scholarly journals Drug-associated thrombocytopenia

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 576-583 ◽  
Author(s):  
Tamam Bakchoul ◽  
Irene Marini
Keyword(s):  
Platelet Count ◽  
Clinical Symptoms ◽  
Scoring Systems ◽  
Severe Thrombocytopenia ◽  
Thromboembolic Complications ◽  
Drug Induced ◽  
Increased Risk ◽  
High Doses ◽  
Risk Of Hemorrhage

Abstract Many drugs have been implicated in drug-induced immune thrombocytopenia (DITP). Patients with DITP develop a drop in platelet count 5 to 10 days after drug administration with an increased risk of hemorrhage. The diagnosis of DITP is often challenging, because most hospitalized patients are taking multiple medications and have comorbidities that can also cause thrombocytopenia. Specialized laboratory diagnostic tests have been developed and are helpful to confirm the diagnosis. Treatment of DITP involves discontinuation of the offending drug. The platelet count usually starts to recover after 4 or 5 half-lives of the responsible drug or drug metabolite. High doses of intravenous immunoglobulin can be given to patients with severe thrombocytopenia and bleeding. Although in most cases, DITP is associated with bleeding, life-threatening thromboembolic complications are common in patients with heparin-induced thrombocytopenia (HIT). Binding of antiplatelet factor 4/heparin antibodies to Fc receptors on platelets and monocytes causes intravascular cellular activation, leading to an intensely prothrombotic state in HIT. The clinical symptoms include a decrease in platelet counts by >50% and/or new thromboembolic complications. Two approaches can help to confirm or rule out HIT: assessment of the clinical presentation using scoring systems and in vitro demonstration of antiplatelet factor 4/heparin antibodies. The cornerstone of HIT management is immediate discontinuation of heparin when the disease is suspected and anticoagulation using nonheparin anticoagulant. In this review, we will provide an update on the pathophysiology, diagnosis, and management of both DITP and HIT.

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

Hematology ◽  
2009 ◽  
Vol 2009 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas L. Ortel
Keyword(s):  
Platelet Count ◽  
Heparin Therapy ◽  
Severe Thrombocytopenia ◽  
Drug Induced ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Increased Risk ◽  
Antibody Levels

Abstract Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin. The thrombocytopenia is typically moderate, with a median platelet count nadir of ~50 to 60 × 109 platelets/L. Severe thrombocytopenia has been described in patients with HIT, and in these patients antibody levels are high and severe clinical outcomes have been reported (eg, disseminated intravascular coagulation with microvascular thrombosis). The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin. A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies. A delayed form of HIT has also been described that develops within days or weeks after the heparin has been discontinued. In contrast to other drug-induced thrombocytopenias, HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism. Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated. Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid, although the last agent is not available in North America. Fondaparinux has been used in a small number of patients with HIT and generally appears to be safe. Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT.

Abstract 16543: Severe Thrombocytopenia is Common in Adults Undergoing Venoarterial Extracorporeal Membrane Oxygenation and is Predictive of Hemorrhage

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tia C Kohs ◽  
Vikram Raghunathan ◽  
Patricia Liu ◽  
Ramin Amirsoltani ◽  
Michael Oakes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Platelet Count ◽  
Extracorporeal Membrane Oxygenation ◽  
Clinical Implications ◽  
Severe Thrombocytopenia ◽  
Multivariate Logistic Regression ◽  
Membrane Oxygenation ◽  
Increased Risk ◽  
Va Ecmo

Introduction: Extracorporeal membrane oxygenation (ECMO) is used to provide circulatory support and facilitate gas exchange via cardiopulmonary bypass. The relationship between ECMO and the incidence of severe thrombocytopenia (platelet count <50 x 10 9 /L) and subsequent clinical consequences are ill defined. We aimed to identify the risk factors for the development of thrombocytopenia and its clinical implications. Methods: This is a single-center retrospective cohort study of adults who received venoarterial (VA) ECMO. We examined consecutive platelet counts while on ECMO. Univariate logistic regression was used to determine if mean platelet count, platelet count range, or severe thrombocytopenia were predictors of overall survival, hemorrhage and thrombosis. A multivariate logistic regression model was used to identify factors that contribute to the development of the aforementioned patient outcomes. Results: In our cohort, 33 patients were included with a mean age of 55 years and duration of ECMO of 5.9 days. All patients received heparin, 33.3% received antiplatelet therapy and 45.5% developed severe thrombocytopenia. In univariate, analysis the development of severe thrombocytopenia increased the odds of major bleeding by 450% (OR 5.500, 95% CI 1.219 - 24.813, P -value 0.027), and the odds of surviving hospitalization decreased 84.1% (OR 0.159, 95% CI 0.033 - 0.773, P -value 0.023). Multivariate logistic regression controlling for additional clinical variables found no significant association between the development of severe thrombocytopenia and rates of thrombosis, hemorrhage, or overall survival. Platelet count decreased over time while on ECMO. Conclusions: Nearly half of the patients requiring VA-ECMO developed severe thrombocytopenia, which was associated with an increased risk of hemorrhage and in-hospital mortality. Additional studies are required to clarify the clinical implications of severe thrombocytopenia in ECMO patients.

