Thrombosis, Embolism, and Infarction

Thrombosis, Embolism and Infarction – kill more than cancer and infectious disease combined

50% of myocardial infarctions are immediately fatal
infarction of heart, lungs, and brain kill more than cancer and infectious disease combined
venous or right atrium emboli infarct lung (pulmonary embolism); left atrium emboli infarct distal organs

thrombus formation is disruption of delicate balance between clotting and anticoagulation (see figure below)

anti-coagulation

pro-coagulation

Virchow’s Triad: Blood, Surface, and Flow – any derangement in any of these factors leads to thrombosis

originally endothelium itself was thought to cause clotting; now known to be associated molecules
prostacyclin, t-PA, and heparin retard clotting; vWF, TF, tPA inhibitor (tPAI), thromboxane A₂ promote it
extracellular matrix is made over several days; it contains collagen and proteoglycan, and has many functions

inflammatory, immune, regulation of growth, absorption of LDL (which increases thrombogenicity)
control process of thrombosis – both activators (vWF) and inhibitors (PGI₂ and tPA)

Healing of Thrombosis

recanalization – healing response in which blood vessels are formed through thrombus or scar tissue

long term healing – organization, fibroblast proliferation, focal deposition of collagen

microscopic events in myocardial infarction

damage is reversible only in the first 30 minutes
4-12 hours – coagulative necrosis, edema (separation of myocytes), acute inflammation, sometimes hemorrhage
18-24 hours – more necrosis, purrhosis (nuclei shrink)
1-3 days – hyperemia (complementary vessels dilate to perfuse necrotic tissue, increasing bloodflow)
3-7 days – macrophages move in, granulation tissue, risk of cardiac aneurism (pericardial sac fills with blood)

process of resolution of a thrombus may also lead to thromboembolism with the possibility of infarction

Clinical Assays for Thrombus

assay for factors generated in the formation of thrombus

platelet factor 4 (PF4) and beta-thromboglobulin (TG) determine extent of platelet release after activation and aggregation

blood levels of fibrinopeptides A and B reflect the conversion of fibrinogen to fibrin by thrombin