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



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.



Types

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

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

• Hemophilia C Very rare– Factor XI deficiency



Incidence

• Hemophilia is quite rare.• Mainly affects males.

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



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.



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



Investigations

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



Management

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

Management


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


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


3. Prophylactic therapy

• Indication:Before surgeryAfter exposure to trauma

• Lines:ReplacementOther lines

Management


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.


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

-Use: Adjuvant therapy for dental procedures


• Fibrin Glue: - Action: Contains fibrinogen, thrombin and factor XIII. Placed in the site of injury to stabilize clot.

-Use: Dental procedures and after circumcision



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.



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

Health & Medicine

Hemophilia