eMedicine Specialties > Neurology > Neuro-vascular Diseases
Cerebral Venous Thrombosis: Treatment & Medication
Updated: Nov 5, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Medical management of the patient with cerebral venous thrombosis (CVT) is similar to that of patients with arterial stroke as far as stabilizing the patient is concerned.
- Patients with altered mental status or hemiplegia should be given nothing by mouth to prevent aspiration. Intravenous fluids should not be hypotonic solutions. Normal saline is recommended at a rate of approximately 1000 mL in 24 hours. To decrease intracranial pressure, the head should be elevated 30-40° at all times. In the treatment of stroke patients, supplemental oxygen has not been shown to be beneficial unless level of consciousness is decreased.
- Seizures should be treated with appropriate anticonvulsants. Fosphenytoin is recommended for treatment of seizures in those patients who require a parenteral formulation. Alternatively, phenobarbital or sodium valproate injection may be utilized if the patient has allergy to phenytoin. Diazepam or lorazepam may be used to treat status epilepticus, but the patient also should be given an anticonvulsant with a longer duration of action to prevent recurrent seizures.
- Specific therapy for CVT involves anticoagulation or thrombolytic therapy. Use of anticoagulation in CVT has been a subject of some debate among neurologists. Concern has been expressed over the possibility of increasing hemorrhage in patients treated in this manner. Studies by de Bruijn and Stam in 199915 and by Einhaupl in 199116 indicated that anticoagulation could be used safely in this condition. The question of effectiveness of anticoagulation is not clear, but most articles tend to point toward improved outcome with utilization of anticoagulation.
- Thrombolytic therapy has been described in several case reports as beneficial in cases of CVT. These patients were treated with infusion of a thrombolytic agent into the dural venous sinus utilizing microcatheter technique. This treatment at present is limited to specialized centers but should be considered for patients with significant deficit.
- A recent report describes the use of a rheolytic catheter device in a patient who had not responded to microcatheter instillation of urokinase. The rheolytic catheter was designed for use in the coronary circulation and delivers 6 high-velocity saline jets through a halo device at the tip of the catheter. This leads to a Bernoulli effect that breaks up the thrombus. In addition, the particulate debris is directed into an effluent lumen for collection into a disposable bag. The catheter was advanced into the sagittal sinus, resulting in restoration of venous flow and reduction of intracranial pressure.
Surgical Care
In cases of severe neurologic deterioration, open thrombectomy and local thrombolytic therapy have been described as beneficial. Patients selected for these procedures have progressed despite adequate anticoagulation and intensive medical care. Ekseth described 3 such patients who all returned to normal lives following this procedure.17
Consultations
- Consultation with a neurosurgeon is indicated in patients with subdural empyema or brain abscess. Consultation should also be considered for patients who have severe deterioration despite aggressive medical management.
- Consultation with an infectious disease specialist is to be considered for patients with cerebral venous thrombosis who have associated infection such as meningitis or sinusitis.
- Consultation with an otolaryngologist may be helpful in patients with associated sinusitis.
Medication
Heparin should be considered seriously in the management of cerebral venous thrombosis (CVT). Conversion to warfarin as maintenance therapy is then suggested. Subcutaneous low molecular weight heparin (Lovenox) also has been used in patients with venous sinus thrombosis.
Thrombolytic therapy may be useful, but all studies so far describe its use only with local instillation by microcatheter or direct instillation at the time of surgical thrombectomy.
Anticoagulants
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.
Heparin
Increases the action of antithrombin III, leading to inactivation of coagulation enzymes thrombin, factor Xa, and factor IXa. Thrombin is the most sensitive to inactivation by heparin. Because heparin is not absorbed from the GI tract, it must be given parenterally. When given IV, effect is immediate. Metabolism of heparin is complex; rapid zero-order metabolism is followed by slower first-order renal clearance. Zero-order process is saturable, leading to an increase in half-life from 30-150 min as dose increased. Weight-based protocol now often used for dosing. When choosing this therapy, risks of its contraindications must be weighed against potential benefits.
