Direct thrombin inhibitors in the treatment of immune-mediated heparin-induced thrombocytopenia.
Heparin was first discovered in 1916 and at present is used in more than 12 million patients a year. In the 1950s, several physicians noticed an uncommon paradoxical phenomenon in which heparin appeared to function as a procoagulant instead of an anticoagulant. This phenomenon is now known as the immune-mediated heparin-induced thrombocytopenia (HIT) and thrombosis syndrome (HITTS). Our understanding of this syndrome has evolved over the last 2 to 3 decades, and therapeutic options are arising. This article will focus on the most extensively studied therapy for HIT, which is the class of drugs known as the direct thrombin inhibitors. Specifically, we will focus on the mechanisms by which direct thrombin inhibitors may be useful in this syndrome, the evidence for their use, and the unique characteristics of the two FDA-approved agents in this class, lepirudin and argatroban.
Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA. jcall@wfubmc.edu
Jason T
JT
Call
Efthymios N
EN
Deliargyris
David C
DC
Sane
D000925:Anticoagulants / Q000009:adverse effects; D001120:Arginine / Q000031:analogs & derivatives; D001665:Binding Sites; D006493:Heparin / Q000009:adverse effects*; D006629:Hirudins / Q000031:analogs & derivatives*; D006801:Humans; D008954:Models, Biological; D010875:Pipecolic Acids / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D013449:Sulfonamides; D013577:Syndrome; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D000925:Anticoagulants; D006629:Hirudins; D010875:Pipecolic Acids; D011994:Recombinant Proteins; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban; C083544:lepirudin