Risk stratification and prognostic value of prothrombin time and activated partial thromboplastin time among COVID-19 patients.

BACKGROUND: COVID-19 is a viral disease caused by a new strain of corona virus. Currently, prognosis and risk stratification of COVID-19 patients is done by the disease's clinical presentation. Therefore, identifying laboratory biomarkers for disease prognosis and risk stratification of COVID-19 patients is critical for prompt treatment. Therefore, the main objective of this study was to assess the risk stratification and prognostic value of basic coagulation parameters and factors associated with disease severity among COVID-19 patients at the Tibebe Ghion Specialized Hospital, COVID-19 treatment center, Northwest Ethiopia. METHODS: A follow-up study was conducted among conveniently recruited COVID-19 patients attended from March to June 2021. Socio-demographic and clinical data were collected using a structured questionnaire and checklist, respectively. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were analyzed by the HUMACLOT DUE PLUS® machine. Descriptive statistics were used to summarize the socio-demographic and clinical characteristics of study participants. Kruskal Wallis tests were used to compare the difference between parametric and non-parametric continuous variables, respectively. The area under the receiver operating characteristic curve (AUC) was used to evaluate the value of PT and APTT in the risk stratification and disease prognosis of COVID-19 patients. Ordinal logistic regression was used to identify the factors associated with disease severity and prognosis. A P-value < 0.05 was defined as statistically significant for all results. RESULT: Baseline PT at a cut-off value ≥ 16.25 seconds differentiated severe COVID-19 patients from mild and moderate patients (AUC: 0.89, 95% CI: 0.83-0.95). PT also differentiated mild COVID-19 patients from moderate and severe patients at a cut-off value ≤ 15.35 seconds (AUC: 0.90, 95% CI: 0.84-0.96). Moreover, alcohol drinkers were a 3.52 times more likely chance of having severe disease than non-drinkers (95% CI: 1.41-8.81). A one-year increment in age also increased the odds of disease severity by 6% (95% CI: 3-9%). An increment of ≥ 0.65 seconds from the baseline PT predicted poor prognosis (AUC: 0.93, 0.87-0.99). CONCLUSIONS AND RECOMMENDATIONS: Prolonged baseline PT was observed in severe COVID-19 patients. Prolonged baseline PT was also predicted to worsen prognosis. An increase from the baseline PT was associated with worsen prognosis. Therefore, PT can be used as a risk stratification and prognostic marker in COVID-19 patients.

Would Tracking Coagulation Together with Inflamation Markers be a Prospect for COVID-19 Disease Prognosis?

BACKGROUND: The purpose of this study is to evaluate the prognostic roles of hemostatic tests including prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, and antithrombin III in the progression of disease, monitorization of severe, mild and moderate cases, and also to show their relationship with inflammatory markers including C-reactive protein (CRP), procalcitonin, and interleukin-6 (IL-6). METHODS: The study comprised 604 patients (360 men and 244 women) with confirmed SARS-CoV-2 infection admitted to Emergency Department of Istanbul Faculty of Medicine between March 15 and April 15, 2020. The variations in the concentration of coagulation tests and inflammatory markers were observed from the admission to hospital to the 10th day with three-day periods. RESULTS: PT level and PT activity of severe cases were significantly different compared to mild cases (p = 0.012, p = 0.010, respectively). Similarly, aPTT and D-dimer levels in severe cases were significantly higher compared to the mild cases. However, fibrinogen levels of mild cases were significantly lower compared to either moderate or severe cases (p < 0.001, for both). The PT, PT activity, aPTT, and D-Dimer levels in severe cases were significantly different compared with the mild cases. However, fibrinogen level was the highest in severe cases, and higher than either mild or moderate cases. CONCLUSIONS: Our findings reveal the vital importance of measuring coagulation parameters at the time of admission and monitoring them at regular intervals in clinical monitoring of COVID-19 patients, in determining the severity of the disease in terms of the patient's prognosis, and in choosing and applying the appropriate treatment at the right time.

Hematologic Evaluation of Children with COVID-19 Infection: Mortality Biomarkers.

