Anticoagulation with temporary Impella device in patients with heparin-induced thrombocytopenia: A case series.

The Impella device is a percutaneous ventricular assist devices that requires administration of heparin via a continuous purge solution. Patients on Impella device support may experience hemolysis with accompanying thrombocytopenia generating suspicion for heparin-induced thrombocytopenia (HIT). However, data and recommendations for use of non-heparin anticoagulants with Impella device are lacking. Therefore, we performed a retrospective cohort analysis of patients requiring bivalirudin during Impella device support to describe the safety and efficacy of bivalirudin as an alternative anticoagulant during Impella device support. Nine patients were included in the evaluation which analyzed Impella device purge flow and purge pressure along with bivalirudin dosing requirements, incidence of thrombosis, and incidence of pump failure. All patients had a positive platelet factor-4 IgG ELISA test, and the serotonin release assay was positive in four patients. After initiation of bivalirudin, the median (15th, 85th percentile) nadir purge flow decreased by 76% (5%, 88%) and the median (15th, 85th percentile) peak purge pressure increased by 86% (21%, 143%). At the time of bivalirudin discontinuation, the median final purge flow and pressure were 2.4 mL/h (74% decrease) and 969 mmHg (89% increase), respectively. Zero patients experienced catastrophic pump failure. Adding low concentration bivalirudin to the purge solution along with systemic bivalirudin may be a reasonable approach.

COVID-19 pandemic: Challenges and solutions from the cardiology pharmacist's perspective.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re-evaluated daily processes and therapies used to treat COVID-19 patients within our institutions from a cardiovascular perspective and share what we have learned. To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID-19 patients by drawing on the experiences of cardiology pharmacists across the country. On March 26, 2020, a conference call was convened composed of 24 cardiology residency-trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID-19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. The collaborative of pharmacists found for the ST-elevation myocardial infarction patient, many institutions were diverting COVID-19 rule-out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision-making processes with their preceptors and assist as pharmacist extenders. Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID-19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times.

Evaluation of an updated insulin infusion protocol at a large academic medical center.

PURPOSE: The performance of an updated insulin infusion protocol was evaluated at a large, academic medical center. METHODS: A retrospective medical record review was performed after a one-month run-in period for all patients at a large, academic, tertiary care medical center in whom the insulin infusion per protocol was administered from January 1 through February 28, 2014. Data were evaluated to determine the median blood glucose (BG) level, time to achieve BG in the target range, number of BG checks per patient per day, time elapsed between each BG check, and the frequency of hypoglycemia (BG concentration of ≤70 mg/dL). RESULTS: A total of 170 patients were included. The median preinfusion BG was 244 mg/dL (interquartile range [IQR], 204-304 mg/dL), which decreased to a median of 168 mg/dL (IQR, 147.5-199.5 mg/dL) when the protocol was utilized. However, 70 patients (41%) had a median BG concentration of ≥180 mg/dL, and 25 patients' (15%) BG value remained above 180 mg/dL. The median time to achieve the goal BG value was 4.2 hours (95% confidence interval, 3.2-5.1 hours). BG checks were performed a median of every 2.1 hours (IQR, 1.4-2.3 hours). Hypoglycemia was rare, occurring in only 2 (1.2%) patients. CONCLUSION: The median BG with an updated insulin infusion protocol approached the upper limit of the target BG range, and 41% of patients had a median BG above the goal range. Protocol specifications for the frequency of BG monitoring were not commonly followed, but the frequency of hypoglycemia was extremely low.

Comparison of Anticoagulation Strategies After Left Ventricular Assist Device Implantation.

Appropriate early anticoagulation after left ventricular assist device (LVAD) implantation has not been established with practices ranging from no anticoagulation to early heparinization. The goal of this study was to evaluate the efficacy and morbidity of three strategies before initiating oral anticoagulation therapy. This was a noninterventional, retrospective, matched historical control cohort study. The primary and secondary endpoints were thrombotic complications (TCs) and bleeding up to 30 days post-LVAD implantation. There was a significant difference in the overall rate of TCs between strategies (p = 0.017). The incidence of TCs was significantly lower in the heparin group versus no bridging (4.9 vs. 27.0%, p = 0.008) on univariate analysis. On multivariate analysis, heparin was independently associated with a lower odds of TCs (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.01-0.85). No differences were observed in bleeding between groups (p = 0.127) on univariate analysis; however, heparin was independently associated with increased odds of bleeding compared with no bridging on multivariate analysis (OR, 2.93; 95% CI, 1.15-7.43). Compared with no bridging, bivalirudin did not significantly differ in TC or bleeding events. Heparin seems to be the most effective regimen to use post-LVAD implantation but may increase the patient's risk for bleeding.

Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to heart transplant.

BACKGROUND: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. OBJECTIVE: To assess blood product use, effectiveness, and safety post-low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. METHODS: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio ≥1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. RESULTS: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. CONCLUSIONS: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non-statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

Safety of "bridging" with eptifibatide for patients with coronary stents before cardiac and non-cardiac surgery.

