Heparin-Associated Thrombocytopenia 1 - HAT 1


The goal of the study was to evaluate treatment with hirudin compared with historical controls among patients with heparin-induced thrombocytopenia (HIT).

Study Design

Study Design:

Patients Enrolled: 82
Mean Follow Up: 35 days
Mean Patient Age: Range 18-84
Female: 63

Patient Populations:

Presence of HIT antibodies and diagnostic decrease in platelet count by ≥30% or to values <100 g/L and/or new TECs during prestudy heparin administration.


Severe renal insufficiency requiring hemodialysis or hemofiltration, anticipated poor compliance, known hypersensitivity to hirudin, or were pregnant.

Drug/Procedures Used:

Patients with HIT were treated with one of the following four intravenous doses of hirudin: a) hirudin 0.4 mg/kg IV bolus, followed by 0.15 mg/kg/h intravenous infusion (n=51 patients with thrombosis); b) thrombolysis plus hirudin 0.2 mg/kg, followed by 0.10 mg/kg/h (n=5 patients with thrombosis); c) hirudin 0.10 mg/kg/h (n=18 patients without thrombosis); or d) during cardiopulmonary bypass surgery (n=8), 0.25 mg/kg bolus and 5 mg boluses as needed). Data were compared to historical controls with HIT (n=120).

Principal Findings:

Treatment was completed in 90% of patients. Acute HIT was present in 75.6% of patients, with the remaining 19.5% classified as latent HIT. Platelet response was achieved in 88.7% of patients. aPTT increased to 1.5 to 3.0 times baseline values in all groups except the bypass group, with the acute HIT groups having the greatest aPTT response.

Among the clinical events in the weeks after HIT confirmation, new thromboembolic complication occurred in 9.9% of hirudin-treated patients, limb amputation in 2.8%, and death in 0% for a combined event rate of 9.9%. At 35 days after HIT confirmation, the composite event rates for hirudin-treated patients was significantly lower compared with historical controls (25.4% vs 52.1%, p=0.014). Among the components of the composite, mortality occurred in 8.6% of the hirudin-treated patients vs 22.3% of historical controls (p=0.071), new thromboembolic complication in 18.4% and 32.1% (p=0.270), and limb amputations in 5.7% and 8.2% (p=0.783), respectively. At 28 days, there was no difference in the composite of bleeding or transfusion (39.6% for hirudin vs 35.3% for historical control, p=0.60) or bleeding requiring transfusion (9.9% vs 9.1%, p=0.59).


Among patients with heparin-induced thrombocytopenia, treatment with hirudin was associated with a substantial portion of patients achieving platelet response and a lower rate of the composite of death, limb amputations, and new thromboembolic complications compared with historical controls, without an increase in bleeding or transfusions.

The HAT 2 trial, performed by the same investigative group, evaluated lepirudin compared with the same historical controls with HIT. In HAT 2, lepirudin was associated with a significantly higher bleeding rate compared with the historical controls, unlike the present study which showed no increase in bleeding with hirudin. Additionally, HAT 2 demonstrated only a trend toward a reduction in the composite of death, limb amputations, and new thromboembolic complications with lepirudin, unlike the present study which showed a significant reduction in the composite endpoint with hirudin.


Greinacher A, et al.Recombinant Hirudin (Lepirudin) Provides Safe and Effective Anticoagulation in Patients With Heparin-Induced Thrombocytopenia. Circulation. 1999;99:73-80.

Clinical Topics: Anticoagulation Management

Keywords: Platelet Count, Thrombosis, Heparin, Cardiopulmonary Bypass, Hirudins, Thrombocytopenia

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