Could platelet mass index (PMI) be a new prognostic biomarker for COVID-19?

Aim: Although most patients with COVID-19 experience respiratory tract infections, severe reactions to the virus may cause coagulation abnormalities that mimic other systemic coagulopathies associated with severe infections, such as disseminated intravascular coagulation and thrombotic microangiopathy. Fluctuations in platelet markers, which are an indicator of the acute phase response for COVID-19, are of clinical importance. The aim of this study is to evaluate the relationship between disease severity and Platelet Mass Index (MPI) parameters in COVID-19 patients. Material(s) and Method(s): This retrospective observational study was conducted with patients who were diagnosed with COVID-19 in a tertiary hospital. The study was continued with the remaining 280 patients. All laboratory data were scanned retrospectively from patient files and hospital information system. Result(s): A very high positive correlation was found between PMI and PLT. The PMI value in women was significantly higher than in men. It was observed that PMI did not differ significantly in terms of mortality, intubation, CPAP and comorbidity. PMI vs. Pneumonia Ct Severity Score, biochemistry parameters (AST, CRP), hemogram parameters (WBC, HGB, HCT, MCV, LYM, MPV EO) and coagulation factors (aPTT and FIB) at various levels of positive/negative, weak and strong, and significant relationship was found. There was no significant relationship between hormone and D-dimer when compared with PMI. Discussion(s): Although platelet count alone does not provide information about the prognosis of the disease, PMI may guide the clinician as an indicator of lung damage in seriously ill patients.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Clinical and laboratory characteristics of SARS-CoV-2 infection in overweight and obese patients.

Objective. To assess the impact of obesity and overweight on the course of COVID-19. Patients and methods. This prospective study included 218 patients with SARS-CoV-2 infection aged 18 to 94 years hospitalized between June 2020 and March 2021. We evaluated their clinical and laboratory parameters and their association with body weight. All patients were divided into 3 groups depending on their body mass index (BMI). Group 1 included 81 patients with grade 1-3 obesity (BMI >=30);group 2 comprised 71 overweight patients (BMI >=25 and <30);group 3 included 66 patients with normal body weight (BMI >=18.5 and <25). We analyzed clinical symptoms (including shortness of breath, fever, myalgia, headache, fatigue, changes in the oropharynx, cough, rhinorrhea, sore throat, anosmia, and diarrhea), prevalence of concomitant disorders and complications, findings of computed tomography and pulse oximetry, and findings of instrumental and laboratory examinations (complete blood count, urine test, electrocardiography, echo cardiography, biochemical assays, including C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, lactate, lactate dehydrogenase, activated partial thromboplastin time, prothrombin index, D-dimer, ferritin). Data analysis was performed using the Statistica 6.0 software. Results. We found that overweight and obese patients were more likely to have the main COVID-19 symptoms and comorbidities than those with normal weight. Overweight and obese patients also required respiratory support more frequently than patients with normal weight. Obese and overweight patients had more severe systemic inflammation (CRP, procalcitonin), cytolysis (ALT, AST), and thrombosis (D-dimer). Conclusion. Our findings suggest that obesity and overweight are the factors associated with a more severe SARS-CoV-2 infection, which should be considered when planning their treatment and developing resource strategies.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Predictive value of immunoglobulin G, activated partial thromboplastin time, platelet, and indirect bilirubin for delayed viral clearance in patients infected with the Omicron variant.

Background: Omicron is the recently emerged highly transmissible severe acute respiratory syndrome coronavirus 2 variant that has caused a dramatic increase in coronavirus disease-2019 infection cases worldwide. This study was to investigate the association between demographic and laboratory findings, and the duration of Omicron viral clearance. Methods: Approximately 278 Omicron cases at the Ruijin Hospital Luwan Branch, Shanghai Jiaotong University School of Medicine were retrospectively analyzed between August 11 and August 31, 2022. Demographic and laboratory data were also collected. The association between demographics, laboratory findings, and duration of Omicron viral clearance was analyzed using Pearson correlation analysis and univariate and multivariate logistic regression. Results: Univariate logistic regression analyses showed that a prolonged viral clearance time was significantly associated with older age and lower immunoglobulin (Ig) G and platelet (PLT) levels. Using multinomial logistic regression analyses, direct bilirubin, IgG, activated partial thromboplastin time (APTT), and PLT were independent factors for longer viral shedding duration. The model combining direct bilirubin, IgG, APTT, and PLT identifies patients infected with Omicron whose viral clearance time was ≥7 days with 62.7% sensitivity and 83.4% specificity. Conclusion: These findings suggest that direct bilirubin, IgG, PLT, and APTT are significant risk factors for a longer viral shedding duration in patients infected with Omicron. Measuring levels of direct bilirubin, IgG, PLT, and APTT is advantageous to identify patients infected with Omicron with longer viral shedding duration.

