Evaluation of hemostatic capacities among commando candidates: Would their blood suit a hemorrhagic war-injured patient in case of blood donation on the battlefield?

BACKGROUND: In case of a warm fresh whole blood transfusion on the battlefield, the blood donation usually occurs just after a combat phase and often after several days on the fields. To explore the hemostatic capacity of such blood, we analyzed the blood of volunteers attending the commando course of the French Navy, considering this course as an experimental model, placing them into the same physiological conditions as those faced by deployed fighters. METHODS: Venous blood was collected at the beginning of the course, mimicking their baseline status, and a second time 6 weeks later, from the remaining candidates, during the actual commando training, mimicking the stress conditions. For each candidate, we observed the differences between the two blood samples. RESULTS: Of the 112 men that attended the first day of the course, only 17 remained 6 weeks later. In the second blood samples, we noted significant increased leucocytes and platelets counts and significant decreased hematocrit and hemoglobin levels. Thrombin generation assays showed significantly lower normalized peak heights (-31%), lower normalized endogenous thrombin potential values (-29%), and lower velocity index (-35%). Normalized lag time and time to peak did not differ. Viscoelastometric testing revealed a significant increasing in clot firmness as assessed by maximum amplitude and amplitude at 6 minutes. The clot speed was significantly increased. CONCLUSION: This work brings new data on coagulation during prolonged and considerable physical exercise. No obvious deleterious modification of hemostatic properties was observed. The decrease of the endogenous thrombin potentials may reflect a better ability to control the thrombin generation once started. Altogether, these results suggest that this blood could suit well a hemorrhagic war-injured patient. LEVEL OF EVIDENCE: Prospective observational cohort study, Level III.

The Utility of Preoperative Labs in Predicting Postoperative Complications Following Primary Total Hip and Knee Arthroplasty.

BACKGROUND: Preoperative testing costs billions of dollars despite little evidence supporting its utility. The purpose of this study was to determine the relationship between abnormal preoperative laboratory tests and postoperative complications following total joint arthroplasty. METHODS: The NSQIP database was used to identify 45,936 primary total hip arthroplasty (THA) and 76,041 pri-mary total knee arthroplasty (TKA) cases performed between 2006 and 2013. Complications within 30 days of surgery were collected and multivariable regression modeling was performed incorporating all significant laboratory values as well as demographics and preoperative comorbidities. RESULTS: For THA patients, abnormal sodium (p = 0.016, OR = 1.89), white count (p = 0.043, OR = 1.73), and partial thromboplastin time (p = 0.028, OR = 1.43) were significantly associated with complications. For TKA patients, abnormal alkaline phosphatase (p = 0.04, OR = 2.12), creatinine (p = 0.003, OR = 1.56), and INR (p = 0.008, OR = 1.99) were significantly predictive of complications. CONCLUSION: Of the 13 laboratory values, only six were significantly associated with complications. These findings may have implications for risk stratification in the inpatient setting.

Investigation of pathological haemorrhage in Maine Coon cats.

OBJECTIVE: Afibrinogenaemic haemorrhage was previously reported in a Maine Coon cat. Two littermates subsequently died from surgical non-haemostasis, suggesting a hereditable coagulopathy. METHODS: We prospectively recruited cats which were: a) Maine Coons with pathological haemorrhage (group 1, n=8), b) healthy familial relatives of group 1 (group 2, n=13) and c) healthy Maine Coons unrelated to groups 1 and 2 (group 3, n=12). Coagulation tests: prothrombin time, activated partial thromboplastin time and thrombin clotting time (TCT) were performed on citrated plasma along with quantification of fibrinogen. Routine haematological examination was performed on EDTA-anticoagulated blood collected contemporaneously. RESULTS: Thirty-three blood samples were analysed. Fibrinogen concentrations were significantly reduced in groups 1 (P<0.01) and 2 (P<0.01) compared with group 3. Similarly, TCT was found to be significantly extended in group 1 (P<0.01) and group 2 (P=0.02) with respect to group 3. CONCLUSIONS: Dysfibrinogenaemia was identified in clinical cases and their healthy relatives, suggesting that this may represent a hereditary condition of Maine Coon cats. Clinicians should be aware of the increased potential for non-haemostasis in this cat breed and consider assessing clotting function before (elective) surgery.

A randomised controlled trial of fibrinogen concentrate during scoliosis surgery.

