hirudin and Myocarditis

Giant-cell myocarditis (GCM) is a rare, idiopathic disorder of young adults with high rates of morbidity and mortality. We describe a unique case of giant cell myocarditis associated with heparin-induced thrombocytopenia and thrombosis syndrome (HITTS). Our patient responded to therapy with bivalirudin, but later succumbed to complications from multiorgan failure. To our knowledge, this is the first reported case of GCM associated with HITTS, which was treated with bivalirudin (Angiomax; The Medicines Company; Parsippany, NJ).

Topics: Adult; Anticoagulants; Fatal Outcome; Giant Cells; Heparin; Hirudins; Humans; Male; Multiple Organ Failure; Myocarditis; Necrosis; Peptide Fragments; Recombinant Proteins; Thrombocytopenia; Thrombosis

Functional inhibition of tissue factor (TF) has been shown to improve coronary blood flow after myocardial ischemia/reperfusion (I/R) injury. TF initiates the coagulation protease cascade, resulting in the generation of the serine protease thrombin and fibrin deposition. Thrombin can also contribute to an inflammatory response by activating various cell types, including vascular endothelial cells. We used a rabbit coronary ligation model to investigate the role of TF in acute myocardial I/R injury. At-risk areas of myocardium showed increased TF expression in the sarcolemma of cardiomyocytes, which was associated with a low level of extravascular fibrin deposition. Functional inhibition of TF activity with an anti-rabbit TF monoclonal antibody administered either 15 minutes before or 30 minutes after coronary ligation reduced infarct size by 61% (P = 0.004) and 44% (P = 0.014), respectively. Similarly, we found that inhibition of thrombin with hirudin reduced infarct size by 59% (P = 0.014). In contrast, defibrinogenating the rabbits with ancrod had no effect on infarct size, suggesting that fibrin deposition does not significantly contribute to infarct size. Functional inhibition of thrombin reduced chemokine expression and inhibition of either TF or thrombin reduced leukocyte infiltration. We propose that cardiomyocyte TF initiates extravascular thrombin generation, which enhances inflammation and injury during myocardial I/R.

Topics: Animals; Antibodies, Monoclonal; Antithrombins; Cell Movement; Chemokines; Fibrin; Fibrinogen; Hirudins; Microscopy, Electron; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocarditis; Myocardium; Neutrophils; Rabbits; Thrombin; Thromboplastin