Incidence and clinical relevance of heparin‐induced antibodies in patients with deep vein thrombosis treated with unfractionated or low‐molecular‐weight heparin

Abstract

Summary. The frequency of heparin-induced thrombocytopenia (HIT) varies between different clinical treatment settings and remains unknown for patients treated with unfractionated (UFH) or low-molecular-weight heparin (LMWH) because of deep vein thrombosis. In this multicentre, open-label study, 1137 patients with deep vein thrombosis were randomly assigned to UFH for 5-7 d, reviparin, a LMWH, for 5-7 d (short-treated group) or reviparin for 28 d (long-treated group). Heparin-platelet factor 4 antibodies (HPF4-A) were determined on d 5-7 and d 21. Heparin-induced thrombocytopenia was defined by clinical evaluation. Two patients in the UFH group (incidence: 0AE53%, 95% confidence interval (CI): 0AE06-1AE91) and two patients in the long-treated LMWH group (incidence: 0AE53%, 95% CI: 0AE06-1AE92) had HIT, while no HIT was observed in the short-treated LMWH group. Pulmonary embolism developed in one of the HIT-patients, who had HPF4-A and was treated with UFH. On d 5-7 the incidence of HPF4-A was 9AE1% in the UFH group, 2AE8% in the shorttreated LMWH group and 3AE7% in the long-treated LMWH group, with a significant increase to 20AE7% in the UFH group and to 7AE5% in the long-treated LMWH group on d 21. Therefore the incidence of HPF4-A and heparininduced thrombocytopenia was lower in patients treated with LMWH compared with UFH for the same duration of treatment.

Initial Treatment of Venous Thromboembolism

“…Despite higher cost, LMWH is generally preferred over UFH because LMWH is associated with a lower incidence of HIT 46 and probably osteoporosis during long-term use. 13 LMWH has been found to be at least as effective in preventing recurrence as oral vitamin K antagonists in unselected patients with VTE, 61 and it appears to be superior with regard to efficacy in patients with underlying malignancy.…”

“…44 In patients receiving heparin for treatment of VTE, both antibody formation and clinical HIT are more common with UFH than LMWH. 46 Platelet count monitoring should be performed during therapy with UFH for early detection of HIT. Recent guidelines suggest minimum monitoring of platelet counts every other day between days 4 and 10 of treatment (with day 0 being the first day of treatment).…”

Treatment and Prevention of Heparin-Induced Thrombocytopenia

“…11,12 The end result is marked generation of thrombin and the formation of venous and arterial thromboses that are the clinical hallmark of HIT. Risk factors for HIT include duration and type of heparin exposure, 13 patient population, [14][15][16] severity of trauma, 17 and gender. 18 Differences in the stoichiometry of heparin/PF4 complexes are believed to explain the 10-fold higher likelihood of HIT in patients who receive unfractionated heparin (UFH) compared with patients who receive low-molecular weight heparin (LMWH) or fondaparinux.…”

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

“…The size of the heparin molecule at least in part determines its affinity for PF4, as has been shown experimentally. 25 Presumably, this makes LMWH less likely to induce HIT than the larger unfractionated heparins. Studies comparing the incidence of HIT antibodies in patients treated with UFH and in those treated with LMWH have confirmed a greater incidence of anti-H-PF4 antibody formation in patients taking UFH than in those taking LMWH, but LMWH may still induce HIT because, within a given preparation of LMWH, the larger molecules are of sufficient size to complex with PF4.…”