thrombosis and embolism
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DESCRIPTIONThrombosis and embolism . By Dr S Homathy. Thrombosis. Thrombosis is the formation of a solid mass (blood clot) from the constituents of blood Platelets Fibrin Entrapped red cells and white cells Within the heart or vascular system in a living organism. - PowerPoint PPT Presentation
Thrombosis and embolism
Thrombosis and embolism By Dr S HomathyThrombosisThrombosis is the formation of a solid mass (blood clot) from the constituents of bloodPlateletsFibrinEntrapped red cells and white cellsWithin the heart or vascular system in a living organismThe development of a clot is life-saving when a large vessel ruptures or is severed.
However, when a thrombus develops within the vascular system, it may be life-threateningThrombosis is the consequence of inappropriate activation ( pathological) of the processes of normal haemostasisNormal HaemostasisMaintain blood in a fluid, clot-free state in normal vesselsAlso inducing the rapid formation of a localized haemostatic plug at the site of injury.Both are influenced by components of the blood vessel wall, platelets the clotting sequence.The integrity of the blood vessel wall is crucial in normal haemostasis as well as in thrombosis.
Normal Haemostasis Vessel injury brief period of arteriolar vasoconstriction (neurogenic reflex ,endothelin)
Endothelial injury exposes ECM (highly thrombogenic material).
Platelets adhere to endothelial cells and ECM, and are activated.
They release their secretary granules.
Platelet aggregation occurs forming haemostatic plug (Primary haemostasis)
Tissue factor (produced by endothelium) activates coagulation formation of thrombin which act on finbrinogen to form fibrin (secondary Haemostsis)
The process continues to form the permanent plug formed by polymerized fibrin and platelet aggregates.
At the same time tissue plasminogen activator (t-PA) is formed and it limits haemostatic plug.
Fibrinolysis is also activated to limit haemostatic plug to the site of injuryNormal EndotheliumEndothelial cells are activated by injury, infection, plasma mediators and cytokines.They have pro-thrombotic and anti-thrombotic functionsEndotheliumThe endothelial cells serve to protect against thrombi formation by
Anti-thrombotic properties:Anti-platelet effect:Non activated platelets do not adhere to endothelium.PGI2, and NO (produced by endothelium) prevent platelet adhesionAnticoagulant properties:Heparin-like molecule activate anti-thrombin IIIThrombomodulin binds thrombin which activate protein C (anticoagulant)Fibrinolytic properties:Endothelium synthesize t-PA (fibrinolysis
Endothelial cells also have the procoagulant propertiesPro-thrombotic properties:Von Willebrand factor:It enhances binding of platelets to ECM.2.Tissue factorProduced by endothelium, it activates extrinsic clotting pathwayPlasminogen activator inhibitors (PAI)
Platelets are assigned a central role in normal haemostasis and thrombosis.
They adhere to sites of endothelial injury,
aggregate to form platelet masses, release granules rich in a variety of secretary products and synthesize several types of prostaglandins.
In normal haemostasis, platelets adhere to the severed margins of a vessel within seconds to a few minutes.
The most important stimulus to such adherence is the exposure of collagen fibrilsOnce adhered, platelets release two types of granules:
(1) alpha granules which contain fibrinogen, beta thromboglobulin, cationic protein platelet factor 4 (a heparin neutralizing protein) (2) dense bodies, which are rich in serotonin, ADP, ATP ionized calciumInitially, the platelet aggregation forms a temporary haemostatic plug which is friable and easily dislocated in rapidly flowing bloodstreams at this time, the clotting sequence leads to the formation of thrombin which is the most powerful platelet aggregator yet identifiedPlatelets : (1) provide a temporary plug capable of controlling blood flow in small vessels in low pressure systems, (2) initiate the development of a permanent plug composed of aggregated platelets and fibrin, (3) release serotonin which augments vasoconstriction and (4) contributes to the coagulation mechanism.
Coagulation systemThe coagulation system plays a major role in normal haemostasis.
Maintenance of normal fluidity of blood involves the interplay between procoagulants and anticoagulants.
When the procoagulants dominate and clotting is triggered inappropriately in the intact cardiovascular system, thrombi result.The critical events in blood clotting are the conversion of prothrombin to thrombin
the subsequent conversion of soluble fibrinogen into the stable fibrin polymerThrombosisThrombosis is influenced by three major factors: VIRCHOWS TRIAD(1) injury to vascular endothelium, (2) alterations in normal blood flow and (3) alterations in the blood (hypercoagulability).
Endothelial injuryEndothelial injury plays a dominant role in the formation of thrombi in arteries and in the heart.
