The Rise and Fall of Antithrombin Supplementation in Cardiac Surgery.

Various cohort studies, both retrospective and prospective, showed that low antithrombin levels after cardiac surgery (at the arrival in the intensive care unit and during the next days) were associated with a number of adverse outcomes, including surgical reexploration and thromboembolic events, eventually leading to prolonged stay in the intensive care. Values lower than 58% to 64% of antithrombin activity were indicative of this higher morbidity with good sensitivity and specificity. The scenario generated the hypothesis that low antithrombin levels needed to be corrected by supplementation to improve postoperative outcome. However, randomized controlled studies run to test this idea failed to demonstrate any benefit of antithrombin supplementation, showing no effects on outcome, neither as preemptive preoperative strategy nor for treating postoperative low antithrombin values. In addition, randomized trials highlighted that those patients who received antithrombin experienced significantly higher incidence of acute kidney injury with a pooled odds ratio of 4.41 (95% CI, 1.90-10.23; P = .001). A strongly decreased thrombin activity after antithrombin correction may eventually affect the efficiency of the glomerular filtration and cause the deterioration of kidney function, but underlying biological mechanisms remain unclear. In conclusion, low levels of antithrombin activity after cardiac surgery should be considered as a marker of greater severity of the patient's conditions and/or of the complexity of the surgical procedure. There are no indications for antithrombin supplementation in cardiac surgery unless for correcting heparin resistance.

Clopidogrel Resistance and Ticagrelor Replacement in Dual Antiplatelet Therapy for Carotid Artery Stenting.

BACKGROUNDS: Resistance to the pharmacological effect of clopidogrel in patients undergoing dual antiplatelet therapy for carotid stenting may increase the risk of periprocedural neurological events. The purpose of the study was to describe the phenomenon of clopidogrel resistance in a series of patients undergoing carotid stenting. METHODS: Data of patients who consecutively underwent carotid stenting from November 2016 to December 2020 for a significant stenosis and who underwent a dual antiplatelet therapy using acetyl-salicylic acid and clopidogrel were prospectively collected. Patients who were already taking a different thienopyridine were excluded. The effectiveness of antiplatelet drugs was assessed by the impedance aggregometry test. Primary endpoint was to evaluate the incidence of clopidogrel resistance and the effectiveness of ticagrelor as alternative therapy. P values < 0.05 were considered statistically significant. RESULTS: Two-hundred patients (80 females, 40%) underwent stenting for carotid stenosis (94% asymptomatic). The phenomenon of clopidogrel resistance was observed in 38 patients (19%), in whom clopidogrel was replaced by ticagrelor (90 mg/bis in die) with 100% effectiveness at aggregometry test. Platelet counts was associated to clopidogrel resistance (P = 0.001). There was no stent thrombosis at 30 days, neither major hemorrhagic events; a total of 12/200 major adverse cardiovascular events occurred (6%), including 1 in the group of patients who took ticagrelor and 11 in group of patients under clopidogrel (2.6% versus 6.7%, P = 0.55). CONCLUSIONS: Clopidogrel was ineffective in 19% of patients undergoing carotid stenting. Platelet count seemed to affect this phenomenon. In these patients, clopidogrel was effectively replaced by ticagrelor.

Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients?

