Apparent heparin resistance from elevated factor VIII during pregnancy.

BACKGROUND: Heparin resistance is the need for more than 35,000 units of heparin per 24 hours to achieve therapeutic activated partial thromboplastin time (APTT) values. Elevated factor VIII can cause apparent heparin resistance by suppressing the APTT result without inhibiting the antithrombotic effect of heparin. CASE: A 41-year-old gravida 2 para 0 presented at 25 weeks of a twin gestation with a deep venous thrombosis that required unusually high doses of heparin, resulting in hematuria. Apparent heparin resistance caused by elevated factor VIII was diagnosed, and the heparin dose was appropriately decreased with anti-Xa heparin monitoring. The deep venous thrombosis and hematuria resolved. CONCLUSION: Factor VIII rises significantly during pregnancy, and can cause apparent heparin resistance. When this occurs, anti-Xa heparin levels are superior to APTT for monitoring heparin therapy.

A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.

CONTEXT: Adverse drug events (ADEs) are the most common type of iatrogenic injury occurring in hospitalized patients. Errors leading to ADEs are often due to restricted availability of information at the time of physician order writing. OBJECTIVES: To develop, implement, and evaluate a computer alert system designed to correct errors that might lead to ADEs and to detect ADEs before maximum injury occurs. DESIGN: Prospective case series. SETTING: A 650-bed community teaching hospital in Phoenix, Ariz. PATIENTS: Consecutive sample of 9306 nonobstetrical adult patients admitted during the last 6 months of 1997. INTERVENTIONS: Thirty-seven drug-specific ADEs were targeted. Our hospital information system was programmed to generate alerts in clinical situations with increased risk for ADE-related injury. A clinical system was developed to ensure physician notification of alerts. MAIN OUTCOME MEASURES: A true-positive alert was defined as one in which the physician wrote orders consistent with the alert recommendation after alert notification. RESULTS: During the 6-month study period, the alert system fired 1116 times and 596 were true-positive alerts (positive predictive value of 53%). The alerts identified opportunities to prevent patient injury secondary to ADEs at a rate of 64 per 1000 admissions. A total of 265 (44%) of the 596 true-positive alerts were unrecognized by the physician prior to alert notification. CONCLUSIONS: Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.

The weight-based heparin dosing nomogram compared with a "standard care" nomogram. A randomized controlled trial.

OBJECTIVE: To determine whether an intravenous heparin dosing nomogram based on body weight achieves therapeutic anticoagulation more rapidly than a "standard care" nomogram. DESIGN: Randomized controlled trial. SETTING: Two community teaching hospitals in Phoenix, Arizona, and Rochester, New York. PARTICIPANTS: One hundred fifteen patients requiring intravenous heparin treatment for venous or arterial thromboembolism or for unstable angina. INTERVENTION: Patients were randomized to the weight-based nomogram (starting dose, 80 units/kg body weight bolus, 18 units/kg per hour infusion) or the standard care nomogram (starting dose, 5000-unit bolus, 1000 units per hour infusion). Activated partial thromboplastin time (APTT) values were monitored every 6 hours, and heparin dose adjustments were determined by the nomograms. MEASUREMENTS: Activated partial thromboplastin times were measured using a widely generalizable laboratory method. The primary outcomes were the time to exceed the therapeutic threshold (APTT > 1.5 times the control) and the time to achieve therapeutic range (APTT, 1.5 to 2.3 times the control). Bleeding complications and recurrent thromboembolism were also compared. RESULTS: Kaplan-Meier curves for the primary outcomes favored the weight-based nomogram (P < 0.001 for both). In the weight-based heparin group, 60 of 62 patients (97%) exceeded the therapeutic threshold within 24 hours, compared with 37 of 48 (77%) in the standard care group (P < 0.002). Only one major bleeding complication occurred (in a standard care patient). Recurrent thromboembolism was more frequent in the standard care group; relative risk, 5.0 (95% CI, 1.1 to 21.9). CONCLUSIONS: The weight-based heparin nomogram is widely generalizable and has proved to be effective, safe, and superior to one based on standard practice.

Toxic effects of drugs used in the ICU. Anticoagulants and thrombolytics. Risks and benefits.

