women to risk of thrombocytopenia and a routine platelet count is suggested.

  18. What Are the Signs and Symptoms of Thrombocytopenia?

    MedlinePlus

    ... Twitter. What Are the Signs and Symptoms of Thrombocytopenia? Mild to serious bleeding causes the main signs and symptoms of thrombocytopenia. Bleeding can occur inside your body (internal bleeding) ...

  19. Thrombophilia in patients with chronic immune thrombocytopenia.

    PubMed

    Wong, Raymond S M; Bakshi, Kalpana; Brainsky, Andres

    2015-01-01

    An increased risk of thromboembolic events among patients with chronic immune thrombocytopenia has been reported but is still not fully understood. A thrombophilia panel (factors suspected/known to denote a thrombophilic state or indicate activation of the clotting cascade) was measured in previously treated patients with chronic immune thrombocytopenia enrolled in an eltrombopag trial to assess potential thrombophilia risk markers. Of 167 patients, 136 (81%) had abnormal levels of at least 1 known or suspected thrombosis risk marker or coagulation cascade activation marker. Six patients reported thromboembolic events, and all of these patients had at least two abnormal analytes in the thrombophilia panel. The presence of multiple baseline thrombophilia risk markers support the theory that chronic immune thrombocytopenia is a pro-thrombotic disease.

  20. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization.

    PubMed

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; van der Bom, Johanna G

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.

  1. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization

    PubMed Central

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A.; de Haas, Masja; de Vooght, Karen M.K.; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C.V.; Hudig, Francisca; van der Bom, Johanna G.

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization. PMID:27634204

  2. Heparin induced thrombocytopenia: diagnosis and management update

    PubMed Central

    Ahmed, I; Majeed, A; Powell, R

    2007-01-01

    Heparin‐induced thrombocytopenia (HIT) is a potentially devastating immune mediated adverse drug reaction caused by the emergence of antibodies that activate platelets in the presence of heparin. Despite thrombocytopenia, bleeding is rare; rather, HIT is strongly associated with thromboembolic complications involving both the arterial and venous systems. A number of laboratory tests are available to confirm the diagnosis; however, when HIT is clinically suspected, treatment should not be withheld pending the result. Fortunately, therapeutic strategies have been refined, and new and effective therapeutic agents are available. Treatment options are focused on inhibiting thrombin formation or direct thrombin inhibition. Warfarin should not be used until the platelet count has recovered. PMID:17823223

  3. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

    PubMed Central

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile

    2017-01-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

  4. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016.

    PubMed

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile; Hoen, Bruno

    2017-04-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia.

  5. Primary autoimmune myelofibrosis with severe thrombocytopenia mimicking immune thrombocytopenia: A case report

    PubMed Central

    Hua, Jian; Matayoshi, Shu; Uchida, Tomoyuki; Inoue, Morihiro; Hagihara, Masao

    2016-01-01

    Patients presenting with bone marrow fibrosis not accompanied by well-established autoimmune diseases, such as systemic lupus erythematosus, or malignant diseases, are considered to have primary autoimmune myelofibrosis (AIMF). Primary AIMF has been reported to follow a benign course and responds well to treatment with immunosuppressive agents. Immune thrombocytopenia (ITP) is also an autoimmune disorder characterized by antiplatelet-antibody-mediated thrombocytopenia in the absence of other causes of thrombocytopenia. We herein present a rare case of a female patient who was diagnosed with primary AIMF. The patient presented with severe thrombocytopenia, which was initially misdiagnosed as ITP. The symptoms of the disease resolved completely following steroid treatment. After withdrawal of the treatment at 1 year from the diagnosis, the bone marrow examination showed no evidence of bone marrow fibrosis or other abnormalities. To date, the patient has been followed up for 2 years without evidence of disease. PMID:28105358

  6. 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.

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

    PubMed Central

    2016-01-01

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

  8. Immune thrombocytopenia in severe neonatal infections.

    PubMed

    Tate, D Y; Carlton, G T; Johnson, D; Sorenson, R L; Nesbit, M; White, J; Thompson, T; Krivit, W

    1981-03-01

    Thrombocytopenia occurs frequently in newborn infants with sepsis, but the exact mechanism remains obscure in those infants who do not have evidence of disseminated intravascular coagulation. Since recent work has suggested a possible immune mechanism for thrombocytopenia observed in adults with sepsis, we have investigated the role of platelet-associated immunoglobulin in severe neonatal infections. To detect PAIgG we use a method employing protein A and peroxidase-antiperoxidase as a labeled antibody. PAIgG was quantitated by phase contrast microscopy and expressed as a reactive index. Our control group included 16 normal newborn infants whose mean RI was 0.65 +/- 0.01 SE. In addition to the control group, five infants with nonimmune thrombocytopenia were included; their mean RI was 0.66 +/- 0.01 SE. Seventeen newborn infants with severe infections were assayed for PAIgG. Eight of nine infants with bacterial infections had increased RI, with a mean of 1.16 +/- 0.03 SE (P less than 0.01). Six of the eight infants with viral infections had elevated RI, with a mean of 1.23 +/- 0.03 SE (P less than 0.01). These findings suggest that an immune mechanism may be involved in the thrombocytopenia of severe neonatal infection.

  9. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  10. Phytochemicals as potential therapeutics for thrombocytopenia.

    PubMed

    Manasa, K; Soumya, R; Vani, R

    2016-04-01

    Medical knowledge has always relied on plants as the main sources of important beneficial compounds. Many species have been recognized to have medicinal properties and beneficial impact on health, e.g. antioxidant activity, digestive stimulation action, anti-inflammatory, antimicrobial, hypolipidemic, antimutagenic and anticarcinogenic potential. This review focuses on the promising role of plants and their products in attenuating thrombocytopenia, a common and complex bleeding disorder. When the platelet count decreases below 150,000/µl, it causes thrombocytopenia. This bleeding disorder is observed in 2.5 % of the normal population. The risk of spontaneous muco-cutaneous bleeding and life threatening intracranial haemorrhage or gastrointestinal bleeding increases rapidly when the platelet count decreases below 10,000/µl. The inability to provide supportive treatment to increase the platelet counts often proves fatal to patients. Currently, treatment for thrombocytopenia includes use of drugs or splenectomy or platelet transfusions, in severe cases. Recently, studies have shown platelet augmenting activity of various plant extracts. The effectiveness, toxicity and side effects of the phytochemicals have to be critically evaluated in clinical trials. An in depth understanding of the role and mechanism of these phytochemicals would lead to their successful implementation in treatment and management of thrombocytopenia and other related bleeding disorders.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-08-01

    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.

  13. Estimation of combat-related blood group alloimmunization and delayed serologic transfusion reactions in U.S. military veterans.

    PubMed

    Tormey, Christopher A; Stack, Gary

    2009-05-01

    The goals of this study were to estimate blood group alloimmunization arising from combat-related transfusion and the prevalence of delayed serologic transfusion reactions (DSTRs) in military veteran patients. Blood group alloantibodies documented in the transfusion records at a Veterans Affairs (VA) medical center were categorized according to whether they developed before ("pre-existing") or during ("hospital-acquired") VA care and whether they were associated with anamnestic immune responses. Combat-related alloantibodies were estimated by adding anamnestic to pre-existing antibodies, revealing that 256 veterans made 322 combat-related alloantibodies. The combat-related alloimmunization rate was 1.37% (256/18,750), and combat-related alloantibodies represented 55.8% (322/577) of total alloantibodies. The highest rate of combat-related alloimmunization was observed in World War II-era veterans. Approximately 11.2% (25/224) of veterans with hospital-acquired antibodies experienced a DSTR due to prior alloimmunization. In conclusion, combat-related alloimmunization accounted for more than half of antibodies in military veterans and was a predisposing factor for DSTRs.

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

    PubMed

    Sriskandarajah, Priya; Davies, Rhys

    2016-05-12

    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.

  15. Miliary tuberculosis presenting with hyponatremia and thrombocytopenia.

    PubMed Central

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

    1976-01-01

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

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

    PubMed

    Seculini Patiño, Carina E; Tabares, Aldo H

    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.

  17. CFU-MK assay for acute thrombocytopenia.

    PubMed

    Parent-Massin, Dominique; Sibiril, Yann

    2008-08-01

    In this unit, protocols to culture human platelet progenitors (Colony Forming Unit-Megakaryocyte; CFU-M) with or without toxicants are described. Platelet progenitors are obtained from human umbilical cord blood. After separation of mononuclear cells, the cell suspension can be cryopreserved or plated immediately. Megakaryocytes are identified by immunocytochemistry. Test chemicals are added to the culture medium before cells are plated. Megakaryocytes are scored after 12 days of culture. IC(10), IC(50) and IC(90) can be calculated by comparison to control cultures. A predictive model is proposed to evaluate the hazard of thrombocytopenia induced by chemicals. When IC(50) and IC(90) are below C(max) in humans, the likelihood of thrombocytopenia is strong.

  18. Hereditary thrombocytopenia, deafness, and renal disease.

    PubMed

    Eckstein, J D; Filip, D J; Watts, J C

    1975-05-01

    The syndrome of hereditary thrombocytopenia, deafness, and renal disease was manifest in at least eight members in three generations of a family. They had a lifelong history of bleeding, usually as epistaxis, bilateral sensorineural deafness starting in late childhood or the teenage years, and persistent proteinuria with varying degrees of renal dysfunction. Two members died at a young age, one from central nervous system hemorrhage, the other from chronic renal failure. Splenectomy and steroid therapy have been of transient benefit. There was dominant inheritance of the syndrome. Hematologic studies showed thrombocytopenia, large platelets, and megakaryocytic hyperplasia of the bone marrow. In contrast to a previous report, our studies showed that affected members had normal in-vitro platelet function and normal ultrastructural platelet morphology. At autopsy, histologic changes in the kidney of one affected family member were indistinguishable from those reported in classic hereditary nephritis with nerve deafness (Alport's syndrome).

  19. 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.

  20. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

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

  1. 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

  2. Thrombocytopenia in Plasmodium vivax Malaria: How Significant?

    PubMed Central

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

    2014-01-01

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

  3. Thrombocytopenia in Plasmodium vivax Malaria: How Significant?

    PubMed

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

    2014-01-01

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

  4. Heparin-induced thrombocytopenia in pediatrics.

    PubMed

    Severin, T; Sutor, A H

    2001-06-01

    As in adult patients, heparin is used for prophylaxis and treatment of thromboembolism in newborns, children, and adolescents. Patients receiving heparin are potentially at risk to develop heparin-induced thrombocytopenia (HIT). HIT type II has been extensively described in the adult population; only a few reports address HIT type II in pediatric patients (total of 15 neonates, 4 young children, 12 older children and adolescents). The available data are discussed, and the case of a patient with recurrent thrombosis and HIT type II without thrombocytopenia is presented. The review of the literature reveals that HIT type II occurs especially in neonates and adolescents, corresponding to the two age peaks of thrombosis in pediatric patients. Risk factors for thrombosis include hereditary factors, immobilization, and surgery. HIT complications are severe and partly lead to life-threatening thromboembolism. In three patients, an increasing heparin demand was found. In five cases, thrombocytopenia was absent. Heparin was replaced mostly by danaparoid sodium; in three patients hirudin was used as an alternative anticoagulant. HIT type II represents a potentially dangerous complication of heparin therapy in pediatric patients and should be taken into consideration whenever heparin is given for prophylactic or therapeutic use in newborns, children, or adolescents.

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

    PubMed

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

    2016-01-01

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

  6. Relapsed hydroxychloroquine induced thrombocytopenia in systemic lupus erythematosus patient.

    PubMed

    Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

    2016-06-02

    Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine.

  7. 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.

  8. [Rh alloimmunization in pregnant women, a look to diagnosis and therapeutic approach].

    PubMed

    Lambertino, José R; Villegas, Silvia M

    2014-11-01

    Prior to the onset of immunoglobulin antiD, many of the fetuses of mothers negative for the antigen "D" developing severe disease, history of prenatal diagnosis of alloimmunization is the perfect example of constructive effort by a diagnosis in order to identify cases in need of therapy to decrease morbidity and increase survival with the least number of invasive procedures and reducing the risks associated with them. Today it is difficult to determine the true prevalence of the disease in our environment, but the understanding of the pathophysiology has helped the evolution of diagnostic tests and better treatment approach to positively impact the evolution of the disease.

  9. Quetiapine-induced leucopenia and thrombocytopenia.

    PubMed

    Shankar, B Ravi

    2007-01-01

    Antipsychotic drugs can cause neutropenia, which can progress to life-threatening agranulocytosis if drug therapy is not interrupted. The newer atypical antipsychotics are reputedly without adverse hematological effects. Quetiapine is a recently introduced atypical antipsychotic. It is a dibenzothiazepine derivative and shows similarities with clozapine in that it is characterized by high 5-HT(2)-relative-to-DA(2) receptor affinity. Although adverse effects are usually mild, the author reports here a case of leucocytopenia and thrombocytopenia with quetiapine treatment that required its discontinuation.

  10. Management of thrombocytopenia due to liver cirrhosis: a review.

    PubMed

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

    2014-03-14

    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.

  11. Gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice

    PubMed Central

    Freeman, Michael L.; Burkum, Claire E.; Lanzer, Kathleen G.; Roberts, Alan D.; Pinkevych, Mykola; Itakura, Asako; Kummer, Lawrence W.; Szaba, Frank M.; Davenport, Miles P.; McCarty, Owen J.T.; Woodland, David L.; Smiley, Stephen T.; Blackman, Marcia A.

    2012-01-01

    Human herpesviruses establish lifelong latency. Viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. Although platelet-specific autoantibodies have been reported in patients infected with the Epstein-Barr virus (EBV), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. The human gammaherpesviruses are tightly restricted in their ability to infect other mammals, so they are difficult to study in live animal models. Here we show that infection of mice with murine gammaherpesvirus-68 (γHV68), a rodent-specific pathogen closely related to EBV, induces the production of platelet-binding antibodies and causes thrombocytopenia. Infection of antibody-deficient mice does not lead to thrombocytopenia, indicating the platelet decrease is mediated by antibody. Additionally, infection with a latency-null recombinant γHV68 does not induce thrombocytopenia, suggesting factors associated with viral latency drive the infection-induced antibody-mediated thrombocytopenia. These studies describe an important animal model of gammaherpesvirus-induced autoimmune thrombocytopenia and demonstrate that this pathology is mediated by antibody and dependent on viral latency. This model will allow studies of the underlying mechanisms of disease progression and the testing of therapeutic strategies for the alleviation of virus-induced thrombocytopenia. PMID:23245703

  12. A difficult diagnosis of Hodgkin lymphoma due to immune thrombocytopenia

    PubMed Central

    Marino, Silvia; Di Cataldo, Andrea; Magro, Gaetano; D'Amico, Salvatore; La Spina, Milena; Di Benedetto, Vincenzo; Meli, Mariaclaudia; Moscheo, Carla; Russo, Giovanna

    2015-01-01

    Key Clinical Message We report a rare clinical presentation of childhood Hodgkin lymphoma with immune thrombocytopenia. Diagnostic biopsy of the abdominal mass was performed after administration of intravenous immunoglobulins, steroids, and platelet transfusion. Concomitant thrombocytopenia complicated the whole diagnosis work up and the initial management of neoplasia. PMID:25838909

  13. Thrombocytopenia in hospitalized patients with severe clostridium difficile infection.

    PubMed

    Fountain, Eric M; Moses, Maggie C; Park, Lawrence P; Woods, Christopher W; Arepally, Gowthami M

    2017-01-01

    Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhea and colitis. The incidence and prognostic significance of thrombocytopenia as related to mode of acquisition (hospital vs. community), NAP1/027 strain, and disease severity has not been examined. We performed a single-institution retrospective analysis of all adult inpatients from 2013 to 2014 diagnosed with CDI during their hospitalization to document the incidence/prevalence of thrombocytopenia and associated outcomes. Severe disease was defined by a composite endpoint of inpatient death, death within 30 days of discharge, presence of septic shock, or need for colectomy during hospitalization. Of the 533 patients diagnosed with CDI, moderate thrombocytopenia (platelet count <100 × 10(9)/L at time of CDI diagnosis) was present in 15 % of the total cohort and incident thrombocytopenia developed in 3 % of patients after admission. Thrombocytopenia was more common in hospital-acquired disease and associated with increased length of stay, but was not associated with treatment failure. Those with moderate thrombocytopenia were more likely to have severe disease, after controlling for white blood cell count, albumin, and creatinine. Moderate thrombocytopenia is associated with poor prognosis and is a potential risk stratification tool for severe CDI.

  14. 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.

  15. 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.

  16. Immune Thrombocytopenia and Obesity: Predictive Relationship

    PubMed Central

    Hanafy, Ehab; Pakra, Mohammed Al

    2017-01-01

    Background: Chronic refractory immune thrombocytopenia (ITP) is defined as the failure of any modality to maintain the platelet count above 20 × 103/μL for an appreciable time without unacceptable toxicity. To date, certain predictive factors have been associated with refractory ITP. However, none of the published studies has declared the possible association between obesity and refractory ITP. Case Reports: We present the cases of 3 children with ITP who failed to achieve remission on different therapeutic approaches including rituximab, vincristine, and romiplostim. The 3 children had obesity as a common feature. Conclusion: We present these cases to propose a possible association between obesity and refractoriness of ITP to different therapeutic approaches and to emphasize the need for further study to establish whether a causal relationship exists. PMID:28331458

  17. Imbalanced immune homeostasis in immune thrombocytopenia

    PubMed Central

    Yazdanbakhsh, Karina

    2017-01-01

    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

  18. 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.

  19. Risk and prognosis of adult primary immune thrombocytopenia.

    PubMed

    Frederiksen, Henrik; Christiansen, Christian Fynbo; Nørgaard, Mette

    2012-04-01

    Adult immune thrombocytopenia was previously considered a benign disease affecting young people and with a low risk of severe bleeding. This view was challenged by studies published during the past decade, as the median age of adult immune thrombocytopenia patients has been found to be 55-60 years and the incidence increases with age. Recent studies reported that mortality and morbidity are increased compared with the general population. In this review, we describe patient-specific factors associated with the outcome of disease, the clinical course of immune thrombocytopenia including the potential adverse impact of some treatments and finally the overall prognosis.

  20. Severe fever with thrombocytopenia syndrome, Shandong Province, China, 2011.

    PubMed

    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; Yu, Xue-Jie

    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%).

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

    PubMed Central

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

    2012-01-01

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

  2. Autosomal dominant thrombocytopenia with microthrombocytes: a family study.

    PubMed

    Jackson, N; Mohammad, S; Zainal, N; Jamaluddin, N; Hishamuddin, M

    1995-12-01

    A family demonstrating autosomal dominant thrombocytopenia is described. A 28-year-old Malay housewife was found to have a platelet count of 40 x 10(9)/l with a low mean platelet volume (6.8 fl) while being investigated prior to ovarian cystectomy. The bone marrow was consistent with immune thrombocytopenia but she failed to respond to appropriate therapy. Five siblings, one parent and one nephew have easy bruising and platelet counts of 39-82 x 10(9)/l. Platelet aggregation studies excluded a major functional defect. Survival of homologous platelets in the circulation was normal. Familial thrombocytopenias are rare but important to differentiate from the common acquired thrombocytopenias in order to spare the patient unnecessary treatments.

  3. Corticosteroid-responsive prolonged thrombocytopenia following dengue haemorrhagic fever.

    PubMed

    Leong, K W; Srinivas, P

    1993-09-01

    A case of prolonged thrombocytopenia following dengue haemorrhagic fever in a 15 year old boy is reported. The mechanism was presumed to be immunological and he responded dramatically to oral prednisolone.

  4. 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

  5. Thrombocytopenia, Platelet Transfusion, and Outcome Following Liver Transplantation.

    PubMed

    Chin, Jun Liong; Hisamuddin, Syafiah Hanis; O'Sullivan, Aoife; Chan, Grace; McCormick, P Aiden

    2016-05-01

    Thrombocytopenia affects patients undergoing liver transplantation. Intraoperative platelet transfusion has been shown to independently influence survival after liver transplantation at 1 and 5 years. We examined the impact of thrombocytopenia and intraoperative platelet transfusion on short-term graft and overall survival after orthotopic liver transplantation (OLT). A total of 399 patients undergoing first OLT were studied. Graft and overall survival in patients with different degrees of thrombocytopenia and with or without intraoperative platelet transfusion were described. The degree of thrombocytopenia prior to OLT did not affect graft or overall survival after transplant. However, graft survival in patients receiving platelets was significantly reduced at 1 year (P= .023) but not at 90 days (P= .093). Overall survival was significantly reduced at both 90 days (P= .040) and 1 year (P= .037) in patients receiving platelets. We conclude that a consistently lower graft and overall survival were observed in patients receiving intraoperative platelet transfusion.

  6. Severe Fever with Thrombocytopenia Syndrome Presenting with Rhabdomyolysis

    PubMed Central

    Hong, Sang-Bum; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging febrile illness. While many kinds of severe complications including acute renal failure have been reported, rhabdomyolysis is rarely reported in association with SFTS. A 54-year-old female farmer was admitted with fever and diffuse myalgia. Laboratory finding showed thrombocytopenia, leukopenia, azotemia, extremely elevated muscle enzyme levels and myoglobinuria. We describe a fatal case of rhabdomyolysis with acute renal failure complicated by SFTS. PMID:28271645

  7. Haemangioma-thrombocytopenia syndrome--a case report.

    PubMed

    Liam, C K; Nuruddin, R

    1989-09-01

    A 29 year old Chinese female who presented with spontaneous purpura, was found to have gross hepatomegaly and thrombocytopenia. The thrombocytopenia responded to steroid therapy but relapsed when the dose of steroid was tapered down. Subsequent investigations revealed that the hepatomegaly was due to a large haemangioma of her liver. For symptomatic hepatic haemangioma, surgical excision is the treatment of choice; this was refused by the patient.

  8. Severe thrombocytopenia due to hypersplenism treated with partial splenic embolisation.

    PubMed

    Hanafiah, Mohammad; Shahizon, Azura Mohamed Mukhari; Low, Soo Fin; Shahrina, Man Harun

    2013-07-05

    A 35-year-old woman with background of liver cirrhosis and portal hypertension secondary to chronic hepatitis C presented with complication of hypersplenism and thrombocytopenia. She developed severe menorrhagia requiring multiple blood transfusions. In addition, her interferon therapy was withheld owing to the underlying thrombocytopenia. Partial splenic embolisation was performed, which improved her platelet counts. Subsequently, the menorrhagia was resolved and her interferon therapy was restarted.

  9. 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

  10. 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

  11. 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.

  12. Eptifibatide-induced thrombocytopenia leading to acute stent thrombosis.

    PubMed

    Dézsi, Döme A; Bokori, György; Faluközy, József; Bujáky, Csaba; Fogarassy, György; Veress, Gábor; Aradi, Dániel

    2016-04-01

    A 71-year old female patient with inferior ST-elevation myocardial infarction underwent primary percutaneous coronary intervention (PCI) within 3 h of symptom onset. She was preloaded with 300 mg aspirin and 600 mg clopidogrel before PCI. Coronary angiogram showed occlusion of the right coronary artery. During PCI, eptifibatide was initiated due to the large thrombus burden. Few hours after the procedure, on eptifibatide infusion, a severe drop in platelet count was observed (from 210,000/μl to 35,000/μl) and the infusion was discontinued. One hour later, still under eptifibatide effect and with severe thrombocytopenia, acute stent thrombosis developed. Lack of prior heparin exposure, quick onset of thrombocytopenia made heparin induced thrombocytopenia improbable that was later excluded by specific immunoassay. However, platelet function testing suggested that eptifibatide induced thrombocytopenia was mediated by activating autoantibodies since platelet reactivity was paradoxically very high at the time of stent thrombosis but decreased radically with eptifibatide washout. The patient was successfully managed without further complications on the basis of platelet function data obtained in the subsequent days. This rare subtype of thrombocytopenia highlights that not only platelet count but also platelet function should be closely monitored in case of severe thrombocytopenia to better balance bleeding and thrombosis.

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

    PubMed

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

    2016-02-16

    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.

  14. Effect of Persistent Thrombocytopenia on Mortality in Surgical Critical Care Patients: A Retrospective Study.

    PubMed

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

    2017-01-01

    Thrombocytopenia is common among surgical critically ill patients. The relationship between the duration of thrombocytopenia and mortality is not well studied. This retrospective 12-month cohort study was designed to evaluate the association between persistent thrombocytopenia and mortality among surgical critically ill patients to determine the risk factors for persistent thrombocytopenia. The study included adult patients consecutively admitted to the surgical intensive care unit (SICU) at our institution. Patients with a diagnosis of thrombocytopenia were identified from a prospective critical care database. We defined patients with persistent thrombocytopenia as those with thrombocytopenia lasting more than 7 consecutive days. The primary outcome of this study was 28-day mortality and the secondary outcomes were lengths of SICU stay and hospital stay. Fifty-one patients experienced persistent thrombocytopenia and 71 experienced nonpersistent thrombocytopenia. Among patients with persistent thrombocytopenia, mortality was significantly higher, and SICU and hospital stays were longer than those with nonpersistent thrombocytopenia. Risk factor analysis failed to predict which patients with thrombocytopenia would develop into persistent thrombocytopenia. Persistent thrombocytopenia is a clinically significant disorder and is associated with poorer outcomes. Future studies are needed to further define this process.

  15. Mycophenolate mofetil therapy for severe immune thrombocytopenia.

    PubMed

    Taylor, Alice; Neave, Lucy; Solanki, Shalini; Westwood, John Paul; Terrinonive, Ilaria; McGuckin, Siobhan; Kothari, Jaimal; Cooper, Nichola; Stasi, Roberto; Scully, Marie

    2015-11-01

    Severe immune thrombocytopenia purpura (ITP) presents a clinical challenge. Second-line treatment options are variable without a precise protocol. We present 46 severe ITP patients treated with mycophenolate mofetil (MMF), retrospectively identified from three London teaching hospitals. Data was collected on patient demographics, co-morbidities and previous treatment strategies. Our key interest was whether there was a sustained response in platelet count to MMF. Patients included 27 males and 19 females whose ages ranged from 19 to 93 years old (median 52·5 years). Twenty-nine had primary ITP and 17 had secondary ITP, a third of whom had viral-associated disease. The standard dose of MMF was 1 g/day. Twenty-four patients (52%) responded with 15 (33%) achieving a complete response. No active viral-associated ITP patients demonstrated a response to MMF, although numbers were small (n = 4). We were not able to demonstrate a difference between responders and non-responders based on gender, age, previous therapies or time since diagnosis of ITP. Three of four previously splenectomized patients responded, two achieving complete response. We conclude that MMF is a useful steroid-sparing immunosuppressant to be considered in the second-line or later treatment of ITP.

  16. Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia.

    PubMed

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

    2015-07-27

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

  17. Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection

    PubMed Central

    Dahal, Sumit; Upadhyay, Smrity; Banjade, Rashmi; Dhakal, Prajwal; Khanal, Nabin; Bhatt, Vijaya Raj

    2017-01-01

    Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant

  18. Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia.

    PubMed

    Greinacher, Andreas; Fuerll, Birgitt; Zinke, Heike; Müllejans, Bernd; Krüger, William; Michetti, Noemi; Motz, Wolfgang; Schwertz, Hansjörg

    2009-08-06

    Glycoprotein (GP) IIbIIIa inhibitors are used in the treatment of acute coronary syndromes. Transient immune-mediated acute thrombocytopenia is a recognized side effect of GPIIbIIIa inhibitors. We provide evidence that GPIIbIIIa inhibitor-induced antibodies can affect megakaryocytes in the presence of eptifibatide. In a patient with acute coronary syndrome, acute thrombocytopenia occurred after a second exposure to eptifibatide 20 days after the initial treatment. Despite the short half-life of eptifibatide (t(1/2) = 2 hours), thrombocytopenia less than 5 x 10(9)/L and gastrointestinal and skin hemorrhage persisted for 4 days. Glycoprotein-specific enzyme-linked immunosorbent assay showed eptifibatide-dependent, GPIIbIIIa-specific antibodies. Bone marrow examination showed predominance of early megakaryocyte stages, and platelet transfusion resulted in an abrupt platelet count increase. Viability of cultured cord blood-derived megakaryocytes was reduced in the presence of eptifibatide and patient IgG fraction. These findings can be explained by impaired megakaryocytopoiesis complicating anti-GPIIbIIIa antibody-mediated immune thrombocytopenia. This mechanism may also apply to some patients with autoimmune thrombocytopenia.

  19. Severe thrombocytopenia in hantavirus-induced nephropathia epidemica.

    PubMed

    Latus, J; Kitterer, D; Segerer, S; Artunc, F; Alscher, M D; Braun, N

    2015-02-01

    Nephropathia epidemica is a milder form of hemorrhagic fever with renal syndrome, caused by Puumala virus. The clinical picture is characterized by a rapid loss of renal function (acute kidney injury) and thrombocytopenia. The purpose of the current analysis was to compare the clinical course of patients presenting with or without severe thrombocytopenia. In 47 out of 456 patients with acute nephropathia epidemica, the nadir count of thrombocytes was available for the acute course of the disease. The clinical course of these patients was further analyzed. No major bleeding (e.g., intracranial bleeding or gastrointestinal bleeding) occurred in either group. Creatinine peak levels were higher and proteinuria was more frequently present in the severely thrombocytopenic group. In conclusion, severe thrombocytopenia is common in nephropathia epidemica and is associated with a more severe course of the disease; however, bleeding complications are rare.

  20. Causes of thrombocytopenia in chronic hepatitis C viral infection.

    PubMed

    Osada, Makoto; Kaneko, Makoto; Sakamoto, Minoru; Endoh, Masumi; Takigawa, Koichi; Suzuki-Inoue, Katsue; Inoue, Osamu; Satoh, Kaneo; Enomoto, Nobuyuki; Yatomi, Yutaka; Ozaki, Yukio

    2012-06-01

    We retrospectively studied 89 patients with chronic hepatitis C virus (HCV) infection, including 50 chronic hepatitis (CH) cases, 18 liver cirrhosis (LC) cases, and 21 LC with hepatocellular carcinoma (LC + HCC) cases, with regard to various factors related with thrombocytopenia. The platelet count decreased with the stage advancement of liver diseases. Multiple regression analysis revealed that splenomegaly and von Willebrand factor (vWF) were explanatory variables that correlated with thrombocytopenia. Splenomegaly appears to be the most responsible factor, although there are a considerable number of thrombocytopenic cases without splenomegaly, suggesting other factors may also be responsible. The vWF level is inversely correlated with the platelet count. Soluble thrombomodulin, a marker of endothelial dysfunction, increases with the advancement of liver fibrosis. It is positively correlated with vWF and inversely with the platelet count. Our present results imply that vascular endothelial dysfunction is also involved in thrombocytopenia during chronic HCV infection.

  1. Immune-mediated thrombocytopenia resulting from sensitivity to oxaliplatin.

    PubMed

    Curtis, Brian R; Kaliszewski, James; Marques, Marisa B; Saif, M Wasif; Nabelle, Lisle; Blank, Jules; McFarland, Janice G; Aster, Richard H

    2006-03-01

    Thrombocytopenia developing in the course of chemotherapy for malignant disease is usually attributed to drug-induced marrow suppression and/or marrow replacement by tumor. We describe two patients who developed severe thrombocytopenia and hemorrhagic symptoms while being treated with oxaliplatin, 5-fluorouracil, and leukovorin for metastatic colon cancer in whom platelet destruction appears to have been caused by oxaliplatin-dependent antibodies specific for the platelet glycoprotein IIb/IIIa complex (alpha(IIb)/beta(3) integrin). Drug-induced immune thrombocytopenia (DITP) should be considered in patients who experience a sudden, isolated drop in platelet levels while being treated with chemotherapeutic agents, especially when adequate numbers of megakaryocytes are present in the bone marrow.

  2. 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.

  3. Modulation of radiation-induced hemopoietic suppression by acute thrombocytopenia

    SciTech Connect

    Ebbe, S.; Phalen, E.; Threatte, G.; Londe, H.

    1985-01-01

    Modifications of radiation-induced hemopoietic suppression by acute thrombocytopenia were evaluated. Immediately before or after exposure to sublethal irradiation, mice were given a single injection of anti-mouse platelet serum (APS), normal heterologous serum, neuraminidase (N'ase), or saline, or no further treatment was provided. Hemopoiesis was evaluated by blood cell counts, hematocrits, and incorporation of (75Se)selenomethionine into platelets. APS and N'ase induced an acute thrombocytopenia from which there was partial recovery before the platelet count started to fall from the radiation. During the second post-treatment week, both thrombocytopoiesis and erythropoiesis were greater in mice that received APS or N'ase in addition to radiation than in control irradiated mice. Differences in leukopoiesis were not apparent. Therefore, both thrombocytopoiesis and erythropoiesis appeared to be responsive to a stimulus generated by acute thrombocytopenia in sublethally irradiated mice.

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

    PubMed

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

    2015-12-01

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

  5. 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.

  6. 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.

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

    PubMed Central

    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

  8. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods.

    PubMed

    Reese, Jessica A; Li, Xiaoning; Hauben, Manfred; Aster, Richard H; Bougie, Daniel W; Curtis, Brian R; George, James N; Vesely, Sara K

    2010-09-23

    Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.

  9. Use of 8-methoxypsoralen and ultraviolet-A pretreated platelet concentrates to prevent alloimmunization against class I major histocompatibility antigens

    SciTech Connect

    Grana, N.H.; Kao, K.J. )

    1991-06-01

    The use of 8-methoxypsoralen (8-MOP) and UV-A irradiation to inactivate contaminating donor leukocytes in platelet concentrates and to prevent primary alloimmunization against donor class I major histocompatibility (MHC) antigens in mice was investigated. CBA/CaH-T6J mice with the H2k haplotype and BALB/cByJ mice with the H2d haplotype were used as donors and recipients, respectively. The mixed leukocyte reaction between these two strains of mice showed that treatment of spleen cells with 500 ng/mL 8-MOP and 5J/cm2 UV-A inhibited 99% of responder and 92% of stimulator function. There was no measurable loss of platelet aggregating activity after the treatment. After two weekly transfusions of platelets without any treatment, 93% of control mice (n = 15) developed anti-H2k antibody. In contrast, only 33% of mice (n = 15) receiving platelets treated with 8-MOP and UV-A became alloimmunized. After six weekly platelet transfusions, all mice became alloimmunized. Nevertheless, the mean titers of anti-H2k antibody in sera of the treated groups were significantly lower than the control groups. One hour posttransfusion recoveries of 51Cr-labeled donor platelets were also higher in mice transfused with the treated platelets. Thus, the pretreatment of platelet concentrates with 8-MOP and UV-A irradiation effectively reduced the alloantigenicity of class I MHC molecules. The implication of this finding in relation to the mechanism by which donor leukocytes allosensitize recipients is discussed.

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

    PubMed

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

    2016-02-01

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

  11. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo.

    PubMed

    Yang, Jun; Riella, Leonardo V; Chock, Susanne; Liu, Tao; Zhao, Xiaozhi; Yuan, Xueli; Paterson, Alison M; Watanabe, Toshihiko; Vanguri, Vijay; Yagita, Hideo; Azuma, Miyuki; Blazar, Bruce R; Freeman, Gordon J; Rodig, Scott J; Sharpe, Arlene H; Chandraker, Anil; Sayegh, Mohamed H

    2011-08-01

    The programmed death ligand 1 (PDL1)/programmed death 1 (PD1) costimulatory pathway plays an important role in the inhibition of alloimmune responses as well as in the induction and maintenance of peripheral tolerance. It has been demonstrated recently that PDL1 also can bind B7.1 to inhibit T cell responses in vitro. Using the bm12 into B6 heart transplant model, we investigated the functional significance of this interaction in alloimmune responses in vivo. PD1 blockade unlike PDL1 blockade failed to accelerate bm12 allograft rejection, suggesting a role for an additional binding partner for PDL1 other than PD1 in transplant rejection. PDL1 blockade was able to accelerate allograft rejection in B7.2-deficient recipients but not B7.1-deficient recipients, indicating that PDL1 interaction with B7.1 was important in inhibiting rejection. Administration of the novel 2H11 anti-PDL1 mAb, which only blocks the PDL1-B7.1 interaction, aggravated chronic injury of bm12 allografts in B6 recipients. Aggravated chronic injury was associated with an increased frequency of alloreactive IFN-γ-, IL-4-, and IL-6-producing splenocytes and a decreased percentage of regulatory T cells in the recipients. Using an in vitro cell culture assay, blockade of the interaction of PDL1 on dendritic cells with B7.1 on T cells increased IFN-γ production from alloreactive CD4(+) T cells, whereas blockade of dendritic cell B7.1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction.

  12. [Guideline for prevention of RhD alloimmunization in RhD negative women].

    PubMed

    Lubuský, Marek; Procházka, M; Simetka, O; Holusková, I

    2010-08-01

    Events following which anti-D immunoglobulin should be given to all RhD negative women with no anti-D antibodies: First trimester indications (50 microg)--termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (100 microg)--amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric haemorrhage; Antenatal prophylaxis at 28th weeks of gestation (250 microg); Delivery of an RhD positive infant * (100 microg); Minimal dose: before 20 weeks gestation--50 microg (250 IU), after 20 weeks gestation **--100 microg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer anti-D immunoglobulin (IgG anti-D) within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum.; FMH (fetomaternal haemorrhage)--If the amount of fetal erythrocytes which entered the maternal circulation is quantitatively determined, administration of 10 microg IgG anti-D per 0.5 ml of fetal erythrocytes or 1 ml of whole blood is indicated. *also if the RhD type of the infant has not been determined or is in doubt, **in conjunction with a test to assess the volume of any fetomaternal hemorrhage.

  13. Fas ligand enhances hematopoietic cell engraftment through abrogation of alloimmune responses and nonimmunogenic interactions.

    PubMed

    Pearl-Yafe, Michal; Yolcu, Esma S; Stein, Jerry; Kaplan, Ofer; Yaniv, Isaac; Shirwan, Haval; Askenasy, Nadir

    2007-06-01

    Early after transplantation, donor lineage-negative bone marrow cells (lin(-) BMC) constitutively upregulated their expression of Fas ligand (FasL), suggesting an involvement of the Fas/FasL axis in engraftment. Following the observation of impaired engraftment in the presence of a dysfunctional Fas/FasL axis in FasL-defective (gld) donors or Fas-defective (lpr) recipients, we expressed a noncleavable FasL chimeric protein on the surface of donor lin(-) BMC. Despite a short life span of the protein in vivo, expression of FasL on the surface of all the donor lin(-) BMC improved the efficiency of engraftment twofold. The FasL-coated donor cells efficiently blunted the host alloimmune responses in primary recipients and retained their hematopoietic reconstituting potential in secondary transplants. Surprisingly, FasL protein improved the efficiency of engraftment in syngeneic transplants. The deficient engraftment in lpr recipients was not reversed in chimeric mice with Fas(-) stroma and Fas(+) BMC, demonstrating that the host marrow stroma was also a target of donor cell FasL. Hematopoietic stem and progenitor cells are insensitive to Fas-mediated apoptosis and thus can exploit the constitutive expression of FasL to exert potent veto activities in the early stages of engraftment. Manipulation of the donor cells using ectopic FasL protein accentuated the immunogenic and nonimmunogenic interactions between the donor cells and the host, alleviating the requirement for a megadose of transplanted cells to achieve a potent veto effect. Disclosure of potential conflicts of interest is found at the end of this article.

  14. 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

  15. Eptifibatide-Induced Thrombocytopenia--When Inhibitor Turns Killer.

    PubMed

    Pothineni, Naga Venkata; Watts, Thomas E; Ding, Zufeng; Dai, Yao; Deshmukh, Abhishek J

    2016-01-01

    Eptifibatide is a commonly and widely used drug for management of acute coronary syndrome and during percutaneous coronary intervention. It is usually well tolerated with no major adverse effects. We report a rare case of life-threatening thrombocytopenia secondary to eptifibatide along with a literature review of available evidence.

  16. Intracerebral hemorrhage caused by varicella-induced thrombocytopenia.

    PubMed

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

    2016-02-16

    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.

  17. Acute eosinophilic pneumonia accompanied by mediastinal lymphadenopathy and thrombocytopenia.

    PubMed Central

    Esme, Hidir; Sahin, Onder; Sezer, Murat; Fidan, Fatma; Unlu, Mehmet

    2006-01-01

    Acute eosinophilic pneumonia, which was described in 1989, is thought to represent a hypersensitivity reaction to unidentified inhaled antigens. Here, we present a case of a marble mine worker with acute eosinophilic pneumonia complicated with mediastinal lymphadenopathy, neutrophilia, thrombocytopenia and acute respiratory distress syndrome. Images Figure 1 Figure 2 PMID:17128696

  18. Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

    PubMed

    Tanaka, Takashi; Inamoto, Yoshihiro; Yamashita, Takuya; Fuji, Shigeo; Okinaka, Keiji; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Fukuda, Takahiro

    2016-05-01

    Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/μL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/μL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag.

  19. Innate Immune Cells Induce Hemorrhage in Tumors during Thrombocytopenia

    PubMed Central

    Ho-Tin-Noé, Benoit; Carbo, Carla; Demers, Mélanie; Cifuni, Stephen M.; Goerge, Tobias; Wagner, Denisa D.

