Search

Abstract Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p

During the acute phase of COVID-19, many patients experience a complex coagulopathy characterized by a procoagulant pattern. The present study investigates the persistence of hemostatic changes in post-COVID patients at a long-term follow up, and the link with the persistence of physical and neuropsychological symptoms. We completed a prospective cohort study on 102 post-COVID patients. Standard coagulation and viscoelastic tests were performed, along with an assessment of persistent symptoms and recording of acute phase details. A procoagulant state was adjudicated in the presence of fibrinogen > 400 mg/dL, or D-dimer > 500 ng/mL, or platelet count > 450,000 cells/µL, or a maxim clot lysis at viscoelastic test < 2%. A procoagulant state was identified in 75% of the patients at 3 months follow up, 50% at 6 months, and 30% at 12–18 months. Factors associated with the persistence of a procoagulant state were age, severity of the acute phase, and persistence of symptoms. Patients with major physical symptoms carry a procoagulant state relative risk of 2.8 (95% confidence interval 1.17–6.7, p = 0.019). The association between persistent symptoms and a procoagulant state raises the hypothesis that an ongoing process of thrombi formation and/or persistent microthrombosis may be responsible for the main physical symptoms in long-COVID patients.

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 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.

Platelet function tests (PFTs) before cardiac surgery are predictive of postoperative bleeding and can guide a correct timing of surgery in patients under P2Y12 inhibitors. Thrombocytopenia affects PFT and may determine postoperative bleeding. The present study aims to investigate the relationship between platelet count and function, and its role in determining postoperative bleeding in cardiac surgery patients pre-treated with P2Y12 inhibitors. The study includes 589 consecutive cardiac surgery patients, tested before surgery with platelet count and multiple electrode aggregometry (MEA) ADPtest (investigating P2Y12 receptor platelet reactivity) and TRAPtest (investigating the thrombin-dependent platelet reactivity). Platelet function was linearly associated (P = 0.001) with platelet count at the ADPtest and the TRAPtest, demonstrating a positive association in the whole spectrum of platelet count. The ADPtest (P = 0.001) and platelet count (P = 0.001) were negatively associated with postoperative bleeding, whereas the TRAPtest was not. At a multivariable analysis, the ADPtest (P = 0.026) and platelet count (P = 0.006) remained independent predictors of postoperative bleeding. The platelet transfusion rate was 5.7% in patients with ADPtest ≥30 U and platelet count ≥150 000 cells/µL, 14.3% in patients with ADPtest ≥30 U and platelet count

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.

Background. Pediatric open-heart surgery with cardiopulmonary bypass (CPB) still remains a risky interventional procedure at high mortality/morbidity. To date, there are no clinical, laboratory, and/or monitoring parameters providing useful information on perioperative stress. We therefore investigated whether blood concentrations of glutathione (GSH), a powerful endogenous antioxidant, changed in the perioperative period. Methods. We conducted an observational study in 35 congenital heart disease (CHD) children in whom perioperative standard laboratory and monitoring parameters and GSH blood levels were assessed at five monitoring time points. Results. GSH showed a pattern characterized by a progressive increase from pre-surgery up to 24 h after surgery, reaching its highest peak at the end of CPB. GSH measured at the end of CPB correlated with CPB duration, cross-clamping, arterial oxygen partial pressure, and with body core temperature. Conclusions. The increase in GSH levels in the perioperative period suggests a compensatory mechanism to oxidative damage during surgical procedure. Caution is needed in controlling different CPB phases, especially systemic reoxygenation in a population that is per se more prone to oxidative stress/damage. The findings may point the way to detecting the optimal temperature and oxygenation target by biomarker monitoring.

BackgroundOperative mortality risk in cardiac surgery is usually assessed using preoperative risk models. However, intraoperative factors may change the risk profile of the patients, and parameters at the admission in the intensive care unit may be relevant in determining the operative mortality. This study investigates the association between a number of parameters at the admission in the intensive care unit and the operative mortality, and verifies the hypothesis that including these parameters into the preoperative risk models may increase the accuracy of prediction of the operative mortality.Methodology929 adult patients who underwent cardiac surgery were admitted to the study. The preoperative risk profile was assessed using the logistic EuroSCORE and the ACEF score. A number of parameters recorded at the admission in the intensive care unit were explored for univariate and multivariable association with the operative mortality.Principal findingsA heart rate higher than 120 beats per minute and a blood lactate value higher than 4 mmol/L at the admission in the intensive care unit were independent predictors of operative mortality, with odds ratio of 6.7 and 13.4 respectively. Including these parameters into the logistic EuroSCORE and the ACEF score increased their accuracy (area under the curve 0.85 to 0.88 for the logistic EuroSCORE and 0.81 to 0.86 for the ACEF score).ConclusionsA double-stage assessment of operative mortality risk provides a higher accuracy of the prediction. Elevated blood lactates and tachycardia reflect a condition of inadequate cardiac output. Their inclusion in the assessment of the severity of the clinical conditions after cardiac surgery may offer a useful tool to introduce more sophisticated hemodynamic monitoring techniques. Comparison between the predicted operative mortality risk before and after the operation may offer an assessment of the operative performance.

Acutely bleeding patients are commonly found in the trauma and major surgery scenarios. They require prompt and effective treatment to restore an adequate hemostatic pattern, to avoid serious and sometimes life-threatening complications.Different prohemostatic treatments are available, including allogeneic blood derivatives (fresh frozen plasma, platelet concentrates, and cryoprecipitates), prothrombin complex concentrates, specific coagulation factors (fibrinogen, recombinant factor XIII, recombinant activated factor VII), and drugs (protamine for patients under heparin treatment, desmopressin, antifibrinolytics).For decades, prohemostatic treatment of the acutely bleeding patient was based on empirical strategies and clinical judgment, both in terms of a correct diagnosis of the mechanism(s) leading to bleeding, and of an assessment of the effects of the treatment. This empirical strategy may lead to excessive or unnecessary use of allogeneic blood products, as well as to an incorrect, inefficacious, or even dangerous treatment. Different monitoring devices are nowadays available for guiding the diagnostic and therapeutic decision-making process in an acutely bleeding patient. This review addresses the available tools for monitoring prohemostatic treatment of the bleeding patient, with a specific respect for point-of-care tests (thromboelastography, thromboelastometry, platelet function tests, and heparin monitoring systems) at the light of the existing evidence. [ABSTRACT FROM AUTHOR]