Heparin-induced thrombocytopenia in medical surgical critical illness.
Chest. 2013 May 30;
Authors: Warkentin TE, Sheppard JA, Heels-Ansdell D, Marshall JC, McIntyre L, Rocha MG, Mehta S, Davies AR, Bersten AD, Crozier TM, Ernest D, Vlahakis NE, Hall RI, Wood GG, Poirier G, Crowther MA, Cook DJ
Abstract
ABSTRACT BACKGROUND: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3746 critically-ill patients, 17 (0.5%) patients developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (5 vs 12 patients; P=0.14), which was statistically significant (3 vs 12 patients; P=0.046) in a prespecified per-protocol analysis which excluded patients with deep-vein thrombosis (DVT) at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis might reduce HIT frequency in ICU patients. METHODS: In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to study drug and other open-label heparin, to determine whether study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. RESULTS: HIT-associated thrombosis occurred in 10/17 (58.8%) patients (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P=0.020), including less seroconversion (P=0.058) and less breakthrough of thrombocytopenia/thrombosis (P=0.032). Anti-PF4/heparin IgG antibodies by ELISA were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%; P<0.001). One patient with HIT-associated DVT died post-UFH bolus, whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. CONCLUSIONS: The lower risk of HIT in ICU patients receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
PMID: 23722881 [PubMed - as supplied by publisher]