Thrombin Generation and Antithrombin Activity in Infants Undergoing Cardiopulmonary Bypass-An Exploratory Study.

OBJECTIVES: Coagulopathic bleeding is a major complication of pediatric cardiac surgery. Investigating perioperative dynamics of thrombin generation and antithrombin (AT) activity might provide more insight into the underlying mechanisms of coagulopathy. This can help develop a targeted hemostatic approach in the future. The authors hypothesized that there is a decline in both thrombin generation and AT activity in infants undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Single academic medical center. PARTICIPANTS: Infants <10 kg of weight undergoing cardiac surgery with CPB. INTERVENTIONS: Blood specimen collection and testing. MEASUREMENTS AND RESULTS: The authors performed assays of thrombin generation and AT activity on the samples of platelet-poor plasma of 25 infants, repeating them at 3 points: before CPB and heparinization, after separation from CPB and protamine administration, and after chest closure. The authors observed a statistically significant decline in thrombin generation shortly after separation from CPB compared with baseline. The geometric mean for lag time was prolonged (4.0 v 5.5 minutes, p = 0.013), and peak thrombin and the net amount of generated thrombin declined almost 3-fold (80.7 v 25.1 nmol, p < 0.001; 1264 v 476 nmol, p < 0.001, respectively). This was accompanied by a decline in AT activity (59.8 v 50.1, p = 0.001). After platelet and cryoprecipitate transfusion, at the case conclusion AT activity had recovered marginally (59.8 v 55.4, p = 0.042), but thrombin generation remained reduced. CONCLUSIONS: In pediatric patients <10 kg undergoing cardiac surgery with CPB, thrombin generation and AT activity decline and do not recover completely after transfusion of platelets and cryoprecipitate.

Estrogen signaling impacts temporomandibular joint and periodontal disease pathology.

Women experience a higher incidence of oral diseases including periodontal diseases and temporomandibular joint disease (TMD) implicating the role of estrogen signaling in disease pathology. Fluctuating levels of estrogen during childbearing age potentiates facial pain, high estrogen levels during pregnancy promote gingivitis, and low levels of estrogen during menopause predisposes the TMJ to degeneration and increases alveolar bone loss. In this review, an overview of estrogen signaling pathways in vitro and in vivo that regulate pregnancy-related gingivitis, TMJ homeostasis, and alveolar bone remodeling is provided. Deciphering the specific estrogen signaling pathways for individual oral diseases is crucial for potential new drug therapies to promote and maintain healthy tissue.

Implementation of an intraoperative blood transport and storage initiative and its effect on reducing red blood cell and plasma waste.

BACKGROUND: The national waste rate for hospital-issued blood products ranges from 0% to 6%, with operating room-responsible waste representing up to 70% of total hospital waste. A common reason for blood product waste is inadequate intraoperative storage. STUDY DESIGN AND METHODS: Our transfusion service database was used to quantify and categorize red blood cell (RBC) and fresh-frozen plasma (FFP) units issued for intraoperative transfusion that were wasted over a 27-month period. Two cohorts were created: 1) before implementation of a blood transport and storage initiative (BTSI)-RBC and plasma waste January 1, 2011-May 31, 2012; 2) after implementation of BTSI-RBC and plasma waste June 1, 2012, to March 31, 2013. The BTSI replaced existing storage coolers (8-hr coolant life span with temperature range of 1-10°C) with a cooler that had a coolant life span of 18 hours and a temperature range of 1 to 6°C and included an improved educational cooler placard and an alert mechanism in the electronic health record. Monthly median RBC and plasma waste and its associated cost were the primary outcomes. RESULTS: An intraoperative BTSI significantly reduced median monthly RBC (1.3% vs. 0.07%) and FFP (0.4% vs. 0%) waste and its associated institutional cost. The majority of blood product waste was due to an unacceptable temperature of unused returned blood products. CONCLUSION: An intraoperative BTSI significantly reduced median monthly RBC and FFP waste. The cost to implement this initiative was small, resulting in a significant estimated return on investment that may be reproducible in institutions other than ours.

Surfactant Interactions and Solvent Phase Solubility Modulate Small Molecule Release from Emulsion Electrospun Fibers.

Emulsion electrospinning provides a tunable system for the development of porous scaffolds for controlled, localized drug delivery in tissue engineering applications. This study aimed to elucidate the role of model drug interactions with emulsion chemistry on loading and release rates from fibers with controlled fiber diameter and fiber volume fraction. Nile Red and Rhodamine B were used as model drugs and encapsulation efficiency and release rates were determined from poly(caprolactone) (PCL) electrospun fibers spun either with no surfactant (Span 80), surfactant, or water-in-oil emulsions. Drug loading efficiency and release rates were modulated by both surfactant and aqueous internal phase in the emulsions as a function of drug molecule hydrophobicity. Overall, these results demonstrate the role of intermolecular interactions and drug phase solubility on the release from emulsion electrospun fibers and highlight the need to independently control these parameters when designing fibers for use as tunable drug delivery systems.