scholarly journals A practical approach to evaluating postoperative thrombocytopenia

2020 ◽  
Vol 4 (4) ◽  
pp. 776-783 ◽  
Author(s):  
Leslie Skeith ◽  
Lisa Baumann Kreuziger ◽  
Mark A. Crowther ◽  
Theodore E. Warkentin
Keyword(s):  
Platelet Count ◽  
Late Onset ◽  
Practical Approach ◽  
Drug Induced ◽  
Heparin Induced Thrombocytopenia ◽  
Replacement Surgery ◽  
Device Implantation ◽  
Increased Risk ◽  
Posttransfusion Purpura ◽  
Heparin Exposure

Abstract Identifying the cause(s) of postoperative thrombocytopenia is challenging. The postoperative period includes numerous interventions, including fluid administration and transfusion of blood products, medication use (including heparin), and increased risk of organ dysfunction and infection. Understanding normal thrombopoietin physiology and the associated expected postoperative platelet count changes is the crucial first step in evaluation. Timing of thrombocytopenia is the most important feature when differentiating causes of postoperative thrombocytopenia. Thrombocytopenia within 4 days of surgery is commonly caused by hemodilution and increased perioperative platelet consumption prior to thrombopoietin-induced platelet count recovery and transient platelet count overshoot. A much broader list of possible conditions that can cause late-onset thrombocytopenia (postoperative day 5 [POD5] or later) is generally divided into consumptive and destructive causes. The former includes common (eg, infection-associated disseminated intravascular coagulation) and rare (eg, postoperative thrombotic thrombocytopenic purpura) conditions, whereas the latter includes such entities as drug-induced immune thrombocytopenia or posttransfusion purpura. Heparin-induced thrombocytopenia is a unique entity associated with thrombosis that is typically related to intraoperative/perioperative heparin exposure, although it can develop following knee replacement surgery even in the absence of heparin exposure. Very late onset (POD10 or later) of thrombocytopenia can indicate bacterial or fungal infection. Lastly, thrombocytopenia after mechanical device implantation requires unique considerations. Understanding the timing and severity of postoperative thrombocytopenia provides a practical approach to a common and challenging consultation.

A Risk Model for Thrombocytopenia Requiring Platelet Transfusion After Cytotoxic Chemotherapy

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 405-410 ◽  
Author(s):  
J.Y. Blay ◽  
A. Le Cesne ◽  
C. Mermet ◽  
C. Maugard ◽  
A. Ravaud ◽  
...  
Keyword(s):  
Risk Factors ◽  
Platelet Count ◽  
High Risk ◽  
Risk Model ◽  
Univariate Analysis ◽  
Cytotoxic Chemotherapy ◽  
Phase Iii ◽  
Severe Thrombocytopenia ◽  
Increased Risk ◽  
Platelet Transfusions

