Basics of Haemophilia: Definition, Prevention, Management

Basics of Hemophilia

1. Basics of Haemophilia Please add your name and affiliation

2. Congenital haemophilia Recessive, X-linked, bleeding disorder 1 Most commonly caused by genetic mutations 1 Factor VIII (FVIII) (haemophilia A) Factor IX (FIX) (haemophilia B) Approximately 1:5000 males are born with congenital haemophilia 1 Spontaneous mutations may occur, resulting in individuals having haemophilia with no prior family history 1 1. Srivastava A et al. Haemophilia 2013;19:e1–47 3 Graph adapted from Srivastava A et al, 2013 1

3. Incidence of different sites of bleeding Haemarthrosis : 70%-80% Muscle/soft tissue: 10%-20% Other major bleeds: 5%-10% Central nervous system (CNS) bleeds: < 5% A. Srivastava et al., WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

4. Joint bleeds Most common manifestation of congenital haemophilia: 70–90 % of all bleeding episodes occur in the joints 1 Shoulder (4%) Elbow (21%) Wrist (2%) Hip (4%) Ankle (42%) Knee (20%) 1. Srivastava A et al. Haemophilia 2013;19:e1–47; 2. Valentino LA et al. Haemophilia 2012;18:310–318; 3. Mejia- Carvajal C et al. Haemophilia 2008;14:119–126; 4. Simpson ML, Valentino LA. Expert Rev Hematol 2012;5:459–468 7

5. Haemophilia: Clinical Classification Cause of bleeding episodes Pattern of bleeding episodes FVIII/FIX activity (% of normal) Classification Spontaneous 24–48 per year <1% Severe Minor trauma 4–6 per year 1%–≤5% Moderate Major trauma Surgery Uncommon >5%–<40% Mild A. Srivastava et al., WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47 Blanchette VS, Key NS, Ljung LR, Manco -Johnson MJ, van Den Berg HM, Srivastava A, J Thromb Haemost 2014; 12:1935–9

6. Congenital haemophilia is transmitted from female carriers Inheritance from a male with congenital haemophilia Inheritance from a female carrier Father X Y Daughter X X Son XY Daughter X X Mother XX Son XY None of the sons will have congenital haemophilia All daughters are carriers Father XY Daughter X X Son X Y Daughter XX Mother X X Son XY Sons have a 50% probability of having congenital haemophilia Daughters have a 50% probability to be carriers Friedman K et al. Wintrobe’s Clinical Hemat 2009;2:1379–1424 4

7. Screening tests for any bleeding disorder Haemophilia: Prolonged aPTT Possible condition PT aPTT BT Platelet count Normal Normal Normal Normal Normal Haemophilia A & B Normal Prolonged Normal Normal vWD Normal Normal or prolonged Normal or prolonged Normal or reduced Platelet defect Normal Normal Normal or prolonged Normal or reduced A. Srivastava et al., WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

8. Factor assay: definitive diagnosis To confirm diagnosis ( Once in life time test provided it is done in a lab with good quality control ) To detect carriers Each coagulation factor must be present in sufficient quantity in order for normal clotting to occur Results are frequently reported as a percentage 50% - 150% : normal A. Srivastava et al., WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

9. Acute bleeds Any sign or symptom PLEASE SUSPECT and TREAT IMMEDIATELY If in doubt, again TREAT IMMEDIATELY Patients usually recognize early symptoms of bleeding even before the manifestation of physical signs This is often described as “aura ” Srivastava et al, WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

10. Joint bleed - definition An unusual sensation ‘aura’ in the joint + Any of the following: (a) increasing swelling or warmth of the skin over the joint; (b) increasing pain (c) progressive loss of range of motion or difficulty in using the limb as compared with baseline. Blanchette VS, Key NS, Ljung LR, Manco -Johnson MJ, van Den Berg HM, Srivastava A, J Thromb Haemost 2014; 12:1935–9

11. Target joint - definition Three or more spontaneous bleeds into a single joint within a consecutive 6-month period. What is NOT a target joint? Blanchette VS, Key NS, Ljung LR, Manco -Johnson MJ, van Den Berg HM, Srivastava A, J Thromb Haemost 2014; 12:1935–9

