Dr. Festus Njuguna Moi University/MTRH HAEMOPHILIA: What we know, future perspectives and the Kenyan Situation. Dr. Festus Njuguna Moi University/MTRH

INTRODUCTION Genetic X-linked disorder Haemophilia A and B Affects 1 per 10,000 deliveries 30% of cases due to new mutations Haemophilia A more common

Range of Factor VIII or IX Activity High levels found in pregnancy Normal range of FVIII & IX ~1/3 of carriers have levels in low or below normal range Level above which bleeding after injury is unlikely Mild hemophilia Moderate hemophilia Severe hemophilia

INTRODUCTION Joint bleeds ( knee, ankle) is the commonest presentation Also causes muscle bleeds, intracranial bleeding, GIT bleeding

Bleeding episodes 70-80% of bleeding episodes are into joints Acute Pain, swelling, interference with normal activities Chronic Synovial hypertrophy and synovitis leading to hemophilic arthropathy, disability Common bleeding sites: Knees 45% Elbow 30% Ankle 15% Shoulder 3% Wrist Hip 2% Other Bleeding Complications in Hemophilia Joint bleeding or hemarthrosis is common in hemophilia and may result in significant long term disability. Approximately 60% of all bleeding episodes in patients with severe hemophilia occur in joints; most commonly involved joints include the knees (more than 50% of these episodes), followed by the elbows, ankles, shoulders, and wrists. The acute symptoms of these bleeding episodes include pain, swelling, and an inability to participate in normal activities. Recurrent hemarthroses lead to chronic inflammation of the joint lining or synovium, called synovitis, followed by synovial hypertrophy, subsequent arthropathy, and disability. Arun B, Kessler CM. Clinical manifestations and therapy of the hemophilias. In: Colman RW, Hirsh J, Marder VJ, Clowes AW, George JN, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000:815-824. Arun B, Kessler CM. In: Colman et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. 2000:815-824. World Federation of Hemophilia (WFH). Guidelines for the Management of Hemophilia 2005. http://www.ehc.eu/fileadmin/dokumente/Gudelines_Mng_Hemophilia.pdf.

LABORATORY EVALUATION Prolonged APTT Mixing studies Factor assays Inhibitor testing

TREATMENT Replace missing factor Whole blood, FFP, cryoprecipitate, factor concentrates( plasma derived, recombinant) RICE( Rest, Ice, compression, Elevation) Physiotherapy Desmopressin ( Factor VIII only)

Factor Replacement On demand therapy Prophylaxis: Maintain factor level above 1% Requires infusion 2-3 times a week at a dose of about 20-40IU/Kg Prophylaxis for Surgery and invasive procedures

INHIBITORS Occur more commonly in Factor VIII deficiency High and low titer levels Immune tolerance may be used Treatment is by use of passing agents: Activated Prothrombin Complex concentrate of Recombinant Activated Factor VII

NEW TREATMENT STRATEGIES Increased half life of the products: PEGylation, Fc or albumin fusion( IX extended 3-6 times while VIII extended to 1.5 times Agents that use alternative mechanisms to activate coagulation( emicuzumab)

New strategies Gene Therapy: Studies ongoing for last 10 years Changes severe to a mild phenotype More successful with factor IX than VIII

KENYAN PERSPECTIVES We expect to have at least 4,000 people with the condition in Kenya Access to diagnosis and care quite limited About 400 patients currently identified. Government not buying factor concentrates. There is ability to confirm diagnosis at KNH, MTRH and some private Laboratories

KENYAN PERSPECTIVES Kenya Haemophilia Association(KHA) is a Patient/Parent/ Health workers association Objectives: Advocacy, awareness creation Improving access through training health care providers, facilitating acquisition of diagnostic equipment

Kenyan perspectives Most of the factor we have is from Donations mainly from WFH. We have extended half life products Treatment available in KNH, MTRH, Coast Provincial hospital, Muranga County Hospital, Upcoming clinic in Kisii county Hospital

Conclusion Replacement of deficient clotting factor is the mainstay of therapy. There are emerging therapies that will reduce need for frequent factor infusions We still have huge gaps in the care of People living with Haemophilia in our country.