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Children with Bleeding Problems Presentation.pptx
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- 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 ParametersResults Normal range Hb 11.5g/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 A. DengueInfection B. Acute Leukemia C. Immune Thrombocytopenia D. Sepsis with DIVC E. Congenital amegakaryocytic Thrombocytopenia F. Congenital Thrombotic Thrombocytopenic Purpura G. I don’t know la…. Ask MO 4
- 5. What is themost appropriate treatment for this child’s thrombocytopenia? A. Bone marrow aspiration & biopsy B. Prednisolone 2mg/kg/day C. Reassurance, TCA daycare in a week and re-check FBC D. IV Immunoglobulin 1g/kg for one dose E. 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 ParametersResults 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. 1. What arethe possible differential diagnoses? I. Von Willebrand disease II. Immune thrombocytopenic purpura III. Hemophilia A, B IV. Thalassemia V. Lab / Sampling Error 2. What further investigations would you like to do? B. Repeat Coagulation Profile C. Peripheral blood smear D. Blood Culture E. Factor level F. Hb Analysis 8
- 9. Content ● Brief overviewof 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
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- 12. Content ● Brief overviewof hemostasis ● Immune thrombocytopenic purpura ● Hemophilia 12
- 13. Content ● Brief overviewof hemostasis ● Immune thrombocytopenic purpura ○ Introduction ○ Pathogenesis ○ Clinical manifestations ○ Diagnosis & investigations ○ Management ● Hemophilia 13
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- 15. What is immunethrombocytopenic 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. Why does ITPhappen? 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
- 17. 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
- 18. 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
- 19. Examples of abnormalitiesthat 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
- 20. Management ● Most childrenremit 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
- 21. ● Treatment isgenerally 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
- 22. Intracranial hemorrhage ● ICHis 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
- 23. Emergency treatment Indications: severebleeding, 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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- 25. Chronic ITP Definition: Persistentthrombocytopenia 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
- 26. 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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- 28. Content ● Brief overviewof hemostasis ● Immune thrombocytopenic purpura ● Hemophilia 29
- 29. Content ● Brief overviewof hemostasis ● Immune thrombocytopenic purpura ● Hemophilia ○ Introduction ○ Pathogenesis ○ Clinical manifestations ○ Diagnosis & investigations ○ Management 30
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- 31. What is hemophilia? ● It’sa 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
- 32. Clinical Manifestation ● Bleedingin 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
- 33. 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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- 35. Classification of hemophilia 36 Factorlevel 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
- 36. Further investigations ● HepatitisB 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
- 37. 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
- 38. ● The percentageof 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
- 39. Complications 1. Joint destruction -Recurrent hemarthroses into the same joint → osteoarthritis → deformity 1. Acquisition of viruses - Hepatitis B, C, HIV 1. Inhibitors - These are antibodies directed against the exogenous factor VIII or IX neutralizing the clotting activity 40
- 40. Supportive treatment 1. Analgesia a.Use PCM +/- opioids b. Avoid IM c. Do not use aspirin / NSAIDs as they will affect platelet function 2. Dental care a. Ensure good dental hygiene - dental caries are a regular source of bleeding b. Dental clearance with factor replacement will be required in some severe cases 3. Immunisation a. Preferably S/C route b. 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
- 41. Back to ourscenarios 47
- 42. Case Scenario 1 A4-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
- 43. Initial lab investigations ParametersResults Normal range Hb 11.5g/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
- 44. What is themost appropriate treatment for this child’s thrombocytopenia? A. Bone marrow aspiration & biopsy B. Prednisolone 2mg/kg/day C. Reassurance, TCA daycare in a week and re-check FBC D. IV Immunoglobulin 1g/kg for one dose E. Anti-RhD immune globulin 25 mcg/kg/day for two days 50
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- 46. Case Scenario 2 A2-year-old boy was 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: General: alert, not in apparent distress, development appropriate for age 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. 52
- 47. Initial lab investigations ParametersResults 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 53
- 48. 1. What arethe possible differential diagnoses? I. Von Willebrand disease II. Immune thrombocytopenic purpura III. Hemophilia A, B IV. Thalassemia A. I, II B. I, III C. II, III, IV D. All the above 1. What further investigations would you like to do? 54
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- 50. References: ● Paediatric Protocol,ch. 73-74 ● CPG Management of ITP, https://www.moh.gov.my/moh/attachments/3911.pdf 56
Editor's Notes
- #2 Questions: 6 months cut-off point for ITP (doesn’t correlate with the IWG classification of ITP)
- #16 Brief introduction
- #18 Pathogenesis
- #19 How does ITP look like?
- #21 Fever / bone / joint pain → Leukemia Family history of low platelets / easy bruisings → Hereditary Macrothrombocytiopenia Risk factors of HIV → HIV infection Skeletal or soft-tissue morphologic abnormalities → collagen disorders Non-petechial rash → Meningococcemia / NAI Lympadenopathy → lymphoproliferative disorders Abnormal Hb, WBC count or morphology not typical of ITP → other blood disorders
- #23 *Treatment do not resolve the condition faster, but can temporarily raise the platelet count much quicker compared to no treatment. There is no evidence that these treatment reduce bleeding complications / mortality / influence progression to chronic ITP
- #25 Platelet transfusion 8-12 units/m2 BSA (2-3 folds more than usual units) as the platelets will be consumed by the hemorrhage to form blood clots and will reduce further circulating platelets
- #28 Rarely indicated in children as spontaneous remissions may still occur up to 15 years from diagnosis Risk of dying from ITP is 0.002%. But post-splenectomy sepsis is 1.4-2.7%
- #33 Though it’ X-linked recessive, 30% of the cases have no family history - they are spontaneous new mutations Another rare form of Hemophilia: Hemophilia C - Factor 11 deficiency (1 in 100,000) In comparison, hemophilia A affects about 12 in 100,000 men and hemophilia B affects about 4 in 100,000 men (Source: Clevelandclinic.org)
- #35 In hemophilia, the APTT is prolonged in moderate and severe hemophilia but may not show prolongation in mild hemophilia. The platelet count and PT time are normal. When APTT is prolonged, the lab will proceed with F8 antigen level. If this is normal, then they will proceed with F9 level.
- #37 Once the factor assay levels are measured, hemophilia is classified. (in other words, the severity of hemophilia is determined by the level of factors)
- #38 Once a child is diagnosed with hemophillia, check the viral status at diagnosis and then yearly. This is because treatment (definitive treatment for hemophillia is factor 8 / 9 concentrate transfusion) carries the risk of acquiring viruses. All hemophiliacs should be immunized against Hepatitis B.
- #41 This can be prevented by prompt and adequate factor replacement Hence immunisation and regular screening is recommended Overall incidence: Hemophilia A 15-25%, Hemophilia B 1-3%. Can develop at any age, but usually 10-20 exposure days. This is suspected when there’s a lack of response to replacement therapy despite high doses. Treatment requires ‘bypassing’ the deficient clotting factors via i) Recombinant activated Factor VII (rfVIIa or Novoseven) and ii) FEIBA (factor eight inhibitor bypass activity). Consultation with hematologists is required.
- #42 Usually there will be rapid pain relief in hemarthroses once missing factor concentrate is infused
- #45 *hypovolemia because large volumes of bloods may be lost in the retroperitoneal space
- #51 Answer: C
- #55 Answer: B Further investigations: To confirm the diagnosis: Specific assays (F8, F9) To rule out other differentials: VWF screening To check for complications or as baseline: biohazard screening (Hep B, Hep C, HIV), RP, LFT Others: carrier screening