Medical News Stories
Heparin-Induced Thrombocytopenia in Medical Surgical Critical Illness
Study Question: What are characteristics associated with heparin-induced thrombocytopenia (HIT) and does the reduced risk of HIT seen with dalteparin compared to unfractionated heparin (UFH) in one trial correlate with decreased seroconversion related to study drug or decreased breakthrough of HIT-related thrombocytopenia and/or thrombosis?
Study Description: This was a retrospective analysis of patients with HIT enrolled in the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT), which was a study comparing dalteparin and UFH in critically ill patients that showed dalteparin not superior in preventing deep vein thrombosis (DVT), but was superior in preventing pulmonary embolism. Dalteparin was also associated with a lower risk of HIT in the PROTECT per-protocol analysis. In the current study, seroconversion related to study drug was defined as a positive serotonin release assay (SRA) at least 5 days after initiation of the study drug. Patients were scored with points (0-2) based on the likelihood of study drug-associated seroconversion and breakthrough thrombosis or thrombocytopenia, as well as the presence of confounding open-label heparin administration. The investigators also compared the risk of anti-PF4/heparin antibody seroconversion in all patients tested for HIT in the PROTECT to determine if there was a lower risk with dalteparin vs. UFH.
Results: There were a total of 17 SRA positive patients. Sixteen had a 4Ts score of 4 (i.e., consistent with HIT). More patients in the UFH group experienced seroconversion to a positive SRA plausibly related to study drug than in the dalteparin group (8 vs. 2, respectively; p = 0.058), although all of these patients received open-label heparin. The UFH group also scored more points than the dalteparin group for possible study drug related thrombocytopenia or thrombosis (19 vs. 6, respectively; p = 0.032). In the IgG specific anti-PF4/heparin enzyme-linked immunosorbent assay (ELISA) test, there were significantly more positive tests with ≥ 0.45 units of optical density (OD) seen with UFH than dalteparin (reference range < 0.45).
Conclusion(s): The reduced incidence of HIT seen with dalteparin, compared with UFH, is related to less seroconversion with dalteparin, as well as decreased clinical breakthrough of HIT.
Perspective: This study provided a noteworthy attempt to examine the precipitating factors of HIT in PROTECT. However, the results of the study may have been biased by the use of the scoring system since there were more patients in the UFH group than the dalteparin group and the authors compared total points in the analysis. Additionally, due to the extensive frequency of open-label heparin, it is difficult to draw appropriate clinical conclusions regarding the cause of the lower HIT incidence with dalteparin absent potentially significant confounding effects.