THROMBOSIS DEFINITION PROCESS OF FORMATION OF SOLID MASS
THROMBOSIS DEFINITION PROCESS OF FORMATION OF SOLID MASS IN CIRCULATION FROM THE CONSTITUENTS OF FLOWING BLOOD • THE MASS IS THROMBUS • THE DANGER BEINGISCHEMIC INJURY THROMBOEMBOLISM.
VENOUS THROMBUS
DEEP VEIN THROMBUS
RUPTURED ATHEROSCLEROTIC PLAQUE WITH THROMBUS
FRESH THROMBUS
SADDLE THROMBUS
ENDOTHELIAL DAMAGE
THROMBUS IN A VESSEL
DEEP VEIN THROMBOsis
PATHOPHYSIOLOGY OF THROMBUS VIRCHOW’S TRIAD 1. ENDOTHELIAL INJURY 2. ALTERATION IN BLOOD FLOW 3. HYPERCOAGULABILITY OF THE BLOOD
1. ENDOTHELIUM • INTACT ENDOTHELIUM HAS FOLLOWING FUNCTIONS 1. PROTECTS FLOWING BLOOD FROM THROMBOGENIC EFFECTS OF SUBENDOTHELIUM 2. ELABORATION OF ANTITHROMBOTIC FACTORSA. HEPARIN LIKE SUBSTANCE WHICH ACCELERATES THE FUNCTION OF ANTITHROMBIN III & INACTIVATES SOME COAGULATION FACTORS.
ENDOTHELIUM • B. THROMBOMODULIN –CONVERTS THROMBIN TO ACTIVATOR OF PROTEIN C, AN ANTICOAGULANT. • C. INHIBITORS OF PLATELET AGGREGATION SUCH AS ADPase, PGI 2 OR PROSTACYCLIN • D. PLASMINOGEN ACTIVATORFIBRINOLYTIC ACTIVITY
ENDOTHELIUM 3. RELEASE PROTHROMBOTIC FACTORS LIKE A. THROMBOPLASTIN OR TISSUE FACTOR
ENDOTHELIUM • B. von WILLEBRAND FACTOR-CAUSE ADHERENCE OF PLATELETS TO SUBENDOTHELIUM • C. PLATELET ACTIVATING FACTORACTIVATOR & AGGREGATOR OF PLATELETS • D. INHIBITOR OF PLASMINOGEN ACTIVATOR THAT SUPPRESSES FIBRINOLYSIS
ENDOTHELIAL INJURY • MAJOR CAUSE OF THROMBI OF HEART & ARTERIES IS ENDOTHELIAL INJURY • CLINICAL CONDITIONS WHERE ENDOTHELIAL INJURY IS SEEN A. MYOCARDIAL INFARCTION, B. MYOCARDITIS, C. CARDIAC SURGERY, D. PROSTHETIC VALVES
CAUSES OF ENDOTHELIAL INJURY E. ULCERATED PLAQUES, F. HAEMODYNAMIC STRESS IN HYPERTENSION, G. ARTERIAL DISEASES, H. DIABETES MELLITUS,
CAUSES OF ENDOTHELIAL INJURY I. ENDOGENOUS CHEMICAL AGENTS HYPERCHOLESTEROLAEMIA, ENDOTOIXINS, J. EXOGENOUS CHEMICAL AGENTSCIGARETTE SMOKE
2. PLATELETS PLAY A CENTRAL ROLE IN NORMAL HAEMOSTASIS ADHESION TO SUBENDOTHELIAL COLLAGEN Von WILLEBRANDS FACTOR IS REQUIRED FOR PLATELET ADHESION PLATELET ACTIVATIONPLATELET RELEASE REACTIONGRANULES ARE RELEASED
ROLE OF PLATELETS PLATELET AGGREGATION BY ADP FROM DENCE BODIES (PLATELET GRANULES) – TEMPORARY HAEMOSTATIC PLUG
3. COAGULATION SYSTEM 1. INTRINSIC PATHWAYCONTACT WITH ABNORMAL SURFACE - ACTIVATION OF F-12 & SEQUENTIAL INTERACTIONS OF FACTORS XI, IX, VIII & FINALLY F- X
3. COAGULATION SYSTEM 2. IN THE EXTRINSIC PATHWAY TISSUE DAMAGE-RELEASE OF TISSUE FACTOR OR THROMBOPLASTIN WHICH INTERACT WITH F – VII AND CALCIUM IONS – ACTIVATES FACTOR X
COAGULATION SYSTEM 3. COMMON PATHWAY-BEGINS WHERE BOTH INTRINSIC & EXTRINSIC PATHWAYS CONVERGE TO ACTIVATE FACTOR X WHICH FORMS COMPLEX WITH F - Va & PLATELET FACTOR 3 IN THE PRESENCE OF CALCIUM IONS.
