Children with Bleeding Problems Presentation.pptx

Children with Bleeding Disorder

1. Children with Bleeding Problems

2. Case Scenario 1 4-year-old girl was brought to ETD by her mother C/O new onset of large bruises on her legs No H/O Trauma Further history: Had URTI several weeks prior. No family history of bleeding disorders. On examination : Alert, not in apparent distress, development appropriate for age Noted large bruises over her legs. No mucosal bleeds. Other systemic examinations were unremarkable. 2

3. Initial lab investigations Parameters Results Normal range Hb 11.5 g/dL 10.5-13.5 Hct 34.0% 33.0-39.0 TWC 6.5x10^9/L 6.0-17.5 Platelets 26x10^9/L 150-400 PT 11.5 s 10.0-12.8 APTT 25.0 s 24.4-33.2 PBF Thrombocytopenia with large platelets, otherwise RBCs and white cells are normal 3

4. Differential Diagnosis Dengue Infection Acute Leukemia Immune Thrombocytopenia Sepsis with DIVC Congenital amegakaryocytic Thrombocytopenia Congenital Thrombotic Thrombocytopenic Purpura I don’t know la…. Ask MO 4

5. What is the most appropriate treatment for this child’s thrombocytopenia? Bone marrow aspiration & biopsy Prednisolone 2mg/kg/day Reassurance, TCA daycare in a week and re-check FBC IV Immunoglobulin 1g/kg for one dose Anti-RhD immune globulin 25 mcg/kg/day for two days 5

6. Case Scenario 2 2-year-old boy, brought to the Emergency Department by his mother for oozing blood from his mouth following a fall 6 hours ago. His mother related that he tended to bleed for prolonged periods from his immunisation sites, but there was no history of bruising or hematoma. There was no known family history of a bleeding disorder. Physical examination: Alert , not in apparent distress Mouth : two small lacerations on the inside of the lower lips, oozing blood Remainder of examinations are unremarkable, notably no petechiae, bruises or joint swellings. 6

7. Initial lab investigations Parameters Results Normal range Hb 12.3 g/dL 10.5-13.5 Hct 35.4% 33.0-39.0 TWC 7.9 x 10^9/L 6.0-17.5 Platelets 368 x 10^9/L 150-400 PT 11.3 s 10.0-12.8 APTT 37.2 s 24.4-33.2 7

8. What are the possible differential diagnoses? Von Willebrand disease Immune thrombocytopenic purpura Hemophilia A, B Thalassemia Lab / Sampling Error What further investigations would you like to do ? Repeat Coagulation Profile Peripheral blood smear Blood Culture Factor level Hb Analysis 8

9. Content Brief overview of hemostasis Immune thrombocytopenic purpura Hemophilia 9

10. Physiology of Hemostasis Hemostasis = prevention of blood loss. When a vessel is severed / ruptured, bleeding is stop through : 1. Vascular spasm 2. Formation of platelet plug 3. Formation of blood clot as a result of blood coagulation 4. Eventual growth of fibrous tissue to close the rupture permanently 10

11. How is a blood clot formed? 11

12. Content Brief overview of hemostasis Immune thrombocytopenic purpura Hemophilia 12

13. Content Brief overview of hemostasis Immune thrombocytopenic purpura Introduction Pathogenesis Clinical manifestations Diagnosis & investigations Management Hemophilia 13

14. IMMUNE THROMBOCYTOPENIC PURPURA 14

15. What is immune thrombocytopenic purpura (ITP)? Acute childhood ITP is a benign self-limiting disorder, presenting with isolated thrombocytopenia (<100x10^9 /L), in the absence of an underlying cause . 5% acute ITP → Recurrence of acute ITP 10% acute ITP → Chronic ITP 15

16. IWG (International Working Group) Proposal on Classification of ITP 16 Phases of disease Newly diagnosed ITP Within 3 months from diagnosis Persistent ITP Between 3-12 months from diagnosis. Includes patients not reaching spontaneous remission or not maintaining complete response off therapy Chronic ITP Lasting for more than 12 months Severe ITP Presence of bleeding symptoms at presentation sufficient to mandate treatment, or occurrence of new bleeding symptoms requiring additional therapeutic intervention with a different platelet-enhancing agent or an increased dose.

