Standardization of Anti-Xa Assay and its Comparison with Activated Partial Thromboplastin Time for Monitoring Unfractionated Heparin Therapy.

Monitoring of anticoagulant activity of unfractionated heparin (UFH) is primarily done with activated partial thromboplastin time (aPTT), which is affected by many factors. Anti-Xa assays are considered to overcome these factors and may provide a better method for monitoring patients on UFH with a narrow therapeutic range. This study aimed to compare the effectiveness of aPTT and anti-Xa assays in UFH monitoring. A prospective non-randomized study was carried out in two stages: first, the anti-Xa assay was standardized using kit instructions; each sample was then analyzed by both tests. The outcomes of the two assays were compared and assessed for agreement of maintaining therapeutic anticoagulant levels. These levels for anti-Xa assay were between 0.3 and 0.7 IU/ml, while it was 1.5-2.5 times the control for aPTT assay. Below this range was regarded as subtherapeutic, and above this as supratherapeutic. A total of 90 samples were tested and analyzed using both assays. Most of them (> 70%) were noted to be in subtherapeutic levels with both tests. The overall concordance was 73.3%, and the estimated kappa value was 0.483 (0.396-0.57). The correlation between aPTT and anti-Xa assay was 0.74 (p < 0.001). With anti-Xa levels in the therapeutic range, aPTT levels were in subtherapeutic in 60% and supratherapeutic in 13.3% cases. Although both the testing strategies had a good agreement and correlation, discordance was observed in interpretative values with anti-Xa levels in therapeutic range and aPTT levels in non-therapeutic range. Its clinical implications need to be evaluated further in future studies.

APTT critical value establishment in four different reagent/instrument systems based on single factor deficiencies.

INTRODUCTION: There are significant differences in the activated partial thromboplastin time (APTT) critical values reported in different studies, most of which does not make recommendations for any specific clear detection systems. The International Council for Standardization in Hematology (ICSH) recommends that APTT critical values be established based on the reagent type, coagulation factor sensitivity and heparin response. The objective of this study was to establish APTT critical values by using different reagents and based on single coagulation factor deficiencies. METHODS: The APTT values were determined in commercial endogenous coagulation factor-deficient plasma at concentrations of 1 IU/dL, 2 IU/dL, 5 IU/dL, 10 IU/dL, 20 IU/dL, and 30 IU/dL by using four assay systems. The retrospective collection of data from patients who lacked factor VIII (FVIII), FIX, or FXI alone was performed. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic accuracy of APTT for identifying patients with an endogenous coagulation factor activity < 5 IU/dL. RESULTS: The APTT values in the plasma samples with the same concentrations of endogenous coagulation factors were significantly different among the four assay systems (P < 0.001). The suggested critical values of APTT were 40.0 s for Sysmex CS5100 (Actin FSL), 58.0 s for Sysmex CS5100 (Actin), 51.8 s for STA-R Evolution (STA-PTTA), and 64.8 s for ACL TOP 700 (HemosIL SynthasIL). On the basis of the ROC curve, the optimal threshold values for APTT (STA-PTTA) were 55.8 s in patients with a simple deficiency of FVIII (sensitivity = 100%, specificity = 85.7%, area under the ROC curve (AUC) = 0.982), 54.3 s in patients with a simple deficiency of FIX (sensitivity = 100%, specificity = 92.9%, AUC = 0.986), and 71.7 s in patients with a simple deficiency of FXI (sensitivity = 100%, specificity = 94.1%, AUC = 0.992), which were closer (difference of 0.6-2.5 s) to the cutoff points for commercial plasma at equal factor levels. CONCLUSIONS: APTT critical values need to be established for different reagents based on the presence of a single coagulation factor deficiency.

Unified Methodology for the Primary Preclinical In Vivo Screening of New Anticoagulant Pharmaceutical Agents from Hematophagous Organisms.

The development of novel anticoagulants requires a comprehensive investigational approach that is capable of characterizing different aspects of antithrombotic activity. The necessary experiments include both in vitro assays and studies on animal models. The required in vivo approaches include the assessment of pharmacokinetic and pharmacodynamic profiles and studies of hemorrhagic and antithrombotic effects. Comparison of anticoagulants with different mechanisms of action and administration types requires unification of the experiment scheme and its adaptation to existing laboratory conditions. The rodent thrombosis models in combination with the assessment of hemostasis parameters and hematological analysis are the classic methods for conducting preclinical studies. We report an approach for the comparative study of the activity of different anticoagulants in vivo, including the investigation of pharmacodynamics and the assessment of hemorrhagic effects (tail-cut bleeding model) and pathological thrombus formation (inferior vena cava stenosis model of venous thrombosis). The reproducibility and uniformity of our set of experiments were illustrated on unfractionated heparin and dabigatran etexilate (the most common pharmaceuticals in antithrombic therapy) as comparator drugs and an experimental drug variegin from the tick Amblyomma variegatum. Variegin is notorious since it is a potential analogue of bivalirudin (Angiomax, Novartis AG, Basel, Switzerland), which is now being actively introduced into antithrombotic therapy.

Coagulation Status Using Clot Wave Analysis in Patients With Prolonged Immobilization.

