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Blood, 1 November 2006, Vol. 108, No. 9, pp. 2937-2941.
Prepublished online as a Blood First Edition Paper on July 20, 2006; DOI 10.1182/blood-2005-11-012450.
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Submitted November 23, 2005
Accepted June 14, 2006
Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia
Theodore E. Warkentin*, Jo-Ann I. Sheppard, Christopher S. Sigouin, Thomas Kohlmann, Petra Eichler, and Andreas Greinacher
Department of Pathology and Molecular Medicine, Department of Medicine, McMaster University
Department of Transfusion Medicine and Immunology, Ernst-Moritz-Arndt University Greifswald
Department of Transfusion Medicine and Immunology, Ernst-Moritz-Arndt-Universitat Greifswald
* Corresponding author; email: twarken{at}mcmaster.ca.
HIT is caused by antibodies against a "self" protein-- platelet factor 4-- bound to heparin. We observed overrepresentation of female gender in 290 patients who developed HIT after cardiac or orthopedic surgery in comparison with national databases (Study 1). We therefore investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (Study 2); and analyzed individual patient data from seven prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH) and patient type (surgical vs medical) (Study 3). All three studies showed female overrepresentation, which for Study 3 was a common OR = 2.37 [95%CI, 1.37-4.09]; p = 0.0015. Study 3 also showed an interaction between gender, heparin and patient type: whereas UFH was more likely than LMWH to cause HIT (p<0.0001), this effect was predominantly seen in females compared with males (common OR, 9.22 vs 1.83; p = 0.0199), and in surgical compared with medical patients (common OR, 13.93 vs 1.75; p = 0.0054). We conclude that females have greater risk of HIT, and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.
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