17. Why does ITP happen? ITP is an autoimmune disorder characterised by autoantibody mediated immunological destruction of normal platelets (mainly occurring in the spleen), in response to an unknown stimulus. 17

18. Clinical manifestations Onset: usually abrupt / acute Duration from onset of thrombocytopenia to normalisation of platelets: a few days to 6 months (average of 3 weeks) Majority gives a history of viral infection 2-4 weeks prior Spectrum of bleeding: mild to life-threatening Cutaneous bleeds (petechiae) → mucosal bleeds (gum bleeds, epistaxis, gross hematuria) → life-threatening bleeds (intracranial hemorrhage) 18

19. Diagnosis & Investigations Diagnosis is based on history, physical examination, blood counts, PBF Physical examination: no hepatosplenomegaly / lymphadenopathy Blood counts: isolated thrombocytopenia, with normal Hb and TWC PBF: normal apart from reduced, larger platelets, no abnormal cells Other tests may be indicated if there’s an atypical presentation 19

20. Examples of abnormalities that might indicate an alternate diagnosis rather than an ITP are: Fever / bone / joint pain Family history of low platelets / easy bruisings Risk factors of HIV Skeletal or soft-tissue morphologic abnormalities Non-petechial rash Lympadenopathy Abnormal Hb, WBC count or morphology not typical of ITP 20

21. Management Most children remit spontaneously . Not all children with acute ITP require hospitalisation Consider hospitalisation in: Severe life-threatening bleeding (e.g. ICH) regardless of platelet counts Plt < 20 x 10^9/L + evidence of bleeding Plt < 20 x 10^9/L without bleeding but inaccessible to health care Observation & monitoring of platelet count, without specific treatment, is appropriate for patients with: Plt > 20 x 10^9/L without bleeding Plt > 30 x 10^9/L with only cutaneous purpura Repeat FBC within the first 7-10 days to ensure there’s no evidence of evolving marrow disorder 21

22. Treatment is generally indicated if there is: Life-threatening bleeding episodes (e.g. ICH) regardless of platelet count Plt < 20 x 10^9/L with mucosal bleeding Plt < 10 x 10^9/L with any bleeding Choice of treatment includes: Oral Prednisolone 2mg/kg/day for 14 days then taper off over 5 days (regardless of response) Oral Prednisolone 4 mg/kg/day for 3-4 days IV Immunoglobulin (IVIG) 0.8g/kg/dose for a single dose 22

23. Intracranial hemorrhage ICH is the most feared complication of ITP 0.1-0.5% The risk is highest with platelet count <20 x 10^9/L, history of head trauma, aspirin use, and presence of cerebral arteriovenous malformation 50% ICH occur after 1 month of presentation 30% ICH occur after 6 months of presentation Early treatment with steroid / IVIG does not prevent late onset ICH 23

24. Emergency treatment Indications: severe bleeding, i.e. severe epistaxis / GI bleeding causing drop in Hb or ICH Treatment options: IV Methylprednisolone 30mg/kg/day for 3 days IVIG 0.8g-1g/kg as a single dose IV Methyprednisolone + IVIG in life-threatening conditions Platelet transfusion in life-threatening hemorrhage KIV emergency splenectomy if other modalities fail KIV neurosurgical intervention in ICH 24

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26. Chronic ITP Definition : Persistent thrombocytopenia after 6 months of onset (20% of cases) Clinical manifestation : wide spectrum ranging from mild asymptomatic low platelet counts → intermittent relapsing symptomatic thrombocytopenia → persistent symptomatic & hemorrhagic disease (rare) Management: Counselling Asymptomatic: observation and precaution during physical activity Symptomatic: short courses of treatments (as for acute ITP) Revisit diagnosis to exclude other causes of thrombocytopenia 2nd line therapies: Steroid pulses (oral Dexamethasone 1mg/kg on 4 consecutive days every 4 weeks for 4 months) Intermittent anti-Rh (D) Ig treatment for Rh D positive (45-50 ug/kg) - may cause drop in Hb levels 26

