Hemophilia in pregnancy

Hemophilia during pregnancy

Dr Samra Siddiq Post graduate resident Gyane unit 1 Services

Hospital

Royal Disease “Hemophilia”

Items to be discussed in this talk

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

Items to be discussed in this talk

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

What is Hemophilia?

• HEMO = BLEEDING• PHILIA = LOVE

• Hemophilia = The Love of Bleeding

Genetic disease of blood coagulation

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

• PARAHAEMOPHILIA• ACQUIRED HAEMOPLILIA

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.• Heamophilia C : 1 in 1 million

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.but not in case of haemophilia C.

Clinical presentation

Severity Factor VIII level PresentationMild 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

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 & APTT: 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.• Postpartum management

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.

• Prenatal diagnosis: by CVS.(best method)

• Amniocentesis • Cordocentesis (factor level)• Fetal cells in maternal blood.• Sex determination by USG at 11 week

•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.

• 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.

Fator XI level shows no change in pregnancy although some individuals show gradual declineLevel 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/dlNOTE…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.

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.

•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

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/mVaccines should be given by S/C routeScreening for congenital hip dislocation should be

delayed till factors level availableIf clotting factors level is decreased and delivery was

traumatic baby should be screened for intracranial bleed by USG and CT brain.

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.

First DeliveryUpon presentation, the patient was without any recent

bleeding. Her FVIII activity level was 0.94 IU /dLand her FVIII inhibitor by Bethesda Assay was negative

4 months prior to her pregnancy. She began prophylaxiswith recombinant FVIII concentrate (Recombinate, BaxterBioscience), at a dose of 40 U/kg ,twice weekly starting inher second trimester. At 72 hours her FVIII activity level

was 7 IU/dL. Care was coordinated with the high-riskobstetrical team. There were no bleeding complications

during the pregnancy.

She was admitted to the hospital for induction of labor at39 weeks of gestation. The labor was induced at term to

ensure adequate control of factor levels and minimize therisks of bleeding. During the labor and delivery period, factor

levels were continuously monitored by the laboratory toavoid 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, andFVIII activity of 7 IU/dl.

• 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.

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

blood loss of 150 mL. No excessive bleeding was noted duringcord clamping. Cord blood sample obtained from the babyrevealed FVIII activity of 86 IU/ dLThe patient’spostpartumcourse was uncomplicated and mother and daughter weredischarged after 3 days continuing on Recombinate for6 weeks postpartum.

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

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

She was admitted for induction of labor at 39 weeks ofgestation. Her physical exam showed no evidence of ecchymoses, petechiae, purpura, or vaginal bleeding. On laboratoryexamination white blood cell count was 7.8hemoglobin 10.5 g/ dLplatelets 267PT12.5seconds, and aPTT 39 seconds. Her FVIII activity was 35 IU/ dLat22 hours after her last treatment. The same protocol of bolusrecombinant FVIII concentrate and induction of labor utilizedin thefirst delivery was used in the second delivery.

The peakFVIII activity was 105 IU/ dLand an 8-hour trough level was63 IU/ dLand her FVIII activity level was maintainedbetween 50 and 100 IU dLuntil delivery.Intravenous morphine, Nubain, and Phenergan were administered intravenously for analgesia.

A female baby wasdelivered after 20 hours of labor. The total blood loss from theuncomplicated vaginal delivery was 200 mL. There was noexcessive bleeding during cord clamping. She experiencedminimum postpartum bleeding and the patient and daughterwere discharged after 4 days with a hemoglobin of 9.4 g /dLcontinuing on Recombinate for 6 weeks postpartum as described post–first delivery

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