Bob L. Lobo

Fondaparinux for the treatment of patients with acute heparininduced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a life-threatening immune response to heparin that is associated with a high risk of thromboembolic complications. We prospectively treated seven subjects with acute HIT with fondaparinux and compared the results to a similar historical control population from the same hospital. Six of the seven fondaparinux-treated subjects were transitioned to warfarin, beginning after platelet count recovery occurred. Ten historical controls were treated with a direct thrombin inhibitor (DTI), eight of which were transitioned to warfarin. The primary study outcome was platelet count recovery which was defined as an increase from baseline by at least 30% of nadir to greater than 100,000/mm(3) by day seven. Seven subjects were prospectively treated with fondaparinux for a median of eight days. Six of the seven had HIT with thrombosis at the time of enrollment. All fondaparinux treated subjects had a complete platelet count recovery, and none experienced a new thromboembolic complication, major bleeding or death by week four. One subject underwent limb amputation. Ten historical controls were treated with a DTI for a median duration of eleven days. Platelet count recovery occurred in eight of the ten historical controls. No new thromboembolic complications or major bleeds occurred but limb gangrene occurred in four controls. The development of limb gangrene in the historical controls may have been a result of delayed recognition of HIT and/or inappropriately early institution of warfarin in the historical controls. This pilot study suggests that fondaparinux may be useful in patients with acute HIT.

Risk of venous thromboembolism in hospitalized patients with peripherally inserted central catheters.

BACKGROUND Peripherally inserted central catheters (PICC) are increasingly used in hospitalized patients. The benefit can be offset by complications such as upper extremity deep vein thrombosis (UEDVT). METHODS Retrospective study of patients who received a PICC while hospitalized at the Methodist University Hospital (MUH) in Memphis, TN. All adult consecutive patients who had PICCs inserted during the study period and who did not have a UEDVT at the time of PICC insertion were included in the study. A UEDVT was defined as a symptomatic event in the ipsilateral extremity, leading to the performance of duplex ultrasonography, which confirmed the diagnosis of UEDVT. Pulmonary embolism (PE) was defined as a symptomatic event prompting the performance of ventilation-perfusion lung scan or spiral computed tomography (CT). RESULTS Among 777 patients, 38 patients experienced 1 or more venous thromboembolisms (VTEs), yielding an incidence of 4.89%. A total of 7444 PICC-days were recorded for 777 patients. This yields a rate of 5.10 VTEs/1000 PICC-days. Compared to patients whose PICC was inserted in the SVC, patients whose PICC was in another location had an increased risk (odds ratio = 2.61 [95% CI = 1.28-5.35]) of VTE. PICC related VTE was significantly more common among patients with a past history of VTE (odds ratio = 10.83 [95% CI = 4.89-23.95]). CONCLUSIONS About 5% of patients undergoing PICC placement in acute care hospitals will develop thromboembolic complications. Thromboembolic complications were especially common among persons with a past history of VTE. Catheter tip location at the time of insertion may be an important modifiable risk factor.

Treatment of Warfarin-related intracranial hemorrhage: A comparison of prothrombin complex concentrate and recombinant activated factor VII

OBJECTIVE Warfarin-related intracranial hemorrhage (ICH) is a devastating complication of warfarin therapy. Several studies have demonstrated successful correction of the international normalized ratio (INR) using prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa). To our knowledge, no study has directly compared these agents for treatment of warfarin-related ICH. METHODS We retrospectively reviewed the charts of 15 patients who received rFVIIa and 9 who received PCC for treatment of warfarin-related ICH over a 2-year period. The primary objective was to compare the efficacy of rFVIIa and PCC in correcting the INR to 1.3 or less. Baseline INR was compared to INR obtained within 1, 3, 6, 12, and 24 hours after rFVIIa or PCC administration. RESULTS Six patients in the rFVIIa group and five in the PCC group had a follow-up INR within 1 hour of agent administration. In the rFVIIa group, the mean INR decreased from 6.1 to 1.1 and from 2.3 to 1.48 in the PCC group. At 6 hours, all rFVIIa patients and six (67%) PCC patients had at least one subsequent INR, with 93% and 50% correcting to an INR of 1.3 or less. Mean dose for all patients included was 53.4 ± 17.5 μg/kg and 27.8 ± 15.4 units/kg for rFVIIa and PCC, respectively. CONCLUSION Correction of the INR is more reliably obtained with rFVIIa when compared to PCC. Larger, prospective studies comparing these therapies for warfarin-related ICH are needed.