BACKGROUND: In this study, we investigated the predictive value of routine coagulation parameters including D-dimer, Prothrombin Time (PT), International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT) and Complete Blood Count (CBC) test parameters in children with COVID-19 infection. METHODS: Retrospective and observational study carried out in Abuzar Hospital, Ahvaz Jundishapur University of Medical Sciences (Ahvaz, Iran) included COVID-19 patients. RESULTS: Deceased patients (n = 5) compared to alive patients (n = 76) showed higher RDW (p = 0.005), PT (p = 0.005), INR (p = 0.004), PTT (p = 0.009), platelet count (p < 0.001), PLR (p < 0.001), and hospitalization time (p < 0.001). The area under the curve (AUC) of RDW was 0.85 (95% CI 0.75 - 0.96) which indicates its high power for mortality prediction in hospitalized children with COVID-19. We did not find significant differences in parameters in comparison between different severities. CONCLUSIONS: To our knowledge, our study is one of the few studies to evaluate routine coagulation tests and the CBC test parameters predictive value in children with COVID-19. RDW has the most power to predict the mortality of children with COVID-19, followed by PT, INR, aPTT, platelet count, PLR, and hospitalization time have a high power to predict the risk of death in patients.

Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm.

Aortic aneurysms are sometimes associated with enhanced-fibrinolytic-type disseminated intravascular coagulation (DIC). In enhanced-fibrinolytic-type DIC, both coagulation and fibrinolysis are markedly activated. Typical cases show decreased platelet counts and fibrinogen levels, increased concentrations of fibrin/fibrinogen degradation products (FDP) and D-dimer, and increased FDP/D-dimer ratios. Thrombin-antithrombin complex or prothrombin fragment 1 + 2, as markers of coagulation activation, and plasmin-α2 plasmin inhibitor complex, a marker of fibrinolytic activation, are all markedly increased. Prolongation of prothrombin time (PT) is not so obvious, and the activated partial thromboplastin time (APTT) is rather shortened in some cases. As a result, DIC can be neither diagnosed nor excluded based on PT and APTT alone. Many of the factors involved in coagulation and fibrinolysis activation are serine proteases. Treatment of enhanced-fibrinolytic-type DIC requires consideration of how to control the function of these serine proteases. The cornerstone of DIC treatment is treatment of the underlying pathology. However, in some cases surgery is either not possible or exacerbates the DIC associated with aortic aneurysm. In such cases, pharmacotherapy becomes even more important. Unfractionated heparin, other heparins, synthetic protease inhibitors, recombinant thrombomodulin, and direct oral anticoagulants (DOACs) are agents that inhibit serine proteases, and all are effective against DIC. Inhibition of activated coagulation factors by anticoagulants is key to the treatment of DIC. Among them, DOACs can be taken orally and is useful for outpatient treatment. Combination therapy of heparin and nafamostat allows fine-adjustment of anticoagulant and antifibrinolytic effects. While warfarin is an anticoagulant, this agent is ineffective in the treatment of DIC because it inhibits the production of coagulation factors as substrates without inhibiting activated coagulation factors. In addition, monotherapy using tranexamic acid in cases of enhanced-fibrinolytic-type DIC may induce fatal thrombosis. If tranexamic acid is needed for DIC, combination with anticoagulant therapy is of critical importance.

The One Hour COVID Test: A Rapid Colorimetric Reverse-Transcription LAMP-Based COVID-19 Test Requiring Minimal Equipment.

At this writing, over 100 million people have tested positive for Corona Virus Disease-19 (COVID-19), and the global death toll from this disease has reached nearly 3 million. Despite the many tests currently available, we have not yet achieved the testing capacity needed to limit the spread of the virus and mitigate suffering worldwide. We have developed the One Hour COVID Test to address this challenge. Our test leverages an easy-to-use, commercially available oral swab kit for sample collection paired with a novel RNA processing protocol and a simple colorimetric assay that requires minimal equipment. The test can be easily scaled via automation and takes 1 h from sample collection to result.

Investigation of the Molecular Mechanism of Coagulopathy in Severe and Critical Patients With COVID-19.

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.

Ultramicronized Palmitoylethanolamide in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation.

Disseminated intravascular coagulation (DIC) is a severe condition characterized by the systemic formation of microthrombi complicated with bleeding tendency and organ dysfunction. In the last years, it represents one of the most frequent consequences of coronavirus disease 2019 (COVID-19). The pathogenesis of DIC is complex, with cross-talk between the coagulant and inflammatory pathways. The objective of this study is to investigate the anti-inflammatory action of ultramicronized palmitoylethanolamide (um-PEA) in a lipopolysaccharide (LPS)-induced DIC model in rats. Experimental DIC was induced by continual infusion of LPS (30 mg/kg) for 4 h through the tail vein. Um-PEA (30 mg/kg) was given orally 30 min before and 1 h after the start of intravenous infusion of LPS. Results showed that um-PEA reduced alteration of coagulation markers, as well as proinflammatory cytokine release in plasma and lung samples, induced by LPS infusion. Furthermore, um-PEA also has the effect of preventing the formation of fibrin deposition and lung damage. Moreover, um-PEA was able to reduce the number of mast cells (MCs) and the release of its serine proteases, which are also necessary for SARS-CoV-2 infection. These results suggest that um-PEA could be considered as a potential therapeutic approach in the management of DIC and in clinical implications associated to coagulopathy and lung dysfunction, such as COVID-19.