BACKGROUND: Postoperative use of platelet function testing to rule out microvascular bleeding due to platelet dysfunction after cardiac surgery still lacks strong reference data and reliable cutoff values, yielding a clinically adequate sensitivity and specificity. The present study aims to investigate the performance of two different point-of-care viscoelastic devices and platelet aggregometry in expressing surgery-dependent platelet dysfunction and anticipating postoperative major bleeding in a cohort of high-risk patients. METHODS: Prospective cohort study of 50 adult patients who were on antiplatelet drugs discontinued for no more than 7 days (clopidogrel and prasugrel) or 5 days (ticagrelor) undergoing cardiac surgery with cardiopulmonary bypass (CPB). Coagulation and platelet function testing, including QUANTRA, ROTEM, and Multiplate, were assessed preoperatively and postoperatively. Chest drain blood loss was measured in the first 12 postoperative hours. Perioperative bleeding was assessed using a modified version of the Universal Definition of Perioperative Bleeding (UDPB) in cardiac surgery, modified to not consider anemia-correcting packed red cells transfusions in the absence of bleeding >600 mL/12 h. Major bleeding was identified as UDPB class II or higher. RESULTS: Multiplate adenosine diphosphate (ADPtest) was significantly ( P = .001) reduced after CPB, whereas TRAPtest was not. The platelet component (PC) as extrapolated by ROTEM data (EXTEM MCF-FIBTEM MCF) was unchanged after CPB, while the A10 PC (PC at 10 minutes) was significantly ( P = .001) reduced. The QUANTRA platelet contribution to clot stiffness (PCS) was significantly ( P = .001) reduced, as well. At the ROC analysis for the predictive ability of the post-CPB platelet function testing, the best discrimination was obtained by the QUANTRA PCS, with an area under the curve (AUC) (95% confidence interval [CI]) of 0.80 (0.66-0.91), P = .001, followed by the ROTEM A10 PC with AUC (95% CI) of 0.75 (0.51-0.99), P = .004, and PC with AUC (95% CI) of 0.74 (0.50-0.99), P = .009. The Multiplate ADPtest had an AUC (95% CI) of 0.67 (0.42-0.91), and the TRAPtest had an AUC (95% CI) of 0.62 (0.37-0.86). The cutoff values identified were 13 hPa for the QUANTRA PCS, 40 mm for the ROTEM A10, and 48.5 mm for the ROTEM PC, with negative predictive values of 84%, 81%, and 86%, respectively, and positive predictive values of 55%, 53%, and 69%, respectively. CONCLUSIONS: QUANTRA PCS, ROTEM A10 PC, and Multiplate ADPtest showed a significant decrease after CPB, whereas ROTEM PC and Multiplate TRAPtest did not. Major bleeding was predicted with a moderate to good discrimination by the post-CPB viscoelastic tests (PCS, PC, and A10 PC).

A Comparative Study of Multiple Electrode Aggregometry Technologies in Cardiac Surgery: Different Values, Same Clinical Relevance.

OBJECTIVES: The assessment of platelet function in cardiac surgery patients who recently received dual-antiplatelet therapy is considered in the existing guidelines. Among available devices, Multiplate (MP) and ROTEM Platelet (RP) are both based on electrical impedance. This study aimed to determine the agreement between MP and RP in cardiac surgery patients under dual-antiplatelet therapy discontinued before surgery. Secondarily, it compared the ability of the MP and RP in predicting postoperative bleeding and the need for platelet transfusion. DESIGN: A prospective cohort study. SETTING: A hospital in Milan, Italy. PARTICIPANTS: Fifty adult patients preoperatively and postoperatively tested. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were studied with adenosine diphosphate (ADP) and thrombin receptor-activating peptide (TRAP) testing on both of the devices. The mean preoperative ADP tests were below the respective lower limit of the reference value, thus reflecting a good ability of these tests to detect the residual or ongoing effects of antiplatelet drugs acting on the P2Y12 receptor. The agreement between the 2 methodologies was very poor for both the ADP and TRAP tests, with a percentage error of 80%. The preoperative ADP tests were predictive for the need of platelet concentrate transfusion, with cut-off values at 35 U for the ADP-MP and 60 Ω/min for the ADP-RP. No correlation was found for postoperative bleeding. CONCLUSION: Both technologies seemed to offer potential benefits in the surgical approach to patients who preoperatively received antiplatelet drugs. However, the results of these tests are not interchangeable, and different cut-off values should be applied.

The multifactorial dynamic perfusion index: A predictive tool of cardiac surgery associated acute kidney injury.

