Daniel A. Lewis

Recombinant factor VIIa for refractory bleeding after cardiac surgery secondary to anticoagulation with the direct thrombin inhibitor lepirudin.

A 56‐year‐old man with heparin‐induced thrombocytopenia with thrombosis syndrome (HITTS) received anticoagulation with recombinant hirudin (lepirudin) for emergency coronary artery bypass graft (CABG) surgery and aortic valve replacement. The patient experienced life‐threatening refractory bleeding that was successfully treated with recombinant factor VIIa. He had a history of infective endocarditis that resulted in severe aortic insufficiency, three‐vessel coronary artery disease, and acute renal failure requiring hemodialysis. The patient was transferred from another hospital for the emergency surgery, but before his transfer, he developed HITTS secondary to therapeutic heparin for a deep vein thrombosis of the lower extremity. The presence of HITTS, the urgent nature of the case, and the availability of the direct thrombin inhibitor led the surgical team to select lepirudin for anticoagulation to facilitate cardiopulmonary bypass. After separation from cardiopulmonary bypass, the patient was in a coagulopathic state due to the inability to reverse the lepirudin and the slowed elimination of the drug secondary to inadequate renal function. As a result, the patient experienced excessive generalized oozing that was unresponsive to traditional therapies and blood product transfusions. Recombinant factor VIIa 35 μg/kg was given as rescue therapy. The bleeding slowed, which allowed placement of chest tubes and closing of the sternum. The patient was transferred to the intensive care unit in stable condition with no evidence of thrombosis in the freshly placed bypass grafts or on the bioprosthetic valve. Recombinant factor VIIa appears to be a suitable option as salvage therapy in patients with refractory bleeding secondary to anticoagulation with a direct thrombin inhibitor during cardiac surgery.

Fondaparinux as a treatment option for heparin-induced thrombocytopenia.

Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small‐scale, in vitro studies have demonstrated a lack of cross‐reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.

A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia

The diagnosis of heparin-induced thrombocytopenia (HIT) is complex and involves integrating both clinical and laboratory findings. Readily available diagnostic tests such as the heparin-dependant antibody assay (HDAA) lack desired specificity when utilised alone. A diagnostic algorithm incorporating the 4T pretest probability score, HDAA, and optical density (OD) value was implemented as a tool to assist in the diagnosis of HIT and with the decision to treat patients. Patients with a 4T score >3 and/or positive HDAA result with an OD ≥1 were considered positive. Utilisation of this algorithm was hypothesised to improve the identification of patients without SRA confirmed HIT and improve overall specificity compared to other diagnostic strategies. Retrospective chart review was conducted and included patients with a positive or equivocal HDAA result and a serotonin release assay result during a two-year period. Each patient was evaluated for the diagnosis of HIT using the algorithm. The specificity and sensitivity of the diagnostic algorithm to identify subjects with SRA confirmed HIT was evaluated. A total of 83 patients were identified for inclusion in the study. The diagnostic algorithm identified 22 patients for direct thrombin inhibitor (DTI) therapy. Nine of these patients were SRA positive. The sensitivity of the algorithm was 0.9 with a specificity of 0.822. The diagnostic algorithm was found to be both more specific and sensitive than other diagnostic strategies including the 4T score alone, HDAA alone, and the combination of the 4T score and HDAA results. This preliminary data suggest a diagnostic algorithm combining 4T score, HDAA, and OD value may be a tool to aid in the identification SRA positive patients for DTI therapy.

Risk Factors for Venous Thromboembolism in Patients with Chronic Liver Disease

BACKGROUND Pharmacologic prophylaxis for venous thromboembolism (VTE) in patients with chronic liver disease (CLD) presents a unique challenge because of coagulopathies associated with the disease. When evaluating whether these patients require VTE prophylaxis upon hospitalization, it would be advantageous if risk factors for the development of VTE in this population were known. OBJECTIVE To evaluate risk factors associated with the development of VTE in patients with CLD. METHODS A retrospective case-control study was conducted. Patients admitted to the University of Kentucky Chandler Hospital from October 2006 to July 2010 with a diagnosis of CLD and VTE were matched in a 1:3 fashion with CLD patients without VTE. The primary objective was to determine whether there were significant differences in laboratory values between the 2 groups. RESULTS During this time, 27 patients with CLD (1.0%) were diagnosed with VTE. These patients had significantly lower median aspartate aminotransferase (AST) (47 vs 70 U/L, p = 0.04), alanine transaminase (ALT) (24.5 vs 36 U/L, p = 0.02), albumin (2.1 vs 2.4 g/dL, p = 0.02) and hematocrit (Hct) (28.3% vs 32%, p = 0.03) values compared to the control patients. Patients with albumin lower than 1.9 g/dL had a 5.1 times greater risk of VTE compared to patients with albumin of 2.8 g/dL and higher (OR 5.14, 95% CI 1.05–25.2). CONCLUSIONS Patients with CLD who developed VTE had significantly lower AST, ALT, albumin, and Hct compared to those of control patients. Studies are necessary to further examine the significance of this finding.

Evaluation of a clinical scoring scale to direct early appropriate therapy in heparin-induced thrombocytopenia.