Acquired Factor VIII Inhibitors: A Case Study.

The physiology of hemostasis is one of high complexity that involves the initiation, amplification, and propagation of the many moving parts of the hemostatic system and its regulatory mechanisms. It is imperative that clinical laboratory professionals have a strong understanding of the many intricacies of the physiology of coagulation and its in vitro testing. An elongated activated partial thromboplastin time can have several causes, and the correct cause must be elucidated in a timely manner for proper treatment. A mixing study with normal pooled plasma should be performed to evaluate for the presence of an inhibitor vs factor deficiency. Factor inhibitors, specifically factor VIII in this case study, should be titered so that the clinician can decide which treatment may work best for the patient. Continued monitoring of factor levels and inhibitor titers should be conducted to follow the resolution or progression of inhibitor presence.

Coagulopathy in Covid-19 patients an observational institutional study at MGMMC, Indore

Introduction- Corona virus disease 2019 (COVID-19), first identified in Wuhan, China in December of 2019, has become a worldwide pandemic. It was declared by (WHO) World health organization as Public health emergency on 30th January 2020. Although respiratory compromise is the cardinal feature of the disease, early studies have suggested that elevated circulating D-dimer levels are associated with mortality, 1, 2 suggesting a distinct coagulation disorder associated with COVID-19 Materials And Methods- All patients aged ≥18 years with confirmed COVID-19 (defined as a positive SARS-CoV-2 reverse-transcriptase polymerase chain reaction test by nasopharyngeal/oropharyngeal swab or sputum specimen) were included in the study. The incidence of bleeding and thrombotic events in COVID-19 patients was assessed. Pulmonary embolism (PE) and deep vein thrombosis (DVT) were confirmed radiographically. Results of 6 routinely drawn coagulation-based laboratory parameters (PT, international normalized ratio [INR], activated partial thromboplastin time [aPTT], D-dimer, fibrinogen, and platelet count), 2 laboratory measures of inflammation (C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]), were evaluated and compared between patients with thrombotic complications (composite of venous thromboembolism, arterial thromboembolism, and clinically significant non-vessel thrombotic complications), patients with bleeding complications, and patients without bleeding or thrombotic complications. Result- In this study, we report the haemostatic manifestations and bleeding and thrombotic complications of 100 COVID-19 patients. In a population managed with standard doses of prophylactic anticoagulation, we found a radiographically confirmed venous thromboembolic rate of 4.8% (7.6% in critically ill patients) Conclusion- In conclusion, we observed that COVID-19 was associated with similar rates of thrombosis and bleeding as seen in hospitalized patients with similar degrees of critical illness. Elevated D-dimer levels at initial presentation predicted bleeding complications, thrombotic complications, critical illness, and death. Beyond D-dimer, thrombosis was primarily associated with inflammatory markers rather than coagulation parameters. We additionally found that elevations in D-dimer on admission predicted critical illness and death, as well as bleeding and thrombotic complications. Inflammatory markers, including CRP and ESR, were also associated with thrombosis. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Acute urticaria with Angioedema in a patient with COVID-19 pneumonia: Favipiravir side effect or a rare cutaneous manifestation

Introduction: Coronavirus disease 2019 (COVID-19) has caused thousands of deaths since it was declared as a pandemic. Recently it continues to be one of the most followed topics in the world in terms of its course and treatment. Favipiravir is a broad-spectrum anti-viral agent that has been shown to be effective against various Coronaviruses in vitro. However, as with any drug use, side effects may develop with the use of favipravir treatment. Case Report: We reported a 55-year-old female patient with acute urticarial with angioedema whom had COVID-19 pneumonia. She had no history of allergy, atopy, previous similar episodes or family history of hereditary angioedema. There is no drug or food consumption that may be suspicious in terms of allergy described by the patient other than favipravir. Conclusion(s): As far as we know, it is the first case reported from our country. Since there is no specific examination for differential diagnosis, we cannot distinguish as a rare side effect due to favipiravir treatment or COVID-19 cutaneous manifestation. As a result, studies involving more cases of COVID-19 skin findings are needed.© Copyright 2020 by Emergency Physicians Association of Turkey.

