refludan and Multiple-Organ-Failure

For patients with heparin-induced thrombocytopenia (HIT), reexposure to heparin is generally not recommended. However, these patients are likely to require anticoagulation therapy at some point in the future. During acute HIT, when thrombocytopenia and anti-heparin-platelet factor 4 antibodies (or HIT antibodies) are present, therapy with heparin must be avoided. In patients with subacute HIT, when platelets have recovered but HIT antibodies are still present, therapy with heparin should be avoided. In patients with a remote history of HIT, when HIT antibodies have cleared, heparin reexposure may be safe, although recurrent HIT has been described in some patients. For all of these patients, the use of alternate anticoagulant agents, including direct thrombin inhibitors and anti-Xa agents, is preferable. There is an increasing amount of data supporting the use of these alternative agents in a wide variety of clinical circumstances, including thromboprophylaxis and treatment of acute thrombosis. Except for a few clinical situations, it is generally possible to avoid heparin reexposure in patients with a history of HIT.

Topics: Angina, Unstable; Antibodies; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Fondaparinux; Heparin; Heparitin Sulfate; Hirudins; Humans; Male; Multiple Organ Failure; Platelet Factor 4; Polysaccharides; Pregnancy; Preoperative Care; Recombinant Proteins; Thrombin; Thrombocytopenia; Venous Thrombosis

Lepirudin is a potent, direct thrombin inhibitor used for anticoagulation in patients with heparin-induced thrombocytopenia type II (HIT). The half-life of lepirudin is prolonged in patients with renal insufficiency. Preliminary studies suggest that it is safe to use lepirudin in patients being treated with intermittent hemodialysis but information regarding its use with continuous renal replacement therapy (CRRT) is scarce. CRRT is used in acute care settings to remove fluid and uremic toxins in patients with renal failure with hemodynamic instability. Patients with HIT, renal failure, and hemodynamic instability pose a complex situation for clinical management. These patients require anticoagulation with nonheparin agents with simultaneous CRRT. There are no guidelines in the literature regarding the management of this patient group. We report our experience with lepirudin at managing four such patients with HIT, being treated with CRRT.

Topics: Aged; Aged, 80 and over; Anticoagulants; Drug Evaluation; Female; Half-Life; Heparin; Hirudins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Systemic Inflammatory Response Syndrome

Topics: Anticoagulants; Cardiopulmonary Bypass; Fatal Outcome; Heart Valve Prosthesis Implantation; Heparin; Hirudin Therapy; Hirudins; Humans; Intraoperative Period; Male; Middle Aged; Mitral Valve; Multiple Organ Failure; Partial Thromboplastin Time; Postoperative Complications; Recombinant Proteins; Thrombocytopenia; Thrombosis

A 60-year-old man was admitted to the hospital with aortic dissection. An operative excision and replacement with a Y-graft was performed. Postoperatively he developed multiple organ dysfunction and required intermittent haemofiltration (anticoagulation with heparin). An ischemia of the left leg occurred at the third postoperative day. The initial platelet count was 99,000/microliter. Continuous haemofiltration (CVVH) was started three days later. Thrombotic obstructions of haemodialysis filters and catheters occurred frequently and heparin-induced thrombocytopenia (HIT II) was suspected. Antibodies against heparin were found in the HIPA test. Despite heparin free citrate dialysis and anticoagulation with danaparoid thrombotic obstructions of filters and catheters continued. Therefore the anticoagulation therapy during CVVH was changed to recombinant hirudin (lepirudin). Starting dose was a bolus of 0.01 mg/kg bw followed by the same amount as maintenance dose per hour. Anticoagulation was adjusted to an increase of aPTT (activated partial thromboplastin time) to 1.5-2 times its normal value. A dose of 0.005 mg/kg bw/h lepirudin was sufficient to maintain adequate anticoagulation. After changing to lepirudin no further catheter obstructions were observed and the platelets recovered slowly. Renal function improved and five weeks after admission endogenous creatinine clearance showed a value of 25 ml/min. We conclude that lepirudin is an effective anticoagulant during CVVH in patients with HIT II. In partly permeable polysulfon filters a dose of 0.005 mg/kg bw/h lepirudin is sufficient to maintain adequate anticoagulation. Monitoring anticoagulation by measuring the increase of aPTT (factor 1.5-2.0) seems to be safe. However, optimally the r-hirudin concentration should be measured directly using the Ecarin clotting time.

Topics: Anticoagulants; Aortic Aneurysm, Abdominal; Aortic Dissection; Blood Vessel Prosthesis Implantation; Hemodiafiltration; Heparin; Hirudin Therapy; Hirudins; Humans; Male; Middle Aged; Multiple Organ Failure; Recombinant Proteins; Thrombocytopenia; Treatment Outcome

Rats which were infected with the gramnegative pathogen Klebsiella pneumoniae develop disseminated intravascular coagulation (DIC), multi-organ failure (MOF) and finally die in a septic shock. We investigated the therapeutic effect of antibiotic (tobramycin) treatment combined with the infusion of the highly specific thrombin inhibitor rec. hirudin. Although administration of 2 mg/kg tobramycin alone leads to a decrease of the bacterial burden, DIC could not be prevented. Infusion of rec. hirudin (0.25 mg/kg x h) for 4 h (start of treatment 1 h post infection), in addition to a bolus administration of tobramycin, led to an amelioration of DIC parameters as fibrinogen, thrombin-antithrombin complex (TAT) and platelets. Serum transaminase levels (GOT, GPT) as a marker of MOF were significantly improved by rec. hirudin, the T50 value increased from 17 h in the tobramycin group to 42 h in the tobramycin+rec. hirudin group, mortality rates were 90% or 60%, respectively. Combination of heparin (100 U/kg x h) and tobramycin was not effective on survival.

Topics: Animals; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Female; Hirudin Therapy; Hirudins; Klebsiella Infections; Klebsiella pneumoniae; Multiple Organ Failure; Rats; Recombinant Proteins; Sepsis; Tobramycin