Thromboelastography versus thromboelastometry for unfractionated heparin monitoring in adult patients on extracorporeal membrane oxygenation.

Background: Monitoring the anticoagulant effect of unfractionated heparin (UFH) in extracorporeal membrane oxygenation (ECMO) patients is complex but critically important to balance the risks of treatment related bleeding and circuit thrombosis. While guidelines recommend using more than one method to monitor UFH activity, the use of thromboelastometry (ROTEM) to monitor UFH in ECMO patients has not been investigated in detail.Methods: This is an observational, single-center retrospective study looking at adult ECMO patients on UFH that had ROTEM and thromboelastography (TEG) tests obtained concurrently. A total of 20 samples were obtained from nine patients during the study period, seven of which were on veno-arterial (VA) ECMO and two of which were on veno-venous (VV) ECMO.Results: Under institutional standard operating practice, when TEG and/or activated partial thromboplastin time (aPTT) were considered therapeutic, intrinsic thromboelastometry clotting time (INTEM CT) was only 1.2 times higher than the normal range. TEG based monitoring compared to aPTT based monitoring tended to result in lower anti-Xa levels and less intensive anticoagulation. For the total cohort, bleeding events, driven by the need for blood transfusions, were more common compared to ischemic events (77% vs 11%; p = 0.02).Conclusion: INTEM CT tended to be less sensitive to lower doses of UFH with a value of 1.2 times higher than the normal range when aPTT and/or TEG were considered therapeutic. Due to the relative insensitivity of ROTEM, our institution decided to continue to use TEG instead of ROTEM. Larger, multicenter trials may be helpful to validate these findings.

Evaluation of Lead-In Direct Oral Anticoagulant Prescribing Practices in Newly Diagnosed Venous Thromboembolism.

Various lead-in dosing strategies have been used in clinical practice for venous thromboembolism (VTE), and guidelines do not currently address if the full lead-in dosing duration is necessary after receiving parenteral anticoagulation. This study aims to identify whether full lead-in dosing duration surrounding parenteral anticoagulation affects thrombotic and bleeding outcomes. A single-center, retrospective cohort study was conducted of hospitalized patients diagnosed with VTE and treated with apixaban or rivaroxaban. Patients were grouped depending on duration of lead-in dosing, with the full lead-in dosing group considered as the appropriate duration of the direct oral anticoagulant. The primary outcome was the recurrence of VTE within the index admission to 6 months. Secondary outcomes included major bleeding, clinically relevant minor bleeding, and mortality. Ninety-three patients were prescribed full lead-in dosing, while 99 patients received reduced lead-in dosing. The primary outcome of recurrent VTE was similar between the reduced lead-in group compared to the full lead-in group (3% vs 2%; P = 1.0). Major bleeding within the index admission was significantly higher in the reduced lead-in group: 11 versus 2 (P = .02). There were no significant differences in other secondary outcomes. Full lead-in dosing compared to reduced lead-in dosing duration for VTE had similar rates of thrombotic and mortality events. The higher rate of major bleeding in the reduced lead-in dosing group likely reflects the prescribing practices in less stable patients. This study provides evidence to support reduced lead-in dosing duration in high-risk patients without compromising efficacy outcomes.

Fixed- versus variable-dose prothrombin complex concentrate protocol for vitamin K antagonist reversal.

Fixed-dose prothrombin complex concentrates (PCCs) for the reversal of vitamin K antagonists may decrease the incidence of thromboembolic events, treatment costs, and treatment delays. However, the ideal fixed dose is unknown, with some studies showing inadequate reversal with suboptimal dosing or in patients with a higher international normalized ratio (INR) or weight. This indicates a need for a modified fixed-dose strategy that considers weight and INR. This study was a retrospective chart review comparing efficacy and safety outcomes of the standard variable-dose protocol versus a fixed-dose protocol. The primary outcome was the proportion of patients who achieved INR reversal. Of the total of 113 patients reviewed, INR reversal to < 1.5 was achieved in 23 patients (46%) in the variable-dose group versus 27 patients (43%) in the fixed-dose group (P = 0.83). Of the 27 patients with ICH, INR reversal to ≤ 1.3 was achieved in five patients (71%) in the variable dose group versus ten patients (50%) in the fixed-dose group (P = 0.41). The rate of INR reversal did not differ significantly between groups, but the fixed-dose group used less PCCs and had lower treatment costs.

Request for an Andexxa Value Analysis.

This perspective is a formal request to the American College of Cardiology and American Heart Association (ACC/AHA) to perform a value analysis on andexanet (Andexxa) similar to what was completed for the PCSK9 inhibitors in the 2018 ACC/AHA Blood Cholesterol guidelines. Based on the safety and efficacy concerns of andexanet alfa, a value statement in and or as an addendum to society guidelines is vital considering the high cost of therapy. In this era of ever-increasing health care costs, every clinician, health system, national society, insurer, and pharmaceutical company should work to be good stewards of our society's resources.

Evaluation of a heparin monitoring protocol for extracorporeal membrane oxygenation and review of the literature.