COAGULATION SYSTEM • THIS COMPLEX ACTIVATES PROTHROMBIN (F-II) TO THROMBIN(FIIa)
REGULATORS OF COAGULATION SYSTEM • 1. PROTEASE INHIBITORS-ACT ON COAGULATION FACTORS & OPPOSE THE FORMATION OF THROMBIN PROTEASE INHIBITORS ARE - ANTITHROMBIN III, PROTEIN C, C 1 INACTIVATOR, α 1 -ANTITRYPSIN, α 2 -MACROGLOBULIN
REGULATORS OF COAGULATION SYSTEM 2. FIBRINOLYTIC SYSTEMPLASMINOGEN ACTIVATOR CONVERTS PLASMINOGEN TO PLASMIN A FIBRINOLYTIC ENZYME RELEASING FIBRIN SPLIT PRODUCTS.
2. HYPERCOAGULABILITY OF THE BLOOD 1. NEPHROTIC SYNDROME 2. ADVANCED CANCER 3. EXTENSIVE TRAUMA, BURNS, PUERPERIUM.
HYPERCOAGULABILITY OF THE BLOOD COAGULATION IS FAVOURED BY ADVANCED AGE, SMOKING, USE OF ORAL CONTRACEPTIVES & OBESITY.
HYPERCOAGULABILITY OF THE BLOOD HYPERCOAGULABILITY MAY BE a. DUE TO INCREASE COAGULATION FACTORS, b. INCREASE IN PLATELET COUNT
HYPERCOAGULABILITY OF THE BLOOD WITH INCREASE IN THEIR ADHESSIVENESS C. DECREASED LEVELS OF COAGULATION INHIBITORS SUCH AS ANTI -THROMBIN III, FIBRIN SPLIT PRODUCTS
3. ALTERATION OF BLOOD FLOW FORMATION OF ARTERIAL & CARDIAC THROMBI IS FACILITATED BY TURBULENCE IN BLOOD FLOW(NORMAL AXIAL FLOW IS DISTURBED) STASIS INITIATES THE VENOUS THROMBI EVEN WITHOUT ENDOTHELIAL INJURY.
TYPES OF THROMBI AND THEIR MORPHOLOGY • THROMBI OCCUR IN HEART, ARTERIES, VEINS & CAPILLARIES • ARTERIAL THROMBI PRODUCE ISCHEMIA & INFARCTION • CARDIAC & VENOUS THROMBI CAUSE EMBOLISM.
MORPHOLOGY OF THROMBI GROSS- VARIES IN SIZE, , SHAPE, COMPOSITION DEPENDING ON THE SITE OF ORIGIN
MORPHOLOGY OF THROMBI ARTERIAL THROMBI ARE WHITE & MURAL, ARE FIRM & PALE • VENOUS THROMBI - RED & OCCLUSIVE, SOFT & GELATINOUS
MORPHOLOGY OF THROMBI DEPENDS ON RATE OF FLOW OF BLOOD RAPID ARTERIAL & CARDIAC CIRCULATION - LINES OF ZAHNALTERNATE LAYERS OF LIGHT STAINING PLATELET AGGREGATES WITH FIBRIN & DARK STAINING LAYERS OF RED CELLS
LINES OF ZAHN-
LINES OF ZAHN-
POSTMORTEM CLOT WITH CURRENT JELLY APPEARANCE
POSTMORTEM CLOT WITH CHICKEN FAT AND CURRENT JELLY APPEARANCE
MORPHOLOGY OF THROMBI • SLOW MOVING FLOW IN VEINS- RED THROMBIABUNDANT RED CELLS, LEUCOCYTES & PLATELETS TRAPPED IN FIBRIN MESHWORK.