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Study of haematological parameters in Covid-19 positive patients at tertiary care hospital

Introduction: Apart from clinical symptoms and pulmonary computed tomography (CT) findings in, confirmed COVID-19 patients' Blood tests have an important role in early diagnosis of the disease and they provide valuable information to physicians regarding the inflammatory status in body. Material(s) and Method(s): A retrospective cross-sectional study was conducted from January 2020 to March 2020 in the Pathology Department of Rural Medical College, Loni. Total of 120 patients from different groups, both genders and between 18 and 75-year age were studied. Result(s): TLC, Neutrophil, NLR, PLR, D-Dimer values were found to have statistical significant (p<0.05) positive correlation with Covid -19 severity.Blood investigations like Lymphocyte and Monocyte count have statistical significant (p<0.05) negative correlation with Covid -19 severity. No significant correlation was observed between haematological tests like Hb, HCT, PLT, LMR and tests of coagulation like PT & APTT with Covid -19 severity. Conclusion(s): We concluded that TLC, NLR and D-dimer tests are important to predict about the severity of disease.Copyright © 2022 Pravara Institute of Medical Sciences. All rights reserved.

Use of viscoelastic tests in the intensive care unit for the evaluation of haemostasis in SARS-CoV-2 infection

Introduction: COVID-19 coagulopathy is associated with poor prognosis and a state of coexisting 'hypercoagulopathy' (HyperC) and hypofibrinolysis, only detected by viscoelastic tests (VET). VET technology has been useful in areas where conventional tests are inadequate, such as screening for HyperC, thrombotic risk assessment and systemic anticoagulants' effect. We aim to characterize the evolution profile of coagulopathy in patients with COVID-19 infection during their intensive care unit (ICU) stay. Method(s): Consecutive recruitment of adult COVID-19 patients admitted to our hospital's ICU, during a 6 months period. Patients with thrombosis in the previous 3 months, pregnancy, under hormone therapy, and congenital coagulopathies were excluded. VET were executed every 5 days, at discharge and in complications and all of them were under low weight molecular heparin (LMWH) therapy. Group 1 (G1), n = 24-less than 10 days in ICU and group 2 (G2), n = 16-more than 10 days in ICU. In G1 there was 1 death (day 3) and in G2 there were 5 deaths (between days 15 and 42). We focused current analysis on VET-Rotem parameters (see Fig. 1). Result(s): Prognostic scores APACHE II, SAPS II and SOFA were higher in G2, but surprisingly G1 patients are more obese. G2 patients had shorter aPTT and lower platelets. The variables CT-HepTem and MCF Extem-MCF-Fib-Tem present a greater difference between groups, but no statistical significance. We observed an initial correlation between basophils number (which is lower) on CT Intem and CT Hep-Tem, lost as progression to cure, probably due to cytoplasm heparin granules. As expected, VET were in accordance with HyperC: short CTs, increased MCFs, and decreased lysis. Conclusion(s): We expected to guide/adjust LMWH dosage, using Rotem profiles, however these were not corrected by LMWH, used transversally, and remained unchanged in all patients during their stay in ICU.

Clinical and laboratory characteristics of SARS-CoV-2 infection in overweight and obese patients.

Objective. To assess the impact of obesity and overweight on the course of COVID-19. Patients and methods. This prospective study included 218 patients with SARS-CoV-2 infection aged 18 to 94 years hospitalized between June 2020 and March 2021. We evaluated their clinical and laboratory parameters and their association with body weight. All patients were divided into 3 groups depending on their body mass index (BMI). Group 1 included 81 patients with grade 1-3 obesity (BMI >=30);group 2 comprised 71 overweight patients (BMI >=25 and <30);group 3 included 66 patients with normal body weight (BMI >=18.5 and <25). We analyzed clinical symptoms (including shortness of breath, fever, myalgia, headache, fatigue, changes in the oropharynx, cough, rhinorrhea, sore throat, anosmia, and diarrhea), prevalence of concomitant disorders and complications, findings of computed tomography and pulse oximetry, and findings of instrumental and laboratory examinations (complete blood count, urine test, electrocardiography, echo cardiography, biochemical assays, including C-reactive protein, procalcitonin, alanine aminotransferase, aspartate aminotransferase, lactate, lactate dehydrogenase, activated partial thromboplastin time, prothrombin index, D-dimer, ferritin). Data analysis was performed using the Statistica 6.0 software. Results. We found that overweight and obese patients were more likely to have the main COVID-19 symptoms and comorbidities than those with normal weight. Overweight and obese patients also required respiratory support more frequently than patients with normal weight. Obese and overweight patients had more severe systemic inflammation (CRP, procalcitonin), cytolysis (ALT, AST), and thrombosis (D-dimer). Conclusion. Our findings suggest that obesity and overweight are the factors associated with a more severe SARS-CoV-2 infection, which should be considered when planning their treatment and developing resource strategies.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Evaluation of the Effect of Favipiravir Use on Inr, Pt, Aptt Tests in Covid-19 Patients