BACKGROUND: Bleeding complications are common with extracorporeal membrane oxygenation (ECMO). We investigated whether a heparin monitoring protocol using activated partial thromboplastin time (aPTT) and thromboelastography (TEG) affected clinical outcomes. METHODS: This retrospective chart review stratified cohorts by study interval: pre-protocol (January 2016-March 2017) or post-protocol (March 2017-December 2017). The protocol defined therapeutic anticoagulation as aPTT of 60-80 seconds and a TEG reaction (TEG-R) time of 2-4× baseline; pre-protocol management used aPTT alone. The primary endpoints were the rates of bleeding and thrombotic events (clinical/device thrombosis) as defined by Extracorporeal Life Support Organization (ELSO) guidelines. Secondary endpoints included time in therapeutic aPTT range, rate of physician compliance with the protocol, time to heparin initiation, intensive care unit length of stay, mortality, and antithrombin III (ATIII) supplementation. RESULTS: The pre-protocol (n=72) and post-protocol (n=51) groups (age 60±12 years; 80% on venoarterial ECMO; average ECMO duration of 6 days) showed no difference in baseline characteristics. Major bleeding events occurred in 69% of pre-protocol patients, versus 67% of post-protocol patients (P=0.85). The post-protocol group had fewer retroperitoneal bleeds (P=0.01) and had a non-significantly lower rate of pulmonary or central nervous system (CNS) bleeding (P=0.07). Thrombotic events occurred in 21% of the pre-protocol group, versus 28% of the post-protocol group (P=0.39). Mortality during ECMO support was significantly lower in the post-protocol group (56.9% vs. 33.3%, P=0.01). The thrombosis rate was higher in patients who received ATIII than in those who did not (48.2% vs. 15.9%, P<0.01). CONCLUSIONS: Major bleeding did not differ between the treatment groups. However, we observed significantly less mortality and retroperitoneal bleeding in the post-protocol group, suggesting an important gain from the intervention. Further study of the value of ATIII supplementation in ECMO patients is needed since we observed that a lower baseline ATIII level may indicate higher risk for thrombosis.

Contemporary Prescription Patterns of Adenosine Diphosphate Receptor Inhibitors in Acute Coronary Syndrome.

PURPOSE: To assess the contemporary use of adenosine diphosphate (ADP) receptor inhibitors in acute coronary syndrome at a large, quaternary academic medical center. METHODS: A retrospective observational study was conducted using health records to compare patients who were treated with ticagrelor (Brilinta, AstraZeneca), prasugrel, or clopidogrel for a primary diagnosis of new-onset acute coronary syndrome between January 2014 and December 2014. RESULTS: A total of 275 patients were identified. Clopidogrel was the most commonly prescribed ADP receptor antagonist (52%), followed by ticagrelor (26%) and prasugrel (22%). Patients who were prescribed clopidogrel were more likely female (P < 0.01), 75 years of age or older (P < 0.01), and 60 kg or less in weight (P = 0.02), and they had more comorbidities. Of the patients on clopidogrel prior to admission, 21% were switched to prasugrel or ticagrelor for inadequate platelet inhibition, restenosis, or new stent placement. Of the patients on ticagrelor or prasugrel prior to admission, 17% were switched to clopidogrel for concerns about bleeding or cost. Clopidogrel was prescribed 13% of the time, prasugrel 13% of the time, and ticagrelor 4% of the time (P = 0.13) outside the recommended use per Food and Drug Administration-approved prescribing information based on relative or absolute contraindications. CONCLUSION: Clopidogrel continues to be the most commonly prescribed antiplatelet agent, particularly in older patients with more comorbidities.

Safety and Effectiveness of Factor VIII Inhibitor Bypassing Activity (FEIBA) and Fresh Frozen Plasma in Oral Anticoagulant-Associated Intracranial Hemorrhage: A Retrospective Analysis.

BACKGROUND: Oral anticoagulant (OAT)-associated intracranial hemorrhage (ICH) is a life-threatening emergency for which prothrombin complex concentrates (PCC) are considered first-line reversal agents. The only approved PCC in the USA for warfarin-associated ICH is non-activated PCC. Little data are available regarding the safety and effectiveness of factor VIII inhibitor bypassing activity (FEIBA) which is an activated prothrombin complex concentrate (aPCC). The aim of this analysis was to assess the safety and effectiveness of FEIBA compared to fresh frozen plasma (FFP) for reversal of OAT-associated ICH. METHODS: Data were retrospectively collected to compare coagulation markers and in-hospital clinical outcomes in patients who received aPCC with or without FFP versus FFP alone for the reversal of OAT-associated ICH. RESULTS: Eighty-four patients met inclusion criteria; 50 patients received FFP alone, and 34 patients received FEIBA (mean dose 20 U/kg) with or without FFP for OAT-associated ICH. The proportion of diagnosed thrombotic events during hospitalization was similar in both groups (8% in the FFP group vs. 12% in the FEIBA group; P = 0.56). Median time to INR < 1.5 was achieved faster in the FEIBA group versus the FFP group (0.5 h [IQR 0.5-1.] vs. 10 h [IQR 5-16.3], respectively; P < 0.001) reflecting a trend toward shorter median time to neurosurgical intervention. Hematoma expansion, length of stay, and all-cause mortality were similar between both groups. CONCLUSIONS: Administration of FEIBA does not appear to increase the risk of thrombotic events compared with FFP. FEIBA administration resulted in faster INR reversal with a trend toward shorter time to neurosurgical intervention. However, there was no difference in hematoma expansion, mortality or length of stay.