Hemostasis, Thromboembolism, and Shock PDF

Hemostasis, Thromboembolism, and Shock Cathy Caudill, PhD Normal fluid homeostasis Encompasses maintenance of: ¢ vessel wall integrity ¢ intravascular pressure ¢ osmolarity within certain limits ¢ blood as a liquid l until injury requires clot formation 68-year-old male with chest pain ¢ Did t...

Hemostasis, Thromboembolism, and Shock Cathy Caudill, PhD Normal fluid homeostasis Encompasses maintenance of: ¢ vessel wall integrity ¢ intravascular pressure ¢ osmolarity within certain limits ¢ blood as a liquid l until injury requires clot formation 68-year-old male with chest pain ¢ Did the clot originate here? l ¢ Did the clot travel here? l ¢ ¢ ¢ thrombus embolus Is this a postmortem clot? What are the characteristic features of different types of clots? What factors increased the risk of developing this clot? Hemostasis and Thrombosis Normal hemostasis is a set of wellregulated processes that accomplish two important functions: ¢ maintain blood in a fluid clot-free state in normal vessels ¢ induce a rapid and localized hemostatic plug at site of vascular injury Inappropriate activation of normal hemostasis = thrombosis Hemostasis: Vasoconstriction Goal: temporarily stop bleeding TRANSIENT Primary Hemostasis bridge between collagen and platelet Goal: form platelet plug promotes platelet aggregation Platelet granules α-Granules fibrinogen fibronectin factors V, VIII platelet factor 4 PDGF TGF- α Dense Bodies (δ-Granules) ADP ATP Ca++ histamine serotonin epinephrine Secondary Hemostasis activates coagulation cascade Goal: cement platelet plug with fibrin Antithrombotic counter-regulation Goal: limit clot to injured site Thrombosis ¢ intravascular coagulation of blood Virchow’s Triad •sites of trauma/inflammation •dysfunctional endothelium •aneurysms •mitral valve stenosis primary = genetic •Factor V mutation (Leiden) secondary = acquired •oral contraceptive use Thrombi may develop anywhere… ¢ mural thrombus l mural thrombus in cardiac chambers or aorta Thrombi are normally attached to underlying vessel or heart wall atheroma ¢ e.g., thrombosis after rupture of atherosclerotic plaques l thrombus rupture exposes subendothelial collagen • thrombus formation ¢ postmortem clots are unattached stenosis occlusion Thrombi are laminated alternating layers of platelets, fibrin, rbcs ¢ not as prominent in veins ¢ not present in postmortem clots ¢ laminated thrombus in a dilated aortic aneurysm Lines of Zahn fibrin red blood cells Arterial vs. Venous Thrombi Arterial (aka cardiac) thrombi usually begin at site of l l endothelial injury (e.g., plaque) turbulence (vessel bifurcation) DVT Venous thrombi l stasis Deep vein thrombosis Arterial vs. Venous Thrombi Arterial (aka cardiac) thrombi usually begin at site of l l most common sites l endothelial injury (e.g., plaque) turbulence (vessel bifurcation) coronary, cerebral, femoral arteries occluded coronary artery Venous thrombi l stasis l veins of lower extremities Arterial vs. Venous Thrombi Arterial (aka cardiac) thrombi usually begin at site of l l endothelial injury (e.g., plaque) turbulence (vessel bifurcation) Venous thrombi l stasis l coronary, cerebral, femoral arteries l veins of lower extremities components l platelets, fibrin, rbcs, degenerating leukocytes l rbcs (aka, red thrombi) other l mural thrombi = in heart chamber wall or aortic lumen l propagating tail tends to fragment à embolus l brain, kidney, spleen l lungs most common sites most likely embolize to Possible outcomes in venous thrombosis Clinical significance ¢ ¢ they cause obstruction of arteries and veins l venous thrombi usually cause congestion and edema distal to obstruction l arterial thrombi may occlude coronary and cerebral arteries, leading to infarction they are possible sources of emboli l l deep leg vein thrombi embolize to the lungs and may cause death arterial thrombi can embolize, but their role in vascular obstruction at critical sites (coronary and brain arteries) is more important Infarction ¢ area of ischemic necrosis caused by occlusion of either arterial supply or venous drainage 99% due to thrombotic or embolic events l almost all due to occlusion of arterial supply l White (anemic) infarcts kidney (healed) spleen heart www.webpath.com What type of necrosis? Red infarcts lung Embolism ¢ detached mass is carried by the blood to another site à lodges in smaller vessel l thrombus • 95% are from deep leg veins l l l l ¢ fat air amniotic fluid foreign bodies almost all originate from thrombi (99%) l “thromboembolism” Fat embolism ¢ occurs in 90% of individuals with fractures l only 10% symptomatic marrow fat bone marrow embolus in pulmonary circulation Air embolism ¢ air introduced by clumsy obstetric procedures l chest wall injuries l decompression sickness l air emboli in jugular vein Amniotic fluid embolism ¢ ¢ uncommon labor/postpartum complication l 1 in 50,000 deliveries l 20-40% mortality amniotic fluid with fetal tissues passes into maternal circulation l skin l lanugo hair l vernix caseosa fat l GI tract or respiratory mucin pulmonary capillaries filled with epithelial squames Foreign body embolism (from crushing and injecting oral meds made with talc filler) Pulmonary thromboembolism causes about 200,000 deaths per year in U.S. ¢ in more than 95% of clinically significant cases, emboli originate from deep leg vein thrombi above the level of the knee (femoral, iliac, popliteal) ¢ l emboli are carried through progressively larger veins, then through right side of heart and finally into pulmonary arteries Pulmonary thromboembolism ¢ size of embolus determines