Dr K K Kaul
Haemophilia is the most commonly known haemorrhagic (bleeding) disorder and belongs to inherited disorders of coagulation. It is usually x-linked recessive disease, but in some rare conditions, it has been found to be acquired.
Prevalence of Haemophilia A&B – in 2019 it was observed that there are around 1,125,000 males that have bleeding disorders and it was also revealed that in every 100,000 males there are 17.1 with haemophilia A & 3.8 with haemophilia B. In 2021 review found 12.8 per 100,000 males for haemophilia A. In India there is no epidemiological data about haemophilia but it is expected that around 100,000 to 1, 30,000 server haemophilia cases are in our country but the total number registered with Haemophilia Federation of India (HFI) is only around 19,000 (ICMR 2019/2023). As per one report there are 3 Lac cases in our country (ndtv.com/india-news). Lack of awareness, lack of diagnostic facilities and high cost of tests are some of the factors for under diagnosis of the bleeding disorders in our country. In our J&K UT total number of registered cases of haemophilia and other clotting factor disorders are 562 (403 cases in Kashmir and 159 cases in Jammu) and the good news is that treatment is available at both the centres i.e GMC Jammu as well as GMC Srinagar.
Sites of serious bleeds: Joints (hemarthrosis), Muscles especially deep compartment (iliopsous, calf, forearm) Mucous membranes in the mouth, gums, nose and genitourinary tract. Joints commonly involved are ankles, knees and elbows. Shoulders, wrists and hips are involved less. Life threatening bleeds: intracranial, neek/throat and gastrointestinal bleeds. These patients must get medical attention immediately (Medical emergency). Frequency of bleeding- Hemarthrosis 70% – 80%, muscle 10% – 20%, other major bleeds 5% to 10% & CNS <5%. Many patients have repeated bleeding in a particular joint and this is called Target joint. Bleeding in the joints if not treated on time and effectively result in severe damage to the joint and disability. Synovitis followed by, cartilage destruction, arthritis and stiffened joints. In later stages complete loss of cartilage and the bone destruction ultimately deforms the joint permanently and even change the shape of the joint.
Aura- this is often described as a tingling sensation and the patient gets the indication that bleeding in the joint is imminent. This is the best time to infuse factors to prevent the bleeding in the joint hence some time home therapy under proper guidance is allowed.
The Royal Disease – Queen Victoria was a carrier of haemophilia B. She passed the mutated gene to 3 of her children. Her two daughters became carriers and her son prince Leopold, had haemophilia. Later the children married many royals across Europe and Russia. Haemophilia B was spread among royals for many generations with royals being either a carrier or haemophilic.
Management- (1) First aid measures for bleeding muscles and joints – PRICE therapy (Protection- Splint, Rest, ICE application, Compression- Crepe bandages, and elevation of the affected part). (2) Appropriate Factor replacement therapy should be given. Recombinant FVIII or FIX is better than plasma derived factors. In limited resource centres plasma derived factors (with safety guidelines during manufacturing as per recommendations) can be used. Extended half life factors are also available and can be given. The factor treatment is either on demand (during bleeding episode) or prophylactic. Regular Prophylactic treatment with factors should be encouraged than on demand therapy. In centres where factors are not available then FFP or Cryoprecipitate should be provided but there is a serious threat of transmission of HIV, HCV, HBV and other dangerous infections and hence should be avoided. Since 2017 Emicizumab which is a humanized bispecific monoclonal antibody (that mimics FVIII co-factor activity in tenase complex and activating FX) is used in the treatment of haemophilia A with or without inhibitors as a prophylactic medicine once a month subcutaneously. It maintains haemostatic activity at 10% – 20%, it cannot be used to treat acute bleeding. In break through bleeds during emicizumab prophylaxis rFVIIa is preferred to aPCC. Many patients who are on emicizumab prophylaxis are doing very well.
Shortly Haemostatic Rebalancing Drugs- will be available in the market. Fitusiran (RNAi) that lowers the level of antithrombin and increasing the thrombin generation in haemophilia A&B patients. Desmopressin is used in mild cases and anti-fibrinolytics are also used. Fibrin sealants are available for topical application on wounds.
Pain Management- Paracetmol/ acetaminophen with or without codeine or tramadol, OR Cox-2 inhibitors (Celecoxib, Meloxicam, Nimesulide) or morphine- under medical supervision. Cox-2 inhibitors should be used with caution in patients with hypertension and renal dysfunction. DO not take Asprin and other NSADS.
Pillars of support – Physiotherapy, Occupational therapy, psychological therapy and haemophilia social worker. This support is necessary to these patients to prevent musculoskeletal complications, disability and keeps the persons in good physical and mental health as well as make the person independent and also the number of bleeds are also decreased. Moving towards Cure – Gene therapy for haemophilia is a curative treatment modality. FDA on November 22, 2022 approved gene therapy for haemophilia B patients in USA. It is given as a single dose by IV infusion. The gene is expressed in the liver to produce FIX protein. Currently gene therapy for haemophilia A is in advance stage of investigation & it is possible that in near future this will be available for the patients.
Costly affair – the treatment of haemophilia is a costly affair. Factor replacement therapy products, by passing agents, Emicizumab & gene therapy are very costly. In India average cost of factor replacement therapy per patient varies from Rs. 1, 95,000 to Rs. 5, 52,000. Emicizumab 30mg injection vial cost Rs. 49971/- and 60mg vial costs Rs. 87,000/-. Gene therapy for haemophilia B at present costs in USA around US $ 3.5 million (Rs. 28.52 Crore).
Miles to go before (we) sleep – although factor replacement therapy and Emicizumab is available but every patient cannot afford it and therefore Govt. is providing these factors at various treatment centres in India.
In J&K UT the Govt. is providing both FVIII, FIX, by passing agents as well as emicizumab to all the registered haemophilic patients and this has improved their physical and mental health and also quality of life significantly. Patients on emicizumab prophylaxsis are saying they have forgotten that they are having haemophilia A as they are attending school regularly, participate in social and religious gatherings and are now independent. Everyone is grateful to the Government for providing all the facility in GMC Jammu and GMC Srinagar. Since we are entering in the era of permanent cure for this lifelong disorder as gene therapy will also be available in our country in near furture. But a big issue initially shall remain a permanent cure on one hand and unaffordable cost on the other and hence miles to go before (we) sleep. HHCN – Haemophilia and Health collective of North India (HHCN) has been constituted recently with an objective to reach a consensus on uniform policy and protocols for optimal Haemophilia care in our Country.
(The author is former Professor and Head Pathology GMC Jammu, Medical Advisor of J&K Thalassaemina & Welfare Society)
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