Factor Xiii, a Subunit, Deficiency Of

Transglutaminase (TG) 2 and Factor (F) XIII-A have both been implicated in cardiovascular protection and repair. This study was designed to differentiate between two competing hypotheses: that TG2 and FXIII-A mediate these functions in mice by fulfilling separate roles, or that they act redundantly in this respect.

Atherosclerosis was assessed in brachiocephalic artery plaques of fat-fed mixed strain apolipoprotein (Apo)e deficient mice that lacked either or both transglutaminases. Cardiac fibrosis was assessed both in the mixed strain mice and also in C57BL/6J Apoe expressing mice lacking either or both transglutaminases.

No difference was found in the density of buried fibrous caps within brachiocephalic plaques from mice expressing or lacking these transglutaminases. Cardiac fibrosis developed in both Apoe/F13a1 double knockout and F13a1 single knockout mice, but not in Tgm2 knockout mice. However, concomitant Tgm2 knockout markedly increased fibrosis, as apparent in both Apoe/Tgm2/F13a1 knockout and Tgm2/F13a1 knockout mice. Amongst F13a1 knockout and Tgm2/F13a1 knockout mice, the extent of fibrosis correlated with hemosiderin deposition, suggesting that TG2 limits the extravasation of blood in the myocardium, which in turn reduces the pro-fibrotic stimulus. The resulting fibrosis was interstitial in nature and caused only minor changes in cardiac function.

These studies confirm that FXIII-A and TG2 fulfil different roles in the mouse myocardium. FXIII-A protects against vascular leakage while TG2 contributes to the stability or repair of the vasculature. The protective function of TG2 must be considered when designing clinical anti-fibrotic therapies based upon FXIII-A or TG2 inhibition.

Essentials Inherited factor XIII deficiency is a very rare bleeding disorder. We used recombinant factor XIII-A in a pregnant patient with factor XIII-A subunit deficiency. The patient had a successful pregnancy outcome with no pregnancy related complications. The dose of recombinant factor XIII-A was minimized by using frequent trough level monitoring.

Inherited factor XIII deficiency is a very rare bleeding disorder, and is one of the causes of recurrent pregnancy loss. The use of plasma-derived FXIII to improve pregnancy outcomes has been reported. We report a 26-year-old woman with FXIII A-subunit (FXIII-A) deficiency who was treated with recombinant FXIII-A and had a successful pregnancy outcome with no pregnancy-related complications. Our case illustrates that the dose of recombinant FXIII-A can be minimized and adjusted on the basis of frequent trough level monitoring.

BACKGROUND Factor XIII deficiency is associated with recurrent miscarriages in women. CASE REPORT In this report, we present a patient with factor XIII deficiency and some comorbidities who had had previous miscarriages. She began treatment with factor XIII subunit A (XIII-A) replacement treatment Recombinant factor XIII (Tretten) at a dose of 2500 units monthly and was able, for the first time, to carry a pregnancy almost to term. Although she experienced some obstetrical complications, she delivered a healthy baby. To the best of our knowledge, this is the first report of the use of Tretten during pregnancy. CONCLUSIONS Tretten, which is not indicated in pregnancy, offered a safe, effective treatment for miscarriages secondary to factor XIII-A deficiency in our patient. Further research is required to confirm this finding.