Factor VIII levels and bleeding according to factor 8 (F8) mutation in pregnant carriers of haemophilia A: a multicentre retrospective cohort study

Abstract

This retrospective cohort study investigated the association between factor 8 (F8) genotype severity and factor VIII (FVIII) levels during pregnancy for 52 women (64 pregnancies) who were heterozygous carriers of mild, moderate or severe haemophilia A. There were no significant differences in FVIII levels for carriers of mild, moderate or severe haemophilia A at baseline [mean (SD) level: mild, 0Á78 (0Á22); moderate, 0Á83 (0Á33); severe, 0Á70 (0Á25) iu/ml; P = 0Á81] or in the third trimester [mean (SD) level: mild, 1Á42 (0Á28); moderate, 1Á47 (0Á41); severe, 1Á37 (0Á49) iu/ ml; P = 0Á80). Post-partum haemorrhage rates were higher for carriers of severe haemophilia A (13/24; 54Á2%) compared to carriers of mild haemophilia A (four of 14; 28Á6%).

JTH in Clinic ‐ Obstetric bleeding: VWD and other inherited bleeding disorders

“…In female genetic carriers of HA, FVIII levels are overall lower than non-carriers before and during pregnancy. Data from Drury-Stewart et al 2 Castaman, 16 Makhamreh et al 38,39 and Collins et al 57 loss associated with evidence of hypovolemia; secondary PPH is defined as excessive bleeding after 24 h up to 12 weeks after delivery. [25][26][27] Older definitions of primary PPH used a different measure for vaginal delivery of 500 mL blood loss, which is still considered abnormal.…”

“…56,57 The presence of a hemophilia A-causative genotype and the severity of that genotype are thus far the best predictors of PPH in genetic carriers of hemophilia A. 57 Treatments include factor replacement and tranexamic acid. 55,58 Desmopressin is used for prophylaxis for delivery in hemophilia A by some, 55 but we tend not to use it for the same reasons as in VWD.…”

“…In female genetic carriers of HA, FVIII levels are overall lower than non‐carriers before and during pregnancy. Data from Drury‐Stewart et al 2 Castaman, 16 Makhamreh et al 38,39 and Collins et al 57 FVIII = factor VIII activity; IBD = inherited bleeding disorder; IU/dl = international units per deciliter; HA = hemophilia A; VWD, von Willebrand disease; VWF, von Willebrand factor; VWF:Ag = VWF antigen; VWF:RCo = VWF ristocetin cofactor activity.…”

“…PPH rates are high in IBDs even with treatment, 55 and factor levels also may not predict bleeding well in IBDs. In hemophilia A, levels in females are poor predictors of bleeding generally and in pregnancy, including some individuals bleeding excessively at levels ≥50 56,57 . The presence of a hemophilia A‐causative genotype and the severity of that genotype are thus far the best predictors of PPH in genetic carriers of hemophilia A 57 .…”

“…In hemophilia A, levels in females are poor predictors of bleeding generally and in pregnancy, including some individuals bleeding excessively at levels ≥50 56,57 . The presence of a hemophilia A‐causative genotype and the severity of that genotype are thus far the best predictors of PPH in genetic carriers of hemophilia A 57 . Treatments include factor replacement and tranexamic acid 55,58 .…”