Poster Board I-94
Heparin-induced thrombocytopenia (HIT), alone or associated with thrombosis (HITT), may develop during anticoagulant treatment with unfractionated heparin (UFH) or low-molecular weight heparin (LWMH). Fondaparinux is a selective inhibitor of coagulation factor Xa which apparently does not react with anti-PF4/heparin antibodies in in vitro testing.
From january 2005 to december 2007 we treated 44 patients who had strong suspect of HIT (12 patients) or HITT (32 patients, of whom 12 had both DVT and PE). Of these, 30 patients were previously exposed to unfractionated heparin (UFH) for major cardiac surgery. The remaining patients were admitted to medical or general surgery wards. In the 32 patients who developed HITT, we applied therapeutic dosages of fondaparinux, i.e. 7.5 mg QD or lower, in accordance with their bleeding risk. The remaining patients were treated with prophylactic dosages of fondaparinux, i.e. 2.5 mg QD. Switch to warfarin was performed as soon as possible. The mean of our patients 4T's score was 6.2, corresponding to high risk patients; the mean of anticorpal optical density (GTI Enhanced®) was 1.4; the mean platelet number was 45 × 109/L.
All patients but four showed sustained normalization of the platelet number. All patients but four showed a significant reduction of their thromboembolic burden. No death related to severe bleeding was recorded. Two episodes of major bleeding were recorded in post-surgical patients (4,5%); 4 episodes of minor bleeding were recorded (9,1%). Four patients underwent dialysis during fondaparinux without bleeding complications. One patient developed acute coronary syndrome during treatment with fondaparinux. Nine patients did not survive (20,5%), with a key role of primitive diseases (i.e. sepsis) causing delay in the diagnostic process of HIT (four of them had a diagnosis of HIT with a mean delay of 7 days). In 16 patients submitted to therapeutic dosages of fondaparinux, anti-PF4/heparin antibody titers were followed over time showing a constant decrease: in one case antibody levels did not decrease up to 6 months after stopping both heparin and fondaparinux. Thirty patients were easily switched from fondaparinux to VKAs without problems in reaching the appropriate INR target.
This report provides further evidence supporting the safety and efficacy of fondaparinux in the treatment of HIT and underlines the importance of an early diagnosis. However, it shows the need of a randomized controlled study between fondaparinux and a registered comparator drug.
Piovella:GlaxoSmithKline: Honoraria, Speakers Bureau; Bayer: Honoraria, Speakers Bureau; Boehringer Ingelheim: Honoraria, Speakers Bureau. Off Label Use: fondaparinux in the treatment of heparin-induced thrombocytopenia.
Asterisk with author names denotes non-ASH members.