Failure of Fondaparinux in Autoimmune Heparin-Induced Thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin that is associated with life-threatening thrombotic complications. More rarely, HIT may begin after stopping of heparin or after flushes of heparin (autoimmune HIT). Fondaparinux has been proposed as a candidate treatment for HIT, but there are few data on its use in autoimmune HIT. An 86-year-old man with a history of diabetes mellitus, arterial hypertension, and hypercholesterolemia was admitted to our hospital for carotid endarterectomy. During surgery, only one heparin dose of 5,000 U was used. Platelet count started to decrease on the 11th day after surgery. Since the patient was not receiving heparin treatment/prophylaxis, HIT was not suspected. On day 19, platelet count was 61 × 103/μL, and the patient was investigated for a diagnosis of HIT. Immunoglobulin (Ig)-G-specific enzyme-linked immunosorbent assay (ELISA) was positive and HIT was confirmed by a platelet aggregation test; fondaparinux 5 mg once a day was started. During fondaparinux treatment, platelet count did not increase and a lower leg deep vein thrombosis occurred. Fondaparinux was stopped and rivaroxaban 15 mg twice a day was started. Platelet count returned to base line after 10 days from fondaparinux withdrawal. There was no thrombotic event or bleeding complication during rivaroxaban treatment. Anecdotal evidence suggests risk of failure of fondaparinux treatment for autoimmune HIT and supports the use of rivaroxaban for treatment of HIT, justifying larger studies.

Therapeutic plasma exchange in severe refractory autoimmune heparin‐induced thrombocytopenia with thrombosis

“…Notably, our present patient demonstrated progression of her thrombotic burden in the setting of fondaparinux. Three prior case reports have similarly demonstrated fondaparinux failure in patients with HITT, with in vitro documentation in two of these cases showing cross‐reactivity based on the augmentation of platelet activation with fondaparinux 6–8 . We did not check for in vitro cross‐reactivity of fondaparinux, but it is possible that in a subset of patients with HITT, fondaparinux may augment platelet activation with antibodies that cross‐react with PF4/fondaparinux complexes.…”

“…Three prior case reports have similarly demonstrated fondaparinux failure in patients with HITT, with in vitro documentation in two of these cases showing cross-reactivity based on the augmentation of platelet activation with fondaparinux. [6][7][8] We did not check for in vitro cross-reactivity of fondaparinux, but it is possible that in a subset of patients with HITT, fondaparinux may augment platelet activation with antibodies that cross-react with PF4/fondaparinux complexes. While these reports remain anecdotal, our present case adds to the growing evidence of fondaparinux's failure in some HITT cases.…”

“…The present study uses a subpopulation 'complete ascertainment' approach to define the incidence of CLL and the numbers of patients requiring treatment annually in the ROI, many of whom may benefit from targeted-therapy treatment in first and second line as being defined by recently completed or ongoing studies. [8][9][10]…”

Autoimmune Heparin-Induced Thrombocytopenia

“…Pistulli and colleagues [163] reported a patient who developed HIT with UFH and LMWH in whom the platelet count continued to decline after switching to therapeutic-dose fondaparinux; these authors found laboratory evidence of increased platelet activation in the presence of fondaparinux. Sartori and Cosmi [164] also reported a case of aHIT following a single dose of UFH that was also associated with clinical evidence of fondaparinux failure (persisting thrombocytopenia, new venous thrombosis), although in vitro studies to document cross-reactivity were not performed.…”

“Autoimmune HIT” antibodies in diagnostic samples are a potential artifact and not associated with more severe outcomes

“…In recent years, there has been increasing use of the term autoimmune heparin-induced thrombocytopenia (aHIT) to describe patients whose blood samples activate platelets in the absence of exogenous heparin (ie, in the no-heparin/buffer-control serotonin release assay [SRA]). 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 This term has been proposed to include not only syndromes in which patients develop anti–PF4-mediated thrombotic thrombocytopenia without proximate heparin exposure, such as spontaneous HIT and vaccine-induced immune thrombotic thrombocytopenia, but also several clinically severe HIT subtypes that occur after heparin exposure. These additional entities include delayed-onset HIT, persistent HIT, heparin flush–induced HIT, and severe HIT with a platelet count <20 000/μL with associated disseminated intravascular coagulation.…”