CIRCULATORY DISTURBANCE
Thrombosis
Introduction:
Thrombosis is the formation of a blood clot (thrombus) within the intact vascular system during life. Unlike a normal hemostatic plug that forms at a site of vascular injury and stops bleeding, a thrombus forms inappropriately and can obstruct blood flow or serve as a source of emboli. Understanding thrombosis is critical in pathology and clinical care because thrombi underlie many conditions such as stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism, and also have important ocular manifestations (e.g., retinal artery/vein occlusions). For optometrists, recognition of the ocular signs of thrombosis and timely referral can prevent permanent vision loss.
Definition
A thrombus is a solid mass of blood constituents formed within the cardiovascular system during life. Thrombosis refers to the pathological process of thrombus formation.
Virchow’s Triad — The Three Predisposing Factors
Virchow described three major factors that predispose to thrombosis. Most clinically significant thrombi arise when one or more of these are present:
- Endothelial injury: Damage to the vascular endothelium exposes subendothelial collagen and tissue factor, promoting platelet adhesion and coagulation (e.g., atherosclerotic plaque rupture, vasculitis, trauma).
- Abnormal blood flow (stasis or turbulence): Turbulence favors platelet adhesion and endothelial injury (arterial thrombosis), while stasis promotes local accumulation of activated clotting factors (venous thrombosis).
- Hypercoagulability (blood): Increased tendency to clot due to inherited or acquired conditions (e.g., factor V Leiden, prothrombin mutation, malignancy, pregnancy, oral contraceptives).
Types of Thrombi (Gross & Microscopic)
- White (arterial) thrombus: Rich in platelets and fibrin, pale, often forms at sites of high flow over atherosclerotic plaques.
- Red (venous) thrombus: Rich in red blood cells trapped in fibrin, forms in low-flow venous systems (deep veins of the leg).
- Lines of Zahn: Alternating light (platelet/fibrin) and dark (RBC-rich) layers seen in thrombi formed in flowing blood—helps distinguish ante-mortem thrombus from post-mortem clot.
- Mural thrombus: Thrombus adherent to vessel wall (heart chambers, aorta).
- Occlusive thrombus: Fills and blocks the lumen.
Common Sites of Thrombosis
- Arterial: coronary arteries, cerebral arteries (leading to ischemic stroke), peripheral arteries, retinal artery.
- Venous: deep veins of lower limbs (DVT), pelvic veins, portal and hepatic veins, cerebral venous sinuses.
- Cardiac: mural thrombi after myocardial infarction, vegetations on valves in infective endocarditis (septic thrombi).
Pathogenesis — How Thrombi Form
- Endothelial activation/injury exposes subendothelial collagen and releases tissue factor → platelet adhesion and activation.
- Platelet aggregation mediated by von Willebrand factor and fibrinogen binding to activated platelet receptors (GPIIb/IIIa).
- Coagulation cascade activation generates thrombin which converts fibrinogen to fibrin, stabilizing the platelet plug.
- Propagation occurs by accumulation of additional platelets and fibrin; in venous thrombi, RBCs become enmeshed in fibrin nets.
- Modulating factors such as antithrombin III, protein C and S, and fibrinolytic activity normally limit thrombus growth; deficiency or inhibition of these factors leads to excessive thrombosis.
Consequences of Thrombosis
- Local obstruction: Ischemia and infarction downstream of an arterial thrombus (e.g., central retinal artery occlusion causes sudden painless vision loss).
- Embolization: Part or whole thrombus detaches and travels to distant site (e.g., DVT → pulmonary embolus; left-sided cardiac thrombus → systemic emboli causing stroke or limb ischemia).
- Organization and recanalization: Thrombus may be invaded by fibroblasts and endothelial cells, forming new channels (recanalization) and resulting in permanent vessel narrowing.
- Infection: Septic thrombi can cause abscesses at embolic sites.
Laboratory and Imaging Investigation
- Complete blood count (CBC): May show leukocytosis if inflammation/infection present.
- D-dimer: Elevated in active thrombosis but non-specific (useful for ruling out DVT/PE in low-risk patients).
- Coagulation profile: PT/INR, aPTT to assess baseline coagulation and guide anticoagulation therapy.
- Tests for thrombophilia: Protein C/S levels, antithrombin III, Factor V Leiden mutation, prothrombin gene mutation, antiphospholipid antibodies.
- Imaging:
- Venous duplex ultrasound — first-line for suspected DVT.
