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Thromboembolism

Thromboembolism is a serious medical condition in which a blood clot (thrombus) forms and may dislodge to travel through the bloodstream as an embolus, obstructing blood vessels and potentially causing organ damage or death. It includes venous thromboembolism (VTE), where clots typically form in deep veins and may lead to pulmonary embolism (PE), and arterial thromboembolism, involving clots from arterial sources or the heart that often cause ischemic stroke or acute limb ischemia. VTE encompasses two main forms: deep vein thrombosis (DVT), in which the clot develops in the deep veins of the legs, pelvis, or arms, and PE, where the clot lodges in the pulmonary arteries of the lungs, impairing blood flow and oxygenation.^[1] VTE affects up to 900,000 individuals annually in the United States (as of 2025), with an incidence of 1 to 2 cases per 1,000 people worldwide, positioning it as the third most common cardiovascular disease after myocardial infarction and stroke.^[2]^[3]^[4] The development of thromboembolism arises from disruptions in the normal balance of blood coagulation, often involving Virchow's triad: stasis of blood flow, endothelial injury, and hypercoagulability.^[5] Common causes include damage to vessel walls from surgery, trauma, or procedures; slowed blood flow due to prolonged immobility; and increased clotting tendency from conditions like cancer, infections, or inflammatory diseases.^[6] Key risk factors encompass advanced age (over 60 years), obesity, smoking, pregnancy or hormone therapy (e.g., oral contraceptives), inherited thrombophilias such as Factor V Leiden mutation, and recent major surgery or acute illness, with up to 80% of VTE cases linked to at least one identifiable risk factor.^[7]^[8] Certain populations, including those with active cancer or neurological disorders causing leg paresis, face particularly high risks, and VTE is more prevalent in Caucasians and African Americans compared to other ethnic groups.^[9]^[10] Symptoms vary by location and severity but often include unilateral leg swelling, pain, warmth, and redness in DVT cases, which may be asymptomatic in up to half of patients until complications arise.^[7] In PE, sudden shortness of breath, sharp chest pain worsened by breathing, rapid heartbeat, coughing up blood, or lightheadedness signals a medical emergency, as it can lead to right heart strain, hypoxemia, or sudden death if untreated.^[11] Complications include chronic issues like post-thrombotic syndrome, causing persistent leg pain, swelling, and ulcers due to vein damage, affecting 20-50% of DVT survivors.^[7] Diagnosis typically involves clinical assessment using tools like the Wells criteria, imaging such as ultrasound for DVT or CT pulmonary angiography for PE, and blood tests like D-dimer.^[1] Treatment centers on anticoagulation with drugs like heparin or direct oral anticoagulants to prevent clot progression and recurrence, with thrombolytics or surgery for severe cases; compression stockings help DVT symptoms.^[1] Prevention for at-risk individuals includes prophylactic anticoagulants during high-risk periods (e.g., post-surgery), early mobilization, and mechanical devices like intermittent pneumatic compression, potentially reducing VTE incidence by up to 50% in hospital settings.^[12] Despite advances, VTE remains a leading preventable cause of hospital-related death, underscoring the need for awareness and risk stratification.^[2]

Epidemiology

Incidence and Prevalence

Thromboembolism includes both venous thromboembolism (VTE), such as deep vein thrombosis and pulmonary embolism, and arterial thromboembolism, such as ischemic stroke and acute myocardial infarction. Globally, the incidence of VTE is approximately 1-2 cases per 1,000 adults annually, with rates varying by region and population characteristics. In the United States, up to 900,000 individuals are affected by VTE annually as of 2025.^[2] Arterial thromboembolic events, exemplified by ischemic strokes, affect between 500,000 and 700,000 individuals newly each year, reflecting the substantial burden of arterial pathology.^[13] Prevalence of VTE is notably higher among hospitalized patients, reaching up to 60% in high-risk groups like those undergoing orthopedic surgery without prophylaxis, compared to 1-2% with appropriate preventive measures. Arterial events are more frequent in the elderly, particularly those over 75 years with underlying cardiovascular disease, where annual incidence rates can exceed 5 per 1,000 in affected populations due to age-related vascular changes and comorbidities.^[14] Demographic variations further influence thromboembolism rates; VTE incidence rises to 1-2 per 1,000 pregnancies, with a pronounced increase postpartum due to hypercoagulable states and venous stasis.^[15] In contrast, arterial thromboembolism shows greater prevalence among men over 50 years with a history of smoking, where tobacco use promotes atherosclerosis and thrombus formation, more than doubling the risk (2- to 4-fold increase) compared to non-smokers.^[16] Regionally, VTE incidence is higher in Western countries, at 1-2 per 1,000 person-years, attributed to lifestyle factors like obesity and immobility, while rates in Asian populations have historically been lower but are increasing.^[17] Emerging data from the 2020s indicate rising arterial thromboembolic events in Asia, driven by urbanization, dietary shifts, and rising cardiovascular risk factors, with pulmonary embolism incidence in China, for instance, showing a fivefold increase over recent decades.^[18]

