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1.
HemaSphere ; 6:3200-3201, 2022.
Article in English | EMBASE | ID: covidwho-2032144

ABSTRACT

Background: Arterial thrombotic events (ATE) are important cause of noncancer-related deaths among patients with cancer. It is estimated that the prevalence of ATE among those patients is between 2-5%. However, data regarding acute myeloid leukemia (AML) related ATE are scarce and far less available than those related to venous thrombotic events. Aims: To determine the incidence of ATE in nonM3-AML patients and to underline the potential risk factors for ATE development. Methods: The single center, retrospective, cohort study was carried out in University Clinical Center of Serbia. Adult patients, who were diagnosed with nonM3-AML between January 2009. and December 2021. were included. In all patients the occurrence of ATE (e.g. a heart attack, a stroke, critical limb ischemia) was assessed during the active treatment and the three months following the last chemotherapy session. Diagnosis of ATE was established using clinical, laboratory and radiological methods. Patients who experienced venous thromboembolism during the treatment period were excluded. Demographic data, presence of obesity, smoking status, history of thrombosis, baseline laboratory findings (complete blood count, fibrinogen, D-dimer, PT, aPTT, LDH), leukemia-related parameters (cytogenetics (including ELN risk stratification), flow cytometry), Khorana score, ECOG PS, HCT CI score, concurrent COVID-19 were collected from patients' health records. The methods of descriptive (mean ± standard deviation, median (range), frequency (%)) and analytic statistics (Student's t-test, chi-squared test) were used. Results: A total of 545 patients (293 males (53.8%)) were included in the study. Median age of the study population was 58 (range: 18-81) years. ATE was noted in 18/545 (3.3%) subjects with following distribution: ischemic stroke 12/18 (66.7%), myocardial infarction 5/18 (27.8%), and acute lower extremity arterial thrombosis 1/18 (5.5%). ATE was diagnosed most commonly during the induction (8 (44.4%) patients), reinduction (3 (16.7%) patients) and consolidation (4 (22.2%) patients) cycles. However, cases of ATE were noted at diagnosis (1 (5.6%) patient), after transplantation (1 (5.6%) patient) or at relapse (1 (5.6%) patient) as well. ATE were significantly more frequent among patients with previous history of thromboembolic events (p = 0.016). Moreover, ATE were more common in patients with adverse cytogenetic abnormalities (p < 0.001). Other examined parameters did not significantly differ between those with and without ATE. Summary/Conclusion: The incidence of arterial thrombosis in our group was 3.3% which is in accordance with the previously published studies. Since the great number of already known risk factors for the arterial thrombosis are modifiable (e.g. smoking, diet, physical activity, excessive drinking?) it is important to actively work on the reduction on those risk factors, especially if the patient has the history of previous thromboembolic event and/or suffer from high risk AML. Prophylactic therapy with antiplatelet agents is aggravated due to the lack of firmer evidences and the presence of thrombocytopenia. Therefore further studies regarding this issue are needed.

4.
Free Radical Biology and Medicine ; 177:S132-S133, 2021.
Article in English | EMBASE | ID: covidwho-1623350

ABSTRACT

Introduction: Disturbed redox homeostasis plays multiple roles in COVID-19 pathogenesis. Still, data on the level of oxidative stress by-products in COVID-19 patients are scarce. Aim: To assess the profile of oxidative stress by-products during the course of acute COVID-19 and get more insight into the origin of the systemic oxidative stress in these patients. Material and methods: Malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG) and advanced oxidation protein products (AOPP), as well as clinical inflammatory and biochemical parameters were determined in plasma of 58 COVID-19 patients, on admission, as well as 7 and 14 days upon admission. Results: The highest levels of MDA and AOPP were observed at the time of diagnosis. Based on correlations between 8-OHdG and ALT activity (p = 0.028) or creatinine concentration (p = 0.003) subclinical liver and kidney damage contribute to systemic oxidative stress in the early phase of disease. Seven days upon admission, a significant drop in MDA and AOPP levels was observed, while plasma concentration of 8-OHdG increased (p < 0.005). At this point, a significant correlation of AOPP with inflammatory biomarkers such as CRP (p = 0.016) and absolute number of neutrophils (p = 0.041) was found. 14 days upon admission, a noticeable increase was observed in AOPP (p = 0.004) and MDA levels (p = 0.038), compared to the second point, but without reaching initial values. Moreover, significant correlation was observed between AOPP (p = 0.046) or MDA (p = 0.029) levels with IL-6, as one of the key inflammatory players. Regarding the biochemical parameters, significant correlation of AOPP levels was found with the activity of plasma non-functional enzymes AST (p = 0.001) and LDH (p = 0.030). Conclusions: Significant changes in MDA, 8-OHdG and AOPP levels exist during the course of COVID-19. Correlation between by-products of oxidative damage and clinical immunological or biochemical parameters confirms the suggested involvement of neutrophils networks, IL-6 production, as well as liver and kidney damage involvement in systemic oxidative stress. Keywords: COVID-19;oxidative stress;MDA;AOPP;8-OHdG.