- CT pulmonary angiography — for pulmonary embolism.
- Carotid Doppler or CT/MR angiography — in arterial thrombotic disease.
- Fundus examination and fluorescein angiography — for retinal artery or vein occlusion.
Clinical Syndromes & Ocular Relevance
- Central Retinal Artery Occlusion (CRAO): Usually due to an embolus (cholesterol, calcific, platelet-fibrin) or in-situ thrombosis of the central retinal artery. Presents with sudden, profound, painless monocular vision loss. Fundus shows a pale retina with a cherry-red spot at the fovea. Urgent systemic and ophthalmic evaluation for carotid disease or cardiac source is required.
- Branch Retinal Artery Occlusion (BRAO): Causes sectoral visual field loss corresponding to the occluded branch.
- Central Retinal Vein Occlusion (CRVO): Often associated with systemic vascular risk factors (hypertension, diabetes, hypercoagulable states). Presents with sudden painless vision loss, dilated tortuous veins, widespread retinal hemorrhages, cotton wool spots, and macular edema. Thrombus formation in the central retinal vein is a key event.
- Branch Retinal Vein Occlusion (BRVO): Sectoral hemorrhages and vision changes correlated to the affected area; often at arteriovenous crossings where the artery compresses the vein.
- Ocular Ischemic Syndrome: Severe carotid artery occlusive disease can cause chronic hypoperfusion of the eye with mid-peripheral retinal hemorrhages and neovascular glaucoma.
- Orbital/ocular surface thrombosis: Rarely, thrombosis of orbital veins or cavernous sinus thrombosis can cause painful proptosis, chemosis, ophthalmoplegia, and vision loss — a surgical/emergent condition often due to infection or sepsis.
Treatment & Prevention
Treatment aims to prevent thrombus extension, embolization, and recurrence, while managing complications. Approach differs for arterial vs venous thrombosis and depends on site and cause.
Acute Management
- Anticoagulation: Heparin (unfractionated heparin or low-molecular-weight heparin) for venous thrombosis and to prevent propagation. Transition to oral anticoagulants (warfarin, DOACs) for long-term therapy depending on indication.
- Thrombolysis / thrombectomy: Considered for selected cases (massive pulmonary embolism with hemodynamic compromise, acute limb ischemia, or selected arterial occlusions). In CRAO, ocular intra-arterial or systemic thrombolysis has been attempted in specialized centers but remains controversial and time-sensitive.
- Antiplatelet therapy: Aspirin or other antiplatelet agents are the mainstay for arterial thrombosis prevention (e.g., prevention of stroke, myocardial infarction).
- Supportive ophthalmic treatment: For retinal vein occlusions — intraocular anti-VEGF injections or steroids to manage macular edema; laser photocoagulation for neovascularization.
Long-term & Preventive Measures
- Identify and treat underlying risk factors: control hypertension, diabetes, hyperlipidemia, smoking cessation, weight management.
- Investigate and manage hypercoagulable states; long-term anticoagulation in appropriate patients.
- Antiplatelet therapy for atherosclerotic arterial disease.
- Carotid endarterectomy or stenting when indicated for severe carotid stenosis to prevent embolic arterial events.
- Perioperative thromboprophylaxis for high-risk surgical patients.
Prognosis
- Depends on site, size of thrombus, rapidity of treatment, and presence of collateral circulation. For example, CRAO often results in permanent severe visual loss despite treatment because retinal neurons are highly sensitive to ischemia.
- CRVO prognosis varies: ischemic CRVO has a worse visual prognosis and higher risk of neovascular complications than non-ischemic CRVO.
- Venous thromboembolism prognosis depends on response to anticoagulation and recurrence risk; pulmonary embolism can be life-threatening.
Key Points for Optometrists
- Recognize sudden, painless monocular vision loss as an emergency — consider CRAO or CRVO and refer urgently.
- Look for fundus signs: cherry-red spot in CRAO; dilated tortuous veins and widespread hemorrhages in CRVO.
- Advise systemic evaluation for vascular risk factors and possible cardiac/carotid sources of emboli.
- Coordinate care with physicians (cardiology, neurology, hematology) for systemic workup and long-term anticoagulation decisions when indicated.
- Monitor and manage ocular complications (macular edema, neovascular glaucoma) in collaboration with retinal specialists.
