Questions about COVID-19 associated coagulopathy: possible answers from the viscoelastic tests.

Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide "dynamic" data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions. In patients with severe COVID-19 infection VETs can supply to clinicians more information about the CAC, identifying the presence of hypercoagulable and hypofibrinolysis states. In the last year, many studies have proposed to explain the underlying characteristics of CAC; however, there remain many unanswered questions. We tried to address some of the important queries about CAC through VETs analysis.

Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia.

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU. Coagulation standard parameters were also evaluated. Forty patients were enrolled into the study. The ICU and the hospital mortality were 10% and 12.5%, respectively. On ICU admission, prothrombin time was slightly reduced and it increased significantly at T10 (T0 = 65.1 ± 9.8 vs T10 = 85.7 ± 1.5, p = 0.002), while activated partial thromboplastin time and fibrinogen values were higher at T0 than T10 (32.2 ± 2.9 vs 27.2 ± 2.1, p = 0.017 and 895.1 ± 110 vs 332.5 ± 50, p = 0.002, respectively); moreover, whole blood thromboelastometry profiles were consistent with hypercoagulability characterized by an acceleration of the propagation phase of blood clot formation [i.e., CFT below the lower limit in INTEM 16/40 patients (40%) and EXTEM 20/40 patients (50%)] and significant higher clot strength [MCF above the upper limit in INTEM 20/40 patients (50%), in EXTEM 28/40 patients (70%) and in FIBTEM 29/40 patients (72.5%)]; however, this hypercoagulable state persists in the first five days, but it decreases ten day after, without returning to normal values. No sign of secondary hyperfibrinolysis or sepsis induced coagulopathy (SIC) were found during the study period. In six patients (15%) a deep vein thrombosis and in 2 patients (5%) a thromboembolic event, were found; 12 patients (30%) had a catheter-related thrombosis. ROTEM analysis confirms that patients with severe COVID-19 pneumonia had a hypercoagulation state that persisted over time.

The clinical impact of pectoral nerve block in an 'enhanced recovery after surgery' program in breast surgery.

Background: Pectoral nerve block (PECS) is increasingly performed in breast surgery. Aim: The study evaluated the clinical impact of these blocks in the postoperative course. Patients & methods: In this case-control study, patients undergoing breast surgery with 'enhanced recovery after surgery' pathways were divided into group 1 (57 patients) in whom PECS was performed before general anesthesia, and group 2 (57 patients) in whom only general anesthesia was effected. Results: Postoperative opioid consumption (p < 0.002), pain at 32 h after surgery (p < 0.005) and the length of stay (p < 0.003) were significantly lower in group 1. Conclusion: Reducing opioid consumption and pain after surgery, PECS could favor a faster recovery with a reduction in length of stay, ensuring a higher turnover of patients undergoing breast surgery.

'Enhanced recovery after surgery' (ERAS) protocols have been recently applied in breast cancer patients in order to improve the postoperative course. However, the incidence of moderate to severe pain after breast surgery is frequent, and a multimodal approach is recommended. In this view, the interfascial plane blocks are advocated as a valid alternative to both paravertebral and epidural blockade. In this study, we evaluated the effects of these blocks on the postoperative course in patients undergoing breast surgery with ERAS protocols. We compared two patient groups: in the first, pectoral blocks were performed before general anesthesia, while in the second no block was carried out. We found that in the patient group receiving the blocks, postoperative opioid consumption (with essentially the same pain after surgery) and length of stay were significantly lower. Therefore, although more robust studies are needed to confirm our findings, these emerging locoregional techniques could favor a faster recovery in the context of ERAS in breast surgery. These results could have important clinical implications in terms of not only reducing healthcare costs but also ensuring a higher turnover of patients undergoing breast surgery.

The multidisciplinary audit in enhanced recovery after surgery (ERAS) colorectal surgery: experience in a single Italian center.