    2009-01-01

    Platelets are crucial regulators of tumor vascular homeostasis and continuously prevent tumor hemorrhage through secretion of their granules. However, the reason for tumor bleeding in the absence of platelets remains unknown. Tumors are associated with inflammation, a cause of hemorrhage in thrombocytopenia. Here, we investigated the role of the inflamed tumor microenvironment in the induction of tumor vessel injury in thrombocytopenic mice. Using s.c. injections of vascular endothelial growth factor or tumor necrosis factor-α combined with depletion of neutrophils, we demonstrate that enhancing the opening of endothelial cell junctions was not sufficient to cause bleeding in the absence of platelets; instead, induction of tissue hemorrhage in thrombocytopenia required recruitment of leukocytes. Immunohistology revealed that thrombocytopenia-induced tumor hemorrhage occurs at sites of macrophage and neutrophil accumulation. Mice deficient in β2 or β3 integrins, which have decreased neutrophil and/or macrophage infiltration in their tumor stroma, were protected from thrombocytopenia-induced tumor hemorrhage, indicating that, in the absence of platelets, stroma-infiltrating leukocytes induced tumor vessel injury. This injury was independent of reactive oxygen species generation and of complement activation, as suggested by the persistence of tumor hemorrhage in C3- and nicotinamide adenine dinucleotide phosphate oxidase-deficient thrombocytopenic mice. Our results show that platelets counteract tumor-associated inflammation and that the absence of this platelet function elicits vascular injuries by tumor-infiltrating innate immune cells. PMID:19729481

  20. A point mutation in the EGF-4 domain of β(3) integrin is responsible for the formation of the Sec(a) platelet alloantigen and affects receptor function.

    PubMed

    Sachs, Ulrich J; Bakchoul, Tamam; Eva, Olga; Giptner, Astrid; Bein, Gregor; Aster, Richard H; Gitter, Maria; Peterson, Julie; Santoso, Sentot

    2012-01-01

    Neonatal alloimmune thrombocytopenia (NAIT) is caused by fetomaternal platelet incompatibility with maternal antibodies crossing the placenta and destroying fetal platelets. Antibodies against human platelet antigen-1a (HPA-1a) and HPA-5b are responsible for the majority of NAIT cases. We observed a suspected NAIT in a newborn with a platelet count of 25 G/l and petechial haemorrhages. Serological analysis of maternal serum revealed an immunisation against αIIbβ3 on paternal platelets only, indicating the presence of an antibody against a new rare alloantigen (Sec(a)) residing on αIIbβ3. The location of Sec(a) on αIIbβ3 was confirmed by immunoprecipitation. Nucleotide sequence analysis of paternal β3 revealed a single nucleotide exchange (G(1818)T) in exon 11 of the β3 gene (ITGB3), changing Lys(580) (wild-type) to Asn(580) (Sec(a)). Two additional members of the family Sec were typed Sec(a) positive, but none of 300 blood donors. Chinese hamster ovary cells expressing Asn(580), but not Lys(580) αIIbβ3, bound anti-Sec(a), which was corroborated by immunoprecipitation. Adhesion of transfected cells onto immobilised fibrinogen showed reduced binding of the Asn(580) variant compared to wild-type αIIbβ3. Analysis of transfected cells with anti-LIBS and PAC-1 antibody showed reduced binding when compared to the wild-type. No such effects were observed with Sec(a) positive platelets, which, however, are heterozygous for the Lys(580)Asn mutation. In this study, we describe a NAIT case caused by maternal alloimmunisation against a new antigen on αIIbβ3. Analysis with mutant transfected cells showed that the Lys(580)Asn mutation responsible for the formation of the Sec(a) antigenic determinant affects αIIbβ3 receptor function.

  1. 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.

  2. Clinical manifestations of the thrombocytopenia and absent radii (TAR) syndrome.

    PubMed

    Gounder, D S; Pullon, H W; Ockelford, P A; Nicol, R O

    1989-10-01

    Six patients with the classical features of the TAR syndrome were diagnosed at birth. In one case an older sibling was also affected. The characteristic features of foreshortened forearms and radially deviated hands were noted in all cases at presentation and confirmed radiologically. With one exception skeletal abnormalities of the lower limbs were also present. Varying degrees of thrombocytopenia were present at birth with three of the five patients having platelet counts below 50 x 10(9)/L. Bone marrow examination was performed in two patients and revealed an absence of normal megakaryocytes. Two patients with severe thrombocytopenia had bleeding complications during infancy requiring transfusion support. Severe gastroenteritis occurred in two patients, in one of whom it was attributed to cow's milk intolerance. In all patients the platelet count has risen progressively since birth. Orthopedic surgical procedures have been performed without hemorrhagic complications.

  3. Typhoid fever presenting as acute cerebellar ataxia and severe thrombocytopenia.

    PubMed

    Cheong, B M K

    2008-03-01

    Typhoid fever being a systemic infection can present in a multitude of ways, involving various systems. Here we describe a case of typhoid fever presenting with acute cerebellar ataxia and marked thrombocytopenia. This atypical presentation is not common in typhoid fever and can lead to misdiagnosis as well as a delay in the initiation of appropriate therapy. Prompt clinical improvement and the return of platelet counts to normal were noted after the patient was started on IV Ceftriaxone.

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

    PubMed

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

    2015-05-01

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

  5. 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.

  6. Severe Fever with Thrombocytopenia Syndrome Presenting with Hemophagocytic Lymphohistiocytosis

    PubMed Central

    Jeong, Gyeongmin; Lim, Ji-Hun; Kim, Hawk; Park, Sun-Whan; Lee, Won-Ja

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the newly discovered SFTS Bunyavirus, and there have been no case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis (HLH) in the English literature. We report a case of SFTS presenting with HLH in a 73-year-old immunocompetent male farmer. Although the patient had poor prognostic factors for SFTS, such as old age and central nervous system symptoms, he recovered fully with supportive care. PMID:27883371

  7. [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.

  8. 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

  9. Thrombopoetin receptor agonist therapy in thrombocytopenia: ITP and beyond.

    PubMed

    Taylor, Alice; Westwood, John Paul; Laskou, Faidra; McGuckin, Siobhan; Scully, Marie

    2017-03-14

    Eltrombopag is well established in treatment of severe immune thrombocytopenia (ITP) and is increasingly commonplace in second-line management. A role is also suggested for both bridging therapy for surgery, as well as treating thrombocytopenia due to non-immune aetiologies. We present the largest single-centre experience with eltrombopag, with our cohort of 62 patients. Patients with severe ITP (n = 34) had 91·2% response, which was sustained over a median of 18·5 months. In 41·4% of ITP cases (n = 14), complete response (CR- platelet count >100 × 10(9) /l) was achieved and in 2 cases, therapy was stopped and CR maintained. In our bridging group (n = 15) with a higher baseline platelet count, 93·3% achieved a CR. In the non-ITP group (n = 13), a response was achieved in 76·9%. In all groups, side effects were transient, with the drug discontinued in 2 patients due to minor complications (rash, nausea, diarrhoea). We conclude that eltrombopag is both effective and well tolerated as therapy in severe ITP. It is also advantageous in ITP patients who do not normally require therapy, but need a temporary platelet count boost pre-procedure. Furthermore, there are potentially far wider implications for the use of eltrombopag in counteracting thrombocytopenia beyond ITP, which merit further investigation.

  10. [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.

  11. Platelet activation determines the severity of thrombocytopenia in dengue infection

    PubMed Central

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  12. Heparin-induced thrombocytopenia complicating support by the Berlin Heart.

    PubMed

    Eghtesady, Pirooz; Nelson, David; Schwartz, Steven M; Wheeler, Derek; Pearl, Jeffrey M; Cripe, Linda H; Manning, Peter B

    2005-01-01

    Since 1992, miniaturized pulsatile air-driven ventricular assist devices (VADs), "Berlin Heart," have been used at many institutions (36 cases in North America in 19 different institutions) for pediatric use. Heparin-induced thrombocytopenia (HIT II) is a significant complication rarely reported in the setting of adult VAD support; no similar report exists concerning pediatric VAD support. We report on a 13-month-old, 8.1 kg girl who required LVAD support for cardiogenic shock of unclear etiology. The patient had a history of multiple surgical repairs for correction of complex congenital heart disease consisting of a series of left heart obstructive lesions (Shone's complex). Despite aggressive ventilatory and inotropic support, the patient continued to deteriorate and subsequently required extracorporeal life support. After 7 days of conventional venoarterial extracorporeal membrane oxygenation, a 10 ml Berlin Heart VAD was implanted. After implantation, the patient developed persistent low-grade fever of unclear etiology, gradual thrombocytopenia, and deterioration of renal function. On postimplant day 10, the pump required replacement because of concerns about an inlet valve thrombus; the explanted device demonstrated a nearly occlusive clot not appreciable from external inspection. Simultaneously, HIT II was diagnosed as a result of hematology workup for persistent thrombocytopenia. We discuss the unique challenges posed by HIT II complicating pediatric VAD support and in relation to the heparin coating of the device.

  13. 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.

  14. Simian Retrovirus 4 Induces Lethal Acute Thrombocytopenia in Japanese Macaques

    PubMed Central

    Yoshikawa, Rokusuke; Sakaguchi, Shoichi; Nakagawa, So; Miura, Tomoyuki; Hirai, Hirohisa

    2015-01-01

    ABSTRACT In 2001-2002, six of seven Japanese macaques (Macaca fuscata) died after developing hemorrhagic syndrome at the Kyoto University Primate Research Institute (KUPRI). While the cause of death was unknown at the time, we detected simian retrovirus 4 (SRV-4) in samples obtained from a similar outbreak in 2008-2011, during which 42 of 43 Japanese macaques died after exhibiting hemorrhagic syndrome. In this study, we isolated SRV-4 strain PRI-172 from a Japanese macaque showing severe thrombocytopenia. When inoculated into four Japanese macaques, the isolate induced severe thrombocytopenia in all within 37 days. We then constructed an infectious molecular clone of strain PRI-172, termed pSR415, and inoculated the clone-derived virus into two Japanese macaques. These animals also developed severe thrombocytopenia in just 31 days after inoculation, and the virus was reisolated from blood, bone marrow, and stool. At necropsy, we observed bleeding from the gingivae and subcutaneous bleeding in all animals. SRV-4 infected a variety of tissues, especially in digestive organs, including colon and stomach, as determined by real-time reverse transcription-PCR (RT-PCR) and immunohistochemical staining. Furthermore, we identified the SRV-4 receptor as ASCT2, a neutral amino acid transporter. ASCT2 mRNA was expressed in a variety of tissues, and the distribution of SRV-4 proviruses in infected Japanese macaques correlated well with the expression levels of ASCT2 mRNA. From these results, we conclude that the causative agent of hemorrhagic syndrome in KUPRI Japanese macaques was SRV-4, and its receptor is ASCT2. IMPORTANCE During two separate outbreaks at the KUPRI, in 2001-2002 and 2008-2011, 96% of Japanese macaques (JM) that developed an unknown hemorrhagic syndrome died. Here, we isolated SRV-4 from a JM developing thrombocytopenia. The SRV-4 isolate and a molecularly cloned SRV-4 induced severe thrombocytopenia in virus-inoculated JMs within 37 days. At necropsy, we

  15. Interferon-α induced severe thrombocytopenia: A case report and review of the literature

    PubMed Central

    Li, Li; Han, Da-Kang; Lu, Jun

    2010-01-01

    We report a case of severe thrombocytopenia following pegylated interferon-α 2a (Peg-IFN-α 2a) treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism. Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-α induced severe thrombocytopenia. PMID:20238410

  16. 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

  17. Thrombocytopenia in Systemic Lupus Erythematosus: Clinical Manifestations, Treatment, and Prognosis in 230 Patients.

    PubMed

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

    2016-02-01

    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/mm, and patients were divided into 3 thrombocytopenia groups according to severity: mild (platelet counts >50,000/mm), moderate (>20,000/mm, ≤50,000/mm), and severe (≤20,000/mm). Clinical characteristics, treatments, and prognoses were compared among the groups. Furthermore, complete remission of thrombocytopenia was defined as platelet counts >100,000/mm 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.

  18. 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

  19. Enoxaparin can be used safely in patients with severe thrombocytopenia due to intensive chemotherapy regimens.

    PubMed

    Herishanu, Yair; Misgav, Mudi; Kirgner, Ilya; Ben-Tal, Ofira; Eldor, Amiram; Naparstek, Ella

    2004-07-01

    Treatment with intensive chemotherapy regimens is frequently complicated by severe thrombocytopenia. During the period of severe thrombocytopenia, anticoagulant treatment is not uncommonly indicated for thromboembolic events or thromboprophylaxis in these patients. We report 10 hematological patients treated with intensive chemotherapy protocols that were anticoagulated with enoxaparin for catheter related central venous thrombosis and thromboprophylaxis. During the period of severe thrombocytopenia the dosages of enoxaparin were reduced and no major bleeding occurred. Based on our experience we suggest that reduced dosages of low molecular weight heparins may be used relatively safely during transient severe thrombocytopenia.

  20. Hematologic Complications of Pregnancy

    PubMed Central

    Townsley, Danielle M.

    2013-01-01

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

  1. 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.

  2. Red blood cell alloimmunization in sickle cell disease and in thalassaemia: current status, future perspectives and potential role of molecular typing.

    PubMed

    Matteocci, A; Pierelli, L

    2014-04-01

    Red blood cell (RBC) transfusions are a milestone in the treatment for sickle cell anaemia (SSA) and for thalassaemia. RBC alloimmunization remains a major challenge of chronic transfusion therapy, and it can lead to adverse life-threatening events. The alloimmunization risk could depend on multiple factors such as the number of transfusions and, most of all, the genetic background. Different ethnic groups are predisposed to immunization because of a significant degree of RBC antigenic mismatch between donor and recipient. There is no universal agreement and standards for the most appropriate selection of RBC units in chronically transfused subjects. Current practice only deals with compatibility of ABO, Rh and K antigens. Molecular RBC antigenic matching extended to other blood group systems is an innovative strategy to ensure a better quality and effectiveness of transfusion therapy.

  3. Inherited Thrombocytopenia with a Different Type of Gene Mutation: A Brief Literature Review and Two Case Studies

    PubMed Central

    Arzanian, Mohammad Taghi

    2016-01-01

    Hereditary thrombocytopenias are rare bleeding disorders, which cause a deficiency of platelets in early infancy. This group of disorders is sometimes associated with abnormal phenotypes, like absence of radius. Diagnosis of this type of thrombocytopenia is usually difficult; other causes of thrombocytopenia, such as immune disorders and infections, must be ruled out. The symptoms of hereditary thrombocytopenia also vary from seldom and mild to severe bleeding and occasionally may first occur in late childhood. In this group of patients, we must differentiate heritable disorders from the acquired types of thrombocytopenia, like immune thrombocytopenic purpura. It is also important to watch for pitfalls to avoid unnecessary and potentially hazardous treatment. Herein, we briefly review the recent literature on hereditary thrombocytopenia and then present the cases of two referred patients. The first case had suffered from persistent thrombocytopenia since early infancy and was diagnosed with congenital amegakaryocytic thrombocytopenia, while the other patient presented with Wiskott - Aldrich syndrome. PMID:28203325

  4. 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.

  5. Severe Fever with Thrombocytopenia Syndrome Complicated by Co-infection with Spotted Fever Group Rickettsiae, China.

    PubMed

    Lu, Qing-Bin; Li, Hao; Zhang, Pan-He; Cui, Ning; Yang, Zhen-Dong; Fan, Ya-Di; Cui, Xiao-Ming; Hu, Jian-Gong; Guo, Chen-Tao; Zhang, Xiao-Ai; Liu, Wei; Cao, Wu-Chun

    2016-11-01

    During 2013-2015 in central China, co-infection with spotted fever group rickettsiae was identified in 77 of 823 patients infected with severe fever with thrombocytopenia syndrome virus. Co-infection resulted in delayed recovery and increased risk for death, prompting clinical practices in the region to consider co-infection in patients with severe fever with thrombocytopenia syndrome.

  6. Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia

    PubMed Central

    Hilton, Douglas J.; Kile, Benjamin T.

    2009-01-01

    The transcription factor c-Myb and coregulator p300 have a key role in maintaining production of controlled numbers of megakaryocytes and platelets. In mice, mutations in c-Myb or p300 cause thrombocytosis in otherwise wild-type animals and can ameliorate the thrombocytopenia in mice lacking the thrombopoietin receptor, c-Mpl, a model for human congenital amegakaryocytic thrombocytopenia. To examine whether inhibition of c-Myb/p300 is effective in other models of thrombocytopenia, the effect of the c-MybPlt4 mutation on thrombocytopenia associated with reduced platelet life span in Bcl-XPlt20/Plt20 mice was assessed, as were responses in c-MybPlt4 and/or p300Plt6 mutant mice to thrombocytopenia associated with antiplatelet antibodies, chemotherapy, or bone marrow transplantation. Homozygosity of the c-MybPlt4 allele ameliorated thrombocytopenia associated with reduced platelet life span, and c-MybPlt4/+ mice exhibited more rapid than normal recovery from thrombocytopenia caused by antiplatelet serum or bone marrow transplantation. Recovery to pretreatment platelet levels was unaltered in 5-fluorouracil–treated c-MybPlt4/+ mice relative to wild-type controls, but enhanced platelet production during subsequent thrombocytosis was evident. More modest enhancement of platelet recovery after 5-fluorouracil or bone marrow transplantation was also evident in p300Plt6/+ animals. The data suggest potential utility of c-Myb/p300 as a target for therapeutic intervention in thrombocytopenia of diverse origins. PMID:19252138

  7. Severe Fever with Thrombocytopenia Syndrome Complicated by Co-infection with Spotted Fever Group Rickettsiae, China

    PubMed Central

    Lu, Qing-Bin; Li, Hao; Zhang, Pan-He; Cui, Ning; Yang, Zhen-Dong; Fan, Ya-Di; Cui, Xiao-Ming; Hu, Jian-Gong; Guo, Chen-Tao; Zhang, Xiao-Ai; Cao, Wu-Chun

    2016-01-01

    During 2013–2015 in central China, co-infection with spotted fever group rickettsiae was identified in 77 of 823 patients infected with severe fever with thrombocytopenia syndrome virus. Co-infection resulted in delayed recovery and increased risk for death, prompting clinical practices in the region to consider co-infection in patients with severe fever with thrombocytopenia syndrome. PMID:27767921

  8. Persistent immune thrombocytopenia heralds the diagnosis of Mycobacterium chimaera prosthetic valve endocarditis.

    PubMed

    Sacco, Keith A; Burton, M Caroline

    2017-01-01

    A 63 year old female was admitted for investigation of worsening renal insufficiency. During hospitalization she developed persistent immune thrombocytopenia refractory to supportive or immunosuppressive treatment. She was diagnosed with Mycobacterium chimaera prosthetic valve endocarditis and thrombocytopenia resolved with anti-mycobacterial therapy.

  9. Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor factors that inhibit transmission of R5 and X4 HIV-1 in women.

    PubMed

    Wang, Y; Underwood, J; Vaughan, R; Harmer, A; Doyle, C; Lehner, T

    2002-09-01

    Studies in humans suggest that allo-immunization induces CC-chemokines, CD8-suppressor factors (SF) and anti-HIV immunity. Here we report that allo-immunization with unmatched leucocytes from partners of women with recurrent spontaneous abortion elicits specific antibodies to the CCR5 receptor. Such antibodies inhibit replication of M-tropic HIV-1 (R5) and MIP-1beta-mediated chemotaxis. These CCR5 antibodies were also found in the sera of multiparous women that were naturally immunized by semi-allogeneic fetal antigens. The specificity of these antibodies was demonstrated by adsorption with CCR5 transfected HEK-293 cells, a baculovirus CCR5 preparation and a peptide of the 2nd extra-cellular loop of CCR5. Allo-immunization also stimulated increased concentrations of the CXC chemokine, SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 (X4) replication. We suggest that allo- immunization may elicit (a) CC chemokines, CCR5 antibodies and CD8-SF that inhibit M-tropic HIV-1 infection and (b) the CXC chemokine SDF-1alpha and CD8-SF that inhibit T-tropic HIV-1 infection.

  10. Helicobacter pylori infection and thrombocytopenia: a single-institution experience in Mexico.

    PubMed

    Estrada-Gómez, Roberto A; Parra-Ortega, Israel; Martínez-Barreda, Carlos; Ruiz-Argüelles, Guillermo J

    2007-01-01

    The association between gastrointestinal H. pylori infection and thrombocytopenia was studied in a single institution in Mexico, over a 5-year period. In 99 individuals with H. pylori infection, the prevalence of thrombocytopenia was 14%, whereas in 23 consecutive patients with chronic refractory thrombocytopenic purpura, the prevalence of H. pylori infection was 60%, this figure being similar to that informed in the general population of Mexico (66%); the association between thrombocytopenia and H. pylori infection was not significant. In 14 patients who were found to have both thrombocytopenia and H. pylori infection, eradication treatment was given and the platelet count recovered in three. It is not still clear if detection of H. pylori infection should be routinely included in the initial workup of chronic thrombocytopenia.

  11. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia: a case report.

    PubMed

    Dickinson, Brian P; Lawrence, Peter F

    2007-01-01

    Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.

  12. Thrombocytopenia associated with Mycoplasma pneumonia during pregnancy: case presentation and approach for differential diagnosis.

    PubMed

    Nishikawa, Aiko; Mimura, Kazuya; Kanagawa, Takeshi; Maeda, Tetsuo; Tomimatsu, Takuji; Kimura, Tadashi

    2015-08-01

    Thrombocytopenia during pregnancy has many different causes, but Mycoplasma pneumoniae is not usually considered one of the several pathogens that induce thrombocytopenia. Herein, we present a case of severe thrombocytopenia that was associated with M. pneumoniae during pregnancy. The patient experienced fever, cough, and cytopenia with M. pneumoniae-specific IgM antibody increasing from 40-fold to 160-fold during the 2 weeks of illness. A diagnosis was made after excluding other diseases that cause thrombocytopenia. The patient was successfully treated with azithromycin hydrate, and she delivered a healthy newborn without any complications. Pregnant women who are infected with M. pneumoniae during pregnancy may develop severe and fatal thrombocytopenia. Prompt diagnosis and initiation of treatment lead to early recovery.

  13. Fatal thrombocytopenia: A rare case with possible explanation

    PubMed Central

    Barik, Ramachandra; Patnaik, A. N.; Gulati, A. S.

    2012-01-01

    A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow. PMID:22629036

  14. Clinical characteristics of immune thrombocytopenia associated with autoimmune disease

    PubMed Central

    Liu, Yuan; Chen, Shiju; Sun, Yuechi; Lin, Qingyan; Liao, Xining; Zhang, Junhui; Luo, Jiao; Qian, Hongyan; Duan, Lihua; Shi, Guixiu

    2016-01-01

    Abstract To clarify clinical characteristics of immune thrombocytopenia (ITP) subsets associated with autoimmune diseases (AIDs). Five thousand five hundred twenty patients were reviewed retrospectively. One hundred four ITP patients were included for analysis. Clinical manifestations at first thrombocytopenic episode were recorded. Systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) accounted for a large part in AIDs associated with secondary ITP. SLE-ITP, pSS-ITP, and primary ITP (pITP) patients were different in several aspects in clinical and immunological characteristics. A subgroup of patients in pITP patients with some obvious autoimmune features (defined as AIF-ITP) such as positive ANA but failing to meet the diagnosis criteria now used for a specific kind of connective tissue diseases were also different with other pITP patients in some immunological features, indicating the difference in the pathogenesis mechanism of those autoimmune featured ITP patients. ITP patients were heterogeneous in clinical characteristics. Further study about the different pathogenesis of ITP subsets especially those AIF-ITP patients who only presented with thrombocytopenia will help us have a better understanding of pathogenesis of ITP and a better management of ITP patients. PMID:27977588

  15. A rare case of acyclovir-induced thrombocytopenia.

    PubMed

    Kamboj, Jasmine; Wu, Fang; Kamboj, Rahul; Suzue, Kimiko; Khosla, Pam

    2014-01-01

    Acyclovir is used for its potent antiviral properties for the mucocutaneous herpes, herpes zoster, herpes encephalitis, and genital herpes simplex. The drug has a very wide distribution involving almost every organ of the body, with excretion into the urine. Urine analysis, kidney function, liver function, and complete blood counts are some of the monitoring parameters. The active triphosphate form of the drug inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA. Because the drug is only absorbed by the cells that are virus infected, acyclovir has minimal side effects at therapeutic doses. However, at high intravenous infusions, severe central nervous system (malaise), gastrointestinal (nausea/vomiting), renal (elevated blood urea nitrogen/creatinine), hepatic (elevated liver enzymes), and skin dyscrasias have been found to occur. There have been few case reports of bone marrow suppression and only one case report so far of acyclovir-related isolated thrombocytopenia. Whether there is any further association between acyclovir and thrombotic thrombocytopenic purpura/hemolytic uremic syndrome is the next dilemma if such an association is established. Here, the authors present a case report of a 58-year-old man with acquired immune deficiency syndrome on highly active antiretroviral therapy who went into severe thrombocytopenia on starting acyclovir.

  16. Invasive Thymoma with Pure Red Cell Aplasia and Amegakaryocytic Thrombocytopenia

    PubMed Central

    Kiyoki, Yusuke; Ueda, Sho; Yamaoka, Masatoshi; Shimizu, Seiich; Inagaki, Masaharu

    2016-01-01

    We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 104/μL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT). On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaokakoga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention. PMID:28053696

  17. Hepatitis B infection is associated with an increased incidence of thrombocytopenia in healthy adults without cirrhosis.

    PubMed

    Joo, E-J; Chang, Y; Yeom, J-S; Lee, Y-G; Ryu, S

    2017-03-01

    The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count <150 000/μL. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95% confidence intervals (CIs) for incident thrombocytopenia. HBsAg was positive in 4857 of 122 200 subjects (4.0%) at baseline. During 883 983 person-years of follow-up, 2037 incident cases of thrombocytopenia were identified (incident rate 2.3 per 1000 person-years). HBsAg-positive subjects had a higher incidence of thrombocytopenia than did healthy controls (11.2 vs 1.9 per 1000 person-years, respectively). The multivariate-adjusted hazard ratio (95% CI) for incident thrombocytopenia comparing HBsAg-positive to HBsAg-negative subjects was 5.71 (5.10-6.38). Strong associations between HBsAg positivity and thrombocytopenia were consistently observed across prespecified subgroups. In this large cohort study of an apparently healthy population, HBsAg positivity was strongly and independently associated with incident thrombocytopenia, indicating that mechanisms of thrombocytopenia other than portal hypertension may exist in healthy HBV carriers.

  18. 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.

  19. CD44 Antibodies and Immune Thrombocytopenia in the Amelioration of Murine Inflammatory Arthritis

    PubMed Central

    Mott, Patrick J.; Lazarus, Alan H.

    2013-01-01

    Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP) that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7), also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics. PMID:23785450

  20. Typing for human platelet alloantigens.

    PubMed

    Juji, T; Saji, H; Satake, M; Tokunaga, K

    1999-01-01

    Antibodies to platelet alloantigens, and sometimes to isoantigens, induce severe clinical problems such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusions (PTR). For example, NAIT affects approximately 1 in 5,000 live births. It is essential, therefore, to screen pregnant women for platelet antibodies in order to save babies' lives. Almost 40 years ago, two platelet alloantigen systems were discovered using relatively simple methods, namely the platelet agglutination test and the complement fixation test. However, these methods were not sensitive enough to identify all antibodies in mothers and patients, even in those with severe clinical problems. Tremendous effort has been devoted to establish more sensitive and reliable methods. In recent years, excellent new serological and immunochemical methods have been established and several new platelet antigen systems have been discovered. Simultaneously, newly developed molecular genetic techniques have been introduced for the typing and analysis of human platelet alloantigen systems. These methods allow DNA typing for cases in which serological typing is not available. In this article, the history of studies on human platelet alloantigen systems and isoantigens, the nomenclature of platelet alloantigen systems and their alleles, the present status of antibody detection and typing techniques and, finally, ethnic variations in platelet antigen profiles are reviewed.

  1. Thrombocytopenia in Plasmodium vivax Malaria Is Related to Platelets Phagocytosis

    PubMed Central

    Coelho, Helena Cristina C.; Lopes, Stefanie C. P.; Pimentel, João Paulo D.; Nogueira, Paulo A.; Costa, Fábio T. M.; Siqueira, André M.; Melo, Gisely C.; Monteiro, Wuelton M.; Malheiro, Adriana; Lacerda, Marcus V. G.

    2013-01-01

    Background Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis. Methods and Findings Thirty-five malaria vivax patients and eight healthy volunteers (HV) were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL) was found in 62.9% (22/35). Mean platelet volume (MPV) was higher in thrombocytopenic patients as compared to non- thrombocytopenic patients (p = 0.017) and a negative correlation was found between platelet count and MPV (r = −0.483; p = 0.003). Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA), incubated with human monocytic cell line (THP-1) and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042) and HV (p = 0.048). A negative correlation was observed between platelet count and phagocytosis index (r = −0.402; p = 0.016). Platelet activation was assessed measuring the expression of P-selectin (CD62-P) in platelets’ surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092). After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17) in the patients’ sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = −0.305; p = 0.037). Conclusion/Significance Collectively, our findings indicate that platelet

  2. High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients.

    PubMed

    Tatari-Calderone, Zohreh; Fasano, Ross M; Miles, Megan R; Pinto, Ligia A; Luban, Naomi L C; Vukmanovic, Stanislav

    2014-07-01

    Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.

  3. Neonatal Liver Failure and Congenital Cirrhosis due to Gestational Alloimmune Liver Disease: A Case Report and Literature Review

    PubMed Central

    Rostirola Guedes, Renata; Kieling, Carlos Oscar; Rossato Adami, Marina; Cerski, Carlos Thadeu Schmidt

    2017-01-01

    Neonatal liver failure (NLF) is a major cause of neonatal morbidity and mortality, presenting as acute liver failure and/or congenital cirrhosis. Many affected patients show antenatal signs of fetal injury. There are several causes of NLF and early diagnosis is mandatory to elucidate the etiology and determine a specific treatment or the best management strategy. Gestational alloimmune liver disease associated with neonatal hemochromatosis (GALD-NH) is a rare but potentially treatable cause of NLF. It should be considered in any neonate with fetal signs of disease and postnatal signs of liver failure with no other identifiable causes. GALD-NH is often diagnosed late and patients are therefore referred late to specialized centers, delaying treatment. This case highlights the consequences of late diagnosis and treatment of GALD-NH and emphasizes the importance of a high grade of suspicion of this disease in order to refer the patient to a specialized center soon enough to perform the appropriate treatment. PMID:28251010

  4. 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

  5. [Electronic platelet counting with particular reference to thrombocytopenias (author's transl)].

    PubMed

    Kuse, R; Burmeister, H; Hausmann, K

    1977-09-29

    Platelet counts in platelet-rich plasma without hematocrit dependent correction were performed by following rapid and simple steps: 1. pre-dilution of 20 microliter of whole blood by an isotonic solution 1:25; 2. stabilized low-speed centrifugation with 55 g for 5 minutes; 3. final dilution 1 : 5000; 4. enumeration by use of a TOA platelet counter PL-100 which has been technically improved in comparison to similar machines. Erroneously high results were obtained after a too short or too low centrifugation. As reason for this artifical small pulses due to disturbances of the flow patterns around the aperture (so-called vortex-effect) can be assumed having been caused by large-volumed erythrocytes and leukocytes in the suspension. The routinely used procedure was reliable for all platelet ranges, especially in thrombocytopenias between 100 X 10(9)/l and 25 X 10(9)l. In lower ranges comparisons with visual counts are essential.

  6. Heparin-induced thrombocytopenia with thrombotic sequelae: a review.

    PubMed

    Goor, Yoav; Goor, Odelia; Eldor, Amiram

    2002-08-01

    Heparin-induced thrombocytopenia (HIT) occurs in 1-5% of patients treated with heparin. The pathogenesis involves the formation of antibodies to heparin-platelet factor 4 complexes, and the major clinical sequelae are thrombotic. Diagnosis is based on a combination of clinical and laboratory data. Treatment consists of stopping heparin, but, insofar as the risk of thrombosis remains high, treatment by alternative antithrombotic agents is indicated. Most clinical experience has been with danaparoid sodium and hirudin. The use of low-molecular-weight heparins (LMWH) in subsequent HIT episodes has been described, but is not recommended, especially with the introduction of new agents, such as oral thrombin inhibitors and pentasaccharides, which are hoped to reduce the use of heparins and the occurrence of HIT.

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

    PubMed Central

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

    2012-01-01

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

  8. Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP)

    PubMed Central

    Zufferey, Anne; Kapur, Rick; Semple, John W.

    2017-01-01

    Immune thrombocytopenia (ITP) is a complex autoimmune disease characterized by low platelet counts. The pathogenesis of ITP remains unclear although both antibody-mediated and/or T cell-mediated platelet destruction are key processes. In addition, impairment of T cells, cytokine imbalances, and the contribution of the bone marrow niche have now been recognized to be important. Treatment strategies are aimed at the restoration of platelet counts compatible with adequate hemostasis rather than achieving physiological platelet counts. The first line treatments focus on the inhibition of autoantibody production and platelet degradation, whereas second-line treatments include immunosuppressive drugs, such as Rituximab, and splenectomy. Finally, third-line treatments aim to stimulate platelet production by megakaryocytes. This review discusses the pathophysiology of ITP and how the different treatment modalities affect the pathogenic mechanisms. PMID:28208757

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

    SciTech Connect

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

    1994-02-01

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

  10. Severe steroid-resistant thrombocytopenia secondary to cytomegalovirus infection in an immunocompetent adult.

    PubMed

    Sugioka, Takashi; Kubota, Yasushi; Wakayama, Kazuo; Kimura, Shinya

    2012-01-01

    Severe thrombocytopenia secondary to cytomegalovirus (CMV) infection is rare in immunocompetent hosts. We describe a case of severe thrombocytopenia secondary to CMV infection in an immunocompetent 30-year-old man who presented with pyrexia and bleeding tendency. A diagnosis of immune thrombocytopenia (ITP) was made following hematological and serological testing, and bone marrow aspiration. Acute CMV infection was confirmed by serological testing, antigenemia, and detection of CMV-DNA. Corticosteroid therapy was ineffective and intravenous immunoglobulin (IVIG) was therefore administered. This resulted in immediate recovery of the platelet count and cessation of nasal bleeding. Early IVIG administration should be considered in steroid-resistant cases.

  11. Romiplostin may revert the thrombocytopenia in graft-versus-host disease.

    PubMed

    Ruiz-Delgado, Guillermo J; Lutz-Presno, Julia; Ruiz-Argüelles, Guillermo J

    2011-03-01

    The thrombocytopenia ensuing during acute graft-versus-host disease (GVHD) is multifactorial and may significantly compromise the prognosis of the patient; non-immune persistent thrombocytopenia has been considered as an adverse prognostic factor in GVHD. We describe here the case of a 10-year-old girl who developed steroid-refractory thrombocytopenia and who responded promptly to the subcutaneous delivery of romiplostin. To the best of our knowledge, this is the first description of the usefulness of the peptibody in the setting of GVHD.

  12. 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.

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

    PubMed Central

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

    2014-01-01

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

  14. Anticoagulation with Bivalirudin during Deep Hypothermic Circulatory Arrest in a Patient with Heparin-Induced Thrombocytopenia

    PubMed Central

    Pericleous, Agamemnon; Fitzmaurice, Mary; Caldwell, Constance; Natividad, Kris; Plestis, Konstadinos A.

    2014-01-01

    Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia. PMID:25593533

  15. Anticoagulation with bivalirudin during deep hypothermic circulatory arrest in a patient with heparin-induced thrombocytopenia.

    PubMed

    Pericleous, Agamemnon; Sadek, Mostafa; Fitzmaurice, Mary; Caldwell, Constance; Natividad, Kris; Plestis, Konstadinos A

    2014-12-01

    Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia.

  16. Guillain-Barré syndrome with associated thrombocytopenia: prompt response to combined corticosteroid and immunoglobulin treatment.

    PubMed

    Corbanese, U; Martinuzzi, A; Possamai, C; Romeo, G; Possamai, G; Trubian, L

    1998-02-01

    We report a case of Guillain-Barré syndrome (GBS), requiring prolonged mechanical ventilation, associated at its presentation with thrombocytopenia, in a 50-year-old woman. She was treated with immunoglobulin, and short-term corticosteroids for thrombocytopenia. In spite of the severe presentation we observed a very good and rapid recovery, which could have been determined by the therapeutic association. The incidence of thrombocytopenia in GBS patients could be underestimated, and should be kept in mind in order to avoid hemorrhagic complications.

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

    PubMed

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

    2013-01-01

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

  18. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia--a case report.

    PubMed

    Dickinson, Brian P; De Ugarte, Daniel A; Reil, Todd D; Beseth, Bryce D; Lawrence, Peter F

    2006-01-01

    Heparin use, both prophylactically and therapeutically, is prevalent among hospitalized patients. Patients on heparin may develop a thrombocytopenia that is self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. The authors present a case report of heparin-induced thrombocytopenia in a patient who underwent aortic arch and aortic valve replacement that resulted in bilateral above-knee amputations. The patient developed limb ischemia related to heparin-associated thrombosis, but had a delay in antibody seroconversion. Early and accurate diagnosis of heparin-induced thrombocytopenia requires a high clinical suspicion and may be present despite the absence of serum antibodies.

  19. Usefulness of thrombocytopenia at admission as a prognostic marker in native valve left-sided infective endocarditis.

    PubMed

    Ferrera, Carlos; Vilacosta, Isidre; Fernández, Cristina; López, Javier; Sarriá, Cristina; Olmos, Carmen; Vivas, David; Sáez, Carmen; Sánchez-Enrique, Cristina; Ortiz, Carlos; San Román, José Alberto

    2015-04-01

    In-hospital mortality of patients with infective endocarditis (IE) remains exceedingly high. Quick recognition of parameters accurately identifying high-risk patients is of paramount importance. The objective of this study was to analyze the incidence and severity of thrombocytopenia at presentation and its prognostic impact in patients with native valve left-sided IE. We studied a cohort of 533 consecutive episodes of native valve left-sided IE prospectively recruited. We distinguished 2 groups: group I (n = 175), episodes who had thrombocytopenia at admission, and group II (n = 358) gathered all the episodes who did not. Thrombocytopenia at admission was defined as a platelet count of <150,000/μl. No differences were found in the need for surgery, but in-hospital mortality was significantly higher in patients with thrombocytopenia (p <0.001). Mortality rate was associated with the degree of thrombocytopenia (p <0.001). In the multivariable analysis, thrombocytopenia at admission was an independent predictor of higher mortality (p = 0.002). A synergistic interaction between thrombocytopenia and Staphylococcus aureus on mortality risk was also observed (p = 0.04). In conclusion, thrombocytopenia at admission is an early risk marker of increased mortality in patients with native valve left-sided IE. Mortality rates increased with increasing severity of thrombocytopenia. Thrombocytopenia at admission should be used as an early marker for risk stratification in patients with native valve IE to identify those at risk of complicated in-hospital evolution and increased mortality.

  20. Acute immune-mediated thrombocytopenia due to oxaliplatin administration: a case report.

    PubMed

    Pietrantonio, Filippo; Di Bartolomeo, Maria; Buzzoni, Roberto; Bajetta, Emilio

    2010-01-01

    Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

  1. 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

  2. Detection of Antileukocytic Antibodies in Blood Serum using Lymphocytes and Latex Microspheres Carrying HLA-Antigens upon Alloimmunization of Women with Recurrent Pregnancy Loss.

    PubMed

    Stepanova, E O; Nikolaeva, M A; Golubeva, E L; Vtorushina, V V; Van'ko, L V; Khodzhaeva, Z S; Krechetova, L V

    2016-03-01

    Anti-HLA-antibodies were detected using cross-reaction of blood serum with allogenic T and B cells and latex microspheres coated with HLA-I and HLA-II antigens. HLA+ and HLA-sera obtained from women before and after allogeneic immunization were tested. The results obtained by these methods significantly differed. The test with latex microspheres detected antibodies to HLA-I and HLA-II antigens with high sensitivity and specificity and can be used for assessment of clinical significance of alloantibody detection when using alloimmunization in the therapy of gestation disorders.

  3. 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

  4. Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children.

    PubMed

    Gesundheit, B; Cividalli, G; Freeman, A; Yatziv, S; Koren, G; Baruchel, S

    2001-05-01

    Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.

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

    PubMed

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

    2016-03-01

    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 × 10/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.

  6. 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.

  7. 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

  8. 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.

  9. Low-level light treatment ameliorates immune thrombocytopenia

    PubMed Central

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

    2016-01-01

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

  10. 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.

  11. State of the art - how I manage immune thrombocytopenia.

    PubMed

    Cooper, Nichola

    2017-03-10

    The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed.

