hirudin and Hypertension--Pulmonary

Unfractionated heparin has been a near universal anticoagulant for cardiac surgery; however it is contraindicated in heparin-induced thrombocytopenia type II. Alternative anticoagulants such as bivalirudin (a direct thrombin inhibitor) are being utilized. Bivalirudin was successfully used in an immunologically complex patient (diagnoses of heparin-induced thrombocytopenia type II, systemic lupus erythematosus, antiphospholipid syndrome, and dialysis-dependent renal failure) requiring cardiopulmonary bypass. Thrombotic events are common in antiphospholipid syndrome patients undergoing cardiac surgery utilizing high-dose heparin. This may represent unrecognized heparin-induced thrombocytopenia type II. Our patient did not experience perioperative thrombotic or bleeding complications. The possible cross-reactivity between heparin induced thrombocytopenia type II and antiphospholipid syndrome has not been investigated.

Topics: Adult; Antibody Specificity; Anticoagulants; Antiphospholipid Syndrome; Autoantibodies; Cross Reactions; Drug Evaluation; Drug Therapy, Combination; Female; Heart Failure; Heparin; Hirudins; Humans; Hypertension, Pulmonary; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Mitral Valve Insufficiency; Peptide Fragments; Platelet Count; Platelet Factor 4; Recombinant Proteins; Renal Dialysis; Thrombocytopenia; Thrombophilia; Warfarin

Patients with heparin-induced thrombocytopenia urgently requiring surgery with cardiopulmonary bypass (CPB) present a unique management challenge that must be addressed by the use of alternative anticoagulants. Although clinical success with the direct thrombin inhibitor hirudin has been reported, there is sparse information in the literature supporting the efficacy of this drug as an anti-thrombotic to prevent fibrin formation during CPB. In this report, we describe the efficacy of this drug to prevent thrombin-mediated fibrin formation during CPB.

Topics: Adult; Anticoagulants; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Fibrinolytic Agents; Fibrinopeptide A; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Hypothermia, Induced; Male; Peptide Fragments; Postoperative Complications; Prothrombin; Pulmonary Embolism; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Thrombectomy; Thrombin; Thrombosis

Patients with heparin-induced thrombocytopenia requiring urgent cardiac surgery present a unique challenge that must be addressed by the use of nonheparin alternatives for anticoagulation during cardiopulmonary bypass. Although isolated cases have been presented involving the use of antithrombin III independent thrombin inhibitor hirudin in this situation, its ability to completely inhibit thrombin activity has not been demonstrated. In this report we describe the efficacy of this drug in inhibiting thrombin during a case requiring prolonged cardiopulmonary bypass.

Topics: Aged; Anticoagulants; Blood Coagulation; Cardiopulmonary Bypass; Chondroitin Sulfates; Contraindications; Dermatan Sulfate; Endarterectomy; Female; Heparin; Heparitin Sulfate; Hirudins; Humans; Hypertension, Pulmonary; Plasma; Platelet Transfusion; Pulmonary Embolism; Recombinant Proteins; Thrombectomy; Thrombin; Thrombocytopenia; Time Factors; Warfarin

Thrombin contracts vascular smooth muscle and stimulates its proliferation. Using a specific thrombin inhibitor, hirudin, we studied whether thrombin contributes to the pulmonary vasoconstriction and vascular proliferation that occurs in pulmonary hypertension. Hirudin was infused intravenously (0.2 mg/h/kg) by minipumps in nine rats during a 3-wk exposure to hypobaric hypoxia (HH). Vehicle (normal saline) was infused in eight hypoxic control (HC) and seven normoxic control (NC) rats. Sufficient hirudin delivery was confirmed by a failure of undiluted plasma from HH, but not from NC and HC, to clot in response to thrombin. When the plasma samples were diluted 1:10, the thrombin time was significantly prolonged in HH when compared with that in both NC and HC. Although hirudin slightly reduced mean pulmonary arterial pressure in open-chest rats, there was no significant difference between the hypoxic groups in total pulmonary resistance, right ventricle weight, morphologic remodeling of lung vessels, or the perfusion pressure-flow relationship in isolated lungs. Vasoconstrictor responses of isolated lungs to angiotensin II and acute hypoxic challenges were not affected by hirudin treatment. We conclude that hirudin, in a dose sufficient to reduce thrombin's catalytic effect on fibrinogen, does not significantly prevent the development of chronic hypoxic pulmonary hypertension.

Topics: Animals; Chronic Disease; Hemodynamics; Hirudins; Hypertension, Pulmonary; Hypoxia; Infusion Pumps, Implantable; Lung; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Specific Pathogen-Free Organisms; Thrombin; Thrombin Time