Objective: Studies have shown that high mortality rates associated with abnormal coagulation response, bleeding and coagulation disorders in COVID-19 patients. In our study, it was aimed to investigate the effect of the use of favipiravir on coagulation tests such as INR, PTT and Aptt. Materials-Methods: 50 patients who had a positive RT-PCR in nasal and throat swabs result and were diagnosed with COVID-19 using favipiravir and 50 non-users favipiravir COVID-19 patients were included. INR, PT, Aptt data were evaluated for all patients. Result(s): Results of patients using favipiravir;INR 1.3+/-0.2, PT(s) 16.4+/-3.4, Aptt(s) 40.7+/-10.1, while the results of patients who did not use favipiravir were INR 1,2+/-0.2, PT(s) 14.6+/-2.5, Aptt(s) was found 38.4+/-7.8. While PT and INR were found to be significantly higher in patients using favipiravir (p<0.05), the elevation in Aptt values was not significant. Conclusion(s): As a result, it was observed that favipiravir prolongs the clotting time. In the light of these RESULTS, it is recommended to consider this in anticoagulant therapy used for treatment.

Opportunities for predicting adverse pregnancy outcomes in severe COVID-19.

Aim: to asses an opportunity for predicting an unfavorable perinatal and maternal pregnancy outcome in severe novel coronavirus infection (NCI) COVID-19. Materials and Methods. A retrospective comparative study of the course and outcomes of pregnancies was performed in 40 patients with a gestational age of 22-42 weeks who had severe and extremely severe COVID-19 in 2021. The main group included 21 cases with an extremely severe course of the disease resulting in maternal mortality;the comparison group consisted of 19 patients with severe COVID-19 who successfully completed pregnancy. The diagnosis of NCI COVID-19 was confirmed in all cases by identifying SARS-CoV-2 RNA by polymerase chain reaction in a nasopharyngeal swab. During the study, all patients (during hospitalization, at the peak of the disease and before death/discharge from the hospital) underwent a comprehensive anamnestic, clinical and laboratory-instrumental examination. There were analyzed clinical blood test, biochemical parameters - lactate dehydrogenase (LDH), alanine aminotransferase, aspartate aminotransferase, creatinine, glucose, total bilirubin, total protein;coagulation parameters - prothrombin level according to Quick and fibrinogen, activated partial thromboplastin time, international normalized ratio;the level of C-reactive protein, procalcitonin, D-dimer, interleukin-6 (IL-6);ultrasound examination was performed during pregnancy (fetometry, placentometry), dopplerometry of uteroplacental blood flow and ultrasound of the pelvic organs, as well as pathomorphological placenta examination. Results. In patients who died from extremely severe NCI COVID-19 (main group), the course of the infection was accompanied by developing of respiratory distress (RD) degree III (chi2 = 12.84;p <= 0.05), and a progressive deterioration in mother's condition and/or fetal distress was an indication for emergency delivery by caesarean section (CS). The course of severe NCI COVID-19 in patients with a favorable outcome (comparison group), as a rule, was accompanied by the development of RD grade I and/or II;most of them were also delivered by CS on an emergency/urgent basis. Predictors of rapid progression of severe NCI COVID-19 in the main group were identified: subfebrile body temperature at the initial stages skewing to high fever during treatment instead of rapid temperature normalization (chi2 = 5.41;p <= 0.05;odds ratio (OR) = 5.0;95 % confidence interval (CI) = 1.23-20.3);lack of leukocytosis at the initial stages (chi2 = 4.91;p <= 0.05;OR = 50;95 % CI = 5.43-460.54) with rapidly increased leukocyte count with persistent stagnation in dynamics until death (chi2 = 19.79, p <= 0.05, OR = 50;95 % CI = 5.43-460.54);severe lymphopenia (chi2 = 8.09;p <= 0.05;OR = 7.29;95 % CI = 1.74-30.56), neutrophilia (chi2 = 10.17;p <= 0.05;OR = 10.29;95 % CI = 2.21-47.84);high LDH values (chi2 = 17.99;p <= 0.05;OR = 31.88;95 % CI = 5.09-199.49);increased IL-6 level at the peak of the disease (chi2 = 9.66;p <= 0.05;OR = 18;95 % CI = 1.99-162.62) and in dynamics, as well as stably high D-dimer values (chi2 = 9.53, p <= 0.05;OR = 11.33;95 % CI = 2.07-62.11). Conclusion. Significant changes observed in clinical and laboratory examination were identified, which reliably reflect the degree of patients' state, to be interpreted as predictors of adverse pregnancy outcomes during NCI COVID-19 and as a potentially justified serious reason for making a decision in the light of timely delivery aimed at a favorable outcome for mother and child. Timely delivery, carried out within the time limits for enabling adequate compensatory capabilities of the pregnant woman's body, demonstrates a rapid normalization of the main laboratory parameters.Copyright © 2023 IRBIS LLC. Pravo. All rights reserved.

