bleedingdisordersinchildren2021-210709092146 (1) (1).pptx

HEMOPHILIA, VON WILLEBRAND , ITP, VIT K DEF

1. Bleeding Disorders in Children Pathophysiology, Etiology, Clinical Features, Management Hemophilia, von Willebrand disease, ITP, VKDD, DR SUMERA AKRAM FCPS Pediatrics, CHPE, MRCPCH 1a SR DEPARTMENT OF PEDIATRIC MEDICINE SMC

2. Bleeding Disorders Pathophysiology

3. How is Hemostasis achieved ? Mechanisms to stop bleeding Vessel wall (vasoconstriction) Platelets (plug formation) Coagulation proteins (fibrin clot formation) Mechanisms to stop coagulation process Anti- coagulant proteins (Protein C, Protein S, Antithrombin III) Fibrinolytic system (Plasminogen)

4. Coagulation Factors I=Fibrinogen II= Prothrombin V= Labile factor,Proaccelerin ( para hemophilia) VII= Stable factor/ Proconvertin (HEMOPHILIA A) VIII= Antihemophilic factor(HEMOPHILIA B) IX= Christmas factor X= Stuart- prower factor( hemophila C) XI= Plasma thromboplastin antecedent XII= Hageman factor XIII= Fibrin stablizing factor

5. K K Vitamin K is an essential factor to a hepatic gamma- glutamyl carboxylase that adds a carboxyl group to glutamic acid residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z. The main role of protein Z appears to be the degradation of factor Xa . This is done by protein Z- related protease inhibitor (ZPI), but the reaction is accelerated 1000- fold by the presence of protein Z K K K Platelets Vascular Cells K Advances in Vascular Medicine 8 September 2014, Article ID 542034, 4 pages http://dx.doi.org/10.1155/2014/542034 and wikipedia.org/coagulation

6. Bleeding Disorders Etiology

7. Causes of Abnormal Bleeding

8. Causes of Abnormal Bleeding Vascular defects Vessel wall defects - - HSP vasculitis Extra - Vascular (supporting tissue) defects - - Hereditary Collagen disorders - - Collagen atrophy Corticosteroids adverse effects Old age (senile purpura) - - Scurvy (Vit C deficiency)

9. Causes of Abnormal Bleeding Platelets defects – Decreased Platelets Thrombocytopenia - - Production decreased - Aplastic anemia, Acute Leukemia, Folic acid and B12 deficiency) - - Consumption increased - (DIC, HUS) - - Destruction increased – - - ITP (Idiopathic Thrombocytopenic Purpura) - - SLE Platelet Function Defects - - Bernard Soulier syndrome - - Glanzmann Thromboasthenia - - Uremia

10. Causes of Abnormal Bleeding Coagulation abnormalities Intrinsic Pathway - - Hemophilia - - von Willebrand disease Extrinsic Pathway - - Factor VII deficiency (very rare) Intrinsic + Extrinsic Pathway - - Liver disease - - Vitamin K deficiency

11. Bleeding Disorders Clinical Features

12. Bleeding Disorders - Clinical Features Trauma / Injury bleeds – bruises, prolonged bleeding Skin bleeds – Petechiae, Purpura Mucosal bleeds – Epistaxis, Oral bleeds Tissue bleeds – Muscle bleeds, Joint bleeds (Hemarthrosis) Life- threatening bleeds – Intracranial hemorrhage

13. Bleeding Disorders – Assessment Patient History History Age of onset Duration of bleeding Site of bleeding Severity of bleeds Obvious cause of bleeds – Trauma, Spontaneous Past History – bleeding after circumcision Family History of Bleeding disorder – parents, siblings, uncles , males, males + females

14. Bleeding Disorders – Assessment Examination Examination Local injury examination Skin Nose, Oral cavity, Throat Lymph nodes Liver, Spleen Complications of Bleeds Pallor - Anemia Vitals – Pulse, Respiration, Blood Pressure, SaO2

15. Bleeding Disorders – Diagnosis

16. Bleeding Disorders Investigations

17. Bleeding Disorders – Investigations Initial investigations – CBC, Platelet Count, Blood peripheral film PT – Prothrombin Time (Extrinsic pathway) APTT – Activated Partial Thromboplastin Time (Intrinsic pathway)

18. Bleeding Disorders – Investigations Subsequent investigations – as needed Bleeding time – prolonged in Vascular or Platelet defects Platelet aggregation tests – Platelet function tests Mixing studies – normal plasma, adsorbed plasma, aged serum Coagulation Factor levels

19. Case Scenario

20. Case Scenario A 5 years old boy is brought to the ER with swollen and painful right ankle after a minor fall. There is history of prolonged bleeding after circumcision in the child. Minor injuries often result in bruises On exam, he is looks pale. Right ankle is swollen and tender. What investigations should be performed ? What is the most likely diagnosis ?