Patients with previously implanted coronary stents are at risk for stent thrombosis if dual-antiplatelet therapy is prematurely discontinued. Bridging with a glycoprotein IIb/IIIa inhibitor has been advocated as an alternative, with few supporting data. The aim of this study was to determine the safety of such a strategy by retrospectively analyzing bleeding in 100 consecutive patients with previously implanted coronary stents who were bridged to surgery with eptifibatide after discontinuing thienopyridine therapy. A propensity-matched control comparison was performed for a subgroup of 71 patients who underwent cardiovascular surgery. Blood transfusions were required in 65% in the bridged group versus 66% in the control group (p = 0.86). The mean numbers of units transfused were 4.84 ± 6.93 and 3.65 ± 7.46, respectively (p >0.25). Rates of return to the operating room for bleeding or tamponade were 10% and 2.9%, respectively (p = 0.085). Increased rates of transfusion were noted for patients who received concomitant aspirin and/or intravenous heparin infusion. In conclusion, there does not appear to be any increase in the need for blood transfusions or rate of return to the operating room for patients being bridged with eptifibatide when thienopyridines are discontinued in the perioperative period, but concomitant use of additional antiplatelet or anticoagulant agents may increase transfusions and delays to surgery. Clinicians who are considering this strategy must weigh the risks of stent thrombosis versus bleeding.

Argatroban anticoagulation in intensive care patients: effects of heart failure and multiple organ system failure.

We retrospectively evaluated argatroban dosing patterns, clinical outcomes, and the effects of heart failure and multiple organ system failure on dosing requirements in 65 adult, intensive care patients administered argatroban anticoagulation for clinically suspected heparin-induced thrombocytopenia (n=56) or history of heparin-induced thrombocytopenia (n=9). Argatroban was initiated then titrated to achieve target activated partial thromboplastin times 1.5 to 3 times normal control (ie, 42-84 seconds). Overall, argatroban was initiated at 1.14+/-0.62 microg/kg/min (mean+/-SD) and administered for 11.4+/-9.5 days, with comparable dosing patterns between patients with suspected, versus previous, heparin-induced thrombocytopenia. Sixty-four (98.5%) patients achieved target activated partial thromboplastin times, typically following no or one dose adjustment. Therapeutic doses were lower in patients with, versus without, heart failure (0.58+/-0.28 vs 0.97+/-0.6 microg/kg/min, P= .042) and decreased as the number of failed organ systems increased from 1 to 2 to =3 (1.10+/-0.67 vs 0.87+/-0.47 vs 0.58+/-0.47 microg/kg/min, P= .008). From argatroban initiation until patient discharge or death, 11 (16.9%) patients (3 off argatroban) developed thromboembolic complications; 14 (21.5%) died (11 off argatroban, 7 from multiple organ system failure); and 1 (1.5%) required amputation. Nine patients (13.8%) experienced bleeding, none fatal. This experience suggests that argatroban administered at approximately 1 micro/kg/min provides adequate levels of anticoagulation in many intensive care unit patients with suspected or previous heparin-induced thrombocytopenia. Reduced doses are needed when heart failure or multiple organ system failure is present.

Heparin-induced thrombocytopenia: treatment options and special considerations.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse effect that typically manifests several days after the start of heparin therapy, although both rapid- and delayed-onset HIT have been described. Its most serious complication is thrombosis. Although not all patients develop thrombosis, it can be life threatening. The risk of developing HIT is related to many factors, including the type of heparin product administered, route of administration, duration of therapy, patient population, and previous exposure to heparin. The diagnosis of HIT is typically based on clinical presentation, exposure to heparin, and presence of thrombocytopenia with or without thrombosis. Antigen and activation laboratory assays are available to support the diagnosis of HIT. However, because of the limited sensitivity and specificity of these assays, bedside probability scales for HIT were developed. When HIT is suspected, prompt cessation of all heparin therapy is necessary, along with initiation of alternative anticoagulant therapy. Two direct thrombin inhibitors--argatroban and lepirudin--are approved for the management of HIT in the United States, and bivalirudin is approved for use in patients with HIT who are undergoing percutaneous coronary intervention. Other agents, although not approved to manage HIT, have also been used; however, their role in therapy requires further evaluation. A comprehensive HIT management strategy involves the evaluation of numerous factors. Many patients, including those undergoing coronary artery bypass surgery, those with acute coronary syndromes, those with hepatic or renal insufficiency, and children, require special attention. Clinicians must become familiar with the available information on this serious adverse effect and its treatment so that optimum patient management strategies may be formulated.

Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory.

Benzocaine (ethyl aminobenzoate), a topical anesthetic widely used before transesophageal echocardiography, has been reported to cause acquired methemoglobinemia. The incidence of benzocaine-induced methemoglobinemia in clinical practice, however, has been difficult to estimate. After systematic review of our institutional experience for clinically recognized cases of benzocaine-induced methemoglobinemia in patients undergoing transesophageal echocardiography, we report an estimated incidence of 0.115% (95% confidence interval 0.037-0.269). This report also provides the largest analysis of the incidence of methemoglobinemia in readministration cases. Although controversy remains as to whether this is an idiosyncratic versus dose-related response, a description of purported patient risk factors is included.