Safety of ECT in patients receiving an oral anticoagulant.

INTRODUCTION: This study assessed the use, tolerability, and safety of anticoagulation via direct oral anticoagulants or warfarin in medical and psychiatric inpatients receiving ECT. METHODS: This retrospective cohort study included 32 patients who received ECT while on either a direct oral anticoagulant (9) or warfarin (23) and spanned 247 encounters at Maine Medical Center between December 2012 and December 2018. Data are presented descriptively and analyzed using SPSS version 25 and Microsoft Excel version 2016. RESULTS: Among the 247 ECT patient encounters, there were few major adverse effects of ECT in this medically complex population. These adverse effects included headache during 4 encounters (1.6%), respiratory distress during 2 encounters (0.8%) and a cardiovascular event during 1 encounter (0.4%). One patient (3.1%) who was receiving concurrent rivaroxaban and venlafaxine experienced gastrointestinal bleeding that was determined to be unrelated to ECT. One patient on fluoxetine and warfarin experienced hemoptysis thought to be secondary to epistaxis. No other major bleeding or clotting event occurred during an ECT session nor for the duration of the hospitalization. DISCUSSION: Direct oral anticoagulants and warfarin appear safe in the treatment of patients with atrial fibrillation or acute venous thromboembolism who are receiving concomitant ECT. Prospective studies are needed to confirm these findings.

Heparin-induced thrombocytopenia with thrombosis in COVID-19 adult respiratory distress syndrome.

Early reports of coronavirus disease 2019 (COVID-19) clinical features describe a hypercoagulable state, and recent guidelines recommend prophylactic anticoagulation for patients with COVID-19 with low-molecular-weight heparin, but this would be contraindicated in the presence of heparin-induced thrombocytopenia (HIT). We address the key clinical question whether HIT is also present during COVID-19. We report 3 cases of thrombocytopenia with antiplatelet factor 4 antibodies among 16 intubated patients with COVID-19 with adult respiratory distress syndrome, a higher-than-expected incidence of 19%. Each patient had evidence of thrombosis (pulmonary embolism, upper extremity venous thromboses, and skin necrosis, respectively). The serotonin release assay confirmed HIT in 1 case, and 2 cases were negative. We believe this is the first reported case of HIT during the COVID-19 pandemic. Recognition that the thrombocytopenia represented HIT in the confirmed case was delayed. We recommend clinicians monitor platelet counts closely during heparin therapy, with a low threshold to evaluate for HIT.

Low-Dose Prothrombin Complex Concentrate in Patients with Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have become an important advancement for patients with end-stage heart failure. Left ventricular assist devices come with the risk of stroke and pump thrombosis, and to mitigate these risks, anticoagulation is given to these patients. With anticoagulation comes increased bleeding risk, and urgent reversal may be necessary. Reports have shown that the risk of thrombosis with prothrombin complex concentrate (PCC) does exist, especially in patients with baseline risk factors for thrombosis. We describe two cases of warfarin reversal with low-dose 4-factor PCC (4F-PCC) in two different LVAD patient scenarios. Low-dose 4F-PCC was administered to one patient with a Heart Mate II (HM II) LVAD, international normalized ratio (INR) of 4.7 on admission and in need of an urgent procedure. He received approximately 16 units/kg of 4F-PCC with reversal of his INR to 2.3 within 45 minutes. The second patient also had a HM II LVAD and presented with a right occipital intraparenchymal hemorrhage and subdural hematoma with an INR of 3.7. He received approximately 11 units/kg of 4F-PCC with INR reversal to 1.6 within 1 hour. Both of these patients had no thrombotic complications and successful reversal of their INR with low-dose 4F-PCC. Further investigation into low-dose 4F-PCC dosing strategies is warranted.

Low-dose compared to manufacturer-recommended dose four-factor prothrombin complex concentrate for acute warfarin reversal.

BACKGROUND: Four-factor PCC is the recommended standard of care for acute warfarin reversal but optimal dosing is unknown. We aim to show that a low-dose strategy is often adequate and may reduce the risk of thromboembolic events when compared to manufacturer-recommended dosing. METHODS: A weight-based dosing strategy of 15-25 units/kg was established as the institutional standard of care in May 2015. This retrospective, before-and-after cohort analysis included patients receiving 4F-PCC according to a manufacturer-recommended (n = 122) or a low-dose (n = 83) strategy. The primary efficacy outcome was a combination of INR reversal on first check and hemostatic efficacy at 24 h. RESULTS: Demographics, indications for warfarin, and presenting INR values were similar between the two groups. Patients in the manufacturer-recommended dose group received significantly more 4F-PCC than the low dose group (2110 units vs. 1530 units). More patients in the manufacturer-recommended dose group achieved the primary endpoint (75.4% vs. 61.4%), with more patients achieving the target INR on recheck in the manufacturer-recommended dose group (95.9% vs. 84.3%) and no difference in hemostatic efficacy between groups (79.5% vs. 74.7%). There was no difference in thromboembolic events at 72 h (4.1% vs. 1.2%) or at 30 days (8.2% vs. 4.8%). Significantly more patients in the manufacturer-recommended dose group died or were transferred to hospice care during hospitalization (21.3% vs. 9.6%). CONCLUSION: Utilization of a low-dose 4F-PCC strategy resulted in fewer patients achieving target INR reversal, but no difference in hemostatic efficacy, thromboembolic events, or survival.

Low-dose Prothrombin Complex Concentrate for Warfarin-Associated Intracranial Hemorrhage with INR Less Than 2.0.

