Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Abstract

Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options.

Małopłytkowość poheparynowa

“…Bovine heparin shows higher immunogenic potential than porcine heparin [7−9, 14, 15]. Although HIT is idiosyncratic in nature and theoretically should not depend on the route of administration and dose [14], its incidence is higher when therapeutic doses of the drug are used compared to prophylactic ones [4,7,8]. It is important to note that the presence of heparin-bonded catheters or vascular prostheses can generate HIT.…”

“…Age is not a risk factor; nonetheless, HIT and its consequences are rarely recognised in children [16]. Female patients are at higher risk of HIT, and the clinical symptoms are more pronounced in females [4,5,7,8,14].…”

“…At a low HIT risk, further diagnostic procedures are not recommended and continuation of heparin therapy is suggested [7,9,14,15]. At a moderate and high HIT risk, the test for antibodies is advised [7−9, 14, 15].…”

“…In general, the lower the concentration of immune complexes in the sample, the closer to zero the optical density is [39]. OD = 1 is generally assumed as a cut-off value [14,40]. When OD < 1, the development of HIT is highly unlikely.…”

Thrombocytopenia

“…Mivel a törzskönyvezett gyógyszerek "off-label" alkalmazása megengedett, szá-míthatunk arra, hogy a rivaroxaban és a dabigatran alkalmazásával kapcsolatos vizsgálatok eredményei is hamarosan közlésre kerülnek. Mindazonáltal problémát okozhat, hogy ezeknek a gyógyszereknek a hatását laboratóriumi vizsgálattal nem tudjuk kontrollálni, és ez, tekintve a HIT-ben zajló súlyos thromboticus folyamatok miatt szükséges erélyes alvadásgátlást, a vérzés veszélyét fokozhatja [38].…”