Bleeding disorder

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Bleeding disorder

  1. 1. Approach to a bleeding disorder, Approach to thrombocytopenia,Idiopathic thrombocytopenia (ITP) Dr. Kalpana Malla MD Pediatrics Manipal Teaching HospitalDownload more documents and slide shows on The Medical Post [ www.themedicalpost.net ]
  2. 2. HEMOSTASIS1. VASCULAR PHASE2. PLATELET PHASE3. COAGULATION PHASE4. FIBRINOLYTIC PHASE
  3. 3. VASCULAR PHASE WHEN A BLOOD VESSEL IS DAMAGED - VASOCONSTRICTION
  4. 4. PLATELET PHASE PLATELETS ADHERE TO THE DAMAGED SURFACE AND FORM A TEMPORARY PLUG
  5. 5. COAGULATION PHASE THROUGH TWO SEPARATE PATHWAYS THERE IS CONVERSION OF FIBRINOGEN TO FIBRIN
  6. 6. FIBRINOLYTIC PHASE ANTICLOTTING MECHANISMS ARE ACTIVATED TO ALLOW CLOT DISINTEGRATION AND REPAIR OF THE DAMAGED VESSEL
  7. 7. HEMOSTASISDEPENDENT UPON: Vessel Wall Integrity Adequate Numbers of Platelets Proper Functioning Platelets Adequate Levels of Clotting Factors Proper Function of Fibrinolytic Pathway
  8. 8. Coagulation cascadeIntrinsic system (surface contact) Extrinsic system (tissue damage) XII XIIa Tissue factor XI XIa IX IXa VIIa VII VIII VIIIa X Xa V Va II IIa (Thrombin) Fibrinogen Fibrin Vitamin K dependant factors
  9. 9. LABORATORY EVALUATION• Platelet Count• Bleeding Time (BT)• Prothrombin Time (PT)• Partial Thromboplastin Time (PTT)• Thrombin Time (TT)
  10. 10. Laboratory Evaluation of the Coagulation PathwaysPartial thromboplastin time(PTT) Prothrombin time(PT) Intrinsic pathway Extrinsic pathway Thrombin time Common pathway Fibrin clot
  11. 11. Laboratory Evaluation of the Coagulation Pathways• PT prolonged in extrinsic and common pathway• APTT prolonged in intrinsic and common pathway• PT &APTT – prolonged in common pathway ,liver dysfunction ,DIC• DIC – thrombin time is also prolonged• Factor XIII deficiency – platelet ,APTT,PT,BT- Normal
  12. 12. Diagnostic Approach• Increased BT –a) Platelet decreased – ITPb) Platelet normal – anaphylactoid purpura• Increased CT –a) only PT prolonged – Factor VII deficiencyb) only APTT prolonged – factor – VIII,IX,XI,XII and von willebrand’s disease
  13. 13. Diagnostic Approachc) Both PT & APTT prolonged –vit –k deficiency, severe liver ds, cong deficiency of factor V, X.fibrinogen deficiency ,DIC
  14. 14. PLATELET COUNT NORMAL 100,000 - 400,000 CELLS/MM3 < 100,000 Thrombocytopenia 50,000 - 100,000 Mild Thrombocytopenia < 50,000 Sev Thrombocytopenia
  15. 15. BLEEDING TIME PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTIONNORMAL VALUE 2-8 MINUTES
  16. 16. PROTHROMBIN TIMEMeasures Effectiveness of the Extrinsic PathwayMnemonic - PETNORMAL VALUE 10-15 SECS
  17. 17. PARTIAL THROMBOPLASTIN TIME Measures Effectiveness of the Intrinsic PathwayMnemonic - PITT NORMAL VALUE 25-40 SECS
  18. 18. THROMBIN TIME Time for Thrombin To Convert Fibrinogen Fibrin A Measure of Fibrinolytic PathwayNORMAL VALUE 9-13 SECS
  19. 19. So What Causes Bleeding Disorders?VESSEL DEFECTS ?PLATELET DISORDERSFACTOR DEFICIENCIESOTHER DISORDERS ?