Abstract Severe thrombocytopenia is a rare but life-threatening side effect of cytotoxic chemotherapy for which risk factors are not well known. Our objective was to delineate a risk model for chemotherapy-induced thrombocytopenia requiring platelet transfusions in cancer patients. Univariate and multivariate analysis of risk factors for chemotherapy-induced thrombocytopenia requiring platelet transfusions were performed on the cohort of the 1,051 patients (CLB 1996) treated with chemotherapy in the Department of Medicine of the Centre Léon Bérard (CLB) in 1996. In univariate analysis, performance status (PS) greater than 1, platelet count less than 150,000/μL at day 1 (d1) before the initiation of chemotherapy, d1 lymphocyte count ≤700/μL, d1 polymorphonuclear leukocyte count less than 1,500/μL, and the type of chemotherapy (high risk v others) were significantly associated (P &lt; .01) with an increased risk of severe thrombocytopenia requiring platelet transfusions. Using logistic regression, d1 platelet count less than 150,000/μL (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.9 to 9.6), d1 lymphocyte counts ≤700/μL (OR, 3.37; 95% CI, 1.77 to 6.4), the type of chemotherapy (OR, 3.38; 95% CI, 1.77 to 6.4), and PS greater than 1 (OR, 2.23; 95% CI, 1.22 to 4.1) were identified as independent risk factors for platelet transfusions. The observed incidences of platelet transfusions were 45%, 13%, 7%, and 1.5% for patients with ≥3, 2, 1, or 0 risk factors, respectively. This model was then tested in 3 groups of patients treated with chemotherapy used as validation samples: (1) the series of 340 patients treated in the CLB in the first 6 months of 1997, (2) the prospective multicentric cohort of 321 patients of the ELYPSE 1 study, and (3) the series of 149 patients with non-Hodgkin's lymphoma treated in the CLB within prospective phase III trials (1987 to 1995). In these 3 groups, the observed incidences of platelet transfusions in the above-defined risk groups did not differ significantly (P &gt; .1) from those calculated in the model. This risk index could be useful to identify patients at high risk for chemotherapy-induced thrombocytopenia requiring platelet transfusions.

scholarly journals A 64-year-old man suffering from ST-elevation myocardial infarction and severe thrombocytopenia: Procedures in the case of a patient not fitting the guidelines

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984052
Author(s):  
Dawid Ilnicki ◽  
Rafał Wyderka ◽  
Przemysław Nowicki ◽  
Alicja Sołtowska ◽  
Jakub Adamowicz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Count ◽  
Coronary Angiography ◽  
Antiplatelet Therapy ◽  
St Elevation Myocardial Infarction ◽  
Severe Thrombocytopenia ◽  
Therapeutic Decisions ◽  
Increased Risk ◽  
Low Platelet Count ◽  
St Elevation

The objective of this case report is to present how the chronic condition significantly complicates life-saving procedures and influences further treatment decisions. A 64-year-old man suffering from arterial hypertension and immune thrombocytopenic purpura presented to the Emergency Department with anterior ST-elevation myocardial infarction. An immediate coronary angiography was performed where critical stenosis of the proximal left anterior descending was found. It was followed by primary percutaneous intervention with bare metal stent. In first laboratory results, extremely low platelet count was found (13 × 109/L). Consulting haematologist advised the use of single antiplatelet therapy and from the second day of hospitalisation only clopidogrel was prescribed. On the sixth day of hospital stay, patient presented acute chest pain with ST elevation in anterior leads. Emergency coronary angiography confirmed acute stent thrombosis and aspiration thrombectomy was performed. It was therefore agreed to continue dual antiplatelet therapy for 4 weeks. As there are no clinical trials where patients with low platelet count are included, all therapeutic decisions must be made based on clinician’s experience and experts’ consensus. Both the risk of haemorrhagic complications and increased risk of thrombosis must be taken into consideration when deciding on patient’s treatment.

FACTOR IX CONCENTRATES ARE THROMBOGENIC AT HIGH DOSES IN DOGS

1987 ◽  
Author(s):  
J Ferguson ◽  
J Dawes ◽  
C V Prowse ◽  
P R Foster ◽  
P A Feldman ◽  
...  
Keyword(s):  
Platelet Count ◽  
Fibrinogen Level ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Fibrinopeptide A ◽  
Blood Products ◽  
Elevated Plasma ◽  
High Doses

A canine model has recently been established to assess the potential thrombogenicity of intravenously infused blood products. Elevated plasma levels of fibrinopeptide A (FpA) were identified as the most sensitive indicator of a thrombogenic response, and this was the only parameter to change significantly when issued batches of factor IX (II + X) concentrate were infused at a dose of 100 iu/kg. After infusion of 200 iu/kg, however, plasma FpA concentrations and FDP titres rose, the APTT was prolonged, and the platelet count and fibrinogen level fell. At this dose, therefore, FIX concentrates which were not identified by in vitro tests as potentially thrombogenic induced a response when infused into dogs.A batch of FIX concentrate which failed the criteria for in vitro thrombogenicity and was therefore not issued for routine use was infused at 100 iu/kg. Plasma FpA levels rose as did the FDP titre, and fibrinogen concentrations fell, but the APTT was only slightly prolonged. The thrombogenic response to 200 iu/kg of issued FIX concentrate was at least as severe as that following infusion of 100 iu/kg of this rejected batch.Thus, there is a threshold dose of FIX concentrate above which a severe thrombogenic response can ensue, and the current in vitro tests may not be a reliable indicator of potential thrombogenicity when FIX concentrates are infused at high doses. This should be taken into account when administering unusually high doses, particularly to patients who may have reduced levels of circulating protease inhibitors.

