We report a case of a 17-year-old white male with multiple fractures and multiorgan failure who developed oliguric acute renal failure requiring continuous renal replacement therapy. Repeated clotting of the extracorporeal circuit (ECC) prevented delivery of a minimally acceptable dose of renal replacement therapy despite adequate anticoagulation and dialysis catheter exchanges. Evaluation for a primary hypercoagulable state was negative, but his fibrinogen was elevated (1,320 mg/dL, normal range: 150-400 mg/dL), which is likely induced by his severe inflammatory state. A single session of therapeutic plasma exchange (TPE) with albumin and normal saline replacement was performed with subsequent drop in fibrinogen to 615 mg/dL. No further episodes of premature ECC clotting occurred, suggesting plasma factor(s) removed may have contributed to the clinical hypercoagulable state. TPE may play an adjunctive role in select cases of recurrent ECC clotting refractory to current anticoagulation techniques.