Bleeding and blood transfusion are common after scoliosis surgery. Fibrinogen is essential for blood clot formation and depletes quickly during haemorrhage. We randomly allocated 102 children 12-18 years old having surgery for idiopathic scoliosis, 51 to intra-operative fibrinogen concentrate 30 mg.kg-1 (maximum 2 g) and 51 to saline placebo. Fibrinogen reduced peri-operative blood loss by a median (95%CI) volume of 155 (5-320) ml, from a median (IQR [range]) of 1035 (818-1420 [400-3030]) ml to 885 (755-1155 [270-2645]) ml, p = 0.04. Seven and four children received allogeneic red blood cell transfusion after fibrinogen and placebo, respectively, p = 0.34. There were no side-effects.

Simple Laboratory Test Utilization Interventions to Reduce Inappropriate Specialty Coagulation Testing.

OBJECTIVES: The naming convention in coagulation may cause confusion in electronic ordering systems, leading to inappropriate test orders. We implemented test utilization efforts and studied utilization before and after interventions for two specialty coagulation assays. METHODS: Two interventions were implemented: test names were changed from factor assay to activity, and residents reviewed all factor V and X requests. A retrospective review of factor V and X activity orders was performed for the period 1 year before and after interventions. RESULTS: After interventions, factor V and X activity orders decreased by approximately 40%. Resulted tests decreased by 53.8% and 47.8%, corresponding to reductions of $2,493.05 and $1,867.80 per year in laboratory charges for factor V and factor X activity, respectively. Abnormal factor V activity results increased from 45% to 59%. Factor V activity orders from outpatient clinics decreased by 21.6%. CONCLUSIONS: Simple interventions can reduce inappropriate specialty coagulation test orders and unnecessary costs.

Intra- and inter- individual rivaroxaban concentrations and potential bleeding risk in patients with atrial fibrillation.

BACKGROUND: Routine laboratory monitoring of rivaroxaban and dose adjustment relating to exposure is currently not recommended. However, in certain clinical situations, assessment of rivaroxaban levels is desirable. OBJECTIVES: To examine inter- and intra-subject plasma rivaroxaban variability in patients with atrial fibrillation (AF) and to correlate these results to clinical outcomes. PATIENTS/METHODS: We included 60 patients with AF treated with rivaroxaban: half on 20 mg daily (R20) and half on 15 mg daily (R15). Three trough and peak blood samples were collected with an interval of 6-8 weeks apart. Plasma rivaroxaban concentration was measured directly by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) and indirectly by anti-Xa for rivaroxaban, prothrombin time (PT), and activated partial thromboplastin time (APTT). RESULTS: Patients on R15 were older (76 ± 6 vs 71 ± 6 years), had lower creatinine clearance (60 ± 26 vs 99 ± 32 mL/min), higher CHADS2 (2.5 ± 1.2 vs 1.8 ± 1.3), all p < 0.01, but had similar rivaroxaban concentrations in trough samples to patients on R20. There was no significant intra-individual variability for trough or peak rivaroxaban concentration assessed by LC-MS/MS, anti-Xa, or PT. Trough rivaroxaban levels determined by LC-MS/MS (48 ± 30 vs 34 ± 26, p = 0.02) and anti-Xa, but not with PT and APTT, were higher in patients with bleeding than in patients without it. CONCLUSIONS: There is a pronounced inter-, but not intra-individual variability in the rivaroxaban trough levels in patients with AF. Assessment of trough rivaroxaban concentration with LC-MS/MS or anti-Xa, but not with APTT or PT, may help to identify patients at increased risk of bleeding.

Mechanical thromboprophylaxis would suffice after total knee arthroplasties in Asian patients?

