Summary

Guidelines drafted by The Indian Academy of Paediatrics cover all aspects of haemophilia management with special emphasis on,

• Factor dosage calculation
• Treatment of acute bleeds
• Pain management and prophylaxis

Haemophilia A and B are inherited X-linked recessive bleeding disorders caused by the deficiency of coagulation factor VIII, and IX respectively. Factor VIII or IX deficiency causes defective intrinsic coagulation pathways such as delayed and decreased generation of thrombin, defective formation of clot, and haemorrhagic diathesis. The haemophilia diagnosis and management guidelines drafted by the Indian Academy of Paediatrics (IAP) give holistic and multi-specialty directives consisting of prophylaxis, acute bleed treatment, and measures for complications.

---

When to suspect haemophilia?

A family history of the patient taken before or at the time of the birth is useful in identifying patients at risk of haemophilia. In India however, because neither antenatal or genetic screening are done, affected patients are usually diagnosed when they present with spontaneous, post-traumatic or post-surgical bleeding episodes in their skin, joints, muscles or mucosa.

In infants, bleeding for longer periods following circumsion or muscle hematomas following vaccinations are signs of possible haemophilia. Also, although bleeding can occur anywhere, the most common sites in infants and toddlers are ankles and knees. In older children, bleeding in knees and elbows are more common.

---

How to diagnose Haemophilia?

Common screening investigations carried out initially include:

• platelet count: 150 to 450 x 10³/µL
• prothrombin time (PT): 11 to 15 seconds
• activated partial thromboplastin time (aPTT): 29 to 35 seconds

Normal Prothrombin Time (PT) and platelet count is seen on screening with prolongation of the activated Partial Thromboplastin Time (aPTT). Factor deficiency is indicated when after incubation the correction in prolonged aPTT occurs on mixing the patient’s plasma with normal plasma in 1:1 ratio.

Factor VIII and IX assays need to be done to determine the diagnosis and the severity of deficiency. The factor activity range is 5-40% for mild hemophilia, and 1-5% for moderate hemophilia and less than 1% for severe hemophilia. When the factor activity ranges from normal to borderline, symptoms may start showing in females carriers. Conditions such as von Willebrand disease, factors XI, XII, high molecular weight kininogen and prekallikrein deficiencies are included as the possible differential diagnosis for hemophilia.

To avoid errors in lab results,

• Patients should be advised not to perform strenuous exercise or take drugs such as aspirin prior to the test
• Samples should ideally be collected near a laboratory and stored at 20 to 25ºC and processed within 4 hours of the collection
• Samples should be centrifuged immediately to separate platelet poor plasma and then transport the frozen plasma in dry ice in cases if the transport to the laboratory is expected to take more than 4 hours
• Samples can be stored for 2 weeks at a temperature of –200ºC or for 6 months weeks at a temperature of –700ºC
• Blood should not be collected from the central catheter to avoid contamination with heparin
• Blood and citrate should be present in the ratio of 9:1 if collecting the blood sample in a citrate vial

Testing in pregnancy

Chorionic villous sampling at 11 to 14 weeks of pregnancy is advised to all pregnant females carriers. Family counselling is done if the foetus is found to be affected, and the option for continuing the pregnancy or medical termination is offered.

In 40-45% cases of severe haemophilia A, the most common factor VIII gene mutation is the inversion of intron 22, and in 1-6% of the cases, the most common mutation of the factor VIII gene is the inversion of intron 1. Missense mutation or point mutations are largely seen in cases of Haemophilia B.

---

How to treat haemophilia?

The treatment of haemophilia is mainly concerned with preventing and minimising the long term morbidity by preventing and treating acute bleeding. In cases of acute bleeding, specific treatment should be started immediately. It is better to give the benefit of the doubt and treat a patient if they are having any life-threatening situation even prior to formally doing any investigations.

Treatment of acute bleeds

Initial management of the patient which should be started immediately involves:

1. RICE (Rest, Ice, Compression and Elevation) as soon as the patient recognises a joint bleed. Ice pack should be applied for 20 minutes once every 4 to 6 hours but there should not be direct skin contact.
2. Factor replacement needs to be given at earliest.
3. As soon as the pain and swelling begin to subside, joint movements should be started and gradually increased.
4. A common problem of children affected with haemophilia is epistaxis. Patients with epistaxis must be taught to breathe through their mouths while sitting in an upright position and pinch their nose with their thumb and index finger for 10 to 15 minutes. This act can be done again if the bleeding does not stop. Local anti-fibrinolytics can also be given in these cases.

Calculation of factor dosages

• Factor VIII (IU per dose) = U/dL desired rise (%) × body weight (kg) × 0.5; (1 U/kg factor VIII raises the body level by 2%; factor VIII t1/2 = 8-12 hours)
• Factor IX (IU per dose) = U/dL desired rise (%) × body weight (kg); (1 U/kg of factor IX raises the body level by 1%; factor IX t1/2 = 18-24 hours).

Factor replacement products which are chosen over cryoprecipitate or fresh frozen plasma because of the reduced formation of the inhibitors include plasma-derived factor concentrate and recombinant factor concentrate.

---

Pain management in patients

Pain management is most commonly treated by paracetamol. COX-2 inhibitors or opioids may be required in cases of severe chronic arthropathy.

---

Haemophilia prophylaxis

1. Factor VIII injections are required on a regular basis in cases of severe haemophilia in order to maintain a factor activity of more than 1% as prophylaxis. Even in cases where the minimum factor level is not maintained over 1% all the time, prophylaxis is found to be beneficial.
2. Prophylaxis aims at preventing bleeding and joint destruction, thus preserving normal musculoskeletal functioning.
3. In cases of mild to moderate bleeding, home-based treatment is possible.

---

Vaccination in haemophilia patients

The ideal route of vaccination is subcutaneous (SC) and not intramuscular (IM) or intradermal and also IM vaccines which are routinely given to children for hepatitis A & B, and influenza can be given SC without compromising their efficacy and immunogenicity.

---

Lifestyle modification

1. In order to build a strong musculoskeletal system, proper fitness is required which can involve regular physical activity and non-contact sport activity such as walking, swimming, cycling, yoga, table tennis. Physical activities such as football and hockey which can result in trauma should be avoided by patients.
2. Drugs such as aspirin and NSAIDs that affect the function of platelets should be avoided.
3. Caries in the teeth can result in bleeding of the gums. Therefore, patients should be advised to maintain proper oral hygiene. 
4. Haemophilic patients should be advised to carry an identity card with information about their diagnosis, severity, prophylaxis regimen, inhibitor status and their emergency contact details.
5. The veins of the hemophilic patient should be properly cared for as they can be considered as lifelines.