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Arterial Embolus and Thrombosis

BASICS

DESCRIPTION

- Emboli - Arise from degenerative, stenotic, and ulcerative atherosclerotic plaques - Bilateral lower extremity disease signifies proximal aortic source. - Unilateral embolic disease signifies disease distal to aortic bifurcation. - More commonly lodge in areas of bifurcation

- Cardiac - Atrial flutter/fibrillation - Valve disease and/or endocarditis - Myocardial infarction - Cardiomyopathy (low ejection fraction)

- Trauma - Blunt or penetrating - Vascular/cardiac interventional procedures

- Computed tomography (CT) with contrast/CT angiography with multiplanar reconstruction is accurate and efficient for diagnosis of arterial occlusions (class IIB indication) (1)[C]. - Magnetic resonance angiography (MRA) with gadolinium enhancement of the extremities has class IA evidence for diagnosing location and degree of stenosis in peripheral arterial disease (PAD) and is useful in selecting patients as candidates for endovascular intervention (1)[C]. - Conventional arteriography - Rarely indicated preoperatively; used intraoperatively after an embolectomy - Crescent-shaped (rounded reverse meniscus sign) or multiple filling defects within an otherwise normal artery implicates an embolus. - Sharp/tapered cutoff sign on arteriography implicates arterial thrombus. - May depict causative factor (e.g., anastomotic stricture)

- Heparin: goal to prevent distal and proximal extension of thrombus, anti-inflammatory effects - 80 U/kg IV loading (or 5,000 to 10,000 U) - Continuous infusion sufficient to double partial thromboplastin time, generally 18 U/kg/hr - Transition to 3- to 6-month period of warfarin therapy is indicated if below-knee bypass is performed with synthetic graft. - Contraindications: heparin allergy, bleeding diathesis, trauma (e.g., head injury), hematuria/hemoptysis, acute aortic dissection

- Thrombolysis - Intra-arterial recombinant tissue plasminogen activator (rt-PA) may be more effective than intra-arterial streptokinase or intravenous (IV) rt-PA in treating distal arterial occlusion, with no change in risk of hemorrhagic complications. - Urokinase - Loading dose: 4,400 IU/kg at a rate of 90 mL/hr over 10 minutes; then 4,400 IU/kg at a rate of 15 mL/hr over 12 hours; may be repeated as needed - Equivalent results to rt-PA although lysis of clot may be faster with intra-arterial rt-PA (2)[A].

- Critical stenosis criteria - Ischemic pain, mild neurologic deficit, weakness of ankle dorsiflexion - Minimal sensory loss; light touch and/or vibratory - No pulsatile flow by Doppler, venous flow present - Treatment - Time to intervention is critical. - Arteriography, either CTA or traditional - Individualize thrombolysis and/or operative procedure (depending on extent of thrombosis and amenability for surgical removal) - Thrombolysis to optimize alternatives - Intraoperative lytic therapy: bypass, patch angioplasty

- Late (nonsalvageable) criteria - Profound sensory loss, muscle paralysis, muscle rigor - Absent capillary refill - Skin mottling - No arterial or venous signals by Doppler - Treatment - Arteriography usually is not warranted. - Attempts at reperfusion contraindicated - Anticoagulation - Definitive amputation, if possible

  • Acute loss of perfusion distal to occlusion of major arteries due to an embolus that migrates to point of occlusion (air, fat, amniotic fluid), or a clot (thrombosis) intrinsic to point of occlusion (most common); both are true emergencies.
  • Following obstruction of the artery, clot extends both proximally and distally, collateral pathways become involved, and process becomes self-propagating. Ultimately, venous circulation can become involved.
  • Golden period of 4 to 6 hours, after which the profound ischemia leads to irreversible cellular death
  • Distribution of emboli: femoral artery, 28%; aortoiliac, 18%; popliteal artery, 17%; brachial, 10%; mesenteric arteries, 5-7%; cerebral (estimated), 15-20%; other, 9%.
  • Classic presentationsBlue toe syndrome: sudden painful, cool, blue toe in the presence of palpable distal pulsesMesenteric ischemia: pain out of proportion to abdominal physical exam, typically begins periumbilically then diffusely painful

EPIDEMIOLOGY

Incidence

  • 50 to 100/100,000 hospital admissions annually
  • Limb ischemia: 13 to 17/10,000 people/year

Prevalence

  • Predominant age: elderly (>65 years)
  • Predominant sex: male > female
  • A leading cause of limb loss in elderly
  • More common in African Americans

ETIOLOGY AND PATHOPHYSIOLOGY

Thrombosis in arterial circulation due to platelet aggregation and adhesion, not fibrin clot formation, as in venous thrombosis á