A new logistic regression derived combined index for early prediction of in-hospital mortality in COVID-19 patients

BACKGROUND: While the type and the number of treatments for Coronavirus Disease 2019 (COVID-19) have substantially evolved since the start of the pandemic a significant number of hospitalized patients continue to succumb. This requires ongoing research in the development and improvement of early risk stratification tools. METHOD(S): We developed a prognostic score using epidemiological, clinical, laboratory, and treatment variables collected on admission in 130 adult COVID-19 patients followed until in-hospital death (N.=38) or discharge (N.=92). Potential variables were selected via multivariable logistic regression modelling conducted using a logistic regression univariate analysis to create a combined index. RESULT(S): Age, Charlson Comorbidity Index, P/F ratio, prothrombin time, C-reactive protein and troponin were the selected variables. AUROC indicated that the model had an excellent AUC value (0.971, 95% CI 0.926 to 0.993) with 100% sensitivity and 83% specificity for in-hospital mortality. The Hosmer-Lemeshow calibration test yielded non-significant P values (chi2=1.79, P=0.99) indicates good calibration. CONCLUSION(S): This newly developed combined index could be useful to predict mortality of hospitalized COVID-19 patients on admission.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Successful Treatment of Subclavian Artery Thrombosis by Catheter-Based Thrombus Aspiration and Thrombolytic Therapy: A Case Report

Clinical Information Patient Initials or Identifier Number: BP4****/22 Relevant Clinical History and Physical Exam: A 55 Y / Female C/C : Pain, numbness, cold sensation & weakness of left upper limb for 2 hours. Risk Factor : Hypertension, diabetes mellitus O/E : Pale, cold and absent of radial, ulnar, brachial pulse of left upper limb. Muscle power 3/5 left side. So2 86%, BP undetectable. Right upper limb were normal. BP 160/90 mm of hg, pules : 112 b/min, RR : 26/min. Body Temperature 37.5 C [Formula presented] [Formula presented] Relevant Test Results Prior to Catheterization: CBC : WBC 7450, HB % 10.8 g/dl, ESR 20mm in 1st hour, Platelets : 262000, SARS Cov2 Antigen : Negative PT 14.3 sec, INR : 1.07 APTT : 32.4 sec. blood group: O positive Serum Creatinine : 1.1 mg/dl Plasma glucose 9.7 mmmol/l HIV Ab : Negative HBs Ag : Negative Anti-HCV : Negative Urine R/E : Normal lipid profile : Cholesterol 280mg/dl Vascular duplex ultrasound of left upper limb : A dilated echogenic thrombus had blocked the left subclaviav artery lumen. Relevant Catheterization Findings: Conventional angiography with the lowest amount of contrast agent through the right femoral artery, revealed that left subclavian artery thrombosis with total occlusion distal to Left internal mammary artery. [Formula presented] [Formula presented] [Formula presented] Interventional Management Procedural Step: A5Fr MPA catheter with side holes was negotiated through a right femoral sheath and was placed in the left subclavian artery. Initially thrombus aspiration was done with Eliminate aspiration catheter (TERUMO) with no success. Then suction was done with the MPA catheter itself with partial removal of thrombus. Then a 5Fr Pigtail catheter was placed inside the thrombus and kept in situ. For residual thrombus 250,000u of Inj. Streptokinase as a thrombolytic drug was given through the Pigtail catheter as bolus over 30 min. The maintenance dose 100,000 u per hour was given over 24 hours through the Pigtail catheter via infusion pump. After 24 hours of thrombolytic therapy, her pain was reduced, the left hand became slightly warm, and distal pulses were feebly palpable. Moreover, the skin colour returned to near normal with improvement of pallor. Bleeding was well controlled at the catheter site. Doppler sounds revealed partial improvement of arterial flow. After evaluation of partial improvement, a low dose 1000 iu per hour of heparin (UFH)was infused intravenously for 24 hours. After 48 hours, repeat angiography via the inserted catheter at the site did not reveal any atherosclerotic plaque and confirm the thrombosis-dissolution. The latter practice demonstrated a good blood flowto the left upper distal limb leaving a little thrombus in the superficial palmer arch. [Formula presented] [Formula presented] [Formula presented] Conclusion(s): Catheter-based thrombus aspiration and thrombolytic therapy is primarily reserved for patients with acute viable limb ischemia. As observed in the presented case, thrombus aspiration and thrombolytic therapy is recommended to be considered as an alternative therapeutic method for patients with arterial thrombosis due to the rapid response, shorter treatment time and lower cost, compared to common and sometimes unsuccessful therapies.Copyright © 2023

