Dr. Garrett is manager of the Health Education Center, Mission Hospitals, Asheville, North Carolina.
New recommendations regarding antithromboticand thrombolytic therapy fromthe American College of Chest Physicians(ACCP) have been published as a supplementto the June 2008 issue of Chest.This update contains the most comprehensiveadvice to date on the prevention,treatment, and long-termmanagement of thromboticdisorders.
For the first time, the guidelinesdedicate a full chapterto the perioperative managementof patients on long-termantithrombotic therapy whorequire surgery or other invasiveprocedures.
The recommendations offer differentoptions for warfarin management: loweringthe dose for simple procedures;or stopping therapy altogether around5 days before surgery and using lowmolecular-weight heparins (LMWHs), orheparin for coverage (bridging). In certaincircumstances, warfarin canbe continued until 48 hoursbefore surgery, when patientsshould be given a low dose ofvitamin K. For aspirin, the recommendationis normally tocontinue therapy. Clopidogrelshould be stopped 7 to 10days before surgery, unlessthe patient has a stent.
Inflammatory bowel disease (IBD) refersto 2 chronic diseases that cause inflammationof the intestines: ulcerative colitis(UC) and Crohn's disease.Patients withIBD have a 3-foldincreasedrisk ofvenousthrombosis.Thromboembolic(TE)disease is a significantcause of morbidityand mortalityin IBD patients.
The results of a retrospective studyconfirm that the IBD cohort had a significantlyincreased rate of venous thromboembolism(VTE). The results suggestedthat the extent and activity of the IBD arehighly associated with TE risk.
The exact mechanism explaining theinitiation of thrombosis remains unclear.Reported abnormalities include activationof markers of the coagulation cascadeand disturbed fibrinolysis. The authorssuggest that colectomy is not protectivefrom recurrent TE disease and that VTEis not an indication for an invasive procedure,particularly in UC patients.
Patients with this condition are oftenexposed to high-risk situations, such ashospitalization, immobilization, or invasiveprocedures. The authors suggestthat even if long-term anticoagulation iscontradicted (high bleeding risk), temporarylow-dose prophylactic anticoagulationshould be strongly considered.
Limited information exists regardingthe cerebrovascular safety of cyclooxygenase-2 inhibitors (coxibs) andtraditional nonsteroidal anti-inflammatorydrugs (NSAIDs). A recentstudyexamined whether specific NSAIDs,including coxibs, are associated withrisk of stroke.
The study reviewed records ofTennessee Medicaid enrollees aged50 to 84 between January 1, 1999,and December 31, 2004. Patientswereincluded if they were continuouslyenrolledin Medicaid and had no strokeor other serious medical illnessinthe year before cohort entry. The 7most commonNSAIDs were examined:celecoxib,rofecoxib, valdecoxib,ibuprofen, naproxen, diclofenac, andindomethacin. Nonusers of NSAIDswere the control group. The outcomesstudied were hospitalization for cerebrovascularevents such as ischemicstroke, intracerebral hemorrhage,and subarachnoid hemorrhage.
The cohort included 336,906 individuals,with 4354 stroke hospitalizations.The nonuser group experienced4.51 strokes per 1000 person-years;5.15 strokes per 1000 person-yearswere reported with rofecoxib use,and 5.95 strokes per 1000 personyears with valdecoxib use. No otherNSAID significantly increased the riskof stroke.
Two recent case reports indicate thatantiretroviral drugs may cause inductionof various isoenzymes of the CYP450system, greatly increasing the dose ofwarfarin required to maintain patients intherapeutic range. The 2 cases suggestpossible interactions between warfarinand nevirapine, nelfinavir, and lopinavir/ritonavir. Nevirapine, a non-nucleosidereverse transcriptase inhibitor, appearsto induce the CYP3A4 and CYP2B6isoenzymes, which could lead to a significantreduction in the R-enantiomerof warfarin and necessitate an increaseddose of warfarin.
The case reports also examined theeffects of protease inhibitors. Nelfinavirand lopinavir/ritonavir appear to inducethe CYP2C9 and CYP1A2 isoenzymes.Coadministration of warfarin and nelfinavirresulted in a 55.6% increase in warfarindose in one of the patients studied;while combination of lopinavir/ritonavirnecessitated a 40% dose increase in apatient who had a stable warfarin dosefor 12 years prior to initiation of highlyactive antiretroviral therapy.