  • EmboliArise from degenerative, stenotic, and ulcerative atherosclerotic plaquesBilateral lower extremity disease signifies proximal aortic source.Unilateral embolic disease signifies disease distal to aortic bifurcation.More commonly lodge in areas of bifurcation
  • CardiacAtrial flutter/fibrillationValve disease and/or endocarditisMyocardial infarctionCardiomyopathy (low ejection fraction)
  • ThrombosisAtherosclerotic occlusive diseaseHypercoagulable statesLow-flow statesEntrapment syndromeVenous gangreneDrug abuseHeparin-induced thrombocytopeniaVascular bypass/grafts
  • TraumaBlunt or penetratingVascular/cardiac interventional procedures
  • Aneurysms: cardiac, aortic, peripheral
  • Paradoxical embolus: venous thrombosis with patent foramen ovale

Genetics

Can be associated with inheritable hypercoagulable and premature atherosclerotic syndromes á

RISK FACTORS

Tobacco abuse, endocarditis, diabetes, drug abuse, cardiac arrhythmia, atherosclerotic disease, trauma, DVT, large vessel aneurysmal disease, prior lower extremity revascularization á

GENERAL PREVENTION

Anticoagulation in atrial arrhythmia, reduction of atherosclerosis risk factors, smoking cessation á

DIAGNOSIS

HISTORY

  • The 5 P's: If any is present, frequent reevaluations are indicated. Can present acutely in patients without significant collateral circulation. Proximal occlusions lead to more rapid progression of findings. Occlusion at aortic bifurcation can produce bilateral findings.Pain: diffuse distally; crescendo in nature; most common symptom in embolism; not alleviated by change of positionPulselessness: mandatory for diagnosis of embolism or thrombosis; pedal pulses subject to observer error; always compare to opposite limb.Pallor: skin color is pale early, cyanotic later. Check extremity temperature. Signs of chronic ischemia are skin atrophy, hair loss, and thick nails.Paresthesia: numbness early with thrombosis. Proprioception and light touch first to be lost; not reliable in diabetics. Loss of pain and pressure indicate advanced ischemia.Paralysis: Motor defect occurs after sensory and indicates profound ischemia.
  • Later symptoms include blisters, skin erosion (ulcer), tissue death/necrosis.

PHYSICAL EXAM

  • To estimate occlusion locationSymptoms typically start one joint below occlusion.Palpable pulses may be absent below occlusion and accentuated above.
  • In acute mesenteric ischemia: Painful periumbilical abdomen initially, later becomes diffusely painful.

DIFFERENTIAL DIAGNOSIS

  • EmboliMyocardial diseases: infarction, arrhythmias (e.g., atrial fibrillation), aneurysmsPain as first symptom
  • ThrombosisAbsence of heart disease: infarction, arrhythmiasChronic vascular historyBilateral changes of chronic ischemiaVascular procedures: bypass/interventionalNumbness rather than pain as first symptom
  • Other conditionsAcute aortic dissection (chest or back pain with rapid clinical deterioration)Acute DVT (massive swelling, pain, warm skin)

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

  • Myocardial/muscle isoenzymes
  • Coagulation parameters
  • Blood pH/bicarbonate
  • Urine myoglobin
  • Electrolytes
  • Amylase

Diagnostic Procedures/Other

  • Computed tomography (CT) with contrast/CT angiography with multiplanar reconstruction is accurate and efficient for diagnosis of arterial occlusions (class IIB indication) (1)[C].
  • Magnetic resonance angiography (MRA) with gadolinium enhancement of the extremities has class IA evidence for diagnosing location and degree of stenosis in peripheral arterial disease (PAD) and is useful in selecting patients as candidates for endovascular intervention (1)[C].
  • Conventional arteriographyRarely indicated preoperatively; used intraoperatively after an embolectomyCrescent-shaped (rounded reverse meniscus sign) or multiple filling defects within an otherwise normal artery implicates an embolus.Sharp/tapered cutoff sign on arteriography implicates arterial thrombus.May depict causative factor (e.g., anastomotic stricture)
  • Electrocardiogram (ECG)
  • Noninvasive/indirectDoppler: presence or absence of flow (<50 mm Hg perfusion in Doppler-heard systolic is indicative of ischemia)Ankle/arm index (AAI; also known as ankle/brachial index [ABI]) = dorsal pedal/ posterior tibial pressure divided by brachial pressure (normal >1.0, favorable >0.30, although <0.90 are abnormal [class IB evidence])Toe pressures - toe-brachial index <0.7 (may be useful in patients with ABI >1.30 (class IIA Indication) (1)[C]

TREATMENT

Initial treatment: hemodynamic stabilization (volume resuscitation, maintenance of end-organ perfusion, and correction of cardiac arrhythmias) á