PURPOSE: Our prospective study evaluated the incidence and location of deep vein thrombosis (DVT), the risk factors for PE and the natural history of DVT after TKA in patients who have received only mechanical compression device without having any chemical thromboprophylaxis or therapeutic treatment. METHODS: We studied 408 consecutive patients (691 knees) who underwent primary TKA; 283 patients had one-stage bilateral TKAs and 125 had unilateral TKAs. Coagulation assays, the full blood count and blood typing tests, and serum chemical profiles were undertaken in all patients on three separate occasions. Molecular genetic testing was performed preoperatively to detect the genetic traits involving DVT. Bilateral simultaneous or unilateral venograms were carried out at 6 or 7 days after operation. Perfusion lung scanning was undertaken before and at 7 or 8 days after operation. RESULTS: In the 691 venograms in 408 patients, only 4 knees (0.6%) were positive for fresh thrombi. In the 4 knees with DVT, thrombi were located in the calf veins. We observed factor V Leiden mutation, antithrombin-III level, and prothrombin promoter G20210A mutation were absent in all patients. We saw no relationship between DVT and coagulation or thrombophilic data. No pulmonary embolism (PE) occurred as shown by negative perfusion lung scan and absence of symptoms. CONCLUSION: We concluded that the combinations of absent thrombophilic polymorphisms with low clinical prothrombotic risk factors led to low prevalence of DVT and virtually absent PE after TKA in the current series of patients, who had received mechanical compression device only without chemical thromboprophylaxis.

FIBTEM as a predictor of intra- and postoperative blood loss in revision total hip arthroplasty: A prospective observational study.

Revision total hip arthroplasty (THA) may cause intra- and postoperative massive bleeding. This prospective observational study evaluated if the maximum clot firmness of FIBTEM (MCFFIB) could act as a predictor of perioperative massive bleeding in revision THA.Fifty-eight adult patients undergoing revision THA were included. Pre- and postoperative MCFFIB, hematological and hemostatic laboratory data, as well as the amount of intra- and postoperative blood loss (IBL and PBL) were obtained.The change rate (MCFFIB-C) between the pre- and postoperative MCFFIB had a significant correlation with IBL (ρ = 0.431, P = .001). Moreover, PBL had a significant correlation with MCFFIB-C (ρ = 0.292, P = .026). The MCFFIB-C cut-off value of ≥ 29% showed the highest sensitivity and specificity for predicting IBL ≥ 1000 mL or PBL ≥500 mL. The incidence of red blood cell transfusion in the postoperative period was higher in patients showing MCFFIB-C ≥ 29% (34% vs 8%, P = .015).The change rate between pre- and postoperative MCFFIB values was correlated well with the amount of IBL or PBL. Moreover, particular change rate of MCFFIB could predict massive bleeding in revision THA.

In vitro investigation of the effects of exogenous sugammadex on coagulation in orthopedic surgical patients.

BACKGROUND: Previous studies have shown that sugammadex resulted in the prolongation of prothrombin time and activated partial thromboplastin time. In this study, we aimed to investigate the in vitro effects of exogenous sugammadex on the coagulation variables of whole blood in healthy patients who underwent orthopedic surgery. METHODS: The effects of sugammadex on coagulations were assessed using thromboelastography (TEG) in kaolin-activated citrated blood samples taken from 14 healthy patients who underwent orthopedic surgery. The in vitro effects of three different concentrations of sugammadex (42, 193, and 301 µg mL- 1) on the TEG profiles were compared with those of the control (0 µg mL- 1). Previous studies indicated that these exogenous concentrations correspond to the approximate maximum plasma concentrations achieved after the administration of 4, 16, and 32 mg kg- 1 sugammadex to healthy subjects. RESULTS: Increased sugammadex concentrations were significantly associated with reduced coagulation, as evidenced by increases in reaction time (r), coagulation time, and time to maximum rate of thrombus generation (TMRTG), and decreases in the angle, maximum amplitude, and maximum rate of thrombus generation. Compared with the control, the median percentage change (interquartile range) in the TEG values of the samples treated with the highest exogenous sugammadex concentration was the greatest for r, 53% (26, 67.3%), and TMRTG, 48% (26, 59%). CONCLUSIONS: This in vitro study suggests that supratherapeutic doses of exogenous sugammadex might be associated with moderate hypocoagulation in the whole blood of healthy subjects. TRIAL REGISTRATION: identifier:  UMIN000029081 , registered 11 September 2017.

Level of agreement between laboratory and point-of-care prothrombin time in patients after stopping or continuation of acenocoumarol anticoagulation: A comparison of diagnostic accuracy.

