Partial Thromboplastin Time Research Articles

Reduce energy consumption in your laboratory – switch ultra-low temperature freezers from – 80 °C to –70 °C. A pilot study on short term storage of plasma samples for coagulation testing

It is common practice in laboratories to store biological samples in ultra-low temperature (ULT) freezers. There is growing interest in raising the temperature of ULT freezers in order to save energy and reduce expenses, as energy conservation becomes increasingly important and sustainable laboratory practices gain popularity. In our laboratory, plasma samples are stored for three months for diagnostic purposes. We therefore took the opportunity to investigate the effect of two different storage temperatures (−70 °C vs −80 °C), on activated partial thromboplastin time (APTT), factor VIII (FVIII), international normalized ratio (INR) and factor VII (FVII) measurements on paired plasma samples collected from 26 individuals after three months of storage. Automated coagulation analysers CS-5100 and ACL TOP were used to perform the tests. We found no consistent difference between the two storage temperatures for any of the four coagulation parameters (all p-values > 0.05). We conclude that the temperature of ULT freezers used to store plasma samples for APTT, FVIII, INR, and FVII measurements can be safely increased from −80 to −70 °C without affecting the stability of the samples.

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

Using heart rate variability to evaluate the association between the autonomic nervous system and coagulation function in patients with endometrial cancer.

The incidence of endometrial cancer (EC) is increasing worldwide, but the specific mechanism of coagulation dysfunction in EC is not fully understood. The objective of the present study was to explore the relationship between autonomic nervous system function and coagulation function in patients with EC using heart rate variability (HRV) analysis. The study included 100 patients with EC who were treated at the Department of Gynecological Oncology of The First Affiliated Hospital of Bengbu Medical University (Bengbu, China) from December 2021 to March 2023. A 5-min resting electrocardiogram was collected from each patient to analyze HRV parameters, including the time domain parameters standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD), and the frequency domain parameters low-frequency power and high-frequency power (HF). Blood samples were submitted to biochemistry tests to measure coagulation markers, namely prothrombin time (PT), international normalized ratio of PT (PT-INR), prothrombin activity (PTA), activated partial thromboplastin time (APTT) and fibrinogen. Bivariate Spearman correlation analyses revealed that PT, PT-INR and APTT were significantly positively correlated with SDNN, RMSSD and HF, while PTA was significantly negatively correlated with RMSSD. Following adjustments for confounding factors, namely age, body mass index, menopause, ligation of the fallopian tubes, diabetes, hypertension, adjuvant chemotherapy and mean heart rate, linear regression analysis demonstrated that SDNN, RMSSD and HF were independent factors influencing PT and PT-INR in patients with EC. The findings of the present study indicate that certain HRV parameters correlate with coagulation markers in EC and provide new insight into the occurrence of cancer-associated coagulation dysfunction.

Metabolic pathways altered by air pollutant exposure in association with coagulation function among the rural elderly

Air pollution exposure has been linked with coagulation function. However, evidence is limited for the relationships between air pollution, coagulation function and metabolomics in humans. We recruited a panel of 130 rural elderly from the Chayashan township in China, all of whom were free of pre-existing cardiovascular diseases and had provided residential address information. We conducted clinical examinations and collected blood samples from these rural elderly for the detection of coagulation biomarkers (e.g, activated partial thromboplastin time, fibrinogen, thrombin time, and prothrombin time) and untargeted metabolites in both December 2021 and August 2022. We used mini ambient air quality monitor to measure the mean levels of five air pollutants (e.g., PM2.5, SO2, NO2, CO and O3) during 1 to 2 weeks before blood sample collection. The Mummichog pathway analysis was used to identified potential metabolic features and pathways. In this study, we identified 5 pathways associated with both air pollution and coagulation function, and further pinpointed eight metabolic features within these pathways. The majority of these features were lipids, including arachidonic acid and linoleic acid. Overall, the findings of this study offer insights into potential mechanisms, particularly lipid metabolism, that may underlie the association between air pollution and coagulation function.