INTRODUCTION: cardiac surgery associated acute kidney injury (CSA-AKI) has a number of preoperative and intraoperative risk factors. Cardiopulmonary bypass (CPB) factors have not yet been elucidated in a single multivariate model. The aim of this study is to develop a dynamic predictive model for CSA-AKI. METHODS: retrospective study on 910 consecutive adult cardiac surgery patients. Baseline data were used to settle a preoperative CSA-AKI risk model (static risk model, SRM); CPB related data were assessed for association with CSA-AKI. CPB duration, nadir oxygen delivery, time of exposure to a low oxygen delivery, nadir mean arterial pressure, peak lactates and red blood cell transfusion were included in a multivariate dynamic perfusion risk (DPR). SRM and DPR were merged into a final logistic regression model (multifactorial dynamic perfusion index, MDPI). The three risk models were assessed for discrimination and calibration. RESULTS: the SRM model had an AUC of 0.696 (95% CI 0.663-0.727), the DPR model of 0.723 (95% CI 0.691-0.753), and the MDPI model an AUC of 0.769 (95% CI 0.739-0.798). The difference in AUC between SRM and DPR was not significant (p = 0.495) whereas the AUC of MDPI was significantly larger than that of SRM (p = 0.004) and DPR (p = 0.015). CONCLUSIONS: inclusion of dynamic indices of the quality of CPB improves the discrimination and calibration of the preoperative risk scores. The MDPI has better predictive ability than the existing static risk models and is a promising tool to integrate different factors into an advanced concept of goal-directed perfusion.

Trials and Tribulations of Viscoelastic-Based Determination of Fibrinogen Concentration.

Acquired fibrinogen deficiency is a major determinant of severe bleeding in different clinical conditions, including cardiac surgery, trauma, postpartum hemorrhage, liver surgery, and transplantation. The existing guidelines recommend to supplement fibrinogen in patients with severe bleeding when the fibrinogen concentration is <1.5 g/L. Viscoelastic tests (VETs) provide a fast determination of the fibrinogen contribution to clot firmness and allow prompt treatment of acquired fibrinogen deficiency. However, different VET devices are presently available on the market, based on different technologies and different activators and platelet inhibitors. The available tests are the functional fibrinogen (FF, thromboelastography), the fibrinogen contribution to clot firmness (fibrinogen determination [FIBTEM], thromboelastometry), and the fibrinogen contribution to clot strength (FCS, sonorheometry). All these tests have a moderate to very good correlation with the Clauss fibrinogen assays; however, when comparing VET-based fibrinogen contribution to clot firmness with Clauss fibrinogen concentration, strong differences occur within the same test under different conditions and between different tests. The most widely studied test is the thromboelastometric FIBTEM; the best predictor of a Clauss fibrinogen <1.5 g/L is placed at a maximum clot firmness around 8 mm of amplitude. Fewer data are available for thromboelastographic FF, but the correspondent value is in the range of 12 mm. Overall, due to an incomplete inhibition of platelet contribution, FF overestimates the fibrinogen contribution with respect to FIBTEM. Data on sonorheometry FCS are limited and conflicting. When addressing the correlation between different tests, it is good in general, but no fixed conversion factors can be proposed, due to a considerable dispersion of the experimental points. In conclusion, VET-based fibrinogen tests are certainly powerful tools that are presently suggested by the existing guidelines; however, when using them for clinical decision-making, users should consider the possible sources of bias, which include the different level of platelet inhibition, the role of platelet count and function, the possible different degrees of blood activation with tissue factor, the important role of factor XIII in stabilizing the fibrin clot, and others.

Platelet Contribution to Clot Strength in Thromboelastometry: Count, Function, or Both?

In thromboelastometry (ROTEMTM) the difference in amplitude between the EXTEM and the FIBTEM is considered an index of platelet contribution to clot strength (PCSamp). The difference in elasticity (PCSel) is rarely used. We investigated the ability of PCSamp and PCSel in reflecting platelet count and function in 103 patients undergoing cardiac surgery, simultaneously measuring ROTEM and platelet function tests (multiple electrode aggregometry ADPtest and TRAPtest, MultiplateTM). PCSamp and PCSel were tested for association with platelet count and function. The PCSamp showed a low (R coefficient 0.32-0.39) association with platelet count and function (ADPtest), whereas the PCSel showed higher values of association (R coefficient 0.55-0.71) with the same variables. No association was found between PCS and TRAPtest. In a multivariable model, both the platelet count (R coefficient 0.60, P = 0.001) and the ADPtest (R coefficient 0.36, P = 0.001) were independently associated with the PCSel. The discrimination properties of the PCSel for the prediction of a low platelet count/function were very good (c-statistics 0.837). In clinical practice, the difference in elasticity between EXTEM and FIBTEM should replace the difference in amplitude.

