Clinical_approach_to_Coagulation_Disorders.pptx

Approach to coagulation

1. Clinical approach to Coagulation Disorders

2. Disorders of blood coagulation Disorders of vessels and platelets

3. Good history Drug history Clinical examination

4. findings Disorders of coagulation Disorders of platelets or vessels petechiae Rare Characteristic Deep disecting hematomas Characteristic Rare Superficial ecchymoses Common usually large & solitary Characteristic ; small & multiple Hemarthrosis Characteristic Rare Delayed bleeding Common Rare Bleeding from superficial cuts & scratches Minimal Persistant often profuse Sex 80-90% of inherited forms – males Relatively more common in females Positive family history Common Rare ( except Vwd )

5. CLOTTING FACTORS Fibrinogen Prothrombin Tissue factor Calcium Factor V Factor VII Factor VIII Factor IX Factor X Factor XI Factor XII Factor XIII Prekallikrein Hmwk platelets Factor I Factor II Factor III , Tissue thromboplastin Factor IV Proaccelerin , labile factor Proconvertin , stable factor Antihemophilic factor Christmas factor Stuart factor; stuart - prower Plasma thromboplastin antecedent Hageman factor Fibrin stabilizing factor Fletchet factor Fitzgerald factor

6. PT APTT HMWK XII PK XI IX VIII VII X V II I TT

7. Laboratory methods

8. Tests of Vascular & Platelet Phases Tests of Coagulation Phase

9. Tests of Vascular & Platelet Phases Bleeding time Platelet enumeration Platelet volume measurement Release reaction & markers of platelet activation Tests of platelet factor 3 activity Clot retraction

10. Bleeding time Depends on rate at which stable platelet plug is formed. Provides a measure of efficiency of vascular and platelet phases But does not discriminate b/w vascular defects, thrombocytopenia & platelet dysfunction. Normal : 3-9 min Valuable in platelet disorders ( qualitative platelet disorders & vonWillebrand’s disease

11. Bleeding time Screen patient for inherited platelet disorders An abnormal bleeding time in a patient with personel and family history of excessive mucocutaneous bleeding would justify further hemostatic testing for platelet dysfunction

12. Aspirin tolerance test To assess the effect of standard dose of aspirin on bleeding time Mild disorders of platelet function might have normal bleeding time Aspirin administration – prolongs BT Slightly – normal individuals Substantially prolonged / precipitate clinical bleeding – Vwd / Qualitative platelet disorders

13. Platelet Enumeration Hemacytometer / direct methods Semiautomated methods Fully automated electronic methods Normal – Phase microscopy : 140- 440,000 / ul Automated : 150-450,000 / ul

14. Artifacts in automated platelet counting : Falsely low platelet counts : Platelet cold agglutinins Paraproteinemias Previous contact of platelet with foreign surfaces such as dialysis membranes Giant platelets Lipemia EDTA-induced platelet clumping

15. Artifacts Falsely high platelet counts- Presence of microspherocytes Fragments of leukemic cells

16. Platelet Volume Measurements Increased in disorders with accelerated platelet turnover as the result of large numbers of megathrombocytes or in patients with Bernard- Soulier syndrome Normal / Decreased in disorders with deficient platelet production, sepsis & big spleen syndromes Some say increased MPV – as evidence of Accelerated Platelet Production

17. Tests of specific platelet function Most widely used & reliable – Platelet Aggregation Historical interest – Platelet adhesiveness & Platelet retention

18. Ristocetin induced platelet aggregation Ristocetin induces platelet agglutination in presence of vWF In von Willebrand’s disease & Bernard- Soulier’s disease – abnormal ristocetin response

19. Kaolin-induced PF-3 Indirect measures of platelet aggregation

20. Clot Retraction Incubate a tube of clotted blood, clot retraction normally apparent within 2 hours Usually deficient when – platelet count is below 50,000/ ul Glanzmann Thrombasthenia

21. Tests of Coagulation Phase Partial thromboplastin time Plasma prothrombin time Whole blood clotting time Thromboplastin generation test Assay of plasma fibrinogen Thrombin time Tests for fibrin – fibrin degradation products Bioassay for coagulation factors Tests for inhibitors of coagulation Tests for physiological inhibitors of coagulation Automated coagulation methods Chromogenic & flurometric techniques

22. Partial Thromboplastin Time Simple test of intrinsic & common pathways of coagulation More sensitive to deficiencies of factors VIII and IX than to deficiencies of factors XI and XII or factors involved in common pathway Test is abnormal when essential factors are below 15 to 30 % of normal value.

23. Activated partial thromboplastin time Using activators – Celite or Kaolin Assay used to evaluate intrinsic coagulation Normal : 25 – 36 sec Abnormal – deficiencies prekallikrein , HMW Kininogen , factors XII,XI,IX,VIII,X & V; Prothrombin /Fibrinogen.

24. 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

25. Plasma Prothrombin Time The production of fibrin by means of Extrinsic and Common Pathway requires tissue thromboplastin and Factor VII , inaddition to factors X, V, Prothrombin and Fibrinogen. These pathways are measured by plasma prothrombin time.

26. Plasma Prothrombin Time Factors V, VII,X,Prothrombin & Fibrinogen Vitamin K dependent – prothrombin factor VII & X Are depressed by Coumarin like drugs PT – widely used for controlling oral anticoagulant therapy

27. Plasma Prothrombin Time PT is more sensitive to deficiencies of factor VII & X than to prothrombin & fibrinogen. Normal : 15 – 18 sec

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

29. Stypven time Venom of Russel’s viper contains enzyme that initiates coagulation by direct activation of factor X and does not require factor VII. One stage Prothrombin time performed with this venom ( stypven time ) – distinguishes b/w deficiency of Factor VII and Factor X .