Mortality and Morbidity

Thromboembolism imposes a substantial burden on mortality, particularly through venous thromboembolism (VTE), which accounts for an estimated 60,000 to 100,000 deaths annually in the United States, many of which are sudden and undiagnosed.^[2] Pulmonary embolism (PE), a severe manifestation of VTE, carries a case-fatality rate of approximately 12% within one month of diagnosis, with overall short-term mortality for PE ranging from 10% to 30% depending on severity and comorbidities.^[19] Untreated PE is associated with a mortality rate as high as 30%, whereas timely treatment with anticoagulation reduces this to 2% to 8%.^[20] For arterial thromboembolism, events such as ischemic stroke exhibit a 30-day mortality rate of around 15% in high-income countries, underscoring the acute lethality of these occlusive complications.^[14] Recurrent thromboembolic events further exacerbate mortality risks. In patients with VTE, recurrence is linked to a 5.2-fold higher hazard of death compared to those without recurrence.^[21] Similarly, arterial events like recurrent stroke significantly elevate overall mortality, with studies indicating that prior thromboembolic history can increase the risk by up to threefold in affected populations.^[22] Beyond immediate fatalities, thromboembolism leads to considerable morbidity, manifesting as chronic conditions that impair quality of life. Post-thrombotic syndrome (PTS) develops in 20% to 50% of patients following deep vein thrombosis (DVT), resulting in persistent leg pain, swelling, and in severe cases, venous ulcers that necessitate ongoing medical management.^[23] For arterial thromboembolism, approximately 50% of stroke survivors experience long-term disability, including 15% to 30% with severe permanent disability affecting mobility, speech, and daily activities, contributing to long-term dependency and healthcare utilization.^[13] Recent studies from the 2020s highlight evolving trends in thromboembolism outcomes, with improved anticoagulation therapies contributing to reduced acute mortality rates—for instance, all-cause mortality after incident VTE stands at 3.1% at 30 days and 19.6% at one year among older adults—yet morbidity is rising due to aging populations and increased survival from initial events.^[24] This shift emphasizes the growing challenge of managing chronic sequelae in an expanding survivor cohort.

Pathophysiology

Virchow's Triad

Virchow's triad, a foundational concept in the understanding of thromboembolism, was introduced by German pathologist Rudolf Virchow in 1856 to describe the key factors contributing to thrombus formation and embolization.^[25] Virchow's work emphasized the cellular basis of pathology, linking peripheral venous thrombi to pulmonary emboli through these interrelated elements, which remain central to contemporary pathophysiology despite advances in molecular biology.^[26] The triad comprises three primary components: stasis of blood flow, endothelial injury, and hypercoagulability. Stasis refers to reduced or turbulent blood flow, which allows the local accumulation of activated clotting factors and promotes the initiation of coagulation at sites such as venous valves or in low-shear areas like the left atrial appendage.^[25] Endothelial injury involves damage to the vascular lining, often from mechanical trauma, inflammation, or toxins, which exposes subendothelial collagen and tissue factor, thereby activating the extrinsic coagulation pathway via factor VII and disrupting natural anticoagulant mechanisms like thrombomodulin expression.^[25] Hypercoagulability encompasses both inherited and acquired states that shift the hemostatic balance toward thrombosis; for instance, the genetic mutation Factor V Leiden impairs the anticoagulant action of activated protein C,^[27] increasing venous thromboembolism risk by 3- to 8-fold in heterozygotes.^[28] These components frequently interact in clinical scenarios, amplifying thrombotic risk; for example, major surgery can simultaneously induce stasis through postoperative immobility and endothelial injury via vessel manipulation or inflammation.^[29] While the triad applies broadly to both venous and arterial thromboembolism, stasis predominates in venous events, whereas endothelial injury plays a more prominent role in arterial ones.^[25] This interplay underscores the multifactorial nature of thromboembolism, guiding preventive strategies in high-risk settings.

