Hemophilia is an inherited disease occur in male

Hemophilia is an inherited disease occur in male

1. CASE PRESENTATION Dr.AIJAZ AHMED F.C.P.S Resident Unit- 2

2. HISTORY 8 year old aashiq ali wt 28 kg resident of badin came via opd with the Complain of…… Swelling over the right thigh after fall 1 week

3. HOPC

4. PAST Hx : insignificant DRUG Hx : insignificant TRANSFUSION Hx : 2 pcv + 1 platelate / ffp in badin VACCINATION Hx : unvaccinated child. DEVELOPMENTAL HX : Normal SOCIOECONOMIC : poor

5. FAMILY HX 3 rd issue of consanguinous marriage. 48 yrs 45 yrs 15y 12y 8y 6 y 3y Prolonged bleeding after circumcision in elder brother

6. GPE VITALS H/R : 95 b/m R/R : 20 b/m Temp : a/f O2 sat : 98 % without O2. B.P : 105/73 mmhg ( systolic and diastolic 90 th centile . SUBVITALS: Anemia: + ( mild) Lymph nodes:- Cyanosis: - Dehydration:- Jaundice: - Edema:- Cl : - Sick looking child lying on the bed with gross visible swelling over right ,oriented to time place and person

7. ANTHROPROMETRIC WEIGHT: 28 kg ( 50th centile ) HEIGHT: 124 cm ( 25 th centile )

8. LOCAL EXAMINATION Gross swelling over the right thigh Tenderness + ve pain with movement + ve decreased range of motion + ve Effusion - ve Warmth _ ve Normal movements in left leg Restricted movements in right leg.

9. Systemic Examination ABD CHEST CVS CNS unremarkable

10. Provisional Diagnosis Hemophilia Osteomylitis Rt femoral fracture Malignancy ? osteosarcoama

11. CBC Hb 8.3 MCV 69 MCH 26 MCHC 31 Plt 427 W.B.C 11.2 Neutro 48 Lymphos 29 Esino 04 baso 6 Mono 12

12. BIOCHMISTRY U 10 CR 0.7 NA 135 K 4.1 CL 105 CONTROL TEST PT 11.4 12.1 APTT 26.6 53 INR 0.9-1.3 1.1

13. ULTRASOUND RIGHT THIGH IMPRESSION : a large heterogenus mass lesion with few spaces of calcification seen , possiblity of malignancy should b considered.

14. MRI RIGHT LEG CONCLUSION : keeping in view the history of trauma , imaging findings likely represent post traumatic hematoma formation showing resolving collection with peripheral enhancement suggesting superimposed infection Needs clinical correlation .

15. COAGULATION STUDIES RESULT RANGE VON WILLEBRAND FACTOR ANTIGEN PLASMA 146 % (50-160) RISTOCETIN COFACTOR PLASMA 44 % (40-150) FACTOR V111 PLASMA 4 % ( 50-149)

16. FINAL DIAGNOSIS HEMOPHILIA FACTOR V111 DEFICIENCY

17. MANAGEMENT Admit Pass iv line Send baseline labs Inj ceftriaxone 1 g( dil ) iv x bd ( dil ) Inj traumal 14mg iv x sos Factor V1111 concentrate 50u/kg

18. Hemophilia

19. Introduction Commonest inherited bleeding disorder Bleeding due to deficiency of FVIII / IX / XI coagulant activity Severity of bleeding is related to FVIII / IX /XI concentration in blood

20. INCIDENCE 1 per 5,000 male births 1 per 10,000 population 85 % - F VIII deficiency 10- 15 % - F IX deficiency Haemophilia A: B= 7:1

21. Mode of Inheritance : X- linked recessive Males affected Females carriers

22. Father with Haemophilia: Daughters are carriers Sons normal Mother with haemophilia gene (carrier) Sons 50:50 normal or affected Daughters 50:50 normal or carriers INHERITANCE

23. FEMALES AFFECTED ONLY WHEN : TURNERS SYNDROME MOSAICISM/LYONISATION MOTHER TO DAUGHTER TRANSMISSION (POSSIBLE THEORETICALLY BUT EXTREMLY RARE)

24. Types: Haemophilia A – deficiency of Factor VIII Haemophilia B – deficiency of Factor IX Haemophilia C – deficiency of Factor XI

25. Severity of Haemophilia Severity Factor level iu /dl (%) Type of presentation Severe < 1 Spontaneous bleeds, Severe bleeding Moderate 1-5 Few bleeds, Haemathrosis - traumatic Mild 5-30 Few bleeds, Post-traumatic Post-dental surgery

26. Pathophysiology: tissue injury platelet plug delayed ( HaemophiliaA&B ) fibrin clot prolonged bleeding

27. CLINICAL FEATURES – SUBTLE Bleeding as a baby rare Prolonged bleed from umbilical cord Muscle hematoma during immunisation Bleeding during circumcision

28. CLINICAL FEATURES – SUBTLE Toddlers - Large and prolonged bleed to trivial injury/cuts/abrasions Lip bleeds (hematomas) First bleeding in childhood Tooth extraction Trauma with walking G um bleeds while brushing teeth

29. CLINICAL FEATURES - FRANK HEMARTHROSIS ( joint bleed) – hallmark of hemophilia Joints affected: in toddlers - ankle (most common) – earliest jt involved due to lack of stability as they assume upright posture Older child – knee, elbow (most common) ** Target joint – recurrent bleeding at a same joint LL > UL