  20. 20. VESSEL DEFECTSVascular purpuras• Infection – meningococcal meningitis, hge measles, typhoid• Drugs – aspirin ,indomethacin, phenytoin , quinine• Anaphylactoid purpura – Henoch-schonlein P• Metabolic – uremia, scurvy
  21. 21. PLATELET DISORDERSThrombocytopenia
  22. 22. FACTOR DEFICIENCIES• Hereditary• Hemophilia – factor VIII deficiency• Christmas ds – factor IX deficiency• Von-Willebrand’s ds• Acquired• Vit – k deficiency• Oral anticoagulant therapy• Liver ds
  23. 23. THRMBOCYTOPENIA- CONGENITAL - TAR syndrome - Fanconi’s anemia - Wiskott Aldrich syndrome- Acquired -Aplastic anemia - BM replacement
  24. 24. DECREASED PRODUCTION:- A) IMMUNE THROMBOCYTOPENIC PURPURA(ITP) B) INFECTIONS - EBV - HIV - HBV - RUBELLA - PARVO-B19 - CMV - TB,TYPHOID
  25. 25. C .Drug induced - NSAID, ATT, AED, QUININE, SULFA,PENICILLIN, FRUSEMIDE, HEPARIN,D . Autoimmune Disorders -SLE, hyperthyroidismE . Malignancy - ALL, AML, Lymphoma, Neuroblastoma
  26. 26. Others- DIC- Microangiopathic Hemolytic Anemia- HUS-Liver disease- Neonatal thrombocytopenia – toxoplasmosis, CMV, herpessimplex, ITP
  27. 27. IDIOPATHIC / IMMUNETHROMBOCYTOPENIC PURPURA DEFINITION : is characterised by -Thrmbocytopenia < 100.000/cm - Shortened PLT. survival -Presence of antiplatelet AB in the plasma. -Increased Megakaryocytes in BM
  28. 28. BACKGROUND Most common causes of symptomatic thrombocytopenia in children. Incidence - 3 and 8 cases per 100,000 children/yr Before a diagnosis of ITP – R/O other common causes of thrombocytopenia(concurrent infection , autoimmune disorders , malignancy , bone marrow failure .. )
  29. 29. CLASSIFICATION1.Acute ITP (children)- PLT returns to normal value before 6mth.2.Chronic ITP (adults) - PLT remains low after 6mth also3.Secondary ITP (follow other diseases4.RECCURRENT:-PLT count decreases after becoming normal
  30. 30. ETIOLOGYUsually benign transient immune-mediated thrombocytolytic conditionAutoantibodies (usually IgG) directed against platelet membrane antigens (especially glycoprotein complex IIb/IIIa) are presentThrombocytopenia results from phagocytosis of antibody-coated platelets by the reticuloendothelial system
  31. 31. ROLE OF SPLEEN1.Auto-antibody production2.Platelet destruction3.Platelet storage
  32. 32. CLINICAL PRESENTATION2- 10 years (peak 2 to 5 years )Patients < 2 years or > 10 years at presentation are atypicalNo seasonal variationHistory of a preceding infection (1-4 wks back), in 50 to 85 % of pediatric casesPost-vaccination cases also have been reported ( MMR )
  33. 33. CLINICAL PRESENTATION• Previously healthy child - sudden Skin and mucous membrane bleeds - Petechiae, purpura ecchymosed, Gingival bleeding and epistaxis , gastrointestinal , genitourinary Conjunctival and retinal hemorrhages may occur Life-threatening bleeding, (ICH), - is very rare, occurring with an incidence of 0.1 to 1.0 %
  34. 34. PetechiaeDo not blanch with pressure
  35. 35. CLINICAL PRESENTATIONNo other systemic symptoms - fever, anorexia, weight loss, or bone or joint painNo significant enlargement of lymph nodes, liver, or spleen is present
  36. 36. LABORATORY STUDIES For the typical case of ITP : CBC platelet count peripheral blood smear (often large platelet forms are seen ) Mean Platelet Volume increased Bleeding time prolonged PT/ APTT normal Platelet antibodies in 70-90 %
  37. 37. Fewer Platelets than normal.
