Thrombosis PDF

Thrombosis THROMBUS VERSUS EMBOLUS It is important to distinguish between thrombi and emboli: A clot that adheres to a vessel wall is called a “thrombus,” whereas an intravascular clot that floats in the blood is termed an “embolus.” Thus, a detached thrombus becomes an em...

Thrombosis THROMBUS VERSUS EMBOLUS It is important to distinguish between thrombi and emboli: A clot that adheres to a vessel wall is called a “thrombus,” whereas an intravascular clot that floats in the blood is termed an “embolus.” Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and decrease tissues of oxygen and nutrients. Resting platelets: - Platelets act as vascular sentries, monitoring the integrity of the endothelium. In the absence of injury, resting platelets circulate freely. Chemical mediators synthesized by endothelial cells: such as prostacyclin and nitric oxide, are synthesized by intact endothelial cells and act as inhibitors of platelet aggregation. Prostacyclin (prostaglandin I2) acts by binding to platelet membrane receptors that are coupled to the synthesis of cyclic adenosine mono phosphate (↑cAMP), this prevents platelet activation. So, Damaged endothelial cells synthesize less prostacyclin so, the binding of prostacyclin to platelet receptors is decreased, resulting in lower levels of cAMP, which leads to platelet activation and aggregation 1-Platelet adhesion When the endothelium is injured, platelets adhere to and cover the exposed collagen of the subendothelium. 2. Platelet activation (collagen.) Receptors on the surface of the adhering platelets are activated by the collagen. This causes morphologic changes in platelets and the release of platelet granules, such as adenosine diphosphate (ADP), thromboxane A2, serotonin, platelet-activation factor, and thrombin. The resting platelets become activated and start to aggregate. 3. Platelet aggregation: -Fibrinogen, a soluble plasma GP, binds to GP IIb/IIIa receptors on two separate platelets, resulting in platelet cross-linking and platelet aggregation. 4. Formation of a clot: - Thrombin (Factor IIa) (called a serine protease), catalyzes the hydrolysis of fibrinogen to fibrin. Subsequent cross-linking of the fibrin strands stabilizes the clot and forms a hemostatic platelet-fibrin plug 5. Fibrinolysis: - Plasminogen is enzymatically processed to plasmin (fibrinolysin) by plasminogen activators in the tissue. Plasmin limits the growth of the clot and dissolves the fibrin network as wounds heal the clot and dissolves the fibrin network as wounds heal. Thrombosis is defined as the formation of a solid or semisolid mass from the constituents of the blood within the vascular system during life.  Pathogenesis: thrombus formed due to the following three factors are called Virchow’s triad:  A: Endothelial injury 1. Mechanical injury: e.g.  Pressure ,rupture and torsion of vessel  2. Degeneration of endothelial cell as in  Atherosclerosis   Myocardial infraction  3. Inflammation: phlebitis and arteritis B: Changes in blood flow: Stasis or turbulence of blood flow 1. Atrial fibrillation 2. aneurysm 3. Incompetent vascular valves and varicose vein. C: Changes in composition of blood: 1. Platelets: quantitative and qualitative changes in the function: e.g. after surgery or radiation  Increase in number  Become stickier  Become more fragile (lysis) lead to release thrombogenic factor. 2- Red blood cells: -Polycythemia: increase red blood cells blood viscosity slowing in blood flow. 3- Fibrinogen/plasma coagulation factors  Increase during pregnancy & following delivery. Types of thrombi: depends on speed of blood flow i. Pale thrombus: composed mainly of platelets and fibrin strands. This type is seen in arteries. ii. Red thrombus: composed of platelets, fibrin strands and red blood cells. this type seen in venous thrombosis.  According to the presence or absence ofpyogenic bacteria, thrombi can be classified to 1- Septic thrombi e.g. those complicating bacterial endocarditis. 2- Aseptic thrombi. Fates (outcome) of a thrombus: thrombus can have one of the following fates: A-Propagation: The thrombus may accumulate more platelets and fibrin & propagate to cause vessel obstruction. B-Embolization: The thrombus may dislodge and travel to other sites in the vasculature. Such a traveling thrombus is called thromboembolus. An embolus may obstruct a vessel. Theobstruction leads to the death of the tissue due to a decreased blood supply is called infarction. Therefore, an embolus can eventually lead to an infarction of an organ. E.g pulmonary infarction can be caused by a thromboembolus from deep venous thrombosis.  