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.

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.

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.

Evaluation of clinical and laboratory data for early diagnosis of heparin-induced thrombocytopenia.

PURPOSE: Results of a study to determine the utility of combining laboratory values and clinical probability scores to improve the detection of heparin-induced thrombocytopenia (HIT) are reported. METHODS: In a retrospective, single-site, chart review-based investigation, 156 cases in which patients with suspected HIT had positive results on a widely used diagnostic test (the anti-heparin/platelet factor 4, or anti-PF4, assay) were identified; in all cases, the blood specimens had been sent to a reference laboratory for confirmation of HIT via serotonin release assay (SRA). After investigator scoring of the clinical probability of HIT in each case by the 4T's method, a multiple logistic regression model was used to evaluate the combined effect of 4T's scores and anti-PF4 assay values in predicting SRA results. RESULTS: 4T's scores indicating an intermediate or high probability of HIT combined with high anti-PF4 test values (i.e., optical density [OD] value of ≥1.4) were strongly predictive of a positive SRA result, as were high-probability 4T's scores alone. Low-probability 4T's scores alone or in combination with anti-PF4 OD values of <1.4 were highly correlated with negative SRA results. Controlling for potential confounding factors, logistic regression analysis indicated that the 4T's score was a better predictor of SRA results than the anti-PF4 test value. CONCLUSION: The combination of anti-PF4 OD values and 4T's scores accurately predicted SRA results, suggesting that the SRA may not be necessary to confirm HIT in patients with a relatively low 4T's score and a low anti-PF4 OD value.

Moderate hypothermia during aortic arch surgery is associated with reduced risk of early mortality.

OBJECTIVE: Selective antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest (HCA) provides cerebral protection during aortic arch surgery. However, the ideal temperature for HCA during ACP remains unknown. Clinical outcomes were compared in patients who underwent moderate (nasopharyngeal temperature, ≥ 20 °C) versus deep (nasopharyngeal temperature, <20 °C) HCA with ACP during aortic arch repair. METHODS: By using a prospectively maintained clinical database, we analyzed data from 221 consecutive patients who underwent aortic arch replacement with HCA and ACP between December 2006 and May 2009. Seventy-eight patients underwent deep hypothermia (mean lowest temperature, 16.8 °C ± 1.7 °C) and 143 patients underwent moderate hypothermia (mean, 22.9 °C ± 1.4 °C) before systemic circulatory arrest was initiated. Multivariate stepwise logistic and linear regressions were performed to determine whether depth of hypothermia independently predicted postoperative outcomes and blood-product use. RESULTS: Compared with moderate hypothermia, deep hypothermia was associated independently with a greater risk of in-hospital death (7.7% vs 0.7%; odds ratio [OR], 9.3; 95% confidence interval [CI], 1.1-81.6; P = .005) and 30-day all-cause mortality (9.0% vs 2.1%; OR, 4.7; 95% CI, 1.2-18.6; P = .02), and with longer cardiopulmonary bypass time (154 ± 62 vs 140 ± 46 min; P = .008). Deep hypothermia also was associated with a higher incidence of stroke, although this association was not statistically significant (7.6% vs 2.8%; P = .073; OR, 4.3; 95% CI, 0.9-12.5). No difference was seen in acute kidney injury, blood product transfusion, or need for surgical re-exploration. CONCLUSIONS: Moderate hypothermia with ACP is associated with lower in-hospital and 30-day mortality, shorter cardiopulmonary bypass time, and fewer neurologic sequelae than deep hypothermia in patients who undergo aortic arch surgery with ACP.

Significance of anaemia in patients with advanced heart failure receiving long-term mechanical circulatory support.

AIMS: The aim of this study was to analyse the prognostic impact of anaemia in patients receiving long-term left ventricular assist device (LVAD) support. METHODS AND RESULTS: We reviewed the data of 65 consecutive patients who underwent LVAD support for at least 6 months. Anaemia was defined as haemoglobin levels <12.0 g/dL. Follow-up was performed 15 months after implantation. Anaemia was present in 30/65 patients (46%) after 6 months of LVAD support. Anaemic patients had higher levels of pre-implant creatinine (1.8 +/- 0.8 vs. 1.4 +/- 0.5 mg/dL; P = 0.04). The presence of anaemia after 6 months correlated with higher levels of creatinine and blood urea nitrogen and lower levels of albumin. Multivariate Cox proportional hazards regression analysis revealed that levels of haemoglobin <12 g/dL [risk ratio (RR), 8.94; 95% confidence interval (CI), 1.09-73.01; P = 0.04], creatinine >1.4 mg/dL (RR, 5.39; 95% CI, 1.78-16.30; P = 0.003), and albumin <1.5 g/L (RR, 3.23; 95% CI, 1.10-9.51; P = 0.03) were associated with all-cause mortality at 15 months. Long-term survival evaluated by Kaplan-Meier analysis was two times higher in non-anaemic patients after 6 months of LVAD support than in anaemic patients (P = 0.01). CONCLUSION: Anaemia is related to adverse outcomes in patients receiving prolonged LVAD support.

Increased leukocyte-platelet interactions during circulatory support with left ventricular assist devices.

The interaction of circulating monocytes and platelets may contribute to thrombosis and inflammation in heart failure. We studied platelet and monocyte activation in 15 patients with end-stage heart failure who underwent left ventricular assist device (LVAD) placement. Blood samples were collected before and at 3, 7, 14, 21, 30, 60, 90, and 180 days after LVAD implantation. We used flow cytometry to measure the expression of platelet surface glycoprotein receptors, platelet activation markers, monocyte markers, the formation of platelet complexes with monocytes (MPC), granulocytes, and lymphocytes, and platelet glycoprotein (GP) IIIa (PLA1/A2) polymorphism. The average preoperative percentage of CD62P-positive platelets was 27% +/- 17%; CD63-positive platelets, 9.7% +/- 8.1%; thrombospondin-positive platelets, 9.9% +/- 6.8%; and MPCs, 10.3% +/- 4.3%. No significant changes were noted in the percent of activated platelets with the three markers. Percentage of MPCs increased over time and peaked at day 21 (26.3% +/- 10.6%, p = 0.0028). In about 40% of patients, activation markers remained high up to 60 days after implantation. We found a significant positive correlation between MPC and CD14 (R = 0.60, p = 0.011), and a negative correlation between MPC and P-selectin glycoprotein ligand-1 (PSGL-1) (R = -0.84, p < 0.0001), and between CD14 and PSGL-1 (R = -0.46, p = 0.022) indicating monocyte activation. These results indicate increased platelet and monocyte activation and interactions in patients undergoing long-term LVAD support.

Intraoperative anticoagulation management during cardiac transplantation for a patient with heparin-induced thrombocytopenia and a left ventricular assist device.

Heparin-induced thrombocytopenia is an immunologically mediated syndrome that is associated with potentially life-threatening arterial and venous thrombosis. Re-exposing patients who have heparin-induced thrombocytopenia to heparin during cardiopulmonary bypass may be hazardous. We describe the re-exposure to unfractionated heparin of a patient with a left ventricular assist device and evidence of heparin-induced thrombocytopenia who needed cardiac transplantation, which was accomplished without complications.