Overuse of antihypertensives in patients with acute ischemic stroke.

Background: The Stroke Council of the American Heart Association/American Stroke Association (AHA/ASA) recommends conservative management of hypertension (HTN) during acute ischemic stroke (AIS), although clinicians often manage blood pressure more aggressively. Our hypothesis was that aggressive management of HTN in patients with AIS is associated with hypotensive events and worsened neurologic outcomes. Methods: The study was a retrospective, observational cohort of patients who were admitted to the hospital with AIS. Classification of neurologic outcomes was based on nurses’ neurologic assessments and were categorized as “worsened,” “stayed the same,” or “improved.” The accuracy of these assessments was verified by review of physician’s progress notes. Management of arterial HTN was recorded in all patients. Results: Fifty medical records of patients with AIS who met inclusion criteria were reviewed. While only 22% of patients met the AHA/ASA criteria for hypertension treatment, 98% of the cohort were given antihypertensive therapy. Relative hypotension occurred in 64% of treated patients. Absolute hypotension associated with antihypertensive medications was uncommon but did occur in 2 of 15 patients who experienced neurologic worsening (13%), in 1 of 28 (3%) of patients who stayed the same, and in none of those who improved. Blood pressure was reduced excessively in all 11 of the patients who met AHA/ASA guidelines for treatment. Conclusions: Adherence to AHA/ASA guidelines for HTN management during AIS was poor. Initiation or intensification of antihypertensive drugs was not associated with worsened neurologic outcomes. Furthermore, relative hypotension, absolute hypotension and excessive reductions in blood pressure were not associated with worsened neurologic outcomes.

Medication-error alerts for warfarin orders detected by a bar-code-assisted medication administration system

PURPOSE Medication-error alerts for warfarin orders detected by a bar-code-assisted medication administration (BCMA) system were evaluated. METHODS All patients receiving warfarin who were admitted to a university medical center between July 1, 2008, and February 6, 2009, in inpatient units with BCMA systems were candidates for inclusion in this study. Medication-error alerts displayed to the nurse administering the warfarin were reviewed to determine whether a true potential error was detected. Each alert was converted to a scenario, and its potential to require treatment or cause patient harm was rated using a validated severity scale of 0-10, where a score of 0 indicated no probable effect on the patient and 10 indicated that the error would likely result in patient death. A severity score was obtained by averaging the scores of four pharmacist reviewers. RESULTS Of the 18,393 warfarin doses ordered during the study period for 2,404 patients, error alerts associated with only 99 warfarin doses were found to be clinically meaningful. The mean ± S.D. severity rating of these alerts was low (2.93 ± 1.42), with a standardized Cronbachs coefficient alpha of 0.845. The mean ± S.D. warfarin dose attempted when the nurse received an alert was 4.10 ± 2.48 mg. The majority of doses with alerts (70%) were for patients who had an active order for warfarin. CONCLUSION Of the large number of medication-error alerts generated through a BCMA system, only a small proportion were considered clinically significant. This indicated that the rate of false-positive alerts was unexpectedly high, increasing the risk of alert fatigue.

