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Clinical_approach_to_Coagulation_Disorders.pptx

The document provides a comprehensive overview of coagulation disorders, including the classification of blood coagulation issues, the importance of clinical examination and drug history, and various laboratory methods used to diagnose these disorders. It details tests related to the vascular and platelet phases, as well as the coagulation phase, highlighting specific tests like PT, APTT, and thrombin time. The analysis of results and confirmatory tests for different types of bleeding disorders is also discussed, along with the implications of various abnormalities in coagulation factors.

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Clinical approach to Coagulation Disorders
 Disorders of blood coagulation  Disorders of vessels and platelets
 Good history  Drug history  Clinical examination
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 ( exceptVwd )
CLOTTING FACTORS  Fibrinogen  Prothrombin  Tissue factor  Calcium  FactorV  FactorVII  FactorVIII  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
PT APTT HMWK XII PK XI IX VIII VII X V II I TT
LABORATORY METHODS
 Tests ofVascular & Platelet Phases  Tests of Coagulation Phase
Tests ofVascular & Platelet Phases  Bleeding time  Platelet enumeration  Platelet volume measurement  Release reaction & markers of platelet activation  Tests of platelet factor 3 activity  Clot retraction
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
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
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
Platelet Enumeration  Hemacytometer / direct methods  Semiautomated methods  Fully automated electronic methods  Normal –  Phase microscopy : 140- 440,000 /ul  Automated : 150-450,000 /ul
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
Artifacts  Falsely high platelet counts-  Presence of microspherocytes  Fragments of leukemic cells
PlateletVolume 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
Tests of specific platelet function  Most widely used & reliable – Platelet Aggregation  Historical interest – Platelet adhesiveness & Platelet retention
Ristocetin induced platelet aggregation  Ristocetin induces platelet agglutination in presence of vWF  In von Willebrand’s disease & Bernard-Soulier’s disease – abnormal ristocetin response
Kaolin-induced PF-3  Indirect measures of platelet aggregation
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
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
Partial Thromboplastin Time  Simple test of intrinsic & common pathways of coagulation  More sensitive to deficiencies of factorsVIII 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.
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.
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
Plasma Prothrombin Time  The production of fibrin by means of Extrinsic and Common Pathway requires tissue thromboplastin and FactorVII , inaddition to factors X,V, Prothrombin and Fibrinogen.These pathways are measured by plasma prothrombin time.
Plasma Prothrombin Time  FactorsV,VII,X,Prothrombin & Fibrinogen  Vitamin K dependent – prothrombin factorVII & X Are depressed by Coumarin like drugs  PT – widely used for controlling oral anticoagulant therapy
Plasma Prothrombin Time  PT is more sensitive to deficiencies of factorVII & X than to prothrombin & fibrinogen.  Normal : 15 – 18 sec
PT TT APTT PT -  APTT,TT, PLC - N HMWK XII PK XI IX VIII VII X V II I * FactorVII deficiency * Anticoagulant therapy
Stypven time  Venom of Russel’s viper contains enzyme that initiates coagulation by direct activation of factor X and does not require factorVII.  One stage Prothrombin time performed with this venom ( stypven time ) – distinguishes b/w deficiency of FactorVII and Factor X .
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 factorVII  Coagualation time is significant only if it is significantly prolonged.
Whole blood clotting time  It is a poor screening test  Prolonged by heparin  But aPTT – monitor heparin anticoagulation
Thromboplastin generation time  2 stage test  Measures the amount and rate of prothrombinase formation by way of intrinsic pathway  Supplanted by specific factor assays
Assay for plasma fibrinogen  Aid in identifying inherited dysfibrinogenemias
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
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
Tests for fibrinolysis  Whole blood clot lysis  But may be normal in hypofibrinogenemia  Specific assays of fibrinolytic components supplanted whole blood clot lysis test
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.
Tests for physiological inhibitors of coagulation  Assays of physiological inhibitors of coagulation – antithrombin III, heparin cofactor II protein C protein S
PRIMARY SCREENING TESTS
 aPPT – BEST SINGLE SCREENING TEST  PT , Prothrombin time  Followed by confirmatory tests
 PT : increased  aPPT : normal  Platelet count : normal  Common : acquired factorVII deficiency ( early liver disease, early vit K deficiency, early warfarin therapy )  Rare : FactorVII inhibitior, dysfibrinogenemia,DIC, inherited factorVII deficiency
 PT : normal  aPTT : increased  Platelet count : normal  Common : deficiency or inhibitor of factorsVIII, IX, XI, von Willebrand’s disease, heparin  Rare : lupus inhibitor
 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
 PT : increased  aPTT : increased  Platelet count : decreased  Common : DIC, Liver diseasee  Rare : heparin therapy with associated thrombocytopenia
 PT : normal  a PPT : normal  Platelet count : decreased  Common : increased platelet destruction, decreased platelet production, hypersplenism  Rare : bernard-soulier syndrome
 PT : normal  aPPT : normal  Platelet count : increased --- myeloproliferative disorder
 PT : normal  aPTT : normal  Platelet count: normal  Common : mildVwd, uremia  Rare : inherited qualitative platelet disorders
CONFIRMATORYTESTS
Thrombocytopenia  Most common acquired bleeding disorder  Bleeding time : prolonged  Clot retraction : deficient
vWD BT : PROLONGED PLATELET COUNT : NORMAL Assays forVIIIc,Vwag, ristocetin cofactor abnormal Von Willebrands disease normal Platelet fn tests Platelet morphology aaglutination Disorder of platelet funtion
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
Disorders of intrinsic pathway PPT :PROLONGED PT : NORMAL DISORDERS OF INTRINSIC PATHWAY BLEEDING ABSENT ASSAY FOR FACTORXII, PREKALLIKREIN,HMWK DEF BLEEDING PRESENT ASSAY FOR FACTOR VIII, IX, X FACTORVIII INHIBITORS, HEPARIN, INHIBITIORS OF LUPUS
Disorders of common pathway PTT : PROLONGED PT : PROLONGED DISORDERS OF COMMON PATHWAY ASSAY FOR FACTORS X,V,PROTHROMBIN, FIBRINOGEN,FDP
DISORDERS OF COMMON OR MULTIPLE PATHWAYS THROMBINTIME FIBRINOGEN LEVEL FDP LEVELS ABNORMAL INTRAVASCULAR COAGULATION HEPARIN LIVER DISEASE DYSFIBRINOGENEMIA PRIMARY FIBRINOLYSIS NORMAL LIVER DISEASE VITAMIN K DEFICIENCY COUMARIN DRUGS
Disorders of extrinsic pathway PTT: NORMAL PT : PROLONGED DISORDERS OF EXTRINSIC PATHWAY ASSAY FOR FACTORVII EARLY LIVER DISEASE COUMARIN DRUGS DYSFIBRINOGENEMIA
Disorders of extrinsic pathway  Coagulation and stypven time are normal
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
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,PLATELE T COUNT, BLEEDING TIME, FACTOR XIII ASSAY,ECLT
LEVEL BLEEDING HISTORY SURGICALPR OCEDURE RECOMMEN DED EVALUATION IV POSITIVE MAJOR/ MINOR LEVEL III TESTS ; IF NEGATIVE – FACTORVIII & IX ASSAY THROMBIN TIME ALPHA2 ANTIPLASMI N ASSAY POSTASPIRIN BLEEDING TIME FACTOR XI ASSAY
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