Acquired hemophilia A and deep vein thrombosis attributable to the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine-case report

Background: Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder that occurs in a sporadic, nonhereditary pattern. It is caused by circulating autoantibodies against clotting factor VIII that are triggered by several conditions. Moreover, AHA is clinically distinct from the inherited form of hemophilia A, with a different natural history and management approach, necessitating a high-index of suspicion in at-risk patients. Coronavirus disease 2019 (COVID-19) has emerged as a multisystemic disease whose manifestations are continuously being evaluated. There are few case reports of AHA associated with COVID-19 infection, while one case of AHA has been associated with COVID-19 vaccination. Similarly, deep venous thrombosis (DVT) frequently complicates COVID-19 infection, but two cases of DVT have been reported following COVID-19 vaccination. We report the occurrence of both AHA and DVT in a 63-year-old male patient within one week of receiving his first dose of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine. Case Description: Patient is a 63-year-old male who presented with a 3-day history of left lower extremity (LLE) swelling and pain. He was hemodynamically stable, but examination showed exquisite tenderness, ecchymosis, and pitting edema at the calf of the LLE. He had normal platelet counts at presentation but had mild anemia (11.9 g/dL) and elevated activated partial thromboplastin time (APTT) of 68.0 seconds. Venous Doppler ultrasound showed acute DVT in the left popliteal vein, necessitating commencement on heparin drip. He developed progressively worsening hematomas, symptomatic anemia that required red cell transfusions, and persistently elevated APTT despite stopping the heparin drip. Work up for pulmonary embolism, malignancy, and disseminated intravascular coagulopathy (DIC) were negative. Antiphospholipid antibodies and lupus anticoagulant were also negative. He had low factor VIII levels, tested positive for factor VIII inhibitor, and PTT mixing studies were consistent with acquired factor inhibitor. Treatment involved administration of Factor Eight Inhibitor Bypassing Activity (FEIBA) as well as intravenous methylprednisolone and cyclophosphamide. Following resolution of active bleeding with evidence of stable hemoglobin concentration, he was discharged home on oral prednisone and cyclophosphamide. Conclusion(s): This case report highlights the possibility of AHA and DVT as rare, potentially life-threatening adverse events that could occur following COVID-19 vaccination, which is currently the most effective tool employed in controlling the COVID-19 pandemic.Copyright © Annals of Blood. All rights reserved.

Novel Monitoring and Dose Adjustment of Argatroban, a Direct Thrombin Inhibitor, to Maintain Therapeutic Anticoagulation in a Patient With Antiphospholipid Antibody Syndrome, Heparin-Induced Thrombocytopenia, and COVID-19 Pneumonia.

