Hemophilia Carriers

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review

“…This variability is partially attributed to X-inactivation or Lyonization, whereby some carriers express the non-mutated X-chromosome more dominantly, resulting in higher levels of FVIII or FIX, while others have a higher proportion of cells expressing the mutated X-chromosome, leading to low factor levels [ 47 , 48 ]. Various factors, such as maternal versus paternal inheritance, age, blood type, von Willebrand factor, body mass index, and C-reactive protein, have historically been suggested to influence factor activity [ 49 ]. A study comparing hemophilia carriers with healthy controls found that the median clotting factor level in carriers was 0.60 IU/mL (range, 0.05–2.19 IU/mL) compared to 1.02 IU/mL (range, 0.45–3.28 IU/mL) in non-carriers.…”

“…Clotting factor levels ranging from 0.05 to 0.60 IU/mL were inversely associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and surgeries [ 47 ]. Most studies investigating the bleeding tendency in hemophilia carriers have relied on self-reported bleeding, rather than direct observation, and reported symptoms include epistaxis, easy bruising, heavy menstrual bleeding (HMB), and post-procedural bleeding, with varying frequencies of each symptom across studies [ 49 ]. Hemarthrosis has also been observed [ 50 ].…”

“…Hemarthrosis has also been observed [ 50 ]. However, studies have yielded contradictory results, with some showing a correlation between bleeding phenotype and factor levels, while others demonstrate that approximately one in four hemophilia carriers with normal FVIII/IX levels (>50 IU/dL) can still have an increased bleeding tendency [ 49 , 51 ].…”

“…Studies concerning the treatment of HMB especially in hemophilia carriers are quite scarce. Treatment options generally include hormonal therapies such as combined oral contraceptives, progesterone-only therapy, or long-acting reversible contraception, as well as hematologic medications such as recombinant or plasma-derived factor concentrates and antifibrinolytic medications in both hemophilia A and B carriers and (DDAVP) only in hemophilia A carriers [ 49 ]. Non-steroidal anti-inflammatory drugs (NSAIDs), commonly used for heavy menstrual bleeding (HMB) in the general population, are not recommended for patients with bleeding disorders due to their antiplatelet effects [ 23 ].…”