BACKGROUND: Current literature underlines the role of periodical feed-back to improve Enhanced Recovery After Surgery (ERAS) path adherence during implementation program. The aim of this retrospective study was to evaluate the clinical impact of an audit program in an ERAS path. METHODS: All elective patients submitted to elective colorectal surgery from November 2018 to January 2020 in our Institution were considered. The sample was divided into two study groups: group 1, including patients enrolled in the first sixth months of ERAS program until the first audit; group 2, patients enrolled in a time period of a six months after the first audit. RESULTS: The final analysis included 46 patients in group 1 and 64 in group 2. Group 2 showed a higher ASA Score (P<0.03), a higher prevalence of right hemicolectomy, and a lower prevalence of left hemicolectomy and anterior rectum resection (RAR) (P<0.016). Group 2 also had a lower prevalence of anastomotic leakage (AL) (P<0.004). Intraoperative normothermia (T>36 C°) in this group was achieved in a larger number of patients in comparison with group 1 (39% vs. 19.5%) (P<0.01). Group 2 experienced a higher average body temperature at admission in recovery room (RR) when compared to Group 1 (35.8 vs. 35.1 C°, P<0.01). CONCLUSIONS: Audit program may represent a useful tool to promote advantageous changes in clinical practice and to favor a better compliance to ERAS program.

Derangement of the coagulation process using subclinical markers and viscoelastic measurements in critically ill patients with coronavirus disease 2019 pneumonia and non-coronavirus disease 2019 pneumonia.

Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with pneumonia. In severe coronavirus disease 2019 (COVID-19) the alteration of coagulation parameters was associated with poor prognosis. We evaluated the difference in coagulopathy between critically ill patients with COVID-19 pneumonia (COVID group) and non-COVID-19 pneumonia (non-COVID group), using traditional coagulation markers and rotational thromboelastometry (ROTEM). Standard laboratory and ROTEM parameters were evaluated in 45 patients (20 COVID group patients and 25 non-COVID group patients) at time of admission to the Intensive Care Unit (ICU) (T0) and at 5 (T5) and 10 days (T10) later. In all evaluations times, platelet count was found higher in COVID group rather than in non-COVID group. At T0, COVID group revealed a fibrinogen value greater than non-COVID group. d-Dimer values were high in both groups and they were not statistically different. At T0 COVID group showed a significant reduction of clot formation time in INTEM and in EXTEM and a significant increase of maximum clot firmness in INTEM, EXTEM and FIBTEM respect to non-COVID group. Moreover, COVID group demonstrated a coagulability state with ROTEM profiles higher than non-COVID group at T5 and T10. Coagulation profiles showed that critically ill patients with COVID-19 pneumonia are characterized by a higher coagulable state than others; this greater procoagulative state persists over time.

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action.

BACKGROUND: Critically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state. The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e. D-dimer). We also evaluated the impact of different doses of low molecular weight heparin (LMWH) on the incidence of bleedings. METHODS: The data of forty-two patients admitted to the Intensive Care Unit (ICU) were retrospectively analyzed. On ICU admission, patients with D-dimer < 3000 ng/mL (Group 1) received enoxaparin 4000 UI (6000 UI, if body mass index >35) subcutaneously b.i.d. and patients with D-dimer ≥ 3000 ng/mL (Group 2) received enoxaparin 100 UI/kg every 12 h. Aspirin was administered to all patients once a day. RESULTS: Both groups presented a high incidence of perivascular thrombosis (40.9% in Group 1 and 30% in Group 2). Patients of Group 2 suffered a higher incidence of venous thromboembolism (VTE) than Group 1 (65% vs 13.6%, p = 0.001). One patient (4.5%) of Group 1 and three patients (15%) of Group 2 suffered from minor bleeding; no patient had major bleeding. Group 2 had a longer ICU and hospital stay than Group 1 (11.5 ±â€¯5.6 vs 9.0 ±â€¯4.8 and 30 ±â€¯4.9 vs 21 ±â€¯2.3, p < 0.05, respectively) as well as increased ICU mortality (25% vs 9.1%). CONCLUSIONS: More severe critically ill COVID-19 patients have a high incidence of VTE and worse outcome, despite the use of heparin at the therapeutic dose. However, the use of heparin did not increase the incidence of bleeding complications.

Risk factors for non-invasive/invasive ventilatory support in patients with COVID-19 pneumonia: A retrospective study within a multidisciplinary approach.

