Medication Summary
The goal of medical management with antithrombotic agents is to prevent progressive neurologic deficits. Antiplatelet therapy and anticoagulation have been used both individually and in combination, with antiplatelet therapy being recommended in most patients with dissection. Current literature continues to demonstrate improved outcomes with systemic anticoagulation.
Anticoagulants, Cardiovascular
Class Summary
Anticoagulants prevent thrombus formation and reduce the number of emboli after arterial dissection. Anticoagulation also aids intimal healing, decreases smooth muscle cell proliferation, and decreases intimal thickening.
Heparin
Heparin potentiates the activity of antithrombin III. It does not actively lyse thrombi, but it inhibits further thrombogenesis. Heparin prevents reaccumulation of a clot after spontaneous fibrinolysis. An activated partial thromboplastin time (aPTT) of 1.5-2 times the control value (50-80 seconds) is therapeutic.
Warfarin sodium (Coumadin, Jantoven)
Warfarin interferes with hepatic vitamin K–dependent carboxylation and is used for prophylaxis and treatment of thromboembolic disorders. It usually prolongs the prothrombin time (PT) in 48 hours.
Enoxaparin (Lovenox)
Enoxaparin is a low-molecular-weight heparin (LMWH) produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). It binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). LMWH differs from UFH by having a higher ratio of anti–factor Xa to anti–factor IIa.
Enoxaparin does not actively lyse thrombi but is able to inhibit further thrombogenesis. It prevents reaccumulation of clot after spontaneous fibrinolysis. Its advantages include intermittent dosing and a decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. There is no point in checking the aPTT; the drug has a wide therapeutic window, and aPTT does not correlate with anticoagulant effect. The average duration of treatment is 7-14 days.
Enoxaparin prevents deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing surgery who are at risk for thromboembolic complications. It is used for prophylaxis in hip replacement surgery (during and after hospitalization), knee replacement surgery, or abdominal surgery in those at risk for thromboembolic complications, as well as in nonsurgical patients at risk for thromboembolic complications secondary to severely restricted mobility during acute illness.
Enoxaparin is used to treat DVT or PE in conjunction with warfarin for inpatient treatment of acute DVT with or without PE or for outpatient treatment of acute DVT without PE.
Desirudin (Iprivask)
Desirudin is a highly selective thrombin inhibitor. It inhibits fibrin formation, activation of coagulation factors, and thrombin induced platelet aggregation. This results in prolongation of the activated partial thromboplastin time.
Lepirudin (Refludan)
Lepirudin, a recombinant hirudin derived from yeast cells, is a highly specific direct thrombin inhibitor. It is indicated for anticoagulation in HIT and associated thromboembolic disease. Its action is independent of antithrombin III. Lepirudin blocks the thrombogenic activity of thrombin. It affects all thrombin-dependent coagulation assays (eg, aPTT values increase in a dose-dependent manner). Adjust the dose on the basis of aPTT ratios (target, 1.5-2.5 times normal) determined every 4 hours and then daily.
Antiplatelet Agents
Class Summary
Antiplatelet agents may be used to treat trauma patients in whom anticoagulation may be contraindicated. A Cochrane review found that the available evidence does not reliably establish whether anticoagulation is superior to antiplatelet therapy in patients with dissection.
Aspirin (Ecotrin, Empirin, Bayer, Anacin)
Aspirin blocks prostaglandin synthetase action and inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2. It acts on the hypothalamic heat-regulating center to reduce fever.
Clopidogrel (Plavix)
Clopidogrel selectively inhibits adenosine diphosphate (ADP) binding to platelet receptors and subsequent ADP-mediated activation of the glycoprotein (GP) IIb/IIIa complex, thereby inhibiting platelet aggregation.
Ticlopidine
Ticlopidine is second-line antiplatelet therapy for patients in whom aspirin is not tolerated or is ineffective.
Dipyridamole 200 mg/aspirin 25 mg (Aggrenox)
Dipyridamole-aspirin is a combination antiplatelet agent that takes advantage of the additive antiplatelet effects of the 2 drugs. Dipyridamole acts via the adenosine-platelet A2-receptor system, whereas aspirin inhibits platelet aggregation by causing irreversible inhibition of cyclooxygenase system, thereby reducing generation of thromboxane A2, a powerful enhancer of platelet aggregation and vasoconstriction.
Thrombolytics
Class Summary
Research into the use of thrombolytics for the treatment of extracranial internal carotid artery dissection has been limited; consequently, the usefulness and appropriateness of this approach have not yet been established.
Alteplase (Activase)
Alteplase, or tissue plasminogen activator (tPA), exerts an effect on the fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. The serum half-life of alteplase is 4-6 minutes but is lengthened when the drug is bound to fibrin in clot.
Alteplase is used in the management of acute myocardial infarction, acute ischemic stroke, and PE. It must be given within 3 hours of stroke onset, and heparin and aspirin must not be given for 24 hours after its administration. The safety and efficacy of concomitant administration with aspirin and heparin during the first 24 hours after symptom onset have not been investigated. Exclude hemorrhage by means of computed tomography. If the patient is hypertensive, give labetalol 10 mg intravenously.
Reteplase (Retavase)
Reteplase is a recombinant tPA that forms plasmin after facilitating cleavage of endogenous plasminogen. In clinical trials, it has been shown to be comparable with tPA in achieving patency at 90 minutes. Heparin and aspirin are usually given concomitantly and afterwards.
Tenecteplase (TNKase)
Tenecteplase is a modified version of alteplase that is made by substituting 3 amino acids. It has a longer half-life than alteplase and thus can be given as a single bolus infused over 5 seconds (as opposed to the 90 minutes required for alteplase). It appears to cause less non–intracranial bleeding than alteplase but carries a comparable risk of intracranial bleeding and stroke.
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Arterial dissection. (A) Tear and elevation of intima from wall of artery, resulting in luminal stenosis. Illustration shows stasis of flow in false lumen beneath elevated intima. This condition creates blind pouch that predisposes patient to thrombus formation. (B) Subadventitial dissection represents hemorrhage between media and adventitia. Artery may become dilated as result of thickening of arterial wall, with some degree of luminal narrowing. Elevation of intimal flap is not commonly associated with this type of dissection. Hemorrhage may extravasate through adventitia, resulting in pseudoaneurysm or fistula formation.