  12. The effect of thrombocytopenia on dermal wound healing.

    PubMed

    Szpaderska, Anna M; Egozi, Eric I; Gamelli, Richard L; DiPietro, Luisa A

    2003-06-01

    The immediate appearance of platelets in wounds and the ability of platelets to release growth factors suggest that platelets are an important trigger of the tissue repair process. To examine the effect of systemic thrombocytopenia on both the inflammatory and proliferative aspects of wound healing, adult mice were rendered thrombocytopenic by intraperitoneal administration of a rabbit antimouse platelet serum. Full-thickness excisional dermal wounds were prepared and analyzed for inflammatory cell content, growth factor production, reepithelialization, collagen synthesis, and angiogenesis at multiple time points after injury. Compared to control mice, thrombocytopenic mice exhibited significantly altered wound inflammation. Wounds of thrombocytopenic mice contained significantly more macrophages and T cells, yet exhibited neutrophil content similar to wounds from control mice. Surprisingly, thrombocytopenic mice exhibited no delay in the reparative aspects of wound healing. The rate of wound reepithelialization, collagen synthesis, and angiogenesis was nearly identical for thrombocytopenic and control mice. Analysis of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor beta1, keratinocyte growth factor, and epidermal growth factor revealed no difference in the levels of these growth factors in the wounds of control and thrombocytopenic mice. Taken together, the results suggest that the presence of platelets may influence wound inflammation, but that platelets do not significantly affect the proliferative aspects of repair, including wound closure, angiogenesis, and collagen synthesis.

  13. Role of Laparoscopic Splenectomy in Elderly Immune Thrombocytopenia

    PubMed Central

    Giudice, Valentina; Rosamilio, Rosa; Serio, Bianca; Di Crescenzo, Rosa Maria; Rossi, Francesca; De Paulis, Amato; Pilone, Vincenzo

    2016-01-01

    Abstract The management of older patients with chronic primary immune thrombocytopenia (ITP) is still very challenging because of the fragility of older patients who frequently have severe comorbidities and/or disabilities. Corticosteroid-based first-line therapies fail in most of the cases and patients require a second-line treatment, choosing between rituximab, thrombopoietin-receptor agonists and splenectomy. The choice of the best treatment in elderly patients is a compromise between effectiveness and safety and laparoscopic splenectomy may be a good option with a complete remission rate of 67% at 60 months. But relapse and complication rates remain higher than in younger splenectomized ITP patients because elderly patients undergo splenectomy with unfavorable conditions (age >60 year-old, presence of comorbidities, or multiple previous treatments) which negatively influence the outcome, regardless the hematological response. For these reasons, a good management of concomitant diseases and the option to not use the splenectomy as the last possible treatment could improve the outcome of old splenectomized patients. PMID:28352821

  14. Long-term complications of splenectomy in adult immune thrombocytopenia

    PubMed Central

    Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

    2016-01-01

    Abstract The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5–528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13–14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP. PMID:27902585

  15. [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.

  16. 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.

  17. 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

  18. 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.

  19. Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte-specific reporter line in zebrafish.

    PubMed

    Lin, Q; Zhang, Y; Zhou, R; Zheng, Y; Zhao, L; Huang, M; Zhang, X; Leung, A Y H; Zhang, W; Zhang, Y

    2016-11-29

    Mutations in the human myeloproliferative leukemia (MPL) protein gene are known to cause congenital amegakaryocytic thrombocytopenia (CAMT). The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. Here, by using the TALEN (transcription activator-like effector nuclease) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl lead to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult hematopoietic stem/progenitor cells. We further demonstrated that thrombocytopenia in mpl mutant zebrafish was caused by impaired Tpo/Mpl/Jak2 signaling, resulting in reduced proliferation of thrombocyte precursors. These results indicate that mpl mutant zebrafish develop thrombocytopenia resembling the human CAMT. To utilize fully zebrafish to study thrombocyte biology and thrombocytopenia disorders, we generated a transgenic reporter line Tg(mpl:eGFP)smu4, in which green fluorescent protein (GFP) expression was driven by the mpl promoter. Detailed characterization of Tg(mpl:eGFP)smu4 fish confirmed that the thrombocyte lineage was specifically marked by GFP expression. In conclusion, we generated the first transmissible congenital thrombocytopenia zebrafish model mimicking human CAMT and a thrombocyte-specific transgenic line. Together with Tg(mpl:eGFP)smu4, mpl mutant zebrafish provide a useful tool for drug screening and study of thrombocytopoiesis.Leukemia advance online publication, 29 November 2016; doi:10.1038/leu.2016.320.

  20. 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

  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. 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.

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

    PubMed

    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."

  4. Antiphospholipid Syndrome in a Pregnant Female Presenting with Severe Thrombocytopenia and Bleeding

    PubMed Central

    Mahajan, Kunal; Katyal, Virender; Arya, Suvrat; Shrama, Meha

    2015-01-01

    The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients, which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk is poorly characterized. The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. We present such a pregnant lady with history of recurrent pregnancy losses who presented with severe thrombocytopenia and bleeding manifestations, who was subsequently diagnosed to have antiphospholipid antibody syndrome. She was initially managed with steroids and when her platelet counts improved, antithrombotic therapy was started. She delivered an uneventful and successful pregnancy outcome without any complications during follow-up. PMID:25722728

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

    PubMed Central

    2014-01-01

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

  6. Polyethylene glycol modification of adenovirus reduces platelet activation, endothelial cell activation, and thrombocytopenia.

    PubMed

    Hofherr, Sean E; Mok, Hoyin; Gushiken, Francisca C; Lopez, Jose A; Barry, Michael A

    2007-09-01

    Thrombocytopenia is one of the complications for in vivo administration of adenovirus serotype 5 (Ad5) vectors after intravenous injection. In this paper, we investigated the mechanism of Ad5-induced thrombocytopenia and how these effects are attenuated by polyethylene glycol (PEG) modification of Ad5 (Ad-PEG). After intravenous injection, accelerated platelet loss was observed in Ad-injected mice but not in their Ad-PEG-injected counterparts. This platelet loss induced by Ad5 corresponded with increases in coagulation D-dimer levels, splenomegaly, and, later, production of megakaryocytes in the bone marrow. In contrast, these responses were blunted or ablated after injection of Ad-PEG. Ad5 activated both platelets and endothelial cells directly in vitro as evidenced by induction of P-selectin and the formation of von Willebrand factor-platelet strings and in vivo as evidenced by the induction of E-selectin messenger RNA. PEGylation blunted these observed activations. These data suggest that Ad5 may induce thrombocytopenia by direct activation of endothelial cells in addition to its direct effects on platelets. This link provides an important clue for the understanding of the mechanisms of thrombocytopenia associated with Ad5. Given that PEGylation blunted interactions of Ad with platelets and endothelial cells, reduced D-dimer formation, reduced thrombocytopenia, and reduced splenomegaly, these data suggest that this simple vector modification may have utility to improve the safety of Ad vectors for human gene therapy.

  7. Antiplatelet drug induced isolated profound thrombocytopenia in interventional cardiology: a review based on individual case reports.

    PubMed

    Höchtl, Thomas; Pachinger, Linda; Unger, Gerhard; Geppert, Alexander; Wojta, Johann; Harenberg, Job; Huber, Kurt

    2007-08-01

    A combination antithrombotic and antiplatelet therapy with clopidogrel, aspirin, glycoprotein IIb/IIIa receptor inhibitors and heparins is routinely used as adjunct therapy in patients undergoing percutaneous coronary intervention (PCI). As all substances inhibit platelet function, bleeding and thrombocytopenia may occur. We report on three patients who developed isolated profound thrombocytopenia (platelet count of < 20,000/mm(3)) within 24 h after initiation of combination antiplatelet and antithrombotic therapy during a 1 year observation period in 443 consecutive patients undergoing PCI and stent implantation. The data from our cardiology unit revealed an incidence of an isolated profound thrombocytopenia in 0.7% of all patients on combination antithrombotic therapy and in 1.5% of patients with GPIIb/IIIa-blockers. In all three cases with isolated profound thrombocytopenia GPIIb/IIIa-blockers were found to be the causative agents. Negative results of HIT-assays excluded heparin induced thrombocytopenia type II. Despite the extremely low platelet count no severe bleeding was observed and in all cases platelet counts normalized within 3-4 days without specific interventions except discontinuation of the responsible agent. These findings are discussed in conjunct with an overview of the recent literature.

  8. Acute Severe Thrombocytopenia Occurring After Administration of Eptifibatide Postpones Emergent Coronary Artery Surgery

    PubMed Central

    Boettcher, Brent T.; Olund, Timothy J.; Pagel, Paul S.

    2016-01-01

    Introduction Eptifibatide is a platelet glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonist that inhibits fibrinogen binding to the activated GP IIb/IIIa site and prevents platelet-platelet interaction and clot formation. GP IIb/IIIa inhibitors improve outcome in patients undergoing percutaneous coronary intervention for acute coronary syndrome. Thrombocytopenia is a complication of GP IIb/IIIa inhibitors, but severe thrombocytopenia is unusual. Most reported cases of severe thrombocytopenia after eptifibatide occurred in patients with acute coronary syndrome. The authors describe a patient who developed acute profound thrombocytopenia after receiving eptifibatide before emergent coronary artery bypass graft surgery. Case Presentation A 67-year-old man with a normal platelet count (220 K/uL) developed atrial fibrillation, left bundle branch block, and respiratory insufficiency consistent with acute coronary syndrome two days after colectomy. He received eptifibatide during cardiac catheterization, where three-vessel coronary artery disease was encountered. Emergent coronary artery surgery was planned, but the platelet count before surgery was 2 K/uL. Eptifibatide was discontinued, surgery was postponed, and acute coronary syndrome was treated with intraaortic balloon counterpulsation. Conclusions The authors describe the second reported case of eptifibatide-induced severe thrombocytopenia associated with cardiac surgery. In this case, discontinuation of eptifibatide and transfusion of apheresis platelets increased the platelet count (137 K/uL) the following day, and the patient subsequently underwent successful coronary artery surgery using cardiopulmonary bypass. PMID:27843778

  9. KIR2DS2 as predictor of thrombocytopenia secondary to pegylated interferon-alpha therapy.

    PubMed

    Rivero-Juarez, A; Gonzalez, R; Frias, M; Manzanares-Martín, B; Rodriguez-Cano, D; Perez-Camacho, I; Gordon, A; Cuenca, F; Camacho, A; Pineda, J A; Peña, J; Rivero, A

    2016-03-15

    Our aim was to evaluate the killer cell immunoglobulin-like receptors (KIRs) as a marker for the development of thrombocytopenia secondary to Peg-interferon (IFN) therapy in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. Patients were naive to HCV treatment, receiving a first course of Peg-IFN/Ribavirin combination therapy. Total platelet count (cells ml(-1)) was determined at each visit, determining platelet decline from baseline to weeks 1, 2, 4, 8 and 12 after starting therapy. The end point of the study was development of thrombocytopenia, defined as a platelet count of <1 50 000 cells ml(-1). Fifty-eight HIV/HCV co-infected patients were included in the study, of whom 20 (34.4%) developed thrombocytopenia. The absence of KIR2DS2 was associated with higher and faster rate of thrombocytopenia (54.2% vs 22.5%; P=0.012; 6.6 vs 10.3 weeks; P=0.008). The absence of KIR2DS2 was associated with a greater decline in platelet count and development of thrombocytopenia during Peg-IFN treatment in HIV/HCV co-infected patients.The Pharmacogenomics Journal advance online publication, 15 March 2016; doi:10.1038/tpj.2016.19.

  10. Antiphospholipid syndrome in a pregnant female presenting with severe thrombocytopenia and bleeding.

    PubMed

    Mahajan, Kunal; Katyal, Virender; Arya, Suvrat; Shrama, Meha

    2015-01-01

    The antiphospholipid antibody syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients, which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk is poorly characterized. The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. We present such a pregnant lady with history of recurrent pregnancy losses who presented with severe thrombocytopenia and bleeding manifestations, who was subsequently diagnosed to have antiphospholipid antibody syndrome. She was initially managed with steroids and when her platelet counts improved, antithrombotic therapy was started. She delivered an uneventful and successful pregnancy outcome without any complications during follow-up.

  11. Thrombocytopenia in MDS: epidemiology, mechanisms, clinical consequences and novel therapeutic strategies.

    PubMed

    Li, W; Morrone, K; Kambhampati, S; Will, B; Steidl, U; Verma, A

    2016-03-01

    Thrombocytopenia is commonly seen in myelodysplastic syndrome (MDS) patients, and bleeding complications are a major cause of morbidity and mortality. Thrombocytopenia is an independent factor for decreased survival and has been incorporated in newer prognostic scoring systems. The mechanisms of thrombocytopenia are multifactorial and involve a differentiation block of megakaryocytic progenitor cells, leading to dysplastic, hypolobated and microscopic appearing megakaryocytes or increased apoptosis of megakaryocytes and their precursors. Dysregulated thrombopoietin (TPO) signaling and increased platelet destruction through immune or nonimmune mechanisms are frequently observed in MDS. The clinical management of patients with low platelet counts remains challenging and approved chemotherapeutic agents such as lenalidomide and azacytidine can also lead to a transient worsening of thrombocytopenia. Platelet transfusion is the only supportive treatment option currently available for clinically significant thrombocytopenia. The TPO receptor agonists romiplostim and eltrombopag have shown clinical activity in clinical trials in MDS. In addition to thrombopoietic effects, eltrombopag can inhibit leukemic cell proliferation via TPO receptor-independent effects. Other approaches such as treatment with cytokines, immunomodulating drugs and signal transduction inhibitors have shown limited activity in selected groups of MDS patients. Combination trials of approved agents with TPO agonists are ongoing and hold promise for this important clinical problem.

  12. 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

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

    PubMed

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

    2014-11-01

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

  14. Detection of antiplatelet antibody in serum and on megakaryocytes of dogs with autoimmune thrombocytopenia.

    PubMed

    Joshi, B C; Jain, N C

    1976-06-01

    Blood and bone marrow samples from 13 thrombocytopenic dogs were examined to determine whether immunologic thrombocytopenia existed. Antiplatelet antibody was detected in serum of 8 of the dogs by platelet factor 3 test or its modification. Moderate to strong immunofluorescence of megakaryocytes was noticed in bone marrow smears stained with rabbit anticanine globulin conjugated with fluorescin isothiocyanate. Negative results were obtained with serum and bone marrow samples collected from 6 of the dogs during therapy for autoimmune thrombocytopenia. Clinical and laboratory findings varied in individual patients with circulating antiplatelet antibodies. Thrombocytopenia was present in all the dogs, with platelet counts ranging from less than 3,000 to 20,000/mu1 of blood. Signs of bleeding in tissues and body cavities were present in all dogs, but anemia was evidenced in only 3 dogs. Differential leukocyte counts were variable. Morphologic abnormalities such as vacuolation and reduced or absence of granulation of the cytoplasm and nuclear fragmentation were seen in some megakaryocytes.

  15. [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.

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

    PubMed

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

    2015-09-01

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

  17. 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

  18. Modulation of alloimmune response by commensal gut microbiota and potential new avenues to influence the outcome of allogeneic transplantation by modification of the 'gut culture'.

    PubMed

    Kanangat, S

    2017-02-01

    Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses. In humans, these are commonly referred to as human leucocyte antigens class I/II-HLA I/II). The class III region, the gamma region in the MHC complex, is mostly associated with regulation of immune responses along with genes associated with complement activation. The adaptive immune responses are orchestrated by T and B cells that are tuned to respond to antigens that are normally foreign to the body, because these cells are educated to avoid self-antigens by a process of thymic education and selection of the T cells that are mostly non-self-reactive which also helps the B cells in eliciting specific immune responses to non-self-antigens. A by-product of this is the ability of the T and B cells to elicit strong immune responses to foreign HLA/MHC (alloimmune response), which developed into the field of histocompatibility testing for allogeneic transplantation of stem cells and organs. Now, we are beginning to learn that such alloimmune responses can be influenced by the microbiota that symbiotically live in our body especially on the mucosal surfaces and on the skin. This review deals with new and emerging data on how the commensal mucosal and skin microbiota influence the immune homeostasis, and how manipulating the commensal microbiota of the mucosa and skin could influence the survival and long-term functions of the allografts. Also, alterations of the microbiota by the inevitable

  19. 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

  20. Thrombocytopenia in Plasmodium falciparum, Plasmodium vivax and mixed infection malaria: a study from Bikaner (Northwestern India).

    PubMed

    Kochar, Dhanpat Kumar; Das, Ashis; Kochar, Abhishek; Middha, Sheetal; Acharya, Jyoti; Tanwar, Gajanand Singh; Gupta, Anjana; Pakalapati, Deepak; Garg, Shilpi; Saxena, Vishal; Subudhi, Amit Kumar; Boopathi, P A; Sirohi, Parmendra; Kochar, Sanjay Kumar

    2010-01-01

    The occurrence, relation and magnitude of thrombocytopenia in different species of malaria are not clearly defined. This study included 1,064 patients admitted with malaria to study thrombocytopenia (platelet count <150,000 /cumm) in Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) mono infection and mixed infection (Pf + Pv). The species diagnosis was done by peripheral blood film (PBF) and rapid diagnostic test (RDT). Validation by polymerase chain reaction (PCR) was done only in patients with severe thrombocytopenia (platelet count <20,000 /cumm). The breakup of patients was 525 (49.34%) Pf, 460 (43.23%) Pv and 79 (7.42%) mixed malaria (Pf + Pv). Thrombocytopenia was observed in 24.6% (262/1064) patients. The risk was greatest in the mixed infections in comparison to monoinfection individually (43.04% [34/79]; mixed vs Pv monoinfection: Odds Ratio [OR] = 1.675 [95% Confidence Interval (CI) 1.029-2.726], p < 0.0366; mixed vs Pf monoinfection: OR=3.911 [95% CI 2.367-6.463], p < 0.0001). Pv monoinfection (31.09% [143/460]) had greater risk compared to Pf monoinfection (16.19% [85/525]; OR = 2.335 [95% CI 1.722-3.167], p < 0.0001). The occurrence of severe thrombocytopenia was also higher in Pv monoinfection (18.18% [26/143]) in comparison to either Pf monoinfection (10.59% [9/85], OR = 1.877 (95% CI 0.834-4.223)) or mixed infection (11.76% [4/34]; OR = 1.667 (95% CI 0.540-5.142) but this association was statistically not significant. Six patients (3 Pv, 2 Pf and 1 mixed) developed severe epistaxis requiring platelet transfusion. There was no relation between parasite density and platelet count as many patients with severe thrombocytopenia had parasite density similar to patients without thrombocytopenia. We found that the association of thrombocytopenia was statistically more significant with P. vivax monoinfection as compared to P. falciparum.

  1. Inflammatory abdominal aortic aneurysm followed by disseminated intravascular coagulation and immune thrombocytopenia.

    PubMed

    Machida, Hisanori; Kobayashi, Makoto; Taguchi, Hirokuni

    2002-11-01

    A 71-year-old man was diagnosed as having an abdominal aortic aneurysm when he was treated for idiopathic interstitial pneumonia (IIP). Three years later, he developed severe thrombocytopenia and had disseminated intravascular coagulation (DIC) that was associated with the inflammatory abdominal aortic aneurysm (IAAA). The coagulation abnormalities were corrected by low-molecular weight heparin, however the platelet count remained low. Bone marrow showed normocellularity with an increase of immature and mature forms of megakaryocytes. Platelet-associated IgG level was high. These findings suggested that the patient had severe thrombocytopenia caused by unusual complications of immune thrombocytopenic purpura and IAAA-associated DIC.

  2. Recurrent spontaneous subdural hematoma secondary to immune thrombocytopenia in a patient with overlap syndrome.

    PubMed

    Goh, K G; Ong, S G

    2015-01-01

    Patients with autoimmune connective tissue disease may manifest as overlap syndrome with features of systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis and myositis. Those presenting with active SLE can present with immune thrombocytopenia (IT) and may be complicated with subdural hematoma which, though rare, is potentially life-threatening. We report here a patient with overlap syndrome who had recurrent spontaneous subdural hematoma due to severe thrombocytopenia which did not respond to corticosteroids and azathioprine. Her platelet count became normal with three doses of low-dose intravenous cyclophosphamide (IV CYC) given at 3-weekly intervals. She remained in remission with maintenance therapy with azathioprine.

  3. Regulation of platelet heterogeneity: effects of thrombocytopenia on platelet volume and density.

    PubMed

    Corash, L; Mok, Y; Levin, J; Baker, G

    1990-03-01

    We have examined the effects of variable degrees of acute thrombocytopenia on platelet levels, mean platelet volume (MPV), and buoyant density after induction of thrombocytopenia by platelet antiserum (PAS) in mice with or without spleens. Mice were studied serially 10-16, 36, 48, 60-64, 84, 108, 144, 180, 228, 276, 348-360, 372, and 516 h after PAS treatment. MPV and platelet count (PC) x 10(6)/microliters for normal intact mice (n = 136) were 4.7 +/- 0.3 fl (SD) and 1.69 +/- 0.52 (SD), respectively. Twelve hours after PAS-induced severe thrombocytopenia (PC less than 0.05 x 10(6)/microliters), MPV increased significantly (p less than 0.01) to 6.4 fl, was maximal at 36 h (8.2 fl), remained elevated until 144 h following PAS treatment, and then returned to normal. Platelet density decreased significantly (p less than 0.05) 64 h after PAS treatment and returned to normal at 144 h. Hematocrits of repeatedly bled intact control mice decreased from 45% to 30%, accompanied by thrombocytosis (maximal PC 2.24 x 10(6)/microliters) without significant changes in either MPV or platelet density. Moderate thrombocytopenia (PC 0.1-0.2 x 10(6)/microliters) in intact mice produced significantly (p less than 0.05) increased MPV, at 5.7 fl 12 h after PAS treatment, with a peak MPV of 7.6 fl (p less than 0.001) at 36 h; MPV returned to normal at 84 h. Platelet density decreased (p less than 0.001) 12 h after PAS treatment and returned to baseline at 228 h. Control splenectomized mice (n = 185) had an MPV of 5.0 fl +/- 0.7 fl and a PC of 2.14 +/- 0.6 x 10(6)/microliters. Comparably severe and moderate thrombocytopenia in splenectomized mice produced alterations in platelet count, MPV, and density similar to those in intact mice, although maximal MPV and the degree of rebound thrombocytosis after severe thrombocytopenia were more marked in splenectomized mice. In response to reduction of the platelet mass in both intact and splenectomized mice, MPV increased in proportion to the

  4. Immune Thrombocytopenia as a Presenting Manifestation of Tuberculosis- Challenge in Resource Constraint Settings

    PubMed Central

    Sahu, Kamal Kant; Dhir, Varun; Singh, Surjit

    2016-01-01

    Tuberculosis can infect almost any organ of our body leading to various presentations and its complication. Various haematological manifestations of tuberculosis are well known. But isolated thrombocytopenia and Immune Thrombocytopenia (ITP) in patients with tuberculosis is very rare. Here we report a case of young man who presented with acute onset of bleeding manifestations in the form of epistaxis and macroscopic haematuria with platelets count of 5×109/L. The patient was diagnosed to have ITP along with clinical and radiological evidence of active tuberculosis. The patient was treated with Anti Tubercular Therapy (ATT) along with Intravenous (IV) pulse of methyl prednisolone followed by tapering dose of oral prednisolone. PMID:27891377

  5. 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.

  6. Severe Thrombocytopenia and Acute Cytomegalovirus Colitis during Primary Human Immunodeficiency Virus Infection

    PubMed Central

    Furuhata, Masanori; Yanagisawa, Naoki; Nishiki, Shingo; Sasaki, Shugo; Suganuma, Akihiko; Imamura, Akifumi; Ajisawa, Atsushi

    2016-01-01

    We herein report the case of a 25-year-old man who was referred to our hospital due to acute cytomegalovirus (CMV) colitis. The initial blood tests showed that the patient had concurrent primary human immunodeficiency virus (HIV) infection and severe thrombocytopenia. Raltegravir-based antiretroviral therapy (ART) was initiated without the use of ganciclovir or corticosteroids and resulted in a rapid clinical improvement. Platelet transfusions were only necessary for a short period, and subsequent colonoscopy revealed a completely healed ulcer. This case implies that ART alone could be effective for treating severe thrombocytopenia during primary HIV and CMV coinfection. PMID:27980271

  7. 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.

  8. 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.

  9. Thrombocytopenia in cirrhosis: Impact of fibrinogen on bleeding risk

    PubMed Central

    Thakrar, Sonali V; Mallett, Susan V

    2017-01-01

    robust assessment of bleeding-risk in thrombocytopenia and cirrhosis. PMID:28293381

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

    PubMed

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

    2006-12-01

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

  11. Genetic homogeneity but IgG subclass-dependent clinical variability of alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies.

    PubMed

    Vivarelli, Marina; Emma, Francesco; Pellé, Thimothée; Gerken, Christopher; Pedicelli, Stefania; Diomedi-Camassei, Francesca; Klaus, Günter; Waldegger, Siegfried; Ronco, Pierre; Debiec, Hanna

    2015-03-01

    Alloimmune antenatal membranous nephropathy (MN) during pregnancy results from antibodies produced by a neutral endopeptidase (NEP)-deficient mother. Here we report two recent cases that provide clues to the severity of renal disease. Mothers of the two children had circulating antibodies against NEP showing the characteristic species-dependent pattern by immunofluorescence on kidney slices. A German mother produced predominantly anti-NEP IgG4 accompanied by a low amount of IgG1. Her child recovered renal function within a few weeks. In sharp contrast, an Italian mother mainly produced complement-fixing anti-NEP IgG1, which also inhibits NEP enzymatic activity, whereas anti-NEP IgG4 has a weak inhibitory potency. Her child was dialyzed for several weeks. A kidney biopsy performed at 12 days of age showed MN, ischemic glomeruli, and arteriolar and tubular lesions. A second biopsy performed at 12 weeks of age showed aggravation with an increased number of collapsed capillary tufts. Both mothers were homozygous for the truncating deletion mutation 466delC and were thus NEP deficient. The 466delC mutation, identified in three previously described families, suggests a founder effect. Because of the potential severity of alloimmune antenatal MN, it is essential to identify families at risk by the detection of anti-NEP antibodies and NEP antigen in urine. On the basis of the five families identified to date, we propose an algorithm for the diagnosis of the disease and the prevention of complications.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Clinical and laboratory characteristics of severe fever with thrombocytopenia syndrome in Chinese patients.

    PubMed

    Weng, Yali; Chen, Nian; Han, Yaping; Xing, Yiping; Li, Jun

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) associated with severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging infectious disease. 12 patients with severe fever with thrombocytopenia syndrome in our study were presented mainly with fever and severe malaise. The clinical manifestations typically became worse on the 6th or 7th day. The average fever time is 9.11 ± 1.54 days. Most of them had multiorgan dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of white blood cells (WBC), platelets (PLT) and serum Ca++, while increase of aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). CD3+CD4+ were significantly decreased, while CD3-CD56+ were significantly increased, whereas CD3+CD8+ were constantly elevated throughout the disease course. Ten to 14 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities. These results indicate that severe fever with thrombocytopenia syndrome has an acute onset and self-limited course. It is a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests is consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to better understand this disease and guide the clinical treatment.

  15. Chronic Subdural Hematoma Associated with Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection in Cameroon

    PubMed Central

    Luchuo, Engelbert Bain; Teuwafeu, Denis; Nepetsoun, Ines; Nkouonlack, Cyrille

    2017-01-01

    Hematological abnormalities including thrombocytopenia are common in patients living with HIV infection. Patients with HIV infection related thrombocytopenia present generally with only minor bleeding problems. But cases of subdural hematoma are very rare. A 61-year-old female with a history of HIV infection of 9 years' duration presented with a 3-month history of generalized headache associated with visual blurring and anterograde amnesia. There was no history of trauma or fever. She was treated empirically for cerebral toxoplasmosis for 6 weeks without any improvement of the symptoms. One week prior to admission, she developed weakness of the left side of the body. Clinical examination revealed left-sided hemiparesis. Computed tomography scan of the brain showed a 25 mm chronic right frontoparietotemporal subdural hematoma compressing the lateral ventricle with midline shift. There was no appreciable cerebral atrophy. A complete blood count showed leucopenia and thrombocytopenia at 92,000 cells/mm3. Her CD4-positive cell count was 48 cells/mm3 despite receiving combination antiretroviral therapy for 9 years. A complete blood count analysis suggestive of thrombocytopenia should raise suspicion of possibilities of noninfectious focal brain lesions like subdural hematoma amongst HIV infected patients presenting with nonspecific neurological symptoms. This will enable prompt diagnosis and allow early appropriate intervention. PMID:28168070

  16. Severe Fever with Thrombocytopenia Syndrome in Patients Suspected of Having Scrub Typhus.

    PubMed

    Wi, Yu Mi; Woo, Hye In; Park, Dahee; Lee, Keun Hwa; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon

    2016-11-01

    To determine prevalence of severe fever with thrombocytopenia syndrome in South Korea, we examined serum samples from patients with fever and insect bite history in scrub typhus-endemic areas. During the 2013 scrub typhus season, prevalence of this syndrome among patients suspected of having scrub typhus was high (23.0%), suggesting possible co-infection.

  17. Severe Fever with Thrombocytopenia Syndrome in Patients Suspected of Having Scrub Typhus

    PubMed Central

    Wi, Yu Mi; Woo, Hye In; Park, Dahee; Kang, Cheol-In; Chung, Doo Ryeon; Song, Jae-Hoon

    2016-01-01

    To determine prevalence of severe fever with thrombocytopenia syndrome in South Korea, we examined serum samples from patients with fever and insect bite history in scrub typhus–endemic areas. During the 2013 scrub typhus season, prevalence of this syndrome among patients suspected of having scrub typhus was high (23.0%), suggesting possible co-infection. PMID:27767909

  18. [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.

  19. Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013.

    PubMed

    Yun, Seok-Min; Lee, Wook-Gyo; Ryou, Jungsang; Yang, Sung-Chan; Park, Sun-Whan; Roh, Jong Yeol; Lee, Ye-Ji; Park, Chan; Han, Myung Guk

    2014-08-01

    We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May-October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

  20. Plasmodium vivax malaria presenting with severe thrombocytopenia, cerebral complications and hydrocephalus.

    PubMed

    Harish, Rekha; Gupta, Sanjeev

    2009-05-01

    Two cases of a one and 4 year old child of plasmodium vivax malaria are reported in association with CNS complications. Both presented with encephalopathy and seizures. One had severe thrombocytopenia, massive intracranial bleed and hydrocephalus requiring shunt surgery while the other had gastrointestinal manifestations, encephalopathy and hydrocephalus. Both responded to quinine but are left with sequelae.

  1. 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

  2. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice.

    PubMed

    de Stoppelaar, Sacha F; van 't Veer, Cornelis; Claushuis, Theodora A M; Albersen, Bregje J A; Roelofs, Joris J T H; van der Poll, Tom

    2014-12-11

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median of 5 × 10(9)/L or to 5 to 13 × 10(9)/L by administration of a depleting antibody in mice infected with Klebsiella via the airways. Thrombocytopenia was associated with strongly impaired survival during pneumonia-derived sepsis proportional to the extent of platelet depletion. Thrombocytopenic mice demonstrated PC-dependent enhanced bacterial growth in lungs, blood, and distant organs. Severe thrombocytopenia resulted in hemorrhage at the primary site of infection, but not in distant organs. PCs of 5 to 13 × 10(9)/L were sufficient to largely maintain hemostasis in infected lungs. Thrombocytopenia did not influence lung inflammation or neutrophil recruitment and did not attenuate local or systemic activation of coagulation or the vascular endothelium. PCs <5 × 10(9)/L even resulted in enhanced coagulation and endothelial cell activation, which coincided with increased proinflammatory cytokine levels. In accordance, low PCs in whole blood enhanced Klebsiella-induced cytokine release in vitro. These data suggest that platelets play an important role in host defense to Klebsiella pneumosepsis.

  3. Effect of thrombocytopenia on the efficacy of Photofrin-based photodynamic therapy in vivo

    NASA Astrophysics Data System (ADS)

    de Vree, Wil J. A.; de Bruijn, Henriette S.; Kraak-Slee, Regina G.; Koster, Johan F.; Sluiter, Wim

    2001-01-01

    Neutrophils are indispensable for successful PDT. Recently it has been observed that the administration of anti-thrombocyte antiserum prevents the occlusion of the microvasculature that normally occurs upon Photofrin-based PDT. We hypothesized that this antiserium treatment would increase the therapeutic efficacy by facilitating the accumulation of neutrophils at the lesion. To study this we implanted the isologous rhabdomyosarcoma R-1 subcutaneously into the thigh of WAG/Raj rats, and treated the tumor by interstitial Photofrin-based PDT. We found that the increasing tumor doubling time after PDT under anti-thrombocyte antiserum-induced thrombocytopenia was significantly higher that in normal rats. Strikingly, the increase in tumor doubling time did not differ if thrombocytopenia was induced before or immediately after illumination. At least 1.5 times more neutrophils than normal accumulated into the PDT-treated tumors under thrombocytopenia. If the rats were rendered granulocytopenic by the administration of anti-granulocyte antiserum first followed by anti-thrombocyte antiserum post PDT, this lead to a considerable loss of the thrombocytopenia- dependent gain in the efficacy of PDT. These findings suggest that the increased accumulation of neutrophils into the tumor underlie the enhanced efficacy of PDT and may implicate that under normal clinical conditions the full granulocyte-dependent kill potential is not utilized due to the presence of activated thrombocytes that cause blood flow stasis.

  4. 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.

  5. 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

  6. Prospective testing for drug-dependent antibodies reduces the incidence of thrombocytopenia observed with the small molecule glycoprotein IIb/IIIa antagonist roxifiban: implications for the etiology of thrombocytopenia.

    PubMed

    Seiffert, Dietmar; Stern, Andrew M; Ebling, William; Rossi, Richard J; Barrett, Yu Chen; Wynn, Richard; Hollis, Gregory F; He, Bokang; Kieras, Cathy J; Pedicord, Donna L; Cromley, Debra A; Hua, Tsushung A; Stein, Robert B; Daly, Robert N; Sferruzza, Anthony; Pieniaszek, Henry J; Billheimer, Jeffrey T

    2003-01-01

    Thrombocytopenia is a relatively common side effect observed during glycoprotein (GP) IIb/IIIa antagonist therapy. With the oral antagonist roxifiban, we observed thrombocytopenia, defined as 50% reduction of platelets over predose values or below 90 000/microL (9 x 10(10)/L), with a frequency of 2% (8 of 386). Thrombocytopenia occurred either early (days 2 to 4) or delayed (days 11 to 16). No additional cases were observed with up to 6 months of treatment. Retrospective analysis provided evidence for drug-dependent antibodies (DDABs) to GP IIb/IIIa in 5 of 6 subjects, suggestive of an immune etiology of thrombocytopenia. The hypothesis that excluding patients based on positive DDAB reaction would reduce the frequency of thrombocytopenia was tested. Patients were screened for DDABs during the study qualification period and, overall, 3.9% of the patients were excluded based on pre-existing DDAB concentrations above a statistically defined medical decision limit. An additional 2.6% were excluded based on therapy-related antibody production during the first 2 weeks. With antibody testing, 0.2% of patients (2 of 1044) developed immune-mediated thrombocytopenia. One case developed a rapidly increasing antibody concentration and presented with thrombocytopenia despite discontinuation of roxifiban therapy. The second case was related to a false-negative test result. The frequency of thrombocytopenia was statistically significantly reduced from 2% to 0.2% (P =.0007) comparing nonscreened and screened patients. Testing for DDABs can reduce the frequency of thrombocytopenia in patients treated with roxifiban and, by analogy, other GP IIb/IIIa antagonists. Thus, DDAB testing may be employed to increase the safety of GP IIb/IIIa antagonists.

  7. Heparin-Induced Thrombocytopenia in Contemporary Cardiac Surgical Practice and Experience With a Protocol for Early Identification.

    PubMed

    Sun, Xiumei; Hill, Peter C; Taylor-PaneK, Sharon L; Corso, Paul J; Lindsay, Joseph

    2016-01-15

    This analysis was designed to (1) examine the impact of heparin-induced thrombocytopenia (HIT) on contemporary cardiac surgical practice and (2) describe the results of a protocol designed for early identification of the presence of the immune mechanisms involved. Consecutive patients who underwent cardiac surgery were screened postoperatively for thrombocytopenia. Patients with thrombocytopenia were tested for antiplatelet factor 4 (PF4)/heparin antibodies by ELISA and clinical evidence of thrombosis sought. Demographics, co-morbidities, operative details, and outcomes were abstracted from the departmental registry. Of 14,415 consecutive patients undergoing cardiac surgery, 1,849 patients (13%) had thrombocytopenia. Of them, 277 patients (15%) had PF4/heparin antibodies and 76 patients (4%) had both antibodies and clinical thrombosis. Antibodies were more frequent: (1) in women (p = 0.01), (2) in patients with an increased body mass index (p <0.01), and (3) in patients with clinical heart failure before surgery (p <0.01). Thirty-day mortality was greatest among the 76 patients with the triad of thrombocytopenia, antibodies, and clinical thrombosis (30%). Of the 1,849 patients with thrombocytopenia, the presence of PF4/heparin antibodies was an independent predictor of 30-day mortality (odds ratio 2.09, 95% CI 1.46 to 2.49; p <0.001). HIT remains an infrequent but very serious complication of heparin therapy in contemporary cardiac surgical practice. The possibility that the presence of HIT antibodies in patients with thrombocytopenia independently increases operative mortality deserves further study.

  8. A swine model of acute thrombocytopenia with prolonged bleeding time produced by busulfan

    PubMed Central

    Abe, Tomoyuki; Kono, Shota; Ohnuki, Takahiro; Hishikawa, Shuji; Kunita, Satoshi; Hanazono, Yutaka

    2016-01-01

    Animal models of thrombocytopenia are indispensable for evaluating the in vivo efficacy of hemostatic agents, cryopreserved platelets, and artificial platelets, but no large animal models are available. In this study, we generated a swine model of acute thrombocytopenia with prolonged bleeding times by administering the chemotherapeutic drug busulfan. First, we tested multiple doses of busulfan (4, 6, and 8 mg/kg) in pigs, and found that 6 mg/kg of busulfan is an optimal dose for producing a safe and moderate thrombocytopenia, with a platelet count of less than 30,000/µl. The pigs administered 6 mg/kg of busulfan (n=8) reached half their initial counts at day 7, counts below 30,000/µl at day 12, and their nadirs at day 15 (on average). The minimal platelet count was 14,000/µl. With this dose of busulfan (6 mg/kg), bleeding times were significantly prolonged in addition to the decrease in platelet counts (r=−0.63, P<0.01), while there were no cases of apparent hemorrhage. White blood cell counts were maintained at over 5,000/µl, and there were no infections or other adverse events including anemia or appetite or body weight loss. All pigs were sacrificed on day 16, with subsequent examination showing a significant reduction in cellularity and colony-forming units in the bone marrow, indicating that thrombocytopenia was the result of myelosuppression. In summary, administration with 6 mg/kg of busulfan induces safe and moderate thrombocytopenia with a prolonged bleeding time in swine. PMID:27333841

  9. Relationship between splenic sequestration and thrombocytopenia in Trypanosoma evansi infection in rats.

    PubMed

    Kipper, M; Da Silva, A S; Oliveira, C B; Andretta, I; Paim, F C; da Silva, C B; Leon, R; Corrêa, K; Stainki, D R; Lopes, S T A; Monteiro, S G

    2011-10-01

    Trypanosoma evansi infections in domestic animals are characterized by anemia and thrombocytopenia. The cause of the platelets decrease is unknown, but researchers suggest that thrombocytopenia may result from damage of the bone marrow, reduced survival of platelets, auto-immune thrombocytopenia, disseminated intravascular coagulation and splenic sequestration. Some of these causes have already been tested by our research group and found to be unrelated. Therefore, this study has the objective of testing the hypothesis that splenic sequestration might be responsible for thrombocytopenia in T. evansi-infected rats. A total of 28 rats assigned to four groups were used in the experiment. Group A rats were splenectomized and infected with T. evansi, group B rats were infected with T. evansi, group C rats were splenectomized, but not infected and group D rats were normal controls. Five days post-infection all rats were anesthetized and blood was collected in order to measure the number of circulating platelets, fibrinogen levels, prothrombin time (PT) and activated partial thromboplastin time (aPTT). The spleens of groups B and D were weighed at necropsy. The infected animals (groups A and B) showed a significant reduction in platelets and increased PT and aPTT when compared to negative control groups (groups C and D). Animals from group A showed increased levels of fibrinogen. The mean weight of spleen differed between group B (2.62g) and group D (0.55g). It was concluded that there is no relationship between thrombocytopenia and splenic sequestration in infection by T. evansi.

  10. Acute profound thrombocytopenia associated with readministration of eptifibatide: case report and review of the literature.

