This presentation gives general overview of hemophilia in pregnancy

2. Royal Disease “Hemophilia”

3. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Cases

4. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Cases

5. What is Hemophilia?
• HEMO = BLEEDING
• PHILIA = LOVE
• Hemophilia = The Love of Bleeding

6. Genetic disease of blood
coagulation

7. What is Hemophilia?
• Hemophilia is a hereditary bleeding
disorder caused by deficiency of
coagulation factor VIII, IX or XI.
• The deficiency is the result of mutations
in the respective clotting factor genes.

9. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

10. Types
• Hemophilia A 80%
– Classic hemophilia
– Factor VIII deficiency
• Hemophilia B 20%
– Christmas disease
– Factor IX deficiency
• Hemophilia C Very rare
– Factor XI deficiency

11. • PARAHAEMOPHILIA
• ACQUIRED HAEMOPLILIA

12. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

13. Incidence
• Hemophilia is quite rare.
• Mainly affects males.
• Hemophilia A: 1 in 10,000 live births.
• Hemophilia B: 1 in 50,000 live births.
• Heamophilia C : 1 in 1 million

14. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

15. Genetics
• Hemophilia inheritance is classically
described as an X linked recessive trait,
leading to mutation in F8 or F9 gene.
• Mainly affects males.
• Females are usually carriers.
• However, spontaneous mutations are
described in 20-30% of hemophiliacs.

16. Different Cases
1. Carrier Mother + Non-hemophiliac Father
Each pregnancy has a
25% chance of resulting
in a female non-carrier,
a 25% chance of a
female carrier, a 25%
chance of non-
hemophiliac male, and a
25% chance of a male
with hemophilia.

17. Different Cases
2. Non-carrier Mother + Father With Hemophilia
Each pregnancy has a
50% chance of a female
carrier and a 50%
chance of a non-
hemophiliac male.
Sons of hemophiliac
fathers and non-carrier
mothers will not have
hemophilia (their X is
always maternal).

18. Different Cases
3. Carrier Mother + Father With Hemophilia
Each pregnancy has a
25% chance of a
female carrier, a 25%
chance of a female
with hemophilia, a
25% chance of a non-
hemophiliac male, and
a 25% chance of a
male with hemophilia.

19. Different Cases
4. Mother With Hemophilia + Father With Hemophilia
Each pregnancy has a
50% chance of
resulting in a female
with hemophilia and a
50% chance of
resulting in a male
with hemophilia.

20. Different Cases
5. Mother With Hemophilia + Non-hemophiliac Father
Each pregnancy has a
50% chance of
resulting in a female
carrier and a 50%
chance of resulting in
a male with
hemophilia.

21. How is a female affected?
• Mother With Hemophilia + Father With
Hemophilia.
• Carrier Mother + Father With Hemophilia.
• Turner syndrome (45 X0).
• Lyonised (inactive) X chromosome.
N.B. Carriers usually have enough clotting
factors from their normal X chromosome
which prevent serious bleeding problems.

22. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

23. Clinical presentation
• The characteristic phenotype in
hemophilia is the bleeding tendency.
• History of bleeding is usually life-long.
• The severity of bleeding in hemophilia is
generally correlated with the clotting
factor level.but not in case of
haemophilia C.

24. Clinical presentation
Severity Factor VIII level Presentation
Mild 5-30% of normal
(6-40 IU/dl)
-Severe bleeding after major
trauma or surgery
-Spontaneous bleeding is rare
-May be asymptomatic
Moderate 1-5% of normal
(1-5 IU/dl)
-Prolonged bleeding after minor
trauma or surgery
-Occasional spontaneous bleeding
Severe <1% of normal
(< 1 IU/dl)
-Spontaneous bleeding into joints
or muscles, without identifiable
hemostatic challenge
-May be serious & life threatening

25. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

26. Investigations
• Platelet count: Normal
• Bleeding time: Normal
• PT: Normal
• Clotting time & APTT: Prolonged
• Factor VIII or Factor IX assay: Decreased

27. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

28. Management
• Prevention of bleeding episodes.
• Replacement therapy.
• Prophylactic therapy.
• Other lines of therapy.
• Management of complications.

29. Management
• Prevention of bleeding episodes.
• Replacement therapy.
• Prophylactic therapy.
• Other lines of therapy.
• Management of complications.

30. 1. Prevention of bleeding episodes.
• Toys that do not have sharp edges.
• Using soft and stuffed toys.
• Padding the crib.
• Using helmets & pads to protect elbows and
knees.
• Avoid games like football.
• Using soft tooth brushes.
• Careful usage of sharp razors.
• Wear Medic Alert ID.

31. Management
• Prevention of bleeding episodes.
• Replacement therapy.
• Prophylactic therapy.
• Other lines of therapy.
• Management of complications.