Platelet function after cardiac surgery and its association with severe postoperative bleeding: the PLATFORM study.

Platelet dysfunction after cardiac surgery is a determinant of postoperative bleeding. The existing guidelines suggest the use of desmopressin and/or platelet concentrate transfusions in case of platelet dysfunction in bleeding patients, but no cut-off values for platelet activity exist in the literature. The Platelet Function in the Operating Room (PLATFORM) study aims to identify the relationship between platelet function after cardiopulmonary bypass and severe bleeding, finding adequate predictive values of platelet function for severe bleeding. The PLATFORM is a prospective cohort study on 490 adult patients receiving cardiac surgery with cardiopulmonary bypass. Patients received platelet function tests (multiple electrode aggregometry ADPtest and TRAPtest) before surgery and after cardiopulmonary bypass, and routine coagulation tests before surgery and at the arrival in the intensive care unit. The post-cardiopulmonary bypass ADPtest and TRAPtest were significantly (P = 0.001) associated with severe bleeding, as well as the post-cardiopulmonary bypass activated partial thromboplastin time, the international normalized ratio, and the fibrinogen concentration. At a multivariable analysis, the ADPtest (odds ratio 0.962, 95% confidence interval 0.936-0.989, P = 0.005) and the activated partial thromboplastin time (odds ratio 1.097, 95% confidence interval 1.016-1.185, P = 0.017) remained independently associated with severe bleeding. The post-cardiopulmonary bypass ADPtest had the best discrimination, with an area under the curve of 0.712. The best positive predictive value (42%) was found at a cut-off ≤8 U. In conclusion, platelet function tests after cardiopulmonary bypass are significantly associated with postoperative bleeding. However, postoperative bleeding has a multifactorial nature, and the measure of platelet function alone does not provide a high positive predictive value for severe bleeding.

A Comparative Study of SEER Sonorheometry Versus Standard Coagulation Tests, Rotational Thromboelastometry, and Multiple Electrode Aggregometry in Cardiac Surgery.

OBJECTIVES: Coagulation point-of-care tests for the diagnosis and management of bleeding commonly are used in cardiac surgery. Recently, a new viscoelastic point-of-care device, Quantra (HemoSonics, Charlottesville, VA), which is based on sonic estimation of elasticity via resonance sonorheometry, entered the market. Prior studies have compared the Quantra parameters with conventional coagulation tests and thromboelastography or rotational thromboelastography, but no study has assessed the correlation of the platelet-derived Quantra parameter platelet contribution to stiffness (PCS) with platelet function assays. The present study compared the Quantra-derived coagulation parameters with conventional coagulation tests, rotational thromboelastography-derived parameters, and platelet function measured using multiplate aggregometry. DESIGN: Prospective cohort study. SETTING: University research hospital. PARTICIPANTS: The study comprised 30 cardiac surgery patients before and after cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Quantra clot stiffness showed a very strong correlation with the EXTEM maximum clot firmness before and after cardiopulmonary bypass and in the overall samples (r values 0.94-0.96). Quantra fibrinogen contribution to stiffness was compared with the corresponding FIBTEM and Clauss fibrinogen levels, which also showed a strong level of correlation (r values between 0.74 and 0.87). Quantra PCS strongly correlated with platelet count (r = 0.71) in the overall samples and moderately with adenosine diphosphate-dependent platelet function (r = 0.67). In a multivariable model, both the adenosine diphosphate test value and the platelet count remained independently associated with Quantra PCS. CONCLUSIONS: Fibrinogen-dependent clot stiffness properties are well-reflected by the Quantra fibrinogen contribution to stiffness parameter, and PCS incorporates platelet count and function.

The Conundrum of Systemic Arterial Pressure Management on Cardiopulmonary Bypass.

The recently released EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass (CPB) in adult cardiac surgery [...].

