Thromboembolism & Infarction PDF

Thromboembolism & Infarction Yahya Al-Ghamdi, MD, FCAP, FASCP Courtsey of Saeed Asiry, MD Objectives Overview of hemostasis Thrombosis Embolism Infarction Morphological changes Clinical correlation Definitions Hemostasis is a series of regulated processes that culminate in the fo...

Thromboembolism & Infarction Yahya Al-Ghamdi, MD, FCAP, FASCP Courtsey of Saeed Asiry, MD Objectives Overview of hemostasis Thrombosis Embolism Infarction Morphological changes Clinical correlation Definitions Hemostasis is a series of regulated processes that culminate in the formation of a blood clot that limits bleeding from an injured vessel. (i.e. physiologic) Thrombosis is the formation of blood clot (thrombus) within non-traumatized, intact vessels.  Hemostasis https://www.semanticscholar.org/paper/Mechanisms-and-regulation-of-the-XII-driven-contact-Labberton/affa5f08f73680c03b5328619f6150fcf991e613/figure/0 https://link.springer.com/chapter/10.1007/978-94-017-7215-0_10 https://www.ahajournals.org/doi/10.1161/strokeaha.110.581256 Thrombosis - “Virchow triad” Abnormal formation of a solid mass from blood Kumar, Vinay; components Abbas, (platelets, Abul red fibrin, entrapped K.;and white Aster, Jon C.. Robbins blood cells) Basic Pathology E-Book (Robbins Pathology) (p. 106). Elsevier Health Sciences. Kindle Edition. 1. Endothelial Injury Severe injury exposes collagen and tissue factor Inflammation and other toxic stimuli - shift the pattern of gene expression in endothelium to one that is “prothrombotic.” called endothelial activation or dysfunction 2. Abnormal Blood Flow Turbulence and stasis are a major contributor in the development of venous thrombi Normal blood flow is laminar such that the platelets (and other blood cellular elements) flow centrally in the vessel lumen, separated from the endothelium by a slower-moving layer of plasma keeps platelets and factors dispersed and inactivated Examples: Aneurysm, arrythmia, Immobilization increases risk of DVT 3. Hypercoagulability Abnormally high tendency of the blood to clot, and is typically caused by alterations in coagulation factors. Hypercoagulability Primary (Genetic) Secondary (Acquired) 3. Hypercoagulability - Primary The factor V Leiden (point mutations in the factor V gene): Factor V resistant to cleavage and inactivation by protein C Point mutation in prothrombin gene: It leads to elevated prothrombin https://www.ahajournals.org/doi/10.1161/strokeaha.110.581256 3. Hypercoagulability - Secondary Prolonged bed rest or immobilization Atrial fibrillation Tissue injury (surgery, fracture, burn) Cancer Prosthetic cardiac valves Disseminated intravascular coagulation (DIC) Heparin-induced thrombocytopenia (HIT) Antiphospholipid syndrome (APS)/lupus anticoagulant 3. Hypercoagulability - Secondary Hyperestrogenic states (pregnancy and postpartum) Oral contraceptive use Sickle cell anemia Smoking Thrombosis – Gross Morphology Pulmonary embolism Pulmonary embolism Mural Thrombus: Cardiac wall Thrombosis - Morphology Fibrin and platelets Red blood cells Lines of Zahn: pale platelet and fibrin layers alternating with darker red cell–rich layers Fate of the Thrombus Propagation: Enlargement Embolization: Transported elsewhere Dissolution: Fibrinolysis Organization and recanalization: ingrowth of endothelial cells, smooth muscle cells, and fibroblasts Organization and recanalization Clinical Features Venous Thrombosis (Phlebothrombosis): Most common in the superficial or deep veins of legs Deep vein thrombosis (DVT): The large leg vein (at, above or below) the knee (e.g., the popliteal, femoral, and iliac veins) Cause localize pain and edema; or asymptomatic Associated with stasis or hypercoagulable state Embolize to lungs >> ischemia, coagulative necrosis, pulmonary hypertension Clinical Features Trousseau Syndrome (migratory thrombophlebitis): - Paraneoplastic; thromboembolic phenomenon seen in disseminated cancers Arterial and Cardiac Thrombosis: Atherosclerosis, myocardial infarction and rheumatic heart disease – thrombosis – embolize to brain, kidneys and spleen Disseminated Intravascular Coagulation (DIC) Pathologic activation of