Coagulation Counseling

SEPTEMBER 01, 2008
Anna D. Garrett, PharmD, BCPS, CPP

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

New Chest Guidelines Published

New recommendations regarding antithrombotic and thrombolytic therapy from the American College of Chest Physicians (ACCP) have been published as a supplement to the June 2008 issue of Chest. This update contains the most comprehensive advice to date on the prevention, treatment, and long-term management of thrombotic disorders.

For the first time, the guidelines dedicate a full chapter to the perioperative management of patients on long-term antithrombotic therapy who require surgery or other invasive procedures.

The recommendations offer different options for warfarin management: lowering the dose for simple procedures; or stopping therapy altogether around 5 days before surgery and using lowmolecular- weight heparins (LMWHs), or heparin for coverage (bridging). In certain circumstances, warfarin can be continued until 48 hours before surgery, when patients should be given a low dose of vitamin K. For aspirin, the recommendation is normally to continue therapy. Clopidogrel should be stopped 7 to 10 days before surgery, unless the patient has a stent.

The Relationship between IBD and TE Risk

Inflammatory bowel disease (IBD) refers to 2 chronic diseases that cause inflammation of the intestines: ulcerative colitis (UC) and Crohn's disease. Patients with IBD have a 3-fold increased risk of venous thrombosis. Thromboembolic (TE) disease is a significant cause of morbidity and mortality in IBD patients.

The results of a retrospective study confirm that the IBD cohort had a significantly increased rate of venous thromboembolism (VTE). The results suggested that the extent and activity of the IBD are highly associated with TE risk.

The exact mechanism explaining the initiation of thrombosis remains unclear. Reported abnormalities include activation of markers of the coagulation cascade and disturbed fibrinolysis. The authors suggest that colectomy is not protective from recurrent TE disease and that VTE is not an indication for an invasive procedure, particularly in UC patients.

Patients with this condition are often exposed to high-risk situations, such as hospitalization, immobilization, or invasive procedures. The authors suggest that even if long-term anticoagulation is contradicted (high bleeding risk), temporary low-dose prophylactic anticoagulation should be strongly considered.

Nonaspirin NSAIDs Do Not Increase Risk of Stroke

Limited information exists regarding the cerebrovascular safety of cyclooxygenase- 2 inhibitors (coxibs) and traditional nonsteroidal anti-inflammatory drugs (NSAIDs). A recent study examined whether specific NSAIDs, including coxibs, are associated with risk of stroke.

The study reviewed records of Tennessee Medicaid enrollees aged 50 to 84 between January 1, 1999, and December 31, 2004. Patients were included if they were continuously enrolled in Medicaid and had no stroke or other serious medical illness in the year before cohort entry. The 7 most common NSAIDs were examined: celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin. Nonusers of NSAIDs were the control group. The outcomes studied were hospitalization for cerebrovascular events such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

The cohort included 336,906 individuals, with 4354 stroke hospitalizations. The nonuser group experienced 4.51 strokes per 1000 person-years; 5.15 strokes per 1000 person-years were reported with rofecoxib use, and 5.95 strokes per 1000 person years with valdecoxib use. No other NSAID significantly increased the risk of stroke.

Antiretroviral Drugs May Interact with Warfarin

Two recent case reports indicate that antiretroviral drugs may cause induction of various isoenzymes of the CYP450 system, greatly increasing the dose of warfarin required to maintain patients in therapeutic range. The 2 cases suggest possible interactions between warfarin and nevirapine, nelfinavir, and lopinavir/ ritonavir. Nevirapine, a non-nucleoside reverse transcriptase inhibitor, appears to induce the CYP3A4 and CYP2B6 isoenzymes, which could lead to a significant reduction in the R-enantiomer of warfarin and necessitate an increased dose of warfarin.

The case reports also examined the effects of protease inhibitors. Nelfinavir and lopinavir/ritonavir appear to induce the CYP2C9 and CYP1A2 isoenzymes. Coadministration of warfarin and nelfinavir resulted in a 55.6% increase in warfarin dose in one of the patients studied; while combination of lopinavir/ritonavir necessitated a 40% dose increase in a patient who had a stable warfarin dose for 12 years prior to initiation of highly active antiretroviral therapy.