Once the endothelium is damaged, subendothelial collagen may be exposed and
tissue thromboplastin, etc., is released and
the sequence of platelet adherence and activation of the clotting sequence follows
Endothelial injury occurs in myocardial infarction, ulcerated atherosclerosis, trauma, and inflammatory disease of vessels.Endothelial dysfunction is also a predisposing factor for thrombosis.
Eg: Hypertension, bacterial endotoxins, hypercholestrolemia, radiation, cigarette smoking.
Blood Stasis and Turbulence of FlowTurbulence enhances endothelial injury.Stasis enhances venous thrombosis.
Both result in:Bringing platelets close to endotheliumAccumulation of clotting factorsPrevent clotting factors inhibitorsEndothelial activation Eg: aortic aneurysm, MI, valve stenosis, rheumatic heart disease, hyperviscosity, sickle cell disease.Stasis and turbulence
Distrupt laminar flow
Prevent dilution of activated clotting factors by fresh flowing blood
Retard the inflow of clotting factor inhibitors and permits build up of thrombi
Promote endothelial cell activationHypercoagulabilityIt is an alteration in coagulation leading to thrombosis.
Primary: (genetic)Factor V mutationProthrombin mutationAntithrombin III deficiencyProtein C or S deficiencySecondary:( acquired )
High risk for thrombosisProlonged immobilizationMyocardial infarctionTissue damageCancerProsthetic cardiac valvesDICLupus anticoagulant
Low risk for thrombosisAFCardiomyopathySickle cell anaemiaNephrotic syndromeContraceptive pillsSmoking
Increased numbers of platelets, increased platelet stickiness, elevated levels of fibrinogen, increased generation of thrombin, etc., have been identified as causing hypercoagulability in various clinical conditions.
Special categories among acquired causes1.Heparin-induced Thrombocytopenia: ( HIT syndrom)When heparin is administered it induces the formation of antibodies that bind platelets and activate them.Occurs when unfractionated heparin is given.Solution give low-molecular Wt heparinHave anticoagulant activityDo not interact with plateletsProlonged serum half life2.Antiphospholipid syndrome (Lupus anticoagulant):Antibodies to phospholipid (eg. Cardiolipin)In-vitro: it inhibits coagulation( inhibit assembly of phospholipid cpx)In-vivo: it induces coagulation
Approximately 20% of patients with a recent sroke were found to have anticardiolipin antibodyMorphology Thrombi may develop in the heart, arteries, veins and capillaries.
Arterial thrombi and cardiac thrombi occur at site of endothelial injury or turbulence of flow.
Venous thrombi occur in areas of blood stasis.
Thrombi usually are attached to the underlying vessel wall (mural thrombi)
Arterial thrombi grow back(retrograde direction) to the heart.
Venous thrombi grow toward the heart.
Arterial and cardiac thrombi are firmly attached to the wall
Grossly and microscopically show
lines of Zahn (layers of fibrin and platelets alternate with layers of RBC and WBC.
Implies thrombosis at a site of blood flow
Venous thrombi do no show clear lamination.Resemble coagulated blood( like clotted in test tube)Microscopic appearance of thrombi
In the heart:Attached to the underlying structureMural thrombi
common causes: MI, dilated cardiomyopathy, arrhythmia, myocarditis, valvular disease.
In arteries: common causes: atherosclerosis,aneurysm.Arterial thrombi usually occlude the lumen, common in coronary, cerebralfemoral arteries. Deep Vein thrombosis (phlebothrombosis) are almost always occlusive, Red / stasis thrombi, 90% occur in lower extremities.Resemble postmortem clotsFirmer , almost always have a point of attachmentTransection reveal vague strands of pale gray fibrin
Under special circumstances thrombi may form on heart vales.
Bacterial and fungal blood-born infection may lead to valve damageDevelopment of large thrombotic masses/ vegetations ( infective endocarditis)Sterile vegetations can also develop on noninfected valves(NBTE)Hypercoagulable states
Libman-sacks endocarditis Occurs in SLE
Classification of Thrombus according to ColorPale, formed of platelets and fibrin, small, grayish white, firm and adherent
Red, formed of red cells and fibrin, dark soft and loosely attached to the vessel
Mixed, common and has pale and red componentsPresence or absence of bacteriaInfected or septic
Non infected or aseptic
Sites of Thrombus Formation1.Thrombus in veins:
More common because of thin wall and slow blood flow:
Phlebothrombosis---- occurs in the veins of the calf Ms and femoral ,iliac veins------ pulmonary emboliIn the varicose veins2.Thrombosis in Arteries
less common than veins because of rapid flow and thick elastic wall but occur in arteries affected by:
Atheroma, polyarteritis nodosa and thromboa