Heparin-associated thrombocytopenia: an update.
The use of heparin may be complicated by two types of thrombocytopenia (HAT): type I occurs early, is transient, and has no clinical relevance, while type II may lead to very severe manifestations (arterial or venous thromboses and more rarely bleedings), that are still underestimated by some clinicians. HAT-type II most frequently develops after use of therapeutic doses of unfractionated heparin (UH) but has also been described less frequently after use of very low doses of UH, of low molecular weight heparins (LMWH), and even of polysulfated glycosaminoglycosans devoid of anticoagulant action. The estimation of the incidence of HAT-type II and of related thromboses is a very difficult matter. Recent observations suggest that thromboses (notably venous) may be more frequent than previously estimated. HAT-type II pathophysiology includes the formation of immune complexes at the surface of platelets; the antigen has been shown to be most often platelet factor 4 bound to heparin while the antibody is recognized by platelet Fc gamma RII receptors. Thromboses result most probably from activation of both platelets (leading to the formation of microparticles) and endothelial cells. Several biological tests are presently available for diagnosing HAT-type II but none of them has been shown to be ideal. The prevention of HAT-type II requires history taking preference of LMWH to UH, early start of oral anticoagulation, and platelet monitoring from the fifth day of heparin therapy. The therapy of HAT-type II implies immediate discontinuation of heparin and avoidance of platelet transfusions, unless severe bleeding occurs. If further antithrombotic treatment is deemed necessary (probably in all cases), several options are possible but presently, the most recommended ones are Org 10172 or Ancrod; embolectomy or thrombolysis may also be required if a new thrombotic event has developed. A very difficult dilemma concerns patients previously sensitized to heparin and who present a clinical situation that theoretically mandates re-exposure to UH, such as by-pass surgery; prostacyclin analogues may be successfully used in such cases. Recent developments in the therapy of HAT-type II include recombinant hirudin or synthetic analogs, or use of some intravenous immunoglobulin preparations. Possible candidates are the heparin synthetic pentasaccharide and recombinant tissue factor pathway inhibitor.
Fondu
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Laboratoire d'Hématologie, Hôpital Universitaire Brugmann, Bruxelles.
D000721:Ancrod / Q000627:therapeutic use; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control
D005343:Fibrinolytic Agents; D006493:Heparin; D000721:Ancrod