    PubMed

    Russell, Kimberly N; Schnabel, Joseph G; Rochetto, Richard P; Tanner, Matthew C

    2009-07-01

    The glycoprotein IIb-IIIa inhibitor eptifibatide has been shown to be beneficial in the treatment of acute coronary syndromes and during percutaneous coronary intervention (PCI). Case reports of acute profound thrombocytopenia have been reported with eptifibatide, yet the true incidence of this reaction is unknown. We describe a 50-year-old woman with severe coronary artery disease who developed acute profound thrombocytopenia after readministration of eptifibatide. Eptifibatide was administered through hospital day 3, when it was discontinued in preparation for coronary angiography and PCI; the drug was restarted on day 5. On hospital day 6, she was noted to have a platelet count below 5 x 10(3)/mm,(3) indicating a profound decrease from a baseline of 456 x 10(3)/mm(3) on admission. Eptifibatide, heparin, vancomycin, and clopidogrel were potential causative agents. Anticoagulation and vancomycin were stopped, and her platelet count increased to 30 x 10(3)/mm(3) on day 7. Subsequent reexposure to heparin and vancomycin yielded no adverse effects. The patient's platelet count increased over the remainder of her hospitalization, and she was discharged home on day 19. Based on clinical presentation and negative heparin platelet factor 4 antibody test, eptifibatide was the most likely cause of thrombocytopenia. Use of the Naranjo adverse drug reaction probability scale indicated that eptifibatide was the probable cause of thrombocytopenia (score of 5); scores of 1 (possible) or 0 (doubtful) were derived with heparin, vancomycin, and clopidogrel. We conducted a literature search and compiled information from published case reports to describe the pattern of onset and recovery of eptifibatide-induced thrombocytopenia. In all patients receiving eptifibatide, routine platelet counts should be monitored at baseline and within 2-6 hours after starting the drug.

  11. Safety analysis of liposomal amphotericin B in adult patients: anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia.

    PubMed

    Shigemi, Akari; Matsumoto, Kazuaki; Ikawa, Kazuro; Yaji, Keiko; Shimodozono, Yoshihiro; Morikawa, Norifumi; Takeda, Yasuo; Yamada, Katsushi

    2011-11-01

    Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has been shown to have a better safety profile than both the deoxycholate and lipid complex forms of amphotericin B; however, the frequency of major side effects is still unclear. Thus, the aim of the present study was to assess retrospectively the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia as well as the relationship between daily dose of L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre-treatment) and anaemia were observed in 7 and 10 of 21 adult patients, respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of L-AmB that are estimated to cause side effects of a low RBC count, anaemia and thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day, respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of total bilirubin, γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7, 8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9 patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not caused in a dose-dependent manner. In conclusion, the present analyses showed that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult patients. It is important to pay attention to causing anaemia and thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and >3.0mg/kg/day, respectively.

  12. Surveillance for thrombocytopenia in persons infected with HIV: results from the multistate Adult and Adolescent Spectrum of Disease Project.

    PubMed

    Sullivan, P S; Hanson, D L; Chu, S Y; Jones, J L; Ciesielski, C A

    1997-04-01

    Thrombocytopenia in persons infected with HIV is prevalent and has numerous causes. To study the occurrence, associations, and effect on survival of thrombocytopenia in HIV-infected persons, we used surveillance data from a longitudinal survey of the medical records of 30,214 HIV-infected patients who received medical care from January 1990 through August 1996 in more than 100 medical clinics in 10 U.S. cities. Thrombocytopenia was defined as a physician diagnosis of thrombocytopenia or a platelet count of < 50,000 platelets/ microliter. Analysis of associations of thrombocytopenia was conducted using logistic regression. In HIV+ patients, the 1-year incidence [corrected] of thrombocytopenia was 8.7% in persons with one or more AIDS-defining opportunistic illnesses (clinical AIDS), 3.1% in patients with a CD4 count < 200 cells/mm3 but not clinical AIDS (immunologic AIDS), and 1.7% in persons without clinical or immunologic AIDS. The incidence of thrombocytopenia was associated with clinical AIDS (adjusted odds ratio [AOR] 2.2; 99% confidence interval [CI] 1.7-3.0), immunologic AIDS (AOR 1.5, CI 1.0-2.1), history of injecting drug use (AOR 1.4, CI 1.0-1.9), anemia (AOR 5.0, CI 3.8-6.7), lymphoma (AOR 3.7, CI 1.3-10.6), and black race (AOR 0.7, CI 0.5-0.9). After controlling for anemia, clinical AIDS, CD4 count, neutropenia, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis, thrombocytopenia was significantly associated with decreased survival (risk ratio 1.7; 95% CI, 1.6-1.8). Thrombocytopenia in HIV-infected persons is an important clinical condition associated with shorter survival.

  13. Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

    PubMed

    Schell, Amy M; Petras, Melissa; Szczepiorkowski, Zbigniew M; Ornstein, Deborah L

    2013-10-01

    We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

  14. Vancomycin-induced Immune Thrombocytopenia Proven by the Detection of Vancomycin-dependent Anti-platelet Antibody with Flow Cytometry

    PubMed Central

    Yamanouchi, Jun; Hato, Takaaki; Shiraishi, Sanshiro; Takeuchi, Kazuto; Yakushijin, Yoshihiro; Yasukawa, Masaki

    2016-01-01

    Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal bleeding, which was quickly resolved after effective platelet transfusion following the cessation of vancomycin administration. This report suggests that the flow cytometric test is useful for the differential diagnosis of thrombocytopenia and platelet transfusion should be performed after the cessation of vancomycin administration. PMID:27746445

  15. 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.

  16. [Persistent thrombocytopenia in a child: morphological examination of blood platelets established the diagnosis of Wiskott-Aldrich syndrome].

    PubMed

    Latger-Cannard, V; Lacroix, F; Devignes, J; Salignac, S; Bensoussan, D; Salmon, A; Mansuy, L; Bordigoni, P; Lecompte, T

    2008-01-01

    Thrombocytopenia frequently occurs in laboratory practice. The present work illustrates, through the presentation of a case report of Wiskott-Aldrich syndrome, the difficulties encountered to identify and characterize thrombocytopenia. The clinicobiological validation of a low platelet count involves both the biologist, who must assume the validation of numeration while mentioning the morphological characteristics of the platelets and other blood cells, as well as the physician who has to interpret these data according to the clinical context.

  17. [Successful Management by Immunoglobulin for Sunitinib-Induced Thrombocytopenia in a Patient with Advanced Metastatic Renal Cell Carcinoma].

    PubMed

    Okazaki, Satoshi; Hori, Jun-ichi; Watanabe, Masaki; Hashizume, Kazumi; Kobayashi, Shin; Azumi, Makoto; Kita, Masafumi; Iwata, Tatsuya; Matsumoto, Seiji; Kakizaki, Hidehiro

    2016-02-01

    An 81-year-old man was referred to our hospital because of a right renal tumor with vena cava thrombus and multiple lung metastases that were detected by computed tomography (CT) scan during evaluation of respiratory discomfort. We started medical treatment with sunitinib at a dose of 50 mg daily in a 2-week-on, 1-week-off schedule after confirming clear cell renal cell carcinoma by tumor biopsy. After 2-week sunitinib treatment, thrombocytopenia continued and platelet count decreased to 1.8×10(9)/l at day 11 after stopping sunitinib. We needed to administer a total of 60 units platelet transfusion because of persistent thrombocytopenia. Bone marrow aspiration did not reveal myelosuppression or carcinoma invasion to bone marrow. Under the clinical diagnosis of drug-induced thrombocytopenia secondary to sunitinib, we started immunoglobulin therapy at day 23 after stopping sunitinib. Platelet count returned to normal 10 days after starting immunoglobulin. The patient developed exacerbating lung metastasis and carcinomatous lymphangiosis during subsequent course and died of renal cell carcinoma 79 days after starting sunitinib. Thrombocytopenia after sunitinib therapy is often encountered but prolonged thrombocytopenia is rare after stopping sunitinib. This case suggests that immunoglobulin therapy is effective for drug-induced prolonged thrombocytopenia through immunological mechanism.

  18. Hepatic angiosarcoma mimicking congenital cytomegalovirus infection in an infant with thrombocytopenia.

    PubMed

    Yoon, Hoi Soo; Choi, Yong-Sung; Im, Ho Joon

    2015-04-01

    Hepatic angiosarcomas are uncommon, highly aggressive tumors, rarely seen in children. A 3-month-old female infant was admitted to hospital for evaluation of multiple petechiae on her body. She had hepatosplenomegaly and scattered petechiae over her entire body. Laboratory tests indicated thrombocytopenia and positive cytomegalovirus (CMV) polymerase chain reaction. Ganciclovir was started, and the platelet count increased. After 4 months the patient was readmitted to hospital for drowsy mental status and eventually died from severe bleeding. Needle biopsy of the liver was performed after receiving written consent from the parents. Pathological findings of the liver lesion included features consistent with hepatic angiosarcoma. There have been no previous reports of hepatic angiosarcoma in Korean infants. Here, we report an infant with hepatosplenomegaly and thrombocytopenia who was diagnosed with hepatic angiosarcoma mimicking congenital CMV infection.

  19. Cationized IVIg as a potential substitute to IVIg for the treatment of experimental immune thrombocytopenia.

    PubMed

    Trépanier, Patrick; St-Amour, Isabelle; Bazin, Renée

    2013-08-01

    In this study, we evaluated the possibility of using cationized IVIg (cIVIg) instead of IVIg as a more effective therapy for the treatment of experimental immune thrombocytopenia in mice. The pharmacokinetics (PK) and biodistribution of cIVIg and IVIg in mice were compared. cIVIg displayed a shorter plasma half-life and an increased organ uptake in both the spleen and liver compared to IVIg, suggesting that cIVIg could be more potent than IVIg to prevent platelet clearance in a mouse model of thrombocytopenia. However, although the biodistribution of cIVIg in the spleen and liver was improved, its ability to prevent platelet clearance in mice remained similar to that of IVIg. Altogether, our data demonstrate the possibility of using chemical cationization of IVIg preparations to increase organ uptake, and also highlight the challenges of developing effective substitutes to IVIg.

  20. 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

  1. Management of heparin-associated thrombocytopenia in pregnancy with subcutaneous r-hirudin.

    PubMed

    Huhle, G; Geberth, M; Hoffmann, U; Heene, D L; Harenberg, J

    2000-01-01

    Heparin-induced thrombocytopenia type II is a serious, immune-mediated complication of heparin therapy. Due to its low cross-reactivity with heparin-associated antibodies (10-20%), danaparoid has successfully been administered in these patients. In recent studies, r-hirudin as a potent and specific thrombin inhibitor, was demonstrated to be a safe and effective anticoagulant. We report a pregnant woman with systemic lupus erythematosus and recurrent venous thromboembolism who suffered from heparin-induced thrombocytopenia type II while treated with dalteparin sodium. Positive cross-reactivities with danaparoid were found. Anticoagulation with 15 mg subcutaneous r-hirudin was performed twice daily from the 25th week of pregnancy until delivery. No thromboembolism or bleeding or fetal toxicity of r-hirudin was detected. Recombinant hirudin is a potent and specific thrombin inhibitor that can be used as a safe and effective anticoagulant in pregnancy.

  2. Severe thrombocytopenia and recurrent epistaxis associated with primary Epstein-Barr virus infection.

    PubMed

    Tilden, William; Valliani, Shahnawaz

    2015-04-09

    Infectious mononucleosis, caused by the Epstein-Barr virus (EBV), generally follows a benign, yet protracted course, with the majority of symptoms being systemic somatic symptoms. Rarely, the clinical picture can be complicated by more acute severe haemotological sequelae of the disease, requiring hospitalisation and causing diagnostic uncertainty, particularly when distinguishing between a viral illness and a lymphoproliferative disorder. We describe the case of a young male patient who presented with headache, recurrent epistaxis and severe thrombocytopenia.

  3. Two Treatment Cases of Severe Fever and Thrombocytopenia Syndrome with Oral Ribavirin and Plasma Exchange

    PubMed Central

    Kwon, Ki Tae

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. The primary symptoms associated with SFTS are fever, thrombocytopenia, leukopenia, nausea, and vomiting. Disease progression shows high mortality rate accompanied with multiple organ failure, bleeding tendency, and altered mentality. However, only supportive care has been the basis for the treatment of SFTS. We are reporting two patients who showed central nervous system manifestation, but cured them with ribavirin together with plasma exchange in an early state. The first case is a 60-year-old male, who was admitted to the hospital with a 7-day history of fever, chills, and thrombocytopenia. He was treated with empirical antibiotics; however, he experienced persistent high fever and an altered mentality has occurred. On hospital day 6, the SFTS virus (SFTSV) result from a real-time reverse transcription-polymerase chain reaction (RT-PCR) was confirmed positive. Therefore, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid for 4 days and then 7.5 mg/kg qid as maintenance dose) was administered orally for 11 days and plasma exchange was performed for 5 days. The clinical outcome has improved. The second case is a 48-year-old male, who was admitted to the hospital with a 10-day history of fever, chills, myalgia, diarrhea, and thrombocytopenia. He was treated with empirical antibiotics. On hospital day 3, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid as maintenance dose) was administered orally for 4 days and plasma exchange was performed for 4 days due to his high fever and altered mentality after a positive SFTSV result from a real-time RT-PCR. The patient had a successful recovery. PMID:28271646

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

    PubMed

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

    2015-11-05

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

  5. Acute ST Elevation Myocardial Infarction in Patients With Immune Thrombocytopenia Purpura: A Case Report

    PubMed Central

    Dhillon, Sandeep K; Lee, Edwin; Fox, John; Rachko, Maurice

    2011-01-01

    Acute myocardial infarction (AMI) in patients with immune thrombocytopenic purpura (ITP) is rare. We describe a case of AMI in patient with ITP. An 81-year-old woman presented with acute inferoposterior MI with low platelet count on admission (34,000/µl). Coronary angiography revealed significant mid right coronary artery (RCA) stenosis with thrombus, subsequently underwent successful percutaneous coronary intervention (PCI). In some patients with immune thrombocytopenia purpura and acute myocardial infarction, percutaneous coronary intervention is a therapeutic option.

  6. Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia

    PubMed Central

    Avšič-Županc, Tatjana; Uršič, Tina; Petrovec, Miroslav

    2016-01-01

    We present an infant with acute fever, thrombocytopenia, and leukopenia, coming from an endemic region for tick-borne encephalitis, human granulocytic anaplasmosis, and hantavirus infection. The primary human herpesvirus 6 infection was diagnosed by seroconversion of specific IgM and IgG and by identification of viral DNA in the acute patient's serum. The patient did not show skin rash suggestive of exanthema subitum during the course of illness. PMID:27980872

  7. Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia.

    PubMed

    Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho; Seo, Kyoung-Won

    2015-01-01

    Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly with improved clinical signs while the third dog with recurrent IMT was euthanized due to its deteriorating condition. This case report describes the efficacy of VLP therapy in refractory IMT patients.

  8. Increased Von Willebrand factor, decreased ADAMTS13 and thrombocytopenia in melioidosis

    PubMed Central

    Löwenberg, Ester C.; Meijers, Joost C. M.; Maude, Rapeephan R.; Day, Nicholas P. J.; Peacock, Sharon J.; van der Poll, Tom; Wiersinga, W. Joost

    2017-01-01

    Background Melioidosis, caused by bioterror treat agent Burkholderia pseudomallei, is an important cause of community-acquired Gram-negative sepsis in Southeast Asia and Northern Australia. New insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. We hypothesized that changes in Von Willebrand factor (VWF) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines and thrombin in melioidosis, and investigated whether this impacted on outcome. Methods/Principal findings We recruited 52 controls and 34 culture-confirmed melioidosis patients at Sappasithiprasong Hospital in Ubon Ratchathani, Thailand. All subjects were diabetic. Platelet counts in melioidosis patients were lower compared to controls (p = 0.0001) and correlated with mortality (p = 0.02). VWF antigen levels were higher in patients (geometric mean, 478 U/dl) compared to controls (166 U/dL, p<0.0001). The high levels of VWF in melioidosis appeared to be due to increased endothelial stimulation (VWF propeptide levels were elevated, p<0.0001) and reduced clearance (ADAMTS13 reduction, p<0.0001). However, VWF antigen levels did not correlate with platelet counts implying that thrombocytopenia in acute melioidosis has an alternative cause. Conclusions/Significance Thrombocytopenia is a key feature of melioidosis and is correlated with mortality. Additionally, excess VWF and ADAMTS13 deficiency are features of acute melioidosis, but are not the primary drivers of thrombocytopenia in melioidosis. Further studies on the role of thrombocytopenia in B. pseudomallei infection are needed. PMID:28296884

  9. Heparin-induced thrombocytopenia and fatal thrombosis in a patient with activated protein C resistance.

    PubMed

    Gardyn, J; Sorkin, P; Kluger, Y; Kabili, S; Klausner, J M; Zivelin, A; Eldor, A

    1995-12-01

    We report a 20-year-old woman who developed heparin-induced thrombocytopenia (HIT) associated with devastating and fatal multiorgan thrombosis. The patient, her mother, and her brother were found to have resistance to activated protein C (APC), and the congenital thrombophilia in this family was verified by the finding of the Arg506 Gln mutation in factor V. This is the first case of HIT and APC resistance. The consequences of this association are discussed.

  10. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia.

    PubMed

    Kapur, Rick; Heitink-Pollé, Katja M J; Porcelijn, Leendert; Bentlage, Arthur E H; Bruin, Marrie C A; Visser, Remco; Roos, Dirk; Schasfoort, Richard B M; de Haas, Masja; van der Schoot, C Ellen; Vidarsson, Gestur

    2015-03-12

    Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients.

  11. Pathogenesis of the delayed phase of Rauscher virus-induced thrombocytopenia

    SciTech Connect

    Grau, G.E.; Morrow, D.; Izui, S.; Lambert, P.H.

    1986-01-01

    BALB/c (H-2/sup d/) mice injected with Rauscher murine leukemia virus (RMuLV) developed two phases of thrombocytopenia: an acute phase, probably due to direct virus-platelet interactions, and a delayed phase, starting 2 to 3 wk after virus injection, which was associated with the infection of megakaryocytes by RMuLV and with the expression of RMuLV gp70 and p30 antigens on platelet membranes. This study was concerned with the pathogenesis of this second phase of thrombocytopenia. During this period, the number of marrow megakaryocytes was increased. A peripheral platelet destruction was further indicated by reduced platelet life span. It was shown that radiolabeled platelets, either normal or infected, were submitted to a more rapid clearance in infected recipients than in normal recipients. This might be due to the splenomegaly observed in infected recipients. However, the immediate clearance of gp70/sup +/ platelets was more accelerated in infected recipients with high titers of serum anti-gp70 antibodies than in infected recipients without detectable serum anti-gp70 antibodies. These results suggest that specific clearance of gp70/sup +/ platelets in the presence of significant amounts of serum antiviral antibodies and nonspecific hypersplenism play a role in the development of delayed thrombocytopenia in RMuLV-infected mice.

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

    PubMed Central

    Antony-Debré, Iléana; Manchev, Vladimir T.; Balayn, Nathalie; Bluteau, Dominique; Tomowiak, Cécile; Legrand, Céline; Langlois, Thierry; Bawa, Olivia; Tosca, Lucie; Tachdjian, Gérard; Leheup, Bruno; Debili, Najet; Plo, Isabelle; Mills, Jason A.; French, Deborah L.; Weiss, Mitchell J.; Solary, Eric; Favier, Remi; Vainchenker, William

    2015-01-01

    To explore how RUNX1 mutations predispose to leukemia, we generated induced pluripotent stem cells (iPSCs) from 2 pedigrees with germline RUNX1 mutations. The first, carrying a missense R174Q mutation, which acts as a dominant-negative mutant, is associated with thrombocytopenia and leukemia, and the second, carrying a monoallelic gene deletion inducing a haploinsufficiency, presents only as thrombocytopenia. Hematopoietic differentiation of these iPSC clones demonstrated profound defects in erythropoiesis and megakaryopoiesis and deregulated expression of RUNX1 targets. iPSC clones from patients with the R174Q mutation specifically generated an increased amount of granulomonocytes, a phenotype reproduced by an 80% RUNX1 knockdown in the H9 human embryonic stem cell line, and a genomic instability. This phenotype, found only with a lower dosage of RUNX1, may account for development of leukemia in patients. Altogether, RUNX1 dosage could explain the differential phenotype according to RUNX1 mutations, with a haploinsufficiency leading to thrombocytopenia alone in a majority of cases whereas a more complete gene deletion predisposes to leukemia. PMID:25490895

  13. Catastrophic antiphospholipid syndrome and heparin-induced thrombocytopenia-related diseases or chance association?

    PubMed

    Tun, Nay T; Krishnamurthy, Mahesh; Snyder, Richard

    2015-03-01

    Antiphospholipid syndrome (APS) and heparin-induced thrombocytopenia (HIT) are thrombotic disorders due to specific autoimmune-mediated antibodies. Catastrophic APS (CAPS), also known as Asherman's syndrome, is a life-threatening severe form of APS. Diagnostic criteria for CAPS include the development of a thrombotic event of three or more organs in less than a week with the presence of antiphospholipid antibodies and microvascular thrombosis on histology. Thrombocytopenia is seen in more than 60% of cases of CAPS. HIT is a life-threatening disorder with the clinical presentation of thrombocytopenia and arterial or venous thrombosis in patients who develop antibodies to heparin and platelet factor 4 typically within 10 days after starting heparin treatment. Due to the multiple similarities in clinical features and pathophysiology of CAPS and HIT, it has been postulated that these two antibody-mediated disorders may be related. We report two cases in which patients diagnosed with CAPS developed HIT very soon during the same admission as well as a case of a patient initially diagnosed with HIT who presented with CAPS years later.

  14. Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome

    PubMed Central

    Kim, Uh Jin; Oh, Tae hoon; Kim, Bansuk; Kim, Seong Eun; Kang, Seung-Ji; Park, Kyung-Hwa; Jung, Sook-In

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (P < 0.05, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all P < 0.05). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS. PMID:28348452

  15. Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice.

    PubMed

    Kyrmizi, Irene; Ioannou, Marianna; Hatziapostolou, Maria; Tsichlis, Philip N; Boumpas, Dimitrios T; Tassiulas, Ioannis

    2013-10-01

    The MAPK3 Tpl2 controls innate and adaptive immunity by regulating TLR, TNF-α, and GPCR signaling in a variety of cell types. Its ablation gives rise to an anti-inflammatory phenotype characterized by resistance to LPS-induced endotoxin shock, DSS-induced colitis, and TNF-α-induced IBD. Here, we address the role of Tpl2 in autoimmunity. Our data show that the ablation and the pharmacological inhibition of Tpl2 protect mice from antiplatelet antibody-induced thrombocytopenia, a model of ITP. Thrombocytopenia in this model and in ITP is caused by phagocytosis of platelets opsonized with antiplatelet antibodies and depends on FcγR activation in splenic and hepatic myeloid cells. Further studies explained how Tpl2 inhibition protects from antibody-induced thrombocytopenia, by showing that Tpl2 is activated by FcγR signals in macrophages and that its activation by these signals is required for ERK activation, cytoplasmic Ca(2+) influx, the induction of cytokine and coreceptor gene expression, and phagocytosis.

  16. Evaluation of thrombocytopenia in patients treated with rhenium-186-HEDP: Guidelines for individual dosage recommendations

    SciTech Connect

    Klerk, J.M.H. de; Schip, A.D. van het; Zonnenberg, B.A

    1994-09-01

    A potential limitation of rhenium-186-1,1-hydroxyethylidene diphosphonate ({sup 186}Re-HEDP) therapy in patients with painful bone metastases is thrombocytopenia. Given the palliative character of this therapy, it is essential to be able to predict the degree of thrombocytopenia before therapy. Thus far, 39 prostatic cancer patients with multiple painful bone metastases were treated. Twenty-one patients underwent the therapy twice, resulting in 60 therapies. From the pre-therapy {sup 99m}Tc-HDP scintigram, the bone scan index (BSI) was determined as an index of the extent of bone involvement. The administered activity ranged from 1104 to 3479 MBq {sup 186}Re-HEDP. The platelet count was lowest 4 wk following therapy. From this value and the pretreatment level, the percentage decrease in the platelet count was determined (47%{+-}19%, range 14%-89%). The BSI ranged from 8 to 93. Regression analysis showed a functional relation (R = 0.78; p < 0.001) of the percentage of platelet decrease with BSI and administered activity normalized to standard body surface area. Using this relation, it is possible to predict thrombocytopenia by pretreatment bone scintigraphy and to adjust the dosage to each patient to avoid unacceptable toxicity. 27 refs., 4 figs., 1 tab.

  17. Heparin-induced thrombocytopenia--a big deal? It should be!

    PubMed

    Jamani, N; Ouwendyk, M

    2000-01-01

    Heparin is the anticoagulant of choice for hemodialysis patients. Risks for developing heparin-induced thrombocytopenia (HIT) are increased in patients regularly receiving heparin. About five to eight per cent of these individuals will develop an adverse antigen-antibody reaction, which will be discussed. As there are many causes of thrombocytopenia, HIT can easily go unnoticed. Tests such as the C-serotonin platelet release assay (SRA) and enzyme-linked immunosorbent assay (ELISA) are available to confirm HIT. Even though these patients may have thrombocytopenia, the threat is not bleeding but thrombosis. In fact, the major concern is that with reexposure to heparin the degree of fibrin clot formation could be severe. Since HIT carries with it a high risk of morbidity and mortality, nurses play a vital role in early diagnosis and prevention of possible life-threatening complications. Management of this heparin allergy includes identifying alternate agents available for use in HIT positive patients. Of the many nursing responsibilities that will be explored, staff and patient education will be emphasized.

  18. Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders

    PubMed Central

    Noris, Patrizia; Biino, Ginevra; Pecci, Alessandro; Civaschi, Elisa; Savoia, Anna; Seri, Marco; Melazzini, Federica; Loffredo, Giuseppe; Russo, Giovanna; Bozzi, Valeria; Notarangelo, Lucia Dora; Gresele, Paolo; Heller, Paula G.; Pujol-Moix, Nuria; Kunishima, Shinji; Cattaneo, Marco; Bussel, James; De Candia, Erica; Cagioni, Claudia; Ramenghi, Ugo; Barozzi, Serena; Fabris, Fabrizio

    2014-01-01

    Abnormalities of platelet size are one of the distinguishing features of inherited thrombocytopenias (ITs), and evaluation of blood films is recommended as an essential step for differential diagnosis of these disorders. Nevertheless, what we presently know about this subject is derived mainly from anecdotal evidence. To improve knowledge in this field, we evaluated platelet size on blood films obtained from 376 patients with all 19 forms of IT identified so far and found that these conditions differ not only in mean platelet diameter, but also in platelet diameter distribution width and the percentage of platelets with increased or reduced diameters. On the basis of these findings, we propose a new classification of ITs according to platelet size. It distinguishes forms with giant platelets, with large platelets, with normal or slightly increased platelet size, and with normal or slightly decreased platelet size. We also measured platelet diameters in 87 patients with immune thrombocytopenia and identified cutoff values for mean platelet diameter and the percentage of platelets with increased or reduced size that have good diagnostic accuracy in differentiating ITs with giant platelets and with normal or slightly decreased platelet size from immune thrombocytopenia and all other forms of IT. PMID:24990887

  19. Hyperhemolytic Syndrome Complicating a Delayed Hemolytic Transfusion Reaction due to anti-P1 Alloimmunization, in a Pregnant Woman with HbO-Arab/β-Thalassemia

    PubMed Central

    Bezirgiannidou, Zoe; Christoforidou, Anna; Kontekaki, Eftychia; Anastasiadis, Athanasios G; Papamichos, Spyros I.; Menexidou, Helen; Margaritis, Dimitrios; Martinis, Georges; Mantadakis, Elpis

    2016-01-01

    Background Hyperhemolytic Syndrome or Hyperhemolytic Transfusion Reaction (HHTR), a life-threatening subset of Delayed Hemolytic Transfusion Reaction (DHTR) is characterized by destruction of both transfused and autologous erythrocytes evidenced by a fall in post transfusion hemoglobin below the pre-transfusion level. Case report We describe a case of DHTR due to anti-P1 alloimmunization manifesting with hyperhemolysis in a 30-year-old Greek Pomak woman with thalassemia intermedia (HbO-Arab/β-thalassemia), during the11th week of her first gestation. She was successfully managed with avoidance of further transfusions and administration of IVIG and corticosteroids. Conclusion A high index of suspicion for HHTR is of vital importance among clinicians especially since optimal methods for its prevention and treatment remain yet to be defined. Early recognition of HHTR leading to prompt cessation of additional transfusions and initiation of immunosuppressive treatment can be life-saving, especially in clinical settings where limited therapeutic options are available, such as in pregnancy. PMID:27872733

  20. Pseudotyping Serotype 5 Adenovirus with the Fiber from Other Serotypes Uncovers a Key Role of the Fiber Protein in Adenovirus 5-Induced Thrombocytopenia.

    PubMed

    Raddi, Najat; Vigant, Frédéric; Wagner-Ballon, Oriane; Giraudier, Stéphane; Custers, Jerome; Hemmi, Silvio; Benihoud, Karim

    2016-02-01

    Adenovirus (Ad) infection in humans is associated with inflammatory responses and thrombocytopenia. Although several studies were conducted in mice models to understand molecular and cellular mechanisms of Ad-induced inflammatory responses, only few of them turned their interest toward the mechanisms of Ad-induced thrombocytopenia. Using different depletion methods, the present study ruled out any significant role of spleen, macrophages, and vitamin K-dependent factor in Ad-induced thrombocytopenia. Interestingly, mice displaying thrombocytopenia expressed high levels of cytokines/chemokines after Ad administration. Most importantly, pseudotyping adenovirus with the fiber protein from other serotypes was associated with reduction of both cytokine/chemokine production and thrombocytopenia. Altogether, our results suggest that capsid fiber protein (and more precisely its shaft) of Ad serotype 5 triggers the cytokine production that leads to Ad-induced thrombocytopenia.

  1. Thrombocytopenia in homosexual patients. Prognosis, response to therapy, and prevalence of antibody to the retrovirus associated with the acquired immunodeficiency syndrome.

    PubMed

    Walsh, C; Krigel, R; Lennette, E; Karpatkin, S

    1985-10-01

    Thirty-three homosexual patients with thrombocytopenia (mean [+/- SE] platelet count, 50 000 +/- 7000/mm3; range, 7 to 135 000/mm3) have been followed for a mean period of 20 +/- 2 months. Six patients have developed the acquired immunodeficiency syndrome 1 to 37 months after the diagnosis of thrombocytopenia. Six patients spontaneously reverted to normal platelet counts 5 to 27 months (median, 10 months) after the diagnosis of thrombocytopenia, in the absence of splenectomy and while not receiving corticosteroids. Sixteen of seventeen patients had a moderate to excellent response while on corticosteroid treatment. Ten of ten patients had an excellent response to splenectomy which has persisted. Fifteen patients did not require treatment for their thrombocytopenia. Thirteen of fourteen patients had antibody against the retrovirus associated with the acquired immunodeficiency syndrome, as did 4 of 12 homosexual controls without thrombocytopenia. Thrombocytopenia in homosexuals is part of the complex related to the acquired immunodeficiency syndrome.

  2. Development of a single-antigen magnetic bead assay (SAMBA) for the sensitive detection of HPA-1a alloantibodies using tag-engineered recombinant soluble β3 integrin.

    PubMed

    Skaik, Younis; Battermann, Anja; Hiller, Oliver; Meyer, Oliver; Figueiredo, Constanca; Salama, Abdulgabar; Blasczyk, Rainer

    2013-05-31

    Timely and accurate testing for human platelet antigen 1a (HPA-1a) alloantibodies is vital for clinical diagnosis of neonatal alloimmune thrombocytopenia (NAIT). Current antigen-specific assays used for the detection of HPA-1 alloantibodies are technically very complex and cumbersome for most diagnostic laboratories. Hence, we designed and applied recombinant soluble (rs) β3 integrins displaying HPA-1a or HPA-1b epitopes for the development of a single-antigen magnetic bead assay (SAMBA). Soluble HPA-1a and HPA-1b were produced recombinantly in human embryonic kidney 293 (HEK293) cells and differentially tagged. The recombinant soluble proteins were then immobilized onto paramagnetic beads and used for analysis of HPA-1 alloantibodies by enzyme-linked immunosorbent assay (ELISA). HPA-1a serum samples (n=7) from NAIT patients, inert sera and sera containing non-HPA-1a antibodies were used to evaluate the sensitivity and specificity of the SAMBA. Fusion of V5-His or GS-SBP-His tags to the rsβ3 integrins resulted in high-yield expression. SAMBA was able to detect all HPA-1a and -1b alloantibodies recognized by monoclonal antibody-specific immobilization of platelet antigens assay (MAIPA). No cross-reactions between the sera were observed. Two out of seven of the HPA-1a alloantibody-containing sera demonstrated weak to moderate reactivity in MAIPA but strong signals in SAMBA. SAMBA provides a very reliable method for the detection of HPA-1 antibodies with high specificity and sensitivity. This simple and rapid assay can be adapted for use in any routine laboratory and can be potentially adapted for use on automated systems.

  3. 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

  4. [Sickle cell anemia and transfusion safety in Bamako, Mali. Seroprevalence of HIV, HBV and HCV infections and alloimmunization belonged to Rh and Kell systems in sickle cell anemia patients].

    PubMed

    Diarra, A B; Guindo, A; Kouriba, B; Dorie, A; Diabaté, D T; Diawara, S I; Fané, B; Touré, B A; Traoré, A; Gulbis, B; Diallo, D A

    2013-12-01

    Red cell transfusion is one of the main treatments in sickle cell disease. However there are potential risks of blood transfusions. In order to propose strategies to improve blood safety in sickle cell disease in Mali, we conducted a prospective study of 133 patients with sickle cell anemia recruited at the sickle cell disease research and control center of Bamako, November 2010 to October 2011. The study aimed to determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections by serum screening and the frequency of red cell alloimmunization before and after blood transfusion. The diagnosis of sickle cell syndrome was made by HPLC, the detection of markers of viral infection was performed by ELISA, and the diagnosis of alloimmunization was conducted by the Indirect Coombs test. Prevalence of viral infections observed at the time of enrolment of patients in the study was 1%, 3% and 1% respectively for HIV, HBV and HCV. Three cases of seroconversion after blood transfusion were detected, including one for HIV, one for HBV and one another for HCV in sickle cell anemia patients. All these patients had received blood from occasional donors. The red cell alloimmunization was observed in 4.4% of patients. All antibodies belonged to Rh system only. Blood transfusion safety in sickle cell anemia patients in Mali should be improved by the introduction of at least the technique for detecting the viral genome in the panel of screening tests and a policy of transfusions of blood units only from regular blood donors.

  5. 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.

  6. Bicytopenia, especially thrombocytopenia in hemodialysis and non-hemodialysis patients treated with linezolid therapy.

    PubMed

    Kato, Hideo; Hamada, Yukihiro; Hagihara, Mao; Hirai, Jun; Yamagishi, Yuka; Matsuura, Katsuhiko; Mikamo, Hiroshige

    2015-10-01

    One of the major adverse events associated with linezolid treatment is pancytopenia. However, there are few reports about the tolerability of linezolid among patients undergoing hemodialysis. This study retrospectively investigated the frequency of bicytopenia (thrombocytopenia and erythropenia) secondary to linezolid treatment in patients undergoing and not-undergoing hemodialysis. In total, 181 patients treated with linezolid from January 2010 to July 2012 at Aichi Medical University Hospital were divided into three groups; patients undergoing hemodialysis (HD group), those with creatinine clearance (CLCR) of <50 mL/min (CLCR < 50 group) and those with CLCR of ≥ 50 mL/min (CLCR ≥ 50 group). The incidence of thrombocytopenia, and changes in the platelet (PLT) counts during and after linezolid therapy were compared among three groups. Thrombocytopenia (<75% of the baseline level) occurred in 125 patients (69.1%). PLT reached its nadir 3-4 days after the end of linezolid therapy. In particular, the PLT nadir in HD group occurred earlier than that in non-HD groups (HD, 11.5 days [4-31 days]; CLCR < 50, 14 days [5-43 days]; CLCR ≥ 50, 15.5 days [4-49 days]; p = 0.11). HD group exhibited the greatest rate of reduction of PLT (HD, 24.0% [0.4-93.8%]; CLCR < 50, 23.8% [0.8-92.9%]; CLCR ≥ 50, 22.4% [0.92-92.9%]; p = 0.003). Finally, HD group exhibited the slowest recovery of PLT to its baseline level (HD, 10 days [5-29 days]; CLCR < 50, 9 days [2-16 days]; CLCR ≥ 50, 8 days [3-17 days]; p = 0.09). The incidence of erythropenia was not significantly different among three groups. These results indicate the need to monitor the PLT count during and after linezolid treatment in patients undergoing hemodialysis.

  7. Jacobsen syndrome without thrombocytopenia: a case report and review of the literature.

    PubMed

    Nalbantoğlu, Burçin; Donma, M Metin; Nişli, Kemal; Paketçi, Cem; Karasu, Erkut; Ozdilek, Burcu; Mintaş, Nuriye Ece

    2013-01-01

    Jacobsen syndrome (JS), a rare disorder with multiple dysmorphic features, is caused by the terminal deletion of chromosome 11q. Typical features include mild to moderate psychomotor retardation, trigonocephaly, facial dysmorphism, cardiac defects, and thrombocytopenia, though none of these features are invariably present. The estimated occurrence of JS is about 1/100,000 births. The female/male ratio is 2:1. The patient admitted to our clinic at 3.5 years of age with a cardiac murmur and facial anomalies. Facial anomalies included trigonocephaly with bulging forehead, hypertelorism, telecanthus, downward slanting palpebral fissures, and a carp-shaped mouth. The patient also had strabismus. An echocardiogram demonstrated perimembranous aneurysmatic ventricular septal defect and a secundum atrial defect. The patient was <3rd percentile for height and weight and showed some developmental delay. Magnetic resonance imaging (MRI) showed hyperintensive gliotic signal changes in periventricular cerebral white matter, and leukodystrophy was suspected. Chromosomal analysis of the patient showed terminal deletion of chromosome 11. The karyotype was designated 46, XX, del(11) (q24.1). A review of published reports shows that the severity of the observed clinical abnormalities in patients with JS is not clearly correlated with the extent of the deletion. Most of the patients with JS had short stature, and some of them had documented growth hormone deficiency, or central or primary hypothyroidism. In patients with the classical phenotype, the diagnosis is suspected on the basis of clinical findings: intellectual disability, facial dysmorphic features and thrombocytopenia. The diagnosis must be confirmed by cytogenetic analysis. For patients who survive the neonatal period and infancy, the life expectancy remains unknown. In this report, we describe a patient with the clinical features of JS without thrombocytopenia. To our knowledge, this is the first case reported from Turkey.

  8. Heparin-induced thrombocytopenia (HIT II) - a drug-associated autoimmune disease.

    PubMed

    Nowak, Götz

    2009-11-01

    Autoimmune thrombocytopenia (ITP) is an acquired autoimmune disease characterised by isolated persistent thrombocytopenia and normal megakaryopoiesis. This definition also applies to heparin-induced thrombocytopenia (HIT II), a frequent side effect of heparin treatment. In HIT II, the immunogen is a coagulation active complex of heparin and platelet factor 4 (PF4). By now, diagnostics of HIT II is often material and time consuming. Three groups of patients were investigated for HIT II antibodies (HIT II-AB): 54 hospitalised stroke patients, 87 hospitalised cardiac patients, and 71 patients on chronic haemodialysis, all treated with heparin. Furthermore, 100 healthy volunteers were investigated. For detection of HIT II-AB the innovative whole blood test PADA-HIT (PADA: platelet adhesion assay) was used. PADA-HIT quantifies the interaction of IgG antibodies with FcgammaIIA receptors by comparing the activation state of platelets in citrated and heparinised whole blood. The occurrence of HIT II-AB in blood was very high with 44 % of stroke patients, 69% of cardiac patients and 38% of haemodialysis patients compared to only 15% of healthy volunteers. This demonstrates a high incidence and a rapid onset of HIT II-AB in patients being acutely treated with heparin. HIT II is one of the most frequent and severe autoimmune diseases bearing a great thrombosis risk. PADA-HIT represents an innovative diagnostic method for detection of autoimmune antibodies of IgG type that are directed against platelet factor 4 (PF4)-heparin-complex. By early and fast diagnostics and appropriate treatment severe complications of HIT II can be prevented.

  9. 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

  10. Association of Primary Biliary Cirrhosis-autoimmune Hepatitis Overlap Syndrome with Immune Thrombocytopenia and Graves' Disease.

    PubMed

    Koyamada, Ryosuke; Higuchi, Takakazu; Kitada, Ayako; Nakagawa, Tomoko; Ikeya, Takashi; Okada, Sadamu; Fujita, Yoshiyuki

    2015-01-01

    A 54-year-old woman suffering from pruritus for five years was diagnosed to have Graves' disease and immune thrombocytopenia (ITP) associated with primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome, which was confirmed histologically after a prompt recovery in the platelet count number following steroid therapy. The association between PBC-AIH overlap syndrome and ITP has been rarely reported and the additional association with Graves' disease has not yet been reported. An underlying global derangement of autoimmunity or shared genetic susceptibility was suspected.

  11. Unusual onset of venous thromboembolism and heparin-induced thrombocytopenia in a patient with essential thrombocythemia.