BACKGROUND: Procedures requiring optimisation of the coagulation status of patients using vitamin K antagonists are frequently postponed due to the late availability of laboratory international normalised ratio (INR) test results. A point-of-care (POC) alternative may facilitate early decision-making in peri-operative patients. OBJECTIVES: To assess the level of agreement between the POC-INR and the laboratory INR in patients who continue or stop vitamin K antagonists to determine whether the POC test may be a good alternative to the laboratory INR. DESIGN: Study of diagnostic accuracy. SETTING: Single-centre study at Zaans Medical Centre, The Netherlands. PATIENTS: Included patients were scheduled for cardioversion (these continued taking vitamin K antagonists), or a surgical procedure (these stopped taking vitamin K antagonists). MAIN OUTCOME MEASURES: The level of agreement and clinical acceptability of the laboratory and POC-INR results, evaluated by Bland-Altman analysis and error grid analysis. RESULTS: The surgical and cardioversion groups consisted of 47 and 46 patients, respectively. The bias in the INR in the surgical group was -0.12 ±â€Š0.09 with limits of agreement of -0.29 to 0.05, whereas the cardioversion group showed a bias in the INR of -0.22 ±â€Š0.36 with limits of agreement from -0.93 to 0.48. The percentage errors between methods in the surgical and cardioversion groups were 16 and 21%, respectively. Error grid analysis showed that the diagnostic accuracy of the POC prothrombin time is clinically acceptable as the difference did not lead to a different clinical decision in the surgical group with INR values less than 1.8. CONCLUSION: The current study shows a good level of agreement and clinical accuracy between the laboratory and POC-INR in patients who stopped anticoagulation intake for surgery. However, in patients who continued their anticoagulation therapy, the agreement between the two methods was less accurate.

Eficacia de la vitamina K en los trastornos de coagulación en los pacientes con enfermedad hepática crónica / Efficacy of vitamin K in coagulation disorders in patients with chronic liver disease

La coagulopatía es el denominador común en la amplia gama de procesos hepático crónicos, efecto principal de la deficiencia de vitamina K. A pesar de la falta de evidencia que sostiene su eficacia, su administración representa una parte del manejo de muchos pacientes con coagulopatía. Por tanto, el objetivo primario de este estudio fue comparar los tiempos de coagulación tras la administración de vitamina K en pacientes con enfermedad hepática crónica y trastornos de coagulación. Se postularon como secundarios la caracterización del paciente hepatópata según grupo nosológico por edad y sexo, así como las diferencias existentes entre las pruebas de coagulación basales con respecto a cada grupo. 72 pacientes fueron reclutados en 4 grupos, grupo 1: hepatitis B inactiva (n=6), grupo 2: hepatitis B crónica-hepatitis C (n=14), grupo 3: cirrosis (n=35) y grupo 4: hepatocarcinoma (n=17), se administraron 3 dosis de vitamina K de 10 mg cada una a intervalos de 24 horas, se midieron tiempo de protrombina (TP), radio normalizado internacional (INR) y tiempo de tromboplastina parcial activado (TPT) basales y cada 24 horas después de cada dosis. Se logró establecer una diferencia estadísticamente significativa en la corrección del tiempo de protrombina (31.04±9.62 a 21.69±8.48 P˂0.0001) así como del INR (2.81±1.013 a 1.92±0.81, P˂0.0001), hubo diferencia en cuanto a grupo diagnóstico y edad de presentación, así como en cuanto a tiempos de coagulación basales según diagnóstico. Por tanto, se demostró la efectividad de la vitamina K en la corrección del TP e INR.(AU)

Coagulopathy is the common denominator in the wide range of chronic liver processes, the main effect of vitamin K deficiency. Despite the lack of evidence supporting its efficacy, its administration represents a part of the management of many patients with coagulopathy. Therefore, the primary objective of this study was to compare clotting times after vitamin K administration in patients with chronic liver disease and coagulation disorders. The characterization of the liver disease patient according to nosological group by age and sex, as well as the differences between the baseline coagulation tests with respect to each group, were postulated as secondary. 72 patients were recruited into 4 groups, group 1: inactive hepatitis B (n = 6), group 2: chronic hepatitis B-hepatitis C (n = 14), group 3: cirrhosis (n = 35) and group 4: hepatocarcinoma ( n = 17), 3 doses of vitamin K of 10 mg each were administered at 24-hour intervals, prothrombin time (TP), international normalized radius (INR) and baseline activated partial thromboplastin time (TPT) were measured and each 24 hours after each dose. It was possible to establish a statistically significant difference in the correction of prothrombin time (31.04 ± 9.62 to 21.69 ± 8.48 P˂0.0001) as well as the INR (2.81 ± 1.013 to 1.92 ± 0.81, P˂0.0001), there was a difference in terms of group Diagnosis and age of presentation, as well as baseline clotting times according to diagnosis. Therefore, the effectiveness of vitamin K in the correction of TP and INR was demonstrated

Overuse of preoperative laboratory coagulation testing and ABO blood typing: a French national study.