30. Bleeding in Haemophilia Acute Haemarthrosis Chronic haemophilic arthropathy Bleeding into muscles Haemophilic pseudo tumour - cysts Haematuria Gastrointestinal bleeding Intracranial bleeding

31. Bleeding in Haemophilia BLEEDING IN CARRIERS Reduced FVIII (IX) levels Mild bleeding tendency Childbirth

32. C/F OF ACUTE HAEMARTHROSIS Abnormal sensation Pain and swelling of joint Limitation of movement - especially flexion Tenderness and heat in the joint Acute symptoms last 3-4 days; full recovery takes weeks

33. Complications : Pain Anaemia (proportionate to bleeding) Constitutional disturbances: fever < 24 hrs anorexia, malaise Chronic arthritis Pressure effects of large haematomas Transfusion acquired infections Inhibitors

34. Lab findings: Hb low – proportional to blood loss Platelets- normal Bleeding time -normal PT normal APTT prolonged > 2-3 times ULN CT prolonged Low levels of F VIII / IX Factor VIII and IX assay : mixing studies Genetic analysis

35. MIXING STUDIES To determine if prolonged PT or PTT is due to a factor deficiency or an inhibitor Normal plasma : all Clotting factors-V,VIII, IX,X,XI,XII Method: add patient plasma to equal volume of normal plasma and repeat PT & PTT Correction of PT & PTT – suggests- deficiency of clotting factors Assays for factors

36. MIXING STUDIES Remains prolonged after mixing study: indicates inhibitor - most common is lupus anticoagulant - therapeutic anticoagulant - rarely ,inhibitors to factors VIII, IX, XI

37. Inhibitors: Antibodies against factors  blocks clotting activity 14-25 % patients who receive factors (VIII/ IX) Failure of a bleeding episode to respond to appropriate replacement therapy  1 st sign of inhibitor Others develop higher titres  desensitisation- higher doses of factors given

38. RADIOLOGICAL INVESTIGATIONS Radiographs of joints USG joints for effusions MRI joints/ abdomen CT head

39. MANAGEMENT - PRINICIPLES Control bleeding episodes – replacement therapy Prophylaxis and prevention Life style modifications Treatment of complications Rehabilitation Antenatal diagnosis and counselling Team effort : pediatrician, hematologist, orthopedician, physiotherapist, dentist

40. REPLACEMENT THERAPY Fresh whole blood FFP Cryoprecipitate Factor concentrates Recombinant factor VIII FIX

41. FFP AND CRYOPPT FFP contains F VIII and IX CRYOPPT contains F-VIII, fibrinogen, VWF 1 unit FFP = 200 units factor VIII/IX 1 unit cryoppt = 100 units factor VIII FVIII 1u/kg Increase plasma factor VIII by 2% ( 2 iu/dl) - t ½ = 8 hrs FIX 1u/kg Increase plasma factor IX by 1% (1iu/dl) - t ½ = 18-20 hrs Risk of HIV, HBV, HCV, CMV transmission

42. FACTOR CONCENTRATES Prothrombin complex concentrates (PCC) - Contain F IX & Vitamin K dependent factors I.e. II, VII, IX, X – high cost Pure factor IX concentrates available Currently high cost

43. THERAPY FOR HAEMOPHILIA FACTOR RECOVERY AFTER I.V. INFUSION Factor VIII 100% Factor IX 30-50% Raise factor levels to: 100 U/dl – life threatening bleeds 35- 40 U/dl – other bleeds

44. Dose of F VIII (U): desired rise in plasma F VIII (U/dl) X body wt (kg) X 0.5 Dose of F IX (U): desired rise in plasma F IX (U/dl) X body wt (kg) X 1.4 DOSAGE CALCULATION

45. Other measures: General supportive measures: bed rest hospitalize for severe bleeds analgesics Local haemostasis Immobilisation Physiotherapy

46. HEMARTHOSIS MANAGEMENT 25 U F-VIII/kg q12h Prompt rx : prevent early sequalae Check APTT Joint immobilisation - 48hrs Early ambulation and physio NSAIDS : Aspirin, indomethacin – with caution- may induce GI bleed Paracetamol, pethidine, diazepam – can be used Home infusions : train for early administration

47. PROPHYLAXIS Mild/moderate hemophilia 10-20 units/kg 2-3 times/week Can have normal life and participate in sports

48. PREVENTION Immunisation : SC not IM Avoid IM injections- apply pressure 5 minutes Avoid contact sports

49. Orthopaedic care- traction, splinting, reconstructive surgery Regular dental exam and hygiene Prophylactic immunization- hep B Counselling P REVENTION

50. DRUGS EACA - aminocaproic acid Tranexemic acid : 25mg/kg/day Desmopressin acetate : increases levels for first 2 days from body stores Danazol Fibrin glue : tooth extraction

51. ANTENATAL DIAGNOSIS 18-20 weeks Male fetuses Fetal blood : Amniotic fluid fibroblasts : DNA probe Chorionic villous sampling : PCR

52. PROPHYLACTIC THERAPY Initiated with the 1 st bleed Home - self or patient infused Small dose FVIII (FIX) 2-3 X /week (  20%-30%) Prevents bleeds Prevents long term sequelae THERAPY FOR SURGERY/ DENTISTRY Prophylactic Enables major procedures - 10 days cover