Plasma-Free Strategy for Cardiac Surgery with Cardiopulmonary Bypass in Infants < 10 kg: A Retrospective, Propensity-Matched Study.

BACKGROUND: Infants < 10 kg undergoing cardiac surgery with cardiopulmonary bypass (CPB) may receive either fresh frozen plasma (FFP) or other solutions in the CPB priming volume. The existing comparative studies are controversial. No study addressed the possibility of total avoidance of FFP throughout the whole perioperative course in this patient population. This retrospective, non-inferiority, propensity-matched study investigates an FFP-free strategy compared to an FFP-based strategy. METHODS: Among patients <10 kg with available viscoelastic measurements, 18 patients who received a total FFP-free strategy were compared to 27 patients (1:1.5 propensity matching) receiving an FFP-based strategy. The primary endpoint was chest drain blood loss in the first 24 postoperative hours. The level of non-inferiority was settled at a difference of 5 mL/kg. RESULTS: The 24-h chest drain blood loss difference between groups was -7.7 mL (95% confidence interval -20.8 to 5.3) in favor of the FFP-based group, and the non-inferiority hypothesis was rejected. The main difference in coagulation profile was a lower level of fibrinogen concentration and FIBTEM maximum clot firmness in the FFP-free group immediately after protamine, at the admission in the ICU and for 48 postoperative hours. No differences in transfusion of red blood cells or platelet concentrate were observed; patients in the FFP-free group did not receive FFP but required a larger dose of fibrinogen concentrate and prothrombin complex concentrate. CONCLUSIONS: An FFP-free strategy in infants < 10 kg operated with CPB is technically feasible but results in an early post-CPB coagulopathy that was not completely compensated with our bleeding management protocol.

Bleeding and Thrombotic Issues during Extracorporeal Membrane Oxygenation.

Extracorporeal Membrane Oxygenation (ECMO) is an advanced life support modality for patients with respiratory or cardiac failure refractory to standard therapy [...].

Microcirculatory Alterations in Critically Ill Patients with COVID-19-Associated Acute Respiratory Distress Syndrome.

BACKGROUND: Presently, a number of specific observations have been performed on microcirculatory function in a coronavirus disease-19 (COVID-19) setting. We hypothesized that, in the critically ill, endothelial dysfunction secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the subsequent inflammation and coagulopathy may lead to microcirculatory alterations, further exacerbated by the hypoxemic state. A dysfunctional microcirculation may represent the hidden motor underlying the development of COVID-19's clinical manifestations. METHODS: A single center, prospective, observational study. We analyzed bedside sublingual microcirculation in twenty-four consecutive COVID-19-associated acute respiratory distress syndrome (ARDS) patients mechanically ventilated in an Intensive Care Unit (ICU), together with macro-hemodynamics, clinical parameters, echocardiography, and laboratory data at a single time-point after ICU admission. All participants were recruited between March and May 2020. RESULTS: The microcirculatory pattern was characterized by increased values of total vessel density and perfused vessel density, a reduced value of proportion of perfused vessels and microvascular flow index, and high values of heterogeneity index. The duration of mechanical ventilation before microcirculation assessment was inversely associated with the proportion of perfused vessels (p = 0.023). Within the macro-hemodynamic parameters, the right ventricle end-diastolic diameter was inversely associated with proportion of perfused vessels and microvascular flow index (p = 0.039 and 0.014, respectively) and directly associated with the heterogeneity index (p = 0.033). CONCLUSIONS: In COVID-19-associated ARDS patients, the microcirculation showed impaired quality of flow parameters coupled with a high vessel density.

When Outcomes Diverge: Age and Cardiovascular Risk as Determinants of Mortality and ICU Admission in COVID-19.

