1) Hereditary bleeding disorders can cause health problems in women, especially related to their reproductive systems like menorrhagia, dysmenorrhea, and hemorrhagic ovarian cysts. 2) Menorrhagia, or prolonged/heavy menstrual bleeding, is common in women with von Willebrand disease, platelet disorders, and other bleeding disorders. It can be assessed and managed through hormonal therapy, hemostatic agents, blood transfusions, or surgery depending on the severity. 3) Preconception counseling is important to discuss issues like genetic implications, pregnancy and delivery risks, and options for prenatal screening or testing. Proper management can help women with bleeding disorders have healthy pregn

1. Health Problems in
Women with
Hereditary Bleeding
Disorders
Magdy El Ekiaby, MD
Shabrawishi HTC, Egypt

3. Hereditary Bleeding Disorders
in Women
 Hereditary platelet vWF vWF
F II F VIII
disorders TFPI F Xa F VIIIa
F IIa
F Xa TF F VIIa F Va F XI
 vWD (1%) Platelet F V
TF bearing cell FV
F Va F XIa
 Hemophilia A & B TF F
VIIa F X
carriers (<1/10,000) F IX F IXa
F Xa
F VIIIa
F XIa F Va
 Coagulation factor Activated platelet
F II F IIa
deficiency I – XIII F IIa
F IIa
(1/0.5 – 2 million) F IIa
F IIa
F IIa
F IIa F IIa
F IIa F IIa

4. Inheritance
 Hereditary bleeding diseases are inherited as recessive
characters
 Women with heterozygote bleeding disorders usually
are asymptomatic, or experience mild bleeding
problems
 In rare cases, there might be compounded
heterozygote inheritance of bleeding disorders in
which case bleeding symptoms may be severe
 Women with homozygote inheritance pattern suffer
from severe bleeding symptoms, particularly those
related to their reproductive system, eg menstrual

5. Reproductive Health
Problems
 Menorrhagea
 Dysmenorrhea
 Hemorrhagic ovarian
cyst
 Pregnancy and delivery
 Impact of bleeding
disorders on women

6. Menstrual Cycle
 Normal menstrual cycle should be less than 7 days
long during which blood loss does not exceed 80 ml*
 Women of modern societies may experience up to 500
cycles during their fertile age
 Chronic disturbance of menses may have its impact on
the health, psychological and social life of the women
 Every effort should be done to identify menorrhagea,
its probable causes, so that it can be properly
managed.
*ACOG, Management of anovulatory bleeding 2000, p.1-12

7. Menorrhagea
 It is defined as prolonged menstruation (>7 days)
and/or excessive blood loss (>80 ml)
 Excessive passage of blood clots, pain and flooding are
also common features of menorrhagea*
 Adolescent girls and perimenopausal women may
suffer most, as the menstrual cycles are usually
anovulatory
*Kadir et al, Haemophilia 2009

8. Hemorrhagic Ovarian Cysts
 In normal women, minor bleeding may occur with
rupture of the graafian follicle
 Women with HBD are more likely to have more
significant bleeding at ovulation in the form of:
 Hemorrhagic ovarian cyst
 Broad ligament hematoma
 Hemoperitoneum
 Prevalence of hemorrhagic ovarian cysts in women
with HBD ranges from 2 – 25%*
*James, Hemophilia 2005

9. Clinical Assessment of
Menorrhagea
 Iron deficiency anemia in women complaining of
menorrhagea is an indication of excessive blood loss
during menstruation
 Iron deficiency anemia will not manifest for a long
time, while menorrhagea may be existing
 Semi-quantitative assessment of menorrhagea can be
done using Pectorial Blood Assessment Chart
(PBAC)*
*Higham et al, Br J Obstet Gynaecol 1990

10. Assessment of menstrual blood loss using the
pictorial blood assessment chart (PBAC)
 Scoring System SCORE:>100 = >80 ml blood loss

11. Prevalence of Menorrhagea in
Women with HBD
Disease Prevalence Reference
vWD 74-92% Kouides et al,
Hemophilia, 2000
Ragni et al,
Hemophilia, 1999
Berbnard-Soulier 51% Lopez et al, Blood 1998
Glanzmann Thromb. 98% George et al, Blood
1990
FXI deficiency 59% Kadir et al, American J
of Hematology 1999
Hemophilia Carrier 57% Kadir et al, Hemophilia
1999
RBD 35 – 70% James, Hemophilia
2005

12. Prevalence of HBD in Women with
Menorrhagea
Disease Prevalence reference
vWD 13% Shankar et al, Bjog 2004
Platelet dysfunction Limited data, up to 47% Philipp et al, J Thromb
& Haemost 2003
RBD Limited data
Menorrhagea should alert clinicians about possibility of an
existing bleeding disorder

13. When do we suspect HBD as a cause of
Menorrhagea?
 Menorrhagea since Menarch
 Recurrent midcycle pain due to ovulation bleeding
 Family History of a bleeding disorder
 Personal history of one or more of the bleeding
symptoms such as epistaxis, notable bruisis,
mucocutaneous bleeding, postoperative and
postpartum bleeding
 Failure to respond to conventional management of
menorrhagea

14. HEMATOLOGICAL WORK UP

15. Management of Menorrhagea

16. Hormonal Therapy
 Levonorgestrel IUS
(Mirena®) is the most
effective medical treatment
of menorrhagea, and is
useful in women with HBD
as well as a reversable
contraceptive tool
 It is implanted for 3-5 years
 It reduces endometrial
proliferation and reduces
blood loss during
menstruation