Inflammation/coagulopathy/fibrinolysis: Dynamic indicators of COVID-19 progression in patients with moderate COVID-19 in Wenzhou, China.

BACKGROUND: The majority of the coronavirus disease 2019 (COVID-19) non-survivors meet the criteria for disseminated intravascular coagulation (DIC). Although timely monitoring of clotting hemorrhagic development during the natural course of COVID-19 is critical for understanding pathogenesis, diagnosis, and treatment of the disease, however, limited data are available on the dynamic processes of inflammation/coagulopathy/fibrinolysis (ICF). METHODS: We monitored the dynamic progression of ICF in patients with moderate COVID-19. Out of 694 COVID-19 inpatients from 10 hospitals in Wenzhou, China, we selected 293 adult patients without comorbidities. These patients were divided into different daily cohorts according to the COVID-19 onset-time. Furthermore, data of 223 COVID-19 patients with comorbidities and 22 critical cases were analyzed. Retrospective data were extracted from electronic medical records. RESULTS: The virus-induced damages to pre-hospitalization patients triggered two ICF fluctuations during the 14-day course of the disease. C-reactive protein (CRP), fibrinogen, and D-dimer levels increased and peaked at day 5 (D) 5 and D9 during the 1st and 2nd fluctuations, respectively. The ICF activities were higher during the 2nd fluctuation. Although 12-day medication returned high CRP concentrations to normal and blocked fibrinogen increase, the D-dimer levels remained high on days 17 ±â€¯2 and 23 ±â€¯2 days of the COVID-19 course. Notably, although the oxygenation index, prothrombin time and activated partial thromboplastin time were within the normal range in critical COVID-19 patients at administration, 86% of these patients had a D-dimer level > 500 µg/L. CONCLUSION: COVID-19 is linked with chronic DIC, which could be responsible for the progression of the disease. Understanding and monitoring ICF progression during COVID-19 can help clinicians in identifying the stage of the disease quickly and accurately and administering suitable treatment.

COVID-19-related laboratory coagulation findings.

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.

Blood coagulation parameter abnormalities in hospitalized patients with confirmed COVID-19 in Ethiopia.

BACKGROUND: Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19). Abnormal coagulation parameters in COVID-19 patients are important prognostic factors of disease severity. The aim of this study was to analyze coagulation profiles of hospitalized COVID-19 patients in Addis Ababa, Ethiopia. METHODS: This prospective cross-sectional study was conducted among 455 Covid-19 patients admitted at Millennium COVID-19 care and treatment center, Addis Ababa, Ethiopia from July 1- October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOT DUE PLUS® coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p<0.05 was defined as statistically significant. RESULT: A prolonged prothrombin time was found in 46.8% of study participants with COVID-19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients. Thrombocytopenia was detected in 22.1% of COVID-19 patients. 50.5% and 51.3% of COVID-19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. CONCLUSION: In this study, prolonged prothrombin time and elevated INR were detected in more than 50% of severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID-19 patients.

A predictive score for progression of COVID-19 in hospitalized persons: a cohort study.

Accurate prediction of the risk of progression of coronavirus disease (COVID-19) is needed at the time of hospitalization. Logistic regression analyses are used to interrogate clinical and laboratory co-variates from every hospital admission from an area of 2 million people with sporadic cases. From a total of 98 subjects, 3 were severe COVID-19 on admission. From the remaining subjects, 24 developed severe/critical symptoms. The predictive model includes four co-variates: age (>60 years; odds ratio [OR] = 12 [2.3, 62]); blood oxygen saturation (<97%; OR = 10.4 [2.04, 53]); C-reactive protein (>5.75 mg/L; OR = 9.3 [1.5, 58]); and prothrombin time (>12.3 s; OR = 6.7 [1.1, 41]). Cutoff value is two factors, and the sensitivity and specificity are 96% and 78% respectively. The area under the receiver-operator characteristic curve is 0.937. This model is suitable in predicting which unselected newly hospitalized persons are at-risk to develop severe/critical COVID-19.

Coagulation dysfunction is associated with severity of COVID-19: A meta-analysis.

