Heparin-induced thrombocytopenia: a historical perspective

Abstract

Heparin was discovered 90 years ago, 1 and within 2 decades it was being widely used as an anticoagulant. 2 The numerous advantages of heparin lend to its broad use including its immediate onset of action, relatively short half-life (ϳ60 minutes), simple laboratory monitoring (aPTT), ability to be reversed (using protamine), and low cost. Despite a long experience of using heparin, the counterintuitive notion that an anticoagulant could be intensely prothrombotic took almost 4 decades to become recognized.Our understanding of heparin-induced thrombocytopenia (HIT) has increased considerably and to a large measure exemplifies the best of translational research. Sometimes, basic studies investigating the pathophysiology of HIT lead to clinical insights. In other instances, clinical observations prompted basic studies. Together, these basic and applied investigations have dramatically enhanced our understanding of the pathogenesis and treatment of HIT. Heparin-induced arterial embolismOn June 1, 1957, at the Fifth Scientific Meeting of the International Society of Angiology in New York, Rodger E. Weismann, an Assistant Professor of Clinical Surgery at the Dartmouth Medical School, and his Resident in Surgery, Dr Richard W. Tobin, described 10 patients who developed arterial embolism during systemic heparin therapy. 3 The first reported embolic event was a femoral artery embolic occlusion, which occurred in a 62-year-old woman who was receiving heparin because of a deep-vein thrombosis (DVT). Three days after successful femoral embolectomy, and while continuing to receive heparin, she developed sudden occlusion of the distal aorta requiring distal aortic and bilateral iliac embolectomies. 3 Multiple thromboemboli were observed in 9 of the 10 patients reported. Six patients died as a result of the thromboembolism, and 2 survivors underwent above-knee amputation. 3 The clots were described as "pale, soft, salmon-colored" and were composed mostly of fibrin, platelets, and leukocytes. The arterial emboli began on average 10 days after commencing heparin treatment.An additional 11 patients were described 5 years later by Roberts and colleagues. 4 These vascular surgeons noted the paradox of "unexplained arterial embolization [occurring] for the first time while being treated with heparin for some condition that could not of itself reasonably be expected to cause arterial emboli. All patients had been receiving heparin for 10 days or more when the initial embolus occurred." Thus, both groups 3,4 noted the temporal hallmark of HIT, a delay of approximately 1 week from initiation of heparin to onset of its thrombotic manifestations. Heparin-induced thrombocytopeniaRoutine platelet count measurements were not routinely performed until the 1970s. This may explain why thrombocytopenia was not reported in the first 24 patients with heparin-induced arterial emboli. [3][4][5][6] In 1969, the term "heparin-induced thrombocytopenia" was used by Natelson 7 to describe a 78-year-old man with pulmonary embolism who developed severe t...

Pitfalls in the diagnosis of heparin‐Induced thrombocytopenia: A 6‐year experience from a reference laboratory

“…Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse effect and the most devastating consequence of heparin therapy [1,2]. HIT can lead to severe morbidity including ischemic limb loss and death [3][4][5].…”

Utilisation de la bivalirudine en chirurgie cardiaque – de l’inhibition indirecte à l’inhibition directe de la thrombine

“…3 An important limitation deserving focused attention is the potential formation of anti-PF4/UFH antibodies and, more importantly, HIT-related thrombotic complications. 30 …”

Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease

“…422 HIT is increasingly recognized as a complication of heparin therapy in adults. It has been described in pediatric patients but may be less prevalent or less severe.…”