Arthur W. Bracey

Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.

BACKGROUND: There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome.

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.

Blood use in patients undergoing repeat coronary artery bypass graft procedures: multivariate analysis

BACKGROUND: The prevailing clinical opinion is that patients undergoing repeat coronary artery bypass graft (CABG) operation require more blood transfusions than do patients undergoing primary CABG operation. To determine the extent of this increased demand and the variables responsible for it, the cases of 196 patients who had undergone primary procedures and 65 patients who had had repeat procedures at the same institution were reviewed.

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.

Analysis of prolonged storage on coagulation Factor (F)V, FVII, and FVIII in thawed plasma: Is it time to extend the expiration date beyond 5 days?

BACKGROUND: According to AABB standards, fresh‐frozen plasma (FFP) should be thawed at 30 to 37°C and expire after 24 hours. An increase in the aggressive management of trauma patients with thawed plasma has heightened the risk of plasma waste. One way to reduce plasma waste is to extend its shelf life, given that the full range of therapeutic efficacy is maintained. We evaluated the effect of prolonged storage at 1 to 6°C on the activity of Factor (F)V, FVII, and FVIII in plasma thawed at 37 or 45°C.

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

The aim of this study was to analyse the prognostic impact of anaemia in patients receiving long‐term left ventricular assist device (LVAD) support.

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.

High-dose Intravenous Dalteparin Can be Monitored Effectively Using Standard Coagulation Times

The objective of this study was to examine the pharmacokinetics of intravenous dalteparin (Fragmin, Pharmacia-Upjohn, Peapack, NJ) and to assess the accuracy of standard coagulation-based monitoring techniques as an estimate of drug concentration with which to guide dosing. Knowledge of the kinetic behavior of low-molecular-weight heparins (LMWHs) and the possible utility of coagulation times for monitoring may aid in the development of safe and effective dosing algorithms for percutaneous coronary interventions. Twenty normal volunteers were treated at 2-week intervals with each of three intravenous dalteparin doses. Measurement of anti-IIa, anti-Xa, activated partial thromboplastin time (aPTT), activated clotting time (ACT), and low-range ACT was performed at baseline and at seven additional time points over 8 hours. The half-life of intravenous dalteparin is 77 minutes with slight dose-related variation. The aPTT, LR-ACT, and standard ACT are prolonged after dalteparin administration with the increase closely correlated to anti-Xa activity (aPTT, r = 0.85; LR-ACT, r = 0.79). Classification of anticoagulation intensity range using aPTT or LR-ACT in comparison to anti-Xa activity (0.5-0.99, 1.0-1.49, 1.5-2, >2) displays a level of agreement (kappa: aPTT = 0.69, LR-ACT = 0.59) that is comparable to values reported for coagulation time guidance of unfractionated heparin administration. Standard coagulation times are sensitive to the anticoagulant effect of dalteparin with a degree of correlation that suggests their utility for estimating drug concentration during high dose therapy. Trials establishing a relationship between monitoring and clinical efficacy, and the risk/reward of different treatment ranges alone or in combination with GPIIb/IIIa inhibitors and clopidogrel, are necessary.

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 4Ts method, a multiple logistic regression model was used to evaluate the combined effect of 4Ts scores and anti-PF4 assay values in predicting SRA results. RESULTS 4Ts 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 4Ts scores alone. Low-probability 4Ts 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 4Ts score was a better predictor of SRA results than the anti-PF4 test value. CONCLUSION The combination of anti-PF4 OD values and 4Ts scores accurately predicted SRA results, suggesting that the SRA may not be necessary to confirm HIT in patients with a relatively low 4Ts score and a low anti-PF4 OD value.

How do we manage patients treated with antithrombotic therapy in the perioperative interval

A s our population ages, the use of anticoagulant and antiplatelet (anti-PLT) drugs is growing because older patients are at increased risk for clinical conditions that require these antithrombotic therapies. For example, atrial fibrillation currently affects 2.66 million patients, which is projected to increase to 12 million patients by 2050, according to Census projections. Long-term anticoagulation therapy is currently estimated to be used in approximately 2.5 million patients in the United States, and anti-PLT therapy is even more widespread. Millions of patients use acetylsalicylic acid (ASA), or aspirin, as a prophylactic measure. Moreover, patients who undergo cardiac stent placement require the more potent antiPLT drug clopidogrel (adenosine 5′-diphosphate [ADP] P2Y12 inhibitor) for 3 months to 1 year or longer, depending on the type of stent. The effect of the widespread use of antithrombotic agents in medical therapy will be enhanced by drug campaigns that are aimed at developing more effective agents, which may be associated with serious bleeding complications. Prasugrel, a recently approved P2Y12 inhibitor, improved cardiac outcomes but significantly increased the risk of life-threatening bleeding—including fatal bleeding—not related to coronary artery bypass grafting (CABG). The pharmacologic effect of anticoagulants is dynamic, and thus physicians who care for patients treated with these agents should actively monitor new developments in this field. Because thrombosis can lead to irreversible damage to key organ systems, such as the central nervous system or the myocardium, a trade-off of increased bleeding risk for antithrombotic therapy is often accepted. Physicians who are responsible for the perioperative care of patients with ongoing or recent anticoagulant or anti-PLT therapy must be adept at managing bleeding risk. They are expected to safely optimize the patient’s coagulation status for surgery or any other invasive procedure and revert to the relative protection of anticoagulation after intervention. To achieve an acceptable balance between coagulation and the risk of thrombosis, the physician must be able to skillfully assess each patient and the surgical intervention at hand. To do so requires an indepth understanding of the data available in this field. Although several guidelines have been promulgated, little first-order scientific data are available from adequately powered, well-designed trials to guide physicians in managing bleeding risk in patients exposed to anticoagulant therapy in the perioperative period. Physicians who practice transfusion medicine should become familiar with the challenges associated with perioperative antithrombotic therapy so that they may advise colleagues on the appropriate role of blood components and factor replacement therapy in the management of these problems. The practice of managing treatment for patients who have undergone antithrombotic therapy in the perioperative setting varies because of a lack of welldefined endpoints. Located in a large cardiac center, we provide a consultative service to aid in managing these cases. Here, we share the available data and describe our personal approach to managing the perioperative care for patients exposed to antithrombotic therapy.