To systematically analyze the blood coagulation features of coronavirus disease 2019 (COVID-19) patients to provide a reference for clinical practice. An electronic search in PubMed, EMbase, Web of Science, Scopus, CNKI, WanFang Data, and VIP databases to identify studies describing the blood coagulation features of COVID-19 patients from 1 January 2020 to 21 April 2020. Three reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies, then, the meta-analysis was performed by using Stata 12.0 software. Thirty-four studies involving 6492 COVID-19 patients were included. Meta-analysis showed that patients with severe disease showed significantly lower platelet count (weighted mean differences [WMD]: -16.29 × 109 /L; 95% confidence interval [CI]: -25.34 to -7.23) and shorter activated partial thromboplastin time (WMD: -0.81 seconds; 95% CI: -1.94 to 0.33) but higher D-dimer levels (WMD: 0.44 µg/mL; 95% CI: 0.29-0.58), higher fibrinogen levels (WMD: 0.51 g/L; 95% CI: 0.33-0.69) and longer prothrombin time (PT; WMD: 0.65 seconds; 95% CI: 0.44-0.86). Patients who died showed significantly higher D-dimer levels (WMD: 6.58 µg/mL; 95% CI: 3.59-9.57), longer PT (WMD: 1.27 seconds; 95% CI: 0.49-2.06) and lower platelet count (WMD: -39.73 × 109 /L; 95% CI: -61.99 to -17.45) than patients who survived. Coagulation dysfunction is common in severe COVID-19 patients and it is associated with severity of COVID-19.

Coagulopathy in COVID-19.

The COVID-19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID-19. The clinical presentation of COVID-19-associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D-dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial-sepsis-associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID-19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID-19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Clinical and laboratory features of hypercoagulability in COVID-19 and other respiratory viral infections amongst predominantly younger adults with few comorbidities.

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.

Analysis of factors for disease progression in 61 patients with COVID-19 in Xiaogan, Hubei, China.

OBJECTIVE: The aim of this study was to retrospectively analyze clinical characteristics and laboratory results of the novel coronavirus pneumonia (COVID-19) patients so as to identify factors related to disease progression. PATIENTS AND METHODS: Sixty-one patients with COVID-19 were divided into two groups: an improvement/stabilization group (n = 53) and a progression group (n = 8). Clinical data were collected to analyze and compare the differences between the two groups. RESULTS: Of the sixty-one patients, thirty-one were male (50.8%), and thirty were female (49.2%), with a median age of 53 years. On admission, significant differences were observed between the two groups with respect to the levels of Creatine Kinase (CK), lymphocytes, D-dimer and creatinine, and prothrombin time (PT). Univariate logistic regression analysis showed that Platelet-to-lymphocyte ratio (PLR), lymphocytes, Mean platelet volume to lymphocyte ratio (MPVLR), CK, White Blood count to mean platelet volume ratio (WMR), Lymphocyte-to-monocyte ratio (LMR), and serum creatinine were important factors for disease progression. Multivariate logistic regression analysis showed that PLR was an independent factor for disease progression in COVID-19 patients. The receiver operating characteristic (ROC) curve revealed that the best predictor of disease progression was CK. Dynamic changes in the laboratory indicators of patients were tracked, and significant differences were found in the variation trends of white blood cell count, neutrophil count, and WMR, which gradually increased in the progression group, but gradually decreased in the improvement/stabilization group. CONCLUSIONS: Risk factors for disease progression included PLR, lymphocytes, MPVLR, CK, WMR, LMR, and creatinine, among which, PLR is an independent risk factor for disease progression in COVID-19 patients.

Epidemiological and Clinical Profile of Pediatric Inflammatory Multisystem Syndrome - Temporally Associated with SARS-CoV-2 (PIMS-TS) in Indian Children.

Background: We describe the demographic, clinical and labo-ratory findings along with the treatment and outcomes among children meeting the case definition of Pediatric Inflammatory Multisystem Syndrome - Temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We analyzed the clinical and laboratory findings of children who presented with PIMS-TS during an 8-week period from May 4, 2020 to July 8, 2020. RESULTS: We report 19 children with a median age of 6 year (IQR: 13 months-16 years), who met the case definition of PIMS-TS. All of them presented with fever. Multi organ involvement (79%), mucocutaneous involvement (74%), cardiovascular symptoms (63%) and gastrointestinal symptoms (42%) were the other features. Elevated levels of C-reactive protein was found in all of them and the majority of them had evidence of coagulopathy; intensive care admissions were needed in 12 (63%) and vasoactive medications were given to 6 (31.5%) children. There were no deaths. CONCLUSION: Children with PIMS-TS present with a wide range of signs and symptoms. Fewer children in this series had coronary artery abnormalities, and there was a low incidence of RT-PCR positivity with high presence of SARS-CoV-2 antibodies.