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Blood Coagulation

Blood Coagulation. Haemostasis part3. DIC. Lab: - fibrinogen - platelet - PT - aPTT - fibrin degradation product acute DIC: - prolongation of aPTT, PT and TT - reduction of platelets, AT III and protein C - decreased fibrinogen

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Blood Coagulation

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  1. Blood Coagulation

  2. Haemostasispart3

  3. DIC Lab: - fibrinogen - platelet - PT - aPTT - fibrin degradation product acute DIC: - prolongation of aPTT, PT and TT - reduction of platelets, AT III and protein C - decreased fibrinogen - elevated fibrin degradation products chronic DIC: - aPTT and PT may be within normal ranges - slightly decreased platelets - elevated fibrin degradation products and D-dimer

  4. Platelet Functional Abnormalities congenital 1 • Bernard-Soulier syndrome • defect in platelet adhesion • autosomal recessive • defect in platelet membrane glycoprotein (GP Ib) • thrombasthenia • defect in platelet aggregation • autosomal recessive • defect in platelet membrane glycoprotein (GP IIb & IIIa) • no fibrinogen linking of platelets • easy bleeding and no clot retraction 2

  5. Platelet Functional Abnormalities acquired • aspirin • inhibits cyclooxygenase suppression of TXA2 synthesis • effect lasts for 72 hours • thrombocythemia • platelet : >3,000,000/ml • functionally abnormal platelets • occasionally seen in myeloproliferative disorders

  6. Approach to the diagnosis of bleeding disorder Clinical Evaluation History Physical Examination Family history Laboratory Evaluation Screening test Specific test

  7. Clinical Features of Bleeding Disorders Platelet disorders Coagulation disorders Site of bleeding Skin Deep in soft tissues (epistaxis, gum, Mucous vaginal, GI tract) membranes, joints, muscles) Petechiae Yes No Ecchymoses (“bruises”) Small, superficial Large, deep Hemarthrosis / muscle bleeding Extremely rare Common Bleeding after cuts & scratches Yes No Bleeding after surgery or trauma Immediate, Delayed (1-2 days), usually mild often severe

  8. Platelet Coagulation Petechiae, Purpura Hematoma, Joint bl.

  9. Tests for Primary Hemostasis • Bleeding time platelet & vascular phases • PFA – 100 system Platelet function • Platelet count Quantification of platelets • Blood smear Quantitative & morphological abnormalities of platelets , Detection of underlying haemotological disorder

  10. PLATELET COUNT • NORMAL 150,000 - 400,000CELLS/MM3 < 100,000Thrombocytopenia 50,000 - 100,000Mild Thrombocytopenia < 50,000Sev Thrombocytopenia

  11. BLEEDING TIME • PROVIDES ASSESSMENT OF PLATELET COUNT AND FUNCTION NORMAL VALUE 2-8 MINUTES

  12. Laboratory diagnosis of the coagulopathies Contact activation Tissue thromboplastin (TF) INTRINSIC EXTRINSIC XII XI IX VIII VII Blood coagulation time APTI Prothrom-bin X V II I COMMON Fibrin

  13. INR • INR: International normalized ratio • was established by the WHO and the International Committee on Thrombosis and Hemostasis for reporting the results of prothrombin tests • All PT results are standardized by this calculation: • INR= ( Patient PT / Control PT)ISI • ISI= International sensitivity index • - Given by the manufacturer for each particular thromboplastin reagent and instrument combination

  14. ACTIVATED THROMBOPLASTIN TIME • Measures Effectiveness of the Intrinsic Pathway& common pathway NORMAL VALUE 25-40 SECS

  15. APTT prolongs.. Intrinsic pathway factor deficiencies (FXII, XI,VIII, IX, HMWK, prekallikrein ) - Inherited or acquired - Consumption (DIC) - PIVKA factors in cumarin therapy 2. Specific inhibitors against FXII, XI, VIII, IX, HMWK, prekallikrein 3. Lupus anticoagulant 4. Non-fractionated heparin therapy

  16. THROMBIN TIME • Time for Thrombin To Convert • Fibrinogen Fibrin • A Measure of Fibrinolytic Pathway NORMAL VALUE 9-13 SECS

  17. TT Prolongs.. 1. Hypo- afibrinogenaemia 2. Dysfibrinogenaemia 3. Non fractionated heparin 4. Fibrinogen/ fibrin degradation product s 5. Chronic liver disease

  18. Diagnosis of bleeding disorders by the screening tests

  19. ANTICOAGULATION & FIBRINOLYSIS Vascular Wall Anti-Coagulation Factors Fibrinolytic Factors

  20. ANTICOAGULATION & FIBRINOLYSISVascular Wall • Endothelial Cell • prostacyclin (PGl2) • heparan sulfate • thrombomodulin • tissue plasminogen activator (tPA) • Muscle • muscular dilation

  21. Protein C • vit K dependent zymogen • produced in liver • inactivates Va and VIIIa Protein S • vit K dependent binding protein • co-factor for protein C • binds C4b-binding protein XII XI IX VIII VII X V II I XIII Stable clot

