eMedicine Specialties > Neurology > Neuro-vascular Diseases
Blood Dyscrasias and Stroke: Treatment & Medication
Updated: Jul 14, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Consultations
Hematologic consultation may be requested in the following complicated situations:
- When clinical diagnosis is uncertain
- To clarify abnormal test results
- For recommendations on management of the blood dyscrasia
Diet
Dietary issues with blood dyscrasias resulting in stroke include the following:
- Hyperhomocystinemia has been attributed to dietary deficiency of vitamin B-6, B-12, or folic acid, especially in older patients with poor nutritional intake.
- Patients with hypercoagulable states that may cause stroke typically take the oral anticoagulant warfarin. For these patients, monitoring vitamin K in the diet is important, as it may alter the efficacy of warfarin.
Medication
Treatment of blood dyscrasias that may cause stroke remains controversial. The risks and benefits of treatment have to be considered in the context of the number of episodes of thrombosis. In patients who are not treated with anticoagulants, prophylaxis should be considered during times of high risk such as pregnancy, immobilization, or the postoperative period.
Patients with hypercoagulable states such as APC resistance; protein C, protein S, and antithrombin III deficiencies; or aPS are treated with anticoagulants for stroke prophylaxis, especially if deep vein thrombosis is present or recurrent thrombotic events have occurred. The anticoagulation regimen usually is started with IV heparin, maintaining the aPTT at 2-3 times normal, until an oral anticoagulant (ie, warfarin) is able to achieve a therapeutic PT (INR).
In protein C and S deficiencies, starting heparin before warfarin is imperative to avoid warfarin-induced skin necrosis. The level of anticoagulation in terms of PT (INR) required for stroke prophylaxis is uncertain. In the treatment of aPS, one retrospective study had reported that an INR of 3.0-3.5 was more effective than the routinely used INR of 2.0-3.0; however, two prospective studies have shown that an INR of 2.0-3.0 is sufficient in aPS. A sizable fraction of neurologists avoid treating patients with stroke with a heparin bolus, as this is thought to increase the risk of intracranial bleed.
Results of the APASS study showed that there was no difference between aspirin and warfarin for treatment of patients with anticardiolipin antibody (aCL) or lupus anticoagulant (LA). It is important to emphasize that the APASS study did not look specifically at antiphospholipid antibody syndrome. However, it was noticed that the risk of recurrent thrombosis was increased in patients who had both aCL and LA. Besides, patients enrolled in the APASS study had low aCL titer and had low INR and the study was criticized for the limitations. Thus, in deciding whether patients need to be treated with warfarin, their LA status and high-titer aCL should also be borne in mind and high-intensity anticoagulation (target INR, >3.0) should be considered in appropriate patients. A clinical trial with defined antiphospholipid antibody syndrome and high titers of aCL and LA with high-intensity regimen of warfarin would probably answer the issue.
Patients with sickle cell anemia and stroke are treated with antiplatelet agents such as aspirin. Other methods of treatment that are advocated are blood transfusion and hydroxyurea8 . The role of bone marrow transplantation is, at best, experimental.9 The roles of other antiplatelet agents, such as ticlopidine and clopidogrel, or combination therapy with aspirin and dipyridamole specifically in prevention of strokes that result from blood dyscrasias have not been evaluated.
Hyperhomocystinemia is treated with vitamin supplementation, usually folic acid and sometimes pyridoxine (vitamin B-6) and vitamin B-12, as well. The Vitamin in Stroke Prevention trial (VISP) addressed the issue.10 Results of the VISP trial did not show any significant benefit of treatment with high doses of folic acid, pyridoxine, and vitamin B-12 in reducing vascular outcomes in patients with nondisabling strokes and elevated homocysteine compared with low doses of these vitamins. However, it did show that there was a persistent and graded association between total homocysteine and outcomes irrespective of the treatment group. A larger study with high baseline homocysteine levels and longer follow up may help resolve the issue.
Several new oral anticoagulant medications are in the final stages of clinical trials for use in the prophylaxis of ischemic thromboembolic stroke. Once approved for use, the potential of such drugs in the arena of stroke treatment is significant.