12. Muscle bleed - Definition Bleeding into a muscle, determined clinically and/or by imaging studies, generally associated with pain and/or swelling and loss of movement over baseline. 13/11/2018 12 Blanchette VS, Key NS, Ljung LR, Manco -Johnson MJ, van Den Berg HM, Srivastava A, J Thromb Haemost 2014; 12:1935–9

13. Acute bleeds Even before developing any sign or symptom If patient with haemophilia describes “aura ” please TREAT IMMEDIATELY Srivastava et al, WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

14. First aid measures: PRICE P rotection (splint), R est, I ce, C ompression, E levation DDAVP in mild – moderate Hemophilia A Timely (within 2 hrs) & adequate clotting factor concentrates critical to outcome Srivastava et al, WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

15. Pain Treating the cause: With clotting factor brings significant pain relief than above agents ASA NSAID Paracetamol /acetaminophen Paracetamol /acetaminophen + Codeine/tramadol Selective COX-2 inhibitor A. Srivastava et al., WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

16. Emergency In severe bleeding episodes that are potentially life-threatening, especially in: Head Neck Chest GI tract Treatment with factor should be initiated immediately, even without any diagnostic assessment Srivastava et al, WFH Guidelines. Guidelines for the management of hemophilia . Haemophilia (2013), 19, e1–e47

17. Haemophilia India : Current scenario * Kar A, Phadnis S, Dharmarajan S & Nakade J. Indian J Med Res 140, July 2014, pp 19-31 $ As per data communicated by Dr Cecil Ross from Hemophilia Federation (India) # World Federation of Hemophilia Report on the annual global survey 2014. Available from URL http://www1.wfh.org/publications/files/pdf-1627.pdf contents last accessed on 10 Dec 2015. Estimated PWH in India: ~75,000 */1.2 billion Diagnosis rate: ~23% Diagnosed PWH: ~17,000 FVIII/IX ~50% FFP/ Cryo ~50% $ PWH – Persons with Hemophilia Under diagnosis: Tip of iceberg has been diagnosed till date Pd – CFC 98% # Recombinant CFC : 2% # Haemophilia India : Challenges Treatment for PWH

18. PWH – Persons with Hemophilia >50% of diagnosed PWH are yet treated with blood products – risk of infection – HIV/HBV/HCV Haemophilia India : Current scenario Haemophilia India : Challenges * Kar A, Phadnis S, Dharmarajan S & Nakade J. Indian J Med Res 140, July 2014, pp 19-31 $ As per data communicated by Dr Cecil Ross from Hemophilia Federation (India) # World Federation of Hemophilia Report on the annual global survey 2014. Available from URL http://www1.wfh.org/publications/files/pdf-1627.pdf contents last accessed on 10 Dec 2015. Estimated PWH in India: ~75,000 */1.2 billion Diagnosis rate: ~23% Diagnosed PWH: ~17,000 FVIII/IX ~50% FFP/ Cryo ~50% $ Pd – CFC 98% # Recombinant CFC : 2% # Treatment for PWH

19. PWH – Persons with Hemophilia Plasma derived CFC - Limited supply / availability due to the source – pooled plasma Haemophilia India : Current scenario Haemophilia India : Challenges * Kar A, Phadnis S, Dharmarajan S & Nakade J. Indian J Med Res 140, July 2014, pp 19-31 $ As per data communicated by Dr Cecil Ross from Hemophilia Federation (India) # World Federation of Hemophilia Report on the annual global survey 2014. Available from URL http://www1.wfh.org/publications/files/pdf-1627.pdf contents last accessed on 10 Dec 2015. Estimated PWH in India: ~75,000 */1.2 billion Diagnosis rate: ~23% Diagnosed PWH: ~17,000 FVIII/IX ~50% FFP/ Cryo ~50% $ Pd – CFC 98% # Recombinant CFC : 2% # Treatment for PWH

20. Disabled (94%) Free from Disability Percentage of PWH with disability PWH (n=148) Kar A, Mirkazemi R, Singh P, Potnis-Lele M, Lohade S, Lalwani A, Saha AS. Disability in Indian patients with haemophilia. Haemophilia. 2007