Anticoagulation is being used increasingly in the critical care areas. Thrombolytic therapy is now commonly used in emergency departments and coronary care units for treatment of AMI. Heparin therapy for unstable angina and for a 48 to 72 hour period following thrombolytic therapy for AMI is becoming commonplace. Beginning warfarin therapy concomitantly with heparin to decrease the total duration of heparin and the duration of hospital stay for DVT therapy is encouraged. The use of low-dose warfarin to prevent DVT in hip surgery, improve catheter patency, and prevent catheter-related subclavian thrombosis is increasing. Along with the increased use of anticoagulation must come a greater appreciation of the complications associated with the agents used, and of how to prevent or treat the hemorrhagic or thrombotic morbidity that may arise. Acute hemorrhage with thrombolytic agents must be recognized and the immediate implementation of conservative and aggressive measures begun. Heparin-induced thrombocytopenia with thrombosis is an often-unrecognized problem that may occur in 1% to 2% of heparin recipients and result in limb amputations. A delayed onset (6-10 days) requires frequent platelet counts for early diagnosis and treatment. The resurgence of warfarin use for prevention of cardiovascular and cerebrovascular disorders demands observation for skin necrosis from protein C and S inhibition. Early recognition of symptoms and syndromes associated with organ system hemorrhage in patients receiving chronic anticoagulation is imperative. The use of antagonists, such as protamine sulfate for heparin, vitamin K1 for warfarin, and antifibrinolytic drugs for thrombolytic agents, may be necessary in treating hemorrhagic events. However, their use may worsen the thromboembolic event initially treated.

Lovastatin use and muscle damage in healthy volunteers undergoing eccentric muscle exercise.

We did a double-blind, placebo-controlled crossover study of 10 healthy young men taking no medications to determine if ingesting lovastatin is associated with more severe muscle damage after exercise. Five men in the first group took 40 mg of lovastatin daily for 30 days while those in the second group took an identical-appearing placebo. Each volunteer then walked downhill on a -14-degree incline on a treadmill at 3 km per hour for an hour. After a 2-week rest, the subjects were crossed over. Serial serum creatine kinase activity was measured immediately before and 8, 24, 48, 72, 120, and 144 hours after each treadmill session. With each subject serving as his own control, peak mean serum creatine kinase activity (/+- SEM) following treadmill after lovastatin therapy was similar to that following placebo (168.4 +/- 25.8 U per liter versus 146.7 +/- 14.7 U per liter, respectively [P = .9]). With an alpha value of .05, we had greater than a 99% chance of detecting a difference in the rise of serum creatine kinase activity of 200 U per liter between groups. Our data suggest that lovastatin is not an independent risk factor for developing exercise-induced muscle damage using this model of exercise in our study population.

Phenytoin absorption in volunteers receiving selected enteral feedings.

Phenytoin absorption is reportedly significantly altered in the presence of continuously administered enteral feedings, resulting in subtherapeutic serum phenytoin concentrations and loss of seizure control. We administered 500 mg of phenytoin as the suspension to five volunteers who were not receiving enteral feeding, again while they ingested protein hydrolysate enteral feedings hourly, and again during hourly ingestions of meat-base enteral feeding. Serum phenytoin concentrations, measured 3, 6, 9, 12, and 24 hours after phenytoin ingestion, were lowest with protein hydrolysate feedings. Mean serum phenytoin concentrations were consistently higher with the meat-base feeding than with the protein hydrolysate formula, although levels did not reach those of the control period. These data are in keeping with our previous observation that it is easier to attain therapeutic serum phenytoin concentrations in patients receiving a meat-base enteral feeding than in those receiving a protein hydrolysate formula.

Phenytoin absorption from tube feedings.

Phenytoin, administered by suspension into a feeding tube through which continuous enteral feedings are being given, is very poorly absorbed. There appears to be very little information regarding this potentially serious problem in the general medical literature. Commonly used doses of phenytoin (300 to 500 mg/d) may result in almost undetectable serum levels. Therapeutic phenytoin levels may be obtained if a very large dose of the drug is given. Our patient required 1800 mg daily in two divided doses to get a serum phenytoin level of 9 micrograms/mL. Commonly used enteral feedings were being delivered by way of a continuous infusion pump. We found one enteral feeding product that did not severely impair the absorption of phenytoin. The mechanism by which enteral feedings impair phenytoin absorption is unknown.