Hemophilia and ITP

for pediatrics UG teaching

1. HEMOPHILIA & ITP Dr M.Sanjeevappa M.D.( Paeds ) Asst.Professor , Dept. of Paediatrics Govt.Medical College Ananthapuramu .

2. HISTORY OF HEMOPHILIA Best known of the hereditary bleeding disorders since 2nd century AD. First coined by Schonlein in 1820s. Originally termed “HAEMORRAPHILIA” i.e. love for haemorrhages but over time contracted to HEMOPHILIA. Hemophilia is often called the DISEASE OF KINGS .

3. PATHOPHYSIOLOGY Activated factor IX complexes with factor VIIIa , calcium, and phosphatidylserine on physiologic membranes to generate factor Xa , which subsequently participates in formation of the prothrombinase complex. Thrombin is crucial for platelet aggregation, fibrin generation, clot retraction, and activation of factor XIII. T he propagation phase of coagulation is impaired, and clot formation is delayed and is not robust and is often friable.

4. DEMOGRAPHICS Incidence : approximately 1 in 5000 males. HEMOPHILIA A : 80% to 85% HEMOPHILIA B : 10% to 15% No racial predilection

5. INHERITANCE OF HEMOPHILIA

6. CLASSIFICATION One IU of factor VIII = amount of factor found in 1 ml of normal plasma. Normal F VIII activity = 50-150% (> 30%). Severe - < 1% Modrate - 1% to 5% Mild - > 5%

7. CLINICAL MANIFESTATIONS Severity F VIII activity Clinical manifestations Severe <1% Spontaneous hemorrhage from early infancy Post circumcision bleeding Frequent spontaneous hemarthrosis Moderate 1-5 % Hemorrhage sec to trauma or surgery Post circumcision bleeding . Occasional spontaneous hemarthrosis Mild > 5% Hemorrhage sec to trauma or surgery Rare spontaneous bleeding

8. CLINICAL MANIFESTATIONS History of Hemorrhage : Post circumcision bleeding Epistaxis Oral mucosal hemorrhage , hemoptysis Prolonged bleeding after minor trauma/surgery Prolonged bleeding after tooth extraction Spontaneous bleeding in joint

9. MUSCULOSKELETAL BLEEDING The hallmark of hemophilia is deep bleeding into joints and muscles. Hemarthrosis – target joint. Intramuscular hemorrhage .

10. LIFE-THREATENING HEMORRHAGES central nervous system (CNS) bleeding. bleeding into and around the airway.

11. LABORATORY EVALUATION Hb / Hct Normal / low PT Normal aPTT Prolonged Platelets Normal B.T Normal C.T Prolonged Factor VIII levels Decreased Inhibitor levels : Low titer 0-10 Bethesda U High titer > 10 Bethesda U

12. IMAGING STUDIES FOR ACUTE BLEEDS Ultrasonography MRI CT Scan

13. MANAGEMENT Prevention of trauma Avoid high-impact contact sports and other activities with a significant risk of trauma Avoid Aspirin/NSAIDs No I.M injections. Short nails Immunization (given S/C) Factor VIII replacement Fresh blood, Cryo -PPT, FFPs (if needed)

14. MANAGEMENT FFPs. Cryoprecipitates . 1ml FFP = 0.7 unit factor VIII. FFP : 10-20 ml / kg will increase factor level 20 - 30 % 1 bag Cryoprecipitates = 75 unit factor VIII

15. MANAGEMENT REPLACEMENT THERAPY : HEMOPHILIA - A ‘‘ Factor VIII” replacement 1unit factor VIII → raises 2 % activity of factor level. Factor VIII concentrates 1 vial=250 units Dose : desired factor level % x Wt(kg) x 0.5 -For life threatening bleeding 80-100% factor level -For mild-moderate bleeding 40 % factor level

16. MANAGEMENT REPLACEMENT THERAPY : HEMOPHILIA - B ‘‘ Factor IX” replacement 1unit factor IX → raises 1% activity of factor level Dose : desired factor level% x Wt(kg) x 1.2 - For life threatening bleeding 80-100% factor level - For mild-moderate bleeding 40 % factor level

17. MANAGEMENT DESMOPRESSIN : synthetic vasopressin analogue The dose of intranasal desmopressin is 150 μg (1 puff) for persons weighing less than 50 kg and 300 μg (1 puff in each nostril ) for persons weighing more than 50 kg . ANTIFIBRINOLYTIC THERAPY: Aminocaproic acid The oral dose of aminocaproic acid is 100 to 200 mg/kg initially(maximum dose, 10 g), followed by 50 to 100 mg/kg per dose every 6 hours (maximum dose, 5 g). Tranexamic acid : The dose of tranexamic acid is 25 mg/kg every 6 to 8 hours.

