Department of Medicine, Section of Nephrology and Hypertension and Hematology/Oncology, Tulane University School of Medicine VA, Medical Center in New Orleans, New Orleans, LA 70112-2699, USA Email: vbatuma{at}tulane.edu
Sir,
Heparin-induced thrombocytopenia syndrome type II (HIT II) poses serious challenges for patients who require anticoagulation. The optimal anticoagulant for HIT II patients who require haemodialysis or plasmapheresis is not clear. Recombinant hirudin (r-hirudin, Refludan; lepirudin (rDNA) for injection, Aventis) has been evaluated as an anticoagulant in haemodialysis patients with HIT II [1] and has been used subsequently with success in patients with HIT II [24]. However, there are no data on the use of r-hirudin for patients requiring procedures that involve plasma filters. We report here successful use of r-hirudin as an anticoagulant in plasmapheresis with plasma filters in a patient with HIT II.
Case.
The patient was a 60-year-old African American male with Waldenström's macroglobulinaemia, hypercoagulability with multiple deep venous thromboses, an inferior vena cava filter, and moderate renal insufficiency (serum creatinine 2 mg/dl, CockcroftGault estimated creatinine clearance 48 ml/min). HIT was diagnosed based on thrombocytopenia as low as 22 000/mm3 after heparin use and confirmed by demonstration of heparin/platelet factor 4 antibodies by enzyme-linked immunosorbent assay. The patient was noted to have an IgM level that had increased to 6.0 g/dl and he developed increasing dyspnea, which was determined to be of non-cardiac origin. The diagnosis of pulmonary emboli was excluded and his serum viscosity was 3.7 U (normal 1.41.8). Thus, it was concluded that the patient's symptoms were probably secondary to hyperviscosity syndrome.
At our VA Medical Center, our nephrology service and dialysis staff perform plasmapheresis using Braun CRRT equipment and ASAHI plasma filters. There is limited information on the pharmacokinetics of r-hirudin in a plasmapheresis circuit; however, it appears that r-hirudin is cleared by plasma filters nearly identically to the clearance of this compound in healthy volunteers with normal renal function [5].
We decided to use hirudin after our initial attempts to perform plasmapheresis without anticoagulation failed as a result of extensive clotting of the filter. We achieved acceptable anticoagulation in this patient using the following protocol. First, we primed the plasma filter circuit with 5 mg/l of r-hirudin. Next, we infused an i.v. bolus of 0.5 mg/kg of r-hirudin intravenously into the patient and followed this with a continuous infusion of 0.2 mg/kg/h of r-hirudin based on the patient's actual weight. The plasma filter showed no evidence of clots. Hirudin plasma levels were not monitored. The activated prothrombin time increased to 60 s (appropriately 1.5x) during the procedure, decreased to 45 s by the next morning, and was normal in all subsequent measurements without evidence of bleeding during or after the procedure. The patient received two treatments using this protocol replacing 160% of his calculated plasma volume on separate days with equal parts of fresh frozen plasma, 5% albumin and normal saline. After the treatment the patient's gamma globulin fraction decreased from 6.9 to 5 g/dl (normal 0.51.7), serum IgM level and viscosity measurements were not repeated. The patient's symptoms attributable to hyperviscosity improved mildly although these clinical improvements were not sustained and the patient expired.
Comment.
We conclude that r-hirudin can be effective and safe in anticoagulation of plasma filters in patients intolerant to heparin at the doses described above. Further studies involving additional patients will be necessary to determine the precise role for r-hirudin in patients with HIT II who require dialysis or plasmapheresis.
References