Anticoagulants
These agents are used for hypercoagulable states such as APC resistance; protein C, protein S, and antithrombin III deficiencies; and aPS. Insufficient evidence exists to make a recommendation. The most recent scientific statements state the following evidence-based recommendations:
- Patients with ischemic stroke or TIA with thrombophilia should be evaluated for DVT (Class I, Level of Evidence A)
- IF no VTE is present, long-term anticoagulants of antiplatelet therapy is reasonable (Class IIa, Level of Evidence C);
- Recurrent event: Consider long-term anticoagulation11 (Class IIb, Level of Evidence C).
For antiphospholipid antibody (APLA) syndrome, the following have been stated:
- Cryptogenic stroke or TIA and possible APLA — antiplatelet therapy is reasonable (Class IIa, Level of Evidence B);
- Cryptogenic stroke or TIA and APLA syndrome with venous and arterial occlusive disease in multiple organs, miscarriages, and livedo reticularis — oral anticoagulation is reasonable (INR 2-3) (Class IIa, Level of Evidence B).
Heparin
Inhibits reaction that leads to clotting of blood; in combination with antithrombin III (heparin cofactor), inhibits thrombosis by inactivating activated factor X, thus preventing formation of thrombin from prothrombin and fibrin from fibrinogen; also prevents formation of fibrin-stabilizing factor.
Adult
800-1200 U/h IV; dosage adjusted according to aPTT
Pediatric
Not established
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase toxicity
Documented hypersensitivity, subacute bacterial endocarditis, active bleeding, history of heparin-induced 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
In neonates, preservative-free heparin is recommended to avoid possible toxicity (gasping syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and shock; caution in elderly patients and women >60 y
Warfarin (Coumadin)
Inhibits synthesis of vitamin K-dependent clotting factors (ie, factors II, VII, IX, and X, proteins C and S); resultant suppression of extrinsic clotting pathway leads to its anticoagulant property.
Adult
5-10 mg PO on day 1; on subsequent days, dosages determined by daily monitoring of PT (INR) until therapeutic INR for particular indication achieved
Pediatric
Not established
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, salicylates, 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
Documented hypersensitivity; risk of hemorrhage, threatened abortion; recent surgery, during and immediately following major surgery or spinal tap; bleeding diathesis (inherited or acquired)
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Do not switch brands after achieving therapeutic response; caution in active TB or diabetes; patients with protein C or S deficiency are at risk of developing skin necrosis; elderly patients (>60 y)
Antiplatelet agents
Used for stroke prophylaxis in blood dyscrasias that lead to ischemic stroke. This includes hypercoagulable states with minor symptoms (ie, anticoagulation not indicated), sickle cell anemia with risk of stroke.
Aspirin (Anacin, Ascriptin, Bayer Aspirin)
Potent inhibitor of prostaglandin synthesis and platelet aggregation. Enteric coated aspirin is preferred, as it minimizes adverse GI effects.
Adult
81-1300 mg/d PO with food; popular doses include 81-325 mg/d in Europe and 325-1300 mg/d in US (FDA in 1999 changed recommendation to 50-325 mg/d)
Most effective dose for stroke prophylaxis not known
Pregnancy: Used only if benefits clearly outweigh risks; low dose (<150 mg/d) used in second and third trimesters
Pediatric
Not established
Effects may decrease with antacids and urinary alkalinizers; serum levels decreased by corticosteroids; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; concomitant anticoagulants; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, severe anemia, asthma; children <16 y with flu, due to association with Reye syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease
More on Blood Dyscrasias and Stroke |
| Overview: Blood Dyscrasias and Stroke |
| Differential Diagnoses & Workup: Blood Dyscrasias and Stroke |
 Treatment & Medication: Blood Dyscrasias and Stroke |
| Follow-up: Blood Dyscrasias and Stroke |
| References |
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References
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Further Reading
Keywords
hypercoagulable state, cerebrovascular event, cerebrovascular accident, coagulation disorder