GENERAL MEASURES

Revascularization of an ischemic area results in return of blood with a low pH and high potassium. This must be closely monitored after treatment. á

MEDICATION

First Line

  • Heparin: goal to prevent distal and proximal extension of thrombus, anti-inflammatory effects80 U/kg IV loading (or 5,000 to 10,000 U)Continuous infusion sufficient to double partial thromboplastin time, generally 18 U/kg/hrTransition to 3- to 6-month period of warfarin therapy is indicated if below-knee bypass is performed with synthetic graft.Contraindications: heparin allergy, bleeding diathesis, trauma (e.g., head injury), hematuria/hemoptysis, acute aortic dissection
  • ThrombolysisIntra-arterial recombinant tissue plasminogen activator (rt-PA) may be more effective than intra-arterial streptokinase or intravenous (IV) rt-PA in treating distal arterial occlusion, with no change in risk of hemorrhagic complications.UrokinaseLoading dose: 4,400 IU/kg at a rate of 90 mL/hr over 10 minutes; then 4,400 IU/kg at a rate of 15 mL/hr over 12 hours; may be repeated as neededEquivalent results to rt-PA although lysis of clot may be faster with intra-arterial rt-PA (2)[A].Do not use thrombolytic agents for >72 hours; risk of systemic/intracranial bleeding increases at this point.Contraindications: nonsalvageable ischemia, recent myocardial infarction, aneurysm, aortic dissection, trauma, uncontrolled hypertension
  • In pediatric femoral artery thrombosis: IV unfractionated heparin for 5 to 7 days, surgery if life or limb threatened

ISSUES FOR REFERRAL

  • Mesenteric ischemia: immediate GI follow-up/endoscopy (mortality of 70%)
  • Renal infarction/nephrotic syndrome: nephrology follow-up

ADDITIONAL THERAPIES

  • For chronic PAD with intermittent claudication, aspirin is preferred to clopidogrel unless with aspirin allergy. Lifelong 75 to 100 mg/day of aspirin is recommended.
  • Clopidogrel 75 mg/day is safe and effective alternative to acetylsalicylic acid (ASA) in patients with intermittent claudication, chronic limb ischemia, prior lower extremity revascularization, or prior amputation for lower extremity ischemia (class I indication) (1)[C].
  • Exercise programs for all patients.
  • Statin therapy: goal low-density lipoprotein (LDL) <100 for all patients with PAD (class I indication) (1)[C]; goal <70 for patients with lower extremity PAD at high risk for ischemic events (class IIA indication) (1)[B]
  • Antihypertensives: Hypertensive patients with lower extremity PAD goal BP <140/90 mm Hg (without diabetes mellitus [DM]) or 130/80 mm Hg in patients with DM or chronic kidney disease (CKD) (class I indication) (1)[C]
  • β-adrenergic blocking drugs are effective antihypertensives and not contraindicated in PAD (class I indication) (1)[C].
  • ACE-inhibitors are reasonable for symptomatic lower extremity PAD to reduce risk of cardiovascular events (class IIA indication) (1)[C].
  • Cilostazol 100 mg PO BID is indicated to improve symptoms and increase walking distance in patients with lower extremity PAD and intermittent claudication (class I indication) (1)[C].

SURGERY/OTHER PROCEDURES

  • Angioplasty, thromboembolectomy, thromboaspiration (clot aspiration), or a combination of these techniques may be required. Less invasive procedures are used when the ischemic limb is not imminently threatened. Catheter-based thrombolytic therapy (class I indication) (1)[C] is effective and beneficial with ischemia of <14 days.
  • Mechanical thrombectomy devices can be used as adjunctive therapy for acute limb ischemia due to peripheral artery occlusion (class IIA indication) (1)[C].
  • Arterial bypass: Extended embolic time may require bypass secondary to intimal damage/fibrosis.
  • IV unfractionated heparin (UFH) at therapeutic levels is considered recommended treatment prior to vascular bypass cross-clamp application.
  • Stents (and other adjunctive techniques such as lasers, cutting balloons, atherectomy devices, and thermal devices) can be useful in the femoral, popliteal, and tibial arteries as salvage therapy for a suboptimal or failed result from balloon dilation (class IIA indication) (1)[C].

