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

Warkentin, Theodore E.
Levine, Mark N.
Hirsh, Jack
Horsewood, Peter
Roberts, Robin S.
Gent, Michael
Kelton, John G.

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.
Supported by grants from the Heart and Stroke Foundation of Ontario and Rhone-Poulenc Rorer. Dr. Warkentin is a Research Scholar of the Heart and Stroke Foundation of Canada. Dr. Levine is a Scientist of the Medical Research Council of Canada. Dr. Hirsh is a Distinguished Research Professor of the Heart and Stroke Foundation of Ontario. Dr. Kelton is a Career Investigator for the Heart and Stroke Foundation of Ontario.

New England Journal of Medicine 332(20):p 1330-1335, May 18, 1995.

Background

Heparin-induced thrombocytopenia, defined by the presence of heparin-dependent IgG antibodies, typically occurs five or more days after the start of heparin therapy and can be complicated by thrombotic events. The frequency of heparin-induced thrombocytopenia and of heparin-dependent IgG antibodies, as well as the relative risk of each in patients given low-molecular-weight heparin, is unknown.

Methods

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

Results

Heparin-induced thrombocytopenia occurred in 9 of 332 patients who received unfractionated heparin and in none of 333 patients who received low-molecular-weight heparin (2.7 percent vs. 0 percent; P = 0.0018). Eight of the 9 patients with heparin-induced thrombocytopenia also had one or more thrombotic events (venous in 7 and arterial in 1), as compared with 117 of 656 patients without heparin-induced thrombocytopenia (88.9 percent vs. 17.8 percent; odds ratio, 36.9; 95 percent confidence interval, 4.8 to 1638; P < 0.001). In the subgroup of 387 patients, the frequency of heparin-dependent IgG antibodies was higher among patients who received unfractionated heparin (7.8 percent, vs. 2.2 percent among patients who received low-molecular-weight heparin; P = 0.02).

Conclusions

Heparin-induced thrombocytopenia, associated thrombotic events, and heparin-dependent IgG antibodies are more common in patients treated with unfractionated heparin than in those treated with low-molecular-weight heparin. (N Engl J Med 1995;332:1330-5.)