3. Hemostasis:

4. Hemostasis: Hemo/Stasis Hemo=خونStasis=سکون

5. مثلث هموستاز: Blood Vessels Platelets Hemostatic Factors

6. Causes of Bleeding(1) Thrombocytopenia: Primary: ITP Neonatal Isoimmune TAR Syndrome Wiskott-Aldrich Syn. Secondary: *Malignancy *Aplastic Anemia *DIC *Sepsis *HUS *Hypersplenism *Autoimmune(SLE)

7. Causes of Bleeding(2) Coagulopathy: Primary: vWF Deficiency Hemophilia Platelet dysfunction Secondary: DIC Anticoagulants Vit K deficiency Hepatic Failure Renal Failure Maternal Anticonvulsant

8. Causes of Bleeding(3) Vascular(Non-Hematologic) Child Abuse Vasculitis Ulcer Varices Ehlers-Danlos Syndrome Telangiectasia Angiodysplasia

9. تقسیم بندی هموستاز: 1)هموستاز اولیه:چند ثانیه بعد از آسیب عروقی ایجاد میشود و از خونریزی از عروق کوچک و ونولها جلوگیری میکند. 2)هموستاز ثانویه:چند دقیقه بعد از آسیب عروقی ایجاد میشود و از خونریزی از عروق بزرگ جلوگیری میکند.

11. Differences of Primary and Secondary Hemostasis: Manifestations Primary Hemostasis: Secondary Hemostasis: Onset of Bleeding ImmediateDelayed-hours or days Site of BleedingSuperficialDeep(joints,…) Physical Exams Petechia,Echymosis Hematoma,Hemarthrosis Family History ADAR or X-link R Response to Therapy Immediate; Local pressure Systemic Therapy

16. Estimation of BT with desired Platelet count BT= 30.5- Platelet count (minute) 3,850

24. Vitamin K Related Factors: Factor II Factor VII Factor IX Factor X

26. Prolonged PTT No clinical bleeding ??? Mild or rare bleeding ??? Frequent,Severe Bleeding ???

28. Prolonged PTT No clinical bleeding Factor XII, HMWK, PK Mild or rare bleeding Factor XI Frequent,Severe Bleeding Factors VIII and IX

29. Prolonged PT ???

31. Prolonged PT Factor VII Deficiency Vitamin K Deficiency(Early) Warfarin anticoagulant ingestion

32. Prolonged PT and PTT ???

34. Prolonged PT and PTT Factor II,V,X Deficiency Vitamin K Deficiency(Late) Warfarin anticoagulant ingestion

35. Prolonged TT ???

37. Prolonged TT Mild or rare bleeding: Afibrinogenemia Frequent,Severe Bleeding: Dysfibrinogenemia Heparin like inhibitors or heparin administration

38. Prolonged PT and/or PTT not corrected with normal plasma Specific or nonspecific inhibitor Syndromes

39. Clot Solubility in 5 M urea Factor XIII deficiency Inhibitor

41. Secondary Hemostasis Approach: 1)What is diagnosis? 2)What is hemostatic level of Factor? 3)What is blood distribution of factor? 4)Which products contain desired factor? 5)What is half life of coagulation factor?

46. APPROACH TO COAGULATION DISORDERS

47. Clinical approach 1.Is the bleeding significant ? 2. Local Vs Systemic ? 3. Platelet Vs Coagulation disorder ? 4. Inherited Vs Acquired ?

48. 1. Demonstration of the defect 2. Identification of the defect(s) 3. Assessment of severity 4. Consequential studies eg. carrier detection 5. Monitoring of treatment Laboratory Approach

49. 1. Platelet count & morphology 2. Bleeding Time(BT) 3. Prothrombin Time(PT) 4. Activated Partial Thromboplastin Time(PTT) 5. Thrombin Time (TT) Screening Tests

50. Collection of blood sample 1. Minimum circulatory stasis 2. Clean venous puncture 3. Proper anticoagulant 4. Proportion of blood to anticoagulant 5. Separation of plasma and storage 6. Effect of stress, pregnancy, drugs 7. Effect of PCV on the proportion of plasma to anticoagulant

51. Coagulation factor deficiency/inhibitor Test plus control plasma - 1:1 Repeat PT/APTT > 50% correction –Yes - Factor deficiency –No - inhibitor Prolonged PT/APTT timed incubation abnormally increasing specific inhibitor no change Lupus Anticoagulant

52. PT TT APTT PT -  APTT, TT, PLC - N HMWK XII PK XI IX VIII VII X V II I * Factor VII deficiency * Anticoagulant therapy

53. APTT -  PT, TT, PLC - N * Factor deficiency * vWD * Inhibitors * Heparin therapy PT TT APTT HMWK XII PK XI IX VIII VII X V II I

54. Mixing tests with APTT APTT of test plasma + Aged plasmaAdsorbed plasmaDiagnosis No correctionCorrectedVIII CorrectedNo correctionIX CorrectedCorrectedXI,XII

55. Prolonged APTT, BT von Willebrand’s disease Ristocetin Induced Platelet Agglutination VIII:C vWF:Ag vWF multimeric analysis Type 1 - Partial deficiency of vWF 2A - Absence of large and interm. multimers 2B - Absence of large multimers 2M- multimers normal, pl. function  2N -  affinity for FVIII 3 - severe deficiency of vWF

56. PT TT APTT PT, APTT -  TT, PLC - N HMWK XII PK XI IX VIII VII X V II I * Common Pathway Factor deficiency * Vitamin K deficiency * Oral anticoagulant therapy * Liver disease

57. Mixing tests with PT PT of test plasma + Aged plasmaadsorbed plasmaDiagnosis CorrectedNot corrected X Not correctedCorrected V Not corrected Partial II

58. PT TT APTT PT, APTT, TT -  PLC - N HMWK XII PK XI IX VIII VII X V II I * Hypo / dysfibrinogenemia * Heparin * Liver disease * Systemic hyperfibrinolysis

59. PT TT * DIC - FDP - D-dimer - Fibrin monomer APTT APTT, PT,TT all  PLC - low HMWK XII PK XI IX VIII VII X V II I

60. PT TT APTT PT, APTT-  TT - N PLC -  HMWK XII PK XI IX VIII VII X V II I Massive transfusion with stored blood

61. Thrombocytopenia Pseudo vs True Bone marrow biopsy to differentiate  production  destruction PT APTT PT, APTT,TT-N PLC -  HMWK XII PK XI IX VIII VII X V II I TT

62. Factor XIII deficiency Thrombasthenia –congenital –drug induced Disorders of vascular hemostasis Factor XIII - clot solubility PT, APTT, TT, PLC - Normal Platelet function –BT –clot retraction –1 minute platelet count –aggregation Tourniquet test

63. Asymptomatic Patient Routine screening tests shows prolonged APTT –Inhibitor - lupus anticoagulant –Factor XII deficiency –Mild congenital factor deficiency

64. Antiphospholipid Antibody Syndrome Criteria by Branch and Silver 1996 Clinical –Recurrent abortion –Recurrent venous thrombosis –Recurrent arterial thrombosis –Persistent thrombocytopenia –Livedo reticularis Laboratory –IgG/IgM anticardiolipin Ab –Lupus anticoagulant Diagnosis –1 clinical + 1 lab criteria –Lab result must be positive on at least 2 occasions more than 3 months apart

65. Kaolin clotting time Dilute Russel’s viper venom time Platelet neutralization test Tissue thromboplastin inhibition test Lupus Anticoagulant