BACKGROUND: Hospital mortality and admission to the Intensive Care Unit (ICU) are markers of disease severity in COVID-19 patients. Cardiovascular co-morbidities are one of the main determinants of negative outcomes. In this study we investigated the impact of cardiovascular co-morbidities on mortality and admission to the ICU in first-wave COVID-19 patients. METHODS: A multicenter, retrospective, cohort study. A total of 1077 patients were analyzed for mortality and ICU admission. Cardiovascular risk factors were explored as determinants of the outcomes after correction for other confounders. RESULTS: In the multivariable model, after correction for age, only a history of heart failure remained independently associated (p = 0.0013) with mortality (hazard ratio 2.22, 95% confidence interval 1.37 to 3.62). Age showed a mortality risk increase of 8% per year (hazard ratio 1.08, 95% confidence interval 1.05 to 1.10, p = 0.001). The transition from ward to the ICU had, as a single determinant, the age, but in a reversed fashion (hazard ratio 0.96, 95% confidence interval 0.94 to 0.98, p = 0.0002). CONCLUSIONS: Once adjusted for the main determinant of mortality (age) heart failure only remained independently associated with mortality. Admission to the ICU was less likely for elderly patients. This may reflect the catastrophic impact of the first wave of COVID-19 pandemic in terms of ICU bed availability in Lombardy, leading to a selection process for ICU admission.

Influence of left ventricular unloading on pediatric post-cardiotomy veno-arterial extracorporeal life support outcomes.

Background: The effectiveness of veno-arterial extracorporeal life support (V-A ECLS) in treating neonatal and pediatric patients with complex congenital heart disease (CHD) and requiring cardio-circulatory assistance is well-known. Nevertheless, the influence of left ventricle (LV) distension and its countermeasure, namely LV unloading, on survival and clinical outcomes in neonates and children treated with V-A ECLS needs still to be addressed. Therefore, the aim of this study was to determine the effects of LV unloading on in-hospital survival and complications in neonates and children treated with V-A ECLS. Methods: The clinical outcomes of 90 pediatric patients with CHD under 16 years of age supported with V-A ECLS for post-cardiotomy cardiogenic shock (CS) were retrospectively reviewed in relationship with the presence or absence of an active LV unloading strategy. Results: The patient cohort included 90 patients (age 19.6 ± 31.54 months, 64.4% males), 42 of whom were vented with different techniques (38 with atrial septostomy (AS) or left atria cannula, two with cannula from LV apex, 1 with intra-aortic balloon pump (IABP), and one with pigtail across the aortic valve). The LV unloading strategy significantly increased the in-hospital survival (odds ratio [OR] = 2.74, 95% CI 1.06-7.08; p = 0.037). On the contrary, extracorporeal cardiopulmonary resuscitation decreased the related survival (OR = 0.32, 95% CI 1.09-0.96; p = 0.041). The most common complications were infections (28.8%), neurological injury (26%), and bleeding (25.6%). However, these did not differently occur in venting and no-venting groups. Conclusion: In pediatric patients with CHD supported with V-A ECLS for post-cardiotomy CS, the LV unloading strategy was associated with increased survival.

Covid-19-Associated Coagulopathy: Biomarkers of Thrombin Generation and Fibrinolysis Leading the Outcome.

Background: Coronavirus Disease 2019 (COVID-19)-associated coagulopathy is characterized by a prothrombotic state not yet comprehensively studied. We investigated the coagulation pattern of patients with COVID-19 acute respiratory distress syndrome (ARDS), comparing patients who survived to those who did not. Methods: In this prospective cohort study on 20 COVID-19 ARDS patients, the following biomarkers were measured: thrombin generation (prothrombin fragment 1 + 2 (PF 1 + 2)), fibrinolysis activation (tissue plasminogen activator (tPA)) and inhibition (plasminogen activator inhibitor 2 (PAI-2)), fibrin synthesis (fibrinopeptide A) and fibrinolysis magnitude (plasmin-antiplasmin complex (PAP) and D-dimers). Measurements were done upon intensive care unit (ICU) admission and after 10-14 days. Results: There was increased thrombin generation; modest or null release of t-PA; and increased levels of PAI-2, fibrinopeptide A, PAP and D-dimers. At baseline, nonsurvivors had a significantly (p = 0.014) higher PAI-2/PAP ratio than survivors (109, interquartile range (IQR) 18.1-216, vs. 8.7, IQR 2.9-12.6). At follow-up, thrombin generation was significantly (p = 0.025) reduced in survivors (PF 1 + 2 from 396 pg/mL, IQR 185-585 to 237 pg/mL, IQR 120-393), whereas it increased in nonsurvivors. Fibrinolysis inhibition at follow-up remained stable in survivors and increased in nonsurvivors, leading to a significant (p = 0.026) difference in PAI-2 levels (161 pg/mL, IQR 50-334, vs. 1088 pg/mL, IQR 177-1565). Conclusion: Severe patterns of COVID-19 ARDS are characterized by a thrombin burst and the consequent coagulation activation. Mechanisms of fibrinolysis regulation appear unbalanced toward fibrinolysis inhibition. This pattern ameliorates in survivors, whereas it worsens in nonsurvivors.

