30% of patients with premature (age <50 yr) peripheral and CNS thromboembolic vascular disease are heterozygotes for homocystinuria ((Homocystinuria (Homocyst[e]inemia))) variants (Nejm 1985;313:709)

Sx:

Cold, pale extremity; decreased sensation and motor strength; pain usually but not always, worse with elevation; claudication, progresses to rest pain (r/o spinal stenosis in elderly)

Embolic incidence to: femoral (34%), brain (20%), popliteal (14%), iliac (13%), viscera (10%), aorta (9%), axillary (5%)

Si:Pale with elevation >1 min, then dependent rubor (reactive erythema) when first put down (Mod Concepts Cardiovasc Dis 1976;45:91); diminished or absent pulses; mottled skin; ischemic ulcers; gangrene

Sx progress over 6 yr though pt may decr activity (Jama 2004;292:453). In embolic, without rx, extremity loss is: axillary 10%, popliteal 12%, femoral 40%, aorta 80%

Gangrene of extremities

r/o

• venous occlusion
• abdominal aortic aneurysm with CHOLESTEROL EMBOLI, sometimes precipitated by warfarin in 3-12 wk (Circ 1967;35:946) angiography or surgical aortic manipulation, presents with blue toes and livedo reticularis without hypotension (the usual cause) or pain, may see emboli in retinal vessels, elevated amylase/lipase, low complement, worsening renal failure, no rx possible, dx w bx's of skin, kidney, etc (Nejm 1993;329:38)
• THROMBOANGIITIS OBLITERANS(BUERGER'S DISEASE) (Nejm 2000;343:864): rare (in US) disease of young male smokers, due to endarteritis obliterans of vasa vasora, presents w claudication especially of instep and has a positive Allen's si (with posterior occlusion of radial and ulnar arteries and the rapid release of 1 leads to rapid filling on that side alone, and is delayed several seconds on other) and superficial thrombophlebitis (40%), treat by stopping smoking, vasodilators, and hyperbaric oxygen to rx ulcers (Nejm 1998;339:672)

Lab: Noninv:Ankle-brachial index (ABI) <0.5 suggestive of significant disease (Ann IM 2002;136:873); even <0.9 being used as sens and specific marker of periph vascular disease in some studies (sponsored by Plavix!) (Jama 2004;292;453). Doppler studies for segmental systolic BPs and Doppler wave forms (Nejm 1983;309:841)

Xray:

Duplex ultrasonography (Brit J Surg 1996;83:404)

Angiography only if plan to do surgery as you would if embolic

Rx:

(Med Let 2004;46:13)

Stop cigarettes; control BP, DM, and cholesterol/lipids

Weight loss; exercise program of walking to pain w/i 5 min and continuing as tolerated, then rest and resume to >30 min walking time at least tiw for at least 6 mo helps (Jama 2006;144:10; Nejm 2002;347:1941; Jama 1995;274:975), or even less frequently (Ann IM 2006;144:10); -blockers may, but don't usually, worsen sx (Arch IM 1991;151:1769) unless coincident nifedipine use (BMJ 1991;303:1100); ASA 325 mg po qd (Lancet 1992;340:143)

Medications (Jama 2006;295:547)

• antiplatelet rx w: ASA i po qd, clopidrogel (Plavix), and/or ticlopidine (Ticlid) 250 mg po bid, or perhaps picotamide (Europe Hrt J 2004;25:1845), which decr claudication and need for bypass surgery, and increases graft patency postop (Nejm 1997;337:1726)
• Cilostazol (Pletal) (Med Let 1999;41:44) 50-100 mg po bid; platelet inhibitor and vasodilator; half-life incr by erythromycin, ketoconazole, diltiazem, omeprazole, grapefruit; adverse effects: headache, diarrhea, dizziness, worse CHF
• Pentoxifylline (Trental) 400 mg po tid for claudication (Can Med Assoc J 1996;155:1053, Ann IM 1985;102:126)
• Heparin sc qd helps modestly (Am J Med 1999;107;234)
• Ginko (Am J Med 2000;108:276) 120-160 mg po qd

Bypass surgery or angioplasty/stent (Nejm 2006;354:1879) if ulcers or intolerable pain

of acute thrombotic or embolic occlusion: embolectomy within 6 h with Fogarty catheter; or thrombolysis iv × 2+ d w indwelling catheter using urokinase for acute (<2 wk) or chronic obstruction, w f/u angioplasty, helps 50-80% (Nejm 1998;338:1105 vs 1148; Ann IM 1994;120:40); anticoagulation with heparin then warfarin