Background: Following publication of guidelines on routine preoperative tests, the French Society of Anaesthesiology and Intensive Care (SFAR), in association with French national public health insurance, conducted a survey to evaluate adherence to guidelines and the economic consequences. Methods: Using the French Hospital Discharge Database and National Health Insurance Information system, tests performed during the 30 days before surgery were analysed for two situations: (1) standard laboratory coagulation tests and ABO blood typing in children able to walk and scheduled for tonsillectomy/adenoidectomy; and (2) ABO blood typing in adults before laparoscopic cholecystectomy, thyroidectomy, lumbar discectomy or breast surgery. Guidelines do not recommend any preoperative tests in these settings. Results: Between 2013 and 2015, a coagulation test was performed in 49% of the 241 017 children who underwent tonsillectomy and 39% of the 133 790 children who underwent adenoidectomy. A similar pattern was observed for ABO blood typing although re-operation rates for bleeding on the first postoperative day were very low (0.12-0.31% for tonsillectomy and 0.01-0.02% for adenoidectomy). Between 2012 and 2015, ABO blood typing was performed in 32-45% of the 1 114 082 patients who underwent one of the four selected procedures. The transfusion rate was very low (0.02-0.31%). The mean cost for the four procedures over the 4 yr period was €5 310 000 (sd €325 000). Conclusions: Standard laboratory coagulation tests and ABO blood typing are still routinely prescribed before surgery and anaesthesia despite current guidelines. This over-prescription represents a high and unnecessary cost, and should therefore be addressed.

Comparison of the ecarin chromogenic assay and diluted thrombin time for quantification of dabigatran concentrations.

Essentials Routine monitoring is unnecessary but measuring dabigatran levels is helpful in certain situations. We compared ecarin chromogenic assay (STA-ECA-II) and dilute thrombin time (dTT) in patient samples. Both tests provided accurate measurements over a wide range of dabigatran concentrations. Adoption of STA-ECA-II and dTT into routine clinical practice will improve patient care. SUMMARY: Background Although routine coagulation monitoring is unnecessary, measuring plasma dabigatran concentrations can be useful for detecting drug accumulation in renal failure or overdose, assessing the contribution of dabigatran to serious bleeding, planning the timing of urgent surgery or intervention, or determining the suitability for thrombolytic therapy for acute ischemic stroke. Dabigatran concentrations can be quantified using chromogenic or clot-based tests, such as the ecarin chromogenic assay (ECA) and the diluted thrombin time (dTT), respectively. Objective The purpose of this study was to compare the results of these assays with dabigatran concentrations measured by the reference standard of mass spectrometry in samples from 50 dabigatran-treated patients collected at peak and trough after at least 4 months of drug intake. Methods Drug levels measured with either the STA Ecarin Chromogenic Assay-II (STA-ECA-II) or dTT were linearly correlated with those determined by mass spectrometry over a wide range of concentrations. Results and Conclusions For detection of levels below 50 ng mL-1 both tests have specificities of at least 96%, suggesting that they accurately detect even low levels of drug. Therefore, regardless of whether a chromogenic or clot-based platform is preferred, the STA-ECA-II and dTT are useful tests for measuring dabigatran concentrations. Unfortunately, neither test is licensed by the United States Food and Drug Administration. Although approved in other jurisdictions, the dTT and STA-ECA-II are not widely or rapidly available in most hospitals. Therefore, cooperation between regulators and hospitals is urgently needed to render these tests readily available to inform patient care.

Patterns and Appropriateness of Thrombophilia Testing in an Academic Medical Center.