  22. AnticoagulationHeparin • Heparin activates Antithrombin III (AT III) • AT III inactivates Thrombin and Factor Xa • rapid onset of action Laboratory monitoring: • aPTT : ~1.5X – 2.5X normal mean • heparin level : 0.2 – 0.4 U/mL by protamine titration 0.35 – 0.70 by Factor Xa inactivation assay XII XI IX VIII VII X aPTT V II I XIII Stable clot

  23. AnticoagulationHeparin AT AT

  24. II

  25. AT II

  26. AT II

  27. AT II

  28. AT II

  29. AT II

  30. Coumadin (Warfarin) Anticoagulants • inhibits hepatic synthesis of vit K-dependent clotting factors (II, VII, IX, X) • competitive inhibition of g-carboxylation inactivate “acarboxy” forms synthesized • onset delayed 3 to 5 days • also inhibits synthesis of protein C & S XII XI IX VIII VII X V PT II I XIII Stable clot

  31. Coagulation Tests 1. Bleeding Time : in vivo test measures adequacy of plt function normal : <6 min. 2. Platelet Count normal : >200,000/mL 3. aPTT : intrinsic pathway (XII, XI, IX, VIII, X, V) used to guide heparin therapy 4. 50/50 mixing study pt’s plasma + nl. plasma if mixing correct aPTT = Pt is deficient in intrinsic factor(s) no correction = circulating anticoagulants or inhibitors 5. Prothrombin Time (PT) : extrinsic pathway (II, VII, V, X) monitoring warfarin/coumadin effects

  32. Coagulation Tests 6. Fibrinogen Level normal : 200 – 500 mg/dL 7. ADP platelet aggregation 8. Ristocetin aggregation test • test for presence or activity of vWF 9. Thrombin Time (TT) normal : 20 – 30 sec • measures 3rd stage of coagulation • prolonged if • def or abnormality of fibrinogen • presence of fibrin split products • presence of heparin

  33. History & Physical Examaremost importantmost sensitivemost specificTests of Hemostasis

  34. Antithrombin III (AT III) • naturally-occuring anticoagulant • binds to factors IXa, Xa, XIa, XIIa (slow) • accelerated by heparin manyfold Implication: Heparin has almost NO anticoagulant action without AT III

  35. Coagulation Factors Roberts HR, et al. Current Concepts for Hemostasis. Anesthesiology 2004;100:3. 722-30.

  36. Fibrinolysis • Plasminogen →plasmin • Release of tPA by the endothelium • Lysis of clot→ FDPs or FSPs • Reopening of blood vessel

  37. Laboratory MonitoringProthrombin Time (PT) • test of extrinsic pathway activity • measures vitamin K - dependent factors activity (factors II, VII, IX, X) • thromboplastin + Ca+2 to plasma = clotting time • normal values: 12-14 seconds • International Normalized Ratio (INR) ▪ standardizes PT reporting • normal values: 0.8 -1.2 seconds

  38. Laboratory MonitoringProthrombin Time (PT) • monitors coumadin therapy • most sensitive to alteration in F VII levels • prolonged: 55 % ↓ of normal F VII activity • antithrombotic activity: reduction of factor II and factor X activity (after several days)

  39. Laboratory MonitoringActivated Partial Prothrombin Time (aPTT) • test for intrinsic and common pathways • dependent on activity of all coagulation factors, except VII and XIII • normal values: 25 -35 seconds • monitors heparin tx & screen for hemophilia

  40. Laboratory MonitoringActivated Prothrombin Time (aPTT) • prolonged: heparin, thrombin inhibitors, fibrin degradation products (FDP) • citrated plasma + surface activators + phospholipid • prolonged only if coagulation factors reduced to < 30 % of normal

  41. Laboratory MonitoringActivated Clotting Time (ACT) • monitors heparin anticoagulation in the OR (cardiac and vascular surgeries) • normal values: 90 - 120 seconds

  42. Laboratory MonitoringThrombin Clotting Time (TCT) • reflects abnormalities in fibrinogen → fibrin • plasma + excessive amount of thrombin • prolonged: heparin, thrombin inhibitors, low fibrinogen, dysfibrinogenemia • monitors hirudin, bivalirudin, LMWH tx • INR & PT may be normal or ↑ • TCT prolonged with adequate therapeutic levels

  43. Laboratory MonitoringThromboelastography (TEG) • continuous profiles during all phases of clot formation • provides more accurate picture of in vivo coagulation process • to evaluate: • hypo / hypercoagulable state • hemophilia • dilutional coagulopathy • rare coagulation disorders anticoagulation tx • coagulation problems with liver transplantation

  44. Thromboelastogram (TEG)

  45. Bleeding time • monitors platelet function • not specific indicator of platelet function • not very reliable • very operator - dependent • variable from each institution

  46. Bleeding time • other factors: degree of venostasis, depth and direction of incision • no evidence as • a predictor of risk of hemorrhage • useful indicator of efficacy of antiplatelet therapy • insensitive to mild platelet defects

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