30. Whole blood clotting time Measures only the time required for the formation of the first traces of thrombin sufficient to produce visible clot. Prolonged only in severe deficiencies of various coagulation factors involved in intrinsic and common pathways. Test result not affected by factor VII Coagualation time is significant only if it is significantly prolonged.

31. Whole blood clotting time It is a poor screening test Prolonged by heparin But aPTT – monitor heparin anticoagulation

32. Thromboplastin generation time 2 stage test Measures the amount and rate of prothrombinase formation by way of intrinsic pathway Supplanted by specific factor assays

33. Assay for plasma fibrinogen Aid in identifying inherited dysfibrinogenemias

34. Thrombin time thrombin is added to plasma, time required for the clot formation is the measure of the rate at which fibrin forms Abnormal – when fibrinogen is below 70-100 mg / dL , by Heparin Prolonged : abnormal fibrinogen, elevated fibrin-FDPs, paraproteinemias , hyperfibrinogenemia Normal :13-17 sec

35. Tests for fibrin – fibrin degradation products Increased in DIC, Fibrinogenolysis Cannot distinguish b/w fibrin degradation products and fibrinogen degradation products. - Measurement of fibrinopeptides , specific FDP ( DD dimer , DDE trimer ) are useful indices of DIC

36. Tests for fibrinolysis Whole blood clot lysis But may be normal in hypofibrinogenemia Specific assays of fibrinolytic components supplanted whole blood clot lysis test

37. Tests for inhibitors of coagulation Abnormalities of any test in coagulation, if caused by deficiency of essential factor, are corrected by addition of small amounts of normal plasma . If inhibitors are present : addition of small amounts of patient’s plasma impair coagulation in normal plasma.

38. Tests for physiological inhibitors of coagulation Assays of physiological inhibitors of coagulation – antithrombin III, heparin cofactor II protein C protein S

39. PRIMARY SCREENING TESTS

40. aPPT – BEST SINGLE SCREENING TEST PT , Prothrombin time Followed by confirmatory tests

41. PT : increased aPPT : normal Platelet count : normal Common : acquired factor VII deficiency ( early liver disease, early vit K deficiency, early warfarin therapy ) Rare : Factor VII inhibitior , dysfibrinogenemia,DIC , inherited factor VII deficiency

42. PT : normal aPTT : increased Platelet count : normal Common : deficiency or inhibitor of factors VIII, IX, XI, von Willebrand’s disease, heparin Rare : lupus inhibitor

43. PT : increased aPTT : increased Platelet count : normal Common : vitamin K deficiency, liver disease, warfaarin , heparin Rare : deficiency / inhibitor of factor X, V prothrombin , fibrinogen, DIC

44. PT : increased aPTT : increased Platelet count : decreased Common : DIC, Liver diseasee Rare : heparin therapy with associated thrombocytopenia

45. PT : normal a PPT : normal Platelet count : decreased Common : increased platelet destruction, decreased platelet production, hypersplenism Rare : bernard-soulier syndrome

46. PT : normal aPPT : normal Platelet count : increased --- myeloproliferative disorder

47. PT : normal aPTT : normal Platelet count: normal Common : mild Vwd , uremia Rare : inherited qualitative platelet disorders

48. Confirmatory tests

49. Thrombocytopenia Most common acquired bleeding disorder Bleeding time : prolonged Clot retraction : deficient

50. vWD BT : PROLONGED PLATELET COUNT : NORMAL Assays for VIIIc,Vwag , ristocetin cofactor abnormal Von Willebrands disease normal Platelet fn tests Platelet morphology aaglutination Disorder of platelet funtion

51. Qualitative platelet disorders Deficient clot retraction is seen in glanzmann thrombasthenia Strikingly large platelets – Bernard Soulier syndrome Elevated platelet count – myeloproliferative disorder Absence of platelet aggregation by ADP, collagen, epinephrine – Glanzmann thrombasthenia

52. Disorders of intrinsic pathway

53. Disorders of common pathway

54. Disorders of extrinsic pathway

55. Disorders of extrinsic pathway Coagulation and stypven time are normal

56. Bleeding disorders with normal primary screening tests vonWillebrand’s disease Mild inherited coagulation disorders : factor XI deficiency Heterozygous carriers for inherited coagulation disorders Factor XIII ( Fibrin stabilizing factor ) deficiency Some forms of dysfibrinogenemia Disordered platelet function- deficient release reaction Hereditary hemorrhagic telangiectasia Allergic and other vascular purpura Alpha2 plasmin inhibitor deficiency Elevated levels of plasminogen activator

57. Preoperative hemostasis evaluation level Bleeding history Surgical procedure Recommended evaluation I NEGATIVE MINOR NONE II NEGATIVE MAJOR PLATELET COUNT, APTT III EQUIVOCAL MAJOR PT,APTT,PLATELET COUNT, BLEEDING TIME, FACTOR XIII ASSAY,ECLT

58. LEVEL BLEEDING HISTORY SURGICALPROCEDURE RECOMMENDED EVALUATION IV POSITIVE MAJOR/MINOR LEVEL III TESTS ; IF NEGATIVE – FACTOR VIII & IX ASSAY THROMBIN TIME ALPHA2 ANTIPLASMIN ASSAY POSTASPIRIN BLEEDING TIME FACTOR XI ASSAY

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