  38. 38. LABORATORY STUDIES For the atypical case of ITP : viral antibody titers (including HIV) Coombs test Reticulocyte count Studies for collagen vascular : ANA , Anti dsDNA, ANCA etc Studies for rheumatoid disorders: RF
  39. 39. Platelet Auto-antibodies Platelet Antigens
  40. 40. LABORATORY STUDIES BONE MARROW EXAMINATION (BME) In the past, BME was performed routinely in children with suspected ITP BME are unnecessary in the "typical" case of childhood ITP Bone marrow aspiration and biopsy is reserved for - atypical presentation BME - who initially was diagnosed as ITP but subsequent clinical course is inconsistent with the natural history of acute ITP
  41. 41. DIFFERENTIAL DIAGNOSIS1. Aplastic anemia2. Leukemia ( ALL )3. Autoimmune disease (SLE)4. HSP5. Infection - hepatitis, HIV6. Drug exposure - heparin, quinidine, sulfonamides
  42. 42. MANAGEMENT 80 to 90 % of cases recover spontaneously within a few months (3-6 months) even without treatment Restriction of activity and avoidance of medications with antiplatelet activity (aspirin , ibuprofen ,NSAID) Guidelines suggest : Platelet counts >30,000 no symptoms – no treatment Platelet counts <30,000 with symptoms – treatment
  43. 43. THERAPYCorticosteroidsIntravenous immunoglobulin (IVIG)Anti-Rho(D) immune globulin
  44. 44. CORTICOSTEROIDS Steroids reduce the risk of symptoms by - 1. Improving vascular integrity 2. Diminishing antibody affinity for the platelet membrane 3. Reducing antibody production 4. Reducing reticuloendothelial system phagocytosis of antibody-coated platelets
  45. 45. Dosage regimensPrednisone 1-4 mg/kg per day for 2 to 4 weeks  Pulse IV methylprednisolone as high as 50 mg/kg per day for 3 to 7 daysOccasionally, a second course of treatment may be necessary if significant hemorrhagic symptoms again develop
  46. 46. CORTICOSTEROIDS Chronic administration of steroids - Avoided Alternative therapies - IVIG or Anti-D should be considered who need prolonged or repeated corticosteroid therapy
  47. 47. IVIG MoA: interferes with macrophage Fc receptor clearance Rapid improvement in platelet numbers - 95% patients within 48 hrs Dose - 400 mg/kg per day for five days - 1 gm/kg for one to two days The higher, shorter dosage schedules appear to be preferable
  48. 48. IVIG The side effects include : 1. Nausea and vomiting (63 %) 2. Headache (56 %) 3. Fever (19 %) 4. Neutropenia (absolute neutrophil count <1500/microL) 30 % Cost must be considered in the selection of therapy for ITP
  49. 49. ANTI-D IMMUNE GLOBULIN (Anti-Rho(D)MoA: anti-D results in blockade of Fc receptors by antibody coated RBCs in place of antibody coated plateletsDose - single dose of 50 µg/kg80-85 % patients show rise in platelets within 48 hrsGiven to children with a Hb > 10 g/dlOne to two weeks after administration, a fall in the Hb level of 1 to 1.5 grams - as a result of mild hemolysis of the patients Rho(D)-positive red cells
  50. 50. OUTCOME80 % -90% - recovers spontaneously within three months of presentation, with or without therapy10 % recovers in the next few months15 to 20 % - have moderate or major hemorrhage 0.1 to 1 % - Life-threatening bleeding(ICH) is rare <5 % with acute ITP have recurrent acute thrombocytopenia
