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Dealing with carriers of hemophilia

Dealing with carriers of hemophilia. Alison Street Alfred Health, Melbourne, Australia Oct 2011. The most famous hemophilia carriers in history. Genotype of the Royal Disease recently identified as IVS 3-3A>G in the Factor IX gene

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Dealing with carriers of hemophilia

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  1. Dealing with carriers of hemophilia Alison Street Alfred Health, Melbourne, Australia Oct 2011

  2. The most famous hemophilia carriers in history

  3. Genotype of the Royal Disease recently identified as IVS 3-3A>G in the Factor IX gene If he were born today what would we advise his female relatives about their own health and carrier status?

  4. She needs to know • It has been estimated that for each male with Factor VIII or IX deficiency that there may be from two up to five female carriers of the responsible genetic mutation which has impact on • her male offspring (50% chance of being affected) • her female offspring (50% chance of being a carrier AND

  5. and implications for herself She may have symptoms of mild hemophilia and risks of bleeding if she has low factor levels Reduced factor levels are found in up to 80% of carriers and 20% have levels in the “mild hemophilia” range (5-30% activity, ref range 50-150%)

  6. Who are the carriers and how should we identify and advise them, particularly in relation to • understanding hemophilia and their own risks of bleeding • understanding their genetic risk of being a carrier and learning about • peri -delivery care?

  7. Bleeding problems in women • The woman may have bleeding problems (particularly with menses) and needs clinical assessment and measurement of the coagulation factor that is reduced in her male relatives • Definitive testing is by genetic analysis • Remember that a normal level of factor does NOT mean that she is not a carrier

  8. Genetics of hemophilia A and B, An Introduction for Clinicians 2009. Carol K Kasper, M.D., Carolyn H. Buzin, Ph.D.

  9. WFH Publications Genetics of Haemophilia Anne Goodeve Sheffield Molecular Genetics Service a.goodeve@shef.ac.uk available on WFH website www.wfh.org

  10. Anne’s presentation introduces hemophilia and its inheritance pattern • It describes the mutations responsible for F VIII and IX deficiency and their analysis • It provides an algorithm for testing and web-based and literature resources • Principally directed at molecular biology services • Updated lab manuals (2010) also now available on WFH website

  11. GENETICS OF HEMOPHILIA A AND B An Introduction for Clinicians, 2009 by Carol K. Kasper, M.D. and Carolyn H. Buzin, Ph.D.

  12. What information is critical to potential carriers? • Advice that phenotype (plasma factor level) information (and its management where support is required,) is essential for procedures to be safely performed • Emphasis, that although factor levels may be reduced in carriers (up to 80%), normal factor levels do NOT exclude carrier status • Provision of current information about hemophilia including DNA analysis where appropriate AND LISTENING TO CONCERNS

  13. Reasons for potential carriers to seek information, including DNA analysis • Gives knowledge of their status including phenotype assessment and personal risks of bleeding • Allows informed reproductive options where culturally appropriate • Permits preparation for delivery • Permits preparation for raising a child with hemophilia

  14. Reasons for potential hemophilia carriers to NOT seek clinical advice or testing • Result may not be thought necessary for personal decision making. • Encouragement required to seek knowledge of personal risks • Fear of altering relationships/family concerns

  15. Consultation with other specialists may be sought by a carrier and can be very valuable. • Carriers at risk of bleeding require “comprehensive care” • Hematologists, who know the problems of hemophilia, should support other consultants to understand the inheritance and clinical consequences of haemophilia as well as addressing the carrier’s own health issues.

  16. Care and treatment of Carriers • With improved care and longevity of men with haemophilia, more carriers are being born • We can define carriers by • Obligate/possible/phenotype status • DNA analysis

  17. Genetic testing, where available, is performed as part of a supportive clinical encounter with • Informed clinicians • Genetic counsellors • Excellent laboratory scientists

  18. When should women know of their carrier status? • Aim to have discussions about the possibility and consequences of being a carrier before marriage and pregnancy • so that women are tested and aware of their bleeding risks and where appropriate their genetic status and reproductive options beforehand

  19. Options for carriers • Depend on personal choices • Cultural, religious, family and societal inputs • Depend on availability of genetic and prenatal services.

  20. Management of pregnancy • Important to co-ordinate services of obstetrician, anesthetist and hematologist and to keep patient and her family informed • Factor level measurement at 34 weeks (Factor VIII levels may rise but not F IX) informs safety of invasive procedures in mother (eg epidural) • Knowledge of the gender of the fetus from ultrasound prepares obstetrician (and parents who wish to know) for delivery options

  21. Management of delivery • Multidisciplinary planning including factor support…WRITE THAT PLAN… • Delivery in a centre of obstetric expertise • Avoidance of invasive fetal monitoring • Avoidance of instrumental delivery • Vaginal vs Caesarean, and read the latest debate in Haemophilia!!

  22. Management of the newborn • Neonatal review for boys at risk • Heightened suspicion for bleeding including intra-cranial hemorrhage and early investigation • Timing of testing for hemophilia • Preparation for procedures e.g. circumcision

  23. Use of DDAVP in pregnancy in symptomatic carriers of FVIII deficiency • Prescribers’ Information advises precaution in pregnancy and contra-indication in lactation • Intermittent use to cover procedures in first and second trimesters of pregnancy has not been associated with harm to pregnancy or fetus • Has been used safely to support epidural blockade

  24. Post partum use of DDAVP or factor replacement in von Willebrand disease is recommended to reduce post-delivery fall in vWF/FVIII levels which usually occurs in the first week but may be delayed • Ensure that mother does not become hyponatremic with DDAVP

  25. Support for Carriers • Needs recognition and management by clinicians • Should be an important issue for program development by national hemophilia societies • World Federation of Hemophilia resources for clinicians and carriers available at www.wfh.org

  26. Many helpful sites for clinicians too

  27. Prince Leopold says • Please encourage your daughters, sisters and anyone else in your family who may be a carrier to learn about hemophilia and have her factor level measured

  28. THANKYOU

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