Simple Coagulation Profile as Predictor of Mortality in Adults Admitted with COVID-19: A Meta-Analysis

Context: COVID-19 severe manifestations must be detected as soon as possible. One of the essential poor characteristics is the involvement of coagulopathy. Simple coagulation parameters, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and platelet, are widely accessible in many health centers. Objectives: This meta-analysis aimed to determine the association between simple coagulation profiles and COVID-19 in-hospital mortality. Method: We systematically searched five databases for studies measuring simple coagulation parameters in COVID-19 on admission. The random-effects and inverse-variance weighting were used in the study, which used a standardized-mean difference of coagulation profile values. The odds ratios were computed using the Mantel-Haenszel formula for dichotomous variables. Results: This meta-analysis comprised a total of 30 studies (9,175 patients). In our meta-analysis, we found that non-survivors had a lower platelet count [SMD = -0.56 (95% CI: -0.79 to -0.33), P < 0.01; OR = 3.00 (95% CI: 1.66 to 5.41), P < 0.01], prolonged PT [SMD = 1.22 (95%CI: 0.71 to 1.72), P < 0.01; OR = 1.86 (95%CI: 1.43 to 2.43), P < 0.01], prolonged aPTT [SMD = 0.24 (95%CI: -0.04 to 0.52), P = 0.99], and increased INR [SMD = 2.21 (95%CI: 0.10 to 4.31), P = 0.04] than survivors. Conclusions: In COVID-19 patients, abnormal simple coagulation parameters on admission, such as platelet, PT, and INR, were associated with mortality outcomes.

Clinical Significance and Prognostic Value of Hemostasis Parameters in 337 Patients with Acute Infective Endocarditis

(1) Background: The aim of this study was to assess the clinical significance and prognostic role of the main hemostasis parameters in infective endocarditis (IE): prothrombin time as international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimers, platelet count, homocysteine. (2) Methods: We studied 337 patients with IE. Clinical, hemato-chemical and echocardiography parameters were analyzed. Coagulation parameters were measured on admission. (3) Results: D-dimers levels (p = 0.012) and a prolonged PT-INR (p = 0.013) were associated with higher in-hospital mortality, while prolonged aPTT (p = 0.021) was associated with increased 1-year mortality. Staphylococcus aureus (S. aureus) infection (p = 0.003), prosthetic valve endocarditis (PVE) (p = 0.001), surgical indication (p = 0.002) and higher D-dimer levels (p = 0.005) were independent predictors of in-hospital mortality. PVE (p = 0.001), a higher Charlson Comorbidity Index (p = 0.049), surgical indication (p = 0.001) and prolonged aPTT (p = 0.012) were independent predictors of 1-year mortality. Higher levels of D-dimers (p < 0.001) and a shorter aPTT (p < 0.001) were associated with embolic complications of IE. S. aureus etiology was bound to higher D-dimers levels (p < 0.001) and a shorter aPTT (p = 0.006). (4) Conclusions: Elevated D-dimers are associated with a higher risk for in-hospital mortality in IE patients. High D-dimers and a short aPTT are associated with a higher risk for embolic events in IE. A longer aPTT is associated with 1-year mortality.

Diagnosis and Treatment of Acquired Hemophilia: One Single-Center Experience from PR. China