    PubMed

    Lapecorella, Mario; Lucchesi, Alessandro; Di Ianni, Mauro; Napolitano, Mariasanta; Coletti, Gino; Di Leonardo, Gabriella; Dell'Orso, Luigi; Barnabei, Remo; Mariani, Guglielmo

    2010-01-01

    Essential thrombocythemia is a hematological disorder characterized by clonal hemopoiesis in the bone marrow and increased number of circulating platelets. It is usually discovered accidentally at the time of routine blood examinations or can become clinically evident with either thrombotic or hemorrhagic complications. In the present article, we describe the case of a 66-year-old woman with pneumonia due to Pneumocystis carinii, who experienced deep vein thrombosis and pulmonary embolism during hospitalization with a subsequent heparin-induced thrombocytopenia. Bone marrow examination performed after clinical improvement revealed the patient to be affected by essential thrombocythemia.

  12. 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

  13. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    PubMed

    Mortensen, Thomas Bech; Frederiksen, Henrik; Marcher, Claus Werenberg; Preiss, Birgitte

    2017-01-04

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

  14. Molecular detection of severe fever with thrombocytopenia syndrome virus (SFTSV) in feral cats from Seoul, Korea.

    PubMed

    Hwang, Jusun; Kang, Jun-Gu; Oh, Sung-Suck; Chae, Jeong-Byoung; Cho, Yun-Kyung; Cho, Young-Sun; Lee, Hang; Chae, Joon-Seok

    2017-01-01

    This study tested serum samples of feral cats from a highly urbanized habitat, Seoul, Korea to determine the infection to severe fever with thrombocytopenia syndrome virus (SFTSV). From 126 samples tested, SFTSV was detected by RT-PCR in 22 (17.5%) cats from various sites of Seoul. Sequences identified from this study were grouped with clusters from China and Japan. Our result provides data that SFTSV may have been circulating in settings that were suspected to have relatively low risk, such as highly urbanized habitats. Thus it warrants further study to investigate the ecology of SFTSV in urban-dwelling animals including ticks, human and other potential host species.

  15. Low Molecular Weight Heparin Induced Skin Necrosis without Platelet Fall Revealing Immunoallergic Heparin Induced Thrombocytopenia

    PubMed Central

    Godet, Thomas; Perbet, Sébastien; Lebreton, Aurélien; Gayraud, Guillaume; Cayot, Sophie; Tremblay, Aymeric; Ravinet, Aurélie; Christophe, Sébastien; Guérin, Renaud; Pascal, Julien; Jabaudon, Matthieu; Hassan, Amr; Sapin, Anne-Françoise; Bazin, Jean-Etienne; Constantin, Jean-Michel

    2013-01-01

    Low molecular weight heparins (LMWH) are commonly used in the ICU setting for thromboprophylaxis as well as curative decoagulation as required during renal replacement therapy (RRT). A rare adverse event revealing immunoallergic LMWH induced thrombopenia (HIT) is skin necrosis at injection sites. We report the case of a patient presenting with skin necrosis witnessing an HIT after RRT, without thrombocytopenia. The mechanism remains unclear. Anti-PF4/heparin antibodies, functional tests (HIPA and/or SRA), and skin biopsy are of great help to evaluate differential diagnosis with a low pretest probability 4T's score. PMID:24307958

  16. 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

  17. Acute Middle Cerebral Artery Occlusion Treated by Thrombectomy in a Patient with Myelodysplastic Syndrome and Severe Thrombocytopenia

    PubMed Central

    Onder, Halil; Murat Arsava, E.; Arat, Anıl; Akif Topcuoglu, M.

    2015-01-01

    Objective Experience on thrombolysis and/or thrombectomy for acute major ischemic strokes in the setting of deep (less than 40,000/mm3) thrombocytopenia is limited. Methods Case report and review of the literature. Results A 63-year-old female with myelodysplastic syndrome presented with left middle cerebral artery stroke within 2 hours of symptom onset. Severe thrombocytopenia (10.000/mm3) precluded systemic thrombolysis. However, endovascular thrombectomy provided successful recanalization and dramatic clinical recovery with NIHSS score decreasing from 20 to 2 soon after the procedure. Her modified Rankin scale was 1 at the end of the third month. Conclusion This exceptional case highlights that neurothrombectomy could be feasible and of justifiable merit even in the setting of critically low thrombocytopenia if a meticulous procedure is followed in subjects with severe acute stroke. PMID:26576212

  18. [Fulminant coagulopathy after bivalirudin use in a patient diagnosed with heparin-induced thrombocytopenia and subject to cardiac bypass surgery].

    PubMed

    de Prada Martín, B; Gualis Cardona, J; Pérez Blanco, I; Martínez Comendador, J M

    2014-03-01

    Patients with a previous history of heparin-induced thrombocytopenia are at a higher risk for thromboembolic events, and heparin administration is formally contraindicated. Bivalirudin has been reported as an alternative therapy whenever an intervention that requires systemic anticoagulation and cardiopulmonary by-pass pump is needed. We present the case of a patient diagnosed with heparin-induced thrombocytopenia and heparin-PF4 (+) antibodies requiring a triple cardiac valve replacement who developed fulminant coagulopathy after bivalirudin administration. A discussion on the serious difficulties that the management of these types of patients involves, as well as a review of prevention strategies are presented.

  19. 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.

  20. 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

  1. Blalock-taussig shunt thrombosis prophylaxis in a patient with jacobsen syndrome and thrombocytopenia.

    PubMed

    Casadonte, Joseph R; Kim, Jennifer M; Dadlani, Gul H; Jacobs, Jeffrey P; Cooper, David S; Stapleton, Gary E

    2011-10-01

    Jacobsen syndrome (JS) is a rare chromosomal anomaly caused by deletions in the distal long arm of chromosome 11. Features of the syndrome include growth and developmental delays, a distinctive facial appearance, and a variety of physical problems including heart defects and bleeding disorders. Congenital heart defects occur in approximately 50% of children with JS. Hypoplastic left heart syndrome (HLHS) has been occasionally reported in association with JS. In such cases, the hematological abnormalities may influence the outcome from single-ventricle palliation through staged surgical reconstruction. Thrombotic obstruction or occlusion of the modified Blalock-Taussig (BT) shunt is a well-documented cause of interstage mortality following the Norwood operation. Although there is no consensus regarding the therapeutic value of antiplatelet therapy during the interstage period following the first stage of palliation, maintenance of shunt patency is critically important. For patients with JS undergoing single-ventricle palliation, decisions regarding antiplatelet therapy during the interstage period may be further complicated by the presence of thrombocytopenia and platelet dysfunction related to JS. We report the case of a patient with HLHS, JS, and thrombocytopenia who underwent the Norwood procedure, and we describe our strategy for prophylaxis against thrombosis of the BT shunt.

  2. Non-surgical contraindication for acute appendicitis with secondary thrombocytopenia: a case report.

    PubMed

    Zhang, Hai-Hong; Gu, Guo-Li; Zhang, Xiang-Yang; Fan, Qin; Wang, Xin-Yan; Wei, Xue-Ming

    2015-03-07

    A 26-year-old man presented with migrated right lower abdominal pain and without any history of hematological systemic diseases. Blood routine test showed a leukocyte count of 22.74 × 10(9)/L, with 91.4% neutrophils, and a platelet count of 4 × 10(9)/L before admission. The case question was whether the team should proceed with surgery. Obviously, a differential diagnosis is essential before making such a decision. Acute appendicitis was easily diagnosed based on clinical findings, including migrating abdominal pain, a leukocyte count of 22.74 × 10(9)/L and the result of abdominal computed tomography scan. However, it was not clear whether the severe thrombocytopenia was primary or secondary. So smear of peripheral blood and aspiration of bone marrow were ordered to exclude hematological diseases. Neither of the tests indicated obvious pathological hematological changes. There was no hepatosplenomegaly found by ultrasound examination of the liver and spleen. Therefore, operative intervention may be a unique clinical scenario in acute severe appendicitis patients with secondary thrombocytopenia.

  3. 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.

  4. Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

    PubMed Central

    Nishijo, Nao; Tsuji, Yasuhiro; Matsunaga, Kazuhisa; Kutsukake, Masahiko; Okazaki, Fumiyasu; Fukumori, Shiro; Kasai, Hidefumi; Hiraki, Yoichi; Sakamaki, Ippei; Yamamoto, Yoshihiro; Karube, Yoshiharu; To, Hideto

    2017-01-01

    Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression.

  5. Left main stent thrombosis complicated by eptifibatide-induced acute thrombocytopenia.

    PubMed

    Yang, Eric H; Perez, Edwin; Zhiroff, Katrine A; Burstein, Steven

    2011-01-01

    A 57-year-old man with a history of coronary artery disease and placement of an implantable cardioverter-defibrillator presented at our emergency room with an anterior ST-elevation myocardial infarction. Cardiac catheterization revealed an acutely occluded left main coronary artery, which was revascularized successfully with a bare-metal stent. Periprocedurally, the patient received aspirin, clopidogrel, unfractionated heparin, and eptifibatide. The patient was discharged a week later, but he returned to the emergency room the same day with recurrence of severe chest pain. Repeat cardiac catheterization revealed an acutely occluded stent, and the patient underwent repeat bare-metal stent placement and readministration of eptifibatide. On the next day, the patient's platelet count dropped acutely to less than 12,000/mm3. A test for heparin-induced thrombocytopenia antibody was negative. After discontinuation of eptifibatide, the patient's platelet count gradually returned to normal, and he was later discharged from the hospital with no complications. Eptifibatide-induced acute thrombocytopenia is a known but rare adverse effect. We review the handful of case reports in the medical literature, with emphasis on the prevalence, observed clinical course, and recently proposed physiologic mechanisms that probably are responsible for this phenomenon.

  6. 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

  7. High Remission Rate of Chronic Immune Thrombocytopenia in Children: Result of 20-Year Follow-Up

    PubMed Central

    Kim, Chae Young; Lee, Eun Hye

    2016-01-01

    Purpose This study examined the outcomes of children with chronic immune thrombocytopenia (ITP). Materials and Methods We retrospectively analyzed the medical records of all patients diagnosed with ITP from January 1992 to December 2011 at our institution. Results A total of 128 patients (64%) satisfied the criteria for newly diagnosed ITP, 31 (15%) for persistent ITP, and 41 (21%) for chronic ITP. The median age at diagnosis was 4.5 years (range, 1 month to 18 years). The median platelet count at diagnosis was 32×109/L. A comparison of the initial treatment data from 2001 to 2011 with those from 1992 to 2000 showed that the number of bone marrow examinations decreased, whereas observation increased. Chronic ITP presented at an older age than newly diagnosed and persistent ITP (6.6 years vs. 3.8 years vs. 4.1 years, respectively); however, the difference did not reach statistical significance (p=0.17). The probability of complete remission of chronic ITP was 50% and 76% at 2 and 5 years after diagnosis, respectively. Patients aged <1 year at diagnosis had a significantly better prognosis than did older patients (hazard ratio, 3.86; p=0.02). Conclusion Children with chronic ITP showed a high remission rate after long-term follow-up. This study suggests that invasive treatments such as splenectomy in children with chronic ITP can be delayed for 4 to 5 years if thrombocytopenia and therapeutic medication do not affect the quality of life. PMID:26632392

  8. Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

    PubMed Central

    Stuchlý, Jan; Kanderová, Veronika; Vlková, Marcela; Heřmanová, Ivana; Slámová, Lucie; Pelák, Ondřej; Taraldsrud, Eli; Jílek, Dalibor; Králíčková, Pavlína; Fevang, Børre; Trková, Marie; Hrušák, Ondřej; Froňková, Eva; Šedivá, Anna; Litzman, Jiří; Kalina, Tomáš

    2017-01-01

    Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning “bins” yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27− CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes’ immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ over three years. Moreover, th-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background. PMID:28054583

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

    PubMed Central

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

    2016-01-01

    Background Patients with a low platelet count (thrombocytopenia) often require the insertion of central lines (central venous catheters (CVCs)). CVCs have a number of uses; these include: administration of chemotherapy; intensive monitoring and treatment of critically-ill patients; administration of total parenteral nutrition; and long-term intermittent intravenous access for patients requiring repeated treatments. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to CVC insertion, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to CVC insertion varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding after a central line insertion appears to be low if an ultrasound-guided technique is used. Patients may therefore be exposed to the risks of a platelet transfusion without any obvious clinical benefit. Objectives To assess the effects of different platelet transfusion thresholds prior to the insertion of a central line in patients with thrombocytopenia (low platelet count). Search methods We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2015, Issue 2), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 23 February 2015. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients of any age with thrombocytopenia requiring insertion of a CVC. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results One RCT was identified that compared different platelet transfusion thresholds prior to insertion of a CVC in people with chronic liver

  10. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    PubMed

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

  11. Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy.

    PubMed

    Buchbinder, David; Nugent, Diane; Hsieh, Loan

    2017-01-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. In approximately one-third of cases, the duration of thrombocytopenia will extend beyond 12 months consistent with a diagnosis of chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe or life-threatening bleeding complications are uncommon. Moreover, spontaneous resolution occurs in the majority of children with chronic ITP necessitating treatment in only those children with ongoing bleeding manifestations or impairment in health-related quality of life (HRQOL). The characterization of thrombopoietin (TPO) and remarkable advancements in our understanding of the pathophysiology of ITP has led to the development of a new class of agents, the TPO-receptor agonists that have documented efficacy in the amelioration of thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a second-generation TPO-receptor agonist that has undergone limited evaluation in the treatment of chronic ITP in children. Evolving data suggest that romiplostim may be a safe and effective agent in the treatment of chronic ITP in children. Additional data are needed to confirm its ability to increase platelet counts, decrease bleeding manifestation, and improve the HRQOL of children and caregivers impacted by chronic ITP.

  12. Thrombocytopenia in pregnancy: do the time of diagnosis and delivery route affect pregnancy outcome in parturients with idiopathic thrombocytopenic purpura?

    PubMed

    Yuce, T; Acar, D; Kalafat, E; Alkilic, A; Cetindag, E; Soylemez, F

    2014-12-01

    The objective of this study was to investigate the determining effects of diagnosis time on pregnancy outcomes in a population of pregnant women with idiopathic thrombocytopenic purpura (ITP). Records of all the pregnant women with thrombocytopenia were evaluated. Those with a confirmed diagnosis of ITP were included in the study. Main outcome measures were antenatal thrombocyte count, postpartum haemorrhage rate, and route of delivery. Foetal outcomes such as foetal thrombocyte count, haemorrhage, and birth weight were also reported as secondary outcome measures. Time of diagnosis either antenatal or preconception did not significantly alter the investigated parameters. Delivery route had no impact on complication rates. Time of diagnosis also did not affect treatment modality. ITP is rare disorder accounting for less than 5 % of all pregnant thrombocytopenias. Time of diagnosis does not affect maternal-foetal outcomes or treatment modality unless diagnosis is made during labour. Compared to gestational thrombocytopenia, treatment rates may differ but treatment modalities remain the same and the effort put into making the differential should be weighed against maternal stress factors for lengthy laboratory evaluation as long as the thrombocytopenia is of pure nature without any systemic involvement.

  13. Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy

    PubMed Central

    Buchbinder, David; Nugent, Diane; Hsieh, Loan

    2017-01-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. In approximately one-third of cases, the duration of thrombocytopenia will extend beyond 12 months consistent with a diagnosis of chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe or life-threatening bleeding complications are uncommon. Moreover, spontaneous resolution occurs in the majority of children with chronic ITP necessitating treatment in only those children with ongoing bleeding manifestations or impairment in health-related quality of life (HRQOL). The characterization of thrombopoietin (TPO) and remarkable advancements in our understanding of the pathophysiology of ITP has led to the development of a new class of agents, the TPO-receptor agonists that have documented efficacy in the amelioration of thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a second-generation TPO-receptor agonist that has undergone limited evaluation in the treatment of chronic ITP in children. Evolving data suggest that romiplostim may be a safe and effective agent in the treatment of chronic ITP in children. Additional data are needed to confirm its ability to increase platelet counts, decrease bleeding manifestation, and improve the HRQOL of children and caregivers impacted by chronic ITP.

  14. 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.

  15. 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

  16. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia

    PubMed Central

    Estcourt, Lise J; Ingram, Callum; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Stanworth, Simon J

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different platelet transfusion thresholds prior to the insertion of a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). PMID:27057148

  17. 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.

  18. 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

  19. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy.

    PubMed

    Hanafy, A S; El Hawary, A T; Hamed, E F; Hassaneen, A M

    2016-07-01

    The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/μl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/μl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/μl to 104.2 ± 15.2 × 10(3)/μl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy.

  20. 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

  1. 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.

  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. Pathogenesis-oriented approaches for the management of corticosteroid-resistant or relapsedprimary immune thrombocytopenia

    PubMed Central

    Liu, Xin-guang

    2016-01-01

    Abstract Primary immune thrombocytopenia (ITP) is a complex autoimmune disorder in which the patient’s immune system reacts with platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. Corticosteroids can induce sustained remission rates in 50% to 75% of patients with active ITP. For these patients who are unresponsive to glucocorticoids, or relapsed after an initial response, multiple second-line treatment modalities can be chosen. However, how to make an optimal therapeutic strategy for a specific patient still remains a major challenge. As the pathogenetic heterogeneity of the ITP is increasingly identified, pathogenesis-oriented approach might offer an opportunity to improve the outcome of corticosteroid-resistant or relapsed ITP.

  4. Spontaneous Heparin-Induced Thrombocytopenia and Venous Thromboembolism following Total Knee Arthroplasty

    PubMed Central

    2017-01-01

    A 72-year-old Caucasian woman was admitted for an elective left total knee arthroplasty. Her surgery was uncomplicated and she was discharged to a rehabilitation facility. Twelve days later, she developed acute shortness of breath followed by a syncopal episode. She was hypoxic and cyanotic, requiring hospitalization and intubation, and was subsequently diagnosed with bilateral submassive pulmonary emboli and bilateral lower extremity deep vein thrombosis. She was started on unfractionated heparin infusion. Within 24 hours of exposure, she had an acute decrease in platelet count to 48,000. Heparin was discontinued and argatroban was initiated due to concern for heparin-induced thrombocytopenia (HIT). Both quantitative enzyme immunoassay and functional assay confirmed the diagnosis of HIT. The patient had no prior lifetime heparin exposure. Given the absence of preceding heparin therapy, this case is consistent with the diagnosis of spontaneous HIT. PMID:28261509

  5. Childhood immune thrombocytopenia: role of rituximab, recombinant thrombopoietin, and other new therapeutics.

    PubMed

    Journeycake, Janna M

    2012-01-01

    Childhood immune thrombocytopenia (ITP) is often considered a benign hematologic disorder. However, 30% of affected children will have a prolonged course and 5%-10% will develop chronic severe refractory disease. Until recently, the only proven therapeutic option for chronic severe ITP was splenectomy, but newer alternatives are now being studied. However, because immunosuppressive agents such as rituximab are not approved for use in ITP and the thrombopoietin receptor agonists are not yet approved in children, the decision to use alternatives to splenectomy needs to be considered carefully. This review describes the factors that should affect decisions to treat ITP at diagnosis and compares the options for the occasional child in whom ITP does not resolve within the first year.

  6. Anesthetic management of patient with systemic lupus erythematosus and thrombocytopenia for vaginal hysterectomy.

    PubMed

    Chauhan, Gaurav; Gupta, Kapil; Kashyap, Chandni; Nayar, Pavan

    2013-01-01

    We report a case of a female having systemic lupus erythematosus, who was on steroid therapy and was scheduled for vaginal hysterectomy. She presented with breathlessness on mild exertion, a characteristic facial malar rash, and a platelet count 56,000 cells/cu mm. The patient was given a subarachnoid block with 2.8 ml 0.5% bupivacaine heavy in L3-L4 intervertebral space. Inj. Hydrocortisone 25 mg was given I.V. intraoperatively and repeated every 6 hours for 24 hours. Anesthetic management included considerations of systemic organ involvement, thrombocytopenia, and perioperative steroid replacement. Spinal block can be given with platelet count > 50,000/cumm. Strict asepsis should be maintained for invasive procedures. Maintenance of normothermia decreases the impact of Raynaud's phenomenon.

  7. Seroprevalence of Severe Fever with Thrombocytopenia Syndrome in Southeastern Korea, 2015

    PubMed Central

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease characterized by fever, thrombocytopenia and diarrhea. SFTS was firstly reported in Korea in 2013 but its seroprevalence in the country has yet to be investigated. Here, we investigate the seroprevalence of SFTS in a Korean population. A cross-sectional study was conducted on patients who had their sera tested for various reasons at a tertiary university hospital on particular days in May 2015. This study was conducted in a tertiary hospital in southeastern Korea. Total antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM), specific to SFTS virus (SFTSV) in serum samples were detected by a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA). A total of 1,069 serum samples were tested. Median age was 59 years (range 12–96 years), and 51.5% were male. Overall, 22 patients (2.1%) were tested positive for anti-SFTSV antibodies. The SFTS seroprevalence increased significantly with age (P = 0.034). The seropositive rate of rural area was higher than that of urban area (7.7% vs. 1.9%, P = 0.040). Seropositive rates were not significantly different among underlying diseases. None of the antibody-positive patients showed typical symptoms or laboratory findings of SFTS at the time of sample collection. Results of real-time reverse transcription polymerase chain reaction (RT-PCR) were negative for all the seropositive patients. Our study shows 2.1% SFTS seroprevalence among the patients visiting a tertiary hospital in Korea. Seroprevalence is higher in older and rural population. PMID:27914128

  8. Macrophages activated by C-reactive protein through Fc gamma RI transfer suppression of immune thrombocytopenia.

    PubMed

    Marjon, Kristopher D; Marnell, Lorraine L; Mold, Carolyn; Du Clos, Terry W

    2009-02-01

    C-reactive protein (CRP) is an acute-phase protein with therapeutic activity in mouse models of systemic lupus erythematosus and other inflammatory and autoimmune diseases. To determine the mechanism by which CRP suppresses immune complex disease, an adoptive transfer system was developed in a model of immune thrombocytopenic purpura (ITP). Injection of 200 microg of CRP 24 h before induction of ITP markedly decreased thrombocytopenia induced by anti-CD41. CRP-treated splenocytes also provided protection from ITP in adoptive transfer. Splenocytes from C57BL/6 mice were treated with 200 microg/ml CRP for 30 min, washed, and injected into mice 24 h before induction of ITP. Injection of 10(6) CRP-treated splenocytes protected mice from thrombocytopenia, as did i.v. Ig-treated but not BSA-treated splenocytes. The suppressive cell induced by CRP was found to be a macrophage by depletion, enrichment, and the use of purified bone marrow-derived macrophages. The induction of protection by CRP-treated cells was dependent on FcRgamma-chain and Syk activation, indicating an activating effect of CRP on the donor cell. Suppression of ITP by CRP-treated splenocytes required Fc gamma RI on the donor cell and Fc gamma RIIb in the recipient mice. These findings suggest that CRP generates suppressive macrophages through Fc gamma RI, which then act through an Fc gamma RIIb-dependent pathway in the recipient to decrease platelet clearance. These results provide insight into the mechanism of CRP regulatory activity in autoimmunity and suggest a potential new therapeutic approach to ITP.

  9. [Levels of antiplatelet factor 4-heparin antibodies and 4T score for heparin induced thrombocytopenia].

    PubMed

    Martinuzzo, Marta E; Cerrato, Graciela S; Iglesias Varela, Maria L; Adamczuk, Yolanda P; Pombo, Gonzalo; Forastiero, Ricardo R

    2012-01-01

    Heparin induced thrombocytopenia (HIT) is an immune-mediated disorder due to antibodies anti platelet factor 4-heparin (HPIA). Thrombocytopenia is often moderate but certain patients can develop morbid thrombotic complications. HPIA detection by ELISA has high sensitivity but low specificity, and low titers (without clinical significance) are frequent. A pretest clinical score (4T's) was developed in order to recognize patients that are at high risk of HIT. The aim of this study was to correlate HPIA levels and the 4T's score of consecutive patients derived to our center. We evaluated 84 patients (35 of them developed thrombosis); the clinical questionnaire was sent along with the sample and was analyzed by an investigator who did not know the patients' characteristics, and 4T's scores were calculated before performing the laboratory tests. HPIA were measured by ELISA (Asserachrom HPIA) that detects IgG, IgM and IgA isotypes, (the only reagent available in our country). 4T's score correlated with HPIA levels (rho spearman 0.472, p < 0.001). Patients with 4T's = 6 had higher absorbance percentages than those with = 5 (67 vs. 39%, p < 0.001), and patients with thrombosis also presented higher titers (59 vs. 39%, p = 0.017) than those who did not develop this complication. In conclusion, high titers of HPIA measured by EIA which detects the 3 isotypes, clearly correlate with 4T's score = 6 and are more frequent in patients who develop thrombosis, just as reported when an IgG specific ELISA is used.

  10. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia

    PubMed Central

    Niihori, Tetsuya; Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kaneko, Takashi; Hashii, Yoshiko; Irie, Masahiro; Sato, Atsushi; Saito-Nanjo, Yuka; Funayama, Ryo; Nagashima, Takeshi; Inoue, Shin-ichi; Nakayama, Keiko; Ozono, Keiichi; Kure, Shigeo; Matsubara, Yoichi; Imaizumi, Masue; Aoki, Yoko

    2015-01-01

    Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8th zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-β-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans. PMID:26581901

  11. Epidemiologic Features and Environmental Risk Factors of Severe Fever with Thrombocytopenia Syndrome, Xinyang, China

    PubMed Central

    Liu, Kun; Cui, Ning; Fang, Li-Qun; Wang, Bing-Jun; Lu, Qing-Bin; Peng, Wei; Li, Hao; Wang, Li-Yuan; Liang, Song; Wang, Hong-Yu; Zhang, Yao-Yun; Zhuang, Lu; Yang, Hong; Gray, Gregory C.; de Vlas, Sake J.; Liu, Wei; Cao, Wu-Chun

    2014-01-01

    Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in rural areas of Central China in 2009, caused by a novel bunyavirus, SFTS virus (SFTSV). The disease usually presents as fever, thrombocytopenia, and leukocytopenia, with case-fatality rates ranging from 2.5% to 30%. Haemaphysalis longicornis was suspected to be the most likely vector of SFTSV. By the end of 2012, the disease had expanded to 13 provinces of China. SFTS patients have been reported in Japan and South Korea, and a disease similar to SFTS has been reported in the United States. Methodology/Principal Findings We characterized the epidemiologic features of 504 confirmed SFTS cases in Xinyang Region, the most severely SFTS-afflicted region in China from 2011 to 2012, and assessed the environmental risk factors. All cases occurred during March to November, with the epidemic peaking from May to July. The patients' ages ranged from 7 to 87 years (median 61 years), and the annual incidence increased with age (χ2 test for trend, P<0.001). The female-to-male ratio of cases was 1.58, and 97.0% of the cases were farmers who resided in the southern and western parts of the region. The Poisson regression analysis revealed that the spatial variations of SFTS incidence were significantly associated with the shrub, forest, and rain-fed cropland areas. Conclusions The distribution of SFTS showed highly significant temporal and spatial heterogeneity in Xinyang Region, with the majority of SFTS cases being elderly farmers who resided in the southern and western parts of the region, mostly acquiring infection between May and July when H. longicornis is highly active. The shrub, rain-fed, and rain-fed cropland areas were associated with high risk for this disease. PMID:24810269

  12. Characterization of severe fever with thrombocytopenia syndrome in rural regions of Zhejiang, China.

    PubMed

    Zhang, Lei; Ye, Ling; Ojcius, David M; Lou, Xiuyu; Wang, Chengwei; feng, Cen; Sun, Yi; Wang, Zhongfa; Li, Shibo; Zhang, Yanjun

    2014-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011-2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be positive for antibodies to the SFTS virus. SFTSV strains were isolated by culture using Vero, and the whole genomic sequences of two SFTSV strains (01 and Zhao) were sequenced and submitted to the GenBank. Homology analysis showed that the similarity of the target nucleocapsid gene from the SFTSV strains from different geographic areas was 94.2-100%. From the constructed phylogenetic tree, it was found that all the SFTSV strains diverged into two main clusters. Only the SFTSV strains from the Zhejiang (Daishan) region of China and the Yamaguchi, Miyazakj regions of Japan, were clustered into lineage II, consistent with both of these regions being isolated areas with similar geographic features. Two out of eight predicted linear B cell epitopes from the nucleocapsid protein showed mutations between the SFTSV strains of different clusters, but did not contribute to the binding ability of the specific SFTSV antibodies. This study confirmed that SFTSV has been circulating naturally and can cause a seasonal prevalence in Daishan, China. The results also suggest that the molecular characteristics of SFTSV are associated with the geographic region and all SFTSV strains can be divided into two genotypes.

  13. 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

  14. Critical issues in hematology: anemia, thrombocytopenia, coagulopathy, and blood product transfusions in critically ill patients.

    PubMed

    Drews, Reed E

    2003-12-01

    Systematic evaluations of anemia, thrombocytopenia, and coagulopathy are essential to identifying and managing their causes successfully. In all cases, clinicians should evaluate RBC measurements alongside WBC and platelet counts and WBC differentials. Multiple competing factors may coexist; certain factors affect RBCs independent of those that affect WBCs or platelets. Ideally, clinicians should examine the peripheral blood smear for morphologic features of RBCs, WBCs, and platelets that provide important clues to the cause of the patient's hematologic disorder. Thrombocytopenia arises from decreased platelet production, increased platelet destruction, or dilutional or distributional causes. Drug-induced thrombocytopenias present diagnostic challenges, because many medicines can cause thrombocytopenia and critically ill patients often receive multiple medications. If they suspect type II HIT, clinicians must promptly discontinue all heparin sources, including LMWHs, without awaiting laboratory confirmation, to avoid thrombotic sequelae. Because warfarin anticoagulation induces acquired protein C deficiency, thereby exacerbating the prothrombotic state of type II HIT, warfarin should be withheld until platelet counts increase to more than 100,000/microL and type II HIT is clearly resolving. The presence of a consumptive coagulopathy in the setting of thrombocytopenia supports a diagnosis of DIC, not TTP-HUS, and is demonstrated by decreasing serum fibrinogen levels, and increasing TTs, PTs, aPTTs, and fibrin degradation products. Increasing D-dimer, levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin. Elevated PTs or a PTTs can result from the absence of factors or the presence of inhibitors. Clinicians should suspect factor inhibitors when the prolonged PT or aPTT does not correct or only partially corrects following an immediate assay of a 1:1 mix of patient and normal plasma. In addition to factor inhibitors

  15. Syndromic mental retardation with thrombocytopenia due to 21q22.11q22.12 deletion: Report of three patients.

    PubMed

    Katzaki, Eleni; Morin, Gilles; Pollazzon, Marzia; Papa, Filomena Tiziana; Buoni, Sabrina; Hayek, Joussef; Andrieux, Joris; Lecerf, Laure; Popovici, Cornel; Receveur, Aline; Mathieu-Dramard, Michèle; Renieri, Alessandra; Mari, Francesca; Philip, Nicole

    2010-07-01

    During the last few years, an increasing number of microdeletion/microduplication syndromes have been delineated. This rapid evolution is mainly due to the availability of microarray technology as a routine diagnostic tool. Microdeletions of the 21q22.11q22.12 region encompassing the RUNX1 gene have been reported in nine patients presenting with syndromic thrombocytopenia and mental retardation. RUNX1 gene is responsible for an autosomal dominant platelet disorder with predisposition to acute myelogenous leukemia. We report on three novel patients with an overlapping "de novo" interstitial deletion involving the band 21q22 characterized by array-CGH. All our patients presented with severe developmental delay, dysmorphic features, behavioral problems, and thrombocytopenia. Comparing the clinical features of our patients with the overlapping ones already reported two potential phenotypes related to 21q22 microdeletion including RUNX1 were highlighted: thrombocytopenia with +/- mild dysmorphic features and syndromic thrombocytopenia with growth and developmental delay.

  16. Seroprevalence and risk factors for severe fever with thrombocytopenia syndrome virus infection in Jiangsu Province, China, 2011.

    PubMed

    Liang, Shuyi; Bao, Changjun; Zhou, Minghao; Hu, Jianli; Tang, Fenyang; Guo, Xiling; Jiao, Yongjun; Zhang, Wenshuai; Luo, Peilin; Li, Luxun; Zhu, Kuanyuan; Tan, Wenwen; Lu, Qimei; Ge, Hengming; Chen, Abao

    2014-02-01

    Severe fever with thrombocytopenia syndrome (SFTS), which is caused by a novel bunyavirus, is an emerging infectious disease in China. In 2011, this new virus was designated as severe fever with thrombocytopenia syndrome virus (SFTSV). The aim of the present study was to determine the seroprevalence and risk factors of SFTSV infection. The investigation was conducted among the general population in Jiangsu Province, China in 2011. A total of 2,510 serum samples were collected. Testing by enzyme-linked immunosorbent assay was conducted to determine the seroprevalence of SFTSV infection. Result showed that the overall seroprevalence of SFTSV infection was 0.44% (11 of 2,510) in seven counties in Jiangsu Province. Multiple variable logistic regression analysis showed that raising goats, farming, and grazing were risk factors for SFTSV infection. Raising goats, farming, and grazing might be important risk factors for virus exposure, and appropriate health education could be useful in preventing infections.

  17. Successful treatment with oseltamivir phosphate in a patient with chronic immune thrombocytopenia positive for anti-GPIb/IX autoantibody.

    PubMed

    Shao, Linlin; Wu, Yang; Zhou, Hai; Qin, Ping; Ni, Heyu; Peng, Jun; Hou, Ming

    2015-01-01

    The management of chronic immune thrombocytopenia (ITP) remains to be a challenge. Oseltamivir phosphate is a sialidase inhibitor agent used to treat influenza in the conventional sense. At present, we demonstrate for the first time that an adult chronic ITP patient with anti-GP Ib/IX autoantibody, who was resistant to corticosteroids, IVIG, recombinant human thrombopoietin, rituximab, danazol and vindesine, but was successfully treated with oseltamivir phosphate. Through flow cytometric analysis of β-galactose and β-GlcNAc exposure on platelet surfaces, we showed that oseltamivir phosphate could reduce the desialylation level of platelet glycoproteins in ITP patient. The substantial alleviation of thrombocytopenia in this case, though not leading to conclusions, lays a foundation for a novel approach for the treatment of ITP.

  18. Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections

    PubMed Central

    SAITO, M; OISHI, K; INOUE, S; DIMAANO, E M; ALERA, M T P; ROBLES, A M P; ESTRELLA, B D; KUMATORI, A; MOJI, K; ALONZO, M T; BUERANO, C C; MATIAS, R R; MORITA, K; NATIVIDAD, F F; NAGATAKE, T

    2004-01-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue haemorrhagic fever (DHF). To develop a better understanding of the roles of platelet-associated IgG (PAIgG) and IgM (PAIgM) in inducing thrombocytopenia and its severity of disease in patients with secondary dengue virus infection, the relationship between the PAIgG or PAIgM levels and disease severity as well as thrombocytopenia was examined in 78 patients with acute phase secondary infection in a prospective hospital-based study. The decrease in platelet count during the acute phase recovered significantly during the convalescent phase. In contrast, the increased levels of PAIgG or PAIgM that occurred during the acute phase of these patients decreased significantly during the convalescent phase. An inverse correlation between platelet count and PAIgG or PAIgM levels was found in these patients. Anti-dengue virus IgG and IgM activity was found in platelet eluates from 10 patients in an acute phase of secondary infection. Increased levels of PAIgG or PAIgM were significantly higher in DHF than those in dengue fever (DF). An increased level of PAIgM was associated independently with the development of DHF, representing a possible predictor of DHF with a high specificity. Our present data suggest that platelet-associated immunoglobulins involving antidengue virus activity play a pivotal role in the induction of thrombocytopenia and the severity of the disease in secondary dengue virus infections. PMID:15498040

  19. Spleen enlargement is a common finding in acute Puumala hantavirus infection and it does not associate with thrombocytopenia.

    PubMed

    Koskela, Sirpa M; Laine, Outi K; Paakkala, Antti S; Mäkelä, Satu M; Mustonen, Jukka T

    2014-10-01

    The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury.

  20. The Pharmacotherapy of Heparin-Induced Thrombocytopenia (HIT) : A Review of Contemporary Therapeutic Challenges in Clinical Practice.

    PubMed

    Hassan, Yahaya; Awaisu, Ahmed; Al-Meman, Ahmad Abdulrahman; Aziz, Noorizan Abd

    2008-04-01

    Our objectives were to discuss a general overview on the description and recognition of heparin-induced thrombocytopenia (HIT) and present a critical review of the traditional and most recent advances in its pharmacotherapy. Computerized searches were done on MEDLINE and Iowa Drug Information Service (IDIS) databases from June 2001 until June 2007 and from May 2005 until May 2007, respectively. Search terms used included 'heparin-induced thrombocytopenia', 'heparin-associated thrombocytopenia', therapeutics, HIT, HAT. We largely selected publications within the timeframe above, but did not exclude commonly referenced and highly regarded older publications. The commonly referenced published articles were obtained through manual searches derived from bibliographic citations and retrievals from the authors' personal files. Pertinent literatures (89 key articles) that were thought to have substantially contributed new information to the therapeutics of HIT within the last 6 years were identified, reviewed and presented. The following limits were used for the MEDLINE and IDIS searches: 'human', drug therapy', 'review', 'meta-analysis', 'clinical trial', and case reports. The therapeutics of HIT is rapidly evolving and needs to consider an evidence - based approach. It is imperative that practitioners be aware of the associated risk and be up-to-date with the current advances in the management of this fatal clinical condition.

  1. Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin β minor chain

    PubMed Central

    Kauppi, Maria; Hilton, Adrienne A.; Metcalf, Donald; Ng, Ashley P.; Hyland, Craig D.; Collinge, Janelle E.; Kile, Benjamin T.; Hilton, Douglas J.; Alexander, Warren S.

    2012-01-01

    Diverse mutations in the genes encoding hemoglobin (Hb) have been characterized in human disease. We describe here a mutation in the mouse Hbb-b2 gene, denoted Plt12, that precisely mimics the human hemoglobin Hotel Dieu variant. The mutation results in increased affinity of Hb for oxygen and Plt12 mutant mice exhibited reduced partial pressure of O2 in the blood, accompanied by erythrocytosis characterized by elevated erythropoietin levels and splenomegaly with excess erythropoiesis. Most homozygous Hbb-b2Plt12/Plt12 mice succumbed to early lethality associated with emphysema, cardiac abnormalities, and liver degeneration. Survivors displayed a marked thrombocytopenia without significant deficiencies in the numbers of megakaryocytes or megakaryocyte progenitor cells. The lifespan of platelets in the circulation of Hbb-b2Plt12/Plt12 mice was normal, and splenectomy did not correct the thrombocytopenia, suggesting that increased sequestration was unlikely to be a major contributor. These data, together with the observation that megakaryocytes in Hbb-b2Plt12/Plt12 mice appeared smaller and deficient in cytoplasm, support a model in which hypoxia causes thrombocytopenia as a consequence of an inability of megakaryocytes, once formed, to properly mature and produce sufficient platelets. The Plt12 mouse is a model of high O2-affinity hemoglobinopathy and provides insights into hematopoiesis under conditions of chronic hypoxia. PMID:22203977

  2. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    PubMed Central

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  3. Alleviation of viper venom induced platelet apoptosis by crocin (Crocus sativus): implications for thrombocytopenia in viper bites.

    PubMed

    Santhosh, M Sebastin; Thushara, R M; Hemshekhar, M; Sunitha, K; Devaraja, S; Kemparaju, K; Girish, K S

    2013-11-01

    Viper envenomations are characterized by prominent local and systemic manifestations including hematological alterations. Snake venom metalloproteinases (SVMPs) and phospholipase A2 (PLA2) plays crucial role in the pathophysiology of hemorrhage by targeting/altering the platelets function which may result in thrombocytopenia. Platelets undergo the classic events of mitochondria-mediated apoptotic pathway due to augmented endogenous reactive oxygen species (ROS) levels. The observed anticoagulant effects during viper envenomations could be due to exacerbated platelet apoptosis and thrombocytopenia. Moreover, antivenin treatments are ineffective against the venom-induced oxidative stress; therefore, it necessitates an auxiliary therapy involving antioxidants which can effectively scavenge the endothelium-generated/endogenous ROS and protect the platelets. The present study explored the effects of viper venom on platelet apoptosis and its amelioration by a phytochemical crocin. The study evaluated the Vipera russelli venom-induced apoptotic events including endogenous ROS generation, intracellular Ca(2+) mobilization, mitochondrial membrane depolarization, cyt-c translocation, caspase activation and phosphatidylserine externalization which were effectively mitigated when the venom was pre-treated with crocin. The study highlights one of the less studied features of venom-induced secondary complications i.e. platelet apoptosis and sheds light on the underlying basis for venom-induced thrombocytopenia, systemic hemorrhage and in vivo anticoagulant effect.

  4. [Simultaneous manifestation of thrombocytopenia -induced endoleak type IV and II as late complication following abdominal stentgraft implantation].

    PubMed

    Kurcz, Jacek; Garcarek, Jerzy; Guziński, Maciej; Janczak, Dariusz; Skóra, Jan

    2012-01-01

    Endoleak type IV occurs very rarely and typically was observed 4-8 weeks following implantation of previous generation stentgrafts. Endoleak type II, although relatively common, typically presents early after stentgraft implantation. In our case combined thrombocytopenia-induced endoleaks type II and IV manifested 22 months following stentgraft implantation. The patient presented with abdominal pain and rapid increase in aneurysm diameter. The patient did not require endovascular intervention, medical treatment proved sufficient to relieve clinical symptoms and to prevent progression of the aneurysmal sac. Thrombocytopenia has not manifested itself again so far. The patient is followed-up with increased frequency. It should be noted that occurrence of type IV endoleak, in particular when associated with other type of endoleak, can result from thrombocytopenia. This type of endoleak should be included in differential diagnosis not only in early postinterventional period but also in long-term follow-up, first of all in patients with first generation stentgrafts implanted, featured by porosity of covering material.

