ORIGINAL ARTICLES   

International Angiology 2011 December;30(6):541-6

Copyright © 2012 EDIZIONI MINERVA MEDICA

language: English

Identifying patient- and treatment-related factors related to amputation risk in cases of heparin-induced thrombocytopenia treated with argatroban

Haas S. ¹, Lewis B. ² ✉

¹ Institut für Experimentelle Onkologie und Therapieforschung der Technischen Universität München, Munich, Germany: 2 Division of Cardiology, Loyola University Medical Center, Maywood, IL, USA

AIM: The efficacy of argatroban as an anticoagulant in patients with heparin-induced thrombocytopenia type II (HIT) was shown in two large trials (ARG 911 and ARG 915) using a composite endpoint of death, amputation and new thrombosis, but no benefit was seen in amputation rate. Factors that influenced patients proceeding to amputation are unclear.
METHODS: We retrospectively undertook exploratory data analyses comparing patient- and treatment-related factors in patients with (N.=48) and without (N.=520) all-cause amputation.
RESULTS: Of the amputation cases, 46% had received warfarin, and 97.9% had severe ischemia/gangrene diagnosed pre-argatroban. Thromboembolic complications prior to argatroban were more common in amputation cases (91.7% vs. 71.9%, P=0.003), with a higher proportion of arterial than venous events (68.2% vs. 52.3%, P=0.031; mean 1.7/patient vs. 1.4/patient, P=0.031), largely occurring in the limbs (94.1%). More females than males suffered amputation (P=0.003), and cardiovascular risk was more frequent in amputation cases than non-amputation (hypertension, P=0.008; peripheral vascular disease (PVD), P<0.001; diabetes, P<0.001). There were no differences in baseline platelet count, platelet recovery (24 h post-argatroban), or weighted mean aPTT between groups; amputation was associated with longer treatment duration (5 vs. 7 days, P=0.001).
CONCLUSION: Almost all amputation cases had severe ischemia prior to argatroban; female gender and cardiovascular risk factors, in particular PVD with peripheral vascular surgery, appear to identify a subgroup of patients at high risk of amputation. The pharmacodynamics of argatroban appeared to be unchanged in the amputation cases suggesting that argatroban action was undiminished in the amputation cases despite the negative outcome of treatment.