C- Dissolution: The thrombus may be removed byfibrinolytic activity. D- Organization and recanalization Organization refers to the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts into the fibrin-rich thrombus. Organization is accompanied by the formation of capillary channels across the thrombus, re-establishing lumen continuity to some extent. This is known as recanalization. Deep venous thrombosis (DVT):  Usually starts in deep veins within the calf muscles.  Patient present with local pain, heat & edema  Has higher incidence in middle aged & elderly people, after surgery   May dislodge and cause pulmonary thromboembolism and infarction.  Embolism Definition: An embolus is a detached intravascular solid, liquid or gaseous mass that is carried by blood to sites distant from its point of origin. After traveling via the blood, the embolus can obstruct a vessel. Causes of embolism: Major form is An embolus can arise from: Thrombus → thromboembolism Rare form is Platelets aggregates o Fragment of a tumor o Fat globules o air o Amniotic fluid in pregnant women (Disseminated Intravascular Coagulation (DIC). o Infected foreign material  Site of impaction 1- Pulmonary circulation 2-systemic circulation  Pulmonary thromboembolism (PTE): refers tothe impaction of an embolus in the pulmonaryarteries & their branches. Vast majority have origin from thrombi within 1- Veins of calf muscles of the leg (DVT) 2- Femoral veins. Clinical outcome of pulmonary thrombo-Embolism Depends on: 1- Severity of occlusion: a. Size of pulmonary artery occluded b. Number on occluding emboli. 2- Cardio-respiratory status of the patient. Site of impaction 1- Main pulmonary trunk 2- Across pulmonary bifurcation (saddle embolus). 3- Medium-sized pulmonary arteries. 4- Small peripheral arteries.  Outcomes of PTE 1- Asymptomatic (60%-80%) Small/rapidly removed by the fibrinolytic activity. 2- Sudden death/acute Rt sided heart failure (massive pulmonary emboli) (5%): occur in: 3- Pulmonary infraction (10-15%)  Relatively small-sized pulmonary artery occluded. 4- Embolic obstruction of medium sized arteriesmanifests as pulmonary hemorrhage but usuallydoes not cause infarction because of dual blood inflow to the area from the bronchial circulation.  If the cardiorespiratory condition of the patient is poor (i.e., if the patient previously had cardiac or pulmonary disease), then obstruction of a mediumsized pulmonary artery by a medium-sized embolus can lead to pulmonary infarction. 5- Pulmonary hypertension (uncommon).  Repeated showering of small thrombi (longduration).  Progressive occlusion of small peripheral branches leads to pulmonary blood pressure Systemic thromboembolism:  Emboli travel through systemic circulation.  Origin of systemic emboli arise from the left side of the heart, due to prosthetic heart valve, rheumatic heart valve disease, infective endocarditis. Arterial emboli almost always cause infraction. Emboli from cases of infective endocarditis led to septic infarcts or abscesses. Systemic thrombi may impact in: 1) Lower extremities (which is the commonest) 2) Brain (common and fatal) 3) Mesenteric vessels (intestinal) 4) Spleen 5) upper extremities (least one)   Clinical significance Depends on:1-Size 2-site of impaction Femoral artery occlusion lead to gangrene of lower limb, not necessarily endangering patient life. Middle cerebral artery occlusion by much small embolus cerebral infarction anddeath. Infarction Infract: is an ischemic necrosis caused by occlusion of either the arterial supply or venous drainage in aparticular tissue Causes: 1) Nearly 99% of all infarcts result from thrombotic or embolic events. 2) Local vasospasm 3)External compression (by pressure) or internal compression (e.g. by tumor) of the vessels. 3) Rupture or torsion (twisting) of blood vessel wall.  Infarcts are classified (types) depending on : A) The basis of their color into : 1) Hemorrhagic (Red) infarcts  Venous occlusion  Loose tissue (spongy)  Double blood supply  e.g. lung 2) Anemic (White) infarcts occur  Arterial occlusion  In solid organ e.g. heart ,kidney and spleen. B) The presence or absence of microbial infection into: 1) Septic infarcts 2) Bland infarcts  Morphological changes of the infarcted area: Cross (naked eye) All infarcts are wedge-shaped. Apex pointed toward focus of vascular occlusion and the periphery of the organ forming the base of the wedge Clinical examples of infarction: A. Myocardial infarction  Usually results from occlusive thrombosis of a major coronary artery.  Is a white infarct.  Can cause sudden death, cardiac failure, etc...        B. Cerebral infarcts  May appear as pale or hemorrhagic  Embolus breaks into smaller emboli(pushed distally) Reopening of the already closed major artery Blood pours into soft area of liquefactive necrosis Extensive hemorrhage into what had been initiallypale infraction  C. Lung infarcts  Are typically dark red& conical (wedge-shaped).  Can cause chest pain, hemoptysis, etc