Infarction
Introduction:
Infarction is a common pathological consequence of impaired blood supply. It is defined as an area of ischemic necrosis caused by obstruction of blood flow, usually due to thrombosis, embolism, or vascular occlusion. Infarcts are important because they underlie serious diseases such as myocardial infarction, cerebral stroke, pulmonary infarction, and retinal infarction. In the eye, vascular occlusion leading to infarction of the retina or optic nerve is a vision-threatening emergency. Optometrists must recognize these presentations promptly for urgent referral and management.
Definition
An infarct is an area of ischemic necrosis in a tissue or organ resulting from obstruction of the arterial supply or venous drainage.
Causes of Infarction
- Thrombosis: In-situ clot formation obstructing blood flow.
- Embolism: Detached material (thromboembolus, fat, air, amniotic fluid) lodging in a vessel.
- Vascular spasm: Sudden constriction, e.g., vasospasm in coronary artery.
- Extrinsic compression: Tumor, torsion (ovarian/testicular torsion), trauma.
- Venous obstruction: Outflow block leading to congestion and necrosis.
Types of Infarction
- White (pale) infarcts: Occur due to arterial occlusion in solid organs with end-arterial circulation such as heart, kidney, spleen, retina. Appear pale due to lack of collateral flow.
- Red (hemorrhagic) infarcts: Occur in tissues with dual blood supply (lungs, intestines) or when venous drainage is blocked. Appear red due to blood seepage into necrotic tissue.
- Septic infarcts: Result from infected emboli (infective endocarditis), leading to abscess formation.
Pathology
- Gross: Infarct is wedge-shaped, with the apex pointing to the occluded vessel.
- Microscopic: Coagulative necrosis is typical in most solid organs. Liquefactive necrosis occurs in the brain due to enzymatic digestion. Inflammatory response surrounds the infarct, followed by fibroblastic repair and scar formation.
Factors Influencing Infarction
- Nature of vascular supply: Organs with dual blood supply (lungs, liver) are less vulnerable; end-arterial organs (retina, brain, kidney, spleen) are highly susceptible.
- Rate of occlusion: Slow occlusion allows collateral circulation to develop; sudden occlusion causes infarction.
- Tissue vulnerability to hypoxia: Neurons are highly sensitive (irreversible injury in 3–4 minutes), myocardial cells (20–30 minutes), fibroblasts (hours).
- Oxygen content of blood: Anemia or hypoxemia increases risk and severity.
Clinical Examples of Infarction
- Myocardial infarction: Due to coronary artery thrombosis or plaque rupture.
- Cerebral infarction (stroke): Due to thromboembolic occlusion of cerebral arteries.
- Pulmonary infarction: Secondary to pulmonary embolism.
- Renal infarction: Arterial occlusion in kidney.
- Retinal infarction: Central retinal artery occlusion causes sudden, profound, painless vision loss.
Ocular Infarction — Special Relevance
- Central Retinal Artery Occlusion (CRAO): Classic example of a white infarct in the retina. Fundus shows a pale retina with a cherry-red spot at the fovea. Irreversible vision loss occurs if circulation is not restored within 90–120 minutes.
- Branch Retinal Artery Occlusion (BRAO): Infarction limited to sector of retina supplied by the branch vessel.
- Anterior Ischemic Optic Neuropathy (AION): Infarction of the optic nerve head due to occlusion of posterior ciliary arteries. Presents with sudden vision loss and swollen optic disc.
- Choroidal infarcts: Seen in giant cell arteritis or after vascular occlusion, producing localized retinal pigment epithelial changes.
Investigations
- Systemic:
- Blood tests for coagulation profile, lipid profile, glucose levels.
- ECG, echocardiography for cardiac infarction.
- Neuroimaging (CT/MRI) for cerebral infarction.
- Ophthalmic:
- Fundus examination (cherry-red spot, pale retina in CRAO).
- Fluorescein angiography: delayed or absent filling of retinal arteries.
- OCT: inner retinal layer thickening in acute infarction.
- ESR and CRP: to rule out giant cell arteritis in AION.
Complications
- Permanent tissue necrosis and functional loss.
- Fibrosis and scarring of infarcted area.
- Infection and abscess formation (septic infarcts).
- Organ-specific complications: heart failure after MI, stroke-related disability, blindness after CRAO.
Management
General Principles
- Immediate restoration of blood flow when possible (reperfusion therapy in myocardial or cerebral infarction).
- Anticoagulants, antiplatelet agents, thrombolytics depending on site and cause.
- Management of underlying risk factors (atherosclerosis, hypertension, diabetes, hyperlipidemia, smoking).