Objective: To deepen the understanding of the clinical manifestations of acquired hemophilia A for timely and correctly treatment. Methods: The clinical data of the acquired hemophilia A patients diagnosed in the hospital from Jan 2006 to Mar 2021 were retrospectively analyzed, and the relevant literature was reviewed. Results: 17 patients with acquired hemophilia A, male: female =10: 7, median age 61 years (19 to 78 years), were diagnosed and treated in the hospital with the median time from the onset to diagnosis 21 days (2 days to 6 months). Six patients had comorbidity, including hepatitis B carrying, chronic myelomonocytic leukemia, diabetes, hypertension and positive autoantibodies, pemphigoid and gastric cancer, respectively. Other 11 patients were healthy before the onset. All patients had large large ecchymosis of skin, and one case was combined with hematuria, and one case with retroperitoneal hematoma. All patients had APTT extension (45s-144.7s) and the prolonged APTT could not be corrected with normal mixed plasma with and without incubation at 37℃ for 2 hours. FVIII activity was 1% - 8.9% and inhibitor titer 2 - 128 Bu/ml. All patients with bleeding were with prothrombin complex/recombinant activated coagulation factor VII, some of them with pd-coagulation factor FVIII preparations. Inhibitors were removed with prednisone acetate (1 case) + chemotherapy (1 case), prednisone acetate / + CTX (11 cases) + chemotherapy (1 case), prednisone acetate/prednisolone + mabthera (2 cases) + CTX (1 case), respectively. The removal time of inhibitor was from 8 days to 4 years. During the treatment process, two patients developed lower extremity venous thrombosis, and one patient was complicated with lung infection. Conclusion: Patients with unexplained bleeding and prolonged APTT should be conducted normal mixed plasma correction test, coagulation factor activity and inhibitor titer examination. After correctly diagnosis, bypass agents /coagulation factor VIII preparations should be given timely for hemostasis, protocol based on glucocorticoid + CTX/mabthera to remove the inhibitor and symptomatic treatment for patients with primary comorbidity disease at the same time. Disclosures No relevant conflicts of interest to declare.

Diagnosis and Management of Acquired Hemophilia A: Case Reports and a Literature Review

Background. Acquired hemophilia A (AHA) is a potentially life-threatening autoimmune hemostatic disorder where autoantibodies that disrupt the functions of factor VIII (FVIII) are present in the circulation. The early diagnosis of AHA is difficult since the symptoms of AHA differ from those of congenital hemophilia A. Furthermore, the management of AHA is also more complex due to the presence of autoantibodies against FVIII (FVIII inhibitors). Here, we present three case reports and conduct a literature review of AHA with the aim to increase awareness and knowledge regarding the diagnosis and treatment of AHA. Case Presentations. We present three patients diagnosed with AHA in these case reports. The first patient was a young female, while the second and third patients were middle-aged and elderly males, respectively. All patients presented with a chief complaint of bruises without hemarthrosis and a history of bleeding. Laboratory examinations of the patients revealed isolated prolonged aPTT, normal PT, and the presence of autoantibodies against factor VIII, which are characteristics of AHA. Patients were then treated with corticosteroids to reduce the titer level of autoantibodies and received factor VIII transfusion to stop bleeding. Conclusion. AHA can be suspected in patients presenting with symptoms of bruises without hemarthrosis and without the history of bleeding. Isolated aPTT elevation with normal PT should raise high suspicion of AHA. The presence of FVIII inhibitors can help to confirm the diagnosis of AHA. Treatment consists of factor VIII transfusion and corticosteroid therapy. Bypassing agents are recommended as an alternative to FVIII transfusion.

Coagulation abnormalities in Dengue fever infection: A systematic review and meta-analysis

Background Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection. Method This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg’s Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles. Result Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively. Conclusion The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.

Effect of Leukoreduction by Pre-Storage Filtration on Coagulation Activity of Canine Plasma Collected for Transfusion

Leukoreduction of blood products is a technique used to prevent leukocyte-induced transfusion reactions and is extensively used in human, but rarely in veterinary patients. The concentration of some coagulation proteins can be affected by the processing steps used for the preparation of leuko-reduced plasma units. In this study, we assessed the effect of leukoreduction on coagulation activity of canine plasma collected for transfusion. Ten plasma units, five obtained from non-leuko-reduced (non-LR) whole blood (WB) units and five from leuko-reduced (LR) WB units were evaluated. Prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factor activities of factors (F) V, VIII, X, XI, and von Willebrand (vWF), fibrinogen and D-dimers content were assessed at collection (baseline value, D0) and after 7 days of frozen storage at −18 °C (D7). Compared to non-LR plasma units, LR units showed a statistically significant prolonged aPTT and reduced FXI activity. Filtration had no significant effect on the other factors and parameters evaluated. Filtration-dependent changes appear to have no impact on the therapeutic quality of plasma obtained from leuko-reduced whole blood, other than for FXI activity. Further studies on a larger sample size comparing the same unit before and after leukoreduction are needed to confirm these findings.