Adult
Initial infusion: 18 U/kg/h IV; aPTT checked in 6 h and q6h after any dosage change, as well as every am; adjust dose according to following parameters
aPTT = <1.2 times control: 80 U/kg bolus with increase of 4 U/kg/h
aPTT = 1.2-1.5 times control: 40 U/kg bolus with increase of 2 U/kg/h
aPTT = 1.5-2.3 times control: No change in infusion rate needed
aPTT = 2.3-3 times control: Decrease infusion rate by 2 U/kg/h
aPTT > 3 times control: Hold infusion for 1 h and decrease rate by 3 U/kg/h
Pediatric
Not established
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Documented hypersensitivity, aneurysm, active or recent bleeding, coagulopathy, endocarditis, hemophilia, hepatic disease, hypertension, inflammatory bowel disease, lumbar puncture/spinal anesthesia, sulfite hypersensitivity, surgery, thrombocytopenia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor platelet count for development of thrombocytopenia; severe hyperkalemia may occur with concomitant use of ACE inhibitors; increased bleeding risk occurs with many drugs, including platelet inhibitors, NSAIDs, valproic acid, Ginkgo biloba, and probenecid
Warfarin (Coumadin)
Interferes with action of vitamin K, a cofactor essential for converting precursor proteins into factors II, VII, IX, and X. Does not affect activity of coagulation factors synthesized prior to exposure to warfarin. Depletion of these mature factors by normal metabolism must occur before therapeutic effects of newly synthesized factors can be seen, thus may take several days to become effective.
Dose influenced by differences in absorption, metabolism, and hemostatic responses to given concentrations; dose must be monitored closely by following PT and INR. Higher initial doses do not appear to improve time required to achieve therapeutic levels but do increase bleeding risk.
Expert opinion is that warfarin treatment should be maintained for 3-6 mo, but no randomized, placebo-controlled trials have addressed this issue.
Adult
Initial: 5 mg PO qd; adjust dose by monitoring INR (target, 2.5)
Pediatric
Initial: 0.2 mg/kg PO up to 10 mg
Maintenance: 0.1 mg/kg/d; INR must be monitored to determine maintenance dose
Monitor INR whenever a medication is added or discontinued; drugs that may decrease anticoagulant effects include griseofulvin, carbamazepine, glutethimide, estrogens, nafcillin, phenytoin, rifampin, barbiturates, cholestyramine, colestipol, vitamin K, spironolactone, oral contraceptives, and sucralfate; medications that may increase anticoagulant effects include oral antibiotics, phenylbutazone, salicylates, sulfonamides, chloral hydrate, clofibrate, diazoxide, anabolic steroids, ketoconazole, ethacrynic acid, miconazole, nalidixic acid, sulfonylureas, allopurinol, chloramphenicol, cimetidine, disulfiram, metronidazole, phenylbutazone, phenytoin, propoxyphene, sulfonamides, gemfibrozil, acetaminophen, and sulindac; supplements such as ginger and Ginkgo biloba should be avoided; green leafy vegetables have high levels of vitamin K, which may decrease INR
Documented hypersensitivity, alcoholism, aneurysm, bleeding, breastfeeding, endocarditis, pregnancy, hemophilia, lumbar puncture, thrombocytopenia, hypertension, leukemia, polycythemia vera, intracranial bleeding, vitamin C deficiency, vitamin K deficiency
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May cause uncontrolled bleeding and should not be used in conditions in which bleeding would be difficult to control, leading to a more catastrophic outcome; medications that inhibit platelet function should be avoided, including aspirin, NSAIDs, and valproic acid; patients with protein S or C deficiency may become transiently hypercoagulable (anticoagulate patient with heparin and then convert to warfarin); do not switch brands after achieving therapeutic response; caution in active tuberculosis or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis
Thrombolytics
These agents cause lysis of the clot. All studies concerning the use of these agents in 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)
Biosynthetic form of human tissue plasminogen activator. Tissue plasminogen activator exerts effect on fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Not given as IV infusion to treat CVT. Refer patient to facility with expertise to perform venous sinus catheterization.
