Medication Summary
Heparin should be considered seriously in the management of cerebral venous thrombosis (CVT), with subsequent conversion to warfarin as maintenance therapy suggested. Subcutaneous low ̶ molecular-weight heparin (Lovenox) also has been used in patients with venous sinus thrombosis.
Thrombolytic therapy may be effective in CVT, but all studies so far describe its use only with local instillation by microcatheter or direct instillation at the time of surgical thrombectomy.
Anticoagulants, Cardiovascular
Class Summary
These medications are used to prevent propagation of the clot to more extensive areas of the cerebral venous system. Studies indicate a tendency toward better outcome in patients treated with anticoagulant therapy than in those who are not treated with anticoagulants. In Einhaupl's study, even patients with cerebral hemorrhage appeared to benefit from anticoagulation. [27]
Heparin
Heparin increases the action of antithrombin III, leading to inactivation of coagulation enzymes thrombin, factor Xa, and factor IXa. Thrombin is the enzyme that is most sensitive to inactivation by heparin.
Because heparin is not absorbed from the GI tract, it must be given parenterally. When given intravenously, its effect is immediate. Metabolism of heparin is complex; rapid zero-order metabolism is followed by slower first-order renal clearance. The saturable phase of heparin clearance is thought to be due to binding to endothelial cell receptors and macrophages in which it is depolymerized. Zero-order process is saturable, leading to an increase in half-life from 30 minutes with a low dose bolus to 150 minutes with a high dose bolus. Weight-based protocol is now often used for dosing. When choosing this therapy, the risks of its contraindications must be weighed against the potential benefits of the drug.
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.
Warfarin (Coumadin, Jantoven)
Warfarin interferes with the action of vitamin K, a cofactor essential for converting precursor proteins into factors II, VII, IX, and X. Warfarin does not affect the activity of coagulation factors synthesized prior to exposure to warfarin. Depletion of these mature factors by normal metabolism must occur before the therapeutic effects of the newly synthesized factors can be seen; thus, warfarin may take several days to become effective.
The dose of warfarin administered is influenced by differences in absorption, metabolism, and hemostatic responses to given concentrations; the dose must be monitored closely by following the prothrombin time (PT) and international normalized ratio (INR). Higher initial doses do not appear to improve the time required to achieve therapeutic levels but do increase the bleeding risk.
The expert opinion is that warfarin treatment should be maintained for 3-6 months, but no randomized, placebo-controlled trials have addressed this issue.
Thrombolytics
Class Summary
These agents cause the lysis of clots. All studies concerning the use of these agents in cerebral venous thrombosis (CVT) involve either direct instillation into the sinus at the time of surgery or the use of microcatheters to reach the venous sinus.
Alteplase (Activase)
Alteplase is a biosynthetic form of human tissue plasminogen activator. Tissue plasminogen activator exerts an effect on the fibrinolytic system that results in the conversion of plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII.
Alteplase is not given as an IV infusion to treat CVT. Refer the patient to a facility with the expertise to perform venous sinus catheterization.
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.
Base the dose on the patient's weight. Initiate treatment as soon as possible after the onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, it must be reconstituted immediately before use.
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Left lateral sinus thrombosis demonstrated on magnetic resonance venography (MRV). This 42-year-old woman presented with sudden onset of headache. Physical examination revealed no neurologic abnormalities.
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Same patient as in the previous image. One week after treatment with heparin, the magnetic resonance (MR) venogram displayed increased flow in the left lateral sinus consistent with early recanalization of the sinus; headache had resolved at this point.
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Magnetic resonance venogram (MRV) - axial view; A = lateral (transverse) sinus; B = sigmoid sinus; C = confluence of sinuses; and D = superior sagittal sinus.
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Magnetic resonance venogram (MRV) - sagittal view; A = lateral (transverse) sinus; C = confluence of sinuses; D = superior sagittal sinus; and E = straight sinus.
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Computed tomography (CT) scan demonstrates a left posterior temporal hematoma in a 38-year-old woman on oral contraceptives (the only identified risk factor).
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Contrast-enhanced magnetic resonance imaging (MRI) scan showing lack of filling of left transverse sinus.
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Axial view of magnetic resonance (MR) venogram demonstrating lack of flow in transverse sinus.
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Coronal view of magnetic resonance (MR) venogram demonstrating lack of flow in the left transverse and sigmoid sinuses.
Tables
|
Treated Group, % (n = 12) |
Nontreated Group, % (n = 21) |
Full recovery |
62.5 |
29 |
Mild disability |
12.5 |
13 |
Severe disability |
12.5 |
9.6 |
Fatal outcome |
12.5 |
48 |
