Management of the thrombotic lesion


 * Associate Editors-In-Chief: Brian C. Bigelow, M.D.

Overview
The presence of angiographically apparent thrombus is associated with poorer outcomes in patients undergoing PCI. Thrombus often embolizes distally and causes no reflow and associated myonecrosis. There are two broad strategies to reduce thrombus burden: mechanical strategies and pharmacologic strategies.

Differentiating Thrombus from Other Angiographic Abnormalities

 * Coronary spasm can also lead to a focal narrowing of the lumen and should be treated with vasodilators
 * A dissection can cause a hazy appearance to the lumen and should be treated with intracoronary stenting

Goals of Treatment
Goals in the management of the thrombotic lesion include:
 * Restoration of normal antegrade flow in the epicardial artery (TIMI Grade 3 Flow)
 * Maintenance of normal perfusion in the downstream capillary bed or microvasculature (TIMI Myocardial Perfusion Grade 3)
 * Resolution of thrombus burden
 * Avoid distal embolization with abrupt cutoff of distal branches and side branches
 * Avoid / reduce thrombotic major adverse cardiac events (MACE) which includes death, MI, recurrent ischemia, urgent target vessel revascularization (TVR).
 * In the setting of ST segment elevation MI, the goal is to achieve greater than 70% ST segment resolution.

Step-By-Step Strategy in the Management of the Thrombotic Lesion

 * The first strategy is to prevent the occurrence of thrombus through the use of upstream antiplatelet and antithrombotic pharmacotherapies including aspirin, thienopyridines, and glycoprotein 2b3a inhibition.
 * The second strategy is to mechanically aspirate thrombus.
 * The third strategy is to direct stent the lesion without pre-dilation to minimize distal embolization.
 * The fourth strategy is to utilize intracoronary fibrinolytic therapy to dissolve clot that is refractory to other forms of treatment and dissolve clot inside branches that may be accessible to mechanical devices.
 * Alternate / additional strategies include the use of distal protection and saphenous vein grafts to minimize distal embolization.

Antiplatelet Therapy

 * The incidence of thrombus on the coronary angiogram can be reduced by and complications of the PCI procedure can be reduced by upstream pharmacologic therapy with antiplatelet therapy including aspirin, platelet glycoprotein IIb/IIIa receptor (GP IIb/IIIa) antagonists in patients who are troponin positive (abciximab, eptifibatide, tirofiban), and ADP receptor/P2Y12 inhibitors (plavix, ticagrelor, prasugrel)
 * Aspirin is a conventional therapy that reduces ischemic complications after PCI.
 * GP IIb/IIIa antagonists are used adjunctively to treat and prevent thrombus formation and decreases ischemic complications post-PCI in patients with angiographic evidence of or suspected thrombus. In patients with STEMI undergoing primary PCI, GP IIb/IIIa antagonists have been shown to reduce mortality in meta-analyses.  There is an ongoing debate as to the optimal timing of their administration (upstream vs in-lab administration).

Antithrombin Therapy

 * Antithrombin Therapy: Ufractionated heparin (UFH), low molecular weight heparin (LMWH). Fondaparinux is not recommended in primary PCI.
 * UFH is a conventionally used thrombin inhibitor that prevents arterial thrombus formation at the site of a vessel wall injury, on catheters, and on equipment during PCI.
 * LMWH: ExTRACT-TIMI 25 demonstrated that there were improved clinical outcomes with LMWH in patients with STEMI undergoing fibrinolysis and subsequent PCI.
 * Direct thrombin inhibitors (DTI): Hirudin, bivalirudin, argatroban may be used as an alternative to heparin and GP IIb/IIIa. The optimal strategy is to pre-load with clopidogrel if a DTI is used, which is the drug of choice in patients with a history of heparin-induced thrombocytopenia.

Thrombolytic Therapy

 * Thrombolytic Therapy: Urokinase (UK), tissue plasminogen activator (tPA) for STEMI when other pharmacologic and mechanical treatments are not successful. Caution: intracoronary administration of fibrinolytic agents is an "off label" the use of these agents (this mode of administration is not been approved by the FDA, but fibrinolytic agents are an FDA approved drug).  The total dose of tPA is 20 mg which is approximately the 1/5 of that generally used for systemic fibrinolysis.  tPA can it be administered 2 mg at a time to evaluate its efficacy.

Thrombus Aspiration

 * Thrombus aspiration can be achieved with the Export, Pronto, and other devices
 * Thrombus aspiration is the preferred treatment and has been associated with improved myocardial perfusion and mortality.
 * Care should be exercised in very proximal lesions in the LAD and the circumflex, as the clot may embolize into the other artery.
 * After aspiration, direct stenting is associated with improved rates of recurrent MI in meta-analyses, improved myocardial perfusion, and improved ST segment resolution. Stenting reduces the risk of abrupt closure.

Direct Stenting

 * Direct placement of the stent without pre-dilation by a balloon has been associated with a reduction in myonecrosis in meta-analyses.

Distal Protection

 * Distal Protection can be achieved with the following devices (Percusurge guardwire, Triactive, Spider wire, Proxis), particularly in saphenous vein grafts
 * Occlusive (Percusurge guardwire, Triactive) and filter (Filterwire) methods may improve safety and efficacy of PCI in patients with thrombotic lesions in SVG; SAFER study of Percusurge device demonstrated lower rate of death/MI
 * Distal embolic protection has not shown to be efficacious in the setting of STEMI in native coronary arteries with either Percusurge (EMERALD trial ) or Filterwire (PROMISE trial ).

Rheolytic Thrombectomy

 * Rheolytic thrombectomy with Possis Angiojet was not found to have any benefit in the setting of STEMI in native coronary arteries in the AIMI trial. Infarct sizes were larger and mortality was higher.

Less Frequently Used Modalities

 * Directional Atherectomy
 * Transluminal Extraction Catheter (TEC)

Management of No Reflow
Distal embolization of thrombus often occurs, and you should be prepared to treat the patient for potential spasm or no-reflow with a calcium channel blocker, adenosine (100 mcg IC) or nitroprusside (100 mcg IC).