5.
Research and Practice in Thrombosis and Haemostasis ; 5(SUPPL 2), 2021.
Article in English | EMBASE | ID: covidwho-1509073

ABSTRACT

Background : Administration of a standard-dose thromboprophylaxis in all hospitalized Coronavirus disease (COVID-19) patients is recommended. However, despite thromboprophylaxis, frequent thrombotic complications are diagnosed. Rotational thromboelastometry (ROTEM) is a method to access hypercoagulable state in whole blood from these patients. Aims : To analyze ROTEM parameters during the entire clinical COVID-19 stages including mild, moderate and critical phases and to assess the extent of hypercoagulablity by profiling ROTEM patterns. Methods : We evaluated coagulation abnormalities via traditional tests and ROTEM profile in a group of 94 patients with confirmed SARS-CoV-2 infection with different severity of pneumonia (34 moderate, 25 severe, 35 critical). Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in extrinsic rotational thromboelastometry (EXTEM) and fibrinogen rotational thromboelastometry (FIBTEM), shorter than normal EXTEM clot formation time (CFT), and higher than normal α-angle were identified as markers of hypercoagulable state. Results : At least one hypercoagulable ROTEM parameter had 62 (66%) patients. Increment in the number of patients with ≥ 2 hypercoagulable parameters, higher EXTEM ( P = .0001), FIBTEM MCF ( P = 0.0001) and maximum lysis decrement ( P = 0.002) with increment in disease severity was observed ( P = 0.0001). Significant positive correlations between IL6 and CT EXTEM ( P = 0.003), MCF EXTEM ( P = 0.033), MCF FIBTEM ( P = 0.01), and negative with ML EXTEM ( P = 0.006) were seen. Conclusions : These findings confirm that a hypercoagulable ROTEM profile characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with elevated IL6. These results underscore the need for different thromboprophylactic approaches for different severity groups.

6.
HemaSphere ; 5(SUPPL 2):641-642, 2021.
Article in English | EMBASE | ID: covidwho-1393455

ABSTRACT

Background: Thrombosis is frequently diagnosed in patients with Coronavirus disease (COVID - 19), despite the use of a standard-dose thromboprophylaxis in all hospitalized. Since conventional coagulation tests (CCTs) reflect only limited parts of the coagulation system and are insufficient to assess hypercoagulability, rotational thromboelastometry (ROTEM) could be more effective in identifying hypercoagulable pattern and patient in high-risk of thrombosis. Aims: 1. To analyze ROTEM parameters across the entire clinical COVID-19 pneumonia spectrum, from moderate to critical. 2. To determine the incidence of hypercoagulable ROTEM patterns and improve risk stratification. Methods: We evaluated coagulation abnormalities via CCTs and ROTEM in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical). Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in both extrinsic pathway (EXTEM) and fibrinogen pathway (FIBTEM), as well as shorter than normal EXTEM clot formation time (CFT) and higher than normal α-angle were classified as markers of hypercoagulable state. Results: At least one hypercoagulable ROTEM parameter had 62 (66%) patients. Increment in the number of patients with ≥ 2 hypercoagulable parameters, higher EXTEM MCF (P = 0.0001), higher FIBTEM MCF (P = 0.0001) and decrement in maximum lysis (P = 0.002) were observedwith increment in disease severity (P = 0.0001). Significant positive correlations between interleukine - 6 (IL6) and CT EXTEM (P = 0.003), MCF EXTEM (P = 0.033), MCF FIBTEM (P = 0.01) as well as negative with ML EXTEM (P = 0.006) were seen. Contrary to hypercoagulable ROTEM pattern which was not predictive for death, hypocoagulability represented by prolonged EXTEM CT (P = 0.0001) and CFT (P = 0.0001), smaller α angle (P = 0.014) and a prolonged FIBTEM CT (P = .0001) was a predictor. Summary/Conclusion: Our findings confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results support the need for different thromboprophylaxis approaches for different severity groups.