Thrombus Formation and Embolization

Thrombus formation begins with the activation of platelets upon exposure to subendothelial collagen and tissue factor following vascular injury or endothelial dysfunction. Platelets adhere to the site via von Willebrand factor and glycoprotein Ib, then aggregate through fibrinogen bridging and release of ADP and thromboxane A2, forming a platelet plug. Simultaneously, the coagulation cascade is initiated: the extrinsic pathway via tissue factor-VIIa complex activates factor X, while the intrinsic pathway involves factors XII, XI, IX, and VIII leading to the same point, culminating in prothrombin activation to thrombin, which converts fibrinogen to fibrin to stabilize the clot. This process results in a fibrin mesh that entraps red blood cells and additional platelets. Venous thrombi, often termed red thrombi, are predominantly composed of fibrin and trapped erythrocytes due to slower blood flow in veins, which promotes stasis and favors the coagulation cascade over platelet aggregation. In contrast, arterial thrombi, known as white thrombi, are richer in platelets because of the high shear stress in arteries, which enhances platelet activation and adhesion while limiting fibrin deposition. These differences arise primarily from hemodynamic variations: venous thrombi typically form in deep leg veins as deep vein thrombosis (DVT), whereas arterial thrombi frequently originate from cardiac sources like atrial fibrillation-induced clots or atherosclerotic plaques in the aorta. Embolization occurs when a portion of the thrombus detaches, propelled by hemodynamic forces such as blood flow turbulence or pressure changes, allowing it to travel through the vasculature. Venous emboli, originating from lower extremity DVT, typically migrate via the inferior vena cava to the pulmonary arteries, causing pulmonary embolism (PE). Arterial emboli, dislodged from proximal sites, lodge in distal arteries, such as cerebral vessels leading to stroke or limb arteries causing ischemia. Following formation, thrombi can propagate by extending along the vessel wall through continued platelet recruitment and fibrin deposition, potentially occluding larger segments. Alternatively, endogenous fibrinolysis mediated by plasmin degrades the fibrin network, enabling partial or complete resolution of the clot via plasminogen activation by tissue plasminogen activator (tPA). These dynamics are influenced by components of Virchow's triad, including stasis, endothelial injury, and hypercoagulability, which predispose to the initial thrombus development.

Venous Thromboembolism

Risk Factors

Risk factors for venous thromboembolism (VTE) are often categorized as non-modifiable and modifiable, aligning with Virchow's triad of stasis, endothelial injury, and hypercoagulability. Non-modifiable factors include advanced age, with risk increasing after 60 years due to reduced venous tone and cumulative comorbidities.^[7] Genetic predispositions, such as inherited thrombophilias (e.g., Factor V Leiden mutation, prothrombin gene mutation), elevate risk by 3- to 8-fold in heterozygous carriers.^[6] Family history of VTE further compounds this, reflecting both genetic and shared environmental influences. Certain ethnic groups, including Caucasians and African Americans, show higher incidence compared to Asians or Hispanics.^[30] Modifiable risk factors predominate and are often transient. Prolonged immobility, such as during long-haul travel (>4 hours), hospitalization, or bed rest, promotes venous stasis and accounts for up to 50% of hospital-associated VTE cases.^[31] Surgery, particularly orthopedic (e.g., hip/knee replacement) or major abdominal procedures, increases risk 10- to 100-fold in the first month post-operation due to endothelial damage and immobility.^[6] Medical conditions like active cancer (risk up to 7-fold higher), infections, inflammatory diseases (e.g., inflammatory bowel disease), heart failure, and stroke with paresis contribute via hypercoagulability or stasis.^[30] Hormonal factors, including pregnancy/postpartum period (5- to 10-fold risk increase), oral contraceptives, or hormone replacement therapy, heighten clotting tendency through estrogen-mediated effects.^[7] Lifestyle elements such as obesity (body mass index >30 kg/m², doubling risk), smoking, and dehydration further amplify susceptibility.^[6] Hospitalization alone raises VTE risk significantly, with up to 80% of cases linked to identifiable factors.^[2]