In patients who require systemic anticoagulation, a reliable monitoring method is required to ensure anticoagulation is maintained within the correct therapeutic window and patients are treated appropriately. When titrating direct thrombin inhibitors (DTIs), dilute thrombin time (dTT) measurements have been demonstrated to be more reliable and accurate than activated partial thromboplastin time (aPTT) measurements and thus often the preferred DTI assessment. However, a clinical need arises when both dTT measurements are not readily available and aPTT measurements are unreliable. CASE SUMMARY: A 57-year-old woman with a history of antiphospholipid antibody syndrome, heparin-induced thrombocytopenia, and multiple prior deep venous thromboses and pulmonary emboli was admitted with COVID-19 pneumonia and intubated due to hypoxic respiratory failure. Argatroban was initiated in place of her home medication warfarin. However, the patient had a prolonged aPTT value at baseline and overnight dTT assay measurements were limited at our institution. A multidisciplinary team of hematology and pharmacy clinicians created a modified patient-specific aPTT target range and argatroban dosing was titrated accordingly. Subsequent aPTT values in the modified target range corresponded to therapeutic dTT values, indicating therapeutic anticoagulation was successfully achieved and maintained. Patient blood samples were additionally evaluated retrospectively using an investigational novel point-of-care test that detected and quantified the argatroban anticoagulant effect. CONCLUSIONS: Therapeutic anticoagulation with a DTI in a patient with unreliable aPTT measurements can be achieved with use of a modified patient-specific aPTT target range. Early validation of an investigational rapid testing alternative for DTI monitoring is promising.

Efficacy and safety of garadacimab in patients with severe COVID-19

Introduction: Garadacimab (GAR;CSL312), a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, FXIIa, and may play a protective role in the progression of COVID-19 related respiratory disease. Aims and objectives: This placebo (PL)-controlled study evaluated efficacy and safety of GAR plus standard of care (SOC) vs PL plus SOC in patients (pts) with severe COVID-19. Method(s): Pts were randomised (1:1) to GAR (700 mg IV) or PL plus SOC. Primary endpoint was incidence of endotracheal intubation (TI) or death up to Day 28. Key secondary endpoints included all-cause mortality and safety (reporting of AEs). aPTT, FXII levels and FXIIa-mediated kallikrein activity (FXIIa-mKA) were measured to indicate target activation. Result(s): In the ITT analysis set (N=124), baseline demographics were balanced between study groups (GAR, n=63;PL, n=61). Incidence of TI or death was 22% for GAR vs 26% (P=0.274) for PL. No difference in all-cause mortality was observed (crude rate: GAR 17.5% vs PL 18.0%). GAR was associated with fewer TEAEs (60.3% vs 67.8%) and SAEs (34 vs 45 events) vs PL. No GAR-related deaths or bleeding were reported, despite permitted heparin coadministration. aPTT prolongation and increased FXII levels were observed with GAR vs PL to Day 14, while FXIIa-mKA was suppressed to Day 28. Conclusion(s): In pts with severe COVID-19, GAR did not confer a clinical benefit over PL. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of GAR that was not associated with bleeding even with co-administered heparin. The safety profile of GAR in pts with severe COVID-19 was benign, as reported in pts treated with GAR for hereditary angioedema.

Abnormal postpartum uterine bleeding in adolescence associated with SARS-CoV-2 infection

Background: With a prevalence of 1-3 cases per million, acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of neutralizing antibodies against factor VIII. Even though diagnosis of this bleeding disorder is rarely established among children and adolescents, AHA may lead to severe, life-threatening hemorrhage in this age group, and therefore it requires special caution. Case report: 19 year old primigravida with confirmed SARS-CoV-2 infection was admitted to hospital due to prolonged vaginal bleeding six weeks postpartum. All gynaecological causes of uterine bleeding were excluded, Foley catheter was placed, but the bleeding still persisted. Coagulation tests revealed isolated deranged aPTT values. Further haematology evaluation demonstrated factor VIII deficiency, presence of factor VIII inhibiting factors, and the diagnosis of AHA was proposed. The anti-inhibitor coagulant complex drug was introduced and patient has responded positively to the treatment. Conclusion(s): Due to disturbance of immune system, pregnancy and postpartum period represent predilection time for AHA development. Furthermore, viral infection in pregnancy, such as COVID-19, might be considered as an additional risk factor for AHA development and several reported cases of AHA after COVID-19 infection support this hypothesis. Even though AHA is a rare disease, due to its high mortality rate of more than 20%, it should be considered in all cases of unusual bleeding of unknown cause in all age groups. Publication of this case report is approved by Institutional Review Board.Copyright © 2023

CLINICAL AND GENETIC DETERMINANTS OF SEVERE COURSE OF COVID-19 IN PREGNANT WOMEN.

