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Special Feature
February 2002

Image of the Month

Arch Surg. 2002;137(2):222. doi:

Answer: Heparin-Induced Thrombocytopenia: Stop All Heparin Therapy and Treat With Lepirudin

Figure 1. Necrotic digits on both hands appearing on postoperative day 5.

Figure 2. Diagram illustrating various sites of possible thrombin inactivation in the coagulation pathway. Asterisk indicates sites of heparin/ inhibition; aPC, activated protein C; and TFPI, tissue factor pathway inhibitor.

Heparin was originally discovered in 1916 from liver extracts. Now it is more commonly prepared from either bovine or porcine mucosal extracts. The mechanism of action is via binding to antithrombin III, which then inactivates the activated coagulation factors IIa, IXa, and Xa (Figure 2). Heparin-induced thrombocytopenia (HIT) occurs in up to 6% of patients receiving heparin therapy for any reason. There are 2 types of HIT that occur clinically. Type I, which is more common, appears early on after the institution of therapy and is mild in nature. The patients tend to be asymptomatic and this type is rarely associated with thromboembolic sequelae. Conversely, type II is delayed in onset and is more severe.1Thromboembolic complications do occur with type II.

In type II HIT, an immune-mediated platelet aggregation caused by IgG and IgM binding to platelet factor 4 complex occurs.2 Platelet activation by antiheparin platelet factor 4 antibodies results, with subsequent release of thrombogenic particles. This may lead to the "white clot" syndrome, associated with limb- and/or life-threatening thromboembolic complications. Risk factors for HIT include history of unfractionated heparin exposure, intravenous fractionated heparin, bovine heparin, and cardiopulmonary bypass.3

The clinical diagnosis of HIT is made when a patient's platelet count decreases below 1500 ×103/µL or 30% to 50% from baseline, an effect that is seen at least 5 days following heparin exposure.4Appropriate confirming laboratory data may include platelet counts, PF4-heparin antibody levels by enzyme-linked immunosorbent assay, heparin-induced platelet aggregation, and serotonin release assay.2,5,6The management of HIT involves the discontinuation of all heparin, including flushes and heparin-coated catheters. The patient must then be treated against further thrombotic episodes with a direct thrombin inhibitor, such as lepirudin.7This is an intravenous medication, which is monitored by maintaining the partial thromboplastin time 2 to 3 times above the baseline level. Hirudin was originally isolated from the salivary glands of the medicinal leech. It is now produced as lepirudin (r-hirudin) by recombinant DNA technology.

Corresponding author: Peter H. Lin, MD, The Emory Clinic, 1365 A Clifton Rd NE, Suite 3323, Atlanta, GA 30322 (e-mail:

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