Hemophilia

Hemophilia during pregnancy

Ahmed Alaa el dinAssistant Lecturer of OB/GYN

Cairo University

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

What is Hemophilia?

• HEMO = BLEEDING• PHILIA = LOVE

• Hemophilia = The Love of Bleeding

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.

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Types

• Hemophilia A 80%– Classic hemophilia – Factor VIII deficiency

• Hemophilia B 20%– Christmas disease – Factor IX deficiency

• Hemophilia C Very rare– Factor XI deficiency

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Incidence

• Hemophilia is quite rare.• Mainly affects males.

• Hemophilia A: 1 in 10,000 live births.• Hemophilia B: 1 in 50,000 live births.

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

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.

Different Cases1. 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.

Different Cases2. 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).

Different Cases3. 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.

Different Cases4. 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.

Different Cases5. 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.

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.

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

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.

Clinical presentation

Severity Factor VIII level PresentationMild 5-30% of normal

(0.05-0.25 IU/ml)-Severe bleeding after major trauma or surgery-Spontaneous bleeding is rare-May be asymptomatic

Moderate 1-5% of normal(0.01-0.05 IU/ml)

-Prolonged bleeding after minor trauma or surgery-Occasional spontaneous bleeding

Severe <1% of normal(<0.01 IU/ml)

-Spontaneous bleeding into joints or muscles, without identifiable hemostatic challenge-May be serious & life threatening

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Investigations

• Platelet count: Normal• Bleeding time: Normal• PT: Normal• Clotting time & PTT: Prolonged• Factor VIII or Factor IX assay: Decreased

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Management

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

Management

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

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.

Management

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

2. Replacement therapy

• Indication:Bleeding or Injury

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

Factor VIII Concentrate

• Factor VIII Concentrate:20 U/kg increases the level by ± 50%.

Clinical Situation Raise factor VIII up toMild bleeding 20-40%

Severe or life threatening bleeding

100%

Management

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

3. Prophylactic therapy

• Indication:Before surgeryAfter exposure to trauma

• Lines:ReplacementOther lines

Management

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

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.

4. Other lines of therapy

• EACA (e –amino caproic acid): - Action: Antifibrinolytic delays clot lysis

-Use: Adjuvant therapy for dental procedures

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

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Hemophilia AND Pregnancy

• Pre-conceptional management.• Antenatal management.• Management during delivery.

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.

Antenatal management

• Prenatal diagnosis: by CVS. • Bleeding: presents according to severity

of factor deficiency.• Desmopressin: Class B (some studies).

• Carriers: show increased levels of both factors VIII and IX.

Management during delivery

• Time: according to obstetric indication.

• Route: according to obstetric indication.

• Reduce risk of bleeding by: avoiding lacerations, minimizing episiotomy use and size, and by maximizing postpartum myometrial contractions and retraction.

Management during delivery

• Newborn: An affected male fetus may develop hematomas with either vaginal or cesarean delivery.

After delivery, the risk of hemorrhage in the neonate increases, especially if circumcision is attempted.

Items to be discussed in this talk

• What is hemophilia?• Types• Incidence• Genetics• Clinical presentation• Investigations• Management• Hemophilia AND pregnancy• Historical facts

Historical Facts

• First reference of hemophilia are mentioned in Jewish texts in the 2nd century AD by Rabbi Simon ben Gamaliel who correctly deduced that sons of a mother -that he did not know at that time- was a hemophilic carrier bled to death after circumcision. Hence he made a ruling that exempted a 3rd newborn Jewish boy of this ritual if 2 previous brothers bled to death from circumcision.

Historical Facts

• In 1800 John Otto wrote a description of the disease where he clearly appreciated the cardinal features: an inherited tendency of males to bleed.

• In 1928 the word Hemophilia was defined.

Historical Facts

• Hemophilia is known as:

“The Royal disease”

Historical Facts Queen Victoria’s pedigree

Spanish House

Russian House

British House

THANK YOU