Heparin-induced thrombocytopenia complicated by warfarin-induced skin necrosis

PURPOSE A case of heparin-induced thrombocytopenia (HIT) complicated by warfarin-induced skin necrosis (WISN) is reported. SUMMARY A patient with a history of hypertension, heart failure, and myocardial infarction was admitted to the hospital after complaining of a two-day history of shortness of breath, diaphoresis, and chest pain. The patient underwent a cardiac catheterization and received several medications, including heparin. Suspicions of HIT occurred when her platelets began to decrease severely and she developed a left groin hematoma and a pseudoaneurysm. Lepirudin was initiated and a heparin platelet factor 4 (PF4) antibody test was performed. The results were negative and lepirudin was discontinued. She was rechallenged with unfractionated heparin (UFH) after surgery of the pseudoaneurysm, but her platelets began to decrease again. A second PF4 test was performed, the results of which were positive. The UFH treatment was discontinued. Warfarin was also initiated after surgery and the patients platelets rapidly increased after heparin was discontinued. She was discharged one week later. Three days after discharge, she was readmitted after complaining of severe pain and swelling of the fatty tissue of her right flank that began the day after she was discharged. Some blistering and necrosis were noted on the lesion. Histological sections showed focal thrombosis of vessels in the deep reticular dermis consistent with WISN. Local wound care was given to manage the WISN, lepirudin was initiated, and warfarin was discontinued and reinstated one week later at a low dosage. CONCLUSION A patient with HIT developed severe skin necrosis after initiation of warfarin therapy.

Pharmacist-managed direct thrombin inhibitor protocol improves care of patients with heparin-induced thrombocytopenia

Use of direct-thrombin inhibitors (DTIs) for the management of patients with heparin-induced thrombocytopenia (HIT) is challenging. A pharmacist-managed DTI protocol was implemented to standardize and improve the care of patients with HIT. A background study that compared DTI protocol–treated patients to those who did not receive treatment with the DTI protocol found that significantly more of the DTI protocol–treated patients received care that was consistent with level 1 guidelines from the American College of Chest Physicians (41% vs 0%). Because outcomes were poor regardless of whether the DTI protocol was used, the protocol was revised to require pharmacist implementation and oversight. A follow-up study compared DTI protocol patients from the background study (non-pharmacist-managed) to the pharmacist-managed DTI protocol group. There were significantly fewer dosing errors, improved nursing documentation, and less reexposure to heparin when the pharmacist was responsible for managing the DTI protocol. A trend toward reduced bleeding was noted. The management of patients with HIT is complex, and there are a number of pitfalls that may lead to poor outcomes. DTIs are high-risk medications that require careful dosing and monitoring to minimize risk for adverse drug events. A DTI protocol may improve care of patients with HIT, and pharmacist oversight of DTI use can help to reduce risk for errors and adverse medication events.

The Role of Computerized Clinical Decision Support in Reducing Inappropriate Medication Administration During Epidural Therapy

Background: The use of epidural anesthesia has been shown to improve outcomes in the postoperative setting. To minimize risk of complications, avoiding certain medications with epidural anesthesia is advised. Objective: This study sought to determine the role of a computerized clinical decision support module implemented into the computerized physician order entry (CPOE) system on the incidence of administration of medications known to increase complications with epidural anesthesia. Methods: This study was a retrospective cohort chart review in adult patients receiving epidural anesthesia for at least 1 day. Patients were identified retrospectively and divided into 2 cohorts, those receiving an epidural 3 months prior to initiation of the module and those receiving an epidural 3 months following implementation. The primary end point was incidence of inappropriate medication administration before and after implementation. Complications of therapy were collected as secondary end points. Results: There was a reduction in the incidence of inappropriate medication administration in the postimplementation group versus the preimplementation group (6.3% vs 12.8%) although statistical significance was not achieved. In addition, the incidence of enoxaparin administration was significantly lower postimplementation than the preimplementation (0% vs 3.9%). There were no significant differences in other complications of therapy. Conclusions: This study demonstrated that application of decision support for this high-risk procedural population was able to eliminate the incidence of the most common inappropriate medication for epidural analgesia, enoxaparin. A reduction in incidence of other inappropriate medications was also observed; however, statistical significance was not reached. The use of computerized clinical decision support can be a powerful tool in reducing or ameliorating medication errors, and further study will be required to determine the most appropriate and effective implementation strategies.