Clinical Presentation

Venous thromboembolism presents variably depending on whether it manifests as deep vein thrombosis (DVT) or pulmonary embolism (PE), with up to 50% of DVT cases remaining asymptomatic until embolization occurs.^[7] Symptoms of lower extremity DVT, the most common site, include unilateral leg swelling, pain or tenderness (often described as cramping or soreness), warmth, and erythema along the affected vein, typically in the calf or thigh.^[32] Upper extremity DVT, less common, may cause arm swelling and pain, often linked to central venous catheters.^[12] Pulmonary embolism, occurring in about 30-50% of untreated DVT cases, signals a medical emergency with abrupt onset symptoms: sudden shortness of breath, pleuritic chest pain (worsened by inspiration), tachypnea, tachycardia, hemoptysis, or syncope.^[11] Low-grade fever and anxiety may accompany these, and massive PE can lead to hypotension, cyanosis, or cardiac arrest.^[33] Post-thrombotic syndrome, a chronic complication in 20-50% of DVT survivors, features persistent limb pain, swelling, skin changes, and venous ulcers due to valvular incompetence and venous hypertension.^[7]

Diagnosis

Diagnosis of venous thromboembolism integrates clinical probability assessment, laboratory tests, and imaging to confirm DVT or PE while minimizing unnecessary anticoagulation. The Wells score for DVT (score ≥2 indicating likely DVT) or PE (score ≥4 suggesting high probability) guides initial evaluation based on symptoms, risk factors, and signs like calf swelling >3 cm or heart rate >100 bpm.^[34] A negative D-dimer blood test (fibrin degradation product assay, sensitivity >95% for ruling out VTE in low-probability cases) avoids further imaging, as levels <500 ng/mL exclude clot presence in outpatient settings.^[35] For DVT, compression ultrasonography is first-line, with sensitivity and specificity >95% for proximal clots; repeat testing may be needed if initial results are negative but suspicion persists.^[36] Venography, using contrast dye, serves as gold standard but is invasive and reserved for equivocal cases. PE diagnosis relies on computed tomography pulmonary angiography (CTPA), offering >90% sensitivity/specificity for detecting emboli in pulmonary arteries. Ventilation-perfusion scintigraphy assesses mismatch in perfusion defects, useful in renal impairment or contrast allergy. Echocardiography identifies right ventricular strain in hemodynamically unstable PE.^[34] Lower extremity ultrasound supports PE suspicion if DVT is found, as it is the source in most cases.

Management

Management of venous thromboembolism prioritizes anticoagulation to prevent clot extension, embolization, and recurrence, tailored to clot location, patient risk, and bleeding potential. Initial therapy often involves parenteral anticoagulants: unfractionated heparin (target aPTT 1.5-2.5 times control) or low-molecular-weight heparin (e.g., enoxaparin 1 mg/kg subcutaneously twice daily) for rapid onset.^[37] Transition to oral agents follows: vitamin K antagonists like warfarin (target INR 2-3) for at least 3 months, or direct oral anticoagulants (DOACs) such as rivaroxaban (15 mg twice daily for 21 days, then 20 mg daily) or apixaban, preferred for non-valvular cases due to fixed dosing and lower bleeding risk.^[35] For massive PE with hemodynamic instability, systemic thrombolysis (e.g., alteplase 100 mg IV over 2 hours) dissolves clots, improving survival by 30-50% in select patients, though with 2-3% major bleeding risk.^[38] Catheter-directed thrombolysis or embolectomy targets localized therapy in high-risk cases. Inferior vena cava (IVC) filters prevent embolization in anticoagulation contraindications, reducing PE recurrence by 50% but not addressing underlying thrombosis.^[37] Compression stockings (20-30 mmHg gradient) alleviate DVT symptoms and reduce post-thrombotic syndrome risk by 50%. Treatment duration: 3 months for provoked VTE, extended lifelong for unprovoked or recurrent events.^[36]

