THROMBOSIS

Why don’t you bleed to death from a minor injury? HAEMOSTASIS Why don’t you bleed to death from a minor injury? Successful haemostasis depends on vessel wall platelets coagulation system fibrinolytic system

Blood Vessels constrict to limit blood loss arteries, veins, capillaries mechanism not fully understood

Platelets adhere to damaged vessel wall adhere to each other form a platelet plug platelet release reaction

Platelet Release Reaction ATP ADP ADP, thromboxane A2 cause platelet aggregation 5HT, platelet factor 3 also released PF3 important in coagulation Platelets coalesce after aggregation

Coagulation Cascade Series of inactive components converted to active components Prothrombin Thrombin Fibrinogen Fibrin

Coagulation 1 ml of blood can generate enough thrombin to convert all the fibrinogen in the body to fibrin Tight regulation therefore required Balance of procoagulant and anticoagulant forces

Control of Coagulation Thrombin destroys factors V and VIII Thrombin inhibitors anti-thrombin III* alpha 1 anti-trypsin alpha 2 macroglobulin protein C and S* * inherited deficiency may thrombosis

Plasminogen activators Fibrinolytic therapy widely used Breakdown of fibrin Plasminogen Plasmin Plasminogen activators Fibrinolytic therapy widely used streptokinase tPA

Endothelium Anti-thrombotic plasminogen activators prostacyclin nitric oxide thrombomodulin

Thrombosis Definition Thrombosis is the formation of a solid mass of blood within the circulatory system INAPPROPRIATE ACTIVATION OF THE HEMOSTATIC PROCESS IN UNINJURED VASCULATURE OR FORMATION OF THROMBUS IN THE SETTING OF RELATIVELY MINIMAL VASCULAR INJURY

FACTORS PREDISPOSING TO THROMBOSIS virchows triad

ENDOTHELIAL INJURY Abnormalities of the vessel wall atheroma direct injury inflammation

ABNORMALITIES OF BLOOD FLOW TURBULENCE Endothelial injury Local areas of stasis Disrupt laminar flow Moves platelets from center of flow to the vessel wall Prevent dilution of activated clotting factors by flowing blood Slow down the inflow of clotting factor inhibitors Promotes endothelial cell

Abnormalities of blood components HYPERCOAGUABILITY: ANY ALTERATION OF THE COAGULATION PATHWAY THAT PREDISPOSES TO THROMBOSIS PRIMARY (GENETIC) FACTOR V GENE MUTATION AND PROTHROMBIN GENE MUTATIONS MOST FREQUENT V becomes resistant to protein c inactivation Prothrombin levels elevated SECONDARY (ACQUIRED) Bed rest – immobilization, post-op obesity, - smokers cancer, atrial fibrillation, myocardial infarction, tissue damage (surgery, burns) post-partum

Appearances of thrombi- Arterial Thrombi Morphology i- pale granular lines of Zahn lower cell content

Arterial Thrombi Morphology Adherent masses of blood that demonstrate areas of pale alternating with areas of red Lines of Zahn

Arterial Thrombi Morphology

Arterial Thrombi Outcome Similar to venous thrombi Resolution Organization/Incorporation/Recanalization Embolization (arterial) Propagation

Disseminated Intravascular Coagulation (DIC) Sudden onset of fibrin thrombi in the microcirculation with consumption of coagulation factors and formation of fibrin degradation products A potential complication of any disease state/process associated with the widespread activation of thrombin

Thrombi Morphology: Venous Appearances of thrombi Venous soft gelatinous deep red higher cell content Usually occlusive Red (because they form in stasis syndrome and have more associated enmeshed RBCs) Long - forming a cast of vein with markings on them from venous valves Red blood cells alternating with peripheral areas of fibrin

Venous Thrombi: Clinical

Venous Thrombi: Outcomes of thrombosis ( Fates): Lysis complete dissolution of thrombus fibrinolytic system active bloodflow re-established most likely when thrombi are small

Outcomes of thrombosis ( Fates): Propagation progressive spread of thrombosis distally in arteries proximally in veins

Outcomes of thrombosis Organisation reparative process ingrowth of fibroblasts and capillaries (similar to granulation tissue) lumen remains obstructed

Outcomes of thrombosis Recanalisation bloodflow re-established but usually incompletely one or more channels formed through organising thrombus

Outcomes of thrombosis Embolism part of thrombus breaks off travels through bloodstream lodges at distant site

VENOUS THROMBI FATES

Effects of thrombosis Arterial Venous ischaemia congestion infarction depends on site and collateral circulation Venous congestion oedema ischaemia infarction

Coronary artery thrombosis

Coronary artery thrombosis