WOMEN WITH BLEEDING DISORDERS Nairobi, Kenya June 25, 2013

OBJECTIVES Discuss the types of bleeding disorders affecting women Distinguish sex-linked inheritance from autosomal inheritance Explain carrier versus non-carrier states in women List common bleeding symptoms in women Identify approaches available to treat bleeding in women Examine ways to treat bleeding episodes specific to women

TYPES OF BLEEDING DISORDERS IN WOMEN -Hemophilia: very rare, more commonly symptomatic carrier -Von Willebrand disease -Other plasma protein (factor) deficiencies -Platelet function defects -Fibrinolysis inhibitor deficiencies -Hereditary hemorrhagic telangiectasia (HHT) -Ehlers-Danlos ADDITIONAL TEXT EXAMPLE

CARRIERS OF HEMOPHILIA For many years, people believed that only men could have symptoms of hemophilia We now know that women who carry the hemophilia gene can experience symptoms. A woman with < 40% factor levels is no different from a man with the same factor levels—she has hemophilia A woman with levels of 40-60% who experiences abnormal bleeding is called a symptomatic carrier

CARRIER VERSUS NON-CARRIER Can occur on sex chromosomes and autosomes Trait generally not expressed in carriers Level of missing protein in carriers can be quite low; even in the mild range Some carriers may be symptomatic Remember: all daughters born to men with hemophilia are obligate carriers.

PLASMA PROTEIN DEFICIENCIES Sometimes called rare bleeding disorders (RBDs) 1 or recessively-inherited coagulation defects (RICDs) 2 Differ from hemophilia A & B 1,2,3 –Genetics –Epidemiology –Clinical presentation –Diagnostic evaluation –Treatment May lack specific protein concentrate for treatment 1 Bolton-Maggs PHBet al. Haemophilia 2004; 10: Mannucci PM, Duga S, Peyvandi F. Blood 2004; 104: Munn, James E. Nursing Care of Children and Adolescents with Cancer and Blood Disorders, Fourth Edition, Glenview, IL; Association of Pediatric Hematology Oncology Nurses; 2011:

PLATELET DISORDERS Giulio Bizzozero discovered function of platelets in 1882 Role of platelets in hemostasis: –Primary hemostatic plug –Secretion of substances to promote Platelet recruitment Vessel contraction Coagulation –Provide optimal surface for coagulation to proceed Giulio Bizzozero Munn, James E. Nursing Care of Children and Adolescents with Cancer and Blood Disorders, Fourth Edition, Glenview, IL; Association of Pediatric Hematology Oncology Nurses; 2011:

PLATELETS Munn, James E. Rare Coagulopathies. In: National Hemophilia Foundation’s Nursing Working Group (ed): Nurses’ Guide to Bleeding Disorders, in print.

PLATELET DISORDERS Defects in any of the functions of platelets can result in bleeding Clinical features: easy bruising, petechiae, mucocutaneous bleeding, menorrhagia, rarely intramuscular bleeding or hemarthrosis Diagnosis: CBC with differential and platelet count, PFA testing, platelet aggregation and secretion studies, electron microscopy Treatment –Antifibrinolytics (IV, oral) –Hormonal suppression (OCPs, IUD) –Platelets –Recombinant activated factor VII Munn, James E. Rare Coagulopathies. In: National Hemophilia Foundation’s Nursing Working Group (ed): Nurses’ Guide to Bleeding Disorders, in print.

FIBRINOLYSIS INHIBITOR PROTEIN DEFICIENCIES Fibrinolysis is the body’s natural response to clot formation Achieved principally through plasmin (enzyme that degrades clots) Natural inhibitors help regulate this process –α 2 -antiplasmin (α 2 -AP) –Plasminogen activator inhibitor-1 (PAI-1) Deficiencies in either can result in bleeding Clinical bleeding is usually mucocutaneous Treatment with antifibrinolytics (IV, oral) Munn, James E. Rare Coagulopathies. In: National Hemophilia Foundation’s Nursing Working Group (ed): Nurses’ Guide to Bleeding Disorders, in print.

OTHER BLEEDING DISORDERS Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) AVMs present in mucosal membranes and may involve other organs Bleeding can be mild or severe Treatment is symptomatic 1 Dupuis-Girod S, Bailly S, Plauchu H. J Thromb Haemost 2010; 8: 1447–1456.