Prevention

Prevention of venous thromboembolism emphasizes risk assessment and targeted prophylaxis, particularly in hospital settings where 70% of cases are healthcare-associated and potentially avoidable.^[31] Pharmacologic prophylaxis with low-molecular-weight heparin, fondaparinux, or DOACs (e.g., rivaroxaban 10 mg daily post-orthopedic surgery) reduces VTE incidence by 40-60% in high-risk surgical patients.^[39] Mechanical methods, including intermittent pneumatic compression devices and graduated compression stockings, enhance venous return and are recommended when anticoagulation is contraindicated, lowering risk by up to 50% in immobilized patients.^[40] Early mobilization post-surgery or during hospitalization—ambulation within 24 hours—mitigates stasis. For travelers, strategies include frequent walking, calf exercises, and hydration during flights >4 hours, potentially halving long-haul VTE risk.^[41] Lifestyle modifications, such as maintaining healthy weight, regular exercise (e.g., 30 minutes daily), and smoking cessation, address modifiable risks long-term. In pregnancy, low-molecular-weight heparin is preferred over DOACs for prophylaxis in high-risk women. Routine VTE risk screening using tools like the Padua Prediction Score guides prophylaxis in medical inpatients.^[39]

Arterial Thromboembolism

Risk Factors

Risk factors for arterial thromboembolism can be broadly categorized into non-modifiable and modifiable categories, with additional contributing elements such as paradoxical embolism playing a role in select cases. Non-modifiable factors include advancing age, particularly beyond 65 years, where the risk escalates exponentially due to progressive arterial wall stiffening and plaque accumulation.^[42] Family history of coronary artery disease (CAD) or stroke independently elevates the likelihood of arterial events, reflecting shared genetic predispositions to thrombotic tendencies.^[43] Male sex is associated with heightened risk for certain arterial thromboembolic events, such as myocardial infarction and peripheral artery occlusion, potentially due to differences in hormonal influences on vascular biology.^[44] Modifiable risk factors predominate in arterial thromboembolism, with atherosclerosis serving as the cornerstone mechanism; plaque rupture accounts for approximately 60-70% of acute coronary thrombotic events, triggering embolization downstream.^[45] Atrial fibrillation substantially amplifies stroke risk by fivefold through stasis-induced thrombus formation in the left atrial appendage, leading to systemic embolization.^[46] Smoking doubles to quadruples the incidence of arterial thromboembolic complications, including stroke and coronary events, via endothelial injury and prothrombotic state induction.^[47] Other modifiable contributors include hyperlipidemia, where low-density lipoprotein (LDL) cholesterol levels exceeding 160 mg/dL promote atheroma formation and plaque instability, thereby facilitating thromboembolic detachment.^[48] Diabetes mellitus approximately doubles the risk of arterial thromboembolism by inducing endothelial damage, which impairs vasodilatory function and enhances platelet aggregation.^[49] Hypertension, defined by systolic blood pressure greater than 140 mmHg, accelerates arterial remodeling and shear stress, increasing the propensity for plaque disruption and subsequent embolization.^[50] Paradoxical embolism represents a rarer pathway, occurring in 1-2% of ischemic strokes, wherein venous thrombi traverse a patent foramen ovale into the arterial circulation, bypassing pulmonary filtration.^[51]