18. IDIOPATHIC (AUTOIMMUNE) THROMBOCYTOPENIC PURPURA(ITP)

19. ITP The most common cause of acute onset of thrombocytopenia in an otherwise well child. Estimated about 1 in 20,000 children. A recent history of viral illness is described in 50-65 % of cases of childhood ITP. The peak age is 1-4 yr . ITP seems to occur more often in late winter and spring

20. PATHOPHYSIOLOGY An autoantibody directed against the platelet surface develops with resultant sudden onset of thrombocytopenia. After binding of the antibody to the platelet surface , circulating antibody-coated platelets are recognized by the Fc receptor on splenic macrophages , ingested, and destroyed.

21. TRIGGERING FACTORS Most common viruses have been described in association with ITP, including Epstein-Barr virus. Helicobacter pylori infection. rarely following the MMR vaccine.

22. CLINICAL MANIFESTATIONS The classic presentation of ITP is a previously healthy 1-4 yr old child who has sudden onset of generalized petechiae and purpura with profound thrombocytopenia (platelet count <10 × 109/L). B leeding from the gums and mucous membranes may be seen. Findings on physical examination are normal, other than the finding of petechiae and purpura

23. CLASSIFICATION of ITP Depending on the basis of symptoms and signs, but not platelet count . Class 1: No symptomes . Class 2: Mild symptoms: – Bruising and petechiae – Occasional minor epistaxis – Very little interference with daily living.

24. CLASSIFICATION of ITP Class 3: Moderate: – More severe skin and mucosal lesions – More troublesome epistaxis and menorrhagia . Class 4: Severe: – Bleeding episodes— menorrhagia , epistaxis , melena — requiring transfusion or hospitalization - Symptoms interfering seriously with the quality of life

25. PROGNOSIS Severe bleeding is rare (<3% of cases ). In 70-80% of children who present with acute ITP , spontaneous resolution occurs within 6months. Fewer than 1% of patients develop an intracranial hemorrhage . 20 % of children who present with acute ITP go on to have chronic ITP

26. LABORATORY FINDINGS Severe thrombocytopenia ( plateletcount <20,000/ cmm ). platelet size is normal or increased . Hb ,TC ,DC should be normal . Bone marrow examination shows normal granulocytic and erythrocytic series, with characteristically normal or increased numbers of megakaryocytes . A direct antiglobulin test (Coombs) should be done 1.to rule out Evans syndrome (autoimmune hemolytic anemia and thrombocytopenia) 2 . Before instituting therapy with IV anti-D.

27. DIFFERENTIAL DIAGNOSIS Autoimmune thrombocytopenia may be an initial manifestation of : 1 . SLE 2 . HIV infection 3 . Common variable immunodeficiency 4. Lymphoma(rarely)

28. TREATMENT Platelet transfusion in ITP is contraindicated unless life-threatening bleeding is present. No therapy other than education and counseling of the family and patient for patients with minimal, mild, and moderate symptoms. Intravenous immunoglobulin (IVIG ): IVIG at a dose of 0.8- 1.0 g/kg/day for 1-2 days induces a rapid rise in platelet count(usually > 20,000/ cmm ) in 95% of patients within 48 hr. IVIG induce a response by downregulating Fc -mediated phagocytosis of antibody-coated platelets.

29. TREATMENT Intravenous anti-D therapy: - For Rh positive patients. - IV anti-D at a dose of 50-75 μg /kg causes a rise in platelet count to > 20,000/ cmm in 80-90 % of patients within48-72 hr . Prednisone : - Doses of prednisone of 1-4 mg/kg/24 hr and continued for 2 - 3 wk or until a rise in platelet count to > 20,000/ cmm has been achieved .

30. TREATMENT S plenectomy in ITP should be reserved for 1 of the following circumstances. 1. The older child (≥4 yr) with severe ITP that has lasted >1 yr (chronic ITP) 2. Life-threatening hemorrhage (ICH) complicates acute ITP 3. Platelet count cannot be corrected rapidly with transfusion of platelets and administration of IVIG and corticosteroids

31. THANK YOU