SEVUparin as a potential Adjunctive Treatment in children with severe malaria: A phase I trial safety and dose finding trial (SEVUSMAART).

Even on the best antimalarial treatments (injectable artesunate) African children with severe malaria have poor outcomes with most deaths occurring early in the course of hospital admission (<24hours). Lactic acidosis, largely due to impairment of the microcirculatory flow due to parasite sequestration, is a main risk factor for poor outcome. There are no adjuvant treatments for severe malaria that target this complication. Sevuparin, a heparin-like drug, binds to Plasmodium falciparum erythrocyte membrane protein blocking merozoite invasion, preventing cytoadherence and transiently de-sequestering infected erythrocytes. Leading to improved microcirculatory flow by reversing/preventing parasite sequestration. If given early during admission this could result in improvements in outcomes. Sevuparin has been shown to be safe and well tolerated in adults with only some mild transient effects on activated partial thromboplastin time (APTT) were reported, without clinical consequences. A Phase I trial designed to provide data on safety, dosing, feasibility of sevuparin as an adjuvant therapy in Kenya and Zambian children with severe malaria complicated by lactic acidosis (> 2mmol/l). Three intravenous doses will be given at admission (0 hours), 8 and 16 hours. APPT will be measured 1 hour after each dose (to assess maximum toxicity). Studying 20 children will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method, which adapts or informs subsequent doses for each child based on the data from previously enrolled children. The MTD will be identified based on the dose-toxicity model updated by each previous patient's APTT results using standard methods. The results of the Phase I trial will identify the final dose to be tested in a Phase II trial in terms of both efficacy and safety outcomes. PACTR number: 202007890194806 (date 20/07/2020) ISRCTN32271864 (date 28/07/2021).

Chemical composition and antioxidant activity of Physalis angulata L. (Solanaceae) and its effect on blood clotting and biofilm formation of some wound bacterial isolates

Physalis angulata a member of the Solanaceae family, is a plant recognized for its significant nutritional and medicinal properties. Widely distributed across tropical and subtropical regions, this plant has garnered attention for its diverse biological activities. The ethanol extract from the plant is being used in this study to investigate its biological and antioxidant properties. The ability of the extract to reduce free radicals was also tested using the compound phenyl-1-picrylhydrazyl). The DPPH method was used because it is a modern color method and is considered the most common and easy to apply, in addition to its speed and superior sensitivity in testing antioxidants for samples of plant extracts, and the values were compared with the value of ascorbic acid IC50. The study also looks at the extract's ability to prevent the formation of biofilms by different pathogens, including E. coli and Staphylococcus strains that were isolated from community labs and Ramadi Teaching Hospital. The ethanol extract demonstrated a noteworthy ability to inhibit the formation of cellular membranes in staphylococcal bacteria and E. coli. The efficacy of the extract at different concentrations (150, 200, 250 mg/mL) was also assessed, revealing that a concentration of 250 mg/mL resulted in significant inhibition rates (74.3% and 61.45% for E. coli). Furthermore, the study explores the impact of ethanol extract on blood coagulation. At high concentrations (150, 200, 250 mg/mL), the extract exhibited properties akin to aspirin and warfarin, extending the clotting times in both total and partial coagulation tests (Prothrombin time, Partial thromboplastin time) at lower concentrations (100, 50, 10 mg/mL), the extract appeared to promote blood clot formation, suggesting a concentration-dependent effect on hemostasis. This dual action positions P.angulate as a potential therapeutic agent, warranting further investigation into its biomedical applications.