Clinical Presentation

Arterial thromboembolism manifests through acute ischemic symptoms in the affected vascular territory, often presenting abruptly due to sudden occlusion by an embolus or in-situ thrombus. The clinical features depend on the site of embolization, leading to organ-specific deficits from tissue hypoperfusion. Common sites include the cerebral, coronary, and peripheral arteries, with symptoms reflecting the rapid onset of ischemia.^[52] In cerebral arterial thromboembolism, patients typically experience sudden onset of focal neurological deficits, such as hemiparesis or hemiplegia on one side of the body, aphasia or dysarthria, and facial droop. These symptoms arise from ischemic stroke due to embolic occlusion of cerebral arteries, often from cardiac sources. A transient ischemic attack (TIA) may serve as a warning sign, featuring similar transient symptoms that resolve within 24 hours, typically much sooner.^[53]^[54] Coronary arterial thromboembolism can precipitate acute myocardial infarction (MI), characterized by severe chest pain or discomfort, often radiating to the left arm, jaw, or back, accompanied by diaphoresis, nausea, shortness of breath, and sometimes vomiting. In patients with diabetes, up to 25% of MIs may be silent, presenting without classic pain but with subtle signs like fatigue or dyspnea due to autonomic neuropathy.^[55]^[56] Peripheral arterial thromboembolism commonly causes acute limb ischemia, with hallmark symptoms encapsulated by the "6 Ps": severe pain (often sudden and disproportionate), pallor of the skin, pulselessness distal to the occlusion, poikilothermy (coolness of the limb), paresthesia (numbness or tingling), and eventual paralysis if untreated. These signs reflect rapid compromise of blood flow to the extremities, most frequently the lower limbs.^[57] Complications of arterial thromboembolism exacerbate morbidity; in acute limb ischemia, prolonged ischemia can lead to rhabdomyolysis from muscle breakdown and myoglobin release, potentially causing acute kidney injury. In MI, cardiogenic shock develops in approximately 5-10% of cases, marked by hypotension, tachycardia, and end-organ hypoperfusion, with an associated in-hospital mortality rate of 40-50%.^[58]^[59]

Diagnosis

Diagnosis of arterial thromboembolism relies on a combination of clinical assessment, laboratory tests, and imaging modalities tailored to the affected vascular territory, emphasizing rapid evaluation to mitigate ischemic damage. Initial evaluation often includes the National Institutes of Health Stroke Scale (NIHSS) for assessing stroke severity, where scores range from 0 (no deficit) to 42 (severe impairment), guiding urgency and prognosis.^[60] Non-contrast computed tomography (CT) is the first-line imaging to exclude intracranial hemorrhage with high sensitivity exceeding 95%, while magnetic resonance imaging (MRI), particularly diffusion-weighted sequences, offers superior detection of acute ischemia with sensitivity around 95%.^[61] For suspected myocardial infarction due to coronary embolism, electrocardiography (ECG) is essential, revealing ST-segment elevation in approximately 50% of cases indicative of transmural ischemia, though non-ST-elevation patterns may predominate in embolic events.^[62] Cardiac troponin levels rise within 3-6 hours of injury, peaking at 12-24 hours and remaining elevated for up to 10-14 days, confirming myocardial necrosis.^[63] Transthoracic echocardiography complements these by identifying regional wall motion abnormalities, which appear within seconds of occlusion and localize the ischemic territory with high specificity. In peripheral arterial thromboembolism, the ankle-brachial index (ABI) provides a non-invasive initial screen, with values below 0.9 signaling significant ischemia and correlating with obstructive disease.^[64] Confirmatory imaging via conventional angiography or CT angiography precisely localizes the embolus, delineating vessel occlusion and guiding intervention, with CT angiography offering rapid, comprehensive visualization of the lower extremity vasculature.^[65] To identify cardioembolic sources such as atrial fibrillation (AF), Holter monitoring is employed, particularly for paroxysmal episodes, detecting new-onset AF in 10-20% of patients with embolic stroke of undetermined source over 24-72 hours of recording.^[66] Prolonged monitoring enhances yield, underscoring its role in secondary prevention strategies.^[67]