OTHER BLEEDING DISORDERS Ehlers-Danlos Syndrome (EDS) Connective tissue (collagen) defect Clinical features –Joint hypermobility –Skin hyperelasticity –Hypertrophic scarring Bruising, spontaneous joint subluxations, poor wound healing Treatment is geared toward prevention or is symptomatic 2 2 Faber P, Craig WL, Duncan JL, Holliday K. Acta Anaesthesiol Scand 2007; 9: Munn, James E. Rare Coagulopathies. In: National Hemophilia Foundation’s Nursing Working Group (ed): Nurses’ Guide to Bleeding Disorders, in print.

INHERITANCE OF BLEEDING DISORDERS Sex-linked: hemophilia, Wiskott-Aldrich Syndrome (platelet disorder) Autosomal: VWD, other factor deficiencies, most platelet disorders, fibrinolysis inhibitor deficiencies, HHT, Ehlers- Danlos -Dominant -Recessive -Heterozygous -Homozygous

COMMON BLEEDING SYMPTOMS IN WOMEN WITH BLEEDING DISORDERS Mucocutaneous bleeding Petechiae Easy bruising Bleeding after trauma or surgery (including dental procedures) Menorrhagia Post-partum hemorrhage Rarely, intramuscular bleeding or hemarthrosis

TREATMENT FOR BLEEDING Avoid IM injections if possible Avoid ASA and ASA-containing products Prepare for surgeries/deliveries in advance No invasive procedures without consultation of HTC team Minor bleedingMajor bleeding R.I.C.EFactor concentrates Direct pressurePlatelets Topical hemostatic agentsCryoprecipitate DDAVPFFP Antifibrinolytics

MENORRHAGIA Excessive uterine bleeding occurring at the expected intervals of the menstrual periods. The bleeding from the uterus starts on schedule but is heavier than usual and may last longer than usual. Menorrhagia may be a sign of an underlying disorder, such as hormone imbalance, endometriosis, uterine fibroids or, rarely, cancer of the uterus. “ MedicineNet.com” – We bring doctors’ knowledge to you.

MENORRHAGIA Common symptom of women with bleeding disorders 1 Obstetricians/gynecologists may not associate menorrhagia with an inherited bleeding disorder 2 May result in unnecessary surgery if not treated appropriately Remember: the index patient identified by Erik von Willebrand in his discovery of a new bleeding disorder was a young girl who eventually died of hemorrhage in her 4 th menstrual cycle 3 1 NHF “For You and Your Doctor” pamphlet (2001). 2 Dilley, A., et al (2001) “Obst. And Gyn: 97 (4), April. 3 von Willebrand, E. (1926)

TREATMENT OF MENORRHAGIA DDAVP Antifibrinolytics Oral contraceptive pills Factor replacement/Blood products IUDs Surgical interventions

TREATMENT OF EXCESSIVE MENORRHAGIA OCP “Formula” to stop recalcitrant menorrhagia Lo-ovral: – 1 pill QID x 2 days – 1 pill TID x 3 days – 1 pill BID x 4 days Resume suppression therapy, usually 1-2 pills per day Use of anti-emetics, analgesics a must

OBSTETRICAL/POST-PARTUM BLEEDING TREATMENT For the mother: Previous bleeding history and response to therapy usually best indicator of OB/post-partum bleeding/treatment Consider treatment at delivery and again at days 5-7 Factor concentrates to raise factor levels to >30% DDAVP – give immediately after delivery or at delivery of baby’s head NSVD is fine; consider cesarean for known carriers

OBSTETRICAL/POST-PARTUM BLEEDING For the baby: -Avoid suction or forceps delivery and fetal scalp monitoring -Take cord blood samples to avoid venipuncture bleeding -Consider cranial ultrasound in boys suspected to have hemophilia prior to discharge from hospital -Pediatrician should be available

SUMMARY Women may have a variety of bleeding disorders that require specialized care Inheritance patterns are different for different bleeding disorders Carriers may be symptomatic and require treatment for bleeding Menorrhagia is one of the most common bleeding manifestations in women Treatments are available Special care must be taken with pregnancy and delivery

WFH RESOURCES Carriers and Women with Hemophilia Reproductive Health in Women with Bleeding Disorders Symptomatic Carriers of Hemophilia Visit the Publications Library at for free copies