21. Case Scenario His investigations Hb 7.6 gm/dl, TLC 5,600, Platelets 2,24000 PT = 14 sec (N = 10 – 13 s) APTT = 88 sec (N = 30 – 35 s) Factor VIII level = 8 % of normal

22. Hemophilia Epidemiology, Etiology, Pathophysiology Clinical Features, Management

23. Hemophilia – Epidemiology and Etiology

24. Hemophilia – Clinical Presentation Subcutaneous bleeds (bruises) after minor trauma Bleeding after circumcision (30 % of patients) Prolonged bleeding after minor injuries Bleeding in Joints (Hemarthrosis) Bleeding in Muscles (Hematoma)

25. Hemophilia – Lab Investigations

26. Hemophilia – Classification

27. Hemophilia – Management Prevention Avoid Trauma – household, roadside, sports Avoid Aspirin and NSAIDs Prophylactic factor transfusion: Keep Factor VIII level more than 40 % Factor VIII concentrates ( lyophylised ) given by IV dose on alternate days

28. Hemophilia – Management Manage Active Bleeds Raise and keep Factor VIII level at 40 – 100 % for 3 – 7 days Desmopressin – Releases Factor VIII from endothelium Tranexamic acid – Inhibits Fibrinolytic system FFP (Fresh Frozen Plasma) – provides Factor VIII Cryoprecipitate – concentrated Factor VIII from plasma Factor VIII concentrates (recombinant) – 250 units / vial

29. VWD Von Willebrand Disease Epidemiology, Etiology, Pathophysiology Clinical Features, Management

30. Von Willebrand Disease – Epidemiology and Etiology Most common inherited bleeding disorder Seen in males and females equally Autosomal Dominant

31. Pathophysiology of von Willebrand disease: Von Willebrand Factor synthesized in WPB bodies of endothelial cells and megakaryocytes. Binds to receptors (gP-1b) on platelets . Primary hemostasis: normal vWF Multimers bind with platelet glycoprotein 1b on one side and sub endothelial collagen on other side – stable plug formation. SECONDARY HEMOSTASIS: Vwf Aslo binds to VIII and prevent its destruction. Deficiency of Von Willebrand Factor results in: Impaired Platelet adhesion Low blood levels of Factor VIII

32. CLASSIFICATION OF vWD

33. Von Willebrand Disease Clinical Presentation

34. Von Willebrand Disease – Lab Investigations CBC – shows severity of blood loss . Normal platelets except in type 2B PT – Prothrombin Time – Normal APTT – Activated Partial Thromboplastin Time – Prolonged especially in type 3, normal in type 1 Bleeding time – prolonged Platelet aggregation study- no response to Ristocetin ( like BSS) Von Willebrand Factor Antigen assay (vWF:Ag) – low Von Willebrand Factor multimer analysis for dx of type 2 subtypes

35. Von Willebrand Disease – Management Active Bleeds Prevention: Avoid Trauma – household, roadside, sports Avoid Aspirin and NSAIDs Treatment: Desmopressin ( analogue of ADH ) – Releases von Willebrand Factor from storage sites- IV , SC, Nasal spray Tranexamic acid – Inhibits Fibrinolytic system FFP (Fresh Frozen Plasma) – provides von Willebrand Factor Von Willebrand Factor concentrates

36. ITP Idiopathic Thrombocytopenic Purpura Epidemiology, Etiology, Pathophysiology Clinical Features, Management

37. ITP (Idiopathic Thrombocytopenic Purpura) Epidemiology and Etiology Seen in Children – 1: 20,000 Onset is often acute Pathophysiology: Immune mediated destruction of Platelets Usually occurs as a Post – viral illness , inflammation, autoimmune- antibodies bind to platelets and make them prone to destruction by macrophages andRES spleen- also suppresuve effect of these antibodies on magakaryocytes in BM- increades destruction and decreseard production.