  5. Dealing with thrombocytopenia during anticoagulation with heparins for active venous thromboembolism: a play-it-safe practical approach

    PubMed Central

    Abdel-Razeq, Hikmat; Ismael, Yousef

    2011-01-01

    Purpose: Thrombocytopenia is not uncommonly encountered following active anticoagulation of thromboembolism with unfractionated or even low-molecular-weight heparins. In this report, and utilizing a case study, we will address issues related to the diagnosis and treatment of heparin-induced thrombocytopenia (HIT) in a community-based clinical practice. Methods: The case of a 73-year-old female patient who was recently diagnosed with gastroesophageal junction cancer and who developed left lower extremity deep vein thrombosis (DVT) while on active chemotherapy is presented. Following the initiation of anticoagulation, a significant drop in platelet counts was noted and a clinical diagnosis of HIT was made. Articles published in English addressing issues related to anticoagulation and thrombocytopenia were accessed from PubMed and are discussed. Results: HIT is not uncommon, but its diagnosis can occasionally be difficult to confirm. Alternative anticoagulants might not be available for immediate use and many require special expertise for appropriate use. Fondaparinux, a synthetic pentasaccharide, is approved for active anticoagulation of DVT and pulmonary embolism and can be given once daily subcutaneously at a fixed dose with no need for monitoring. Many recent reports described the successful use of this agent in the treatment of HIT. Conclusion: HIT can be difficult to diagnose; diagnostic tests are generally not available in most hospitals and the available ones lack the sensitivity and specificity needed to confirm such diagnosis. Additionally, the alternative anticoagulants are not widely available. In such circumstances, fondaparinux can be used as an alternative anticoagulant. PMID:21753883

  6. 'Sailing in troubled waters': a review of the use of anticoagulation in adult cancer patients with thrombocytopenia.

    PubMed

    Ibrahim, Rami B; Skewes, Michelle D; Kuriakose, Philip

    2016-09-01

    Simply providing anticoagulation therapy is not as straightforward of a solution in cancer patients who have concurrent thrombocytopenia owing to the increased risk of bleeding complications. Currently, few guidelines are in place to assist clinicians in safely managing thrombocytopenic cancer patients on anticoagulation. The purpose of this review is to critically examine the available body of biomedical literature surrounding anticoagulant use against the backdrop of cancer-related thrombocytopenia in adult patients. Available evidence for the use of parenteral anticoagulants (low molecular weight heparins, unfractionated heparin, pentasaccharides, and direct thrombin inhibitors) and oral anticoagulants (vitamin K antagonists and novel oral anticoagulants) in thrombocytopenic cancer patients is described. The review revealed many inconsistencies between reports on this topic, which made it difficult to draw firm conclusions as to, for example, the ideal well tolerated anticoagulant dose in thrombocytopenic cancer patients? Intriguingly, critical clinical information including (but not limited) patient platelet nadirs, platelet counts during bleeding episodes, and platelet transfusion support was absent from a not-so-insignificant number of publications. Despite these shortcomings, the review sets out to formulate recommendations on the management of anticoagulation, at prophylactic or treatment doses, in adult cancer patients who also have concurrent thrombocytopenia. It also enlists a call for the medical community, by mapping select clinical guideposts, for further research in this setting. With the inclusion of these criteria in future studies, only then formal recommendations on the ideal safe dosage of anticoagulants in cancer patients, based on solid evidence, are conceived.

  7. Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia.

    PubMed

    Nurden, Paquita; Debili, Najet; Vainchenker, William; Bobe, Regis; Bredoux, Raymonde; Corvazier, Elisabeth; Combrie, Robert; Fressinaud, Edith; Meyer, Dominique; Nurden, Alan T; Enouf, Jocelyne

    2006-10-15

    In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibalpha (GPIbalpha). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbalpha N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbalpha, alphaIIb, and beta3 were normally present. Proteins involved in Ca(2+) homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca(2+) ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP(3)-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34(+) cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.

  8. Family Cluster Analysis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Korea

    PubMed Central

    Yoo, Jeong Rae; Heo, Sang Taek; Park, Dahee; Kim, Hyemin; Fukuma, Aiko; Fukushi, Shuetsu; Shimojima, Masayuki; Lee, Keun Hwa

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is tick-borne viral disease that was first suspected in China in 2009. The causative virus (SFTSV) was isolated in 2009 and reported in 2011, and SFTSV expanded its geographic distribution in 2012–2013, from China to South Korea and Japan. Most SFTSV infections occur through Haemaphysalis longicornis. However, SFTSV infection can also occur between family members, and nosocomial transmission of SFTSV is also possible through close contact with a patient. In this study, we first analyzed clinical, epidemiological, and laboratory data for SFTS patients and family members of an index patient in Korea. The S segment of SFTSV was amplified from the sera of three patients, and the S segment of SFTSV and IgG specific to SFTSV were detected in the serum from one family member; although this individual had no history of exposure to H. longicornis, she frequently had close contact with the index patient. In Korea, SFTSV infection among family members does not have to be reported, and we suggest that person-to-person transmission of SFTSV among family members is possible in Korea. PMID:27928083

  9. Interleukin-7 is decreased and maybe plays a pro-inflammatory function in primary immune thrombocytopenia.

    PubMed

    Li, Hui-Yuan; Zhang, Dong-Lei; Zhang, Xian; Liu, Xiao-Fan; Xue, Feng; Yang, Ren-Chi

    2015-01-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease with many immune dysfunctions, including over-proliferation and apoptosis resistance of auto-reactive lymphocytes. This study aimed to determine the effects of interleukin (IL)-7 on the cytokine production and survival of peripheral blood mononuclear cells and bone marrow mononuclear cells from ITP patients. We found that the plasma IL-7 levels in peripheral blood from ITP patients were lower than that of the normal controls, and it had positive correlation with platelet counts. However, the levels of IL-7 did not change in bone marrow serum of ITP patients compared with that of normal controls. The result of further stimulation experiments in vitro showed that IL-7 up-regulated the apoptosis of autologous platelets, promoted the proliferation and secretion of interferon-γ, tumor necrosis factor-α as well as IL-10 of lymphocyte both from peripheral blood and bone marrow. As the role of IL-7 in apoptosis-resistance and stimulation of pro-inflammatory cytokines, we speculated that decreased IL-7 in peripheral blood, maybe, is a consequence of the negative feedback of the pro-inflammatory function in ITP patients.

  10. MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.

    PubMed

    Rauch, Philipp J; Ellegast, Jana M; Widmer, Corinne C; Fritsch, Kristin; Goede, Jeroen S; Valk, Peter J M; Löwenberg, Bob; Takizawa, Hitoshi; Manz, Markus G

    2016-11-03

    Although the molecular pathways that cause acute myeloid leukemia (AML) are increasingly well understood, the pathogenesis of peripheral blood cytopenia, a major cause of AML mortality, remains obscure. A prevailing assumption states that AML spatially displaces nonleukemic hematopoiesis from the bone marrow. However, examining an initial cohort of 223 AML patients, we found no correlation between bone marrow blast content and cytopenia, questioning the displacement theory. Measuring serum concentration of thrombopoietin (TPO), a key regulator of hematopoietic stem cells and megakaryocytes, revealed loss of physiologic negative correlation with platelet count in AML cases with blasts expressing MPL, the thrombopoietin (scavenging) receptor. Mechanistic studies demonstrated that MPL(hi) blasts could indeed clear TPO, likely therefore leading to insufficient cytokine levels for nonleukemic hematopoiesis. Microarray analysis in an independent multicenter study cohort of 437 AML cases validated MPL expression as a central predictor of thrombocytopenia and neutropenia in AML. Moreover, t(8;21) AML cases demonstrated the highest average MPL expression and lowest average platelet and absolute neutrophil counts among subgroups. Our work thus explains the pathophysiology of peripheral blood cytopenia in a relevant number of AML cases.

  11. Helicobacter pylori infection is not correlated with subclinical thrombocytopenia: a cross-sectional study.

    PubMed

    Samson, Annette D; Schipperus, Martin R; Langers, Alexandra M J; Dekkers, Olaf M

    2014-01-01

    In a small percentage of patients with immune thrombocytopenia (ITP), H. pylori eradication has a positive effect on platelet counts. Whether H. pylori infection is associated with a lower thrombocyte count in persons without clinical ITP is unknown. We performed a cross-sectional study to compare thrombocyte count between H. pylori infected (n=108) and H. pylori non-infected patients (n=600) who underwent a diagnostic gastroscopy. The mean thrombocyte count in H. pylori negative patients was 257 × 10(9)/l, in H. pylori positive patients 252 × 10(9)/l (mean difference 5 × 10(9)/l, 95% CI: -23 to 14). Subgroup analysis did not show significant differences either. In the patient group without apparent comorbidity, there were no subjects with thrombocyte counts <120. In 36 H. pylori positive patients in whom data post-eradication was available, platelet counts pre- and post-eradication were similar. In conclusion, this study could not demonstrate a lower thrombocyte count in H. pylori infected patients or in subgroups of H. pylori infected patients compared to non-infected subjects.

  12. 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

    2016-09-08

    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.

  13. Human Antibody Neutralizes Severe Fever with Thrombocytopenia Syndrome Virus, an Emerging Hemorrhagic Fever Virus

    PubMed Central

    Guo, Xiling; Zhang, Li; Zhang, Wenshuai; Chi, Ying; Zeng, Xiaoyan; Li, Xian; Qi, Xian; Jin, Qiu; Zhang, Xiao; Huang, Mingming; Wang, Hua; Chen, Yin; Bao, Changjun; Hu, Jianli; Liang, Shuyi; Bao, Lin; Wu, Tao

    2013-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly discovered member of the Bunyaviridae family, is the causative agent of an emerging hemorrhagic fever, SFTS, in China. Currently, there are no vaccines or effective therapies against SFTS. In this study, a combinatorial human antibody library was constructed from the peripheral lymphocytes of 5 patients who had recovered from SFTS. The library was screened against purified virions for the production of single-chain variable-region fragments (ScFv). Of the 6 positive clones, one clone (monoclonal antibody [MAb] 4-5) showed neutralizing activity against SFTSV infection in Vero cells. MAb 4-5 was found to effectively neutralize all of the clinical isolates of SFTSV tested, which were isolated from patients in China from 2010 to 2012. MAb 4-5 was found to bind a linear epitope in the ectodomain of glycoprotein Gn. Its neutralizing activity is attributed to blockage of the interactions between the Gn protein and the cellular receptor, indicating that inhibition of virus-cell attachment is its main mechanism. These data suggest that MAb 4-5 can be used as a promising candidate molecule for immunotherapy against SFTSV infection. PMID:23863504

  14. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults.

    PubMed

    Gómez-Almaguer, David; Herrera-Rojas, Miguel A; Jaime-Pérez, José C; Gómez-De León, Andrés; Cantú-Rodríguez, Olga G; Gutiérrez-Aguirre, César H; Tarín-Arzaga, Luz; Hernández-Reyes, Jesús; Ruiz-Arguelles, Guillermo J

    2014-06-19

    Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 10(9)/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 10(9)/L) was achieved in 50% of patients and response at 6 months (platelets ≥30 <100 × 10(9)/L) was achieved in another 25%; relapse-free survival was 66.7% at 12 months (median response duration of 8.3 months). In conclusion, eltrombopag/dexamethasone is a feasible frontline therapy for ITP. This trial is registered at www.clinicaltrials.gov as NCT01652599.

  15. Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies.

    PubMed

    Langeberg, Wendy J; Schoonen, W Marieke; Eisen, Melissa; Gamelin, Laurence; Stryker, Scott

    2016-06-01

    This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists.

  16. Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

    PubMed Central

    Audia, Sylvain; Samson, Maxime; Guy, Julien; Janikashvili, Nona; Fraszczak, Jennifer; Trad, Malika; Ciudad, Marion; Leguy, Vanessa; Berthier, Sabine; Petrella, Tony; Aho-Glélé, Serge; Martin, Laurent; Maynadié, Marc; Lorcerie, Bernard; Rat, Patrick; Cheynel, Nicolas; Katsanis, Emmanuel; Larmonier, Nicolas

    2011-01-01

    Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug. PMID:21876120

  17. Absolute lymphocyte count and risk of short-term infection in patients with immune thrombocytopenia.

    PubMed

    Hu, Ming-Hung; Yu, Yuan-Bin; Huang, Yu-Chung; Gau, Jyh-Pyng; Hsiao, Liang-Tsai; Liu, Jin-Hwang; Chen, Ming-Huang; Chiou, Tzeon-Jye; Chen, Po-Min; Tzeng, Cheng-Hwai; Liu, Chun-Yu

    2014-06-01

    Patients with immune thrombocytopenia (ITP) may be at increased risk of infection because of the steroids and other immunosuppressive agents used in its treatment. This study aimed to identify events that are associated with infection within 6 months of diagnosis and the impact that infection has on survival. We retrospectively evaluated 239 patients (107 men, 132 women; median age 61 years) diagnosed between January 1997 and August 2011. Every patient received steroid treatment according to the platelet count and the extent of bleeding. Logistic regression analysis was used to identify risk factors associated with the development of infection within 6 months of ITP being diagnosed. Sixty-two patients (25.9 %) developed an infection within 6 months of diagnosis. Multivariate analysis revealed that a lower absolute lymphocyte count (ALC) at diagnosis (<1 × 10(9)/l) was an independent risk factor for infection (P = 0.039; 95 % confidence interval, 1.033-3.599; odds ratio, 1.928). The time to infection event is significant shorter in those of low ALC, compared with those of higher ALC (P = 0.032). Furthermore, the 1-year mortality rate after ITP diagnosis was significantly higher in those patients who developed an infection (P = 0.001). ITP patients with a low absolute lymphocyte count at diagnosis have an increased risk of infection, and those who develop infections have lower 1-year survival.

  18. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    PubMed Central

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  19. Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China.

    PubMed

    Luo, Li-Mei; Zhao, Li; Wen, Hong-Ling; Zhang, Zhen-Tang; Liu, Jian-Wei; Fang, Li-Zhu; Xue, Zai-Feng; Ma, Dong-Qiang; Zhang, Xiao-Shuang; Ding, Shu-Jun; Lei, Xiao-Ying; Yu, Xue-jie

    2015-10-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, we also analyzed the prevalence of SFTSV infection among H. longicornis ticks collected from vegetation in Shandong Province, China. Our results showed a low prevalence of SFTSV among collected ticks (0.2%, 8/3,300 ticks), and we showed that ticks fed on SFTSV-infected mice could acquire the virus and transstadially and transovarially transmit it to other developmental stages of ticks. Furthermore, SFTSV-infected ticks could transmit the virus to mice during feeding. Our findings indicate ticks could serve as a vector and reservoir of SFTSV.

  20. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis.

    PubMed

    Liu, Quan; He, Biao; Huang, Si-Yang; Wei, Feng; Zhu, Xing-Quan

    2014-08-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV.

  1. Systemic neosporosis in a dog treated for immune-mediated thrombocytopenia and hemolytic anemia.

    PubMed

    Magaña, Angie; Sánchez, Félix; Villa, Karina; Rivera, Liliana; Morales, Elizabeth

    2015-12-01

    A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case.

  2. Subcutaneous anti-D globulin application is a safe treatment option of immune thrombocytopenia in children.

    PubMed

    Trebo, Monika M; Frey, Eva; Gadner, Helmut; Minkov, Milen

    2010-04-01

    Subcutaneous (sc) administration of anti-D seems to offer the same efficacy as intravenous administration but with less side effects. Here we report our experience with sc anti-D for pediatric immune thrombocytopenia (ITP). A total of 12 children with a median age of 11.2 years had been treated by sc anti-D. They received a median of 2 sc anti-D applications (range 1-31) with a dosage of 250-375 IE/kg body weight. Only in one out of a total of 102 single applications, a minimal and self-limited side effect (chills) had been observed. The mean platelet count was almost doubled after sc anti-D (p < 0.0001). After a median follow-up of 11.4 months, all patients are alive without major bleeding and stay well. We conclude that sc anti-D: is not only an efficient means of treating ITP in children but is also a safe and convenient one.

  3. Systemic Inflammatory Response and Severe Thrombocytopenia after Endovascular Thoracic Aortic Aneurysm Repair

    PubMed Central

    Silvestrin, Valentina; Bonvini, Stefano; Antonello, Michele; Grego, Franco; Vettor, Roberto

    2017-01-01

    After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm. Treatment with prednisone (50 mg/bid) for two weeks did not improve the clinical and laboratory findings. We utilized danazol, a weak androgen that has been shown to be effective in the treatment of immune and idiopathic thrombocytopenic purpura, and after 12 days of treatment with danazol (200 mg/bid), the patient improved progressively and platelet number increased up to 53,000/μL. Patients undergoing endovascular repair of thoracic aortic aneurysm should be carefully monitored for the development of postimplantation syndrome. This clinical condition is relatively common after the endovascular repair of aortic aneurysm but is rarely observed after endovascular repair of thoracic aortic aneurysms. The different known therapeutical approaches are still empiric, with reported beneficial effects with the use of NSAID, corticosteroids, and danazol. PMID:28154580

  4. A National Assessment of the Epidemiology of Severe Fever with Thrombocytopenia Syndrome, China

    PubMed Central

    Liu, Kun; Zhou, Hang; Sun, Ruo-Xi; Yao, Hong-Wu; Li, Yu; Wang, Li-Ping; Di Mu; Li, Xin-Lou; Yang, Yang; Gray, Gregory C.; Cui, Ning; Yin, Wen-Wu; Fang, Li-Qun; Yu, Hong-Jie; Cao, Wu-Chun

    2015-01-01

    First discovered in rural areas of middle-eastern China in 2009, severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis affecting hundreds of cases reported in China each year. Using the national surveillance data from 2010 to 2013, we conducted this retrospective epidemiological study and risk assessment of SFTS in China. We found that the incidence of SFTS and its epidemic areas are continuing to grow, but the case fatality rate (CFR) has steadily decreased. SFTS most commonly affected elderly farmers who acquired infection between May and July in middle-eastern China. However, other epidemiological characteristics such as incidence, sex ratio, CFR, and seasonality differ substantially across the affected provinces, which seem to be consistent with local agricultural activities and the seasonal abundance of ticks. Spatial scan statistics detected three hot spots of SFTS that accounted for 69.1% of SFTS cases in China. There was a strong association of SFTS incidence with temporal changes in the climate within the clusters. Multivariate modeling identified climate conditions, elevation, forest coverage, cattle density, and the presence of Haemaphysalis longicornis ticks as independent risk factors in the distribution of SFTS, based on which a predicted risk map of the disease was derived. PMID:25902910

  5. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents.

    PubMed

    Ghanima, Waleed; Junker, Peter; Hasselbalch, Hans Carl; Boiocchi, Leonardo; Geyer, Julia T; Feng, Xingmin; Gudbrandsdottir, Sif; Orazi, Attilio; Bussel, James B

    2011-10-01

    This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on-treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1·4 years of treatment was graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment Procollagen III N-propeptide (PIIINP) (6·6 μg/l) was significantly higher than on-treatment levels (5·6 μg/l); both were higher than controls (3·4 μg/l; P < 0·001). PIIINP was negatively correlated with treatment duration (r = -0·49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)-beta and basic-Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis.

  6. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group.

    PubMed

    Rodeghiero, Francesco; Michel, Marc; Gernsheimer, Terry; Ruggeri, Marco; Blanchette, Victor; Bussel, James B; Cines, Douglas B; Cooper, Nichola; Godeau, Bertrand; Greinacher, Andreas; Imbach, Paul; Khellaf, Mehdi; Klaassen, Robert J; Kühne, Thomas; Liebman, Howard; Mazzucconi, Maria Gabriella; Newland, Adrian; Pabinger, Ingrid; Tosetto, Alberto; Stasi, Roberto

    2013-04-04

    In a previous publication on new terminology, definitions, and outcome criteria for immune thrombocytopenia (ITP), the International Working Group (IWG) on ITP acknowledged that response to treatment should consist of clinically meaningful end points such as bleeding manifestations and that platelet count may not be the ideal parameter for capturing the benefits of therapy. The IWG now proposes a consensus-based ITP-specific bleeding assessment tool (ITP-BAT) with definitions and terminology consistent with those adopted for other bleeding disorders. Bleeding manifestations were grouped into three major domains: skin (S), visible mucosae (M), and organs (O), with gradation of severity (SMOG). Each bleeding manifestation is assessed at the time of examination. Severity is graded from 0 to 3 or 4, with grade 5 for any fatal bleeding. Bleeding reported by the patient without medical documentation is graded 1. Within each domain, the same grade is assigned to bleeding manifestations of similar clinical impact. The "worst bleeding manifestation since the last visit" (observation period) is graded (a suitable database collection form is provided), and the highest grade within each domain is recorded. The SMOG system provides a consistent description of the bleeding phenotype in ITP, and the IWG unanimously supports its adoption and validation in future clinical studies.

  7. Thrombosis during off pump LVAD placement in a patient with heparin induced thrombocytopenia using bivalirudin.

    PubMed

    Awad, Hamdy; Bryant, Richard; Malik, Obaid; Dimitrova, Galina; Sai-Sudhakar, Chittoor Bhaskar

    2013-04-29

    Here we present our attempt at off pump HeartMate II left ventricular assist device (LVAD) implantation using the anticoagulant bivalirudin in a patient with heparin induced thrombocytopenia, which resulted in thrombosis within the LVAD device. This required that our procedure be converted to on pump, and a new HeartMate II LVAD device to be implanted. In our view, this thrombotic event may have been caused by a number of factors that include bivalirudin's (1) short half-life of about 20 minutes, (2) decreased activity with blood stasis, (3) inability to prevent clot propagation, and (4) uncertainty with real-time monitoring of therapeutic levels. To prevent future thrombotic events, it may be beneficial to immediately deair the LVAD device prior to the coring of the left ventricle during off pump LVAD placement. In addition, a solution other than blood may be used for priming. If blood is used for priming of the LVAD device, the duration of blood stasis should not exceed 20 minutes when bivalirudin is being used for anticoagulation. Furthermore, this case emphasizes the importance of having a backup LVAD device available and ready to use during surgical procedures.

  8. Effect of steroids on the activation status of platelets in patients with Immune thrombocytopenia (ITP).

    PubMed

    Bhoria, Preeti; Sharma, Saniya; Varma, Neelam; Malhotra, Pankaj; Varma, Subhash; Luthra-Guptasarma, Manni

    2015-01-01

    The activation status of platelets in Immune Thrombocytopenia (ITP) patients--which is still somewhat controversial--is of potential interest, because activated platelets tend to aggregate (leading to excessive clotting or thromboembolic events) but cannot do so when platelet numbers are low, as in ITP. Although corticosteroids are the first line of therapy in ITP, the effect of steroids on activation of platelets has not been evaluated so far. We examined the status of platelet activation (with and without stimulation with ADP) in ITP patients, at the start of therapy (pre-steroid treatment, naive) and post-steroid treatment (classified on the basis of steroid responsiveness). We used flow cytometry to evaluate the levels of expression of P-selectin, and PAC-1 binding to platelets of 55 ITP patients and a similar number of healthy controls, treated with and without ADP. We found that platelets in ITP patients exist in an activated state. In patients who are responsive to steroids, the treatment reverses this situation. Also, the fold activation of platelets upon treatment with ADP is more in healthy controls than in ITP patients; treatment with steroids causes platelets in steroid-responsive patients to become more responsive to ADP-activation, similar to healthy controls. Thus steroids may cause changes in the ability of platelets to get activated with an agonist like ADP. Our results provide new insights into how, and why, steroid therapy helps in the treatment of ITP.

  9. A national assessment of the epidemiology of severe fever with thrombocytopenia syndrome, China.

    PubMed

    Liu, Kun; Zhou, Hang; Sun, Ruo-Xi; Yao, Hong-Wu; Li, Yu; Wang, Li-Ping; Mu, Di; Li, Xin-Lou; Yang, Yang; Gray, Gregory C; Cui, Ning; Yin, Wen-Wu; Fang, Li-Qun; Yu, Hong-Jie; Cao, Wu-Chun

    2015-04-23

    First discovered in rural areas of middle-eastern China in 2009, severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis affecting hundreds of cases reported in China each year. Using the national surveillance data from 2010 to 2013, we conducted this retrospective epidemiological study and risk assessment of SFTS in China. We found that the incidence of SFTS and its epidemic areas are continuing to grow, but the case fatality rate (CFR) has steadily decreased. SFTS most commonly affected elderly farmers who acquired infection between May and July in middle-eastern China. However, other epidemiological characteristics such as incidence, sex ratio, CFR, and seasonality differ substantially across the affected provinces, which seem to be consistent with local agricultural activities and the seasonal abundance of ticks. Spatial scan statistics detected three hot spots of SFTS that accounted for 69.1% of SFTS cases in China. There was a strong association of SFTS incidence with temporal changes in the climate within the clusters. Multivariate modeling identified climate conditions, elevation, forest coverage, cattle density, and the presence of Haemaphysalis longicornis ticks as independent risk factors in the distribution of SFTS, based on which a predicted risk map of the disease was derived.

  10. Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients.

    PubMed

    Stirnemann, Jérôme; Kaddouri, Najett; Khellaf, Medhi; Morin, Anne-Sophie; Prendki, Virginie; Michel, Marc; Mekinian, Arsène; Bierling, Philippe; Fenaux, Pierre; Godeau, Bertrand; Fain, Olivier

    2016-03-01

    Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10(9) platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6-13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan-Meier curve). Predictive factors (univariate analysis) of an initial and long-term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.

  11. The Efficacy of Colchicine and Dapsone Combination Therapy in Relapsed Immune Thrombocytopenia

    PubMed Central

    Rattanathammethee, Thanawat; Theerajangkhaphichai, Wasan; Rattarittamrong, Ekarat; Hantrakool, Sasinee; Chai-Adisaksopha, Chatree; Norasetthada, Lalita; Tantiworawit, Adisak

    2017-01-01

    The aim of the present paper is to evaluate the efficacy and safety of colchicine and dapsone combination therapy in cases of steroid-dependent, relapsed and refractory immune thrombocytopenia (ITP). This is a retrospective study of ITP patients who attended the Hematology Clinic at Chiang Mai University Hospital (Thailand) from 1 January 2008 to 30 September 2014. Medical records and clinical data were reviewed for efficacy and adverse effects. Sixty-four ITP patients received the combination therapy. The median age was 46 years and 70.3% were female. The majority (65.6%) were relapsed ITP patients. Median platelet count before starting treatment was 22.6×109/L. The response rate was 82.8%, with 75.0% of patients having a complete response. Median time to response was 8 weeks. The response rate was higher in relapsed patients (90.4%) compared to refractory (61.5%) and steroid-dependent patients (77.8%). Steroid treatment was discontinued in 30 patients (50%) following combination therapy. The most common side effect was hemolysis due to dapsone which was found in eight patients (12.5%). We can therefore conclude that combination therapy with colchicine and dapsone is an alternative second-line therapy option in relapsed ITP cases with acceptable side effects. PMID:28286634

  12. The management of filter-related caval thrombosis complicated by heparin-induced thrombocytopenia and thrombosis

    PubMed Central

    Shi, Wanyin; Lou, Wensheng; He, Xu; Liu, Changjian; Gu, Jianping

    2015-01-01

    This report evaluates the efficiency and safety of catheter-directed thrombolysis (CDT) using tissue plasminogen activator (tPA) and argatroban for the treatment of IVC filter thrombosis complicated by heparin-induced thrombocytopenia (HIT). From October 2012 to December 2014, 19 patients with unilateral lower extremity deep venous thrombosis were treated with standard anticoagulation, filter placement and urokinase-based CDT, all of whom developed IVC filter thrombosis and HIT. A revised protocol (tPA-based CDT and argatroban-based anticoagulation) was performed to treat IVC thrombosis. The extent of lysis was graded from I to III. Technical and clinical outcomes and complications were monitored. A total of 22 filters were implanted, 20 of which were retrieved later. The technical success rate of revised CDT for IVC thrombosis was 100%. On evaluating IVC thrombus, thirteen cases (68.4%, 13/19) were identified as grade III (complete resolution of thrombus) and six (31.6%, 6/19) as grade II (50-99% resolution of thrombus). No major bleeding related to CDT occurred. HIT in all patients was successfully treated with argatroban. Two patients with malignant tumor died during the follow-up. For patients with IVC filter thrombosis complicated by HIT, it seems tPA-based CDT and argatroban is an alternative regimen. PMID:26550230

  13. Platelet PlA2 Polymorphism and the risk for thrombosis in heparin-induced thrombocytopenia.

    PubMed

    Harris, Kenneth; Nguyen, Phan; Van Cott, Elizabeth M

    2008-02-01

    Platelet glycoprotein (GP) IIb/IIIa has an important role in platelet aggregation. A polymorphism of platelet GPIIIa (PlA2, also called HPA1b) has been associated with a higher risk of thrombosis, but its implication in heparin-induced thrombocytopenia (HIT) is unclear. To investigate the hypothesis that the PlA2 polymorphism influences the prothrombotic effects of HIT, we conducted a prospective study of 66 consecutive patients with a laboratory diagnosis of HIT. The end point of the study was the diagnosis of a thrombus within 30 days of the positive HIT test result. The Diagnostica Stago (Asnières, France) enzyme-linked immunosorbent assay was used to detect HIT antibodies, and a polymerase chain reaction assay was used to detect the PlA2 polymorphism. Of the 66 patients, thrombotic complications developed in 27 (41%). Patients with the PlA2 allele demonstrated a significantly higher thrombosis risk than did patients without (69% vs 32%; P = .0088; odds ratio, 4.68; 95% confidence interval, 1.39-15.72). The risk was stronger for arterial thrombosis and for patients 60 years or older. There was a significant association between the PlA2 polymorphism of GPIIIa and the risk of thrombosis in patients with HIT antibodies.

  14. Management of children and adolescents with primary immune thrombocytopenia: controversies and solutions.

    PubMed

    Kühne, T; Imbach, P

    2013-01-01

    The management including diagnostic procedures, prophylaxis, treatment and follow-up of patients with primary immune thrombocytopenia (ITP) in childhood is controversial due to limited clinical data, difficulties in the estimation of individual bleeding risk and heterogeneity of pathophysiology potentially causing various treatment responses. Advances in the management of children include increased international collaborations, improved quality of diagnosis and treatment, increased clinical data, refinement of consensus statements where clinical evidence is absent, new drugs and last but not least establishment of watch-and-wait strategies. The Intercontinental Cooperative ITP Study Group promotes international collaboration since more than 10 years based on a worldwide network and experience in registries. Future considerations include concentration of available resources, strengthening international collaboration, focusing on most important scientific and clinical questions, such as identification of the subgroup of patients that benefits most from prophylactic platelet-enhancing treatments and investigation of treatment endpoints other than concepts solely based on the platelet count, including bleeding symptoms, health-related quality of life and economical aspects of treatments.

  15. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.

    PubMed

    Tamary, Hannah; Roganovic, Jelena; Chitlur, Meera; Nugent, Diane J

    2010-07-01

    The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

  16. Autoimmune hemolytic anemia and autoimmune thrombocytopenia at diagnosis and during follow-up of Hodgkin lymphoma.

    PubMed

    Dimou, Maria; Angelopoulou, Maria K; Pangalis, Gerassimos A; Georgiou, Georgios; Kalpadakis, Christina; Pappi, Vassiliki; Tsopra, Olga; Koutsoukos, Konstantinos; Zografos, Eleftherios; Boutsikas, George; Moschogianni, Maria; Vardounioti, Ioanna; Petevi, Kyriaki; Karali, Vassiliki; Kanellopoulos, Alexandros; Ntalageorgos, Themis; Yiakoumis, Xanthis; Bartzis, Vasiliki; Bitsani, Aikaterini; Pessach, Elias; Efthimiou, Anna; Korkolopoulou, Penelope; Rassidakis, George; Kyrtsonis, Marie-Christine; Patsouris, Efstratios; Meletis, John; Panayiotidis, Panayiotis; Vassilakopoulos, Theodoros P

    2012-08-01

    Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.

  17. [Primary immune thrombocytopenia in adults in Mexico: national characteristics and the relation to international literature].

    PubMed

    Meillón-García, Luis Antonio; García-Chávez, Jaime; Gómez-Almaguer, David; Gutiérrez-Espíndola, Guillermo R; Martínez-Murillo, Carlos

    2014-01-01

    In order to identify the clinical approach of a sample of Mexican hematologists for primary immune thrombocytopenia (ITP) in adults in Mexico, we applied an electronic survey via the internet to identify common practices for the diagnosis and treatment of ITP and draw a comparison between the information from these hematologists with international guidelines or the international literature. The results were analyzed using measures of central tendency. The sample was 21 medical hematologists, predominantly from Mexico City (average age: 51.4 years). A total of 66.7% of the surveyed physicians use international guidelines to make therapeutic decisions, and 43% defined ITP including the numerical concept (< 100 x 10(9)/l). We found some differences between requested clinical exams and tests indicated by the guidelines. In first-line treatment (except emergency), 91% of the participants start with prednisone and 24% use dexamethasone. Danazol is used in persistent ITP by most (41%) of the specialists. In second-line treatment, 67% would indicate splenectomy. Some differences were found between clinical practice of the hematologists in Mexico versus guidelines recommendations.

  18. RhIG for the treatment of immune thrombocytopenia: consensus and controversy

    PubMed Central

    Despotovic, Jenny M.; Lambert, Michele P.; Herman, Jay H.; Gernsheimer, Terry B.; McCrae, Keith R.; Tarantino, Michael D.; Bussel, James B.

    2012-01-01

    Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection. PMID:21981825

  19. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins.

    PubMed

    Pituch-Noworolska, Anna; Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2015-01-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose.

  20. Sulodexide for hemodialysis anticoagulation in heparin-induced thrombocytopenia type II.

    PubMed

    Borawski, Jacek; Zbroch, Edyta; Rydzewska-Rosolowska, Alicja; Pawlak, Krystyna; Mysliwiec, Michal

    2007-01-01

    Heparin-induced thrombocytopenia type II (HIT II) is an immune-mediated prothrombotic state. It requires cessation of all forms of heparin exposure. In maintenance hemodialysis (HD) patients, alternative anticoagulants (i.e. bivalirudin, danaparoid, fondaparinux) may be tried for HD procedure anticoagulation. Sulodexide (SLX) - a purified glycosaminoglycan preparation (80% heparan sulfate and 20% dermatan sulfate) - is not neutralized by platelet factor 4 and may be useful in HIT II. A 32-year-old man on continuous ambulatory peritoneal dilaysis (CAPD) and with protracted atrial fibrillation was given enoxaparin prophylaxis. On day 4, his platelets dropped from 119,000/micronL to 27,000/micronL and HIT II was diagnosed by positive heparin-induced platelet aggregation. While enoxaparin was withdrawn, the platelet count increased and remained stable. In the meantime, atrial fibrillation subsided but the patient developed pseudomonal peritonitis; the catheter was removed and the patient was switched to HD with SLX as an anticoagulant (bolus of 30 mg at HD onset). He was uneventfully treated with HD for 6 weeks and then reverted to CAPD. The widely available and inexpensive SLX may be a new, effective and potentially promising alternative anticoagulant in HD patients with HIT II.

  1. Structure-activity relationships of pyrazole derivatives as potential therapeutics for immune thrombocytopenias.

    PubMed

    Purohit, Meena K; Chakka, Sai Kumar; Scovell, Iain; Neschadim, Anton; Bello, Angelica M; Salum, Noruê; Katsman, Yulia; Bareau, Madeleine C; Branch, Donald R; Kotra, Lakshmi P

    2014-05-01

    Idiopathic or immune thrombocytopenia (ITP) is a serious clinical disorder involving the destruction of platelets by macrophages. Small molecule therapeutics are highly sought after to ease the burden on current therapies derived from human sources. Earlier, we discovered that dimers of five-membered heterocycles exhibited potential to inhibit phagocytosis of human RBCs by macrophages. Here, we reveal a structure-activity relationship of the bis-pyrazole class of molecules with -C-C-, -C-N- and -C-O- linkers, and their evaluation as inhibitors of phagocytosis of antibody-opsonized human RBCs as potential therapeutics for ITP. We have uncovered three potential candidates, 37, 47 and 50, all carrying a different linker connecting the two pyrazole moieties. Among these compounds, hydroxypyrazole derivative 50 is the most potent compound with an IC50 of 14 ± 9 μM for inhibiting the phagocytosis of antibody-opsonized human RBCs by macrophages. None of the compounds exhibited significant potential to induce apoptosis in peripheral blood mononuclear cells (PBMCs). Current study has revealed specific functional features, such as up to 2-atom spacer arm and alkyl substitution at one of the N(1) positions of the bivalent pyrazole core to be important for the inhibitory activity.

  2. Atomic description of the immune complex involved in heparin-induced thrombocytopenia

    DOE PAGES

    Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; ...

    2015-09-22

    Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Bindingmore » of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.« less

  3. Atomic description of the immune complex involved in heparin-induced thrombocytopenia

    SciTech Connect

    Cai, Zheng; Yarovoi, Serge V.; Zhu, Zhiqiang; Rauova, Lubica; Hayes, Vincent; Lebedeva, Tatiana; Liu, Qun; Poncz, Mortimer; Arepally, Gowthami; Cines, Douglas B.; Greene, Mark I.

    2015-09-22

    Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by immune complexes containing platelet factor 4 (PF4), antibodies to PF4 and heparin or cellular glycosaminoglycans (GAGs). Here we solve the crystal structures of the: (1) PF4 tetramer/fondaparinux complex, (2) PF4 tetramer/KKO-Fab complex (a murine monoclonal HIT-like antibody) and (3) PF4 monomer/RTO-Fab complex (a non-HIT anti-PF4 monoclonal antibody). Fondaparinux binds to the ‘closed’ end of the PF4 tetramer and stabilizes its conformation. This interaction in turn stabilizes the epitope for KKO on the ‘open’ end of the tetramer. Fondaparinux and KKO thereby collaborate to ‘stabilize’ the ternary pathogenic immune complex. Binding of RTO to PF4 monomers prevents PF4 tetramerization and inhibits KKO and human HIT IgG-induced platelet activation and platelet aggregation in vitro, and thrombus progression in vivo. Lastly, the atomic structures provide a basis to develop new diagnostics and non-anticoagulant therapeutics for HIT.

  4. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

    PubMed

    Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

    2016-07-01

    Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease.

  5. Heparin-Induced Thrombocytopenia Associated with a Heparin-Bonded Stent Graft.

    PubMed

    Blas, Joseph-Vincent V; Carsten, Christopher G; Gray, Bruce H

    2016-05-01

    We describe a case of heparin-induced thrombocytopenia (HIT) in association with heparin-bonded stent grafts. A 61-year-old man with claudication secondary to a left superficial femoral artery (SFA) occlusion was treated with 2 heparin-bonded polytetrafluorethylene (hep-PTFE) grafts. Despite the use of antiplatelet medication, he presented with thrombosed hep-PTFE grafts 1 week after initial treatment. An additional hep-PTFE graft was placed at the SFA origin because of migration of the first graft. He was discharged on anticoagulation; however, he presented again 2 weeks later with recurrent SFA thrombosis and a platelet count of 60,000, raising suspicion for HIT. All exogenous forms of heparin were discontinued, and he was started on an alternative anticoagulant. The patient returned again 5 days after being discharged with recurrent symptoms of acute limb ischemia. He underwent a left femoropopliteal artery bypass with autogenous conduit and removal of the grafts. He has since had an uneventful recovery. We believe HIT should be considered as a potential cause of hep-PTFE graft thrombosis. Diagnosis and management of these patients is complex and may require explantation of the graft.

  6. [Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

    PubMed

    Miyata, Shigeki; Maeda, Takuma

    2016-03-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  7. Identification of a novel SBF2 missense mutation associated with a rare case of thrombocytopenia using whole-exome sequencing.