VENOUS THROMBI
RED THROBUS IN INFERIOR VENA CAVA
THROMBUS IN A VESSEL
RUPTURED ATHEROSCLEROTIC PLAQUE WITH THROMBUS
ANTIMORTEM THROMBI & POSTMORTEM CLOTS • ANTIMORTEM THROMBI- GROSSDRY, GRANULAR, FIRM, FRIABLE, ADHERENT TO VESSEL WALL, MAY OR MAY NOT FIT THEIR VASCULAR CONTOURS, LINES OF ZAHNS PRESENT
ANTIMORTEM THROMBI & POSTMORTEM CLOTS • POSTMORTEM CLOT- GROSSLY GELATINOUS, SOFT, RUBBERY, NOT ATTACHED TO THE VESSEL WALL, TAKES THE SHAPE OF THE VESSEL WALL OR IT’S BIFURCATION, • THE SURFACE IS CHICKEN FAT YELLOW COVERING THE UNDERLYING RED CURRENT JELLY
FATE OF THROMBI 1. RESOLUTION- ACTIVATION OF FIBRINOLYTIC SYSTEM-RELEASE OF PLASMIN-DISSOLVE THROMBUS, PHAGOCYTES PHAGOCYTOSE THROMBUS , PROTEOLYTIC ENZYMES FROM LEUCOCYTES & ENDOTHELIUM DIGEST THE COAGULUM
FATE OF THROMBI • 2. ORGANISATION - CAPILLARIES GROW, FIBROBLASTS GROW TO PRODUCE GRANULATION TISSUECOLLAGENOUS TISSUE COVERED BY ENDOTHNELIUM- RECANALISATION HYALINISATION , CALCIFICATION TO FORM PHLEBOLITHS.
A THROMBOSIS OF A CORONARY ARTERY IS SHOWN HERE IN CROSS SECTION.
RECANALISATION OF CORONARY ARTERY THROMBOSIS
FATE OF THROMBUS 3. PROPAGATION- THROMBUS MAY ENLARGE IN SIZE DUE TO MORE & MORE DEPOSITION OF CONSTITUENTS OF BLOOD
PROPOGATED THROMBUS
FATE OF THROMBUS MAY CAUSE OBSTRUCTION TO SOME IMPORTANT VESSEL 4. THROMBOEMBOLISMGET DETACHED FROM VESSEL WALL, RELEASED INTO BLOOD STREAM AS EMBOLI.
VENOUS THROMBI WITH THROMBOEMBOLISM
FACTORS PREDISPOSING TO THROMBOSIS • 1. GENETIC(PRIMARY) FACTORSa. DEFICIENCY OF ANTITHROMBIN, PROTEIN C OR S, b. DEFECTS IN FIBRINOLYSIS c. MUTATION IN FACTOR V
FACTORS PREDISPOSING TO THROMBOSIS • 2. ACQUIRED (SECONDARY ) FACTORSA - RISK FACTORSADVANCED AGE, PROLONGED BED REST, IMMOBILISATION, USE OF ORAL CONTRACEPTIVES, CIGARETTE SMOKING, TISSUE DAMAGE (TRAUMA, FRACTURE, BURNS)
FACTORS PREDISPOSING TO THROMBOSIS • CLINICAL CONDITIONS PREDISPOSING TO THROMBOSIS a. HEART DISEASES- MI, CHF, MITRAL STENOSIS, CARDIOMYOPATHY b. ATHEROSCLEROSIS,
FACTORS PREDISPOSING TO THROMBOSIS c. ANEURYSMS OF AORTA & OTHER VESSELS, VARICOSITIES OF LEG VEINS d. NEPHROTIC SYNDROME,
FACTORS PREDISPOSING TO THROMBOSIS f. DISSEMINATED CANCERS, g. LATE PREGNANCY & f. PUERPERIUM.
