In a patient under 45 years old with myocardial infarction and no conventional atherosclerotic risk factors, what is the most common hypercoagulable disorder and how should it be screened and managed?

Antiphospholipid Syndrome: The Leading Hypercoagulable Disorder in Young MI

Antiphospholipid syndrome (APS) is the most important hypercoagulable disorder causing myocardial infarction in young adults without traditional atherosclerotic risk factors, and should be systematically screened for in all patients under 45 years presenting with MI. 1, 2

Why APS is the Primary Concern

APS represents a major cause of cardiovascular events in young people and should be at the top of your differential when evaluating young MI patients without conventional risk factors. 3 The syndrome is characterized by:

• Young age at presentation (mean age 41 years) with no sex predominance (45% female) 2
• Normal or near-normal coronary arteries (75% show either normal vessels or acute thrombosis without underlying atherosclerosis) 2
• High recurrence risk (6 patients had recurrent MI within 3 months in systematic review) 2
• In-hospital mortality of approximately 7.5% (3/40 cases) 2

Screening Protocol for APS

Laboratory Testing Required

Test for the following antiphospholipid antibodies on two separate occasions, 12 weeks apart: 4

• Anticardiolipin IgG and IgM antibodies 5, 4
• Anti-β2 glycoprotein I IgG and IgM antibodies 5
• Lupus anticoagulant 5

Supporting Laboratory Clues

Look for these abnormalities that suggest APS: 2

• Thrombocytopenia (average platelet count 130,000/mm³ in APS-MI patients)
• Elevated partial thromboplastin time (prolonged in all reported cases with available data)

Risk Stratification Tool

Calculate the adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) to quantify coronary thrombosis risk: 5

• Hyperlipidemia: 3 points
• Arterial hypertension: 1 point
• Anticardiolipin IgG/IgM positive: 5 points
• Anti-β2 glycoprotein I IgG/IgM positive: 4 points
• Lupus anticoagulant positive: 4 points

Patients with acute MI have significantly higher aGAPSS scores (mean 11.9) compared to other thrombotic events (mean 9.2). 5

Acute Management Strategy

Immediate Revascularization

• Primary PCI with aspiration thrombectomy is the preferred approach for STEMI presentation (45% of APS-MI cases present as STEMI) 2, 4
• Be prepared for higher rates of stent thrombosis compared to conventional MI patients 1

Anticoagulation Regimen

Triple therapy for 1 month, then transition to dual therapy: 4

1. Initial triple therapy (1 month):

   • Aspirin
   • Clopidogrel
   • Warfarin (target INR 2.0-3.0)

2. Long-term dual therapy (indefinite):

   • Clopidogrel
   • Warfarin (target INR 2.0-3.0)

Critical Anticoagulation Caveat

Do NOT use direct oral anticoagulants (DOACs) in APS patients with arterial thrombosis—they carry high recurrence risk. 1 Vitamin K antagonists (warfarin) remain the only evidence-based anticoagulant for arterial APS. 1, 3

Broader Hypercoagulable Workup

While APS is the most common, evaluate for other hypercoagulable states documented in 20-50% of young ischemic events: 6

• Inherited thrombophilias (Factor V Leiden, prothrombin gene mutation, protein C/S deficiency, antithrombin deficiency)
• Systemic lupus erythematosus (APS frequently coexists with SLE) 4
• Other autoimmune conditions (rheumatoid arthritis, psoriasis) 6

Additional Non-Atherosclerotic Causes to Screen

The 2023 AHA/ACC guidelines mandate evaluation for these alternative etiologies in young MI: 7, 6

• Spontaneous coronary artery dissection (SCAD) - especially in young women and peripartum period 6
• Coronary artery anomalies - anomalous origin from opposite sinus with interarterial course 6
• Myocardial bridging - causes exercise-induced ischemia 6
• Kawasaki disease sequelae - accounts for 5% of ACS in adults <40 years 6
• Cocaine use - increases MI risk 24-fold in first hour after use 6

Long-Term Management Imperatives

Secondary Prevention

• Indefinite anticoagulation with warfarin (INR 2.0-3.0) is mandatory for arterial APS 1, 3
• Aggressive cardiovascular risk factor modification despite young age 3
• Avoid oral contraceptives in young women with APS 8

Monitoring Strategy

• Longitudinal cardiovascular specialist follow-up is essential given high recurrence risk 7, 9
• Family screening for inherited thrombophilias and familial hypercholesterolemia 7, 9

Common Pitfalls to Avoid

1. Assuming normal coronaries exclude MI - 75% of APS-MI patients have angiographically normal vessels or isolated thrombus 2
2. Using DOACs instead of warfarin - this increases recurrent arterial thrombosis risk 1
3. Single antibody testing - diagnosis requires positive tests 12 weeks apart 4
4. Premature discontinuation of anticoagulation - these patients require lifelong therapy 1, 3