Medical Care
Fresh frozen plasma (FFP), cryoprecipitate, and factor XIII (FXIII) concentrates have been used for replacement of factor XIII and the treatment of acute bleeding. For years, the treatment of choice has been plasma-derived factor XIII concentrate that is pasteurized to provide virologic safety and is less likely than plasma to cause systemic reactions. Recombinant factor XIII-A2 (Tretten) was approved by the FDA in December 2013 and presents an alternative in the treatment of congenital factor XIII A-subunit deficiency. Approval was based on results from a study that demonstrated the safety and efficacy of rFXIII A-subunit. The phase 3 trial included 41 patients and showed that when compared to an historic control group of individuals who did not receive routine FXIII infusions, preventive treatment with monthly 35 IU/kg rFXIII A-subunit injections significantly decreased the number of treatment-requiring bleeding episodes. [9]
Because levels of factor XIII above 3-5% are usually sufficient to prevent spontaneous bleeding and because the plasma half-life is long (7-12 d), prophylaxis is the management strategy of choice. Prophylactic therapy with factor XIII concentrate 10-20 U/kg every 4-6 weeks or rFXIII A-subunit 35 IU/kg monthly provides adequate plasma levels in most patients. The dose and frequency should be tailored to plasma levels and clinical efficacy for each patient. [10]
The half-life of factor XIII is shorter during pregnancy; therefore, treating pregnant patients requires more frequent dosing. In addition, a booster dose is recommended during labor to decrease the risk of bleeding in the mother.
A retrospective study by Rugeri et al of women with severe factor XIII deficiency found that of four patients in whom a total of 37 pregnancies occurred, there were 30 fetal miscarriages, with 24 of those taking place when the pregnancy involved no prophylactic treatment. All full-term pregnancies were in women who underwent prophylactic therapy. [11]
Neonates at risk for factor XIII deficiency because of their family history should be screened at birth and treated promptly if factor XIII deficiency is found. [12]
Surgical Care
In preparation for surgical procedures, patients should receive factor XIII concentrate immediately before surgery to ensure optimal hemostasis and wound healing.
A retrospective study of perioperative acquired factor XIII deficiency by Fahlbusch et al found that in pediatric patients undergoing cardiopulmonary bypass, neither preoperative nor postoperative factor XIII activity accurately predicted the need for postoperative transfusion. There was also no link seen between factor XIII activity and postoperative chest tube drainage loss. [13]
Consultations
Consult a hematologist and/or hemostasis specialist for patients who require factor XIII replacement therapy.
Genetic counseling and family studies should be part of a complete evaluation.
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Activation of factor XIII (FXIII) by thrombin and calcium is a 2-step process. Thrombin cleaves an arginine-lysine bond in the A subunit and calcium causes dissociation of the B subunit, exposing the active site on the A subunit (XIIIa).