32. 2. Replacement therapy
• Indication:
Bleeding or Injury

33. 2. Replacement therapy
• Fresh whole blood
• Whole plasma
• Fresh Frozen Plasma
• Cryoprecipitate
• Factor VIII or IX Concentrate
• Recombinant Factor VII (Novo-Seven): to
bypass factor VIII in the coagulation
pathway

34. Factor VIII Concentrate
• Factor VIII Concentrate:
20 U/kg increases the level by ± 50%.
Clinical Situation Raise factor VIII up to
Mild bleeding 20-40%
Severe or life threatening
bleeding
100%

35. Management
• Prevention of bleeding episodes.
• Replacement therapy.
• Prophylactic therapy.
• Other lines of therapy.
• Management of complications.

36. 3. Prophylactic therapy
• Indication:
Before surgery
After exposure to trauma
• Lines:
Replacement
Other lines

37. Management
• Prevention of bleeding episodes.
• Replacement therapy.
• Prophylactic therapy.
• Other lines of therapy.
• Management of complications.

38. 4. Other lines of therapy
• Desmopressin:
- Action: stimulates the release of stored factor VIII
and von Willebrand factor. von Willebrand factor
carries and binds factor VIII, which then can stay in
the blood stream longer.
-Administration: Injection or Nasal spray.
-Use:
Before dental work.
For treating mild bleeding from the mouth or nose.

39. 4. Other lines of therapy
• EACA (e –amino caproic acid):
- Action: Antifibrinolytic  delays clot lysis
-Use: Adjuvant therapy for dental procedures

40. 4. Other lines of therapy
• Fibrin Glue:
- Action: Contains fibrinogen, thrombin and factor
XIII. Placed in the site of injury to stabilize clot.
-Use: Dental procedures and after circumcision

41. Items to be discussed in this talk
• What is hemophilia?
• Types
• Incidence
• Genetics
• Clinical presentation
• Investigations
• Management
• Hemophilia AND pregnancy
• Historical facts

42. Hemophilia AND Pregnancy
• Pre-conceptional management.
• Antenatal management.
• Management during delivery.
• Postpartum management

43. Pre-conceptional management
• Counseling:
Whenever the mother has hemophilia A or B,
all of her sons will have the disease, and all of
her daughters will be carriers. If she is a carrier,
half of her sons will inherit the disease and
half of her daughters will be carriers.
• Pre-implantation genetic diagnosis: has been
recently introduced for hemophilia since 2007.

44. • Prenatal diagnosis: by CVS.(best
method)
• Amniocentesis
• Cordocentesis (factor level)
• Fetal cells in maternal blood.
• Sex determination by USG at 11 week

46. •ANTENATAL MANAGEMENT
•Factor VIII usually increases in pregnancy
•Replacement rarely required ….mostly in
early pregnancy events
(ectopic,miscarriage,CVS,amniocentesis)
•Factor IX level does not increase in
pregnancy.more haemostatic support would
be required in form of recombinant factors.
•No role desmopressin in haemophilia B
•In case of replacement therapy hep A and B
immunization should be checked.

47. • Clotting factors level should be checked at
booking ,28 week,34 weeks
• If level is 50 IU/dl it is sufficient to avoid
bleeding in pregnancy,diagnostic
procedures,SVD,C/S.
• If greater than 50IU/dl then sufficient for
local anesthesia.

48. Fator XI level shows no change in pregnancy
although some individuals show gradual decline
Level should be checked at booking,28 weeks,34
weeks,prior to invasive procedures.
If level is < than 15IU/dl then 16-30% chances of
bleeding.prophylasix should be given on daily
basis till level rises to 70IU/dl
NOTE…level should not be greater than 100IU/dl
(associated with thrombosis)
If patient has history of thrombosis or
atherosclerosis factor replacement is not
advisable alternative support should be given
with FFP,transamin.

49. INTRAPARTUM MANAGEMENT
• Time: according to obstetric indications
• mode: controversial.
• Should be least traumatic
• SVD is preffered mode
• main concern is intracerebral bleeding so
complicated forceps delivery, rotational
foceps,ventouse extraction,scalp electrodes,fetal
blood sampling should be avioded.
• Low cavity forceps can be considered
• If there is delay in labour or safe vaginal delivery is
less likely then do C/S.

50. •On admissiom to labour suit……
•CBC
•Coagulation profile
•Cross match blood
•Clotting factors level
•If clotting factor level is < than 50 IU/dl then
•I/m anelgesis should be avoided
•Suspect baby to be haemophilic
Reduce risk of bleeding by: avoiding lacerations,
minimizing episiotomy use and size, and by maximizing
postpartum myometrial contractions and retraction

51. Management after delivery
NEOBORN
Cord blood should be taken to determine clotting
factors level.
Vit k prophylasix should be given by oral rather than
I/m
Vaccines should be given by S/C route
Screening for congenital hip dislocation should be
delayed till factors level available
If clotting factors level is decreased and delivery was
traumatic baby should be screened for intracranial
bleed by USG and CT brain.