7.
HemaSphere ; 5(SUPPL 2):385, 2021.
Article in English | EMBASE | ID: covidwho-1393437

ABSTRACT

Background: During the past one year different protocols addressing the treatment of acute leukemia (AL) during the coronavirus disease 2019 (COVID-19) outbreak have emerged. However, reliable data regarding this topic are still deficient, since only case series with heterogeneous patient population with different hematologic malignancies are available. Aims: To determine clinical characteristics of COVID-19 and to assess risk factors for mortality in patients with AL. Methods: This prospective study included 51 consecutive adult patients actively treated for AL, with verified SARS-CoV-2 infection treated at two Clinical Centres in Central Serbia. The study enrolled all symptomatic and asymptomatic patients regardless of severity of the infection. Baseline data including age, sex, body mass index, comorbidities, AL type, disease status (newly diagnosed, complete remission (CR), relapsed/ refractory (RR)), treatment (intensive, low-intensity chemotherapy, supportive care), time since AL diagnosis, outcome, laboratory parameters at the onset of infection were collected. Moreover, dana regarding COVID-19 symptoms, disease severity, COVID-19-specific therapies and time to PCR negativity were collected. Methods of descriptive and analytical statistics were used. Results: Most patients (80.4%) had acute myeloid leukemia (AML). At time of COVID-19 diagnosis 35.3% of patients were newly diagnosed with AL. Concurrent diagnosis of COVID-19 and AML was made in 5.89% patients, 23.5% were RR and 41.2% were in CR. Intensive chemotherapy was administered in 80.4% of our patients. At the time of COVID-19 diagnosis 29.4% patients had bone marrow aplasia. Intrahospital transmission was probable in 50.98% patients. Five patients who were initially asymptomatic andwith negative PCR test at the time of admission developed COVID19 symptoms within the first 48 hours. The most common symptoms of COVID-19 were fever (70.4%), fatigue (66.7%) and dyspnea (39.2%). Asymptomatic, mild to moderate, severe and critical COVID-19 was registered in 9.8%, 43.1%, 37.3% and 9.8% patients, respectively. Median time to PCR negativity was 18 days (range 10-50). Mortality for the entire cohort was 17/51 (29.4%). In all cases death was associated with COVID-19 pneumonia. Among COVID-19 symptoms dyspnea (OR 12.536 (95% CI: 3.106 - 50.597)), cephalgia (OR 5.36 (95% CI: 1.200 - 26.482) and fatigue (OR 5.921(95% CI: 1.168 - 30.019) were associated with higher mortality. Patients newly diagnosed with AL (OR 6.00 (95% CI 1.133 - 15.188) and patients with bone marrow aplasia (OR 4.148 (95% CI 1.133 - 15.188) had a significantly worse outcome in comparison with patients in CR. Additionally, pneumonia severity (OR 14.963 (95% CI 3.212 - 69.700) and need for oxygen therapy (OR 6.455 (95% CI 2.56 - 20.262) were associated with higher mortality risk. Among laboratory parameters lower platelet count (OR 0.985 (95% CI 0.973 - 0.996)), prolonged prothrombin time (OR 1.554 (95% CI 1.104 - 2.186)), higher ISTH DIC score (OR 2.122 (95% CI 1.258 - 3.576), C-reactive protein (OR 1.011 (95% CI 1.004 - 1018) and LDH (OR 1.001 (95% CI 1.000 - 1.003) were predictive for death. Summary/Conclusion: Baring in mind high mortality rate, and rate of intrahospital transmission, rigorous isolation of AL patients, permanent symptoms monitoring and prompt testing should be prioritized. Careful risk-benefit assessment regarding the continuing of anticancer therapy is required in patients receiving palliative therapy and intensive induction therapy. Conversely, there is no reason to withhold therapy for the patients in CR.

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