Anticoagulation methods used and role of antithrombin III level monitoring in children on continuous renal replacement therapy: an observational cross-sectional study

BackgroundIn critically ill cases, CRRT is a renal replacement intervention. The most common reason why CRRT terminates prematurely (non-electively) is clotting in the extracorporeal circuit, more especially in the filter.Aim of workTo determine the frequency of thrombotic and hemorrhage complications throughout CRRT, the role of antithrombin III level monitoring, the type of anticoagulation, and the dose and laboratory tests utilized to monitor it.MethodThe study was carried out on 58 children who were undergoing CRRT. The children underwent a comprehensive history-taking, assessment, CRRT prescription parameters and alterations, vascular access data, anticoagulation type, dose, and adjustment, as well as monitoring of antithrombin III levels. Furthermore, any extracorporeal circuit clotting or bleeding was documented.ResultsOf the 58 sessions that were examined, 25 (43.1%) resulted in filter clotting. The indication was cured in 16 cases (27.6%), 8 cases (13.8%) resulted in the patient’s mortality, and 9 cases (15.5%) had life-threatening bleeding. The remaining 33 cases (56.9%) were not terminated with filter clotting. Forty-one (70.7%) of studied sessions used unfractionated heparin as anticoagulation, 22.4% used heparin-protamine, 5.2% was not anticoagulated, and one circuit (1.7%) was anticoagulated using regional citrate.Filter clotting incidence was significantly related to activated partial thromboplastin time (a PTT) value at the end of sessions (P value = 0.000), and platelets count after 4 h of session initiation (P value = 0.048). Antithrombin III levels pre-heparin infusion less than 80 were found in patients who received higher doses of a heparin bolus dose, median dose 35 (IQR 20–35), this relation is statistically significant (P value = 0.042).ConclusionIn the 58 cases that were examined, the incidence of bleeding was 32.8%; however, 19% of the cases were not severe. The incidence of filter clotting was 43.1% in the study group. a PTT value at the end of sessions, and platelets count after 4 h could be predictors of thrombotic complications during CRRT, antithrombin III deficiency before sessions is a predictor of filter clotting.

Undetected intraabdominal sepsis due to prolonged corticosteroid therapy in systemic lupus erythematosus: a case report and literature review

Gastrointestinal manifestations are not included in the criteria for diagnosing systemic lupus erythematosus (SLE) by the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019, however, gastrointestinal disorders are one of the potentially fatal complications of SLE. Mesenteric vasculitis and thrombosis are the two main mechanisms that cause gastrointestinal disorders in SLE patients. Long-term immunosuppressants used by SLE patients might alter the immune system’s response to infection, leading to immunoparalysis. The delay in recognizing might cause sepsis, thus increasing the mortality risk. A 47-year-old woman with a history of SLE complained of hematochezia. The patient had been consistently consuming 12 mg of methylprednisolone every day for the past five years without doctor’s supervision. Past medical history of congestive heart failure (CHF) caused by coronary arterial disease (CAD). After 24 days hospitalized for observation of hematochezia, an emergency laparotomy was performed due to deterioration caused by peritonitis. Intraoperative, 60 cm of jejunal necrosis was identified and intestinal resection was done. The patient’s condition improved in two days after emergency laparotomy and intensive treatment. The undetected intraabdominal sepsis caused by jejunal infarction and gut necrosis due to long-term use of corticosteroid that masked the manifestations of severe infection in the gastrointestinal tract infarction and necrosis. Abbreviations: NLR - neutrophil to lymphocyte ratio; SGOT - serum glutamic oxaloacetic transminase; SGPT - serum glutamic pyruvic transminase; eGFR - estimated glomerular filtration rate; PT - prothrombin time; APTT - activated partial thromboplastin time; INR - international normalized ratio Keywords: Systemic lupus erythematosus, Intraabdominal sepsis, Immunoparalysis, Corticosteroid Citation: Leman YE, Irawany V, Manggala SK. Undetected intraabdominal sepsis due to prolonged corticosteroid therapy in systemic lupus erythematosus: a case report and literature review. Anaesth. pain intensive care 2024;28(4):765−771; DOI: 10.35975/apic.v28i4.2525 Received: March 13, 2024; Reviewed: May 17, 2024; Accepted: May 21, 2024