  51. 51. CHRONIC ITP Definition - persistence of thrombocytopenia beyond six months from the time of diagnosis 10 % of patients with typical ITP will have chronic ITP Patients who have atypical features at presentation are more likely to have chronic disease
  52. 52. CHRONIC ITP ( Management )Aim of treatment - should focus on minimizing the risk for bleedingMany patients will require no treatment Even after years, a significant proportion of such patients will improve
  53. 53. CHRONIC ITP ( Management )Corticosteroids :  Periodic short courses or pulses of corticosteroids  For steroid dependent patients - alternate day dosing may be effective in preventing bleeding while reducing side effects
  54. 54. CHRONIC ITP ( Management )Immunoglobulin therapy : IVIG or anti-Rho(D)- effective in chronic ITP who are resistant to steroids All of these strategies offer temporary relief of symptoms and improvement in platelet numbers Very costly
  55. 55. CHRONIC ITP ( Management )Splenectomy : Effective in 60 to 90 % of children with chronic ITP Overwhelming post-splenectomy infection Presplenectomy immunizations and subsequent penicillin prophylaxis are necessary for all age groups
  56. 56. CHRONIC ITP ( Management )Splenectomy : No universally accepted standards for the timing of splenectomy in chronic ITP Guidelines recommend waiting until at least 12 months after diagnosis 8)Immunosupressive agents - Cyclophoshamide
  57. 57. Acute ITP Chronic ITPMostly children Mostly adultsMale/Female = Male/Female = -Acute onset Usually gradual onsetPlt. Count mostly Plt. Count 20 – 50000/mm < , /mmSpontaneous Spontaneous remission rare remission frequent Chronic recurrent courseMortality : - Duration - mo -yrsDuration – 2-6 wks
  58. 58. Neonatal thrombocytopeniaSystemic illness1.Cong infections – rubella, CMV, toxoplasmosis, syphillis2.Gram –ve sepsis
  59. 59. Neonatal thrombocytopeniaDue to transfer of maternal antibodies directed against fetal platelets1. Neonatal alloimmune TP-(NATP) – development of maternal antibody against antigens present on fetal platelets - develops symptoms in first few days of life- No maternal thrombocytopenia
  60. 60. Neonatal thrombocytopenia2. Baby of ITP mother-• Symptoms in perinatal period• Resolves within 2-4 months• IVIG & steroids
  61. 61. TTP• Thrombotic Thrombocytopenic purpura• Pentad – fever, microangiopathic hemolytic anemia, thrombocytopenia,impaired renal function ,CNS changes• Usually adolescents & adults• Treatment – plasmapheresis – 80-95% effective• Steroids & splenectomy
  62. 62. Platelet transfusions• Source – Platelet concentrate (Random donor) Each donor unit should increase platelet count ~10,000 /µl – Pheresis platelets (Single donor)• Storage – Up to 5 days at room temperature• “Platelet trigger” – Bone marrow suppressed patient (>10-20,000/µl) – Bleeding/surgical patient (>50,000/µl)
  63. 63. Danzol 400 mg/m2/d for 3 mth.9)PLASMAPHERESIS10) T/T Of life threatening ITP:-PLT. TRANSFUSIONSOLUMEDROL 500 Mg/m2/day IV TID.IVIG 2g/kgemergency Splenectomy.Vincristine 2 mg/kg IV.PROGNOSIS;-EXCELENT 70-80 % recover ithin 6mth.spontaneous remission in 1 yr- 5yrs.