    PubMed

    Abuzenadah, Adel M; Zaher, Galila F; Dallol, Ashraf; Damanhouri, Ghazi A; Chaudhary, Adeel G; Al-Sayes, Faten; Gari, Mamdooh A; AlZahrani, Mofareh; Hindawi, Salwa; Al-Qahtani, Mohammed H

    2013-11-01

    We describe in this report a case of a 6-years-old female who presented at the age of 1 month with a mucocutaneous bleeding and suspected thrombocytopenia. The patient's condition was refractory to the known idiopathic thrombocytopenic purpura treatments and congenital form of Thrombocytopenia was suspected following the delivery of a male sibling with the same phenotype. The patient also manifested fair colored hair and skin relative to her family however she did not have any detectable neurologic or other immunologic abnormalities. In order to further understand this condition, we have used whole-exome sequencing of the patient's DNA as well as her father's with the assumption that her condition is transmitted in an autosomal recessive manner. We have identified a missense change c.659C>G (p.Thr220Arg) in the SBF2 (also known as MTMR13) gene that causes a mutation in the DENN domain of the protein. This mutation was validated by traditional Sanger sequencing and analyzed in the remaining family members were it was found to segregate in the homozygous state in the affected siblings and in the heterozygous state in both parents. This novel mutation in the DENN domain of SBF2 maybe interfering with its putative association with the Rab family of small GTPases which are important mediators of vesicle transport and membrane trafficking. In conclusion, we have identified a novel mutation that is associated with severe thrombocytopenia. The fact that this mutation is found in SBF2 gene may indicate that the underlying cause of thrombocytopenia in our patient is either a new variant form of Griscelli syndrome (through the Rab GTPases action) or a variant Charcot-Marie-Tooth type 4 disease as SBF2 truncating mutations were previously identified in sufferers of this disease. This finding will help to accurately diagnose and classify similar cases of congenital thrombocytopenia and provide further proof to the power of whole-exome sequencing in personalizing patients

  8. Use of platelet transfusions prior to lumbar punctures or epidural anaesthesia for the prevention of complications in people with thrombocytopenia

    PubMed Central

    Estcourt, Lise J; Ingram, Callum; Doree, Carolyn; Trivella, Marialena; Stanworth, Simon J

    2016-01-01

    Background People with a low platelet count (thrombocytopenia) often require lumbar punctures or an epidural anaesthetic. Lumbar punctures can be diagnostic (haematological malignancies, epidural haematoma, meningitis) or therapeutic (spinal anaesthetic, administration of chemotherapy). Epidural catheters are placed for administration of epidural anaesthetic. Current practice in many countries is to correct thrombocytopenia with platelet transfusions prior to lumbar punctures and epidural anaesthesia, in order to mitigate the risk of serious procedure-related bleeding. However, the platelet count threshold recommended prior to these procedures varies significantly from country to country. This indicates significant uncertainty among clinicians of the correct management of these patients. The risk of bleeding appears to be low but if bleeding occurs it can be very serious (spinal haematoma). Therefore, people may 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 a lumbar puncture or epidural anaesthesia in people with thrombocytopenia (low platelet count). Search methods We searched for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), EMBASE (from 1974), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 3 March 2016. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people of any age with thrombocytopenia requiring insertion of a lumbar puncture needle or epidural catheter. We only included RCTs published in English. Data collection and analysis We used standard methodological procedures expected by Cochrane. Main results We identified no completed or ongoing RCTs in English. We did not exclude any completed or ongoing RCTs

  9. Immune-mediated Hemolytic Anemia and Thrombocytopenia in the Dog: A retrospective study of 55 cases diagnosed from 1979 through 1983 at the Western College of Veterinary Medicine

    PubMed Central

    Jackson, Marion L.; Kruth, Stephen A.

    1985-01-01

    All recognized cases (n = 55) of immune-mediated hemolytic anemia and immune-mediated thrombocytopenia in dogs presented to the Western College of Veterinary Medicine from 1969 through 1983 were reviewed. Specific areas of concern were: association with other conditions, therapeutic response, prognosis, relapse rate and final outcome. Of these 55 cases, 19 were immune-mediated hemolytic anemia, 26 were immune-mediated thrombocytopenia and 10 were both immune-mediated hemolytic anemia and thrombocytopenia. Females were slightly over-represented and the mean age was 6.4 years. Therapy consisted of various combinations of immuno-suppressive drugs and in some cases, whole blood transfusion and splenectomy. No firm conclusions could be made regarding therapeutic efficacy, as a result of variation in treatment protocol and the occasional unavailability of follow-up data. Well over half of all cases were diagnosed as idiopathic. Precipitating factors or diseases most frequently implicated in secondary immune-mediated thrombocytopenia or hemolytic anemia were: recent vaccination, drug therapy, obstetrical complications, stress, recent viral infection and neoplasia. Twice as many cases of immune-mediated hemolytic anemia were seen in the cooler months (October to March), although this could not be related to antibody class or thermal reactivity. Immune-mediated thrombocytopenia both as a single disease and combined with immune-mediated hemolytic anemia had no seasonal incidence. History, clinical findings and hematological and clinical chemistry findings were consistent with data previously reported, with the exception of icterus, which appeared to be of higher incidence than most reports, being present in almost 50% of immune-mediated hemolytic anemia cases. Just over half of all dogs survived, although the survival rate was highest for immune-mediated hemolytic anemia, followed closely by immune-mediated thrombocytopenia and lowest for the combined disease. Immune

  10. Role of platelet function and platelet membrane glycoproteins in children with primary immune thrombocytopenia

    PubMed Central

    Liu, Wen-Jun; Bai, Jing; Guo, Qu-Lian; Huang, Zhe; Yang, Hong; Bai, Yong-Qi

    2016-01-01

    The aim of the present study was to examine and understand changes in platelet functions prior to and after the treatment of primary immune thrombocytopenia (ITP) in children. An automatic hematology analyzer and whole blood flow cytometry were used to detect immature platelet fraction (IPF), IPC and membrane glycoproteins (CD62p, PAC-1 and CD42b) in ITP children (ITP group), children with complete response after ITP treatment (ITP-CR group) and children with elective surgery (normal control group). The results showed that, levels of platelet count (PLT) and plateletcrit in the ITP group were lower alhtough the levels of mean platelet volume, platelet distribution width and platelet-large cell ratio (P-LCR) were higher than those in the normal control and ITP-CR groups. PLT in the ITP-CR group was lower than that in the normal controls. Additionally, IPF% was higher in the normal control and ITP-CR groups, IPC was lower in the ITP group compared to the normal control and ITP-CR groups. Furthermore, prior to ADP activation, the expression levels of CD62p, PAC-1 and CD42b in the ITP group were lower in ITP group than those in the normal control and ITP-CR groups. The expression level of PAC-1 was lower in the ITP-CR and normal control groups. No differences were identified in CD62p and CD42b expression levels. Following ATP activation, CD62p, PAC-1 and CD42b expression in the ITP group was lower than that in the normal control and ITP-CR groups. PAC-1 expression was lower while CD62p expression was higher in the ITP-CR group compared to the normal control group. In conclusion, the activation of platelets in ITP children was low. Decreased platelet function, platelet parameters and platelet glycoproteins may be used as markers for monitoring the treatment efficacy in ITP children. PMID:27431926

  11. Platelet ligands and ADAMTS13 during Puumala hantavirus infection and associated thrombocytopenia.

    PubMed

    Laine, Outi; Mäkelä, Satu; Mustonen, Jukka; Helminen, Mika; Vaheri, Antti; Lassila, Riitta; Joutsi-Korhonen, Lotta

    2011-09-01

    We aimed here to elucidate the role of adhesive platelet ligands and endothelial involvement during the acute phase of Puumala hantavirus (PUUV) infection. Nineteen hospital-treated patients with serologically confirmed diagnosis of acute PUUV infection were included. Patient charts were reviewed for clinical and basic laboratory data. Plasma levels of von Willebrand factor antigen (VWF:Ag), ristocetin cofactor (VWF:RCo), factor VIII (FVIII:C) and a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13 (ADAMTS13) activities as well as fibrinogen and fibronectin were measured three times acutely and once during the recovery phase. VWF:Ag and VWF:RCo were nearly three-fold higher acutely compared with recovery (median 252 vs. 88%, and mean 267 vs. 98%, respectively; P<0.001 for both), whereas FVIII:C was only slightly elevated (median 118 vs. 88%, P=0.002) and remarkably failed to show association with VWF in the acute phase. ADAMTS13 activity and fibronectin concentration were lower in the acute compared with the recovery phase (median 56 vs. 63%, P=0.003, and median 221 vs. 330 μmol/l, P=0.001, respectively). Fibrinogen raised acutely (mean 5.0 vs. 3.3 g/l, P<0.001), negatively correlating with the platelet count (r=-0.468, P=0.043). Markedly upregulated fibrinogen and VWF together with decreased levels of ADAMTS13 activity and fibronectin were observed during acute PUUV infection. VWF and FVIII:C did not associate during the acute phase, whereas thrombocytopenia correlated negatively with fibrinogen. These findings imply several rearranged interactions between platelets and their ligands.

  12. Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015

    PubMed Central

    Choi, Seong Jin; Park, Sang-Won; Bae, In-Gyu; Kim, Sung-Han; Ryu, Seong Yeol; Kim, Hyun Ah; Jang, Hee-Chang; Hur, Jian; Jun, Jae-Bum; Jung, Younghee; Chang, Hyun-Ha; Kim, Young Keun; Yi, Jongyoun; Kim, Kye-Hyung; Hwang, Jeong-Hwan; Kim, Yeon-Sook; Jeong, Hye Won; Song, Kyoung-Ho; Park, Wan Beom; Kim, Eu Suk; Oh, Myoung-don

    2016-01-01

    Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. Methods/Principal Findings SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. Conclusions SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. PMID:28033338

  13. Function of eltrombopag-induced platelets compared to platelets from control patients with immune thrombocytopenia.

    PubMed

    Haselboeck, Johanna; Kaider, Alexandra; Pabinger, Ingrid; Panzer, Simon

    2013-04-01

    Data on the in vivo function of platelets induced by the thrombopoietin receptor agonist eltrombopag are scarce. To assess a possible influence of eltrombopag we compared platelet function of eltrombopag-treated immune thrombocytopenia (ITP) patients (group 1; n=10) after treatment response to that from control ITP patients (group 2; n=12). We further analysed platelet function at baseline and after one, three, and four weeks of eltrombopag treatment and estimated daily changes of platelet function during the eltrombopag-induced platelet rise. The formation of platelet-monocyte aggregates (PMA), P-selectin expression [MFI], and platelet adhesion under high shear conditions (surface coverage, SC) in vivo and after in vitro addition of agonists (ADP, TRAP-6, Collagen) were similar between both groups after response to eltrombopag treatment. Only TRAP-6 induced a lower SC in the eltrombopag group (p=0.03). All platelet function parameters except for Collagen-induced P-selectin expression changed significantly during treatment with eltrombopag. PMA, naïve and after addition of ADP or TRAP-6 increased with increasing platelet counts. P-selectin expression decreased, when measured without and upon addition of ADP, increased in the presence of TRAP-6, and remained unchanged after addition of Collagen. SC increased during the eltrombopag-induced platelet rise. All significant changes of platelet function correlated to changes in platelet counts. Two patients developed venous thromboses during eltrombopag treatment, but no association with any distinct single platelet function parameter or combinations thereof was identifiable. Thus, eltrombopag-induced platelets function similar to those from control ITP patients without discernible increased hyper-reactivity.

  14. Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using Monoclonal Antibodies to the Nucleocapsid Protein

    PubMed Central

    Fukuma, Aiko; Fukushi, Shuetsu; Yoshikawa, Tomoki; Tani, Hideki; Taniguchi, Satoshi; Kurosu, Takeshi; Egawa, Kazutaka; Suda, Yuto; Singh, Harpal; Nomachi, Taro; Gokuden, Mutsuyo; Ando, Katsuyuki; Kida, Kouji; Kan, Miki; Kato, Nobuyuki; Yoshikawa, Akira; Kitamoto, Hiroaki; Sato, Yuko; Suzuki, Tadaki; Hasegawa, Hideki; Morikawa, Shigeru; Shimojima, Masayuki; Saijo, Masayuki

    2016-01-01

    Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas. Methodology/Principal Findings We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350–1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag-capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were positive for IgG antibodies against SFTSV. Conclusions The newly developed Ag-capture ELISA is useful for SFTS diagnosis in acute phase patients with high levels of viremia. PMID:27045364

  15. Age Is a Critical Risk Factor for Severe Fever with Thrombocytopenia Syndrome

    PubMed Central

    Ding, Shujun; Niu, Guoyu; Xu, Xuehua; Li, Jinping; Zhang, Xiaomei; Yin, Haiying; Zhang, Naijie; Jiang, Xiaolin; Wang, Shiwen; Liang, Mifang; Wang, Xianjun; Yu, Xue-jie

    2014-01-01

    Background Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease in East Asia. SFTS is a tick borne hemorrhagic fever caused by SFTSV, a new bunyavirus named after the syndrome. We investigated the epidemiology of SFTS in Laizhou County, Shandong Province, China. Methods We collected serum specimens of all patients who were clinically diagnosed as suspected SFTS cases in 2010 and 2011 in Laizhou County. The patients' serum specimens were tested for SFTSV by real time fluorescence quantitative PCR (RT-qPCR). We collected 1,060 serum specimens from healthy human volunteers by random sampling in Laizhou County in 2011. Healthy persons' serum specimens were tested for specific SFTSV IgG antibody by ELISA. Results 71 SFTS cases were diagnosed in Laizhou County in 2010 and 2011, which resulted in the incidence rate of 4.1/100,000 annually. The patients ranged from 15 years old to 87 years old and the median age of the patients were 59 years old. The incidence rate of SFTS was significantly higher in patients over 40 years old and fatal cases only occurred in patients over 50 years old. 3.3% (35/1,060) of healthy people were positive to SFTSV IgG antibody. The SFTSV antibody positive rate was not significantly different among people at different age groups. Conclusion Our results revealed that seroprevalence of SFTSV in healthy people in Laizhou County was not significantly different among age groups, but SFTS patients were mainly elderly people, suggesting that age is the critical risk factor or determinant for SFTS morbidity and mortality. PMID:25369237

  16. Efficacy of eltrombopag in management of bleeding symptoms associated with chronic immune thrombocytopenia.

    PubMed

    Tarantino, Michael D; Fogarty, Patrick; Mayer, Bhabita; Vasey, Sandra Y; Brainsky, Andres

    2013-04-01

    Bleeding is of particular clinical importance in the management of chronic immune thrombocytopenia (ITP), which involves impaired platelet production and accelerated destruction. We report the first comprehensive analysis of the impact of eltrombopag on bleeding in five clinical studies of adult chronic ITP: two 6-week phase 2 (TRA100773A) and phase 3 (TRA100773B) studies; a 6-month phase 3 study (RAISE); a phase 2 repeat-dose study (REPEAT); and a phase 3 extension study (EXTEND). Bleeding was assessed using the World Health Organization Bleeding Scale and categorized as no bleeding (grade 0), any bleeding (grades 1-4), and clinically significant bleeding (grades 2-4). Bleeding was also assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Across all studies, bleeding at baseline ranged from 50 to 73% for eltrombopag-treated patients; by week 2, bleeding had decreased, ranging from 26 to 39%. This trend was maintained throughout treatment. Similar results were observed for clinically significant bleeding. No such trend was seen in placebo-treated patients for any bleeding or clinically significant bleeding. For TRA100773B and RAISE, the odds of any bleeding across the entire treatment period were 51 and 76% lower for eltrombopag-treated versus placebo-treated patients (P=0.021, P<0.001). The odds of clinically significant bleeding in RAISE were 65% lower (P<0.001). In conclusion, analysis of prospective data from five clinical studies demonstrates that eltrombopag significantly reduces bleeding in adult patients with chronic ITP.

  17. Hospitalizations in pediatric patients with immune thrombocytopenia in the United States

    PubMed Central

    Tarantino, Michael D.; Danese, Mark; Klaassen, Robert J.; Duryea, Jennifer; Eisen, Melissa; Bussel, James

    2016-01-01

    Abstract To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality. In 2009, there were an estimated 4499 hospitalizations in children aged 6 months–17 years with ITP; 43% in children aged 1–5 years; and 47% with emergency department encounters. The mean hospitalization cost was $5398, mean LOS 2.0 days, with 0.3% mortality (n = 13). With any bleeding (15.2%, including gastrointestinal 2.0%, hematuria 1.3%, intracranial hemorrhage [ICH] 0.6%), mean hospitalization cost was $7215, LOS 2.5 days, with 1.5% mortality. For ICH (0.6%, n = 27), mean cost was $40 209, LOS 8.5 days, with 21% mortality. With infections (14%, including upper respiratory 5.2%, viral 4.9%, bacterial 1.9%), the mean cost was $6928, LOS 2.9 days, with 0.9% mortality. Septic shock was reported in 0.3% of discharges. Utilization included immunoglobulin administration (37%) and splenectomies (2.3%). Factors associated with higher costs included age >6 years, ICH, hematuria, transfusion, splenectomy, and bone marrow diagnostics (p < 0.05). In conclusion, of the 4499 hospitalizations with ITP, mortality rates of 1.5%, 21%, and 0.9% were seen with any bleeding, ICH, and infection, respectively. Higher costs were associated with clinically significant bleeding and procedures. Future analyses may reveal effects of the implementation of more recent ITP guidelines and use of additional treatments. PMID:26941022

  18. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program.

    PubMed

    McGowan, Kelly E; Makari, Joy; Diamantouros, Artemis; Bucci, Claudia; Rempel, Peter; Selby, Rita; Geerts, William

    2016-04-21

    Heparin-induced thrombocytopenia (HIT) is an adverse drug reaction occurring in up to 5% of patients exposed to unfractionated heparin (UFH). We examined the impact of a hospital-wide strategy for avoiding heparin on the incidence of HIT, HIT with thrombosis (HITT), and HIT-related costs. The Avoid-Heparin Initiative, implemented at a tertiary care hospital in Toronto, Ontario, Canada, since 2006, involved replacing UFH with low-molecular-weight heparin (LMWH) for prophylactic and therapeutic indications. Consecutive cases with suspected HIT from 2003 through 2012 were reviewed. Rates of suspected HIT, adjudicated HIT, and HITT, along with HIT-related expenditures were compared in the pre-intervention (2003-2005) and the avoid-heparin (2007-2012) phases. The annual rate of suspected HIT decreased 42%, from 85.5 per 10 000 admissions in the pre-intervention phase to 49.0 per 10 000 admissions in the avoid-heparin phase ( ITALIC! P< .001). The annual rate of patients with a positive HIT assay decreased 63% from 16.5 to 6.1 per 10 000 admissions ( ITALIC! P< .001), adjudicated HIT decreased 79% from 10.7 to 2.2 per 10 000 admissions ( ITALIC! P< .001), and HITT decreased 91% from 4.6 to 0.4 per 10 000 admissions ( ITALIC! P< .001). Hospital HIT-related expenditures decreased by $266 938 per year in the avoid-heparin phase. To the best of our knowledge, this is the first study demonstrating the success and feasibility of a hospital-wide HIT prevention strategy.

  19. Macrothrombocytopenia and developmental delay with a de novo CDC42 mutation: Yet another locus for thrombocytopenia and developmental delay.

    PubMed

    Takenouchi, Toshiki; Kosaki, Rika; Niizuma, Takahiro; Hata, Kenichiro; Kosaki, Kenjiro

    2015-11-01

    The combinatory phenotype of thrombocytopenia and developmental delay has been described for two genetic conditions: a chromosome 11q deletion that is referred to as Jacobsen syndrome, and a 21q22 microdeletion syndrome. Herein, we report a young girl who presented with persistent macrothrombocytopenia and a developmental delay. Whole exome sequencing revealed a de novo amino acid substitution in CDC42, a critical regulator of the cytoskeleton. Our observation recapitulates observations in mice lacking Cdc42. We suggest that this CDC42 mutation may represent yet another mechanism leading to the combinatory phenotype of persistent macrothrombocytopenia and developmental delay.

  20. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

    PubMed

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

  1. A patient with isochromosome 18q, radial-thumb aplasia, thrombocytopenia, and an unbalanced 10;18 chromosome translocation.

    PubMed

    Sahoo, Trilochan; Naeem, Rizwan; Pham, Kim; Chheng, Sou; Noblin, Sarah T; Bacino, Carlos A; Gambello, Michael J

    2005-02-15

    We report on the clinical and cytogenetic findings in a newborn with a de novo isochromosome 18q. Radial/thumb aplasia and thrombocytopenia were significant features in addition to multiple congenital anomalies. Comparison with reported cases suggests that the genes for such features are located on the 18q arm. An additional finding of a non-reciprocal translocation between chromosome 18p telomere and chromosome 10q telomere was also observed in a majority of cells examined. This additional rearrangement likely has minimal phenotypic consequences, but does raise the possibility that cryptic translocations of telomeric ends of the deleted arm in isochromosome cases may be more common than appreciated.

  2. Outcome based on treatment protocol in patients with primary canine immune-mediated thrombocytopenia: 46 cases (2000–2013)

    PubMed Central

    Scuderi, Margaret Ann; Snead, Elizabeth; Mehain, Susan; Waldner, Cheryl; Epp, Tasha

    2016-01-01

    This study investigated the relationship between treatment protocol, survival to discharge, and relapse in 46 dogs diagnosed with primary immune-mediated thrombocytopenia (ITP) at the Western College of Veterinary Medicine between 2000 and 2013. Treatment was at the discretion of the attending clinician and consisted of either a corticosteroid alone or a corticosteroid plus a secondary therapy. There was no association between survival to discharge and treatment protocol (P = 0.23). Of the surviving in-patients, 39% experienced a relapse. Our study failed to show a significant difference in survival and relapse based on treatment protocol. PMID:27152040

  3. RHD zygosity predicts degree of platelet response to anti-D immune globulin treatment in children with immune thrombocytopenia.

    PubMed

    Despotovic, Jenny M; McGann, Patrick T; Smeltzer, Matthew; Aygun, Banu; Ware, Russell E

    2013-09-01

    Anti-D immunoglobulin is a common front-line treatment for childhood immune thrombocytopenia (ITP) that typically results in a rapid and significant increase in platelet count. Unpredictable treatment responses and interpatient variability limit more widespread use. We hypothesized that anti-D response variability is influenced by RHD gene zygosity and erythrocyte D antigen expression. We compared RHD zygosity and quantitative D antigen expression to anti-D treatment results. Hemizygous RHD subjects demonstrated significantly higher platelet increases and peak platelet counts than homozygous RHD subjects. Future studies should investigate the mechanisms by which RHD zygosity and D antigen expression affect platelet responses to anti-D immunoglobulin.

  4. Thrombocytopenia-associated multiple organ failure or severe haemolysis, elevated liver enzymes, low platelet count in a postpartum case.

    PubMed

    Jagia, Manish; Taqi, Salah; Hanafi, Mahmoud; Aisha, Fakeir

    2013-01-01

    Thrombocytopenia-associated multiple organ failure (TAMOF) is a thrombotic microangiopathic syndrome that includes thrombotic thrombocytopenic purpura, secondary thrombotic microangiopathy, and disseminated intravascular coagulation. We report a case of postpartum female who presented with TAMOF or severe Haemolysis, elevated liver enzymes, low platelet count (HELLP) which was managed with plasma exchange. This case report is to make clinicians aware that TAMOF, severe HELLP, and other differential diagnosis in a postpartum case have a thin differentiating line and plasma exchange can be considered as one of the management options.

  5. A case report of thrombocytopenia-associated multiple organ failure secondary to Salmonella enterica serotype Typhi infection in a pediatric patient: successful treatment with plasma exchange.

    PubMed

    Yildirim, Inci; Ceyhan, Mehmet; Bayrakci, Benan; Uysal, Mutlu; Kuskonmaz, Baris; Ozaltin, Fatih

    2010-04-01

    A high proportion of the patients with Salmonella enterica serotype Typhi infection develop severe sepsis. The mortality rate is high despite aggressive antimicrobial therapy in these patients. The case of a 10-year-old boy who developed thrombocytopenia-associated multiple organ failure (TAMOF) secondary to S. typhi infection is reported. The patient did not respond to antimicrobial treatment, including ciprofloxacin, in addition to conventional supportive measures, so plasma exchange was performed. The thrombocytopenia and organ failure had resolved after 3 days of plasma exchange therapy. Plasma exchange is suggested to be a life-saving intervention in a child with TAMOF secondary to S. typhi infection.

  6. An outbreak of late-term abortions, premature births, and congenital deformities associated with a bovine viral diarrhea virus 1 subtype b that induces thrombocytopenia.

    PubMed

    Blanchard, Patricia C; Ridpath, Julia F; Walker, Jennifer B; Hietala, Sharon K

    2010-01-01

    Bovine viral diarrhea virus 1 (BVDV-1) subtype b was isolated from premature Holstein calves from a dairy herd that experienced an outbreak of premature births, late-term abortions, brachygnathism, growth retardation, malformations of the brain and cranium, and rare extracranial skeletal malformations in calves born to first-calf heifers. Experimental inoculation of 3 colostrum-deprived calves aged 2-4 months old with this BVDV isolate resulted in thrombocytopenia, lymphopenia, and leukopenia. Outbreaks of brachygnathism are rarely associated with BVDV, and thrombocytopenia is rarely associated with BVDV-1 strains.

  7. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

    PubMed Central

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

  8. Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

    PubMed

    Laine, Outi K; Koskela, Sirpa M; Outinen, Tuula K; Joutsi-Korhonen, Lotta; Huhtala, Heini; Vaheri, Antti; Hurme, Mikko A; Jylhävä, Juulia; Mäkelä, Satu M; Mustonen, Jukka T

    2014-09-01

    Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection.

  9. Characterization of Glycoprotein-Mediated Entry of Severe Fever with Thrombocytopenia Syndrome Virus

    PubMed Central

    Tani, Hideki; Shimojima, Masayuki; Fukushi, Shuetsu; Yoshikawa, Tomoki; Fukuma, Aiko; Taniguchi, Satoshi; Morikawa, Shigeru

    2016-01-01

    ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever with a high case fatality rate caused by SFTS virus (SFTSV). Effective vaccines and specific therapies for SFTS are urgently sought, and investigation into virus-host cell interactions is expected to contribute to the development of antiviral strategies. In this study, we have developed a pseudotype vesicular stomatitis virus (VSV) bearing the unmodified Gn/Gc glycoproteins (GPs) of SFTSV (SFTSVpv). We have analyzed the host cell entry of this pseudotype virus and native SFTSV. Both SFTSVpv and SFTSV exhibited high infectivity in various mammalian cell lines. The use of lysosomotropic agents indicated that virus entry occurred via pH-dependent endocytosis. SFTSVpv and SFTSV infectivity was neutralized by serial dilutions of convalescent-phase patient sera. Entry of SFTSVpv and growth of SFTSV were increased in Raji cells expressing not only the C-type lectin dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) but also DC-SIGN-related (DC-SIGNR) and liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin). 25-Hydroxycholesterol (25HC), a soluble oxysterol metabolite, inhibited the cell entry of SFTSVpv and the membrane fusion of SFTSV. These results indicate that pH-dependent endocytosis of SFTSVpv and SFTSV is enhanced by attachment to certain C-type lectins. SFTSVpv is an appropriate model for the investigation of SFTSV-GP-mediated cell entry and virus neutralization at lower biosafety levels. Furthermore, 25HC may represent a potential antiviral agent against SFTS. IMPORTANCE SFTSV is a recently discovered bunyavirus associated with SFTS, a viral hemorrhagic fever with a high case fatality rate endemic to China, South Korea, and Japan. Because little is known about the characteristics of the envelope protein and entry mechanisms of SFTSV, further studies will be required for the development of a vaccine or effective

  10. Identification of anti-thrombopoietin receptor antibody in prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation treated successfully with eltrombopag.

    PubMed

    Fujimi, Akihito; Kamihara, Yusuke; Hashimoto, Akari; Kanisawa, Yuji; Nakajima, Chisa; Hayasaka, Naotaka; Yamada, Shota; Okuda, Toshinori; Minami, Shinya; Ono, Kaoru; Iyama, Satoshi; Kato, Junji

    2015-10-01

    A 55-year-old female with stage IVA follicular lymphoma in third complete remission underwent allogeneic peripheral blood stem cell transplantation. Neutrophil engraftment was achieved on day +18; however, platelet counts remained below 10 × 10(3)/µL, necessitating transfusions twice a week for more than 3 months. Bone marrow showed a decreased number of megakaryocytes with hypolobulated nuclei. No graft versus host disease, viral infection, or disease relapse was observed. Furthermore, severe thrombocytopenia below 5.0 × 10(3)/µL refractory to transfusion appeared on day +240 after influenza virus infection. Treatments with intravenous immunoglobulin, romiplostim, and rituximab were administered without any recovery. Subsequently, eltrombopag was initiated on day +443, after which platelet counts rose gradually and continued to rise above 20 × 10(3)/µL after 10 weeks of administration. The serum thrombopoietin (TPO) level was markedly elevated, and anti-TPO receptor (TPOR) antibody was detected in the patient's serum. Anti-TPOR antibody may play an important role in some cases of prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation with unknown etiology, and eltrombopag could be a novel therapeutic option for such cases.

  11. Romiplostim for severe thrombocytopenia in the treatment of chronic hepatitis C virus infection: a new option for clinicians?

    PubMed

    Buccoliero, Giovanni; Urbano, Tiziana; Massa, Patrizio; Resta, Francesco; Pisconti, Salvatore

    2014-01-01

    We describe a case of a 64-year-old man with a history of ITP which had required several treatments including splenectomy, and with chronic hepatitis C virus (HCV) infection untreated due to severe thrombocytopenia. In March 2011, platelet count was 14,000/mmc and a thrombopoietic therapy with romiplostim was initiated at the dose of 2 mcg/kg/week that was increased to 8 mcg/kg/week. At week 32, platelet count was 65,000/mmc and an anti-HCV therapy with peginterferon and ribavirin was then started. At baseline laboratory tests indicated AST 99IU/l, ALT 125UI/l, HCV_RNA 3,220 UI/ml and HCV genotype 2a/2c. An early virological response (EVR) with normalization of transaminases in the course of antiviral therapy, such as a sustained virological response (SVR) after its interruption were recorded. Therefore a satisfactory platelet count (range 54.000-179.000/mmc) at the dose of 4 mcg/week during antiviral therapy, such as at the dose of 2 mcg/kg/week after antiviral interruption (range 65.000-292.000/mmc) was recorded. Romiplostim proved effective and safe in the course of antiviral treatment. Therefore it permitted the start of anti-HCV therapy despite severe thrombocytopenia and also avoided any peg-interferon dosage modification or discontinuation. Further prospective studies in larger patient cohort should be encouraged to validate this strategy.

  12. Eptifibatide-induced thrombocytopenia and thrombosis in humans require FcγRIIa and the integrin β3 cytoplasmic domain

    PubMed Central

    Gao, Cunji; Boylan, Brian; Bougie, Dan; Gill, Joan C.; Birenbaum, Jessica; Newman, Debra K.; Aster, Richard H.; Newman, Peter J.

    2009-01-01

    Thrombocytopenia and thrombosis following treatment with the integrin αIIbβ3 antagonist eptifibatide are rare complications caused by patient antibodies specific for ligand-occupied αIIbβ3. Whether such antibodies induce platelet clearance by simple opsonization, by inducing mild platelet activation, or both is poorly understood. To gain insight into the mechanism by which eptifibatide-dependent antibodies initiate platelet clearance, we incubated normal human platelets with patient serum containing an αIIbβ3-specific, eptifibatide-dependent antibody. We observed that in the presence of eptifibatide, patient IgG induced platelet secretion and aggregation as well as tyrosine phosphorylation of the integrin β3 cytoplasmic domain, the platelet FcγRIIa Fc receptor, the protein-tyrosine kinase Syk, and phospholipase Cγ2. Each activation event was inhibited by preincubation of the platelets with Fab fragments of the FcγRIIa-specific mAb IV.3 or with the Src family kinase inhibitor PP2. Patient serum plus eptifibatide did not, however, activate platelets from a patient with a variant form of Glanzmann thrombasthenia that expressed normal levels of FcγRIIa and the αIIbβ3 complex but lacked most of the β3 cytoplasmic domain. Taken together, these data suggest a novel mechanism whereby eptifibatide-dependent antibodies engage the integrin β3 subunit such that FcγRIIa and its downstream signaling components become activated, resulting in thrombocytopenia and a predisposition to thrombosis. PMID:19197137

  13. Spatial Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in China Using a Geographically Weighted Logistic Regression Model

    PubMed Central

    Wu, Liang; Deng, Fei; Xie, Zhong; Hu, Sheng; Shen, Shu; Shi, Junming; Liu, Dan

    2016-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which has had a serious impact on public health in parts of Asia. There is no specific antiviral drug or vaccine for SFTSV and, therefore, it is important to determine the factors that influence the occurrence of SFTSV infections. This study aimed to explore the spatial associations between SFTSV infections and several potential determinants, and to predict the high-risk areas in mainland China. The analysis was carried out at the level of provinces in mainland China. The potential explanatory variables that were investigated consisted of meteorological factors (average temperature, average monthly precipitation and average relative humidity), the average proportion of rural population and the average proportion of primary industries over three years (2010–2012). We constructed a geographically weighted logistic regression (GWLR) model in order to explore the associations between the selected variables and confirmed cases of SFTSV. The study showed that: (1) meteorological factors have a strong influence on the SFTSV cover; (2) a GWLR model is suitable for exploring SFTSV cover in mainland China; (3) our findings can be used for predicting high-risk areas and highlighting when meteorological factors pose a risk in order to aid in the implementation of public health strategies. PMID:27845737

  14. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia

    PubMed Central

    Lee-Sherick, Alisa B.; Callaghan, Michael; Noris, Patrizia; Savoia, Anna; Rajpurkar, Madhvi; Jones, Kenneth; Gowan, Katherine; Balduini, Carlo; Pecci, Alessandro; Gnan, Chiara; De Rocco, Daniela; Doubek, Michael; Li, Ling; Lu, Lily; Leung, Richard; Landolt-Marticorena, Carolina; Hunger, Stephen; Heller, Paula; Gutierrez-Hartmann, Arthur; Xiayuan, Liang; Pluthero, Fred G.; Rowley, Jesse W.; Weyrich, Andrew S.

    2015-01-01

    Some familial platelet disorders are associated with predisposition to leukemia, myelodysplastic syndrome (MDS) or dyserythropoietic anemia.1,2 We identified a family with autosomal dominant thrombocytopenia, high erythrocyte mean corpuscular volume (MCV) and two occurrences of B-cell precursor acute lymphoblastic leukemia (ALL). Whole exome sequencing identified a heterozygous single nucleotide change in ETV6 (Ets Variant Gene 6), c.641C>T, encoding a p.Pro214Leu substitution in the central domain, segregating with thrombocytopenia and elevated MCV. A screen of 23 families with similar phenotype found two with ETV6 mutations. One family had the p.Pro214Leu mutation and one individual with ALL. The other family had a c.1252A>G transition producing a p.Arg418Gly substitution in the DNA binding domain, with alternative splicing and exon-skipping. Functional characterization of these mutations showed aberrant cellular localization of mutant and endogenous ETV6, decreased transcriptional repression and altered megakaryocyte maturation. Our findings underscore a key role for ETV6 in platelet formation and leukemia predisposition. PMID:25807284

  15. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    PubMed

    Żmigrodzka, M; Guzera, M; Winnicka, A

    2016-01-01

    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  16. Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia.

    PubMed

    Robak, Tadeusz; Windyga, Jerzy; Trelinski, Jacek; von Depka Prondzinski, Mario; Giagounidis, Aristoteles; Doyen, Chantal; Janssens, Ann; Alvarez-Román, María Teresa; Jarque, Isidro; Loscertales, Javier; Rus, Gloria Pérez; Hellmann, Andrzej; Jêdrzejczak, Wieslaw Wiktor; Kuliczkowski, Kazimierz; Golubovic, Lana M; Celeketic, Dusica; Cucuianu, Andrei; Gheorghita, Emanuil; Lazaroiu, Mihaela; Shpilberg, Ofer; Attias, Dina; Karyagina, Elena; Svetlana, Kalinina; Vilchevska, Kateryna; Cooper, Nichola; Talks, Kate; Prabhu, Mukhyaprana; Sripada, Prasad; Bharadwaj, T P R; Næsted, Henrik; Skartved, Niels J Ø; Frandsen, Torben P; Flensburg, Mimi F; Andersen, Peter S; Petersen, Jørgen

    2012-11-01

    Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD(+) patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 μg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 μg/kg platelet responses, defined as platelet count ≥ 30 × 10(9)/L and an increase in platelet count by > 20 × 10(9)/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.

  17. Eptifibatide-induced thrombocytopenia and thrombosis in humans require FcgammaRIIa and the integrin beta3 cytoplasmic domain.

    PubMed

    Gao, Cunji; Boylan, Brian; Bougie, Dan; Gill, Joan C; Birenbaum, Jessica; Newman, Debra K; Aster, Richard H; Newman, Peter J

    2009-03-01

    Thrombocytopenia and thrombosis following treatment with the integrin alphaIIbbeta3 antagonist eptifibatide are rare complications caused by patient antibodies specific for ligand-occupied alphaIIbbeta3. Whether such antibodies induce platelet clearance by simple opsonization, by inducing mild platelet activation, or both is poorly understood. To gain insight into the mechanism by which eptifibatide-dependent antibodies initiate platelet clearance, we incubated normal human platelets with patient serum containing an alphaIIbbeta3-specific, eptifibatide-dependent antibody. We observed that in the presence of eptifibatide, patient IgG induced platelet secretion and aggregation as well as tyrosine phosphorylation of the integrin beta3 cytoplasmic domain, the platelet FcgammaRIIa Fc receptor, the protein-tyrosine kinase Syk, and phospholipase Cgamma2. Each activation event was inhibited by preincubation of the platelets with Fab fragments of the FcgammaRIIa-specific mAb IV.3 or with the Src family kinase inhibitor PP2. Patient serum plus eptifibatide did not, however, activate platelets from a patient with a variant form of Glanzmann thrombasthenia that expressed normal levels of FcgammaRIIa and the alphaIIbbeta3 complex but lacked most of the beta3 cytoplasmic domain. Taken together, these data suggest a novel mechanism whereby eptifibatide-dependent antibodies engage the integrin beta3 subunit such that FcgammaRIIa and its downstream signaling components become activated, resulting in thrombocytopenia and a predisposition to thrombosis.

  18. Circulating myeloid-derived suppressor cells predict disease activity and treatment response in patients with immune thrombocytopenia

    PubMed Central

    Zhou, J.; Zhou, Y.; Wen, J.; Sun, X.; Zhang, X.

    2017-01-01

    Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells’ differentiation and maturation. Therefore, we speculate that MDSCs might also be involved in the immune-dysregulation mechanism of ITP. In this study, we tested MDSCs and Treg cells in peripheral blood samples of twenty-five ITP patients and ten healthy donors. We found that MDSCs and Treg cells decreased simultaneously in active ITP patients. Relapsed ITP patients showed lower MDSCs levels compared with new patients. All patients received immunosuppressive treatment including dexamethasone alone or in combination with intravenous immune globulin. We found that MDSCs’ level after treatment correlated with platelet recovery. Our study is the first that focused on MDSCs’ role in ITP. Based on our results, we concluded that circulating MDSCs could predict disease activity and treatment response in ITP patients. This preliminary conclusion indicates a substantial significance of MDSCs in the pathophysiology and clinical treatment of ITP, which deserves further investigation. PMID:28225866

  19. The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence

    PubMed Central

    Meillier, Andrew

    2016-01-01

    Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD. PMID:27800187

  20. Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS).

    PubMed

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

    2013-05-30

    Long-term follow-up of children with immune thrombocytopenia (ITP) indicates that the majority undergo remission and severe thrombocytopenia is infrequent. Details regarding bleeding manifestations, however, remain poorly categorized. We report here long-term data from the Intercontinental Cooperative ITP Study Group Registry II focusing on natural history, bleeding manifestations, and management. Data on 1345 subjects were collected at diagnosis and at 28 days, 6, 12, and 24 months thereafter. Median platelet counts were 214 × 10(9)/L (interquartile range [IQR] 227, range 1-748), 211 × 10(9)/L (IQR 192, range 1-594), and 215 × 10(9)/L (IQR 198, range 1-598) at 6, 12, and 24 months, respectively, and a platelet count <20 × 10(9)/L was uncommon (7%, 7%, and 4%, respectively). Remission occurred in 37% of patients between 28 days and 6 months, 16% between 6 and 12 months, and 24% between 12 and 24 months. There were no reports of intracranial hemorrhage, and the most common site of bleeding was skin. In patients with severe thrombocytopenia we observed a trend toward more drug treatment with increasing number of bleeding sites. Our data support that ITP is a benign condition for most affected children and that major hemorrhage, even with prolonged severe thrombocytopenia, is rare.

  1. Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

    PubMed

    Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

    2015-07-01

    Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.

  2. Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

    PubMed Central

    Okamoto, Munehiro; Miyazawa, Takayuki; Morikawa, Shigeru; Ono, Fumiko; Nakamura, Shota; Sato, Eiji; Yoshida, Tomoyuki; Yoshikawa, Rokusuke; Sakai, Kouji; Mizutani, Tetsuya; Nagata, Noriyo; Takano, Jun-ichiro; Okabayashi, Sachi; Hamano, Masataka; Fujimoto, Koji; Nakaya, Takaaki; Iida, Tetsuya; Horii, Toshihiro; Miyabe-Nishiwaki, Takako; Watanabe, Akino; Kaneko, Akihisa; Saito, Akatsuki; Matsui, Atsushi; Hayakawa, Toshiyuki; Suzuki, Juri; Akari, Hirofumi; Matsuzawa, Tetsuro; Hirai, Hirohisa

    2015-01-01

    We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers. PMID:25743183

  3. Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome during an Outbreak in South Korea, 2013–2015

    PubMed Central

    Park, Sun-Whan; Ryou, Jungsang; Choi, Woo-Young; Han, Myung-Guk; Lee, Won-Ja

    2016-01-01

    Since the first reported case of severe fever with thrombocytopenia syndrome (SFTS) in South Korea in 2013, between 2013 and 2015, we collected 1,697 serum samples from suspected patients who experienced symptoms of SFTS. We performed reverse transcriptase polymerase chain reaction using total RNA extracted from the patients' sera. When viral RNA was detected in the sera, SFTS was diagnosed. Among the 1,697 samples, 170 were positive for SFTS virus. We then analyzed the epidemiologic features of these 170 cases. As a result, we found that the annual number of cases increased steadily. However, the annual case fatality rate exhibited a downward trend. The majority of patients were aged ≥ 60 years, and most cases occurred during May–October in the eastern and southern parts of the country. These results may be useful for effective SFTS control by describing the clinical and epidemiologic features of the disease in South Korea. PMID:27928084

  4. Induction of immune tolerance to platelet antigen by short-term thrombopoietin treatment in a mouse model of immune thrombocytopenia.