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.

512 A CASE OF AN IDIOPATHIC ACQUIRED HEMOPHILIA A IN AN ELDERLY WOMAN

Introduction Acquired Hemophilia is a bleeding diathesis caused by autoantibodies that interfere with factor VIII (FVIII). Reasons for autoantibodies production are not clear but may be related to gene polymorphisms and/or CD4+ T lymphocytes. 1.3 to 1.5 cases per million population per year are reported in the UK. Half of the cases are secondary to malignancy, pregnancy related conditions, connective tissue disorders or drug reactions while the rest are idiopathic. Case Report We report a case of an acquired hemophilia A in an 86-year-old lady with underlying type 2 diabetes, hypertension, and cognitive impairment, being treated as the left lower limb cellulitis with antibiotics. She was found to have a sudden hemoglobin drop and her CT (Abdomen) confirmed a spontaneous intra-abdominal hematoma. Clotting profile showed prolonged APTT to 168.5 seconds, being not corrected at mixing study, with normal PT and INR. The FVIII assay was reduced to 18.4 iU/dL with FVIII inhibitor concentration of 0.7 Bu. Viral and autoimmune screenings were negative. The idiopathic acquired hemophilia A was diagnosed. Red blood cell transfusions, bypassing agents (FEIBA) and oral tranexamic acid were given for acute bleeding episode. Concomitantly, oral prednisolone was used to reduce the inhibitor levels. Repeated FVIII assay showed 121 iU/dL and 199iU/dL on day 6 and 12, respectively. Steroid was continued for the next 4 weeks and then gradually tapered. No further bleeding episode was noted. Conclusion The diagnosis of acquired hemophilia should be considered in any elderly patient with prolonged APTT. Mixing study is to measure the presence of inhibitors of coagulation or to detect coagulation factor deficiency. Quantitative coagulation factor assays and Bethesda Assays are performed for definitive diagnosis. Immunosuppressive regimens are the mainstay treatment. However, premorbid conditions and co-morbidities should be taken into consideration before initiating the aggressive immunosuppressive therapy in the elderly patients.

Evaluation of the merit of the methanolic extract of Andrographis paniculata to supplement anti-snake venom in reversing secondary hemostatic abnormalities induced by Naja naja venom

Increasing evidence suggests a sizable involvement of hemotoxins in the morbidity associated with envenomation by the Indian spectacled cobra, Naja naja (N.N). This study investigates the ability of Indian polyvalent anti-snake venom (ASV), methanolic extract of Andrographis paniculata (MAP) and their combination in reversing the hemostatic abnormalities, viz. activated partial thromboplastin time(aPTT), prothrombin time(PT) and thrombin time(TT) in citrated plasma. These parameters were assessed in 2 groups of experiments. Group 1: Without the prior incubation of plasma with venom and Group 2: With prior incubation of plasma with venom for 90 min at 37°C. Venom caused significant (p < 0.001) prolongation in aPTT (175%), PT (49%) and TT (34%) in Group 1 and ASV could completely bring them back to normal. MAP showed a concentration-dependent reversal in aPTT, normalization of PT and prolongation of TT. When low concentration of ASV was supplemented with MAP, their combined effect in normalizing aPTT and PT improved by 37% and 26% respectively when compared to ASV alone. In Group 2, venom caused significant (p < 0.001) prolongation in aPTT (231%), PT (312%) and TT (245%). ASV had limited effect in reversing aPTT (52%), TT (31%) but completely normalized PT. MAP was marginally effective in reversing the prolonged aPTT and PT but caused further prolongation of TT. Combination of ASV and MAP was more effective than ASV alone in reversing venom-induced increase in aPTT (52%) and PT (29%). The study proved that, a drastic reduction of ASV by 70%, could be effectively supplemented by MAP in combating hemostatic abnormalities induced by NN venom.