Lecture 18 - Thrombosis

• Thrombosis • Embolism • Infarctions

• Department of pathology • Dr.Bushra Al-Ayadhy

Thrombosis Definition The formation of a a solid, structured mass (a thrombus) within an intact cardiovascular system. Cougulum unstructured when blood clots outside circulatory system

Normal hemostasis Three contributors to maintain normal hemostasis 1-Vascular wall (endothelium and underlying connective tissue) 2-Platelets 3-Clotting factors

Virchow’s triad Three influences on thrombogenesis 1.Endothelial injury (atherosclerosis, vasculitis, trauma, radiation, bacterial toxins) 2. Alteration in normal flow (turbulence in arteries e.g atherosclerotic plaque and stasis in the heart e.g dilatation and veins e.g abnormally dilated varicose veins, DVT) 3. Hypercoagulability of blood ( antithrombin III def, urinary excretion in nephrotic syndrome, procougulants secretion by tumour cells, tissue factors release after trauma, burns or delivery)

Morphology • • • •

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Firmly attached to wall Occlusive or Non-occlusive (cardiac chamber and aorta)(mural ie applied to the wall) On the arterial side gray-red [Pale layers of platelets and fibrin alternate with darker layers of more red cell (lines of Zahn)] Sites Left ventricle overlying a myocardial infarction, auricular appendages in AF, aorta overlying ulcerated or fissured atheroma, atherosclerotic large arteries e.g iliacs, carotids, aneurysmal sac On the venous side Red-blue Sites Dilated superficial veins, deep veins embolizing to the lungs Formation of valvular vegetations Infective endocarditis- bacterial or fungus-laden thrombi on valvular leaflets or mural endocardium complicating blood-borne infections Nonbacterial thrombotic endocarditis small vegetations on any valve in patients with SLE or disseminated cancer

2. 3. 4. 5.

Fate of a thrombus Propagate to obstruct a vessel or branch of it Embolize to distant site Resolve (fibrinolytic action) Organize and recanalize ( invaded by BV’s and fibroblasts)

- Diminish vascular flow - Infarction (localized areas of ischemic necrosis) - Fragment and create emboli (obstructive free-floating intravascular masses)

Clinical significance of deep vein thrombosis of the legs • Common clinical problem, silent or embolize to the lungs It occurs in: • Advanced age ( reduce physical activity with venous stasis, atherosclerosis with endothelial damage) • Bed rest (vascular stasis and hypercoagulability) • Heart diseases • Myocardial infarction (dyskinesis of ventricle wall, endocardial cell injury and stasis) • Congestive heart failure • Valvular damage or CHD’s ( turbulence endocardial damage, may lead to bacterial seeding and IE) • Rheumatic mitral stenosis (left atrial and auricular enlargement with AF leading to turbulence and stasis) • Tissue injury (fractures, burns, extensive soft tissue injury releases tissue factors and reduce physical activity) • Visceral cancer (migratory thrombophlebitis Trousseau’s phenomenon cancer cell releases procougulants esp. pancreatic and GI cancers) • Late pregnancy and post-delivery period • Oral contraception (high dose estrogen)

Infarction Definition A localized area of ischemic necrosis in an organ or tissue resulting from sudden occlusion of its arterial supply - Thrombotic or embolic in most cases - Rarely, caused by spasm e.g coronary arteries, twisting of an a mobile organ e.g loop of bowel, ovary, compression of the wall of an artery e.g expansile tumour

2. 3. 4. 5.

Factors that modify the outcome General status of CVS (anemia and CHF increase the likelihood) Anatomic pattern-dual blood supply (L&L), interconnecting anastomosis (SI& Circle of W) Vulnerability of tissue to ischemia e.g N, RPTE in kidneys and myocardial cells Rate of development of the occlusion

Morphology Pale (white) solid organs with end arteries e.g K& S Hemorrhagic (red), -loose tissues e.g L, venous occlusion e.g ovary torsion, anastomotic circulation e.g SI Ischemic cougulative necrosis Wedge shape apex at the vascular obstruction base at the external surface of the organ with eventual replacement by a scar Liquefactive necrosis e.g Brain Myocardial, cerebral and pulmonary infarction are responsible for half of all deaths.

Embolism Definition An intravascular solid, liquid, or gaseous mass carried by blood to a site distant from its origin. (98% arise from a thrombi) OthersDebris from atheromatous plaque (atheroemboli) Fat emboli

Fate of emboli • Emboli arising in veins impact the lungs ( Pulmonary embolism) • Emboli arising in arteries impact in the legs, brain and organs (systemic embolism)

Pulmonary embolism (PE) Occlusion of pulmonary arteries 95% arise in deep deep veins of the legs Consequences Large (5%) impact in the major pulmonary arteries or astride the bifurcation of pulmonary artery (saddle embolus) Sudden death, acute cor pulmonale (RHF) Small emboli (60 to 80%) Clinically silent, transient chest pain, hemoptysis, infarction Medium sized (20 to 35%) occlude medium sized peripheral pulmonary branches leading to infarction Multiple recurrent small-right heart strain- chronic cor pulmonale-pulmonary hypertension Clinical significance Silent Symptomatic but respond to fibrinolytic treatment Catastrophic (5 to 10% mortality rate)

Arterial emboli (Systemic embolism) • Most (70 to 75%) arise from thrombi in the heart, secondary to myocardial infarction • 5 to 10% arise from auricular thrombi • 1 to 2% arise from thrombi in dilated cardiac chambers (cardiomyopathy, myocarditis) • Debris from ulcerated atheromata prosthetic valves IE and paradoxic emboli • 15% origin unknown Site of lodgment in the lower extremities (70 to 75%0, brain (10%) and other organs (10%)

Fat embolism 3. Most common after thromboembolism with intravascular globules of fat 4. Fractures of large bones with fatty marrow 5. Extensive trauma to fatty tissue 6. Rarely in DM, SCA, pancreatitis

Fat embolism syndrome Thrombocytopenia (adhesion of platelets to fat microemboli), petechia in skin & conjuctiva, respiratory difficulty, coma, death Pathogenesis • Fat globules from tissue enter venous channels at site of injury, enters venous channels, intravascular formation of fat globules • Activation of coagulation with DIC • Free fatty acids are released injure capillaries, transudation of fluid and thrombi formation Morphology Intravascular fat globules in micro vessels esp. lungs, brain, kidneys Lungs- hyaline membranes within alveolar spaces

Amniotic fluid embolism A sudden complication of delivery marked by respiratory difficulty, cyanosis, vascular collapse progressing into convulsions, coma and death Pathogenesis • A tear in the placental membranes – infusion of amniotic fluid – embolization to pulmonary circulation of debris e.g fetal epithelial squames, lanugo hair. • Release of vasoconstrictors (PG) • Release of thrombogenic factors – DIC • Blockade of pulmonary circulation by microthrombi Morphology Amniotic debris in pulmonary capillaries

Air or Gas Embolism Deep sea divers and underwater construction workers exposed to increased atmospheric pressure of O2 mixed with nitrogen or helium With rapid decompression, excess gas is released in the circulation as gas bubbles • The “bends” small vessels in muscles and around joints • The”Chokes”with lodgment in the lungs • In Bone Marrow, ischemic necrosis (head of femur, tibia, humeri) Recompression (resolubilises the gas bubbles and permit slow decompression)