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.

A survey of US hospitals on platelet inventory management, transfusion practice, and platelet availability.

BACKGROUND: A survey of US hospitals was conducted to increase our understanding of the current state of platelet (PLT) practice and supply. The survey captures information on transfusion practice and inventory management, including stock levels, outdate rates, ability to return or transfer PLTs, and low dose PLTs. Notably, the survey also elucidates PLT availability challenges and impact to patient care. STUDY DESIGN AND METHODS: A 27 question online survey was distributed directly to over 995 US hospitals and indirectly through blood centers to many more between September 27 and October 25, 2019. Descriptive statistics were used for respondent characteristics. Bivariate analysis was performed and correlation coefficients, chi square tests, and p values determined statistical significance of relationships between variables. RESULTS: Four hundred and eighty-one hospitals completed the survey of which 21.6%, 53.2%, and 25.2% were characterized as small, medium, and large hospitals, respectively. Some key observations from this survey include: (1) there is an opportunity for greater adherence to evidence-based guidelines; (2) higher outdate rates occur in hospitals stocking less than five PLTs and the ability to return or transfer PLTs lowers outdates; (3) use of low dose apheresis PLTs varies; and (4) decreased PLT availability is commonly reported, especially in hospitals with high usage, and can lead to delays in transfusions or surgeries. CONCLUSION: This survey represents a comprehensive national assessment of inventory management practices and PLT availability challenges in US hospitals. Findings from this survey can be used to guide further research, help shape future guidance for industry, and assist with policy decisions.

Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions.

BACKGROUND: Plasma is frequently administered to patients with prolonged INR prior to invasive procedures. However, there is limited evidence evaluating efficacy and safety. STUDY DESIGN AND METHODS: We performed a pilot trial in hospitalized patients with INR between 1.5 and 2.5 undergoing procedures conducted outside the operating room. We excluded patients undergoing procedures proximal to the central nervous system, platelet counts <40,000/µl, or congenital or acquired coagulation disorders unresponsive to plasma. We randomly allocated patients stratified by hospital and history of cirrhosis to receive plasma transfusion (10-15 cc/kg) or no transfusion. The primary outcome was change in hemoglobin concentration within 2 days of procedure. RESULTS: We enrolled 57 patients, mean age 56.0, 34 (59.6%) with cirrhosis, and mean INR 1.92 (SD = 0.27). In the intention to treat analysis, there were 10 of 27 (38.5%) participants in the plasma arm with a post procedure INR <1.5 and one of 30 (3.6%) in the no treatment arm (p < .01). The mean INR after receiving plasma transfusion was -0.24 (SD 0.26) lower than baseline. The change from pre-procedure hemoglobin level to lowest level within 2 days was -0.6 (SD = 1.0) in the plasma transfusion arm and -0.4 (SD = 0.6) in the no transfusion arm (p = .29). Adverse outcomes were uncommon. DISCUSSION: We found no differences in change in hemoglobin concentration in those treated with plasma compared to no treatment. The change in INR was small and corrected to less than 1.5 in minority of patients. Large trials are required to establish if plasma is safe and efficacious.

Viscoelastic Haemostatic Assays in Cardiovascular Critical Care.

The initiation and management of anticoagulation is a fundamental practice for a wide variety of indications in cardiovascular critical care, including the management of patients with acute MI, stroke prevention in patients with AF or mechanical valves, as well as the prevention of device thrombosis and thromboembolic events with the use of mechanical circulatory support and ventricular assist devices. The frequent use of antiplatelet and anticoagulation therapy, in addition to the presence of concomitant conditions that may lead to a propensity to bleed, such as renal and liver dysfunction, present unique challenges. The use of viscoelastic haemostatic assays provides an additional tool allowing clinicians to strike a delicate balance of attaining adequate anticoagulation while minimising the risk of bleeding complications. In this review, the authors discuss the role that viscoelastic haemostatic assay plays in cardiac populations (including cardiac surgery, heart transplantation, extracorporeal membrane oxygenation, acute coronary syndrome and left ventricular assist devices), and identify areas in need of further study.