CLINICAL EFFECTS OF THROMBOSIS • DEPENDS ON SITE OF THROMBI, RAPIDITY OF FORMATION & NATURE OF THROMBI • 1. CARDIAC THROMBI- SUDDEN DEATH • 2. ARTERIAL THROMBI - INFARCTIONLEADING TO GANGRENE, SUDDEN DEATH IN CASE OF CORONARY ARTERY THROMBOSIS
CLINICAL EFFECTS OF THROMBOSIS • 3. VENOUS THROMBITHROMBOEMBOLISM, OEDEMA, POOR WOUND HEALING, SKIN ULCERS, PAINFUL THROMBOSED VEINS(THROMBOPHLEBITIS),
CLINICAL EFFECTS OF THROMBOSIS PAINFUL WHITE LEG (PHLEGMASIA ALBA DOLENS) DUE TO ILEOFEMORAL VENOUS THROMBOSIS IN POSTPARTUM CASES, THROMBOPHLEBITIS MIGRANS IN CANCER ( TROUSSEAU SIGN )
CLINICAL EFFECTS OF THROMBOSIS • 4. CAPILLARY THROMBI- MAY GIVE RISE TO DIC
DISSEMINATED INTRAVASCULAR COAGULATION DEFIBRINATION SYNDROME OR CONSUMPTION COAGULOPATHY IS A COMPLEX THROMBOHAEMORRHAGIC DISORDER (INTRAVASCULAR COAGULATION AND HAEMORRHAGE)
DISSEMINATED INTRAVASCULAR COAGULATION • ETIOLOGY 1. MASSIVE TISSUE INJURY- IN OBSTETRICAL SYNDROMESa. ABRUPTIO PLACENTAE,
DISSEMINATED INTRAVASCULAR COAGULATION b AMNIOTIC FLUID EMBOLISM, c. RETAINED DEAD FETUS, OTHER CONDITIONS LIKE MASSIVE TRAUMA, METASTATIC MALIGNANCIES, SURGERY
DIC • 2. INFECTIONS - ENDOTOXAEMIA, GRAM-NEGATIVE AND MENINGOCOCCAL SEPTICAEMIA, CERTAIN VIRAL INFECTIONS, MALARIA, ASPERGILLOSIS
DIC • 3. WIDESPREAD ENDOTHELIAL DAMAGEAORTIC ANEURYSM, HAEMOLYTIC URAEMIC SYNDROME, SEVERE BURNS, ACUTE GLOMERUONEPHRITIS
ETIOLOGY OF DIC 4. MISCELLANEOUS CAUSES LIKE SNAKE BITE , SHOCK, HEAT STROKE, ACUTE INTRAVASCULAR HAEMOLYSIS
PATHOGENESIS OF DIC -4 PHASES 1. ACTIVATION OF COAGULATIONETIOLOGIC FACTORS LISTED ABOVE INITIATE WIDESPREAD ACTIVATION OF COAGULATION PATHWAY BY RELEASE OF TISSUE FACTOR
PATHOGENESIS OF DIC-4 PHASES 2. THROMBOTIC PHASEENDOTHELIAL DAMAGE-PLATELET AGGREGATION AND ADHESION – DEPOSITION OF SMALL THROMBI AND EMBOLI THROUHOUT THE MICROVASCULATURE
DIC 4 PHASES 3. CONSUMPTION PHASE – CONSUMPTION OF COAGULATION FACTORS AND PLATELETS 4. SECONDARY FIBRINOLYSISPROTECTIVE MECHANISM AT THE SITE OF INTRAVASCULAR COAGULATION- FIBRIN SPLIT PRODUCTS
DIC CLINICAL FEATURES OF DIC 2 MAIN FEAURES OF DIC ARE 1. BLEEDING 2. ORGAN DAMAGE DUE TO ISCHEMIA 3. MICROANGIOPATHIC HAEMOLYTIC ANAEMIA 4. THROMBOSIS IN LARGER ARTERIES AND VEINS
LABORATORY INVESTIGATIONS IN DIC 1. PLATELET COUNT – LOW 2. PERIPHERAL SMEAR- FEATURES OF MICROANGIOPATHIC ANAEMIASCHISTOCYTES-DAMAGE TO RBCS CAUSED BY TRAPPING AND PASSAGE THROUGH THE FIBRIN THROMBI
LABORATORY FINDINGS IN DIC 3. PROTHROMBIN TIME , THROMBIN TIME, ACTIVATED PARTIAL THROMBOPLASTIN TIME ARE ALL PROLONGED
LABORATORY FINDINGS IN DIC 4. PLASMA FIBRINOGEN LEVELSREDUCED DUE TO CONSUMPTION COAGULOPATHY 5. FIBRIN DEGRADATION PRODUCTS - ARE RAISED DUE TO FIBRINOLYSIS
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