Adult
1 mg/cm infused via venous sinus catheter throughout clot, then 1-2 mg/h
Pediatric
Not established
Drugs that alter platelet function (eg, aspirin, dipyridamole, abciximab) may increase risk of bleeding prior to, during, or after alteplase therapy; may give heparin with and after alteplase infusions to reduce risk of rethrombosis; either heparin or alteplase may cause bleeding complications
Documented hypersensitivity, aneurysm, arteriovenous malformation, bleeding, coagulopathy, endocarditis, diabetic retinopathy, mitral stenosis, recent surgery, pregnancy, breastfeeding
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for bleeding, especially at arterial puncture sites, with coadministration of vitamin K antagonists; control and monitor BP frequently during and following alteplase administration (when managing acute ischemic stroke); do not use >0.9 mg/kg to manage acute ischemic stroke; doses >0.9 mg/kg may cause intracranial hemorrhage
Urokinase (Abbokinase)
Produced by kidney, converts plasminogen to plasmin by cleaving arginine-valine bond in plasminogen. Degradation products of fibrin and fibrinogen exert clinically significant anticoagulant effect. Erythrocyte aggregation and plasma viscosity also are reported to decrease.
Given in CVT by catheterization of venous sinus or by direct instillation at surgery during thrombectomy.
Adult
250,000 U/h instilled directly or via venous sinus catheter; additional doses of 50,000 U; total dose 1,000,000 U over 2 h
Pediatric
Not established
Effects increased with coadministration of aminocaproic acid, anticoagulants, antineoplastic agents, antithymocyte globulin, cefamandole, cefoperazone, Ginkgo biloba, NSAIDs, platelet inhibitors, porfimer, strontium-89 chloride, sulfinpyrazone, tranexamic acid, valproic acid
Documented hypersensitivity, aneurysm, arteriovenous malformation, bleeding, coagulopathy, endocarditis, diabetic retinopathy, mitral stenosis, recent surgery, pregnancy, breastfeeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients receiving IM administration of medications or with severe hypertension or trauma or surgery in previous 10 d; do not measure BP in lower extremities, because may dislodge DVT; monitor therapy by performing PT, aPTT, TT, or fibrinogen approximately 4 h after initiation of therapy
Streptokinase (Kabikinase, Streptase)
Facilitates thrombolysis through formation of an activator complex with plasminogen. Indirectly cleaves arginine-valine bond in plasminogen, forming plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Degradation products of fibrin and fibrinogen have significant anticoagulant effect.
Adult
Instilled directly or via venous sinus catheter
Pediatric
Only anecdotal reports describe use in children, and that in arterial occlusion; doses used were as follows
Loading dose: 1000-3000 IU/kg; followed by infusion of 1000-1500 IU/kg/h; in CVT, administered by direct infusion via catheter
Effects are increased with coadministration of aminocaproic acid, anticoagulants, antineoplastic agents, antithymocyte globulin, cefamandole, cefoperazone, Ginkgo biloba, NSAIDs, platelet inhibitors, porfimer, strontium-89 chloride, sulfinpyrazone, tranexamic acid, valproic acid
Documented hypersensitivity, aneurysm, arteriovenous malformation, bleeding, coagulopathy, endocarditis, diabetic retinopathy, mitral stenosis, recent surgery, pregnancy, breastfeeding
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in severe hypertension, IM administration of medications, trauma or surgery in previous 10 d; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be <2 times the normal control value following infusion of streptokinase and before (re)instituting heparin; do not take BP in lower extremities, as possible DVT may be dislodged; PT, aPTT, TT, or fibrinogen should be monitored 4 h after initiation of therapy; in addition to bleeding complications inherent in thrombolytic agents, repeated administration of streptokinase can result in tolerance as well as hypersensitivity
More on Cerebral Venous Thrombosis |
| Overview: Cerebral Venous Thrombosis |
| Differential Diagnoses & Workup: Cerebral Venous Thrombosis |
 Treatment & Medication: Cerebral Venous Thrombosis |
| Follow-up: Cerebral Venous Thrombosis |
| Multimedia: Cerebral Venous Thrombosis |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
cerebral venous thrombosis, CVT, sagittal sinus thrombosis, lateral sinus thrombosis, jugular foramen syndrome, cavernous sinus thrombosis, thrombus, clotting, blood clot, cerebral hemorrhage, venous thrombosis, cranial nerve palsies, cerebral infarction