Hemostasis disorders, thrombosis and thrombocytopenia in patients with covid-19 and pneumonia with complicated acute renal injury

«Hemostasis disorders, thrombosis and thrombocytopenia in patients with covid-19 and pneumonia with complicated acute renal injury» Relevance. Thrombosis is one of the most dangerous complications of COVID-19 not only at the peak of the disease, but also in the long term. During the pandemic, the issues of medical prevention of thrombotic complications have been repeatedly reviewed, clarified and supplemented, but the only correct tactics for their prevention and treatment do not yet exist.The purpose of the study. To determine the frequency and nature of the development of venous and arterial thrombosis and thrombocytopenia in severe patients with COVID-19 and pneumonia, complicated by acute renal damage, the course of the disease, including fatal ones.Material and methods. Data on inpatient treatment and diagnosis of 216 COVID-19 patients with viral pneumonia and signs of acute renal injury (AKI) according to KDIGO 2012 criteria. Group 1. Deceased patients with severe COVID-19 and pneumonia, with unreliable signs of AKI, 75 (men 19, women 56), ratio 1:2.9. Age from 29 to 87 years. Ventilation in 56 (74.7 %) Group 2. Deceased patients with COVID-19 and pneumonia with significant signs of AKI, 77 (men 34, women 43), ratio 1:1.3. Age from 41 to 88 years. Ventilation in 53 (70.7 %) Group 3. Recovered patients with AKI or CKD, 64 (men 41, women 23, ratio 1:0.56, age from 43 to 89 years). Ventilation in 1 (1.6 %). The study of hemostasis. Activated partial thromboplastin time according to the modified method of plasma recalcification reaction according to Baluda V. P. et al. (1980). The level of fibrinogen in blood plasma by the ethanol method according to Breen F., Tullis J. (1982). The concentration of D-dimer in the blood by microlatex agglutination with photometric registration of the reaction (immunoturbidimetry).Results. In deceased inpatient patients with Covid-19 and pneumonia, a high incidence of arterial and venous thrombosis of various localization was detected, up to 46–56 %. The thrombotic danger was largely associated with an increased level of D-dimer and the duration of its increase in the blood of patients. Thrombocytopenia was diagnosed in 47–58 % of patients and was a significant risk factor for the development of fatal outcomes. In cases of detection of thrombocytopenia in patients below 20 thousand cells in microl., its character was assessed on a 4Ts scale to identify the syndrome of heparin-associated thrombocytopenia. 92–97 % of patients were prescribed heparins, including such fractionated (low molecular weight) ones as enoxaparin, nadroparin, dalteparin and fundaparinux. Only a small proportion of cases of combination of thrombosis and thrombocytopenia (about 2.3 %) were due to the nature of drug therapy and the development of heparin-associated thrombocytopenia syndrome.Conclusion. The data obtained indicate the high importance of thrombotic mechanisms involving D-dimer in the pathogenesis and outcomes of the disease in groups of deceased patients with covid-19, pneumonia and AKI and the predominant importance of vascular damage in the activation of the thrombotic cascade in them.

Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study

BackgroundPreoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. ObjectivesTo assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk MethodsA multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation. ResultsEighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%). ConclusionSensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.

Bioclinical features of haemophilia patients in Benin in 2023: Towards better care.

