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Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies
| Content Provider | Scilit |
|---|---|
| Author | Krauel, Krystin Hackbarth, Christine Fürll, Birgitt Greinacher, Andreas |
| Copyright Year | 2012 |
| Description | Heparin is a widely used anticoagulant. Because of its negative charge, it forms complexes with positively charged platelet factor 4 (PF4). This can induce anti-PF4/heparin IgG Abs. Resulting immune complexes activate platelets, leading to the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). HIT requires treatment with alternative anticoagulants. Approved for HIT are 2 direct thrombin inhibitors (DTI; lepirudin, argatroban) and danaparoid. They are niche products with limitations. We assessed the effects of the DTI dabigatran, the direct factor Xa-inhibitor rivaroxaban, and of 2-O, 3-O desulfated heparin (ODSH; a partially desulfated heparin with minimal anticoagulant effects) on PF4/heparin complexes and the interaction of anti-PF4/heparin Abs with platelets. Neither dabigatran nor rivaroxaban had any effect on the interaction of PF4 or anti-PF4/heparin Abs with platelets. In contrast, ODSH inhibited PF4 binding to gel-filtered platelets, displaced PF4 from a PF4-transfected cell line, displaced PF4/heparin complexes from platelet surfaces, and inhibited anti-PF4/heparin Ab binding to PF4/heparin complexes and subsequent platelet activation. Dabigatran and rivaroxaban seem to be options for alternative anticoagulation in patients with a history of HIT. ODSH prevents formation of immunogenic PF4/heparin complexes, and, when given together with heparin, may have the potential to reduce the risk for HIT during treatment with heparin. |
| Related Links | https://ashpublications.org/blood/article-pdf/119/5/1248/1355748/zh800512001248.pdf |
| Ending Page | 1255 |
| Page Count | 8 |
| Starting Page | 1248 |
| DOI | 10.1182/blood-2011-05-353391 |
| Journal | Blood |
| Issue Number | 5 |
| Volume Number | 119 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2012-02-02 |
| Access Restriction | Open |
| Subject Keyword | Hematology Treatment Platelet Anti Pf4/heparin Dabigatran Anticoagulant Pf4/heparin Complexes Antibodies Rivaroxaban Journal: Blood (Vol- 84, Issue- 5) |
| Content Type | Text |
| Resource Type | Article |