27. Splenectomy Rarely indicated Indication: life-threatening bleeding event Severe lifestyle restriction with no or transient success with intermittent IVIG, pulsed steroids or anti-D immunoglobulin Pre-splenectomy: immunize against pneumococcus, hemophilus & meningococcus Post-splenectomy: lifelong penicillin prophylaxis (oral / IM) + pneumococcal booster every 5 years Up to 70% of patients may achieve complete remission post-splenectomy 27

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29. Content Brief overview of hemostasis Immune thrombocytopenic purpura Hemophilia 29

30. Content Brief overview of hemostasis Immune thrombocytopenic purpura Hemophilia Introduction Pathogenesis Clinical manifestations Diagnosis & investigations Management 30

31. HEMOPHILIA 31

32. What is hemophilia? It’s a group of blood disorders in which there’s a defect in the clotting mechanism Most common hemophilias: Hemophilia A (Factor VIII deficiency) - 85% Hemophilia B (Factor IX deficiency) - 15% X-linked recessive 32

33. Clinical Manifestation Bleeding in the neonatal period is unusual Usually presents with easy bruising when crawling & walking (9-12 months) Hemarthrosis is characteristic of hemophilia: affects large joints (knee, ankle, elbow), swollen, painful joints Epistaxis, gum bleeding, hematuria, intracranial hemorrhages Bleeding may be spontaneous / post-trauma, operation or dental procedures 33

34. Diagnostic investigations FBC Coagulation profile: PT, APTT Specific factor assay: FVIII level (low in Hemophilia A) Specific factor assay: FIX level (low in Hemophilia B) Bleeding time if applicable Von Willebrand screen even if APTT normal 34

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36. Classification of hemophilia 36 Factor level Classification Clinical presentation <1% Severe Spontaneous bleeding, risk of intracranial hemorrhage 1-5% Moderate Bleeding may only occur with trauma, surgery or dental procedures 5-25% Mild

37. Further investigations Hepatitis B surface antigen, anti-HBS antibody Hepatitis C antibody HIV serology RP, LFT Platelet aggregation if high suspicion of platelet defect Diagnosis of carrier status for genetic counselling Mother of newly diagnosed son with hemophilia Female siblings of boys with hemophilia Daughter of a man with hemophilia 37

38. Treatment Definitive treatment: Factor replacement The dose of factor replacement depends on the type and severity of bleed Dose of factor required can also be calculated using the formulas below: Units of Factor VIII: (% rise required) x (weight in kg) x 0.5 Units of Factor IX: (% rise required) x (weight in kg) x 1.4 38 Type of bleed Factor VIII dose Factor XI dose Hemarthrosis 20 U/kg 40 U/kg Soft tissue or muscle bleeds 30-40 U/kg 60-80 U/kg Intracranial hemorrhage / surgery 50 U/kg 100 U/kg

39. The percentage of factor aimed for depends on the type of bleed: For hemarthrosis, aim 30-40% level For soft tissue or muscle bleed, aim 40-50% level For ICH / patients going for surgery, aim 100% level Factor VIII is given every 8-12 hours; Factor IX is given every 12-24 hours Duration of treatment depends on the type of bleed: Hemarthrosis 2-3 days Soft tissue bleeds 4-5 days Intracranial bleeds / surgery 7-10 days 39

40. Complications Joint destruction Recurrent hemarthroses into the same joint → osteoarthritis → deformity Acquisition of viruses Hepatitis B, C, HIV Inhibitors These are antibodies directed against the exogenous factor VIII or IX neutralizing the clotting activity 40

41. Supportive treatment Analgesia Use PCM +/- opioids Avoid IM Do not use aspirin / NSAIDs as they will affect platelet function Dental care Ensure good dental hygiene - dental caries are a regular source of bleeding Dental clearance with factor replacement will be required in some severe cases Immunisation Preferably S/C route Give under factor cover if hematomas are a problem ** All hemophiliacs should be registered with Hemophilia Society and have a medic-alert bracelet / chain and carry a book in which the diagnosis, classification of severity, types of bleeds and admissions are recorded 41