BACKGROUND: Clinical guidelines recommend against routine use of thrombophilia testing in patients with acute thromboembolism. Thrombophilia testing rarely changes acute management of a thrombotic event. OBJECTIVE: To determine appropriateness of thrombophilia testing in a teaching hospital. DESIGN: Retrospective cohort study. SETTING: One academic medical center in Utah. PARTICIPANTS: All patients who received thrombophilia testing between July 1, 2014, and December 31, 2014. MAIN MEASUREMENTS: Proportion of thrombophilia tests occurring in situations associated with minimal clinical utility, defined as tests meeting at least 1 of the following criteria: discharged before results available; test type not recommended; testing in situations associated with decreased accuracy; duplicate testing; and testing following a provoked thrombotic event. RESULTS: Overall, 163 patients received a total of 1451 thrombophilia tests for stroke (50% of tests; 35% of patients), venous thromboembolism (21% of tests; 21% of patients), and pregnancy-related conditions (15% of tests; 25% of patients). Of the 39 different test types performed, the most common were cardiolipin IgG and IgM antibodies (9% each), lupus anticoagulant (9%), and ß2-glycoprotein 1 IgG and IgM antibodies (8% each). In total, 911 tests (63%) were performed in situations associated with minimal clinical utility, with 126 patients (77%) receiving at least one such test. Only 2 patients (1%) had clear documentation of being offered genetic consultation. CONCLUSIONS: Thrombophilia testing in this single-center study was often associated with minimal clinical utility. Strategies to improve testing practices (eg, hematology specialty consult prior to inpatient testing, improved order panels) might help minimize inappropriate testing and promote value-driven care.

[Reducing the number of orders for coagulation tests in the standard emergency department blood work-up]. / Reducción de la determinación de coagulación en las pruebas analíticas básicas en los servicios de urgencias.

OBJECTIVES: To evaluate the usefulness of a clinical protocol developed to reduce the number of orders for coagulation tests. MATERIAL AND METHODS: Quasi-experimental study with historical controls. We retrospectively included all patients whose records showed that a coagulation test had been ordered in the emergency department. We analyzed the number of tests ordered under the protocol and the number ordered during the period of standard practice. RESULTS: Orders for coagulation tests were given for 657 patients (77.2%) when physicians followed standard practices and for 448 (55.5%) when they followed the protocol (P <.001). Unnecessary tests numbered 431 (65.6%) and 227 (50.6%) in the standard-practice and protocol periods, respectively (P <.002). One patient (0.15% [95% CI, 0.004%-0.8%]) had significantly altered coagulation (international normalized ratio, 1.8), but none (0% [95% CI, 0%-0.6%]) required treatment and no treatment plans were changed based on a finding of unexpected coagulation disorder. CONCLUSION: The protocol to guide the ordering of coagulation tests has managed to reduce unnecessary tests and thus improve management of this health service resource.

OBJETIVO: Valorar el impacto de un protocolo de solicitud de coagulación para reducir determinaciones innecesarias. METODO: Estudio cuasiexperimental con control histórico. La selección de pacientes se realizó de forma retrospectiva. Se incluyeron de forma consecutiva todos los pacientes a los que se les realizó una analítica urgente. Se analizó la solicitud estándar frente a la aplicación del protocolo. RESULTADOS: En el grupo estándar se determinaron 657 coagulaciones (77,2%) y en el grupo protocolo 448 (55,5%) (p < 0,001), y fueron innecesarias 431 (65,6%) y 227 (50,6%) (p < 0,002), respectivamente. Un paciente [0,15% (IC 95%: 0,004-0,8)] mostró alteración de la coagulación significativa (INR 1,8), pero ninguno [0% (IC 95%,0-0,6)] requirió intervención terapéutica o cambio de plan clínico basado en la detección de una coagulopatía inesperada. CONCLUSIONES: La aplicación de un protocolo ha conseguido la reducción del número estudios de coagulación innecesarios con la consiguiente mejora en la gestión de este recurso.

Utility of Sonoclot in Prediction of Postoperative Bleeding in Pediatric Patients Undergoing Cardiac Surgery for Congenital Cyanotic Heart Disease: A Prospective Observational Study.