To analyse the demographic, clinical and laboratory data of Beninese patients with haemophilia. A prospective survey was conducted in three different hospitals of Benin from April 2021 to March 2022, to analyse clinical and biological features of patients with haemophilia previously diagnosed or identified based on personal/family history. A total of 101 patients were studied, 97 with haemophilia A and 4 with haemophilia B, including 26 new cases identified after family investigation. Their median age was 11 years, and the most frequent initial manifestations were cutaneous-mucosal haemorrhages (29.70%) and post-circumcision haemorrhages (25.74%). Previous joint bleedings were present in 77% of them, with an arthropathy in 65 cases, which particularly affected the knees (75%), elbows (41%) and ankles (29%). Factor VIII (FVIII) levels combined with activated partial thromboplastin time (APTT) values did not always enable, as would be expected, the distinction between severe and moderate haemophilia, since they were>1 IU/dl in 31 of 74 patients with APTT>80s, and between 1 and 2 IU/dl in 26 other cases with previous joint haemorrhages, including 18 with chronic arthropathy. Therefore, for these patients, severe haemophilia could not be excluded, and this uncertainty probably reflects technical difficulties affecting the pre-analytical and analytical stages of the APTT and FVIII/IX assays. Our study proved that haemophilia is a significant reality in Benin, but also remains under-diagnosed in some districts of the country. In addition, more reliable biological tests are needed in the future to better define the severity of the disease and improve treatment of patients.

Changes in blood biochemistry thrombosis parameters 24 hours after stent-assisted endovascular treatment of intracranial aneurysms.

This study aims to elucidate the early changes in blood biochemistry thrombosis parameters following stent-assisted endovascular treatment of intracranial aneurysms. Consecutive patients with unruptured aneurysms undergoing stent implantation during endovascular treatment were included in this prospective study with approval from the local ethics committee. Blood samples were collected immediately before and 24 h after the procedure for biochemical analysis, including basic thrombosis indicators, bleeding tests, and a complete blood count. The study included 80 patients (60 women, 20 men) with 134 aneurysms. A total of 135 stents (110 flow-diverting, 25 standard) were used. Additionally, intrasaccular coiling was utilized in 28 aneurysms among 27 patients. Following the procedure, there was a significant decrease in activated partial thromboplastin time, fibrinogen, hemoglobin, and platelet levels, and a significant increase in prothrombin time, D-dimer, von Willebrand factor (vWF) activity/antigen ratio, and leukocyte levels in all patients. Correlation analyses revealed significant positive associations between platelet and fibrinogen levels, and a negative association between D-dimer and fibrinogen levels in the coil (-) group. Additionally, there was a significant negative correlation between aneurysm volume and vWF activity/antigen ratio, and procedure duration and thrombocyte count, while a positive association was found between aneurysm number and leukocyte count in the coil (-) group. Analysis of blood chemistry alterations indicates that intravascular thrombosis occurs in the intracranial circulation following stent-assisted endovascular treatment of intracranial aneurysms. This thrombotic process is more pronounced in patients whose aneurysms were left open (i.e. flow-diverting stent alone).

An Investigative Study of Prothrombin Time, Activated Partial Thromboplastin Time and Antithrombin Levels in Patients with Ischaemic Stroke

Background: The haemostatic system maintains a balance between prothrombotic and antithrombotic components in the body. The role of this system in ischaemic stroke is not certain. Objective: Prothrombin time (PT) and Activated Partial Thromboplastin Time(APTT) are widely used screening tests to assess the haemostatic cascade. We sought to evaluate the relevance of these test and antithrombin (AT) levels in patients with ischaemic stroke. Methods: AT, platelet count, PT and APTT tests were carried out for 65 patients with ischaemic stroke and 65 controls with no history of stroke. Results: The mean age of stroke subjects was 60.4 ± 12.3yrs. PT and APTT in the test and control groups were similar and Antithrombin levels did not show significant difference. But there was a significant association between functional AT deficiency and diabetes mellitus in the ischaemic stroke group. A significant negative correlation existed between functional AT activity and prothrombin and between AT Ag levels and APTT Conclusion: There was no difference in the Antithrombin levels, PT and APTT values in patients with ischaemic stroke and those without a history of stroke and carrying out these tests routinely to assess hypercoagulable states in ischaemic stroke patients may not have any diagnostic value in our population.