OBJECTIVES: To investigate risk factors for non-invasive/invasive ventilatory support (NI/I-VS) in patients with coronavirus disease 2019 (COVID-19). METHODS: All consecutive patients admitted to the Infectious Diseases Unit and Intensive Care Unit (ICU) of Santa Maria Annunziata Hospital (Florence, Italy), from February 25 to April 25, 2020, with a confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as the need for continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) (non-invasive ventilation) or mechanical ventilation, not including low-flow systems of oxygen therapy such as the Venturi mask or nasal cannula. RESULTS: Ninety-seven patients were enrolled; 61.9% (60/97) were male and the median patient age was 64 years. The in-hospital mortality was 9.3%. Thirty-five of the 97 patients (36%) required ICU admission and 94.8% (92/97) were prescribed oxygen therapy: 10.8% (10/92) by nasal cannula, 44.5% (41/92) by Venturi mask, 31.5% (29/92) by CPAP, 2.2% (2/92) by BPAP, and 10.8% (10/92) by mechanical ventilation following intubation. On univariate analysis, patients with a body mass index >30, type II diabetes mellitus, and those presenting with dyspnoea, asthenia, SOFA score ≥2 points, PaO2/FiO2 <300, temperature >38 °C, increased levels of lactate dehydrogenase (LDH), alanine aminotransferase, and C-reactive protein, and a d-dimer >1000 ng/mL at admission more frequently underwent NI/I-VS. Multivariate logistic regression analysis confirmed temperature >38 °C (odds ratio (OR) 21.2, 95% confidential interval (95% CI) 3.5-124.5, p = 0.001), LDH >250 U/l (OR 15.2, 95% CI 1.8-128.8, p = 0.012), and d-dimer >1000 ng/mL (OR 4.5, 95% CI 1.2-17.3, p = 0.027) as significantly associated with the requirement for NI/I-VS. A non-significant trend (p = 0.051) was described for PaO2/FiO2 <300. CONCLUSIONS: Temperature >38 °C, LDH > 250 U/l, and d-dimer >1000 ng/mL were found to be independent risk factors for NI/I-VS in COVID-19 patients. In order to quickly identify patients likely at risk of developing a critical illness, inflammatory markers should be assessed upon hospital admission.

Gender and anti-thrombotic therapy: from biology to clinical implications.

Cardiovascular diseases actually remain the leading cause of death and morbidity in Western countries, and it is the most common cause of death in American women accounting for about one third of all deaths. Women remain underrepresented in published trial literature relative to their disease prevalence. Strong evidence do exists demonstrating gender differences in efficacy (ischemic risk) and safety (bleeding risk) associated with antithrombotic treatment, mostly related to different values of body mass, and renal function in women than men. Several data show a higher platelet reactivity in females and a higher prevalence of high platelet reactivity on aspirin and clopidogrel therapy. In primary prevention, the use of aspirin is associated with a higher reduction of risk for ischemic stroke in females and for myocardial infarction in males. In the setting of ACS, female gender is associated with a significantly higher risk of bleeding. In summary, there are some gender-related aspects of guidance in the complex spectrum of the net clinical benefit related to antithrombotic treatment.

Delirium in elderly patients hospitalized in internal medicine wards.

A prospective observational study was conducted to evaluate the impact of delirium on geriatric inpatients in internal medical wards and to identify predisposing factors for the development of delirium. The study included all patients aged 65 years and older, who were consecutively admitted to the internal medicine wards of two public hospitals in Florence, Italy. On admission, 29 baseline risk factors were examined, cognitive impairment was evaluated by Short Portable Mental Status Questionnaire, and prevalent delirium cases were diagnosed by Confusion Assessment Method (CAM). Enrolled patients were evaluated daily with CAM to detect incident delirium cases. Among the 560 included patients, 19 (3 %) had delirium on admission (prevalent) and 44 (8 %) developed delirium during hospitalization (incident). Prevalent delirium cases were excluded from the statistical analysis. Incident delirium was associated with increased length of hospital stay (p < 0.01) and institutionalization (p < 0.01, OR 3.026). Multivariate analysis found that cognitive impairment on admission (p < 0.0002), diabetes (p < 0.05, OR 1.936), chronic kidney failure (p < 0.05, OR 2.078) and male gender (p < 0.05, OR 2.178) was significantly associated with the development of delirium during hospitalization. Results show that delirium impact is relevant to older patients hospitalized in internal medicine wards. The present study confirms cognitive impairment as a risk factor for incident delirium. The cognitive evaluation proved to be an important instrument to improve identification of patients at high risk for delirium. In this context, our study may contribute to improve application of preventive strategies.