    PubMed

    Nishimoto, Tetsuya; Numajiri, Miku; Nakazaki, Hisataka; Okazaki, Yuka; Kuwana, Masataka

    2014-10-01

    Immune thrombocytopenia (ITP) is an autoimmune disorder caused by IgG anti-platelet autoantibodies. Thrombopoietin (TPO) receptor agonists are highly effective in inducing the recovery of platelet counts in ITP patients. Although these agents are thought to promote platelet production without affecting the autoimmune pathogenesis of the disease, a small subset of ITP patients exhibits sustained platelet recovery after treatment termination. To investigate mechanisms involved in this sustained recovery, we evaluated the effects of short-term TPO treatment using a mouse ITP model generated by Foxp3(+) T regulatory cell (Treg) depletion. After treatment, platelet recovery was sustained, along with complete suppression of both anti-platelet autoantibody production and T-cell responses to platelet autoantigens. TPO treatment also promoted the peripheral induction of Foxp3(+) Tregs in conjunction with elevated circulating TGF-β levels. In summary, thrombopoietic agents are capable of inducing immune tolerance to platelet autoantigens, thereby suppressing the autoimmune pathogenesis of ITP.

  5. Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody (rituximab).

    PubMed

    Ibrahim, Khalid; Maghfoor, Irfan; Elghazaly, Assem; Bakshi, Nasir; Mohamed, Said Y; Aljurf, Mahmoud

    2011-01-01

    Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders.

  6. Heparin-Induced-Thrombocytopenia Causing Massive Aortic Thrombosis after Ascending Aortic Replacement for Type A Acute Aortic Dissection

    PubMed Central

    Imoto, Kiyotaka; Uchida, Keiji; Isoda, Susumu; Karube, Norihisa; Yasuda, Shota; Masuda, Munetaka

    2016-01-01

    A 77-year-old woman underwent emergency ascending aortic replacement for type A acute aortic dissection. Fifteen days after the operation, she had motor and sensory disturbances in the lower limbs. Computed tomography revealed multiple aortic thrombi and disrupted blood flow in the right external iliac and left common iliac arteries. She underwent an emergency thrombectomy for acute limb ischemia. Because heparin- induced-thrombocytopenia (HIT) was suspected to have caused the multiple aortic thrombi, we postoperatively changed the anticoagulant therapy from heparin to argatroban. Seventeen days after the first operation, gastrointestinal bleeding developed, and the patient died of mesenteric ischemia caused by HIT. Arterial embolization caused by HIT after cardiovascular surgery is a rare, but fatal event. To avoid fatal complications, early diagnosis and early treatment are essential. Use of a scoring system would probably facilitate early diagnosis. PMID:26780951

  7. Characteristics and Factors Associated with Death among Patients Hospitalized for Severe Fever with Thrombocytopenia Syndrome, South Korea, 2013.

    PubMed

    Shin, Jaeseung; Kwon, Donghyok; Youn, Seung-Ki; Park, Ji-Hyuk

    2015-10-01

    In South Korea, nationwide surveillance for severe fever with thrombocytopenia syndrome (SFTS) began during 2013. Among 301 surveillance cases, 35 hospitalized case-patients in 25 areas were confirmed by using virologic testing, and 16 (46%) case-patients subsequently died. The SFTS cases occurred during May-November and peaked during June (9 cases, 26%). The incidence of SFTS was higher in the southern regions of South Korea. Age and neurologic symptoms, including decreased level of consciousness and slurred speech, were heavily associated with death; neurologic symptoms during the first week after disease onset were also associated with death. Although melena was common among patients who died, no other hemorrhagic manifestations were substantively more common among those who died. No effective treatments, including ribavirin, were identified. Expansion of SFTS surveillance to include the outpatient sector and development of an antibody test would enhance completeness of SFTS detection in South Korea.

  8. Successful Implantation of a Left Ventricular Assist Device in a Patient with Heparin-Induced Thrombocytopenia and Thrombosis

    PubMed Central

    Garland, Cassandra; Somogyi, David

    2014-01-01

    Abstract: We report the case of a 27-year-old woman with signs of heparin-induced thrombocytopenia and thrombosis (HITT) and left heart failure presenting for urgent implantation of a left ventricular assist device (LVAD). HITT can occur in 4.2–6.1% of patients with LVADs. If the patient remains hemodynamically stable, implantation can be delayed for several months until the heparin/PF-4 antibodies decline allowing the use of heparin on cardiopulmonary bypass, However, in most cases related to cardiogenic shock, surgery cannot be delayed. We present the case of a patient who underwent implantation of a HeartMate II LVAD and discuss management strategy using bivalirudin during cardiopulmonary bypass. PMID:25208434

  9. An Anti-Coagulation Conundrum: Implantation of Total Artificial Heart in a Patient with Heparin-Induced Thrombocytopenia Type II

    PubMed Central

    Cios, Theodore J.; Salamanca-Padilla, Yuliana; Guvakov, Dmitri

    2017-01-01

    Patient: Male, 44 Final Diagnosis: Heparin-induced thrombocytopenia Type II Symptoms: Congestive heart failure • short of breath Medication: — Clinical Procedure: LVAD explantation • TAH insertion Specialty: Anesthesiology Objective: Rare co-existance of disease or pathology Background: Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of heparin administration. It can present a major clinical dilemma for physicians caring for patients requiring life-saving urgent or emergent cardiac surgery. Studies have been published examining the use of alternative anticoagulants for patients undergoing cardiopulmonary bypass (CPB), however, evidence does not clearly support any particular approach. Presently, there are no large-scale, prospective randomized studies examining the impact of alternative anticoagulants on clinical outcomes for HIT-positive patients requiring cardiac surgery. Case Report: We present the case of a patient who underwent SynCardia Total Artificial Heart (TAH) implantation following a recent left ventricular assist device (LVAD) placement. The patient was receiving argatroban for type II HIT with anuric renal failure, and developed a thrombus which occluded the inflow cannula of the LVAD. Based on a published study and after establishing consensus with the surgical, anesthesiology, perfusion, and hematology teams, we decided to use tirofiban as an antiplatelet agent to inhibit the platelet aggregation induced by heparin, and ultimately used heparin as the anticoagulant for cardiopulmonary bypass. Conclusions: When selecting anticoagulation for a HIT-positive patient requiring CPB, so that benefits outweigh risks, it is of paramount importance that the decision be based on a multitude of factors. The team caring for the patient should have a shared mental model and be familiar with the pharmacology, devices used, and local practices. These three elements should be integrated with patient-specific comorbidities

  10. Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis.

    PubMed

    Guo, C-T; Lu, Q-B; Ding, S-J; Hu, C-Y; Hu, J-G; Wo, Y; Fan, Y-D; Wang, X-J; Qin, S-L; Cui, N; Yang, Z-D; Zhang, X-A; Liu, W; Cao, W-C

    2016-04-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.

  11. Effect of short-term, high-dose methylprednisolone on oxidative stress in children with acute immune thrombocytopenia

    PubMed Central

    Cura, Musa; Koç, Ahmet; Aksoy, Nurten

    2016-01-01

    Background Immune thrombocytopenia (ITP) is the most common cause of acquired childhood thrombocytopenia and is characterized by increased immune-mediated destruction of circulating thrombocytes. Oxidative damage may be involved in ITP pathogenesis; paraoxonase (PON) and arylesterase (ARE) enzymes are closely associated with the cellular antioxidant system. We investigated the effect of short-term high-dose methylprednisolone (HDMP) treatment on the total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and PON and ARE enzymatic activity in children with acute ITP. Methods Thirty children with acute ITP constituted the study group and 30 healthy children constituted the control group. Children with acute ITP were treated with HDMP: 30 mg/kg for 3 days, then 20 mg/kg for 4 days. The TOS, TAC, OSI, PON, and ARE levels were determined before and after 7 days of HDMP treatment. Results The TAC level (P<0.001), and PON (P<0.001) and ARE (P=0.001) activities were lower and the TOS (P=0.003) and OSI (P<0.001) levels were higher in children with acute ITP than those in healthy children in the control group. We also observed statistically significant increases in the TAC (P<0.01), PON (P<0.001) and ARE levels (P=0.001) and decreases in the TOS (P<0.05) and OSI levels (P<0.05) with 7 days of HDMP treatment compared to their values before treatment. Conclusion Our study demonstrated increased oxidative stress (OSI and TOC) and decreased antioxidant capacity (TAC), PON, and ARE in ITP patients and that steroid treatment could be effective in reducing the oxidative stress. PMID:28090489

  12. Sustained response to combination therapy in a patient with chronic hepatitis C and thrombocytopenia secondary to alpha-interferon.

    PubMed

    Jiménez-Sáenz, M; Rojas, M; Piñar, A; Salas, E; Rebollo, J; Carmona, I; Herrerías-Esteban, J M; Herrerías-Gutiérrez, J M

    2000-05-01

    Recent data suggest that hepatitis C viral (HCV) infection may induce a significant autoimmune reaction to platelets, but the mechanism is unknown. Many patients with chronic hepatitis C, in fact, have high levels of platelet-associated immunoglobulin G (PAIgG) and HCV-RNA is present in the platelets of 100% of those patients with thrombocytopenia and high PAIgG levels. Hepatitis C virus infection has been associated with the development of thrombocytopenic purpura, sometimes triggered during interferon (IFN) therapy. In such cases, the treatment of the underlying disease is a difficult problem to solve. We report the case of a patient with chronic hepatitis C, who developed life-threatening thrombocytopenic purpura after a prolonged course of IFN-alpha2b over a 4-year period. Treatment with anti-immunoglobulin gammaglobulin (Polyglobin; Química Farmaceutica Bayer, Barcelona, Spain) had a transient effect on the platelet count, but prolonged therapy with prednisone was necessary for definitive relief of the haematological complication. Two years later, the patient was treated with combined therapy, including ribavirin (1200 mg/day) and IFN-alpha2b (5 mU, t.i.w.) for 12 months. This therapy induced a sustained response, both biochemical and virological, without haematological complications. This observation suggests that ribavirin may be of benefit in the treatment of immune-mediated thrombocytopenia in patients with chronic hepatitis C, preventing the harmful effect of IFN-alpha but also allowing both drugs to be combined so as to increase the probability of sustained remission of the liver disease.

  13. [Two cases of severe cutaneous vasculitis with thrombocytopenia associated with hepatic cirrhosis: autoimmune and infective-inflammatory component with endothelial lesion and restrictive pulmonary pattern in one case].

    PubMed

    de Andrade Júnior, D R; Warth, M do P; Morrone, L F; Calich, I; de Andrade, D R

    1992-01-01

    Two clinical cases of female patients with hepatic cirrhosis and autoimmune multisystemic involvement with infectious intercurrent are reported. Case 1 presented infective endocarditis and erysipelas on the left thigh. In the course of the clinical picture a cutaneous vasculitis developed in the same place together with autoimmune thrombocytopenia, leukopenia and pulmonary restrictive picture with inflammatory pattern. There are also elevate immune complexes and complement consumption. Case 2 presented erysipelas on the left thigh cutaneous vasculitis and complement consumption. In Case 1 the infective endocarditis was treated with antibiotic therapy during 4 weeks followed by 1 mg/kg corticoid (Prednisone) with thrombocytopenia and leukopenia reversion. Case 2 presented an improvement with antibiotic only. The relation between chronic liver diseases and systemic autoimmune phenomena is commented, special attention being paid to the cutaneous, hematological and pulmonary affection.

  14. Pancytopenia with severe thrombocytopenia in a patient treated with twice-weekly LDL-apheresis by polyacrylate adsorption from whole blood.

    PubMed

    Nowack, Rainer; Wiedemann, Günther

    2010-01-01

    Pancytopenia with severe thrombocytopenia occurred in a patient treated with low-density lipoprotein (LDL)-apheresis by polyacrylate adsorption from whole blood, after treatment frequency had been increased from once to twice a week. Cell counts recovered with discontinuation of LDL-apheresis, but thrombocytopenia recurred after resumption of twice-weekly treatments. Thrombocyte counts remained stable following the replacement of polyacrylate adsorption from whole blood by double-filtration plasmapheresis. The complications' close coincidence with twice-weekly polyacrylate adsorption from whole blood suggests a causal relationship, although by a still unknown mechanism. Monitoring of thrombocytes should be advised in patients treated with LDL-apheresis by polyacrylate adsorption from whole blood.

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

    PubMed

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

    2014-10-01

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

  16. Helicobacter pylori infection influences the severity of thrombocytopenia and its treatment response in chronic hepatitis B patients with compensatory cirrhosis: A multicenter, observational study.

    PubMed

    Zhang, Xiao-Hui; He, Yun; Feng, Ru; Xu, Lan-Ping; Jiang, Qian; Jiang, Hao; Lu, Jin; Fu, Hai-Xia; Liu, Hui; Wang, Jing-Wen; Wang, Qian-Ming; Feng, Fei-Er; Zhu, Xiao-Lu; Xu, Lin-Lin; Xie, Yang-Di; Ma, Hui; Wang, Hao; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-01-01

    The role of Helicobacter pylori (H. pylori) infection on thrombocytopenia in chronic hepatitis B (CHB) related compensatory cirrhotic patients is unknown. We conducted an observational study to determine whether H. pylori plays a role in these patients. A total of 255 patients from three centers in China were enrolled in the study. All patients received nucleoside analogs (NA) therapy and were screened for H. pylori infection. Patients were divided into three groups based on their H. pylori infection status and the therapy administered: patients without H. pylori infection who received NA therapy alone (N = 146); patients with H. pylori infection who received NA therapy alone (n = 48); and patients with H. pylori infection who received H. pylori eradication combined with NA therapy (N = 61). We observed that in CHB compensatory cirrhotic patients with H. pylori infection, the platelets count was significantly lower relative to uninfected patients (31 versus 60 × 10(9)/L, p < 0.01). During a 2-year follow-up, the elevation in platelet count was significantly higher in HBV/H. pylori co-infected patients who received the NA and H. pylori eradication treatment compared to the other two groups (p < 0.01). It suggested that H. pylori infection and eradication treatment combined with NA were independent risk factors associated with platelets response during treatment of thrombocytopenia in CHB compensatory cirrhosis (p < 0.01). In conclusion, H. pylori infection may associate with thrombocytopenia in CHB compensatory cirrhosis. H. pylori eradication combined with NA treatment may prove to be beneficial to CHB compensatory cirrhotic patients with thrombocytopenia who are infected with H. pylori.

  17. Report of successful use of argatroban as an alternative anticoagulant during coronary stent implantation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome.

    PubMed

    Lewis, B E; Iaffaldano, R; McKiernan, T L; Rao, L; Donkin, J; Wallenga, J M

    1996-06-01

    Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is a severe complication of heparin caused by an antibody response to the heparin-platelet factor 4 complex which results in severe thrombosis. Heparin rechallenge in HITTS patients carries a high risk of inducing thrombosis. Antithrombin agents represent treatment alternatives in HITTS patients who require anticoagulation. We report successful coronary stent implantation in a HITTS patient using the antithrombin agent argatroban.

  18. Alternative agents versus prophylactic platelet transfusion for preventing bleeding in patients with thrombocytopenia due to chronic bone marrow failure: a network meta-analysis and systematic review

    PubMed Central

    Desborough, Michael; Estcourt, Lise J; Chaimani, Anna; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Hadjinicolaou, Andreas V; Vyas, Paresh; Stanworth, Simon J

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To compare the relative efficacy of different treatments for thrombocytopenia (artificial platelet substitutes, platelet-poor plasma, fibrinogen, rFVIIa, rFXIII, thrombopoietin mimetics, antifibrinolytic drugs or platelet transfusions) in patients with chronic bone marrow failure and to derive a hierarchy of potential alternate treatments to platelet transfusions. PMID:27069420

  19. Comparison of the effects of antibody-coated liposomes, IVIG, and anti-RBC immunotherapy in a murine model of passive chronic immune thrombocytopenia

    PubMed Central

    Deng, Rong

    2007-01-01

    The present work evaluated antibody-coated liposomes as a new treatment strategy for immune thrombocytopenic purpura (ITP) through the use of a mouse model of the disease. Effects of antimethotrexate antibody (AMI)–coated liposomes and intravenous immunoglobulin (IVIG)–coated liposomes (15, 30, 60 μmol lipid/kg) were compared with the effects of IVIG (0.4, 1, 2 g/kg) and anti–red blood cell (anti-RBC) monoclonal antibody immunotherapy (TER119, 5, 15, 25, and 50 μg/mouse) on MWReg30-induced thrombocytopenia. Each treatment was found to attenuate thrombocytopenia in a dose-dependent manner and, consistent with previous work, IVIG was found to increase antiplatelet antibody clearance in a dose-dependent manner. TER119 demonstrated greater effects on thrombocytopenia relative to other therapies (peak platelet counts: 224% ± 34% of initial platelet counts for 50 μg TER119/mouse versus 160% ± 34% for 2 g/kg IVIG, 88% ± 36% for 60 μmol lipid/kg AMI-coated liposomes, and 80% ± 25% for 60 μmol lipid/kg IVIG-coated liposomes). However, the effects of TER119 were associated with severe hemolysis, as TER119 decreased RBC counts by approximately 50%. The present work demonstrated that antibody-coated liposomes attenuated thrombocytopenia in this model at a much lower immunoglobulin dose than that required for IVIG effects and, in contrast with TER119, antibody-coated liposomes increased platelet counts without altering RBC counts. PMID:17132715

  20. Efficacy of T-705 (Favipiravir) in the Treatment of Infections with Lethal Severe Fever with Thrombocytopenia Syndrome Virus

    PubMed Central

    Tani, Hideki; Fukuma, Aiko; Fukushi, Shuetsu; Taniguchi, Satoshi; Yoshikawa, Tomoki; Iwata-Yoshikawa, Naoko; Sato, Yuko; Suzuki, Tadaki; Nagata, Noriyo; Hasegawa, Hideki; Kawai, Yasuhiro; Uda, Akihiko; Morikawa, Shigeru; Shimojima, Masayuki; Watanabe, Haruo

    2016-01-01

    ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging hemorrhagic fever. This disease has a high case fatality rate and is endemic to China, South Korea, and Japan. Because there are currently no effective therapeutics for SFTS, potent and safe antivirals are needed for the treatment of SFTS. The inhibitory effect of T-705 (favipiravir) on the replication of SFTSV in Vero cells was evaluated. Mice lacking the type I interferon receptor (IFNAR−/−) were used as an in vivo lethal model for SFTSV infection. T-705, which has been licensed as an anti-influenza drug in Japan, inhibits SFTSV replication both in vitro and in vivo. T-705 inhibited replication of SFTSV in Vero cells by 5 log units, with a 50% inhibitory concentration (IC50) and IC90 of 6.0 µM and 22 µM, respectively. Intraperitoneal or oral administration of T-705 for 5 days to IFNAR−/− mice infected with lethal SFTSV significantly improved survival rates (100% survival) without causing body weight loss and reduced the viral load in the serum. Ribavirin also inhibited SFTSV replication. However, it was less effective than T-705 both in vitro and in vivo. A time-of-drug-addition study revealed that therapeutic T-705 treatment of SFTSV infection in IFNAR−/− mice was effective. These results suggest that T-705 is a promising candidate for the treatment of SFTS. IMPORTANCE Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a recently identified emerging viral infectious disease. Despite the medical importance of this disease, there are currently neither vaccines nor effective therapeutics for SFTS. T-705, which is a pyrazine derivative, has shown broad antiviral activity against various RNA viruses. The present study demonstrated, for the first time to our knowledge, the efficacy of T-705 in treating SFTSV infection in a mouse lethal model. T-705 showed a high efficacy in the treatment of SFTSV infection in

  1. Significant thrombocytopenia associated with the addition of rituximab to a combination of fludarabine and cyclophosphamide in the treatment of relapsed follicular lymphoma.

    PubMed

    Leo, Eugen; Scheuer, Lars; Schmidt-Wolf, Ingo G H; Kerowgan, Mohammed; Schmitt, Christina; Leo, Albrecht; Baumbach, Tanja; Kraemer, Alwin; Mey, Ulrich; Benner, Axel; Parwaresch, Reza; Ho, Anthony D

    2004-10-01

    Fludarabine in combination with cyclophosphamide is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma. The anti-CD20 antibody rituximab has been employed successfully for the same indications. No such data were available on a combined use of these agents. Therefore, we conducted a phase II study to evaluate the safety and efficacy of a combination of rituximab (375 mg/m2), fludarabine (4 x 25 mg/m2) and cyclophosphamide (1 x 750 mg/m2), for the treatment of relapsed follicular lymphoma. An unexpected, severe hematologic toxicity with significant, prolonged thrombocytopenias WHO grade III/IV in 6 (35%) of 17 patients treated in total occurred, leading to early termination of the trial. Cytologic and serologic analyses point toward a direct toxic effect. Older patients (mean age 64.7 vs. 56.5 yr) were significantly (P = 0.02) more likely to suffer from this toxicity, whereas no other clinical or hematologic parameter differed statistically between the patients suffering from thrombocytopenia and those who did not. The addition of rituximab to fludarabine/cyclophosphamide employed at doses given above in relapsed follicular lymphoma may have led to this increase in thrombocytopenias. Therefore, caution should be exercised when combining these drugs for the treatment of patients with relapsed follicular lymphoma, especially when treating older patients.

  2. Modeling Severe Fever with Thrombocytopenia Syndrome Virus Infection in Golden Syrian Hamsters: Importance of STAT2 in Preventing Disease and Effective Treatment with Favipiravir.

    PubMed

    Gowen, Brian B; Westover, Jonna B; Miao, Jinxin; Van Wettere, Arnaud J; Rigas, Johanna D; Hickerson, Brady T; Jung, Kie-Hoon; Li, Rong; Conrad, Bettina L; Nielson, Skot; Furuta, Yousuke; Wang, Zhongde

    2017-02-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality in China, South Korea, and Japan, with key features of disease being intense fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be in the 30% range, and no antivirals or vaccines are approved for use for treatment and prevention of SFTS. There is evidence that in human cells, SFTSV sequesters STAT proteins in replication complexes, thereby inhibiting type I interferon signaling. Here, we demonstrate that hamsters devoid of functional STAT2 are highly susceptible to as few as 10 PFU of SFTSV, with animals generally succumbing within 5 to 6 days after subcutaneous challenge. The disease included marked thrombocytopenia and inflammatory disease characteristic of the condition in humans. Infectious virus titers were present in the blood and most tissues 3 days after virus challenge, and severe inflammatory lesions were found in the spleen and liver samples of SFTSV-infected hamsters. We also show that SFTSV infection in STAT2 knockout (KO) hamsters is responsive to favipiravir treatment, which protected all animals from lethal disease and reduced serum and tissue viral loads by 3 to 6 orders of magnitude. Taken together, our results provide additional insights into the pathogenesis of SFTSV infection and support the use of the newly described STAT2 KO hamster model for evaluation of promising antiviral therapies.

  3. Chickens treated with a nitric oxide inhibitor became more resistant to Plasmodium gallinaceum infection due to reduced anemia, thrombocytopenia and inflammation.

    PubMed

    de Macchi, Barbarella Matos; Miranda, Farlen José Bebber; de Souza, Fernanda Silva; de Carvalho, Eulógio Carlos Queiroz; Albernaz, Antônio Peixoto; do Nascimento, José Luiz Martins; DaMatta, Renato Augusto

    2013-02-11

    Malaria is a serious infectious disease caused by parasites of the Plasmodium genus that affect different vertebrate hosts. Severe malaria leads to host death and involves different pathophysiological phenomena such as anemia, thrombocytopenia and inflammation. Nitric oxide (NO) is an important effector molecule in this disease, but little is known about its role in avian malaria models. Plasmodium gallinaceum-infected chickens were treated with aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase, to observe the role of NO in the pathogenesis of this avian model. AG increased the survival of chickens, but also induced higher parasitemia. Treated chickens demonstrated reduced anemia and thrombocytopenia. Moreover, erythrocytes at different stages of maturation, heterophils, monocytes and thrombocytes were infected by Plasmodium gallinaceum and animals presented a generalized leucopenia. Activated leukocytes and thrombocytes with elongated double nuclei were observed in chickens with higher parasitemia; however, eosinophils were not involved in the infection. AG reduced levels of hemozoin in the spleen and liver, indicating lower inflammation. Taken together, the results suggest that AG reduced anemia, thrombocytopenia and inflammation, explaining the greater survival rate of the treated chickens.

  4. SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome.

    PubMed

    Trkova, Marie; Becvarova, Vera; Hynek, Martin; Hnykova, Lenka; Hlavova, Eva; Kreckova, Gabriela; Kulovany, Eduard; Cutka, David; Zatloukalova, Jitka; Markova, Kristyna; Sukova, Martina; Horacek, Jiri; Stejskal, David

    2012-10-01

    Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia.

  5. Clinical and molecular-cytogenetic evaluation of a family with partial Jacobsen syndrome without thrombocytopenia caused by an approximately 5 Mb deletion del(11)(q24.3).

    PubMed

    Bernaciak, Joanna; Szczałuba, Krzysztof; Derwińska, Katarzyna; Wiśniowiecka-Kowalnik, Barbara; Bocian, Ewa; Sasiadek, Maria Małgorzata; Makowska, Izabela; Stankiewicz, Paweł; Smigiel, Robert

    2008-10-01

    Clinical manifestations of Jacobsen syndrome (JBS) depend on the size of the 11qter deletion, which usually varies between approximately 7 and 20 Mb. Typical JBS features include developmental delay/mental retardation, short stature, congenital heart defects, thrombocytopenia, and characteristic dysmorphic facial features. We report on a family in which a 4-year-old girl as well as her mother and maternal uncle present with subtle features of JBS. Notably, neither thrombocytopenia nor congenital anomalies were detected in this family. Cytogenetic analyses revealed normal karyotypes. Using fluorescence in situ hybridization (FISH) and whole-genome oligonucleotide array CGH analyses, we identified an approximately 5 Mb deletion of the terminal part of chromosome 11q in all the three affected family members. The deletion breakpoint was mapped between 129,511,419 and 129,519,794 bp. This is the smallest deletion reported in a JBS patient. Interestingly, the FLI1 (friend leukemia virus integration 1) hematopoiesis factor gene located approximately 6.5 Mb from 11qter and usually deleted in patients with JBS, is intact. Our data support previous hypotheses that FLI1 haploinsufficiency is responsible for thrombocytopenia in patients with JBS.

  6. Japanese variant of multicentric castleman's disease associated with serositis and thrombocytopenia--a report of two cases: is TAFRO syndrome (Castleman- Kojima disease) a distinct clinicopathological entity?

    PubMed

    Masaki, Yasufumi; Nakajima, Akio; Iwao, Haruka; Kurose, Nozomu; Sato, Tomomi; Nakamura, Takuji; Miki, Miyuki; Sakai, Tomoyuki; Kawanami, Takafumi; Sawaki, Toshioki; Fujita, Yoshimasa; Tanaka, Masao; Fukushima, Toshihiro; Okazaki, Toshiro; Umehara, Hisanori

    2013-01-01

    Multicentric Castleman's disease (MCD) is a polyclonal lymphoproliferative disorder that manifests as marked hyper-γ-globulinemia, severe inflammation, anemia, and thrombocytosis. Recently, Takai et al. reported a new disease concept, TAFRO syndrome, named from thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. Furthermore, Kojima et al. reported Japanese MCD cases with effusion and thrombocytopenia (Castleman-Kojima disease). Here, we report two cases of MCD associated with marked pleural effusion, ascites, and thrombocytopenia, and discuss the independence of the TAFRO syndrome (Castleman-Kojima disease). Case 1: A 57-year-old woman had fever, anemia, anasarca, and some small cervical lymphadenopathy. Although she had been administered steroid therapy, and full-coverage antibiotics, her general condition, including fever, systemic inflammation, and anasarca, deteriorated steadily. We administered chemotherapy [CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) regimen], but despite a transient improvement, she died due to septic shock. Case 2: A 73-year-old man with a history of aplastic anemia and remission presented with fever, severe inflammation, and anasarca. Prednisolone was administered (15 mg daily), and his hyperinflammation once improved. Nevertheless, his general condition, including pleural effusion and ascites, worsened, and C-reactive protein and interleukin-6 levels showed marked increases. The patient died due to multiorgan failure. Cases of TAFRO syndrome (Castleman-Kojima disease) are still rare. Therefore, it is necessary to conduct multicenter clinical surveys including similar cases, such as ours, to reach a consensus regarding diagnostic criteria, therapeutic strategy, and pathophysiological etiology for this syndrome.

  7. Safety and Efficacy of a Single Dose of Anti-D (WinRho®) in Severe Thrombocytopenia Secondary to Dengue Virus Infection

    PubMed Central

    Pannu, Ashok Kumar; Bhalla, Ashish; Singhal, Mayank; Suri, Vikas; Shafiq, Nusrat; Varma, Subhash

    2017-01-01

    Objective: To evaluate the efficacy of a single intravenous (IV) dose of anti-D in severe thrombocytopenia (<20,000) due to dengue virus (DEV) infection. Materials and Methods: An open label, investigator-initiated, randomized interventional study was conducted that included thirty dengue patients (all positive for IgM enzyme-linked immunosorbent assay) with severe thrombocytopenia (<20,000/mm3). Patients were randomized to receive anti-D (50 μg/kg single IV dose) plus supportive therapy or supportive therapy alone. Results: The rate of rise in platelet count was significantly high in the intervention group at 24, 36, and 48 h. At the end of 48 h, 60% patients in the intervention group achieved a platelet count of ≥50,000/mm3 as compared to 6.7% in the control group (P = 0.0019). The requirement of the platelet concentrate infusion in the control group was significantly higher, i.e. 342 ml (±193) as compared to the intervention group requiring only 187 ml (±79). The intervention group showed a significant improvement in bleeding manifestations in all the patients by 24 h in Grade 2 bleed (P = 0.032) and by 48 h in Grade 1 bleed (P = 0.014). Conclusions: Severe thrombocytopenia (≤20,000/mm3) secondary to DEV infection was rapidly and safely reversed by administration of a single dose of 50 μg/kg (250 IU/kg) anti-D IV. PMID:28250602

  8. A simple and practical score model for predicting the mortality of severe fever with thrombocytopenia syndrome patients

    PubMed Central

    Xiong, Shue; Zhang, Wenjing; Li, Mingyue; Xiong, Yan; Li, Mengmeng; Wang, Hua; Yang, Dongliang; Peng, Cheng; Zheng, Xin

    2016-01-01

    Abstract Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease with a high fatality rate. The risk factors for death are not clearly identified, and there is no clinical score model to predict the prognosis. We retrospectively collected the clinical information of clinical symptoms and laboratory parameters of SFTS patients on admission. After analyzing the clinical characteristics of 179 SFTS patients, we found that an elevated level of neurologic symptoms, respiratory symptoms, viral load, and a lower level of monocyte percentage were the critical risk factors for mortality. We used the 4 variables to assemble a score formula named the SFTS index [SFTSI = 5 × Neurologic symptoms-level + 4 × Respiratory symptoms-level + 3 × LG10 Viral load – 2 × LN Monocyte% – 7]. The AURC of this model was 0.964, which was higher than the AURC 0.913 of the viral load especially among the patients with higher viral loads (0.936 vs 0.821). We identified that the neurologic symptoms, respiratory symptoms, viral load, and monocyte percentage were the critical risk factors for SFTS mortality. The clinical score model of SFTSI provides a practical method for clinicians to stratify patients with SFTS and to adopt prompt effective treatment strategies. PMID:28033271

  9. Is Autoimmune Thrombocytopenia Itself the Primary Disease in the Presence of Second Diseases Data from a Long-Term Observation

    PubMed Central

    Aboud, Nasra; Depré, Fabian; Salama, Abdulgabar

    2017-01-01

    Background Dependent on the absence or presence of associated diseases, autoimmune thrombocytopenia (ITP) can be classified as primary or secondary form. The manifestation of the associated diseases is not temporally defined and may occur during observation. Thus the question which disease is the primary one remains unanswered. Methods All 386 patients included in this study were treated by a single primary physician between 1996 and 2015 at the Charité Berlin and met current ITP criteria. Medical records and investigations were reviewed to assess diseases associated with ITP. Results Initially, the vast majority of patients presented with primary ITP (isolated disease). Based on our findings, ITP was found to be associated with other abnormalities in most cases. These abnormalities included: positive direct antiglobulin test in 49 of 386 tested patients (13%), affections of the thyroid gland in 41 of 386 tested patients (11%), infections in 30 (8%), solid malignancies in 20 (5%) and hematological malignancies in 10 patients (3%), as well as many other miscellaneous diseases. Moreover, of 160 patients who did not receive prior intravenous immunoglobulin treatment, 40 (25%) showed antibody deficiency. Conclusion In conclusion, the incidence of ‘true’ ITP as a primary disease is less common than has yet been suggested. Additionally, there is evidence that ITP itself predispose affected subjects toward development of other diseases. PMID:28275330

  10. Molecular Evolution and Spatial Transmission of Severe Fever with Thrombocytopenia Syndrome Virus Based on Complete Genome Sequences

    PubMed Central

    Liu, Jian-Wei; Zhao, Li; Luo, Li-Mei; Liu, Miao-Miao; Sun, Yue; Su, Xiang; Yu, Xue-jie

    2016-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) was a novel tick-borne bunyavirus that caused hemorrhagic fever with a high fatality rate in East Asia. In this study we analyzed the complete genome sequences of 122 SFTSV strains to determine the phylogeny, evolution and reassortment of the virus. We revealed that the evolutionary rate of three genome segments were different, with highest in the S segment and lowest in the L segment. The SFTSV strains were phylogenetically classified into 5 lineages (A, B, C, D and E) with each genome segment. SFTSV strains from China were classified in all 5 lineages, strains from South Korea were classified into 3 lineages (A, D, and E), and all strains from Japan were classified in only linage E. Using the average evolutionary rate of the three genome segments, we found that the extant SFTSV originated 20–87 years ago in the Dabie Mountain area in central China. The viruses were then transmitted to other areas of China, Japan and South Korea. We also found that six SFTSV strains were reassortants. Selection pressure analysis suggested that SFTSV was under purifying selection according to the four genes (RNA-dependent RNA polymerase, glycoprotein, nucleocapsid protein, non-structural protein), and two sites (37, 1033) of glycoproteins were identified as being under strong positive selection. We concluded that SFTSV originated in central China and spread to other places recently and the virus was under purifying selection with high frequency of reassortment. PMID:26999664

  11. Antigenic complementarity in the origins of autoimmunity: a general theory illustrated with a case study of idiopathic thrombocytopenia purpura.

    PubMed

    Root-Bernstein, Robert; Couturier, Jacob

    2006-03-01

    We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

  12. Severe fever with thrombocytopenia syndrome virus inhibits exogenous Type I IFN signaling pathway through its NSs in vitro

    PubMed Central

    Li, Shilin; Jiao, Baihai; Wu, Jianqin; Zeng, Peibin; Chen, Limin

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus (SFTS virus, SFTSV). At present there is still no specific antiviral treatment for SFTSV; To understand which cells support SFTSV life cycle and whether SFTSV infection activates host innate immunity, four different cell lines (Vero, Hela, Huh7.5.1, and Huh7.0) were infected with SFTSV. Intracellular/extracellular viral RNA and expression of IFNα, and IFNß were detected by real-time RT- PCR following infection. To confirm the role of non-structural protein (NSs) of SFTSV in exogenous IFNα-induced Jak/STAT signaling, p-STAT1 (Western Blot), ISRE activity (Luciferase assay) and ISG expression (real-time PCR) were examined following IFNα stimulation in the presence or absence of over-expression of NSs in Hela cells. Our study showed that all the four cell lines supported SFTSV life cycle and SFTSV activated host innate immunity to produce type I IFNs in Hela cells but not in Huh7.0, Huh7.5.1 or Vero cells. NSs inhibited exogenous IFNα-induced Jak/STAT signaling as shown by decreased p-STAT1 level, suppressed ISRE activity and down-regulated ISG expression. Suppression of the exogenous Type I IFN-induced Jak/STAT signaling by NSs might be one of the mechanisms of SFTSV to evade host immune surveillance. PMID:28234991

  13. X-linked thrombocytopenia with thalassemia displays bone marrow reticulin fibrosis and enhanced angiogenesis: comparisons with primary myelofibrosis.

    PubMed

    Åström, Maria; Hahn-Strömberg, Victoria; Zetterberg, Eva; Vedin, Inger; Merup, Mats; Palmblad, Jan

    2015-03-01

    X-linked thrombocytopenia with thalassemia (XLTT) is caused by the mutation 216R > Q in exon 4 of the GATA1 gene. Male hemizygous patients display macrothrombocytopenia, splenomegaly, and a β-thalassemia trait. We describe two XLTT families where three males were initially misdiagnosed as having primary myelofibrosis (PMF) and all five investigated males showed mild-moderate bone marrow (BM) reticulin fibrosis. Comparative investigations were performed on blood samples and BM biopsies from males with XLTT, PMF patients and healthy controls. Like PMF, XLTT presented with high BM microvessel density, low GATA1 protein levels in megakaryocytes, and elevated blood CD34+ cell counts. But unlike PMF, the BM microvessel pericyte coverage was low in XLTT, and no collagen fibrosis was found. Further, as evaluated by immunohistochemistry, expressions of the growth factors VEGF, AGGF1, and CTGF were low in XLTT megakaryocytes and microvessels but high in PMF. Thus, although the reticulin fibrosis in XLTT might simulate PMF, opposing stromal and megakaryocyte features may facilitate differential diagnosis. Additional comparisons between these disorders may increase the understanding of mechanisms behind BM fibrosis in relation to pathological megakaryopoiesis.

  14. Recurrent heparin-induced thrombocytopenia due to heparin rinsing before priming the machine in a hemodialysis patient: A case report.

    PubMed

    Lim, Jin Han; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2016-10-13

    Heparin has remained the most commonly used anticoagulant for patients undergoing hemodialysis. It is usually safe to use but can have severe adverse effects in some cases. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin. It results from an autoantibody directed against endogenous platelet factor 4 (PF4) in complex with heparin, which activates platelets and can cause catastrophic arterial and venous thromboses. Here, we present the case of an 80-year-old woman with a recent diagnosis of chronic renal failure who developed acute HIT (platelet count nadir, 15 × 10(9) /L) on day 7 of hemodialysis performed with routine heparin anticoagulation, who despite subsequent heparin-free hemodialysis (with argatroban and warfarin) developed recurrent HIT (complicated by acute cerebral infarction) on day 11 that we attributed to "rinsing" of the circuit with heparin-containing saline (3,000 units of unfractionated heparin, with subsequent saline washing) performed pre-dialysis as per routine. After stopping heparin rinsing, the platelet count recovered completely, without further thrombotic or other sequelae. Our experience indicates that for patients with acute HIT, besides the well-known practice of using non-heparin anticoagulation during dialysis and avoiding heparin "locking" of dialysis catheters, it is also important to avoid inadvertent rinsing of the circuit with heparin during preparation for hemodialysis.

  15. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.

    PubMed

    Albert, Michael H; Bittner, Tanja C; Nonoyama, Shigeaki; Notarangelo, Lucia Dora; Burns, Siobhan; Imai, Kohsuke; Espanol, Teresa; Fasth, Anders; Pellier, Isabelle; Strauss, Gabriele; Morio, Tomohiro; Gathmann, Benjamin; Noordzij, Jeroen G; Fillat, Cristina; Hoenig, Manfred; Nathrath, Michaela; Meindl, Alfons; Pagel, Philipp; Wintergerst, Uwe; Fischer, Alain; Thrasher, Adrian J; Belohradsky, Bernd H; Ochs, Hans D

    2010-04-22

    A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.

  16. Trends in anti-D immune globulin for childhood immune thrombocytopenia: usage, response rates, and adverse effects.

    PubMed

    Long, Michelle; Kalish, Leslie A; Neufeld, Ellis J; Grace, Rachael F

    2012-03-01

    In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years.

  17. Effect of thrombopoietin receptor agonists on the apoptotic profile of platelets in patients with chronic immune thrombocytopenia.

    PubMed

    Mitchell, William Beau; Pinheiro, Mariana P; Boulad, Nayla; Kaplan, David; Edison, Michele N; Psaila, Bethan; Karpoff, Marissa; White, Michael J; Josefsson, Emma C; Kile, Benjamin T; Bussel, James B

    2014-12-01

    Platelet survival depends upon mediators of apoptosis e.g., Bcl-xL, Bax, and Bak, which are regulated by thrombopoietin (TPO)-mediated