coagulation cascade > widespread formation of thrombi in the microcirculation > ischemia and infarction >> organ damage, particularly of the brain, lungs, heart, and kidneys Consumptive coagulopathy: Uses up platelets and coagulation factors > Thrombosis can evolve into a bleeding catastrophe such as hemorrhagic stroke or hypovolemic shock Secondary to another disease process: Obstetric complications Advanced malignancy Sepsis Embolism An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction Emboli travel through the blood until they encounter vessels too small to permit further passage, causing partial or complete vascular occlusion Pulmonary Embolism Originate from deep venous thromboses and are the most common form of thromboembolic lesions Can occlude the main pulmonary artery, lodge at the pulmonary artery bifurcation (saddle embolus), or pass out into the smaller branching arteries Pulmonary Embolism Rarely, a venous embolus passes through an interatrial or interventricular defect and gains access to the systemic arterial circulation (paradoxical embolism) Outcome: Clinically silent: Undergo organization Infarction (Coagulative necrosis) Pulmonary hypertension >> right ventricular heart failure (cor pulmonale) Sudden death Pulmonary Embolism Systemic Thromboembolism Mostly arise from intracardiac mural thrombi (any reason) Most come to rest in the lower extremities (75%) or the brain (10%), but other tissues, including the intestines, kidneys, spleen, and upper extremities, may be involved The consequences of systemic emboli depend on the vulnerability of the affected tissues to ischemia, the caliber of the occluded vessel, and whether a collateral blood supply exists Fat and Marrow Embolism Microscopic fat globules—sometimes with associated hematopoietic bone marrow—can be found in the pulmonary vasculature after fractures of long bones or, rarely, in the setting of soft tissue trauma and burns Air Embolism Gas bubbles within the circulation can coalesce to form frothy masses that obstruct vascular flow and cause distal ischemic injury Decompression sickness: When air is breathed at high pressure (e.g., scuba and deep-sea diving) nitrogen is dissolved in the blood and tissues If the diver then ascends (depressurizes) too rapidly, the nitrogen comes out of solution in the tissues and the blood Infarction Is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage Arterial thrombosis or arterial embolism underlies the vast majority of infarctions Infarction Venous thrombosis most common outcome is just congestion Infarcts caused by venous thrombosis are more likely in organs with a single efferent vein (e.g., testis and ovary) Infarction - Morphology Red (hemorrhagic) or white (anemic) and may be septic or bland Red infarcts: (1) With venous occlusions (e.g., testicular or ovarian torsion) (2) In tissues with dual circulations (e.g., lung and small intestine) that allow blood to flow from collaterals Infarction - Morphology White infarcts: Occur with arterial occlusions in solid organs with end- arterial circulation (e.g., heart, spleen, and kidney) Infarction - Morphology Red infarction in Lung White infarction in Spleen Infarction - Morphology The dominant histology is ischemic coagulative necrosis Acute inflammation is present along the margins of infarcts within a few hours The brain (CNS) infarction results in liquefactive necrosis Most infarcts are ultimately replaced by scar Kidney scarring Question A 72-year-old male with a past medical history of hypertension and DM presented to the ER with a sudden right side weakness. He recently had a long flight from NY. His right leg is painful, hot and shows swelling located around and below the knee. Examination of this patient heart will most likely show: A. Myocardial infarction B. Cardiomyopathy C. Ventricular septal defect D. Mitral valve stenosis References Kumar V, Abbas AK, Aster JC. Robbins & Cotran Pathologic Basis of Disease. Philadelphia, PA: Elsevier Saunders; 2014, 9th Edition Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. Philadelphia, PA: Elsevier Saunders; 2017,10th Edition www.amboss.com Thank You Questions? [email protected]