Risk factors for unfavorable clinical outcome in patients with documented heparin-induced thrombocytopenia.

BACKGROUND: Prognostic factors for unfavorable clinical outcome in patients with heparin-induced thrombocytopenia (HIT) are largely unknown. DESIGN AND METHODS: In this multicenter, retrospective, case-control study, all HIT patients were treated with danaparoid. Study cases were HIT patients with an unfavorable clinical outcome. Controls were HIT patients who were not study cases. Unfavorable clinical outcome was defined as the occurrence of at least one of the following clinical events: death within 60 days after HIT start date, or venous or arterial thromboembolism, amputation, major bleeding, or disseminated intra-vascular coagulation between 48 hours and 60 days after HIT start date. RESULTS: Compared with controls (n=65), thrombotic episodes within 48 hours of HIT start date were more frequent (59.2% versus 32.3%; p=0.004), the median time between HIT start date and initiation of danaparoid infusion was longer (3.0 versus 1.0 days; p=0.001), and this treatment was more frequently underdosed (43.8% versus 18.8%; p=0.004) in study cases (n=49). Upon multivariate analysis, all these three parameters were significant predictive factors for unfavorable clinical outcome. The adjusted odds ratios [95% confidence interval] were 6.6 [2.5-17.3] for time between HIT start date and danaparoid initiation over 48 hours, 4.3 [1.5-12.0] for danaparoid underdosing, and 3.2 [1.3-8.0] for presence of a thromboembolic episode at HIT start date. CONCLUSIONS: This study supports the recommendations concerning the management of HIT patients, namely discontinuation of all heparin administration once the diagnosis is suspected and prompt initiation of an alternative anticoagulant drug with a strict adherence to doses specifically recommended for these patients.

[Use of ecarin clotting time in whole blood for monitoring recombinant hirudine treatment during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia]. / Utilisation du temps de coagulation par l'écarine en sang total pour la surveillance d'un traitement anticoagulant par lépirudine (Refludan au cours de circulation extracorporelle dans un contexte de thrombopénie induite par l'héparine.

Lepirudin (Refludan is a recombinant hirudin, approved for anticoagulation treatment of heparin-induced thrombocytopenia patients with thrombosis. We report here our method for laboratory monitoring with ecarin clotting time (ECT) of hirudin therapy as anticoagulation for cardiac surgery. Ecarin is extracted from the Echis carinatus snake venom and directly converts prothrombin to its intermediate, meizothrombin. This one binds in a stoechiometric way to hirudin to be proportioned in whole blood. The activation of coagulation starts up only when the totality of the hirudin is bound to the meizothrombin. To minimize the effect of dilution related to the CEC on the prothrombin and fibrinogen levels, thus lengthening the ECT, the specimen to be tested is diluted with normal whole blood. In 1997, when we have performed our first surgery with cardiopulmonary bypass, only one team (Pötzsch et al., 1997) had described the use of the ECT in whole blood. We describe in this work our assay to dose hirudin with ECT after dilution in whole blood. This assay was used during 8 CEC among 7 patients affected with HIT (n = 6) or potentially sensitized with heparin (n = 1). Experimental conditions and interpretation of the assay are reported here. This test is fast enough to provide useful information for adjusting the dose during cardiopulmonary bypass.

Practical approach to the diagnosis and management of thrombocytopenia associated with tirofiban treatment.

Anti-GPIIb/IIIa associated thrombocytopenia has been reported in most large trials, but very little data is available regarding tirofiban. We report three cases of thrombocytopenia, most likely attributed to tirofiban (two moderate and one severe). For each patient, laboratory investigation has allowed us to exclude another cause of thrombocytopenia, particularly heparin-induced thrombocytopenia. Platelet count recovery could be earlier with tirofiban than with abciximab. Some suggestions are proposed for practical management of these patients with persistent thrombotic risk, who are sometimes candidates for cardiopulmonary bypass surgery.