Evaluation of bleeding rates in renal transplant patients on therapeutic intravenous heparin.

In patients who need anticoagulation, it is a challenge to provide the optimal balance between enough anticoagulant to prevent the formation of a thrombus and too much, which may cause a bleeding event.1 As many as 10% of adult patients experience thrombotic events following renal transplantation.2 Most thrombotic events occur in the initial 48 hours after surgery, but they can occur up to 14 days after renal transplantation.2 It is especially important in this population to achieve that balance in anticoagulation therapy, because immediate graft loss may occur if patients experience thrombosis of the renal artery or vein.2 Heparin may be used in the perioperative phase in an attempt to prevent thrombotic events, especially in patients with hypercoagulable states.3-5 In the general population, major bleeding occurs in up to 7% of patients who receive therapeutic intravenous (IV) heparin.1,6 Because one of the risk factors for heparin-induced bleeding is recent surgery, it would be expected that there would be increased bleeding risk in the early postoperative transplantation period.6 Patients with chronic renal failure may have impaired hemostasis. Platelet production may be disturbed due to the accumulation of protein biodegradation products. Bleeding tendencies may be further increased due to clotting factor deficiencies and vascular defects. Conversely, in uremic patients, clotting factors VII and XIII and fibrinogen may be increased, leading to an increased thrombosis risk. The clotting inhibitors protein C and S, antithrombin III, and heparin cofactor II activity may also be impaired. Unfortunately, complete improvement in hemostasis does not occur after successful renal transplantation.7 A previous study by Mathis et al2 evaluated bleeding events due to therapeutic IV heparin in renal transplant patients to prevent perioperative thrombosis. They found no link between the immunosuppressive agents used in the study (primary agents: cyclosporine, mycophenolate, prednisone; alternatives: tacrolimus and rapamycin) and risk of bleeding. However, there was a trend toward increased rates of bleeding in patients who received antibiotic prophylaxis for surgery for longer periods of time (P = .053); cefotetan was used more frequently in patients who experienced bleeding (P = .091). A literature search regarding bleeding rates in renal transplant patients found trials in the early postoperative transplantation period, with bleeding occurring in 60% to 64.3% of patients.2,5,8 No literature was found regarding bleeding rates in renal transplant patients who were receiving therapeutic IV heparin at any time beyond the early transplantation period. The perceived increase in susceptibility to bleeding in renal transplant patients receiving IV heparin (any time after transplantation) led to our assessment of renal transplant patients’ bleeding rates on IV heparin, titrated to a therapeutic activated partial thromboplastin time (aPTT; 56-93 seconds; 1.5 to 2 times normal, institution specific) compared to nontransplant patients.