Eltrombopag Can Stimulate Trilineage Hematopoiesis In Patients with Refractory Severe Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4427-4427
Author(s):  
Matthew J. Olnes ◽  
Yong Tang ◽  
Susan Soto ◽  
Elaine M Sloand ◽  
Philip Scheinberg ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Aplastic Anemia ◽  
Severe Aplastic Anemia ◽  
Successful Outcome ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Platelet Counts ◽  
Transfusion Independence

Abstract Abstract 4427 Severe aplastic anemia (SAA) is characterized by trilineage marrow hypoplasia and a paucity of hematopoietic stem cell progenitors. SAA is treated with immunosuppression or allogeneic stem cell transplantation (SCT), with a successful outcome in a majority. However, 20–40% of patients without a suitable donor for SCT do not respond to immunosuppression and may have persistent severe thrombocytopenia. Thrombopoietin (TPO) is the principal regulator of platelet production, and it exerts its effects through binding the megakaryocyte progenitor TPO receptor mpl, which stimulates production of mature megakaryocytes and platelets. Eltrombopag, a small molecule TPO mimetic that binds to mpl, increases platelet counts in healthy subjects, and in patients with chronic immune thrombocytopenic purpura. Both TPO and eltrombopag stimulate more primitive multilineage progenitors and stem cells in vitro. Patients with SAA and thrombocytopenia have very elevated TPO levels; nevertheless, we asked whether pharmacologic doses of eltrombopag could stimulate hematopoiesis in these patients without other options. We are conducting a pilot phase II study of eltrombopag in SAA patients with severe thrombocytopenia refractory to immunosuppressive therapy. Consecutive eligible adult patients were treated with oral eltrombopag at an initial dose of 50 mg daily, with escalation to a maximum dose 150 mg daily, with the goal of maintaining a platelet count of >20,000/uL above baseline. Treatment response was measured after three months and was defined as platelet count increases to 20,000/uL above baseline, or stable platelet counts with transfusion-independence for a minimum of 8 weeks. Nine patients have been enrolled and six are evaluable for response to date. Two patients did not respond to treatment. Three patients achieved platelet responses by 12 weeks of treatment, and all have sustained their responses (median follow up 10 months). Four patients exhibited improved hemoglobin levels 12 weeks after starting treatment (median hemoglobin increase of 2.1 g/dL) and two patients who were previously dependent on packed red blood cell transfusions have achieved transfusion-independence. Three neutropenic patients exhibited increased neutrophil counts after treatment with eltrombopag (median increase 0.46K cells/uL). These results provide evidence that eltrombopag can improve platelet counts in patients with severe refractory thrombocytopenia, and perhaps more surprisingly, have a clinically relevant impact on erythropoiesis and myelopoiesis. Updated data will be presented at the Society's meeting. Disclosures: Off Label Use: Eltrombopag for thrombocytopenia in refractory severe aplastic anemia patients.

scholarly journals Preoperative Thrombocytopenia and Postoperative Outcomes after Noncardiac Surgery

2014 ◽  
Vol 120 (1) ◽  
pp. 62-75 ◽  
Author(s):  
Laurent G. Glance ◽  
Neil Blumberg ◽  
Michael P. Eaton ◽  
Stewart J. Lustik ◽  
Turner M. Osler ◽  
...  
Keyword(s):  
Platelet Count ◽  
Blood Transfusion ◽  
Noncardiac Surgery ◽  
Multivariable Logistic Regression Analysis ◽  
Severe Thrombocytopenia ◽  
Normal Platelet ◽  
Clinical Indications ◽  
Increased Risk ◽  
Coagulation Testing ◽  
Using Data