42. Specific guideline management Intracranial hemorrhage Give factor replacement before suspected bleed is confirmed by CT scan Hemophilia A: aim to increase Factor VIII level to 100% Hemophilia B: aim to increase Factor IX level to 80% if monoclonal factor IX is used or 50% if prothrombin complex concentrate (PCC) is used Urgent CT scan: If CT scan confirms ICH, maintain factor level 80-100% for Day 1-7, and 50% for Day 8-21. If CT scan shows no evidence of ICH, admit 1 day for observation Follow up CT scan after 2 weeks Lab investigations: Pre-treatment: factor assay level and inhibitor level. Post-treatment: factor assay level (½ hour after infusion) to ensure required factor level is achieved (if the level is not achieved, consider development of inhibitors). Then repeat in 3-5 days to ensure adequate levels have been achieved and no inhibitor has developed. 42

43. 2. Surgery Pre-op investigations: Coagulation profile (PT, APTT) Pre-factor assay level and inhibitor level Blood grouping, full antibody screening and full cross matching if required Calculate dose for transfusion Infuse patient with appropriate factors ½ hour prior op Preferable levels: 80-100% factor VIII 70% monoclonal factor IX 505 if prothrombin complex concentrate (PCC) used Post-transfusion: check specific factor level ½ hour post-transfusion or after surgery to ensure correct factor level is achieved Clotting factor level should be maintained above 50% during op and 24 hours after surgery Maintain adequate factor levels: Days 1-3: 60-80% Days 4-7: 40-60% Days 8-14: 30-50% Repeat factor assay and check inhibitor level on Day 3 to ensure adequate levels. Post-op minimum 10-14 days replacement therapy is recommended. 43

44. 3. Iliopsoas bleed Symptoms: pain / discomfort in the lower abdomen / upper thigh Signs: hip flexed, internally rotated, unable to extend Danger: hypovolemia Management: Factor replacement: 50U/kg stat, followed by 25U/kg BD till asymptomatic, then 20U/kg every other day for 10-14 days USG / CT scan to diagnose Physiotherapy: when pain subsides Repeat USG to assess progress 44

45. 4. Hematuria Management: Bed rest Hydration (1.5 x maintenance) Monitor for first 24 hours: UFEME, urine C&S If bleeding persists for >24 hours, start factor concentrate infusion Perform KUB & USG of the kidneys **DO NOT give anti-fibrinolytic drugs (tranexamic acid) because this may cause formation of clots in the tubules which may not recanalize 45

46. 5. Hemarthroses (joint hemorrhages) Most spontaneous hemarthroses respond to a single infusion of factor concentrate. Aim for a level of 30-40%. If swelling / spasm is present, treatment to a level of 50% is required. Infusion may have to be repeated at 12-24 hours interval until pain subsides Minor hemarthroses may not require immobilisation, elastic bandage or slings. Ice may help in pain relief. Severe hemarthroses: Splint in position of comfort Rest Early physiotherapy 46

47. Back to our scenarios 47

48. Case Scenario 1 A 4-year-old girl was brought to the Emergency Department by her mother with a complaint of new onset of large bruises on her legs. The mother could not recall any recent falls or bumps that would have caused the bruises. Further history noted the child experienced flu-like symptoms several weeks prior. There was no family history of bleeding disorders. On examination: General: Alert, not in apparent distress, development appropriate for age Noted large bruises over her legs. Otherwise no mucosal bleeds. Other systemic examinations were unremarkable. 48

49. Initial lab investigations Parameters Results Normal range Hb 11.5 g/dL 10.5-13.5 Hct 34.0% 33.0-39.0 TWC 6.5x10^9/L 6.0-17.5 Platelets 26x10^9/L 150-400 PT 11.5 s 10.0-12.8 APTT 25.0 s 24.4-33.2 PBF Thrombocytopenia with large platelets, otherwise RBCs and white cells are normal 49

50. What is the most appropriate treatment for this child’s thrombocytopenia? Bone marrow aspiration & biopsy Prednisolone 2mg/kg/day Reassurance, TCA daycare in a week and re-check FBC IV Immunoglobulin 1g/kg for one dose Anti-RhD immune globulin 25 mcg/kg/day for two days 50