Management

Management of arterial thromboembolism focuses on rapid reperfusion to restore blood flow, minimize tissue damage, and prevent complications, followed by therapies to reduce recurrence. Treatment strategies vary by site of occlusion—cerebral, coronary, or peripheral—and are informed by clinical presentation and imaging confirmation of thrombus location.^[68]^[69] For ischemic stroke due to thromboembolism, intravenous thrombolysis with alteplase (tPA) is recommended within 4.5 hours of symptom onset in eligible patients, improving the likelihood of minimal or no disability by approximately 30% at 3 months compared to placebo.^[70]^[68] Mechanical thrombectomy is indicated for large vessel occlusions, with benefits extending up to 24 hours in select patients based on perfusion imaging, achieving higher rates of functional independence (modified Rankin Scale 0-2 at 90 days) than medical therapy alone.^[68] In acute myocardial infarction (MI) from coronary thromboembolism, primary percutaneous coronary intervention (PCI) with stenting is the preferred reperfusion strategy, targeting a door-to-balloon time of less than 90 minutes to optimize myocardial salvage and reduce mortality.^[69] Dual antiplatelet therapy, typically aspirin combined with a P2Y12 inhibitor such as ticagrelor or prasugrel (preferred over clopidogrel in PCI patients), is initiated immediately to inhibit platelet aggregation and prevent stent thrombosis.^[69] Peripheral arterial thromboembolism causing acute limb ischemia is managed with urgent revascularization, where surgical embolectomy is first-line for viable or marginally threatened limbs to extract the embolus and restore perfusion. Catheter-directed thrombolysis serves as an alternative for non-occlusive or distal thrombi, while long-term anticoagulation is essential if a cardioembolic source, such as atrial fibrillation, is identified. Secondary prevention emphasizes risk factor modification and pharmacotherapy to mitigate recurrent arterial events. High-intensity statin therapy is recommended post-event to lower LDL cholesterol by at least 50%, reducing major vascular events by about 25% in patients with established atherosclerotic disease.^[71]^[72] Beta-blockers are indicated long-term after MI to reduce cardiovascular mortality and recurrent infarction by 20-22%, particularly in patients with reduced left ventricular ejection fraction or ongoing ischemia.^[71]

Prevention

Prevention of arterial thromboembolism primarily involves addressing modifiable risk factors through lifestyle modifications and pharmacologic interventions aimed at stabilizing atherosclerotic plaques, controlling cardiovascular risk factors, and preventing cardioembolic events, particularly in patients with atrial fibrillation (AF). These strategies target underlying atherosclerosis and arrhythmias to reduce the incidence of events such as myocardial infarction, ischemic stroke, and peripheral arterial occlusion. Guidelines from major cardiovascular societies emphasize a multifaceted approach, integrating patient education, regular monitoring, and evidence-based therapies to achieve long-term risk reduction. Lifestyle interventions form the cornerstone of prevention. Smoking cessation dramatically lowers risk; quitting at any time after diagnosis in patients with stable coronary artery disease reduces the risk of major cardiovascular events by nearly 50% within one year. Regular physical activity, such as moderate-intensity aerobic exercise for at least 30 minutes per day on most days of the week, can reduce cardiovascular disease mortality by 22% to 31%, with benefits accruing from improved endothelial function and reduced inflammation. Adherence to a Mediterranean diet, rich in fruits, vegetables, whole grains, fish, and olive oil, has been shown to decrease the progression of atherosclerosis and stabilize vulnerable plaques, thereby mitigating the risk of plaque rupture and subsequent thrombosis. Pharmacologic measures focus on lipid and blood pressure management in high-risk individuals. Statins are recommended to achieve low-density lipoprotein cholesterol (LDL-C) levels below 70 mg/dL in patients with very high-risk atherosclerotic cardiovascular disease (ASCVD), as this threshold guides the addition of non-statin therapies to further lower event rates. For hypertension, antihypertensive therapy should target blood pressure below 130/80 mmHg in adults to prevent cardiovascular complications, with this goal supported by evidence from large-scale trials demonstrating reduced stroke and myocardial infarction incidence. In patients with AF, a major source of cardioembolic arterial thromboembolism, oral anticoagulation is essential for those at elevated risk. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists; initiation is indicated for men with a CHA2DS2-VASc score of 2 or more and women with a score of 3 or more, as anticoagulation reduces stroke risk by approximately 60% compared to no therapy or antiplatelet agents alone. This risk stratification tool incorporates factors such as age, sex, heart failure, hypertension, diabetes, prior stroke, and vascular disease to guide therapy decisions. Screening for subclinical carotid artery stenosis using duplex ultrasound is considered in select high-risk populations, such as those over 70 years or with a history of cardiovascular disease. For asymptomatic stenosis exceeding 70%, intervention such as carotid endarterectomy may be warranted in patients with low perioperative risk and expected life expectancy greater than five years, based on demonstrated reductions in stroke rates from randomized trials.

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