  64. 64. Approach to the thrombocytopenic patient• History – Is the patient bleeding? – Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease) – Is there a history of medications, alcohol use, or recent transfusion? – Are there risk factors for HIV infection? – Is there a family history of thrombocytopenia? – Do the sites of bleeding suggest a platelet defect?• Assess the number and function of platelets – CBC with peripheral smear – Platelet function study
  65. 65. Platelet transfusions• Source – Platelet concentrate (Random donor) – Pheresis platelets (Single donor)• Target level – Bone marrow suppressed patient (>10-20,000/µl) – Bleeding/surgical patient (>50,000/µl)
  66. 66. Platelet transfusions - complications• Transfusion reactions – Higher incidence than in RBC transfusions – Related to length of storage/leukocytes/RBC mismatch – Bacterial contamination• Platelet transfusion refractoriness – Alloimmune destruction of platelets (HLA antigens) – Non-immune refractoriness • Microangiopathic hemolytic anemia • Coagulopathy • Splenic sequestration • Fever and infection • Medications (Amphotericin, vancomycin, ATG, Interferons)
  67. 67. Approach to the WERLHOF’S DISEASE• History – Is the patient bleeding? – Are there symptoms of a secondary illness? (neoplasm, infection, autoimmune disease) – Is there a history of medications, alcohol use, or recent transfusion? – Are there risk factors for HIV infection? – Is there a family history of thrombocytopenia? – Do the sites of bleeding suggest a platelet defect?• Assess the number and function of platelets – CBC with peripheral smear – Bleeding time or platelet aggregation study – TORNIQUET / RUMPEL-LEEDE TEST:-
  68. 68. THROMBOTIC THROMBOCYTOPENIC PURPURA(TTP) MOSCHOWITZ’S SYNDROMEDEF:- It is rare acquired multisystem disease.CLASSIFICATION :-1) PRIMARY = ACUTE ,CHRONIC, RELAPSING & CONGENITAL.2)SECONDARY = CTD, SBE, MALIGNANCY, INFECTION & DRUGS.CLINICAL FEATURES :- Consumptive thrombocytopeniaMicroangiopathic H. anaemia.Fever, Jaundice,Neurologic & Renal manifestations
  69. 69. DIAGNOSIS :-TPC ,Hb % , Haptoglobin , hemoglobinuriaDecreased plasma factor - VIII & vWF.GINGIVAL BIOPSY = Presense of segmantal hyaline microthrombi inthe microvasculature.TREATMENT : -PLASMAPHERESISFFPSTEROIDSANTIPLATELETS AGENTS.SPLENECTOMY.
  70. 70. NONTHROMBOCYTOPENIC PURPURA1)ANAPHYLACTOID PURPURA2)INFECTIONS (Meningococcus, measles, rubella, SBE)3)DRUGS(SULFA)4)PURPURA FACTITIA:-It is a self inflictted lesions in a linear fashion commonly over accessibleparts of body due to Psychopathic disorder.
  71. 71. THROMBOCYTOPATHYPLT. function disorders :-1)BERNARD SOULIER SYNDROME2)GLANZMAN’S THROMBASTHENIA3)ALPORT SYNDROME(PF-3 deficiency)4)CTD =EHLERS DANLOS SYNDROMEPSEUDOXANTHOMA ELASTICUMMARFAN’S SYNDROMEOSTEOGENESIS IMPERFECTA.
  72. 72. ESSENTIAL THROMBOCYTHEMIADiagnosed by :-TPC > 6000.000/cmm, Hb% <13gm%RCM < 36ML/KG.NORMAL IRON IN BM.ABNORMAL PLT FUNCTION TEST.NO KNOWN CAUSE OF THROMBOCTYTOSIS- ve philadelphia chromosome.-ve BM fibrosis.Thrombotic & haemorrhagic features common.TREATMENT:- Anti-platelet agents = ASA, Dipyridamole(3-6 mg/kg/dPLT lowering drugs = Hydroxyurea - 20-30mg/kg od Alpha 2- interferon.
  73. 73. Thank youDownload more documents and slide shows on The Medical Post [ www.themedicalpost.net ]

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