Ocular Infarction (CRAO, AION)
- Emergency measures: Ocular massage, lowering intraocular pressure (IV acetazolamide, mannitol), breathing carbogen to dilate vessels. These are of limited benefit if not performed within 1–2 hours.
- Identify systemic cause: Carotid Doppler, echocardiography, ESR/CRP for arteritis.
- Long-term management: Control systemic vascular risk factors, antiplatelet therapy, treatment of giant cell arteritis with high-dose steroids if suspected.
Ophthalmic Importance for Optometrists
- Optometrists may be first to observe ocular infarcts during fundus examination (cherry-red spot, sectoral pallor, swollen disc).
- CRAO and AION are ophthalmic emergencies; immediate referral to an ophthalmologist and systemic physician is mandatory.
- Optometrists should check blood pressure, inquire about systemic risk factors, and educate patients about urgent systemic evaluation.
- In patients with known cardiovascular disease, regular ocular check-ups may help in early recognition of vascular complications.
Embolism
Introduction:
An embolism is the lodging of an intravascular object (embolus) that traveled from a distant site, causing obstruction of blood flow in a vessel. Emboli can be fragments of thrombus, fat, air, amniotic fluid, cholesterol crystals, tumor fragments, or foreign material. Embolic events are clinically important because they may produce sudden ischemia and infarction in vital organs — brain (stroke), lungs (pulmonary embolism), kidney, spleen, and eye (retinal artery occlusion). For optometry students, recognition of embolic retinal disease and understanding its systemic implications (e.g., cardiac or carotid sources) is essential for timely referral and prevention of further embolic events.
Definition
An embolus is any intravascular material that travels through the bloodstream and lodges at a site distant from its origin, producing vascular occlusion. Embolism refers to the process or the clinical event caused by such lodging.
Types of Emboli
- Thromboembolism: Most common type — a fragment of thrombus breaks off (e.g., deep vein thrombosis → pulmonary embolism; left heart thrombus or aortic/carotid thrombus → systemic emboli such as retinal artery emboli).
- Septic emboli: Infected emboli from infective endocarditis or septic thrombophlebitis — may cause abscesses at embolic sites.
- Fat embolism: After long-bone fractures or orthopedic surgery — causes pulmonary and cerebral symptoms; may cause retinal microemboli.
- Air embolism: Due to trauma, surgical procedures, or central venous catheter insertion — large pulmonary or cerebral consequences possible.
- Amniotic fluid embolism: Rare, catastrophic event during labour/delivery — causes DIC and multi-organ failure.
- Cholesterol (athero) emboli (Hollenhorst plaques): Cholesterol crystals or plaque debris from ulcerated atherosclerotic plaques (usually carotid or aortic) — classically lodge in retinal arterioles and appear as bright, refractile plaques on fundus exam.
- Tumor emboli: Malignant cells or tumor fragments causing vascular occlusion and metastatic seeding.
- Foreign material: Injected particles, talc (in IV drug users), or other iatrogenic materials.
Pathogenesis
- An embolus originates at a primary site (e.g., thrombus in deep veins, cardiac mural thrombus, atherosclerotic plaque) and is dislodged into the circulation.
- Embolus travels with blood flow until it reaches a vessel too small to pass through, lodging and producing partial or complete occlusion.
- Downstream ischemia and infarction follow, severity depending on vessel size, collateral circulation, tissue vulnerability, and duration of occlusion.
- Septic emboli additionally carry microorganisms, creating focal infections or abscesses at the embolic site.
Clinical Consequences by Embolus Type & Site
- Pulmonary embolism (PE): Usually from DVT — sudden dyspnea, chest pain, hypoxia; large PE can cause hemodynamic collapse.
- Systemic arterial embolism: From left heart (AF, MI with mural thrombus), aortic/aortic arch plaques — may cause stroke, limb ischemia, renal or splenic infarction, or ocular emboli (retinal artery occlusion).
- Retinal embolism: Causes sudden, painless monocular visual loss or transient visual obscurations (amaurosis fugax) depending on whether occlusion is permanent or transient. Visual field defect matches territory supplied by occluded arteriole.
- Septic emboli: Fever plus focal infarct/abscess signs, often in setting of infective endocarditis.
- Fat embolism syndrome: Respiratory distress, petechial rash, neurological signs — typically 24–72 hours after injury.
- Air embolism: Sudden cardiorespiratory or neurologic collapse depending on size and route.
