Excess Factor XIII (FXIII) Consumption During Cardiopulmonary Bypass Surgery in a Patient with Congenital FXIII Deficiency

FXIII is an essential component of normal hemostasis. Congenital deficiency of FXIII activity is a rare autosomal recessive bleeding disorder with an estimated incidence of one in 3–5 million. A fibrin-stabilizing FXIII concentrate that provides both A and B subunits of FXIII was FDA approved last year for routine prophylactic treatment of congenital FXIII deficiency. There are few data available on replacement of FXIII concentrate in patients with congenital deficiency undergoing surgery and there is no published information on managing FXIII deficient patients undergoing cardiopulmonary bypass (CPB) surgery. It is known that FXIII levels decrease in normal individuals who are placed on the cardiopulmonary bypass pump.

A 52 year old man with congenital FXIII deficiency (baseline level 20%) underwent an aortic valve replacement. On the day of surgery, immediately prior to intubation, he was given a dose of FXIII concentrate (42 U/kg) which had previously been shown to correct his FXIII level to 100%. Early in surgery, the patient became hypotensive and did not respond to vasopressors, so the chest was opened urgently, internal CPR was performed and the patient was placed on cardiopulmonary bypass. He experienced heavy, poorly controlled bleeding intraoperatively. Factor XIII levels were checked intraoperatively at 3 hrs and 7 hrs post administration of the pre-op FXIII dose, and were 40% and 43% respectively. These levels were considerably lower than expected based on FXIII pharmacokinetic studies done 2 weeks prior to surgery. He received an additional dose of FXIII concentrate (42 U/kg) 8 hours after the original pre-op dose. During surgery he also received 9 units of PRBCs, 3 units of platelets, 7 units of FFP and a single dose of rFVIIa (90 mcg/kg) during the period of excessive bleeding, with ultimate control of bleeding; the patient was transferred to the surgical ICU 6 hours after the surgery was started. He recovered uneventfully and his post-operative FXIII levels were consistent with the published FXIII concentrate half-life of 6–8 days.

Studies have shown that plasma levels of FXIII decrease by 10–33% in a general population of patients undergoing CPB surgery which is presumed to be due to FXIII consumption during extracorporeal circulation. This raises concerns for effective replacement of FXIII in cases of congenital FXIII deficiency. In the case presented, FXIII levels were approximately 60% lower than anticipated based on pre-surgical pharmacokinetic testing of exogenous FXIII concentrate, and likely resulted in significant clinical bleeding intraoperatively. Further information is needed on surgical management, especially in cases involving extracorporeal circulation; collection of such cases in a registry may be helpful to improve our understanding on how to care for these patients. For now, we recommend using an increased dose of FXIII prior to such surgeries as the 100% correction dose determined in a preoperative challenge test was not enough to restore this patient's FXIII levels during surgery and prevent intraoperative bleeding.

Off Label Use: FXIII CONCENTRATE IN SURGERY. Leissinger:CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.