Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin

Abstract

Heparin-induced thrombocytopenia (HIT)is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the crossreactivity of HIT sera with fondaparinux. Using a prospective, blinded study design, 39 clinically and serologically confirmed sera from patients with HIT and 15 control sera were sent to 3 different laboratories, each of which specialized in a particular HIT assay. These include the serotonin release assay, heparin-induced platelet agglutination assay, and platelet aggregation assay. Two of 82 assays (2.4%) performed in the presence of control sera were positive, both with unfractionated heparin. In the presence of HIT sera, 75 of 94 (79.8%) evaluable assays were positive with unfractionated heparin; fondaparinux was significantly (P < .001) less reactive than unfractionated heparin, only 3 of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, these results suggest that fondaparinux is nonreactive to HIT sera and raise the possibility that the drug may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT. (Blood. 2005;105:139-144)

Severe and persistent heparin‐induced thrombocytopenia despite fondaparinux treatment

“…In vitro studies demonstrated that in most of the cases fondaparinux did not activate platelets in the presence of anti-PF4/heparin antibodies [10]. Fondaparinux was also shown to reduce the risk of developing HIT in patients with baseline platelet-activating heparin-dependent antibodies [11].…”

Avaliação da tromboflebite jugular experimental em equinos tratados com heparina

“…Estudos recentes relatam que o fondaparinux apresenta eficiência e risco hemorrágico similares aos observados com HBPM, com a vantagem de apresentar menor risco de trombocitopenia induzida pela heparina (TIH) [16,21,26,27,28].…”

Use of fondaparinux in a patient with antiphospholipid antibody syndrome and heparin‐associated thrombocytopenia

“…Fondaparinux, which does not require APTT monitoring, has been successfully used for treatment of HIT as well as thrombosis prophylaxis in patients with a history of heparin sensitivity [6][7][8]. A recent prospective blinded study has demonstrated that fondaparinux does not react to sera of patients with HIT, further supporting its potential use in this setting [9]. Currently, there are no published reports of fondaparinux use as thrombosis treatment or as prophylaxis in APS, although its potential use in pregnancy has been evaluated in a mouse model.…”

“…Due to the rarity of the disorder, the available data on the incidence of bleeding episodes, prevalent clinical manifestations and treatment modalities are scarce [2][3][4][5][6][7]. Afibrinogenemia is sometimes associated with symptoms that are unusual in patients with defects of coagulation factors, such as thrombotic complications and miscarriages [8][9][10][11][12]. However, knowledge on the incidence and significance of these unusual symptoms is influenced by publication bias.…”