Heparin-Induced Thrombocytopenia with Low Molecular Weight Heparin

Abstract & Commentary

By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.

Synopsis: In this prospective study of 1754 medical patients receiving low molecular weight heparin (LMWH), Prandoni and colleagues found a 0.8% incidence of heparin induced thrombocytopenia. The incidence was similar to a prior study they performed in medical patients receiving unfractionated heparin (UFH). Prior heparin exposure was associated with an increased risk of HIT. These data raise the possibility that HIT occurs more commonly in medical patients than previously appreciated and the incidence may not necessarily be significantly lower than with UFH. Clinicians must remain aware of the possibility of HIT, even in patients receiving either LMWH or UFH.

Source: Prandoni P, et al. The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study. Blood. 2005;106:3049-3054.

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune complication related to heparin exposure, especially unfractionated heparin (UFH). The syndrome is characterized by falling platelet counts and a paradoxical proclivity toward thrombosis. It usually occurs 5 days or more after heparin exposure although HIT may develop sooner in patients with recent heparin exposure. The incidence has been shown to be significantly lower with the use of low molecular weight heparin (LMWH). In a randomized controlled study, only 1/720 (0.1%) patients treated with LMWH developed HIT compared to 8/356 (2.2%) receiving UFH. The low incidence of HIT with LMWH has raised questions whether patients on LWMH require surveillance for HIT.

Prandoni and investigators report a large prospective study of medical patients receiving LMWH for thrombosis prophylaxis and treatment and report the incidence of HIT. In this multicenter trial, the 1754 evaluable patients were followed platelet counts, serology for heparin induced antibodies, and clinical events.

Twenty-one percent received prophylaxis LMWH and the remainder received either intermediate/fixed dosing or therapeutic doses. Prior exposure to UFH or MWH was present in 34%. Twenty-nine patients had an unexpected decline of > 50% in platelets not accounted for by other factors but only 14/29 tested positive for heparin-induced antibodies. The incidence of HIT was 0.8% (14/1754; 95% CI, 0.31-1.12%). There was no difference in incidence of those receiving LMWH for prophylaxis compared to treatment LMWH. The incidence was 1.7% among those with prior heparin exposure. Most patients received anticoagulation for HIT but 4/14 developed symptomatic thrombosis.

Commentary

LMWH has found widespread use as an UFH substitute for both thrombosis prophylaxis and treatment owing to equal or superior efficacy and reduced need for monitoring. Another potential benefit of LMWH has been the significantly lower incidence of one of the most serious complications of UFH—heparin-induced thrombocytopenia. Limited data has addressed the incidence of HIT in medical patients. From a clinical perspective, HIT, either recognized or undiagnosed, often leads to consultation by a hematologist/oncologist.

In a prior study by the same group using UFH, a very similar incidence of HIT of 0.84% was found compared to the 0.8% incidence detected her with LMWH. While one can not draw definitive conclusions in non-randomized studies, the findings are intriguing and contradict prior work suggesting a much lower incidence of HIT with LMWH. The data imply HIT may occur more commonly in medical patients than previously appreciated. Although a 0.8% incidence is low, the serious ramifications of a missed diagnosis raise concerns about whether routine platelet monitoring may be needed for patients receiving LMWH, especially in the first two weeks of therapy. The increased incidence in patients with prior exposure may point to a group where a high index of suspicion is warranted.

References

1. Lindhoff-Last E, et al. Incidence and clinical relevance of heparin-induced antibodies in patients with deep vein thrombosis treated with unfractionated or low-molecular-weight heparin. Br J Haematol. 2002;118:1137-1142.