Understanding Hemophilia in Women and Carriers

Bleeding disorders in women Bleeding disorders in women Nargesbeigom Mirbehbahani professor of pediatric hematology and oncology Golestan university of medical sciences

The most severe forms of hemophilia typically affect males; females have conventionally been designated as carriers. Carriers often do not show symptoms of hemophilia because, although they have an abnormal F8 or F9 gene on one X chromosome, their other X chromosome contains a normal F8 or F9 gene that generally works as normal to produce factor levels in the lower limit of the normal range.

A proportion of carriers have low factor VIII ( A proportion of carriers have low factor VIII (FVIII) factor IX ( factor IX (FIX) FIX) activity due to activity due to lyonization suppression of one of the two X chromosomes; suppression of one of the two X chromosomes; also called X inactivation), called X inactivation), can result in mild, can result in mild, moderate, even severe hemophilia in rare instances. even severe hemophilia in rare instances. Symptomatic females should be designated as having Symptomatic females should be designated as having hemophilia of a specified severity, hemophilia of a specified severity, like males with hemophilia. hemophilia. FVIII) or or lyonization ( (the random the random also moderate, or or like males with

INHERITANCE OF HEMOPHILIA Obligate carriers include: Obligate carriers include: any biological daughter of a father with any biological daughter of a father with hemophilia; hemophilia; any biological mother of a child with hemophilia who any biological mother of a child with hemophilia who also has at least one other family member with hemophilia ( also has at least one other family member with hemophilia (i. i.e., brother, brother, maternal grandfather, maternal grandfather, uncle, uncle, nephew, who is a known carrier of hemophilia ( who is a known carrier of hemophilia (i. i.e., maternal grandmother, maternal grandmother, aunt, aunt, niece, niece, or female cousin); biological mother of two or more children with hemophilia. biological mother of two or more children with hemophilia. Potential carriers include: Potential carriers include: any biological daughter, any biological daughter, sister, maternal grandmother, maternal grandmother, aunt, aunt, niece, niece, or female cousin of a carrier of hemophilia; hemophilia; a biological mother of a child with hemophilia and no a biological mother of a child with hemophilia and no known family history of hemophilia or carriers of hemophilia known family history of hemophilia or carriers of hemophilia. . e., her her or nephew, or male cousin) or male cousin) or e., her mother, her mother, sister, or female cousin); any sister, any mother, sister, mother, or female cousin of a carrier of

FACTOR LEVELS IN CARRIERS Carriers with FVIII/ Carriers with FVIII/FIX levels in the normal range may never FIX levels in the normal range may never require require factor replacement therapy. factor replacement therapy. However, factor levels in the lower range of normal ( factor levels in the lower range of normal (i. i.e., IU/ IU/dLexperience dLexperience bleeding problems similar to males with mild bleeding problems similar to males with mild hemophilia ( hemophilia (e. e.g., g., hemorrhaging after dental extraction, hemorrhaging after dental extraction, surgery, or trauma) or trauma) as well as problems that are specific to women, as well as problems that are specific to women, such as prolonged or heavy menstrual bleeding. as prolonged or heavy menstrual bleeding. Carriers who exhibit a greater bleeding tendency than would be Carriers who exhibit a greater bleeding tendency than would be predicted by their factor level, predicted by their factor level, as in males, as in males, may have a second coagulation defect, coagulation defect, such as a von such as a von Willebrand variant or a congenital platelet defect. variant or a congenital platelet defect. However, some carriers with some carriers with e., below below 50 50 surgery, such may have a second Willebrand factor ( factor (VWF) VWF) gene gene

PRENATAL DIAGNOSIS Prenatal diagnosis is usually offered to help with Prenatal diagnosis is usually offered to help with reproductive planning and risk assessment. reproductive planning and risk assessment. Determination of whether a male fetus is affected by Determination of whether a male fetus is affected by hemophilia assists parents and healthcare providers hemophilia assists parents and healthcare providers in making decisions regarding pregnancy in making decisions regarding pregnancy management, management, such as caesarean delivery of a fetus such as caesarean delivery of a fetus with severe disease to with severe disease to reduce reduce intracranial hemorrhage ( hemorrhage (ICH) ICH) and maternal anesthesia for and maternal anesthesia for childbirth childbirth. . intracranial

PREGNANCY AND PRENATAL PLANNING Management of care for all pregnant carriers Management of care for all pregnant carriers should involve close cooperation between the should involve close cooperation between the hemophilia and obstetric teams. hemophilia and obstetric teams. It is important important to have a clear plan for delivery that to have a clear plan for delivery that is shared with the is shared with the carrier carrier and written in her medica medical l It is and written in her

NEWBORN TESTING Cord blood should be collected from all male Cord blood should be collected from all male newborn infants of carriers of hemophilia to newborn infants of carriers of hemophilia to assess clotting factor levels for early assess clotting factor levels for early identification and management of hemophilia. identification and management of hemophilia. The test results should be conveyed to the The test results should be conveyed to the parents by an appropriate member of the parents by an appropriate member of the hemophilia team. hemophilia team.

Normally in newborn and pre Normally in newborn and pre- -term infants without hemophilia, hemophilia, FVIII levels at birth are within the normal FVIII levels at birth are within the normal adult range or mildly increased. adult range or mildly increased. Therefore, possible to diagnose most cases of hemophilia A at possible to diagnose most cases of hemophilia A at birth; birth; the exception being in mild hemophilia A, the exception being in mild hemophilia A, wherein a FVIII result at the lower end of the normal wherein a FVIII result at the lower end of the normal range should be repeated when the infant range should be repeated when the infant is around 6 6months months of age. of age. term infants without Therefore, it is it is is around

In contrast to FVIII, In contrast to FVIII, FIX levels at birth are FIX levels at birth are significantly lower than normal in newborns significantly lower than normal in newborns without hemophilia and even more so in without hemophilia and even more so in preterm preterm infants. infants. 23 23 While it is usually possible While it is usually possible to make a diagnosis of severe or moderate to make a diagnosis of severe or moderate hemophilia B in the neonatal period, hemophilia B in the neonatal period, infants who may be mildly affected will require repeat who may be mildly affected will require repeat screening at screening at 3 3- -6 6 months of age. months of age. infants

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