Ocular Manifestations of Embolism
- Hollenhorst plaque (cholesterol embolus): Bright, refractile, yellow–orange cholesterol crystal lodged at retinal arteriolar bifurcations. Often asymptomatic but indicates high risk of cerebrovascular events and carotid atherosclerosis.
- Platelet-fibrin or calcific emboli: Appear dull white (fibrin-platelet) or large and chalky (calcific) — calcific emboli often originate from cardiac valves and can completely occlude the central retinal artery producing profound vision loss.
- Amaurosis fugax: Transient monocular blindness due to temporary embolic occlusion — may be a warning sign of impending stroke.
- Central retinal artery occlusion (CRAO): Embolic CRAO frequently leads to permanent severe visual loss; fundus shows pale retina and cherry-red spot.
- Branch retinal artery occlusion (BRAO): Sectoral retinal whitening and corresponding visual field loss.
- Retinal microembolization: Multiple tiny emboli may cause scattered retinal ischemic lesions and visual disturbances.
Investigations
- Ocular exam: Careful funduscopy to identify embolic material (Hollenhorst plaque, calcific or platelet-fibrin embolus), retinal pallor, and distribution of infarction.
- Visual field testing: To document and localize visual defects.
- Fluorescein angiography: Demonstrates delayed or absent arterial filling corresponding to embolic occlusion.
- Carotid Doppler ultrasound: To detect carotid atherosclerotic plaques as potential source of cholesterol emboli.
- Cardiac evaluation: ECG, transthoracic or transesophageal echocardiography to look for mural thrombus, valvular vegetations, or cardiac sources of emboli.
- Blood tests: CBC, coagulation profile, inflammatory markers (ESR/CRP), blood cultures if infection suspected.
- Cross-sectional imaging: CT/MR angiography of head and neck if cerebral ischemia is suspected or to evaluate vascular anatomy.
Management
Management depends on embolus type, embolic site, and patient stability. It includes acute measures to restore perfusion where possible, prevention of further embolization, and treatment of the embolic source.
Immediate/Ocular-Specific Measures
- Urgent referral: Any suspected retinal arterial embolus producing acute visual loss requires immediate ophthalmology and systemic vascular workup.
- CRAO acute measures (time-sensitive; evidence variable): Ocular massage, lowering intraocular pressure (IV acetazolamide, topical beta-blocker, paracentesis in selected cases), inhalation of carbogen (95% O2/5% CO2), and urgent thrombolysis in selected centers. These measures have limited proven efficacy and must be considered within a very narrow therapeutic window.
- Supportive care: Monitor and manage complications (macular ischemia, neovascularization). Visual rehabilitation if irreversible damage occurs.
Treat the Source & Prevent Recurrence
- Antiplatelet therapy: Aspirin or dual antiplatelet therapy as indicated for atherothrombotic disease.
- Anticoagulation: For cardioembolic sources (e.g., atrial fibrillation) — warfarin or DOACs per cardiology guidance.
- Carotid revascularization: Endarterectomy or stenting for significant symptomatic carotid stenosis to prevent further emboli.
- Infective endocarditis: Prolonged IV antibiotics and possible surgical valve intervention to remove the nidus of septic emboli.
- Fat/air embolism: Supportive care in ICU, oxygenation, and stabilization; hyperbaric oxygen in select air embolism cases.
- Management of cardiovascular risk factors: Hypertension, diabetes, dyslipidemia, smoking cessation.
Prognosis
- Prognosis varies by embolus size and lodged site. Small cholesterol emboli may be asymptomatic but indicate high systemic vascular risk. Large calcific or thrombotic emboli causing CRAO/BRAO often produce permanent visual impairment.
- Risk of further embolic events is significant if the source is not identified and treated — e.g., carotid plaque or cardiac mural thrombus.
- Septic emboli carry risk of abscess formation and increased mortality if untreated.
Key Points for Optometrists
- Carefully inspect retinal arterioles for refractile emboli (Hollenhorst plaques) during routine fundus exams — finding such a plaque warrants immediate communication with the patient’s physician and referral for vascular workup.
- Any sudden, painless monocular visual loss or transient monocular visual obscuration (amaurosis fugax) should prompt urgent referral — these are potential embolic phenomena and warnings of cerebrovascular risk.
- Document findings (fundus photos, visual fields) and ensure rapid systemic evaluation (carotid and cardiac imaging) to locate the embolic source and prevent catastrophic events like stroke.
- Educate patients about cardiovascular risk factor modification and the importance of follow-up with cardiology/neurology when embolic disease is suspected.
