Abstract
Background: Severe congenital protein C deficiency (SCPCD) is a rare inherited disorder characterized by recurrent thrombosis, disseminated intravascular coagulation, and purpura fulminans. Due to limitations in traditional therapeutic options (anticoagulation, FFP, PCC), plasma-derived protein C concentrates have been used for both prophylactic and therapeutic indications. However, there are few reports of protein C infusion therapy in adults, with limited understanding of pharmacokinetics and no dosing guidelines available. We report the use of protein C concentrate in an individualized dose-finding study, in an adult patient in preparation for renal transplantation.
Case: A 35 year old female (68 kg) with SCPCD (baseline PC activity < 0.10 U/mL) with an extensive personal and family history of thrombosis was to undergo renal transplant. Her thrombotic history included DVT and PE (age 4), recurrent DVT with PE (age 6), mesenteric vein thrombosis (age 6), arterial thrombosis in bowel (age 10), DVT (age 10), extensive superficial venous thrombosis (age 27), pregnancy-associated DVT (age 32), and internal jugular vein thrombosis (age 34), for which she was on long-term therapeutic Enoxaparin. She developed end-stage renal disease in March 2015 (age 33) in the setting of pregnancy-associated HELLP syndrome, and is currently awaiting a deceased donor renal transplant. In anticipation of her upcoming transplant, an intravenous protein C infusion trial was performed to establish a perioperative management plan.
Results: The patient was admitted to hospital for this dose-finding study. She was administered Ceprotin® (human plasma-derived, virally-inactivated protein C concentrate) with an initial intravenous bolus (59 IU/kg) followed by an infusion (5 IU/kg/hr) to maintain a target PC level of 0.65-1.30 U/mL (see Table). Protein C activity was measured every 6 hours, and target levels were achieved over the 30-hour duration of the trial. The patient experienced no adverse events during the infusion trial.
Conclusion: In this case report, target protein C levels were maintained using bolus and continuous infusion rates of protein C concentrate that were approximately half of those recommended by the manufacturer. This personalized trial, while resource-intensive, provided a feasible and safe method of preparing for a high-risk surgical procedure that could be adapted to other similar clinical situations.
Crowther: Leo Pharma: Research Funding; Shinogi: Consultancy; Boehringer Ingelheim: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Pfizer: Honoraria; Portola: Consultancy.