Plasmapheresis in Patients With Heparin-induced Thrombocytopenia Requiring Ventricular Assist Device.

Anticoagulation with unfractionated heparin is vital to reduce the risk of thromboembolic events during cardiopulmonary bypass and left ventricular assist device placement. However patients with heparin-induced thrombocytopenia are at risk of developing immune-mediated thrombotic events. We describe 2 patients with heparin-induced thrombocytopenia confirmed via serotonin release assay who were successfully treated with plasmapheresis exchange before left ventricular assist device placement.

Long-term Experience with Rapid Screening for Platelet Bacterial Contamination in a High-volume Transfusion Service.

Bacterial sepsis after platelet transfusion is a major cause of transfusion-transmitted infections in the US. The Food and Drug Administration (FDA) recommends performing quality control for platelet bacterial detection on days 4 and 5 before platelet transfusion. We assessed the feasibility of implementing the Pan Genera Detection (PGD) test, an FDA-approved immunoassay for platelet bacterial detection, for the primary and secondary bacterial screening of platelet units in a high-volume setting. Records were reviewed from January 2010 through December 2015. All apheresis platelets underwent primary screening by using culture methods. Additional screening with the PGD test was performed daily until February 2013, when PGD testing of apheresis platelets was performed at the start of storage day 5. In April 2015, PGD testing of apheresis platelet products was performed at the start of storage day 4. Post-storage pooled whole blood-derived platelets were screened by using the PGD test on the day of use. During the 6-year study period, 16,839 PGD tests were performed. If the PGD test was reactive, repeat PGD testing was performed. In cases of repeat reactivity, units were quarantined and cultured. Initially, 42 (0.25%) tests were reactive; 26/42 (61.91%) were repeatedly reactive and resulted in an overall PGD repeat reactivity rate of 0.15%. Only one sample grew coagulase-negative Staphylococcus No transfusion-transmitted infections were reported. The PGD bacterial detection assay was feasible and efficient in our high-volume transfusion service.

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.

Bleeding in patients receiving non-vitamin K oral anticoagulants: clinical trial evidence.

In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience. We will review the phase III evidence for each of the available NOACs in different antithrombotic indications, including atrial fibrillation (in the absence of significant mitral stenosis or mechanical heart valves); prophylaxis of venous thromboembolism (VTE) in patients undergoing orthopedic surgery; and acute and long-term treatment of VTE. Further, we will illustrate scenarios in which the evidence is stronger for a particular agent in the context of the overall positive safety and efficacy profile of NOACs in general. Limitations of the factor Xa inhibitors include the lack of a specific antidote in case of a bleeding emergency (an approved agent is available for reversing the effect of the direct thrombin inhibitor). We discuss the options for mitigating bleeding and describe the ongoing developments towards specific reversal agents. In conclusion, the available data for efficacy and safety, together with reliable pharmacokinetics obviating the need for regular monitoring, indicate that NOACs may offer substantial benefits for patients with nonvalvular atrial fibrillation or VTE.

Therapeutic Plasma Exchange for Urgent Rivaroxaban Reversal.

Direct oral anticoagulants, which include the factor Xa inhibitor rivaroxaban, have some advantages over vitamin K antagonists in regard to stroke prevention in patients with atrial fibrillation. However, no antidotes to reverse the effect of oral anticoagulants are commercially available, which can complicate treating patients in whom reversal is urgent. We faced this challenge in a kidney transplant candidate, a 65-year-old man with end-stage renal disease who had been taking rivaroxaban for paroxysmal atrial fibrillation. When a deceased-donor kidney became available, we needed to rapidly reduce the patient's bleeding risk, while minimizing the cold ischemic time of the donor kidney. Therefore, we decided to take an experimental approach and perform therapeutic plasma exchange. The patient's plasma anti-factor Xa level decreased from 0.4 IU/mL immediately before treatment to 0.21 IU/mL afterward, indicating that rivaroxaban had been actively removed from circulation. Waste fluid showed significant anti-Xa activity, indicating that the risk of rebound anticoagulation had been mitigated. The patient subsequently underwent successful kidney transplantation. To our knowledge, this is the first report of therapeutic plasma exchange to reverse the effects of rivaroxaban in a patient undergoing urgent surgery. This treatment may also be suitable for patients who have life-threatening, large-volume bleeding, especially in the presence of substantial kidney or liver dysfunction.

