Overview of Hemophilia: Inherited Bleeding Disorders

2. HEMOPHILIA Dr. Saira Mahmood PGR Pediatrics Department SHZ, RYK

3. Refers to a group of inherited bleeding disorder that results from a deficiency of specific clotting factors. Types:-  Hemophilia A or classic hemophilia(Factor VIII deficiency)  Hemophilia B or Christmas disease(Factor IX deficiency)  Hemophilia C(Factor XI deficiency)

9. Platelets disorder Coagulation disorders Vascular disorders

10. Inherited and Acquired Quantitative and Qualitative

11. •Vitamin c deficency •Hemolytic uremic syndrome •Henoch schonlein purpura Metabolic and inflammatory •Osler rendu weber disease •Ehler danlos syndrome Inherited

12. • Hemophilia • Von willbrand disease • Disorder of fibrinogen Hereditary • Vitamin k deficiency • Liver disease • DIC • Massive transfusion • Heparin or anticoagulant therapy • Renal disease Acquired

13. After injury the initial haemostatic event is formation of platelet plug together with generation of fibrin clot, which prevents further hemorrhage. In hemophilia clot formation is delayed and inadequate, leading to failure of formation of tight cross linked fibrin clot to support the plug. This leads to formation of soft, friable clots.

14.  Occurs in approx. 1:5,000 males • 85% having factor VIII deficiency • 10-15% having factor IX deficiency.  No apparent racial predilection.  X-linked recessive traits.  Reduced level of clotting factor protein.  In 45-50% of patients with severe hemophilia A, internal inversion within the factor VIII gene resulting in no protein production.

16.  Hemostatic level:  factor VIII is >30-40%.  factor IX >25-30%.  The lower limit of levels in normal individuals is approx. 50%.  Mild Hemophilia: Levels >5% , Significant trauma to cause bleeding.  Moderate Hemophilia: Levels 1-5%, mild trauma to cause bleeding.  Severe Hemophilia: < 1% clotting factor activity, bleeding is often spontaneous.

18.  It may present at birth or may occur in the fetus.  2% of neonates with hemophilia sustain ICH.  30% of male infants with hemophilia bleed with circumcision.  Obvious symptoms include Easy Bruising I/M hematomas Hemarthroses Bleeding from minor traumatic lacerations of mouth.    

19. “target” joint.   Bleeding into the iliopsoas muscle,may present as hypovolemic shock, with only a vague area of referred pain in the groin. Prolonged bleeding after dental surgery and trauma

20. It is the hallmark of hemophillic bleed. It can be induced by trauma or may be spontaneous Earliest joint hemorrhage appear in ankle but in older children knee and elbow are commonly involved joints.

23. In infant with severe bleeding manifestation, the differentials include Severe thrombocytopenia  Severe platelet function disorders such as Bernard- Soulier syndrome and Glanzmann thrombasthenia.  Vit. K deficiency

25. o CBC o Bleeding Time o PT o aPTT o Factor Level by factor assay => aPTT value is usually 2-3 times the upper limit of normal. =>in 25 to 30 percent patients who receive factor infusions may develop antibodies.

27. Early psychosocial intervention  Avoidance of aspirin and other NSAIDs  Vaccinations against Hepatitis B  Screening for Hepatitis B, C , HIV and abnormalities in LFTs(for patients exposed to plasma derived products).  Avoidance of voilent contact sports.  Anticipatory guidance and high risk behaviors

28. Early, appropiate therapy is hallmark of excellent hemophilia care. In mild to moderate bleed, factor level should be attained to hemostatic level , in the range of 35 to 50 percent. In severe bleed, factor level should be attained to 100 percent. Calculation of the dose:- Dose of rFVIII(IU)  =% desired(rise in rFVIII)x Body wt(kg) x 0.5 Dose of rFIX (IU)  =% desired(rise in plasma FIX ) x body wt(kg) x 1.4

29.  Each unit of FVIII per kilogram of body weight infused intravenously will raise the plasma FVIII level approximately 2 IU dL. The half-life of FVIII is approximately 8–12 h.  As FFP contains all the coagulation factors, it is used to treat coagulation factor deficiencies. One ml of fresh frozen plasma contains 1 unit of factor activity. It is generally difficult to achieve FVIII levels higher than 30 IU dL with FFP alone  Cryoprecipitate is preferable to FFP for the treatment of hemophilia A and VWD. A bag of cryoprecipitate made from one unit of FFP (200–250 mL) may contain 70–80 units of FVIII in a volume of 30–40 mL.

30. Hemarthrosis 50-60IU/kg factor concentrate on day 1, then 20 IU/kg on next day, consider every alternate day until joint function is normal. Consider Prophylaxis Significant subcutaneous hematoma 50 IU/kg concentrate on day 1 then 20IU/kg on alternate day until resolved Mouth, tooth extraction 20IU/kg concentrate, antifibrinolytic therapy Epistaxis Apply pressure for 15-20 min, antifibrinolytic therapy, 20 IU/kg if treatment fails Major surgery, life threatening hemorrhage 50-75IU/kg factor concentrate then 25IU/kg q8-12hr for 5- 7 days Then 50IU/kg concentrate q24hr for 7 days, monitor factor VIII levels Iliopsoas hemorrhage 50IU/kg concentrate then 25IU/kg q12hr until asymptomatic then 20IU/kg every other day for total of 10- 14 days. Hematuria Bed rest, 1.5 times maintenance fluids, if not controlled in 1-2 days then 20IU/kg concentrate, if not controlled then give prednisone Prophylaxis 20-40IU/kg concentrate every other day to achieve a trough level of >1%

31.  In mild hemophilia A:- patient ‘s endogenously produced factor VIII can be released by the administration of desmopressin acetate.  The dose is 150 µg (1 puff) for children weighing <50 kg and 300 µg (2 puffs) for children and young adults weighing >50 kg

32.  Chronic Arthropathy.  Risk of transfusion-transmitted infectious diseases.  Inhibitor Formation