Objectives: to determine the clinical and genetic determinants of the severe course of COVID-19 in pregnant women in order to identify a risk group and search for therapeutic targets. Materials and methods. 21 patients (group 1) with a severe course of COVID-19 who required intensive care in the Anesthesiology and Intensive Care Unit (AICU) and 126 pregnant women with moderate severity treated in the Infectious-Obstetrics Unit (IOCU) were examined (group 2). Genomic DNA for molecular genetic analysis of gene variants ACE (I/D, rs 4340), PGR (Alu insertion), ESR1 (A351G, rs 9340799), PON1 (C108T, rs 705379) was isolated from the peripheral blood of patients using a commercial Quick-DNA Miniprep Plus Kit (Zymo Research, USA). Variants of ACE and PGR genes were determined using allele-specific polymerase chain reaction;polymerase chain reaction followed by restriction analysis was used to determine ESR1 and PON1 gene variants. Results. Severe course of COVID-19 is observed in 18.2% of pregnant women, critical condition in 7.5%. A third of AICU patients are over 35 years old. Somatic anamnesis was complicated in 23.8% of patients;thyroid gland pathology (14.3%) and varicose disease (19.0%) prevailed. A significant factor in the severe course of COVID-19 is obesity of the III-IV degree in 28.5% cases. The severe course of the disease was associated with complications of pregnancy (oligohydramnios - 52.4%, ahydramnios - 14.3%, fetal growth retardation syndrome - 33.3%, circulatory disorders - 57.1%, fetal distress - 47.6%, preeclampsia - 14.3%), labor (caesarean section - 57.1%, premature birth - 28.6%), disorders of newborns state (asphyxia - 35.6%). These patients are characterized by anemia (58.7%), thrombocytopenia (23.8%), leukocytosis (33.3%), lymphopenia (90.5%), a shift of the leukocyte formula to the left (an increase of rod-nuclear leukocytes by 85.7%). There were significantly increased levels of transaminases: alanine aminotransferase in 47.6%, aspartate aminotransferase in 76.2%. Prothrombotic changes are indicated by a decrease in prothrombin time and activated partial thromboplastin time in 66.7%, which is confirmed by an increase in D-dimer in 85.7% of patients up to the maximum 15,000 ng/ml in 9.5% of women. An increase in inflammation markers (C-reactive protein and interleukin-6 in all AICU patients, procalcitonin in 66.7%) is a reflection of the destructive effect of inflammatory processes. The genetic determinants of the severe course of COVID-19 in pregnant women can be the ID genotype of the ACE I/D rs4340 polymorphism (81.0%), the T2/T2 PROGINS genotype (19.0%), the ESR1 A351G rs9340799 GG genotype (28.5%). Conclusions. The use of separate clinical, laboratory and genetic indicators in pregnant women with COVID-19 will contribute to the selection of the risk group of a coronavirus severe course and the determination of targets of therapeutic impact.Copyright © 2022 Trylyst. All rights reserved.

Review: Coagulation Panel in Patients with SARS-CoV2 Infection (COVID-19)

The 2019 novel coronavirus (SARS-CoV2) is the causal agent of the newly-termed Coronavirus Disease 2019 (COVID-19). In January 2020, the World Health Association (WHO) declared the COVID-19 as an epidemic. Abnormal coagulation parameters in COVID-19 patients currently are considered as prognostic factors of severity. Our aim is to summarize the current data available in the literature. Materials and Methods. An electronic search was performed in the Database of publications on coronavirus disease (COVID-19) of the World Health Organization. Thrombin Time (TT), Prothrombin Time (PT), Fibrinogen (FIB), Activated Partial Thromboplastin Time (APPT), and D-Dimer have been detected as parameters to study in every COVID-19 patient. Clinical Application. The coagulation function panel has been described to be altered in critical COVID-2019 patients. DIC, which plays an important role in advanced stage, is known to be associated with sepsis. Anticoagulant therapy, mainly with low molecular weight heparin (LMWH), appears to be associated with better prognosis in patients with severe COVID-19. Discussion. Coagulation function in patients with SARS-CoV2 infection is significantly deranged compared with normal patients. FIB and D-Dimer/FDP are the most significantly altered values and the early deetection of alteration could be useful to address therapies. D-Dimer/FDP (DD/FDP) alteration correlates with severity. Markedly elevated D-Dimer can be used to guide the introduction of anticoagulation therapy and evaluate prognosis of COVID-19. In every patient admitted with SARS-CoV2 infection PT, FIB, D-Dimer/FDP, and platelets must be ordered. We suggest daily extraction for every patient admitted and tested positive for COVID-19.Copyright © 2020 by the Association of Clinical Scientists, Inc.