RESUMO
Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a "self" protein-platelet factor 4-bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.
Assuntos
Heparina/efeitos adversos , Caracteres Sexuais , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Fatores de Risco , Procedimentos Cirúrgicos OperatóriosRESUMO
OBJECTIVES: Patients receiving mechanical circulatory support are at risk for the development of heparin-induced thrombocytopenia due to the prolonged postoperative use of heparin. We evaluated their antibody status and outcome. METHODS: Between 2003 and 2004, 115 patients received mechanical circulatory support for more than 5 days. Blood samples from postoperative day 7 were retrospectively analyzed for anti-platelet factor 4/heparin antibodies and heparin-induced platelet activation. RESULTS: Overall, 12 (10.6%) patients had heparin-induced thrombocytopenia as defined by in vitro platelet activation, 28 (24.8%) had nonactivating antibodies, and 73 (64.6%) were classified as negative for antibodies. Patients positive for heparin-induced thrombocytopenia had the highest levels of anti-platelet factor 4/heparin immunoglobulin G antibodies. Freedom from thromboembolism was 33%, 33%, and 16% at 1, 3, and 6 months for positive patients, 77%, 68%, and 55% for negative patients (P < .001), and 70%, 53%, and 53% for patients with nonactivating antibodies (P = .068), respectively. The relative risk for thromboembolism in antibody positive patients peaked in the first month of support (odds ratio 7.46, P = .002). Independent risk factors for thromboembolic events included higher anti-platelet factor 4/heparin antibody titers, female gender, and higher fibrinogen levels. CONCLUSION: Heparin-induced thrombocytopenia was more prevalent in patients receiving mechanical circulatory support than in other cardiac patients. Frequent antibody screening is recommended due to the increased risk of thromboembolism. Heparin alternatives should be subjected to clinical trials in these high-risk patients.
Assuntos
Anticoagulantes/efeitos adversos , Coração Auxiliar , Heparina/efeitos adversos , Trombocitopenia/induzido quimicamente , Anticorpos/sangue , Anticoagulantes/imunologia , Feminino , Heparina/imunologia , Humanos , Masculino , Fator Plaquetário 4/imunologia , Estudos Retrospectivos , Trombocitopenia/epidemiologiaRESUMO
Immune mediated heparin induced thrombocytopenia (HIT) is a prothrombotic adverse effect of heparin. However, only a subgroup of patients with HIT develops thromboembolic complications. We aimed to identify risk factors for developing HITassociated thrombosis. We analyzed a registry of patients with clinical suspicion of HIT who tested positive using a sensitive functional assay. Patient information was obtained by a standardized questionnaire. By multivariate analysis the association of age, gender, type of patient population, and magnitude of the platelet count decline with the frequency, type (venous or arterial), and temporal pattern of thrombotic events was assessed. In 408 HIT patients we observed predominance of venous thrombosis (2.4:1), with 40% of patients developing a pulmonary embolism. However, in the subgroup of post-cardiovascular surgery patients there was predominance of arterial thrombosis (1:8.5). The type of arterial thrombosis (limb artery thrombosis > thrombotic stroke > myocardial infarction) was the converse of that observed with typical atherothrombotic clots in non-HIT populations. In 59.8% of patients HIT-related thrombosis manifested either on the same day a platelet count decrease >50% was documented (26.3%) or before the decrease in platelet counts (33.5%). The most important risk factors for thrombosis were orthopedic/trauma surgery and the magnitude of platelet count decrease. HIT-associated thrombosis occurs in a considerable proportion of patients before platelet counts decrease by more than 50%.
Assuntos
Heparina/farmacologia , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombose/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Plaquetas/citologia , Plaquetas/metabolismo , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
Heparin-induced thrombocytopenia (HIT), a serious complication of heparin therapy, mandates heparin cessation and alternative anticoagulation. We report a patient with a history of HIT who successfully underwent cardiopulmonary bypass (CPB) using short-term reexposure to heparin and perioperative therapy with argatroban. No bleeding complications or HIT-related problems occurred. The pharmacokinetics of argatroban, especially its hepatic rather than renal elimination, makes it the drug of choice for some HIT patients in whom other alternative anticoagulants (eg, danaparoid and hirudin) are less well suited. Because of interference with the international normalized ratio (INR), switching from argatroban to oral anticoagulants is not straightforward.
Assuntos
Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Ponte Cardiopulmonar , Heparina/efeitos adversos , Ácidos Pipecólicos/uso terapêutico , Trombocitopenia/induzido quimicamente , Adulto , Anticoagulantes/administração & dosagem , Arginina/análogos & derivados , Feminino , Humanos , Ácidos Pipecólicos/administração & dosagem , SulfonamidasRESUMO
Recombinant hirudin has been found to be immunogenic in patients treated with lepirudin following heparin-induced thrombocytopenia (HIT). We assessed the incidence of immunoglobulin G (IgG) antihirudin antibodies by enzyme-linked immunosorbent assay in 112 patients enrolled in a dose-finding study with desirudin. Patients received desirudin subcutaneously following orthopedic hip surgery at 10 mg twice a day (n = 17), 15 mg twice a day (n = 75), and 20 mg twice a day (n = 20). Of 112 patients, 11 (9.8%) developed antihirudin antibodies independently of the dose. The rate of immunization did not differ from that observed in HIT patients treated with lepirudin (P =.113). Plasma concentrations of desirudin did not differ between antihirudin antibody-positive and -negative patients. Antihirudin antibodies had no impact on incidences of deep vein thrombosis and/or pulmonary embolism, allergic reactions, and hemorrhage. However, the total number of immunized patients observed was low and so infrequent (but severe) effects of antihirudin antibodies cannot be excluded.