where it will lodge saddle embolus •straddles left and right pulmonary arteries embolus in a pulmonary artery branch Systemic thromboembolism most originate from intracardiac mural thrombi (thrombi in heart) ¢ usually lodge in lower extremities and brain ¢ l also heart, intestines, kidneys, spleen, eye Consequences of embolism ¢ most pulmonary emboli are clinically silent l l ¢ depends on l l l ¢ 60-80% due to dual blood supply of lungs collateral blood supply of tissue tissue’s vulnerability to ischemia caliber of occluded vessel most important consequence = Infarction Edema Due to ¢ increased hydrostatic pressure l impaired venous return • l arteriolar dilation • ¢ congestive heart failure neurohumoral dysregulation diminished plasma osmotic pressure l hypoproteinemia • albumin most important player • • • l malnutrition sodium retention • • ¢ nephrotic syndrome glomerulopathies renal insufficiency ↑renin-angiotensin-aldosterone lymphatic obstruction l inflammatory • l e.g., filariasis neoplastic obstruction • • Breast cancer post-treatment Reduced plasma osmotic pressure Hypoproteinemia ¢ albumin most important for homeostasis l l ¢ nephrotic syndrome protein-losing glomerulopathies malnutrition Kwashiorkor Sodium retention ¢ renal insufficiency Lymphatic obstruction ¢ Inflammatory l e.g., filariasis Wuchereria bancrofti Lymphatic obstruction ¢ Breast cancer or post-treatment peau d’orange Types of edema ¢ ¢ ¢ ¢ hydrothorax hydroperitoneum (ascites) hydropericardium anasarca l severe edema with subcutaneous swelling hydropericardium hydrothorax anasarca ascites Edema: Distribution dependent on cause ¢ Dependent edema influenced by gravity l legs when standing, sacrum (or scrotum) when recumbent l prominent feature of right-sided congestive heart failure l Edema: Distribution dependent on cause Generalized edema ¢ affects all body parts equally ¢ feature of renal dysfunction or nephrotic syndrome ¢ may initially manifest in tissues with loose connective matrix à periorbital edema ¢ pitting edema Pitting edema Edema: distribution dependent on cause Pulmonary edema ¢ lungs 2-3x normal weight ¢ sectioning = frothy, bloodtinged fluid ¢ most common in left-sided heart failure ¢ renal failure, ARDS, pulmonary infections, hypersensitivity reactions Most common cause of pulmonary edema = left-sided heart failure Hyperemia and Congestion ¢ ¢ ¢ active ↑ inflow red tissue does not cause ischemia ¢ ¢ ¢ passive ↓ outflow cyanosis (blue-red) close association with edema Congestion example: CRVO and BRVO ¢ A thrombus forms in the vein draining the retina, leading to congestion and subsequent edema and hemorrhage Hemorrhage ¢ extravasation of blood due to vessel rupture BRVO Types of hemorrhage ¢ ¢ Hematoma l accumulation of blood within a tissue l bruise à massive retroperitoneal hematoma from a dissecting aortic aneurysm Petechiae l 1-2 mm hemorrhages into skin, mucous membranes, or serosa l associated with • locally increased intravascular pressure • low platelet counts/defective clotting Types of hemorrhage ¢ Purpura l ≥3 mm hemorrhages l same association as petechiae, but also secondary to • trauma • vasculitis ¢ Ecchymoses l large (>1-2 cm) subcutaneous hematomas l usually after trauma l erythrocytes degraded and phagocytosed by macrophages • hemoglobin à bilirubin à hemosiderin Large accumulations of blood in body cavities hemopericardium hemothorax hemoperitoneum jaundice massive breakdown of rbcs releases bilirubin hemarthrosis Clinical significance of hemorrhage Depends on ¢ Volume l <20% blood volume loss is tolerated l >20% loss à hypovolemic shock ¢ Site l bleeding that is trivial in subcutaneous tissues may be fatal in brain l Chronic or recurrent external blood loss can lead to iron-deficiency anemia • peptic ulcer, menstruation l Iron can be recovered and re-used for hemoglobin synthesis if bleeding is internal to body cavity or tissue Shock ¢ ¢ ¢ aka, cardiovascular collapse final common pathway for a number of potentially lethal clinical events l severe hemorrhage l extensive trauma or burns l large MI l massive pulmonary embolism l sepsis characterized by systemic hypoperfusion l caused by reduction in • cardiac output • circulating blood volume l results in hypotension, followed by impaired tissue perfusion and cellular hypoxia Types of shock Cardiogenic shock ¢ results from myocardial pump failure Hypovolemic shock ¢ results from loss of blood or plasma volume Neurogenic shock ¢ loss of vascular tone and peripheral pooling of blood Anaphylactic shock ¢ generalized IgE-mediated hypersensitivity response l systemic vasodilation and increased vascular permeability Septic shock ¢ results from host immune response to infectious organisms (septicemia is not necessary) Types of Shock Disseminated Intravascular Coagulation ¢ Secondary complication in a variety of diseases l DIC is NOT a primary disease Disseminated Intravascular Coagulation ¢ consequence of widespread activation of the coagulation system l through endothelial injury l release of thromboplastic substances into the circulation Disseminated Intravascular Coagulation ¢ As a consequence of the thrombotic diathesis, there is consumption of platelets, fibrin, coagulation factors and, secondarily, activation of fibrinolytic mechanisms l leads to a hemorrhagic diathesis DIC mechanisms ¢ ¢ release of tissue factor or thromboplastic substances into the circulation widespread injury to endothelial cells Triggers of DIC: Delivery (obstetrical complications) Infections (usually gram- bacilli) Cancer (mucin-producing) Infant with DIC due to Haemophilus influenzae type B infection