BACKGROUND: Prothrombin complex concentrates (PCCs) have become the first-line therapy for warfarin reversal in the setting of central nervous system (CNS) hemorrhage. Randomized, controlled studies comparing agents for warfarin reversal excluded patients with international normalized ratio (INR) <2, yet INR values of 1.6-1.9 are also associated with poor outcomes. METHODS: We retrospectively reviewed our use of a low-dose (15 units/kg) strategy of 4-factor PCC (4F-PCC) on warfarin reversal (INR 1.6-1.9) in the setting of both traumatic and spontaneous intracranial bleeding. RESULTS: A total of 21/134 (15.7%) patients with either spontaneous or traumatic intracranial hemorrhage presented with an INR value of 1.6-1.9. Nine patients (43%) presented with traumatic bleeding and 12 (57%) with spontaneous bleeding. The median (IQR) presenting INR was 1.8 (1.7, 1.9) which decreased to 1.3 (1.2, 1.3) following the administration of low-dose 4F-PCC (median dose = 1062 units; 15.2 units/kg). A total of 19/20 (95%) patients achieved a goal INR value of ≤1.5 on the first check following dosing and 17/20 (85%) achieved an INR value ≤1.3. One patient did not have follow-up INR testing due to withdrawal of life support. No patient experienced hematoma expansion within 48 h of 4F-PCC, and there were no thromboembolic events within 72 h of administration. CONCLUSIONS: The administration of low dose (15 units/kg) of 4F-PCC for urgent warfarin reversal in the setting of CNS hemorrhage was effective in correcting the INR in patients presenting with INR values of 1.6-1.9. Further assessment of low-dose PCC for urgent reversal of modest INR elevation is warranted.

Implementation of a Simplistic Bivalirudin-Warfarin Transition Protocol Is Associated With Improved Achievement of INR Values Within the Therapeutic Range.

BACKGROUND: Transition from bivalirudin to long-term warfarin therapy is often difficult to execute due to bivalirudin prolongation of the international normalized ratio (INR), and literature to help guide this transition is extremely limited. OBJECTIVE: To assess the transition from bivalirudin to warfarin after implementation of an institution-wide transition protocol. METHODS: In this retrospective quasiexperimental study, adult patients receiving bivalirudin directly followed by warfarin for nonprocedural systemic anticoagulation were evaluated to determine the frequency of successful transition to warfarin. Participants were compared before (preprotocol) and after (postprotocol) the implementation of the transition protocol. RESULTS: A total of 39 patients met inclusion criteria and were included in the analysis (preprotocol = 19; postprotocol = 20). The percentage of patients achieving a successful transition was significantly higher in the postprotocol group compared with the preprotocol group (80.0% vs 42.1%, P = 0.015). Bleeding events were similar between the 2 groups (23.1% vs 16.7%, P = 0.689). Withholding of warfarin doses or the use of anticoagulant reversal agents or blood transfusions for supratherapeutic INR levels, surgical procedures, or drop in hemoglobin was numerically lower in the postprotocol group compared with the preprotocol group (16.7% vs 46.2%, P = 0.202). CONCLUSION: Implementation of a simplistic bivalirudin-warfarin transition protocol significantly increased the frequency of therapeutic INR results on bivalirudin discontinuation. Additionally, patients treated according to this protocol were less likely to have warfarin doses withheld or require reversal agents. Larger studies testing this transition strategy are warranted.

Key articles and guidelines in the management of patients undergoing cardiac surgery.

Significant numbers of patients undergo cardiac surgery worldwide each year. A large evidence base exists regarding the optimal pre-, intra-, and postoperative mediation management for patients undergoing coronary artery bypass grafting (CABG) surgery, valve replacements or repairs, and mechanical circulatory support (MCS). Prevention and treatment of perioperative arrhythmias, perioperative antimicrobial prophylaxis, prevention of thrombosis, and bleeding through proper management of perioperative antiplatelet and anticoagulant therapies, and the use of pharmacotherapy to optimize both short- and long-term patient outcomes after cardiac surgery are the focus of this first compilation of guidelines and key articles in this patient population to be published in the Journal of Pharmacy Practice.

Association of antipsychotic and antidepressant drugs with Q-T interval prolongation.

PURPOSE: The association of antipsychotic and antidepressant drugs with Q-T interval prolongation is reviewed. SUMMARY: Prolongation of the Q-T interval can be of particular concern to practitioners when prescribing antidepressants and antipsychotics. Patients may be at a greater risk for developing fatal arrhythmias when taking many of these drugs. In general, antipsychotics cause Q-T interval prolongation at a higher rate than do antidepressants. The typical antipsychotics thioridazine, pimozide, and intravenous haloperidol all have the highest potential for Q-T interval prolongation. The tricyclic antidepressants have a higher rate of Q-T interval prolongation than do selective serotonin-reuptake inhibitors (SSRIs), particularly at higher concentrations and in cases of overdose. In addition, nonpharmacologic risk factors such as existing heart disease, female sex, electrolyte abnormalities, hepatic insufficiency, and stimulant drug abuse contribute to the risk for developing these arrhythmias, as do pharmacologic factors such as multidrug therapy and high dosages of drugs known to prolong the Q-T interval. Risk factors may be identified in the patient's history and demographic information. However, all pharmacists may not have this information readily available to them. CONCLUSION: Antipsychotics cause Q-Tc interval prolongation at a higher rate than do antidepressants, and the typical anti-psychotics thioridazine, pimozide, and i.v. haloperidol all have the highest potential for Q-Tc interval prolongation. Tricyclic antidepressants have a higher rate of Q-Tc interval prolongation than do the SSRIs, particularly at higher concentrations and in overdose situations. The frequency of adverse events associated with drug-induced Q-T interval prolongation is unknown.