Abstract Background: Most studies examining the prognostic value of preoperative coagulation testing are too small to examine the predictive value of routine preoperative coagulation testing in patients having noncardiac surgery. Methods: Using data from the American College of Surgeons National Surgical Quality Improvement database, the authors performed a retrospective observational study on 316,644 patients having noncardiac surgery who did not have clinical indications for preoperative coagulation testing. The authors used multivariable logistic regression analysis to explore the association between platelet count abnormalities and red cell transfusion, mortality, and major complications. Results: Thrombocytopenia or thrombocytosis occurred in 1 in 14 patients without clinical indications for preoperative platelet testing. Patients with mild thrombocytopenia (101,000–150,000 µl−1), moderate-to-severe thrombocytopenia (&lt;100,000 µl−1), and thrombocytosis (≥450,000 µl−1) were significantly more likely to be transfused (7.3%, 11.8%, 8.9%, 3.1%) and had significantly higher 30-day mortality rates (1.5%, 2.6%, 0.9%, 0.5%) compared with patients with a normal platelet count. In the multivariable analyses, mild thrombocytopenia (adjusted odds ratio [AOR], 1.28; 95% CI, 1.18–1.39) and moderate-to-severe thrombocytopenia (AOR, 1.76; 95% CI, 1.49–2.08), and thrombocytosis (AOR, 1.44; 95% CI, 1.30–1.60) were associated with increased risk of blood transfusion. Mild thrombocytopenia (AOR, 1.31; 95% CI, 1.11–1.56) and moderate-to-severe thrombocytopenia (AOR, 1.93; 95% CI, 1.43–2.61) were also associated with increased risk of 30-day mortality, whereas thrombocytosis was not (AOR, 0.94; 95% CI, 0.72–1.22). Conclusion: Platelet count abnormalities found in the course of routine preoperative screening are associated with a higher risk of blood transfusion and death.

Thromboelastometry in Patients Receiving Platelet Transfusion after Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3630-3630
Author(s):  
Henning Dehmel ◽  
Andreas Tiede ◽  
Silvia Horter ◽  
Arnold Ganser ◽  
Mario von Depka
Keyword(s):  
Platelet Count ◽  
Platelet Transfusion ◽  
Reference Range ◽  
Bleeding Risk ◽  
Substantial Improvement ◽  
Severe Thrombocytopenia ◽  
Bleeding Events ◽  
Bleeding Symptom ◽  
Before And After ◽  
Risk Of Hemorrhage

Abstract Prophylactic platelet transfusion is frequently administered to reduce the risk of hemorrhage in patients undergoing chemotherapy for leukemia or cancer. A platelet count of 10 or 20x109 L−1 is often used as an occasion for platelet transfusion. In clinical studies, the bleeding risk was similar using either threshold (Rebulla, NEJM1997; 337:1870, Wand, Blood1998; 91:3601). Moreover, serious bleeding events were not related to the patients’ platelet count. Thromboelastometry with ROTEM® Whole-Blood Coagulation Analyzer (Pentapharm, Munich, Germany) is a method that may provide a better estimate of the risk of hemorrhage because it also depends on platelet function and plasma coagulation. We therefore performed a pilot study in 13 adult patients receiving prophylactic platelet transfusion after chemotherapy for leukemia or lymphoma. ROTEM® was performed using an ellagic acid based activating reagent (in-TEM®, Pentapharm). Clotting profiles were evaluated using the following thromboelastometric measures: clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF). The median platelet count before transfusion was 9x109 L−1 (range 1 to 20). CT was within the normal range in all patients (median 168 s, range 125–212, reference range 100–240). In contrast, a prolonged CFT (median 139 s, range 51–4526, reference range 30–110) and reduced MCF (median 34 mm, range 19–54, reference range 50–72) was recorded. Correlation between platelet count and CFT (R=−0.41, Spearman) or MCF (R=+0.48) was weak and not statistically significant. 15 min after platelet transfusion, there was an increase in platelet count (median 39x109 L−1, range 23–48) and a substantial improvement of CFT (median 99 s, range 44–332) and MCF (median 49 mm, range 40–64). Changes in thromboelastometric measures were due to platelet transfusion as the addition of cytochalasin D (fib-TEM®, Pentapharm) resulted in identical profiles before and after transfusion. Changes in platelet count correlated with changes in MCF (R=+0.73, P<0.01), but not CFT (R=−0.40, P=0.17). Comparing patients who had a maximum of one mild bleeding symptom (n=9) with patients who experienced one severe or at least two mild bleeding symptoms (n=4), there was no difference in platelet counts (median 10 vs. 9x109 L−1, p=0.77). In contrast, there was a trend towards a shorter CFT (median 111 vs. 388 s, P=0.09) and higher MCF (median 39 vs. 29.5 mm, P=0.09) in the group of non-bleeding patients. In summary, ROTEM® seems to be a sensitive method to detect hemostatic changes in patients with severe thrombocytopenia receiving platelet transfusion and to identify thrombocytopenic patients with an increased bleeding risk. Therefore, further studies to evaluate ROTEM® as a means to estimate the bleeding risk in thrombocytopenic patients are warranted.