The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES: Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS: Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS: At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6-13.5) elevated D-dimer levels (5.5 µg/mL, interquartile range 2.5-6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2  = .506, P = .003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time-related decrease of fibrinogen levels, D-dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038). CONCLUSION: The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.

Gender-based differences in platelet function and platelet reactivity to P2Y12 inhibitors.

BACKGROUND: Gender influences platelet biology. Women have a larger platelet count, but gender-based differences in platelet function remain debated. We performed a study addressing gender-based differences in platelet function using point-of-care platelet function tests (PFT). METHODS: The patient population consisted of 760 cardiac surgery patients where preoperative PFT (multiple-electrode aggregometry [MEA]) were available. Platelet count and function at the ADPtest and TRAPtest were compared in the overall population and separately in patients with or without residual effects of P2Y12 inhibitors. RESULTS: Women had a significantly (P = 0.001) higher platelet count but a non-significantly higher platelet reactivity to ADP. In clopidogrel-treated patients, the platelets ADP reactivity was significantly (P = 0.031) higher in women, and platelet count was the main determinant of platelet hyper-reactivity. Within patients under full clopidogrel effects, women with a platelet count ≥ 200,000 cells/µL had a significantly (P = 0.023) higher rate of high-on-treatment platelet reactivity (HTPR, 45.5%) with respect to males with a platelet count < 200,000 cells/µL (11.9%), with a relative risk of 6.2 (95% confidence interval 1.4-29). CONCLUSIONS: Our findings confirm that women have a larger platelet count than men, and that this is associated to a trend towards a higher platelet reactivity. HTPR is largely represented in women with a high platelet count. This generates the hypothesis that women requiring P2Y12 inhibitors could potentially benefit from larger doses of drug or should be treated with anti-platelet agents with a low rate of HTPR.

Validation of renal-risk models for the prediction of non-renal replacement therapy cardiac surgery-associated acute kidney injury.

BACKGROUND: Cardiac surgery-associated acute kidney injury (AKI) is a serious complication of cardiac surgery, even when renal replacement therapy (RRT) is not required. The existing risk models for cardiac surgery associated AKI are designed to predict AKI requiring RRT (RRT-AKI). The aim of this study is to validate three risk models for the prediction of RRT-dependent and non-RRT AKI after cardiac surgery. METHODS: Retrospective analysis on 7675 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for stage 1 and 2. RRT AKI and non-RRT AKI were defined according to the need for RRT. Three risk models were validated separately for RRT and non-RRT AKI: the Cleveland Risk Score, the Bedside Risk Score, and the Simplified Renal Index Scoring Scheme. Discrimination power was assessed with Receiver Operating Characteristics analysis and c-statistics. RESULTS: There were 502 (6.5%) non-RRT AKI events, 128 (1.7%) RRT-AKI events, and 7045 (91.8%) no-events. The three models performed well for predicting RRT-AKI (c-statistics 0.75-0.79) and poorly for predicting non-RRT AKI (c-statistics 0.54-0.59). The models had an excellent calibration for RRT-AKI but not for non-RRT AKI. Preoperative serum creatinine and estimated glomerular filtration rate were associated with RRT AKI but not with non-RRT AKI. Mortality was 12.2% in non-RRT AKI and 46.9% in RRT-AKI, significantly (P = 0.001) higher than in patients without AKI (1.3%). CONCLUSIONS: The existing risk models are inadequate for predicting non-RRT AKI following cardiac surgery, both in terms of discrimination and calibration.