/publications/issue/2009/2009-01/2009-01-9969

Coagulation Counseling

Author: Anna D. Garrett, PharmD, BCPS, CPP


Dr. Garrett is manager of the Health Education Center at Mission Hospitals in Asheville, North Carolina.


Laxatives May Interfere with Warfarin

Excessive use of stimulant laxatives, such as senna, may interfere with warfarin therapy. A case was recently reported of a patient who used excessive senna. The patient presented with bloody stools and an international normalized ratio (INR) of 11.9. The interaction may be due to diarrhea, which can develop if laxatives are overused. Diarrhea is known to decrease the absorption of vitamin K, which can lead to elevated INRs and bleeding. Patients should be counseled to use herbal laxatives with care. Natural products that are promoted for weight loss and detoxification may contain ingredients such as aloe, cascara, or European buckthorn, all of which have laxative properties.


Alteplase Effective for Stroke up to 4.5 Hours After the Event

Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered > 3 hours after the onset of symptoms have not been established. A recent study of patients with ischemic stroke, confirmed by computed tomography showed a benefit of the drug when given beyond the typical 3-hour limit. Researchers studied a total of 821 patients given alteplase or placebo 3 to 4.5 hours after the onset of stroke symptoms. The major end point studied was disability at 90 days.

The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase (52.4%) than with placebo (45.2%). The incidence of intracranial hemorrhage was higher with alteplase. Mortality did not differ between the groups. The authors concluded that alteplase may offer significant benefit to patients beyond the time that is specified by the manufacturer; however, further study is needed.


Protein C and S Deficiency Increase TE Risk

Protein C, protein S, and antithrombin deficiencies are associated with increased risk of thromboembolism (TE). Dutch researchers recently conducted a retrospective study of 552 subjects representing 84 families to determine if a history of venous TE predisposed the subjects to arterial TE (ATE). Detailed information on previous venous TE, ATE, anticoagulant use, and atherosclerosis risk factors was collected.

Of 552 subjects, 35% had protein S, 39% had protein C, and 26% had antithrombin deficiency. Overall, annual incidences of ATE were 0.34% in deficient subjects versus 0.17% in nondeficient subjects; the hazard ratio was 2.3. After adjusting for atherosclerosis risk factors and clustering within families, deficient subjects had a 4.7-fold higher risk for ATE before 55 years of age versus 1.1 thereafter, compared with nondeficient family members. For separate deficiencies, the risks were 4.6-, 6.9-, and 1.1-fold higher in protein S?, protein C?, and antithrombindeficient subjects, respectively, before 55 years of age. History of venous TE was not related to subsequent ATE.

The researchers concluded that subjects with protein S or protein C deficiency, but not antithrombin deficiency, have a higher risk for ATE before 55 years of age that is independent of prior venous TE.


Cigarette Smoking Decreases Platelet Aggregation

Researchers have discovered that cigarette smoking is an independent predictor of the level of platelet aggregation a patient exhibits. This finding may help explain the variability in response to clopidogrel therapy. Cigarette smoking induces the CYP1A2 isoenzyme of the cytochrome P450 system and enhances the antiplatelet effect of clopidogrel, researchers reported in a recent issue of the Journal of the American College of Cardiology.

Earlier work in this area of study showed that responders to clopidogrel therapy were more often smokers. The current paper expands on that initial observation and demonstrates how an external factor, smoking, can influence platelet reactivity in patients treated with a prodrug that is metabolized by the hepatic cytochrome P450 pathway. The researchers studied 104 current smokers and 155 nonsmokers who were undergoing elective coronary stenting. They were either already on clopidogrel or received a 600-mg loading dose. Current smokers on chronic clopidogrel showed significantly greater platelet inhibition and significantly lower platelet aggregation than their nonsmoking counterparts. This also was true of smokers who received the loading dose, compared with nonsmokers who received the loading dose. Smoking was a highly significant independent predictor of low platelet aggregation.