38. Characteristics of ITP: Isloated thrombocytopenia( platelets count < 100x109/L , often < 20x 109 / L) A healthy child with no concerning features on history and ex Normal CBC and peripheral film ex ( except low platelets) Remember: alternate diagnosis if – severe pallor, jaundice, hepatosplenomegaly and lymphadenopathy , bone pains, anorexia, wt loss, fever, rash, arthritis, mouth ulcers, family history, liver, spleen , lymph nodes.

39. ITP (Idiopathic Thrombocytopenic Purpura) Clinical Presentation usually preceded by 3weeks with viral infection , sometimes post vaccination ITP (Idiopathic Thrombocytopenic Purpura) usually presents with p etechiae and bruising on skin - mild75-80% Epistaxis and gum Bleeding -moderate 15-20% Prolonged epistaxis. Gut bleed, muscle or joint – severe 3-5% Life threatening bleed like intracranial< 1%

40. ITP (Idiopathic Thrombocytopenic Purpura) Lab Investigations CBC – Thrombocytopenia Platelet Count 20,000 – 40,000 Peripheral smear: manual platelet count and platelet morphology ( large platelets in BSS) AND rule out abnormal cells. PT /APTT – Normal Bleeding time – prolonged Work up to rule out secondary ITP: IMMUNOLOGIC( RA, ANA, anti DsDNA, complement levels) Viral serology( hep B, C, HIV , CMV, EBV) Bone Marrow Exam – Megakaryocytes increased and to rule out other diagnosis

41. ITP (Idiopathic Thrombocytopenic Purpura) Differential Diagnosis Acute Leukemia : sick , pancytopenia hepatosplenomegaly and lymphadenopathy APLASTIC ANEMIA: low platelets may be the initial manifestation of aplastic anemia preceded by pancytopenia B12 and Folate def Hemolytic uremic syndrome: diarrhea, low HB%, fragmented cells in smear, deranged RFT TTP: rare in children Platelet function disorder: Bernard soulier syndrome SLE (Systemic Lupus Erythematosus) Post – Viral Infection Thrombocytopenia Drugs (adverse effect) – Sulphonamides, Carbamazepine Congenital Hypoplastic Anemia ( TAR Fanconi Anemia)

42. CLINICAL CLASSIFICATION AND NATURAL HISTROY OF ITP

43. Management flow chart for acute and chronic ITP

44. Vitamin K deficiency disorders Epidemiology, Etiology, Pathophysiology Clinical Features, Management

45. Vitamin K deficiency disorders Epidemiology and Etiology Seen in newborns or infancy Deficiency of Vitamin K is in the diet or due to Malabsorption Deficiency of Vitamin K impairs production of Coagulation Factors II, VII, IX, X Onset is often acute Usually presents with Purpura (spontaneous skin bleeds)

46. Vitamin K deficiency disorders Etiology Exclusive breastfeeding Liver disease Biliary atresia Severe malnutrition Malabsorption (Fat soluble Vitamin) Prolonged Antibiotic use

47. Vitamin K deficiency disorders Clinical Presentation Purpura (skin bleeds) Mucosal bleeds (oral cavity) Hematemesis (blood in vomit) Melena (blood in stool) Hematuria (blood in urine) Umbilical bleeding Intracranial hemorrhage

48. Vitamin K deficiency disorders Lab Investigations CBC – Anemia due to bleeding Platelet Count = Normal PT – Prothrombin Time – Prolonged APTT – Activated Partial Thromboplastin Time – Prolonged

49. Vitamin K deficiency disorders Management Vitamin K IV dose (NO IM doses) Fresh frozen plasma (to provide preformed coagulation factors) Packed RBC transfusion (to correct anemia)

50. Vitamin K deficiency disorders Prevention VITAMIN K at BIRTH to every Newborn 1 mg IM at day 1 OR 1 mg ORAL at day 1, 7, 28 of life DOSES of Vitamin K Exclusive breast feeding (monthly) Malabsorption (monthly) Liver disease (weekly) Cholestasis (weekly)

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