OBJECTIVES: To assess the utility of Sonoclot in prediction of postoperative bleeding in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass for congenital cyanotic heart disease. DESIGN: Prospective, observational study. SETTING: Single university hospital. PARTICIPANTS: Eighty-seven pediatric patients undergoing cardiac surgery for congenital cyanotic heart disease. INTERVENTIONS: Laboratory coagulation parameters (prothrombin time, international normalization ratio, activated partial thromboplastin time, fibrinogen, D-dimer) as well as point-of-care Sonoclot glass bead activation time, clot rate, and platelet function (gbPF) were done before induction of anesthesia and following heparin reversal after termination of cardiopulmonary bypass (CPB) in all patients. MEASUREMENTS AND MAIN RESULTS: Postoperative blood loss was monitored by the amount of chest tube drainage. The primary outcome was to define Sonoclot parameters for prediction of postoperative bleeding. Secondary outcomes studied were amount of postoperative blood loss, transfusion requirement of various blood products, incidence of surgical re-exploration, duration of postoperative mechanical ventilation, intensive care unit and hospital stay. Among studied subjects, 37.9% (33 of 87 patients) were designated as bleeders while 62.1% (54 of 87 patients) were non-bleeders. Lower age, D-dimer, and gbPF test after termination of CPB following heparin neutralization were predictive for postoperative bleeders. Among these, post-protamine gbPF had the highest area under the curve (0.725), 95% confidence interval (0.619-0.831) for prediction of postoperative bleeders. Duration of mechanical ventilation (26.41±36.44 v 8.25±6.36 h, respectively, p = 0.001), intensive care unit stay (7.36 ± 4.05 v 4.96 ± 2.49, p = 0.001), and hospital stay (11.69±4.82 v 8.63±3.48 p = 0.001) were higher in bleeders; however, incidence of re-exploration was comparable between both groups. CONCLUSION: Postoperative bleeders may be predicted independently by post-CPB gbPF, postoperative D-dimer, and lower age of patients. Among these, post-CPB gbPF has maximum predictive value.

Equiosmolar Solutions of Hypertonic Saline and Mannitol Do Not Impair Blood Coagulation During Elective Intracranial Surgery.

BACKGROUND: The authors investigated the effect of equiosmolar, equivolemic solutions of 3% hypertonic saline (HS) and 20% mannitol on blood coagulation assessed by rotational thromboelastometry (ROTEM) and standard coagulation tests during elective craniotomy. METHODS: In a prospective, randomized, double-blind trial, 40 patients undergoing elective craniotomy were randomized to receive 5 mL/kg of either 20% mannitol or 3% HS for intraoperative brain relaxation. Fibrinogen, activated partial thromboplastin time, prothrombin time, hemoglobin, hematocrit, and platelet count were simultaneously measured intraoperatively with ROTEM for EXTEM, INTEM, and FIBTEM analysis. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. RESULTS: No significant differences between groups were found in ROTEM variables CT, CFT, MCF, α-angle (EXTEM and INTEM), and MCF (FIBTEM) nor standard coagulation tests. ROTEM parameters did not show changes after administration of hyperosmolar solutions relating to basal values, except for an increase of CFT EXTEM (118±28 vs. 128±26 s) and decrease of CT INTEM (160±18 vs. 148±15 s) with values within normal range. Significant decreases from baseline levels were observed for hematocrit (-7%), platelet count (-10%), and fibrinogen (-13%) after HS infusion, and hematocrit (-9%), platelet count (-13%), and fibrinogen (-9%) after mannitol infusion, but remaining normal. CONCLUSIONS: The use of 5 mL/kg of equiosmolar solutions of 3% HS and 20% mannitol applied to reach a brain relaxation during elective craniotomy does not induce coagulation impairment as evidenced by ROTEM and standard coagulation tests.

Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study.

BACKGROUND AND AIMS: Several studies report the use of thromboelatography (TEG) to monitor coagulation in pediatric cardiac surgery. The aim of this study was to compare baseline and intraoperative TEG, TEG-functional fibrinogen, and standard coagulation assays in children with cyanotic and acyanotic congenital heart disease (CHD) undergoing cardiac surgery. METHODS: This is a prospective observational study of 63 children aged <24 months undergoing cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria included preoperative anticoagulant therapy and hepatic failure. We collected blood at anesthesia induction (T1), at lowest temperature after CPB start (T2), and after heparin neutralization (T3). Coagulation was evaluated by TEG (reaction time [R]), k, alpha-angle, maximum amplitude (MA), MA-fibrinogen (MA-fib), and by standard coagulation assays (prothrombin time, activated partial thromboplastin time, fibrinogen level, platelet [PLT] count). RESULTS: Sixty-three patients were enrolled (38 cyanotic and 25 acyanotic). Median age was 4 [IQR 2-6] months and median weight was 5 [IQR 3.7-6.5] kg. Most common surgeries were: ventricular septal defect repair (n = 13), Fallot correction (n = 11), and arterial switch operation (n = 10). Cyanotic and acyanotic children were well matched: R, k, MA, and MA-fib at T1, T2, and T3 were not significantly different between cyanotic and acyanotic children. At T2, significant correlations were showed between MA and PLT count (r = 0.4; P = 0.0008) and k and plasma fibrinogen level (r = -0.54; P < 0.0001). At T3, significant correlations were showed between MA and PLT count (r = 0.5; P < 0.0001), G and PLT count (r = 0.6; P < 0.0001), and MA-fib and plasma fibrinogen level (r = 0.5; P = 0.002). CONCLUSIONS: According to our findings, cyanosis does not affect TEG parameters in children with CHD. PLT count and plasma fibrinogen significantly correlated (are significantly associated) with MA and MA-fib respectively, suggesting that use of TEG after protamine administration may be prompted for improved hemostatic monitoring in the perioperative phase.