Background. Heparin-induced thrombocytopenia (HIT) is a serious adverse effect associated with heparin therapy. Current laboratory confirmation for immune mediated HIT often results in false positives and unnecessary treatment, exposing individuals to possible complications. As a result, clinical evaluation has been recommended in conjunction with laboratory testing. We hypothesize that utilization of a clinical scoring scale, the 4T’s, will result in the initial appropriate therapy for suspected HIT. Methods. This is a retrospective chart review of 108 patients who underwent ELISA testing for HIT at a university hospital. The 4T’s scale was applied, stratifying individuals into low, intermediate, and high-risk categories. Each risk score was compared to the ELISA results to determine if the 4T’s can predict the diagnosis of HIT and result in appropriate management. ELISA optical density scores as well as incidence of adverse events were also compared among risk categories. Study Results. Individuals with low risk correlate with a negative ELISA compared to intermediate and high-risk individuals (p = 0.01 and p<0.01) and also were significantly more likely to predict institution of appropriate therapy (p<0.01). Median optical density scores were 0.184 (0.046—2.116), 0.226 (0.067—1.887), and 0.476 (0.096—1.309) for low, intermediate, and high 4T scores. Major adverse events include thrombosis and bleeding. Conclusions. Individuals with low risk were more likely to receive initial, appropriate therapy and were also significantly more likely to have a negative ELISA test result. Individuals with low risk determined by the 4T score therefore may have therapy and serologic testing for HIT withheld.

Effects of a Pharmacist-to-Dose Computerized Request on Promptness of Antimicrobial Therapy

OBJECTIVES To examine the effects of computerized requests for pharmacist-to-dose (PTD), an advanced clinical decision support tool for dosing guidance, on antimicrobial therapy with vancomycin and aminoglycosides, describe PTD request utilization, and identify factors that may prolong this process. DESIGN A retrospective review was conducted of patients hospitalized from Jan 2004 to Jun 2006 with suspected pneumonia who received vancomycin, tobramycin, or gentamicin via PTD (study) or routine provider order entry (control). MEASUREMENTS The primary endpoint was time to pharmacist completion of PTD request. Secondary data points included medication turn-around times for first doses of vancomycin or aminoglycosides and for first doses of any antibiotic, dose adjustment for renal dysfunction, medication errors, and time of order entry. Multivariate analysis was conducted to identify predictors of total time to pharmacist verification and time to administration of first doses of vancomycin or aminoglycosides. RESULTS Median time for pharmacist completion of PTD requests was 29 minutes. Delays were noted in the study group (n = 49) by comparison with the control group (n = 48) for median time to first dose of vancomycin or aminoglycoside (185 vs. 138 min, p = 0.45) and for any antibiotic (134 vs. 118 min, p = 0.42), respectively. Fewer medication errors were reported in the study group (5 vs. 18 errors, p = 0.002). In a multivariate model, PTD was not significantly predictive of time to pharmacy verification or medication turn-around time. CONCLUSIONS Pharmacists completed pharmacist-to-dose consultations for dosing guidance of vancomycin and aminoglycosides within a median of 30 minutes. Implementation of a computerized request for clinical pharmacists to provide medication-related clinical decision support increased medication turn-around time of vancomycin and aminoglycosides and reduced medication errors. Consultation of clinical pharmacists by computerized request for initial antibiotic dosing of medications with narrow therapeutic windows is an option for medication-related clinical decision support but providers should be aware that consultation may delay medication turn-around time.

Glimepiride-Induced Hypoglycemia With Ciprofloxacin, Metronidazole, and Acute Kidney Injury

A 79-year-old white male presented to the emergency room with altered mental status and a blood glucose of 28 mg/dL. He was taking glimepiride 1 mg by mouth daily prior to admission and had recently been prescribed ciprofloxacin and metronidazole for diverticulitis. The patient was also found to have acute-on-chronic renal failure upon presentation. Escalated dextrose infusion with repeated doses of D50W and glucagon failed to sustain his blood glucose, which remained in the range of 30 to 50 mg/dL. Salvage treatment with intravenous octreotide was implemented successfully; only one dose of D50W was required after octreotide initiation and blood glucose normalized within several hours. In the presence of this patients complex medication therapy, we explore the contributing causes of hypoglycemia. Fluoroquinolones are widely associated with dysglycemias, particularly in diabetic patients receiving hypoglycemic agents. Similarly, renal insufficiency has been implicated to precipitate hypoglycemia with sulfonylureas, with dosage adjustment being required almost class-wide. We also recognize a theoretical drug interaction mediated by metronidazole-induced CYP 2C9 inhibition of glimepiride metabolism. Sulfonylurea-induced hypoglycemia can be serious and refractory to traditional therapy and can be exacerbated by multiple factors, such as drug interactions or impaired renal function. In the era of complex medication therapy for patient populations with multiple disease states, we present a severe episode of glimepiride-induced hypoglycemia with multiple causative factors.

Review of Alcohol Withdrawal in the Hospitalized Patient: Management

Hospitalized orthopedic patients commonly require management of chronic disease states, one of which is alcohol withdrawal syndrome. This article is the second in a two-part series reviewing alcohol withdrawal in the hospitalized patient. Part one appeared in the May 2007 issue of Orthopedics.

Drug Selection in a Patient With a History of Hypersensitivity Reactions: A Practical Approach for the Orthopedist

Drug allergies are specific to characteristics of the medications chemical structure.

Preventing the Harm of a Closer Look: Contrast-induced Nephropathy in Adults

Contrast media is administered to many patients in hospitals nationwide. Although the use of contrast and dyes is widespread and has a well accepted use among the medical profession, contrast-induced nephropathy can be a common and potentially harmful complication. Identifying patients at risk, attempting to minimize risk, and using preventative strategies should be priorities to decrease the harmful effects that are associated with the administration of contrast media. This article provides a general overview of contrast-induced nephropathy and a brief review of the risk factors and prophylactic treatment.