Evaluation of an integrated activated partial thromboplastin time (Cephen LS/Cephen) for the detection of lupus anticoagulant.

It is recommended to use two chronometric assays of different principles for the diagnosis of lupus anticoagulant (LA), consisting in diluted Russell Viper Venom Time (dRVVT) and activated Partial Thromboplastin Time (aPTT). Yet, there are only a few integrated aPTT assays; this study aims to evaluate one of them: Cephen LS/Cephen (Hyphen Biomed). 249 samples of patients were included in this study. Normal reference ranges were determined with platelet-poor plasma (PPP) from healthy blood donors. Performances were then evaluated by comparing Cephen LS/Cephen test results to the results of the laboratory's reference assay for the diagnosis of LA and to clinical data, both on non-anticoagulated and anticoagulated patients' samples (Unfractioned heparin (UFH), Low Molecular Weight Heparin (LMWH), Vitamin K Antagonists (VKA) and apixaban). Interference of UFH, LMWH and VKA were also evaluated thanks to spiking experiment of increasing heparin concentrations or factor deficiency. Cephen LS/Cephen test had 48.6% sensitivity towards LA. Although UFH and VKA seemed to interfere with this assay and were likely to cause false negative, LMWH and apixaban did not. Finally, combination of Cephen LS/ Cephen with dRVVT had 89.0% sensitivity. Cephen LS/Cephen seems relevant for LA diagnosis, in combination with dRVVT, and might be used in patients undergoing LMWH or apixaban therapy.

Cigarette smoking and its effect on coagulation profile, hematological parameters, and oxygen saturation in healthy blood donor

Background: Cigarette smoking causes millions of deaths all around the world each year as it is one of the leading causes of cancer and cardiovascular diseases. Aims and Objectives: The study aimed to study the effect of cigarette smoking on coagulation profile, hematological parameters, and oxygen saturation in healthy blood donors. Materials and Methods: A case–control study was carried out at the Department of Pathology, Era’s Lucknow Medical College which is a tertiary care center, and took place between September 2018 and September 2020 (24 months). Results: Cigarette smoking has adverse effects on hematological parameters (red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin, red cell distribution width, and total leukocyte count) and coagulation profile (prothrombin time, activated partial thromboplastin time, and international normalized ratio). In our study, no adverse effects are seen on oxygen saturation though. Conclusion: Our study shows that hematological parameters and coagulation profile were altered in donors who were smokers and thus, it should be considered during blood donation. Although oxygen saturation was not adversely affected, this study strongly recommends the need for further studies to be done on this parameter of donated blood.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

Relation between antithrombin-III activity and activated clotting time for cardiopulmonary bypass.

Heparin resistance (HR) is observed before cardiopulmonary bypass (CPB), despite with normal antithrombin III (AT-III) levels. The relationships between preoperative AT-III activity and activated clotting time (ACT) after the first heparin dose should be clarified. We retrospectively analyzed the data of 818 patients who underwent CPB surgery, with the initial heparin of 300, 400, and 500IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480s.There were no significant correlations between the AT-III activity and Post ACT in all patients, including 143 patients with AT-III activity < 80% and 675 patients with AT-III activity of ≥ 80%. Also, there were no significant correlations between the AT-III activity and Post ACT in 74 patients who received heparin of 300IU/kg, in 186 patients with 400IU/kg, and in 339 patients with 500IU/kg. After identifying smoking, HR, activated partial thromboplastin time, fibrinogen degradation products (FDP), and ACT as influencing factors, multiple comparisons using the Steel-Dwass test showed significant difference in FDP and HR among the patients who received heparin of 300IU/kg, 400IU/kg, and 500IU/kg. There is no association between preoperative AT-III activity and ACT after the first heparin administration for CPB, even in different dose of heparin. Rather, the higher the initial UFH dose is, the higher ACT may be, regardless of the AT-III activity.