Surfactant location and internal phase volume fraction dictate emulsion electrospun fiber morphology and modulate drug release and cell response.

Emulsion electrospinning is a versatile technique used to create fibrous meshes for applications in drug delivery and tissue engineering. In this study, the effects of surfactant and increasing internal phase volume fraction on emulsion electrospun fiber morphology were investigated. The fiber diameter, surface topography, internal architecture, mesh hydrophobicity, and fiber volume fraction were all characterized and the resulting effects on model drug release and cell response were determined. Surfactant relocation to the fiber surface resulted in alterations to fiber surface topography and internal morphology, increased rate of water adsorption into the mesh, and reduced burst effects of drug release. Increasing the internal phase volume fraction within the emulsion resulted in minimal change to fiber diameter, surface morphology, fiber volume fraction, and rate of water adsorption illustrating the ability to increase drug loading without affecting fiber properties. Lastly, all meshes promoted cell adhesion and good viability with a trend of increased MTT absorbance from cells on the surfactant and emulsion fibers possibly suggesting that an increase in surface area via smaller fiber diameter and fiber volume fraction increases metabolic activity. Overall, these studies indicate that fiber morphology and mesh hydrophobicity can be tuned by controlling surfactant location within fibers and internal phase volume fraction. Modulating fiber properties within the emulsion electrospun mesh is important to achieve controlled drug release and cell response for tissue engineering applications.

Total Red Blood Cell Transfusions for Chronic Hemodialysis Patients in a Single Center, 2009-2013.

BACKGROUND: Anemia management in chronic hemodialysis (HD) has been affected by the implementation of the prospective payment system (PPS) and changes in clinical guidelines. These factors could impact red blood cell (RBC) transfusion in HD patients. Our distinctive care system contains complete records for all RBC transfusions among our HD patients. AIMS: To determine RBC transfusions in patients with prevalent chronic HD, site of administration (inpatient or outpatient), and ordering physician specialty for inpatients; compare pre- and post-PPS RBC transfusions; and compare RBC transfusions during changes in desired outpatient hemoglobin (Hb) range for patients with chronic HD. METHODS: Retrospective analysis of medical and blood bank records for patients with prevalent chronic HD July 2009 through June 2013. RESULTS: In total, 310-356 patients were studied. Mean (SD) units of RBCs per 100 patients per month for the study's 48 months were outpatient, 2.6 (1.5), and inpatient, 9.4 (4.6). Outpatient pre-PPS RBC units transfused were 2.1 (0.6) vs. post-PPS of 2.6 (1.5; p = 0.22, t test); for inpatients pre-PPS, 7.9 (4.5) RBC units per month vs. post-PPS, 11.5 (5.1; p = 0.11, t test). Inpatient RBC transfusions accounted for 75.2% (14.2%) of all RBC transfusions; 67.3% (16.3%) of inpatient transfusions were ordered by nonnephrologists. Changes in desired Hb range for outpatient HD patients did not lead to changes in RBC transfusions. CONCLUSIONS: No changes in RBC transfusions occurred among our patients with chronic HD with PPS implementation and in desired Hb range during the study period. Most transfusions were given in inpatient settings by nonnephrologists.

Ideal hemoglobin transfusion target for resuscitation of massive-transfusion patients.

BACKGROUND: Overtransfusion of packed red blood cells is known to increase the risk of death in stable patients. With the delineation of minimum transfusion ratios in hemorrhaging patients complete, attention must be turned to the other end of the massive transfusion spectrum-that of defining the maximum transfusion of packed red blood cells. We aimed to define the ideal hemoglobin range 24 hours after anatomic hemostasis associated with the lowest mortality. METHODS: Massive-transfusion patients (≥10 units packed red blood cells within 24 hours) were reviewed from 2010-2013. The hemoglobin 24 ± 6 hours after anatomic hemostasis was used to stratify patients into undertransfusion (<8.0 g/dL), hemoglobin transfusion target (8.0-11.9 g/dL), and overtransfusion (>12.0 g/dL) groups; patients not surviving to 24 hours were excluded. RESULTS: We identified 418 patients (351 [84%] in the hemoglobin transfusion target group, 38 [9%] in the undertransfusion group, and 29 [7%] in the overtransfusion group) with an overall mortality of 18%. Undertransfusion patients had the greatest risk of death (odds ratio 3.3; 95% confidence interval 1.6-6.7) followed by overtransfusion patients (odds ratio 2.5; 95% confidence interval 1.1-5.6). Though pretransfusion hemoglobin was similar (9.5 ± 2.2 g/dL vs 9.5 ± 2.3 g/dL), overtransfusion patients had greater hemoglobin values during massive transfusion (8.3 ± 3.0 g/dL vs 6.9 ± 1.4 g/dL), persisting until hospital dismissal/death (11.4 ± 2.3 g/dL vs 9.6 ± 1.1 g/dL). In total, 657.4 excess packed red blood cell units were transfused (1.9 ± 1.5 per patient). CONCLUSION: Overtransfusion patients had increased mortality, comparable to undertransfusion patients, despite younger age and fewer comorbidities. Shorter massive transfusion durations foster a scenario in which patients are at greater risk of overtransfusion.