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Time is of the essenceUnless contraindicated, systemic heparinization to decrease clot propagation and prophylaxis against further emboli
  • Early subcritical stenosis criteriaMild ischemic pain, normal neurologic examCapillary refill presentArterial signals present by Doppler in distal extremityAnkle/arm index >0.30TreatmentHeparin (see "Medication"Ł)ArteriographyEmbolismSurgical removal if acceptable operative risk; for example, balloon embolectomyAnticoagulation versus intra-arterial thrombolytics if prohibitive riskThrombosisTrial of thrombolytics and correction of arterial defect if good riskAnticoagulation if poor risk or thrombolytics contraindicated
  • Critical stenosis criteriaIschemic pain, mild neurologic deficit, weakness of ankle dorsiflexionMinimal sensory loss; light touch and/or vibratoryNo pulsatile flow by Doppler, venous flow presentTreatmentTime to intervention is critical.Arteriography, either CTA or traditionalIndividualize thrombolysis and/or operative procedure (depending on extent of thrombosis and amenability for surgical removal)Thrombolysis to optimize alternativesIntraoperative lytic therapy: bypass, patch angioplasty
  • Late (nonsalvageable) criteriaProfound sensory loss, muscle paralysis, muscle rigorAbsent capillary refillSkin mottlingNo arterial or venous signals by DopplerTreatmentArteriography usually is not warranted.Attempts at reperfusion contraindicatedAnticoagulationDefinitive amputation, if possible

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

After definitive treatment of an embolus, evaluate for other complications of atherosclerosis (carotid stenosis, aortic aneurysm, peripheral vascular disease, and coronary arterial disease). á

Patient Monitoring

Postoperative monitoring: anticoagulation; establish brisk diuresis, continued resuscitation, and further diagnostics, including echocardiography and other studies; monitor perfusion stability; treat/eliminate causative factors. á

PROGNOSIS

  • 90% good outcome with prompt treatment; delayed/untreated is associated with high mortality and limb loss.
  • 20-30% hospital mortality associated with causative factors

COMPLICATIONS

  • Acidosis, myoglobinuria, acute renal failure, hyperkalemia
  • Recurrent occlusion or failure to remove clot/obstruction
  • Compartment syndromes/reperfusion syndrome, delayed or acute. Predisposing factors include combined arterial injury, profound and prolonged ischemia, and hypotension.
  • Clinical findings of compartment syndrome: severe pain; pain with passive muscle movement; hypesthesias of nerves in compartment; paralysis of nerves, especially peroneal foot drop; tender, tense edema; compartment pressure >30 to 45 mm Hg
  • Consequences of unrecognized compartment syndrome are as follows:Acute: amputation, sepsis, myoglobin renal failure, shock, multiple organ failureDelayed: ischemic contracture, infection, causalgia, gangrene

REFERENCES

11 Anderson áJL, Halperin áJL, Albert áNM, et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(13):1425-1443.22 Robertson áI, Kessel áDO, Berridge áDC. Fibrinolytic agents for peripheral arterial occlusion. Cochrane Database Syst Rev. 2013;12:CD001099.

ADDITIONAL READING

  • Alonso-Coello áP, Bellmunt áS, McGorrian áC, et al. Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e669S-e690S.
  • Barmase áM, Kang áM, Wig áJ, et al. Role of multidetector CT angiography in the evaluation of suspected mesenteric ischemia. Eur J Radiol. 2011;80(3):e582-e587.
  • Creager áMA, Kaufman áJA, Conte áMS. Clinical practice. Acute limb ischemia. N Engl J Med. 2012;366(23):2198-2206.
  • Hynes áBG, Margey áRJ, Ruggiero áNII, et al. Endovascular management of acute limb ischemia. Ann Vasc Surg. 2012;26(1):110-124.
  • Yikilmaz áA, Karahan áOI, Senol áS, et al. Value of multislice computed tomography in the diagnosis of acute mesenteric ischemia. Eur J Radiol. 2011;80(2):297-302.

CODES

ICD10

  • I74.9 Embolism and thrombosis of unspecified artery
  • I74.3 Embolism and thrombosis of arteries of the lower extremities
  • I74.5 Embolism and thrombosis of iliac artery
  • I66.9 Occlusion and stenosis of unspecified cerebral artery
  • I74.8 Embolism and thrombosis of other arteries
  • I74.4 Embolism and thrombosis of arteries of extremities, unspecified
  • I74.2 Embolism and thrombosis of arteries of the upper extremities

ICD9

  • 444.9 Embolism and thrombosis of unspecified artery
  • 444.22 Arterial embolism and thrombosis of lower extremity
  • 444.81 Embolism and thrombosis of iliac artery
  • 434.10 Cerebral embolism without mention of cerebral infarction
  • 444.89 Embolism and thrombosis of other specified artery

SNOMED

  • Arterial embolus and thrombosis (disorder)
  • Femoral artery embolus
  • Embolism of iliac artery
  • Cerebral embolism (disorder)
  • Popliteal artery embolus
  • lower limb arterial embolus (disorder)
  • Embolism and thrombosis of the brachial artery

CLINICAL PEARLS

  • 5 P's of occlusion: pain, pallor, paresthesia, pulselessness, and paralysis
  • Golden period: 4 to 6 hours, after which the profound ischemia leads to irreversible cellular death