Heparin-Induced Thrombocytopenia in Patients Treated with Low-Molecular-Weight Heparin or Unfractionated Heparin

doi:10.1056/NEJM199505183322003

Volume 332:1330-1336		May 18, 1995		Number 20

Heparin-Induced Thrombocytopenia in Patients Treated with Low-Molecular-Weight Heparin or Unfractionated Heparin

Theodore E. Warkentin, M.D., Mark N. Levine, M.D., Jack Hirsh, M.D., Peter Horsewood, Ph.D., Robin S. Roberts, M.Tech., Michael Gent, D.Sc., and John G. Kelton, M.D.

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ABSTRACT

Background Heparin-induced thrombocytopenia, defined by thepresence of heparin-dependent IgG antibodies, typically occursfive or more days after the start of heparin therapy and canbe complicated by thrombotic events. The frequency of heparin-inducedthrombocytopenia and of heparin-dependent IgG antibodies, aswell as the relative risk of each in patients given low-molecular-weightheparin, is unknown.

Methods We obtained daily platelet counts in 665 patients ina randomized, double-blind clinical trial comparing unfractionatedheparin with low-molecular-weight heparin as prophylaxis afterhip surgery. Heparin-induced thrombocytopenia was defined asa decrease in the platelet count below 150,000 per cubic millimeterthat began five or more days after the start of heparin therapy,and a positive test for heparin-dependent IgG antibodies. Wealso tested a representative subgroup of 387 patients for heparin-dependentIgG antibodies regardless of their platelet counts.

Results Heparin-induced thrombocytopenia occurred in 9 of 332patients who received unfractionated heparin and in none of333 patients who received low-molecular-weight heparin (2.7percent vs. 0 percent; P = 0.0018). Eight of the 9 patientswith heparin-induced thrombocytopenia also had one or more thromboticevents (venous in 7 and arterial in 1), as compared with 117of 656 patients without heparin-induced thrombocytopenia (88.9percent vs. 17.8 percent; odds ratio, 36.9; 95 percent confidenceinterval, 4.8 to 1638; P<0.001). In the subgroup of 387 patients,the frequency of heparin-dependent IgG antibodies was higheramong patients who received unfractionated heparin (7.8 percent,vs. 2.2 percent among patients who received low-molecular-weightheparin; P = 0.02).

Conclusions Heparin-induced thrombocytopenia, associated thromboticevents, and heparin-dependent IgG antibodies are more commonin patients treated with unfractionated heparin than in thosetreated with low-molecular-weight heparin.

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From the Departments of Pathology (T.E.W., P.H., J.G.K.), Clinical Epidemiology and Biostatistics (M.N.L., J.H., R.S.R., M.G.), and Medicine (T.E.W., M.N.L., J.H., J.G.K.), McMaster University; the Hamilton Civic Hospitals (T.E.W., M.N.L., J.H.); the Hamilton Civic Hospital Research Centre (M.N.L., J.H., R.S.R., M.G.); and the McMaster University Medical Centre (P.H., J.G.K.) — all in Hamilton, Ontario, Canada.

Address reprint requests to Dr. Warkentin at the Department of Laboratory Medicine, Hamilton Civic Hospitals (General Division), 237 Barton St. E., Hamilton, ON L8L 2X2, Canada.

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N Engl J Med 1995; 333:1006-1007, Oct 12, 1995. Correspondence

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