52. In hamophilia A factor VIII level fall quickly to
pre pregnancy level
Level shoul b maimtained at 50IU/dl for 3
days in SVD and or 5 days in C/S.
Desmopressin can be given as it does not
enter breast milk.

53. First Delivery
Upon presentation, the patient was without any recent
bleeding. Her FVIII activity level was 0.94 IU /dL
and her FVIII inhibitor by Bethesda Assay was negative
4 months prior to her pregnancy. She began prophylaxis
with recombinant FVIII concentrate (Recombinate, Baxter
Bioscience), at a dose of 40 U/kg ,twice weekly starting in
her second trimester. At 72 hours her FVIII activity level
was 7 IU/dL. Care was coordinated with the high-risk
obstetrical team. There were no bleeding complications
during the pregnancy.

54. She was admitted to the hospital for induction of labor at
39 weeks of gestation. The labor was induced at term to
ensure adequate control of factor levels and minimize the
risks of bleeding. During the labor and delivery period, factor
levels were continuously monitored by the laboratory to
avoid obstetric complications. Her physical exam was
unremarkable, with no evidence of ecchymoses, petechiae,
purpura, or vaginal bleeding. On laboratory examination white
blood cell count was 7.4
hemoglobin 11.6 g/ dL
platelets 249
prothrombin time (PT) 14.1 seconds
activated partial thromboplastin time (aPTT) 32 seconds, and
FVIII activity of 7 IU/dl.

55. • The patient received a bolus infusion of
Recombinate 50 U/kg
• with a 1-hour peak FVIII activity of 111 IU/
dL
• and an 8-hour trough level of 75 IU /dL
• This was followed by 25 U/ kg
• every 8 hours intravenously to maintain
her FVIII activity level between 50 IU/ dL-
100 IU /dL until delivery.

56. Morphine, Nubain (EndoPharmaceuticals, Chadds Ford,
PA), and Phenergan (Baxter Healthcare Corp., Deerfield, IL)
were administered intravenously for analgesia during labour
as she refused epidural anesthesia. A female baby was delivered by
vaginal delivery after 36 hours of labour.

57. blood loss of 150 mL. No excessive bleeding was noted during
cord clamping. Cord blood sample obtained from the baby
revealed FVIII activity of 86 IU/ dL
The patient’spostpartum
course was uncomplicated and mother and daughter were
discharged after 3 days continuing on Recombinate for
6 weeks postpartum.

58. Dosing was as followed: 25 U/ kg every 12 hours days 2 to 5
25 U /kg daily days 6 to 14
and25 U/ kg
every other day until cessation of postpartum
vaginal spotting at 6 weeks. The patient was slightly anemic at
discharge with hemoglobin of 10 g/ dL
A 6-week postpartum Bethesda Assay was negative for an FVIII
inhibitor.

59. Second Delivery
Two years later the patient presented again at 8 weeks of
gestation. Her FVIII activity level was 1 IU/ dL.
at baseline her FVIII inhibitor by Bethesda Assay was negative. Again
prophylaxis with recombinant FVIII concentrate (Recombinate) at a
dose of 40 U/ kg twice weekly was started in the
second trimester. A 72-hour FVIII activity trough level was 7.8
IU/ dL

60. She was admitted for induction of labor at 39 weeks of
gestation. Her physical exam showed no evidence of ecchymoses,
petechiae, purpura, or vaginal bleeding. On laboratory
examination white blood cell count was 7.8
hemoglobin 10.5 g/ dL
platelets 267
PT12.5seconds, and aPTT 39 seconds. Her FVIII activity was 35 IU/ dL
at
22 hours after her last treatment. The same protocol of bolus
recombinant FVIII concentrate and induction of labor utilized
in thefirst delivery was used in the second delivery.

61. The peak
FVIII activity was 105 IU/ dL
and an 8-hour trough level was
63 IU/ dL
and her FVIII activity level was
maintained
between 50 and 100 IU dL
until delivery.
Intravenous morphine, Nubain,
and Phenergan were administered
intravenously for analgesia.

62. A female baby was
delivered after 20 hours of labor. The total blood loss from the
uncomplicated vaginal delivery was 200 mL. There was no
excessive bleeding during cord clamping. She experienced
minimum postpartum bleeding and the patient and daughter
were discharged after 4 days with a hemoglobin of 9.4 g /dL
continuing on Recombinate for 6 weeks postpartum as described
post–first delivery