Clinical Characteristics Analysis of EBV-associated Hemophagocytic Lymphohistiocytosis Patients with Acute Kidney Injury

To analyze the clinical characteristics of patients with Epstein-Barr virus(EBV)-associated hemophagocytic lymphohistiocytosis(HLH) with acute kidney injury(AKI). EBV-HLH patients who were hospitalized in our hospital from January 2014 to December 2020 were collected, and their clinical characteristics, treatment, concurrent acute kidney injury and prognosis were retrospectively analyzed. In this study, the incidence of AKI complicated by EBV-HLH was 65.5%, and the 28-day mortality rate was 15.3%. Compared with non-AKI group, patients in the AKI group had higher levels of bilirubin, lactate dehydrogenase, creatinine, urea nitrogen, and β2-microglobulin（β2-MG）, poorer coagulation, and lower soluble IL-2 receptor （sCD25）. Patients in the AKI group had a higher proportion of chemotherapy, transplantation, mechanical ventilation, and the application of vasoactive medications, and were hospitalized for longer periods of time, with higher in-hospital mortality rates and 28-day mortality rates. Patients in the AKI group were analyzed in subgroups according to the Kidney Disease Improving Global Outcomes （KDIGO）classification, and the levels of leukocytes, bilirubin, albumin, creatinine, urea nitrogen, β2-MG, activated partial thromboplastin time （APTT）, and prothrombin time activity （PTA）were more responsive to the severity of the patient's condition. KDIGO grade 2 and 3 had higher proportions of receiving transplants, diuretics, organ support (mechanical ventilation, application of vasoactive medications, and renal replacement therapy), and admissions to the intensive care unit （ICU）, and with higher in-hospital mortality rates and 28-day mortality rates. Regression analysis found that creatinine, β2-MG, APTT, transplantation, and chemotherapy were independent risk factors for the development of AKI; the application of vasoactive drugs was both an independent risk factor for the development of AKI and for death at 28 days; and chemotherapy, length of hospitalization, and HGB and fibrinogen levels were protective factors for death at 28 days. AKI in EBV-HLH has high incidence and high rate of progression to severe disease and death, early attention should be given and strengthened in order to carry out early treatment and improve the prognosis of patients.

Effect of oral tranexamic acid on postoperative bleeding in spinal surgery: a randomized controlled trial.

This study aimed to investigate the effect of oral administration of tranexamic acid (TXA) on reducing intraoperative bleeding during spinal surgeries. The study was a single-center, double-blind, randomized, placebo-controlled clinical trial. Participants were individuals over 20 years old who underwent spinal surgery. Patients received 1.5g of TXA orally, 2 h before surgery. Intraoperative bleeding volume, blood volume in the drain after surgery, length of hospital stays after surgery, incidence of nausea or vomiting, decrease in hemoglobin (Hb) level, and postoperative coagulation test results were evaluated in each group. In this study, patients were assigned to each study group based on inclusion and exclusion criteria. The mean age of patients was 69.6±6.47 years, and 65% were male. There was no significant difference in age, sex, pre and postoperative Hb levels, prothrombin time (PT), or international normalized ratio (INR) between the study groups. Intraoperative bleeding volume and blood volume in the drain after surgery were significantly lower in the TXA group. Additionally, the length of hospital stay after surgery was significantly shorter in the TXA group. The incidence of nausea or vomiting was significantly higher in the TXA group. Furthermore, postoperative partial thromboplastin time (PTT) was significantly higher in the TXA group compared to the placebo group. Oral administration of TXA before spinal surgery leads to a significant reduction in intraoperative and postoperative bleeding without significant adverse effects and also reduces the length of hospital stay.

Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia

Background: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4–6 g dL−1 using apheresis in sheep. Methods: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. Results: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL−1 in the apheresis group compared to 9.1 g dL−1 in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 106/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges. Conclusions: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.