17. Hormonal Therapy
 Combined hormonal therapy to reduce blood loss by
thinning the endometrium and probably increasing
FVIII & vWF levels, such as contraceptive pills,
transdermal contraceptive patches & vaginal rings
 Oral progestogens
 Gonadotropin-releasing hormone (GnRH) analogues
(stop ovulation)

18. Hemostatic Therapy
 Anti-fibrinolytics
 DDAVP
 Specific clotting factor concentrates
 Blood component transfusion

19. Anti-fibrinolytic Agents
 Tanexamic acid and Epsilon Amino Caproic Acid
(EACA), are known to have hemostatic effect and
may help to control menorrhagea
 Oral Tranexamic acid (1g, 3 – 4 times daily) during
menstrual period is known to reduce menorrhagea
 Usually it is well tolerated but side effects include
nausea, vomiting, headache and diarrhea

20. DDAVP
 DDAVP (1-desamino-8-D-vasopressin), a synthetic
vasopressin that stimulates release of vWF and FVIII
from their endothelial stores
 It has a formulation for treatment of nocturnal
enuresis and a hemostatic form
 The hemostatic form comes as a nasal spray and
ampoules which are administered subcutaneously or
by iv infusion
 For management of menorrhagea a daily dose of 150 –
300 micro-gram for a maximum of 3-4 days during
heaviest days of the cycle

21. DDAVP
 It is mainly effective in Hemophilia A carriers, vWD
(except type 2B) and to some extent in Glanzmann
thrombasthenia and Bernard-Soulier Syndrome
 Side effects include tachycardia, flushing, and
headache
 Small risk of hyponatremia and water intoxication
with repeated doses, so better advise water intake
restriction during therapy

22. Acute Adolescent Menorrhagea
 Usually achieved by a combination of hemostatic
agents and high doses of hormonal therapy
 In severe cases specific factor concentrates and
intravenous anti-fibrinolytics may help
 rFVIIa is successful in patients with severe platelet
dysfunction
 Platelet transfusion (HLA matched whenever possible)
may be required in cases of severe thrombocytopenia
and thrombasthenia

23. Counselling
 Issues of counselling include:
 Marriage
 Preconception

24. Marriage
 Women with bleeding
disorders usually have
social and psychological
problems connected
with marriage
 Couples & their
relatives usually have
questions about sexual
life, hymen defloration,
risks of pregnancy and
delivery as well as
disease inheritance

25. Preconception
 Advantages:
 Provides adequate information on the genetic
implications of their disorders, the available
reproductive choices, and options for prenatal diagnosis
 Allows planning for pregnancy and establishing how
and where pregnancy can be best managed
 Immunization against HBV & HAV for those likely to
receive blood transfusion
 DDAVP test dose to assess response
 General hematenic supplmentation

26. Prenatal Diagnosis (PND)
 Particularly important in hemophilia carrier due to the
severity of the disease in the male offspring
 It is also of importance in heterozygote carriers in
cases of consanguineous marriage
 PND diagnostic methods include:
 Chorion Villus Sampling (CVS), weeks 11-14
1% risk of
 Amniocentesis, weeks 15-20 abortion
 Cordocentesis, weeks 18-20
 Fetal sex determination
 Pre-implantation diagnosis

27. Antenatal management
 Increased levels of vWF, FVIII, Fibrinogen as well as
plasminogen activator inhibitors, particularly during
third trimester of pregnancy, reduces bleeding episodes
and complications in women with HBDs
(Bremme, Best Pract Res Clin Hematol, 2003)
 20% of normal pregnancies may wetness a bleeding
episode due to obstetric problems, which should not
be overlooked in women with HBDs
 Women with FI & FXIII deficiency are particularly at
risk of miscarriage, placental abruption and preterm
delivery which may require factor replacement during
pregnancy (Chi & Kadir,

28. Labour & delivery
 Third trimester coagulation factor levels should be known before
delivery and factor replacement may be considered in those with
low levels
 DDAVP may be used in hemophilia carriers and vWD during
delivery with caution
 Matched packed RBCs should be reserved for emergency
bleeding
 Cesarean section as well as other obstetrical procedures should be
evaluated for least traumatic manipulation of the fetus
 Cord fetal blood sample to assess if the baby has inherited the
bleeding disorder

29. Postpartum management
 Elevated coagulation and antifibrinolytic levels during
pregnancy, slowly return to its low levels in the
postpartum period
 It is recommended to use prophylaxis of deficient
hemostatic agent immediately before delivery as well
as for 3-4 days after normal vaginal delivery and 5-7
days after cesarean section
 14-21 days postpartum a secondary hemorrhage can
be expected

30. Hemostatic materials

31. Suggested hemostatic levels

32. Quality of life
 Women with HBD suffer many bleeding problems
during their fertile life
 Many of these women experience anemia, fatigue
which affects their marital, familial, social and
practical life
 They are at a higher risk of postpartum hemorrhage,
which may lead to severe morbidity and risk of
mortality

33. Conclusion
 The prevalence of HBD is not insignificant
 Women suffering from menorrhagea, particularly
since adolescence should be investigated to exclude
HBD
 Women with HBD should receive care for their
reproductive life in specialized centers, or at least
under common supervision from an obstetrician and a
hematologist
 Proper management of women with HBD can greatly
improve the quality of their lives