Use of Factor XIII (FXIII) concentrate in patients with congenital FXIII deficiency undergoing surgical procedures

Abstract

BACKGROUND:Patients with congenital Factor XIII (FXIII) deficiency have impaired fibrin stabilization and are at high risk for surgical bleeding. Data regarding the use of FXIII concentrates before and during surgery are lacking. The objective of this study was to report the use of plasma-derived FXIII concentrate (Corifact in the United States; Fibrogammin P in other countries) in patients with congenital FXIII deficiency undergoing surgical procedures. STUDY DESIGN AND METHODS: FXIII concentrate at preoperative doses ranging from 25 to 40 U/kg was administered to six patients with congenital FXIII deficiency undergoing major or minor surgeries. RESULTS: FXIII concentrate was administered immediately before surgery for five surgical cases; three of these patients achieved excellent hemostasis during and after surgery, while two had intraoperative bleeding. In one surgical case, a regular prophylactic dose of FXIII concentrate was administered to the patient 1 week before minor surgery. FXIII concentrate provided rapid replacement of FXIII activity. In all but one of the patients given a dose of FXIII designed to increase FXIII levels more than 50%, there was satisfactory intraoperative and postoperative hemostasis. One patient undergoing aortic valve replacement on cardiopulmonary bypass (CPB) was the exception. Intraoperative bleeding in this patient was associated with lower-than-expected blood levels of FXIII. CONCLUSION: Preoperative plasma-derived FXIII concentrate allowed for sufficient hemostasis in most patients with FXIII deficiencies. Additional doses were necessary to achieve hemostasis in one patient who underwent a CPB procedure. F actor XIII (FXIII) deficiency is a rare autosomal recessive congenital bleeding disorder resulting from defects in genes encoding the "A"-chain or "B"-chain subunits of the FXIII coagulation protein.1 FXIII is capable of cross-linking a variety of proteins, but its function in cross-linking fibrin is crucial for clot stabilization and the prevention of bleeding. The incidence of severe FXIII deficiency (<1% FXIII) is estimated to be one in 5 million people, 2 but the true incidence of FXIII deficiency is unknown, as heterozygous patients will have higher baseline FXIII levels and may not exhibit overt symptoms.1 Patients with severe FXIII deficiencies usually present with umbilical cord bleeding, mucosal bleeding, poor wound healing, primary intracranial hemorrhage, or spontaneous miscarriage. Patients with less severe FXIII deficiency (with levels from 2%-50% activity) are rarely symptomatic, and may only be diagnosed after an invasive procedure or other hemostatic challenge. Traditionally, FXIII deficiency has been assessed qualitatively by plasma clot solubility in concentrated urea, acetic acid, or monochloroacetic acid.3 However, since clot solubility ABBREVIATION: CPB = cardiopulmonary bypass. Although not licensed in Canada, Fibrogammin P has been widely used under the Special Access Programme of Health Canada. In 2013, the US Food and Drug Administration approve...

Effect of Thrombus Composition and Viscosity on Sonoreperfusion Efficacy in a Model of Micro-Vascular Obstruction

“…Platelet contractile proteins result in thrombus contraction and increased fibrin density. Furthermore, factor XIII, released by activated platelets, facilitates fibrin cross-linking and increases thrombus stability (Janbain et al 2015). Arterial thrombi have more plasminogen activator inhibitor-1 (PAI-1) (Tynngard et al 2006), which inactivates tPA, allowing less endogenous lysis versus venous thrombi.…”

Developing the First Recombinant Factor XIII for Congenital Factor XIII Deficiency: Clinical Challenges and Successes

“…In a recent report of six patients with congenital FXIII deficiency undergoing surgery covered by pd-FXIII, one patient experienced intraoperative bleeding while another experienced postoperative bleeding despite, in both cases, FXIII activity levels of approximately 0.4 IU/mL. 18 One of these patients, a 53-year-old man undergoing aortic valve replacement, showed fast consumption of pd-FXIII while on cardiopulmonary bypass. The authors concluded that sufficient pd-FXIII should be administered immediately before major surgery to achieve FXIII activity levels exceeding 0.5 IU/mL (1.0 IU/mL in patients undergoing prolonged or complicated surgeries).…”

“…13 Although FXIII activity as low as 0.03 to 0.1 IU/mL is thought to be sufficient for preventing spontaneous hemorrhages in most patients, 3,5,12,17 bleeding complications have been reported with FXIII activity levels as high as 0.4 IU/mL. 13,18 In terms of diagnosis, it is important to recognize that the results of standard screening tests (e.g., prothrombin time, activated partial thromboplastin time, fibrinogen, and complete blood counts) appear normal in FXIII deficiency. Consequently, the diagnosis requires the performance of specific FXIII activity assays (measuring functional activity, immunological antigen levels, or clot solubility) of variable sensitivity.…”

Diagnosis and Management of Congenital and Acquired FXIII Deficiencies

“…Although all six patients were on regular prophylaxis, an additional preoperative dose of FXIII 25 to 40 U/kg was administered. 60 Postoperative correction dose depended on the surgical procedure and/or on FXIII activity during or after the surgery.…”