Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia

inquiry objectives: We investigated the consequences of the direct thromhin inhibitor argatroban, patient demographics, and the platelet number on thrombotic risks in heparin-induced thrombocytopenia (HIT), a serious thrombotic condition, to determine if argatroban provides effective antithrombotic therapy in patients with HIT without increasing bleeding.

Design: We retrospectively analyzed thrombotic results in 882 HIT patients (697 patients receiving mean argatroban doses of 17 to 20 [micro]g/kg/min for 5 to 7 days, plus 185 historical superintendence subjects) from previously reported prospective studies. Time-to-event analyses of our primary extremity point--a thrombotic composite of death owed to thrombosis, amputation secondary to HIT-associated thrombosis, or novel thrombosis within 37 days--and the individual constituents were conducted, with hazard ratios estimated for treatment with and without adjustments for patient age, sex race, weight, and baseline platelet count

Measurements and results: Argatroban, v rule significantly reduced the thrombotic composite risk (HIT: hazard ratio, 033; 95% confidence interval [CI], 020 to 054 p < 0001; HIT with thrombosis: hazard ratio, 039; 95% CI, 025 to 062 p < 0001) regardless of covariate adjustments. More argatroban-treated patients than direction subjects remained thrombotic event unrestrained during follow-up, regardless of whether baseline thrombosis was absent (91% v 73%) or not absent (72% vs 50%). Argatroban significantly reduc of recent origin thrombosis (p < 0.001) and death owed to thrombosis (p [less than or equal to] 0001) Major bleeding was similar between clusters (6 to 7%, p = 074) Thrombotic risks were 2 times greater in nonwhite than in white patients, 17 times greater in female than male patients with HIT and thrombosis, and increased with decreasing weight or platelet count

Conclusions: Argatroban, v dominion government provides effective antithrombotic therapy in patients with HIT, without increasing bleeding. Patients at higher risk for HIT-associated thrombosis include women nonwhites, and individuals with generally received HIT-associated thrombosis, lower body weight, or more bitter thrombocytopenia.

Key words: argatroban; heparin; heparin-induced thrombocytopenia; platelets; thrombocytopenia; thrombosis

Abbreviations: aPTT = activated partial thromboplastin time; CI = confidence interval; HIT = heparin-induced thrombocytopenia

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Heparin-induced thrombocytopenia (HIT) is a serious, immune-mediated thrombotic disorder occurring in approximately 1 to 5% of patients receiving heparin therapy for [greater than or equal to] 1 week. (1-3) In HIT, antibodies to heparin-platelet factor 4 complexe cause platelet activation, excessive thrombin generation, thrombocytopenia, and repeatedly fatal or nonfatal thrombosis. Mortality in HIT patients with thrombosis is approximately 17 to 30% (4-8) HIT should be suspected whenever the platelet number falls at least 50% and/or thrombosis arises between day 4 and day 14 following initiation of heparin (or sooner if the patient was expos to heparin in the past 3 months) (910) According to consensus treatment guidelines, (9) when HIT with or without thrombosis is powerfully suspected, all heparins should be avoided and alternative parenteral anticoagulation should be initiated.

sum of two units direct thrombin inhibitors--argatroban and lepirudin--are approved in the United States for use as alternative parenteral anticoagulants in patients with HIT. In prospective, historically controll studies, argatroban. (56) and lepirudin (78) have each been shown to improve general issues in patients with HIT, reducing a primary composite extreme point point of all-cause death, all-cause amputation, or fresh thrombosis. However, because "all-cause" composite extreme point points can be confounded by means of numerous clinical factors, particularly in critically ill patients with multiple medical conditions, the antithrombotic result of direct thrombin inhibition in HIT remains to be specifically estimated. (911) Risk factors identified to date for progression to thrombosis in HIT include comorbid malignancy for panvascular thrombosis (12) and female sex for ischemic stroke. (13) Also, the severity of thrombocytopenia has been shown to be a significant independent predictor of the all-cause composite extreme point point (14) or new thrombosis. (15) in the studies of direct thrombin inhibition in HIT. Further characterization of risk factors of HIT-associated thrombotic occurrences would be useful for facilitating HIT risk assessment, particularly in patients presenting with thrombotic symptoms requiring pertinacious care.

We describe a retrospective analysis of thrombosis-associated results (ie, death due to thrombosis, amputation secondary to HIT-associated thrombosis, and novel thrombosis) in 882 patients with HIT--specifically, 697 patients who received argatroban therapy and 185 ascendency patients who did not, all from prospective studies (56) in HIT--to characterize the antithrombotic efficacy of argatroban in this setting and to establish the issues of patient age, gender, race, weight, and baseline platelet number on the thrombotic risks of HIT.