What conditions predispose to arterial thrombosis and how is it managed?

Conditions Predisposing to Arterial Thrombosis

Arterial thrombosis occurs primarily at sites of atherosclerotic plaque rupture, which exposes thrombogenic subendothelium to platelets and coagulation proteins, forming platelet-rich thrombi under high-flow conditions. 1

Primary Pathophysiologic Mechanism

Atherosclerotic plaque rupture is the principal cause of arterial thrombosis, exposing the subendothelial matrix and triggering platelet aggregation followed by coagulation cascade activation. 2 This process occurs in regions of disturbed flow where high shear stress predominates. 1

• Arterial thrombi are composed predominantly of platelet aggregates bound by thin fibrin strands, reflecting the high-shear, high-flow environment. 1, 2
• Plaque-related hemorrhage can further narrow the vessel lumen and disturb flow, promoting additional thrombus formation. 1, 2
• When flow becomes slow, stenosis is severe, or the thrombogenic stimulus is intense, thrombi may become totally occlusive. 1

Major Clinical Conditions Associated with Arterial Thrombosis

Atherosclerotic Vascular Disease

• Atherosclerosis is the most common underlying condition for arterial thrombosis, affecting large- and medium-diameter arteries throughout the arterial tree. 1, 3
• Atherothrombosis is a systemic disease process—occurrence of an ischemic event in one arterial territory implies other territories may be affected even if clinically silent. 3

Acute Coronary Syndromes

• Thrombus formation on fissured or disrupted atherosclerotic plaque is the main pathogenetic mechanism for myocardial infarction and unstable angina. 4
• Myocardial infarction results from acute total occlusion, while unstable angina results from mural thrombus formation. 4

Ischemic Stroke

• Atherothrombosis accounts for less than 50% of ischemic strokes, but represents a critical mechanism when plaque rupture occurs in cerebral vessels. 3

Peripheral Arterial Disease

• Intermittent claudication and critical limb ischemia are nearly totally dependent on atherothrombotic mechanisms. 3

Kawasaki Disease with Coronary Aneurysms

• Patients with large or giant coronary aneurysms (≥8 mm or Z score ≥10) are at particularly high risk for coronary artery thrombosis. 1
• Thrombosis is promoted by markedly abnormal flow conditions with low wall shear stress, stasis, and activation of platelets, clotting factors, and endothelium. 1
• Most giant aneurysms at postmortem examination are lined by chronic thrombus. 1

Prothrombotic Hematologic Conditions

• Antiphospholipid antibody syndrome is associated with both arterial and venous thrombosis. 2
• Homocystinuria can cause simultaneous arterial and venous occlusions with rapidly progressive arteriosclerotic disease. 2
• Disseminated intravascular coagulation (DIC) triggers widespread microvascular thrombosis affecting both arterial and venous systems. 1, 2

Management Approach

Acute Arterial Thrombosis

For acute limb or organ-threatening ischemia, immediate anticoagulation with heparin (unless contraindicated) and urgent evaluation for revascularization are essential. 5

• Classification determines urgency: Category IIa (marginally threatened) and IIb (immediately threatened) require urgent or emergency revascularization via endovascular or surgical approaches. 5
• For acute coronary thrombosis, routine revascularization in addition to guideline-directed medical therapy reduces mortality and infarction rates. 5
• Acute ischemic stroke from large vessel occlusion requires endovascular treatment (mechanical thrombectomy) using stent-retrievers and aspiration, with intravenous alteplase. 5

Chronic Prevention Strategies

All patients with atherothrombotic disease require both antiplatelet therapy and cardiovascular risk factor modification. 3, 6

Antiplatelet Therapy

• Antiplatelet agents are mandatory because arterial thrombi are platelet-rich and form under high-shear conditions. 1, 2
• Current standard includes aspirin, thienopyridines (clopidogrel), and glycoprotein IIb/IIIa antagonists for high-risk situations. 7
• For Kawasaki disease with giant aneurysms, combination therapy with low-dose aspirin (3-5 mg/kg/day) plus anticoagulation (warfarin INR 2.0-3.0 or LMWH) is recommended. 1

Risk Factor Modification

• Smoking cessation, control of hyperlipidemia, diabetes, and hypertension are essential. 5, 6
• Lipid-lowering, antihypertensive, and antiglycemic drugs favorably influence atherosclerotic progression. 6

Special Considerations for Kawasaki Disease

Patients with rapidly expanding coronary aneurysms or maximum Z score ≥10 should receive systemic anticoagulation with LMWH or warfarin (INR 2.0-3.0) in addition to low-dose aspirin. 1

• For exceptionally high-risk patients (giant aneurysms with recent thrombosis history), "triple therapy" with aspirin, a second antiplatelet agent, and anticoagulation may be considered. 1
• Ibuprofen and other NSAIDs are harmful in patients taking aspirin for antiplatelet effects. 1
• Echocardiography surveillance should be performed at least twice weekly while coronaries are rapidly expanding, then at least weekly during the first 45 days. 1

Critical Pitfalls to Avoid

• Do not delay revascularization in critical limb ischemia—progression to irreversible tissue loss, wet gangrene with sepsis, or loss of revascularization window can occur rapidly. 8
• Do not underestimate cardiovascular risk in patients with arterial thrombosis in one vascular bed—they require comprehensive cardiac evaluation as atherothrombosis is a systemic disease. 8, 3
• Do not rely on aspirin monotherapy for high-risk arterial thrombosis situations—up to 15% of high-risk acute coronary syndrome patients continue to suffer ischemic events, partly due to aspirin non-responsiveness. 7
• Recognize that thrombus formation contributes to plaque growth even when subclinical—most thrombotic reactions remain parietal but infiltrate with smooth muscle cells, accelerating atherosclerosis. 3