Role of Molecular Mimickry of Hepatitis C Virus (HCV) Protein with Platelet GPIIIa in Hepatitis C-Related Immunologic Thrombocytopenia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 398-398
Author(s):  
Wei Zhang ◽  
Michael A. Nardi ◽  
William Borkowsky ◽  
Simon Karpatkin
Keyword(s):  
Platelet Count ◽  
Hepatitis C ◽  
Phage Library ◽  
Drug Abusers ◽  
Severe Thrombocytopenia ◽  
Linear Epitope ◽  
Wild Type ◽  
Conserved Core

Abstract HIV-ITP patients have a unique Ab against platelet GPIIIa49-66 which induces oxidative platelet fragmentation in the absence of complement (Cell106: 551, 2001; JCI113: 973, 2004). Since HCV-ITP, like HIV-ITP, is associated with circulating immune complexes, we asked whether the complexes could contain platelet fragments induced by oxidative platelet fragmentation and whether HCV-ITP could be induced by molecular mimickry with an HCV peptide. The incidence of Hepatitis-C related ITP varies from 10–40% increasing with severity of liver disease. HIV-ITP is more frequent in drug abusers compared to non-drug abusers (37% vs 16%); and more severe in HIV-drug abusers than non-drug abusers (platelets &lt;10,000/ul in 52% vs 9%). A striking feature of HIV-infection in drug abusers is the frequent co-infection with HCV. HCV infection in non-drug abusers (~30%) increase to 90% in drug abusers. We asked whether coinfection with HCV facilitates ITP, and if so, which would be the mechanism. We screened a 7 mer peptide phage library with anti-GPIIIa49-66 Ab as bait for peptides showing homology sequences with HCV protein. Three clones had 70% homology with HCV protein, as well as a non-conserved core envelope 1 peptide, PHC09 (SAIHIRNASG). Three additional non-conserved envelope 1 peptides with 70% homology for PHC09 were found in the NIH data base (PHC09-H4, PHC09-H5 and PHC09-H6). The envelope 1 protein is a known neutralizing HCV epitope reactive with human MoAb vs 12 different HCV Envelope 1 isolates, containing the candidate linear epitope _ _ RN_SG_Y_. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with PHC09 and correlated inversely with platelet count r2=0.7, p&lt;0.01, n=15. Ab raised against this peptide in GPIIIa −/− mice induced severe thrombocytopenia in wild-type mice, n=4. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro, n=5. Drug abusers dually infected with HCV and HIV had a greater incidence and severity of thrombocytopenia (&lt;30,000/ul) in 8/15 dually infected patients compared to 2/15 HCV-ITP (p&lt;0.025) or 3/15 HIV-ITP patients (p=0.06). This was associated with a greater incidence and titer of anti-GPIIIa49-66 Ab in 12/15 HCV-HIV-ITP compared to 2/15 HCV-ITP (P=0.001) or 6/15 HIV-ITP patients (p&lt;0.05). They also had a greater incidence of anti PHC09 Ab in 10/15 HCV-HIV-ITP patients compared to 3/15 HCV-ITP (p=0.004) or 1/15 HIV-ITP patients (p=0.001). Similar findings were obtained with PHC09-H5. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab titers vs PHC09 and significantly lowered their platelet count by 60%, compared to controls, P&lt;0.001. Anti-PHC09 Ab correlated inversely with platelet count, r2=0.63, n=15, P&lt;0.05, n=8. Thus, 1) HCV-ITP complexes contain anti-PHC09 Ab capable of inducing oxidative platelet fragmentation; 2) HCV-ITP can be induced by molecular mimickry with HCV core envelope 1 protein, PHC09; 3) Dually infected ITP drug abusers with HIV and HCV have greater titers of anti-GPIIIa49-66/PHC09 Ab than HCV-ITP or HIV-ITP patients and more severe thrombocytopenia.

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