A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.

OBJECTIVE: This study investigated postoperative hemostasis of patients subjected to conventional protamine dosing compared with protamine dosing based on a pharmacokinetic (PK) model following cardiopulmonary bypass. DESIGN: Retrospective case-control study. SETTING: Tertiary university hospital. PARTICIPANTS: Patients undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: In 56 patients, protamine was dosed in a fixed ratio (CD), while 62 patients received protamine based on the PK model. MEASUREMENTS AND MAIN RESULTS: There was no difference in heparin administration (414±107 mg (CD) v 403±90 mg (PK); p = 0.54), whereas protamine dosing was considerably different with a protamine-to-heparin dosing ratio of 1.1±0.3 for the CD group and 0.5±0.1 for the PK group (p<0.001). The changes in activated coagulation time (ΔACT) values (ACT after protamine minus preoperative ACT;+17±77 s v+6±15 s; p = 0.31) were equal between groups. Yet, the thromboelastometric intrinsically activated coagulation test clotting time (CT; 250±76 s v 203±44 s; p<0.001) and intrinsically activated coagulation test without the heparin effect CT (275±105 v 198±32 s; p<0.001) were prolonged in the CD group. Median packed red blood cell transfusion (0 [0-2] v 0 [0-0]), fresh frozen plasma transfusion (1 [0-2] v 0 [0-0]), and platelet concentrate transfusion (0 [0-1] v 0 [0-0]) were different between the fixed ratio and PK group, respectively (all p<0.001). CONCLUSIONS: This study showed that patient-tailored protamine dosing based on a PK model was associated with a reduction in protamine dosing, with better hemostatic test results when compared with fixed-ratio protamine dosing.

Perioperative coagulation assessment of patients undergoing major elective orthopedic surgery.

Traditional coagulative parameters are of limited use in identifying perioperative coagulopathy occurring in patients undergoing major elective orthopedic surgery (MEOS). The aim of our study was to evaluate the coagulation changes in patients undergoing MEOS and to facilitate an early detection of perioperative coagulopathy in patients experiencing major intraoperative bleeding. We enrolled 40 consecutive patients (M/F 10/30, age range 34-90 years) who underwent MEOS at the Orthopedic Unit of the Padua University Hospital, Italy, between January 2014 and January 2015. Blood samples were obtained at the following time points: T0-pre: 30 min before surgery; T0-post: 30 min after the end of the procedure; T1: morning of the first postoperative day; T2: 7 ± 2 days after surgery. Patients who experienced an intraoperative blood loss ≥250 mL/h were considered as cases. Routine coagulative parameters, thromboelastometry and thrombin generation (TG) profiles were evaluated. At baseline, a significantly lower platelet count and FIBTEM MCF/AUC were observed in patents with excessive bleeding (p < 0.05 and 0.02/0.01, respectively). At T0-post and T1 intervals, cases showed hypocoagulation characterized by a significantly low platelet count (p = 0.001), prolonged CFT INTEM/EXTEM, reduction of alpha-angle and MaxV INTEM/EXTEM, MCF and AUC INTEM/EXTEM/FIBTEM (p < 0.05 in all comparisons). The only TG parameter standing out between study groups was time to peak at T0-pre. A low platelet count and fibrinogen activity were associated with significant intraoperative bleeding in patients undergoing MEOS. Thromboelastometry performed by ROTEM(®) identifies patients with coagulopathy.