Emergency use of prethawed Group A plasma in trauma patients.

BACKGROUND: Massive transfusion protocols lead to increased use of the rare universal plasma donor, Type AB, potentially limiting supply. Owing to safety data, with a goal of avoiding shortages, our blood bank exploited Group A rather than AB for all emergency release plasma transfusions. We hypothesized that ABO-incompatible plasma transfusions had mortality similar to ABO-compatible transfusions. METHODS: Review of all trauma patients receiving emergency release plasma (Group A) from 2008 to 2011 was performed. ABO compatibility was determined post hoc. Deaths before blood typing were eliminated. p < 0.05 was considered statistically significant. RESULTS: Of the 254 patients, 35 (14%) received ABO-incompatible and 219 (86%) received ABO-compatible transfusions. There was no difference in age (56 years vs. 59 years), sex (63% vs. 63% male), Injury Severity Score (ISS) (25 vs. 22), or time spent in the trauma bay (24 vs. 26.5 minutes). Median blood product units transfused were similar: emergency release plasma (2 vs. 2), total plasma at 24 hours (6 vs. 4), total red blood cells at 24 hours (5 vs. 4), plasma-red blood cells at 24 hours (1.3:1 vs. 1.1:1), and plasma deficits at 24 hours (2 vs. 1). Overall complications were similar (43% vs. 35%) as were rates of possible transfusion-related acute lung injury (2.9% vs. 1.8%), acute lung injury (3.7% vs. 2.5%), adult respiratory distress syndrome (2.9% vs. 1.8%), deep venous thrombosis (2.9% vs. 4.1%), pulmonary embolism (5.8% vs. 7.3%), and death (20% vs. 22%). Ventilator (6 vs. 3), intensive care unit (4 vs. 3), and hospital days (9 vs. 7) were similar. There were no hemolytic reactions. Mortality was significantly lower in [corrected] the patients that [corrected] received incompatible plasma during [corrected] if concurrent with a massive transfusion (8% vs. 40%, p = 0.044). Group AB plasma use was decreased by 96.6%. CONCLUSION: Use of Group A for emergency release plasma resulted in ABO-incompatible transfusions; however, this had little effect on clinical outcomes. Blood banks reticent to adopt massive transfusion protocols owing to supply concerns may safely use plasma Group A, expanding the pool of emergency release plasma donors. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

Computerized bar code-based blood identification systems and near-miss transfusion episodes and transfusion errors.

OBJECTIVE: To determine whether the use of a computerized bar code-based blood identification system resulted in a reduction in transfusion errors or near-miss transfusion episodes. PATIENTS AND METHODS: Our institution instituted a computerized bar code-based blood identification system in October 2006. After institutional review board approval, we performed a retrospective study of transfusion errors from January 1, 2002, through December 31, 2005, and from January 1, 2007, through December 31, 2010. RESULTS: A total of 388,837 U were transfused during the 2002-2005 period. There were 6 misidentification episodes of a blood product being transfused to the wrong patient during that period (incidence of 1 in 64,806 U or 1.5 per 100,000 transfusions; 95% CI, 0.6-3.3 per 100,000 transfusions). There was 1 reported near-miss transfusion episode (incidence of 0.3 per 100,000 transfusions; 95% CI, <0.1-1.4 per 100,000 transfusions). A total of 304,136 U were transfused during the 2007-2010 period. There was 1 misidentification episode of a blood product transfused to the wrong patient during that period when the blood bag and patient's armband were scanned after starting to transfuse the unit (incidence of 1 in 304,136 U or 0.3 per 100,000 transfusions; 95% CI, <0.1-1.8 per 100,000 transfusions; P=.14). There were 34 reported near-miss transfusion errors (incidence of 11.2 per 100,000 transfusions; 95% CI, 7.7-15.6 per 100,000 transfusions; P<.001). CONCLUSION: Institution of a computerized bar code-based blood identification system was associated with a large increase in discovered near-miss events.