Characteristics of thawed pooled cryoprecipitate stored at refrigerated temperature for 24 hours.

BACKGROUND: The need for thawed cryoprecipitate is growing. However, according to current guidelines, the shelf-life of pooled thawed cryoprecipitate at room temperature is limited because of possible bacterial contamination and loss of clotting factor activity. Here we assessed microbial growth and retention of clotting activity in cryoprecipitate stored at 4 °C after thawing to see whether its shelf life could be safely extended. MATERIALS AND METHODS: Pooled thawed cryoprecipitate units (n=10) were maintained at room temperature for 6 hours and then placed at 1-6 °C for 18 hours after thawing. We examined the cryoprecipitate pools for fibrinogen, factor VIII, and von Willebrand factor activity at the following time points: 0 hours (immediately after thawing), after 6 hours at room temperature, and after 24 hours at 1-6 °C. A 5-mL aliquot from each pool was collected for aerobic and anaerobic bacterial cultures at the 24-hour time point. RESULTS: Mean fibrinogen concentration and von Willebrand factor activity were similar at each time point, but factor VIII activity decreased significantly over the storage period. Bacterial growth was not detected in any cultured pooled sample. DISCUSSION: Extended storing of thawed cryoprecipitate at 1-6 °C does not appear to increase the risk of bacterial contamination or affect coagulation factor activity.

Use of an Intravascular Warming Catheter during Off-Pump Coronary Artery Bypass Surgery in a Patient with Severe Cold Hemagglutinin Disease.

Cold hemagglutinin disease with broad thermal amplitude and high titers presents challenges in treating cardiac-surgery patients. Careful planning is needed to prevent the activation of cold agglutinins and the agglutination of red blood cells as the patient's temperature drops during surgery. We describe our approach to mitigating cold agglutinin formation in a 77-year-old man with severe cold hemagglutinin disease who underwent off-pump coronary artery bypass surgery without the use of preoperative plasmapheresis. This experience shows that the use of an intravascular warming catheter can maintain normothermia and prevent the activation and subsequent formation of cold agglutinins. To our knowledge, this is the first reported use of this technique in a patient with cold hemagglutinin disease. The chief feature in this approach is the use of optimal thermal maintenance-rather than the more usual decrease in cold-agglutinin content by means of therapeutic plasma exchange.

Proposed diagnostic criteria for the case definition of amniotic fluid embolism in research studies.

Amniotic fluid embolism is a leading cause of maternal mortality in developed countries. Our understanding of risk factors, diagnosis, treatment, and prognosis is hampered by a lack of uniform clinical case definition; neither histologic nor laboratory findings have been identified unique to this condition. Amniotic fluid embolism is often overdiagnosed in critically ill peripartum women, particularly when an element of coagulopathy is involved. Previously proposed case definitions for amniotic fluid embolism are nonspecific, and when viewed through the eyes of individuals with experience in critical care obstetrics, would include women with a number of medical conditions much more common than amniotic fluid embolism. We convened a working group under the auspices of a committee of the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation whose task was to develop uniform diagnostic criteria for the research reporting of amniotic fluid embolism. These criteria rely on the presence of the classic triad of hemodynamic and respiratory compromise accompanied by strictly defined disseminated intravascular coagulopathy. It is anticipated that limiting research reports involving amniotic fluid embolism to women who meet these criteria will enhance the validity of published data and assist in the identification of risk factors, effective treatments, and possibly useful biomarkers for this condition. A registry has been established in conjunction with the Perinatal Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development to collect both clinical information and laboratory specimens of women with suspected amniotic fluid embolism in the hopes of identifying unique biomarkers of this condition.