Congenital factor XIII deficiency in women: a systematic review of literature

Abstract

Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder. There is a paucity of data in the literature about obstetrics and gynaecological problems in women affected by FXIII deficiency. The aim of this study was to examine gynaecological problems and obstetric complications and outcome in women with congenital FXIII deficiency. An electronic search was performed to identify the published literature on PUBMED, MEDLINE, EMBASE, Journals @OVID and CINAHL Plus databases using the following keywords: 'congenital factor XIII deficiency' AND 'women OR Pregnancy'. A total of 39 relevant articles were found and included in this systematic review; 27 case reports and 12 case series dating from 1964 to 2012. A total of 121 women were identified. Menorrhagia (26%) was the second most common bleeding reported after umbilical bleeding. Ovulation bleeding reported in 8% of women. Among 63 women, 192 pregnancies were reported; of these, 127 (66%) resulted in a miscarriage and 65 (34%) reached viability stage. In 136 pregnancies without prophylactic therapy, 124 (91%) resulted in a miscarriage and 12(9%) progressed to viability stage. Antepartum haemorrhage occurred in 5/65 (8%) pregnancies reaching viability stage while postpartum haemorrhage (PPH) seen in 16 (25%) cases. Women with congenital FXIII deficiency suffer significant bleeding complications. Menorrhagia and ovulation bleeding are common gynaecological problems and more prevalent than reported. Pregnancies in women with FXIII deficiency have a significant risk of miscarriage, placental abruption and PPH if not on prophylaxis treatment.

Rare bleeding disorders: diagnosis and treatment

“…Prophylactic FXIII infusions are recommended in FXIII-A-deficient pregnant women to prevent fetal loss. 58 When FXIII concentrate is not available, FFP and cryoprecipitate should be considered, the latter being preferable due to higher FXIII content. 59 Plasma-derived FXIII has been used for several years and has been shown to be safe and effective; a new recombinant FXIII-A 2 concentrate (rFXIII-A 2 ) is available, and a phase 3 clinical trial (ClinicalTrials.gov identifier: #00713648) that was recently completed demonstrated that rFXIII is safe and effective in bleed prevention in congenital FXIII-A subunit-deficient patients.…”

Mild factor XIII deficiency and concurrent hypofibrinogenemia

“…This may suggest that individuals with mild FXIII deficiency may benefit from FXIII replacement at the onset of labor, and may not require additional dosing during the postpartum period because of the 11-14-day half-life of FXIII. Our patient had early pregnancy-associated bleeding between 8 and 12 weeks, and may have also benefited from a dose of FXIII during the initial stages of pregnancy to maintain implantation [16].…”

“…The approximately 50% decrease in this patient's FXIII level from her baseline of 51% to a nadir of 26% during labor suggests that delivery may present a higher than suspected bleeding challenge to women, even in those women with only mildly decreased, nonpregnant FXIII levels. In normal women, FXIII levels have been noted to decline during pregnancy, with the most significant decrease noted in the third trimester [16]. It remains uncertain whether the reduction in FXIII activity is an effect of reduced production, increased plasma volume, or increased consumption [12].…”

Management of Inherited Bleeding Disorders in Pregnancy

“…157,158 Factor II and factor V do not increase during pregnancy; 87,159 factor XIII decreases during normal pregnancy. 160 If available, specific recombinant or virally inactivated plasma-derived factor concentrates should be used in preference to FFP or cryoprecipitate. 123 Tranexamic acid may be useful alone for minor bleeds or as an adjunct to replacement therapy without significantly increasing the risk of thrombosis.…”

“…182 Prophylaxis should be continued and intensified in pregnancy to reduce the risk of pregnancy loss and PPH. 160,183 Although there has been a suggestion that heterozygous carriers may experience trauma-related bleeding, 156 this has not been studied systematically and there is evidence that maintaining levels of 0.03-0.10 iu/ml can be sufficient to prevent bleeding in severely affected patients. 184,185 Evidence level 3…”