Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
Citations 0
Special Feature
February 2002

Image of the Month

Author Affiliations



Copyright 2002 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2002

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.

Back to top
Article Information

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

Baglin  TP Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and treatment. J Clin Pathol. 2001;54272- 274Article
Rugeri  LBauters  ATrillot  N  et al.  Hemostasis and thrombosis: clinical usefulness of combined use of platelet aggregation test and anti PF4-H antibodies elisa test for the diagnosis of heparin induced thrombocytopenia. Hematology. 1999;4367- 373
Manfredi  JAWall  RPSane  DCBraden  GA Lepirudin as a safe alternative for effective anticoagulation in patients with known heparin-induced thrombocytopenia undergoing percutaneous coronary intervention: case reports. Catheter Cardiovasc Interv. 2001;52468- 472Article
Warkentin  TEKelton  JG Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;3441286- 1292Article
Harenberg  JWang  LCHoffman  UHuhle  GFeuring  M Laboratory diagnosis of heparin-induced thrombocytopenia type II after clearance of platelet factor 4/ heparin complex. J Lab Clin Med. 2001;137408- 413Article
Elalamy  ILecrubier  CHorellou  MHConard  JSamama  MM Heparin-induced thrombocytopenia: laboratory diagnosis and management. Ann Med. 2000;32(suppl 1)60- 67
Greinacher  ALubenow  N Recombinant hirudin in clinical practice: focus on lepirudin. Circulation. 2001;1031479- 1484Article