Correspondence

Heparin-Induced Thrombocytopenia with Thromboembolic Arterial Occlusion Treated with Recombinant Hirudin

N Engl J Med 1997; 337:1389November 6, 1997

Article

To the Editor:

Lepirudin (Refludan) is a genetically engineered recombinant form of hirudin that is used for anticoagulation therapy in patients with heparin-induced thrombocytopenia due to heparin-dependent antiplatelet antibodies.1 We report a case of combined intraoperative and postoperative lepirudin treatment of a patient with heparin-induced thrombocytopenia and acute arterial occlusion.

A 60-year-old woman (weight, 71 kg; height, 160 cm) had been receiving 7500 IU of unfractionated heparin sodium twice a day subcutaneously for five days for prophylaxis against venous thrombosis while a paraspinal cystic lesion in the region of the thoracic spine was being investigated. She was transferred to our hospital because of an ischemic right leg. There was a marked decrease in the platelet count (from 207,000 per microliter to 45,000 per microliter). Platelet aggregates were seen on the blood smear; other blood-cell counts were normal. A heparin antibody–induced platelet-aggregation assay confirmed the presence of antibodies that caused platelet activation in vitro in the presence of heparin. After the diagnosis of acute thromboembolic occlusion of the right femoral artery was confirmed, an embolectomy was successfully performed. No further heparin was given. To prevent arterial thrombosis during the intraoperative clamping phase, we administered 0.2 mg of lepirudin per kilogram of body weight as an intravenous bolus before clamping (equivalent to a dose of 14 mg with a body weight of 70 kg; there is no adequate antagonist of lepirudin). The lepirudin dose was then reduced from 16 mg per hour to 4 mg per hour throughout the inpatient period. This treatment kept the partial-thromboplastin time at about 1.5 to 2 times normal (20 to 40 seconds).

After three days the platelet count rose from 45,000 per microliter to 108,000 per microliter. After nine days, the platelet count was 396,000 per microliter. The patient's renal function was normal (creatinine, 1.1 mg per deciliter; urea, 9 mg per deciliter). She was discharged from the hospital after two weeks without sequelae, and there have been no bleeding complications.

Patients have received lepirudin as prophylaxis against thrombosis after hip replacement.2 Our case report suggests that lepirudin may also be suitable for intraoperative and postoperative administration in patients with heparin-induced thromboembolic vascular occlusion.

Oliver H. Schmidt, M.D.
Werner Lang, M.D.
University Hospital, 91054 Erlangen, Germany

2 References

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   Kibbe MR, Rhee RY. Heparin-induced thrombocytopenia: pathophysiology. Semin Vasc Surg 1996;9:284-291
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   Eriksson BI, Ekman S, Kalebo P, Zachrisson B, Bach D, Close P. Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393. Lancet 1996;347:635-639
   CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   Karl-Georg Fischer. (2004) The Role of Recombinant Hirudins in the Management of Thrombotic Disorders. BioDrugs 18:4, 235-268
   CrossRef

2. 2

   Andreas Greinacher, Petra Eichler, Norbert Lubenow, Volker Kiefel. (2001) DRUG-INDUCED AND DRUG-DEPENDENT IMMUNE THROMBOCYTOPENIAS. Reviews in Clinical and Experimental Hematology 5:3, 166-200
   CrossRef

3. 3

   Norbert Lubenow, Andreas Greinacher. (2001) Drugs for the Prevention and Treatment of Thrombosis in Patients with Heparin-Induced Thrombocytopenia. American Journal of Cardiovascular Drugs 1:6, 429-443
   CrossRef

4. 4

   Norbert Lubenow, Andreas Greinacher. (2000) Heparin-Induced Thrombocytopenia. BioDrugs 14:2, 109-125
   CrossRef

5. 5

   &NA;. (1997) Heparin. Reactions Weekly &NA;:678, 8
   CrossRef