Background Prolonged immobilization is widely recognized as a risk factor for thromboembolism. In this prospective study, we investigated the changes in clot waveform analysis (CWA) parameters in prolonged immobilized patients following lower limb trauma. CWA is an advanced method for assessing global coagulation that involves continuously monitoring changes in light transmittance, absorbance, or light scattering during routine clotting tests. Additionally, we also aim to determine the CWA parameters between day one and after day three of immobilization. Methods A total of 30 patients with prolonged immobilization were enrolled in this study. The plasma of these patients was collected on the first day of their admission and subsequently obtained again after day three of immobilization. Prothrombin time (PT)-based CWA and activated partial thromboplastin time (aPTT)-based CWA were performed using the ACL TOP 300 CTS (Werfen: Bedford, USA) coagulation analyzer, which utilizes the optical method for clot detection. Plasma samples for 20 normal controls were recruited from a healthy blood donor. The CWA parameters generated during clot formation were analyzed. For the comparison of CWA parameters between patients with prolonged immobilization and healthy controls, the Mann-Whitney test was used. A paired t-test was used for the comparison of clot wave parameters between day one and after day three of immobilization. This study was approved by the Universiti Sains Malaysia Research Ethics Committee. Result The mean values of PT and aPTT in healthy controls were 11.66 seconds and 33.98 seconds, respectively. There was no statistically significant difference between the patients and the healthy controls in the median values of aPTT (P=0.935). However, patients with prolonged immobilization exhibited significantly higher median PT CWA parameter values than controls (P=0.007). These parameters included the delta change (P<0.001), peak time velocity (P=0.008), and height velocity (P<0.001). On the other hand, the delta change (P<0.001) and height velocity (P<0.001) of the aPTT CWA parameters were significantly higher in patients with prolonged immobilization than in controls. In patients with prolonged immobilization, there was no significant difference in PT CWA parameters between day one and after day three of immobilization, while for aPTT CWA, all parameters were higher on day three, except for the endpoint time. Conclusion Patients with prolonged immobilization exhibit increased PT and aPTT CWA parameters compared to normal controls. CWA parameters could aid in identifying patients at risk of developing thrombosis through changes in the clot waveform. However, further study is needed to fully utilize additional information from routine coagulation testing.

Immune-stealth VP28-conjugated heparin nanoparticles for enhanced and reversible anticoagulation.

Heparins are a family of sulfated linear negatively charged polysaccharides that have been widely used for their anticoagulant, antithrombotic, antitumor, anti-inflammatory, and antiviral properties. Additionally, it has been used for acute cerebral infarction relief as well as other pharmacological actions. However, heparin's self-aggregated macrocomplex may reduce blood circulation time and induce life-threatening thrombocytopenia (HIT) complicating the use of heparins. Nonetheless, the conjugation of heparin to immuno-stealth biomolecules may overcome these obstacles. An immunostealth recombinant viral capsid protein (VP28) was expressed and conjugated with heparin to form a novel nanoparticle (VP28-heparin). VP28-heparin was characterized and tested to determine its immunogenicity, anticoagulation properties, effects on total platelet count, and risk of inducing HIT in animal models. The synthesized VP28-heparin trimeric nanoparticle was non-immunogenic, possessed an average hydrodynamic size (8.81 ± 0.58 nm) optimal for the evasion renal filtration and reticuloendothelial system uptake (hence prolonging circulating half-life). Additionally, VP28-heparin did not induce mouse death or reduce blood platelet count when administered at a high dosein vivo(hence reducing HIT risks). The VP28-heparin nanoparticle also exhibited superior anticoagulation properties (2.2× higher prothrombin time) and comparable activated partial thromboplastin time, but longer anticoagulation period when compared to unfractionated heparin. The anticoagulative effects of the VP28-heparin can also be reversed using protamine sulfate. Thus, VP28-heparin may be an effective and safe heparin derivative for therapeutic use.

Pre-analytical errors in coagulation testing: a case series.

OBJECTIVES: Prevention of pre-analytical issues in coagulation testing is of paramount importance for good laboratory performance. In addition to common issues like hemolysed, icteric, or lipemic samples, some specific pre-analytical errors of coagulation testing include clotted specimens, improper blood-to-anticoagulant ratio, contamination with other anticoagulants, etc. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are very commonly affected tests due to pre-analytical variables. The impact these parameters possess on surgical decision-making and various life-saving interventions are substantial therefore we cannot afford laxity and casual mistakes in carrying out these critical investigations at all. CASE PRESENTATION: In this case series, a total of 4 cases of unexpectedly deranged coagulation profiles have been described which were reported incorrectly due to the overall casual approach towards these critical investigations. We have also mentioned how the treating clinician and lab physician retrospectively accessed relevant information in the nick of time to bring back reassurance. CONCLUSIONS: Like every other critical investigation, analytical errors can occur in coagulation parameters due to various avoidable pre-analytical variables. The release of spurious results for coagulation parameters sets alarm bells ringing causing much agony to the treating doctor and patient. Only a disciplined and careful approach taken by hospital and lab staff towards each sample regardless of its criticality can negate these stressful errors to a large extent.

Evaluation of Citrated Plasma After Thawing for Routine Coagulation Testing.

OBJECTIVE: We aim to find the time in which a thawed citrate plasma sample that was preserved can be analyzed for routine coagulation testing without losing precision. METHODS: Whole blood samples from 30 healthy volunteers were collected in 3.2% sodium citrate vacutainer and centrifuged to separate platelet-poor plasma. Each sample was then aliquoted, one aliquot was used immediately for prothrombin time (PT)-international normalized ratio (INR) and activated partial thromboplastin time (APTT), four were stored at -20°C, and four were stored at -80°C for 24 hours. After 24 hours, the aliquots were taken out and thawed at 37°C in water bath and analyzed after 15, 30, 60, and 120 minutes. STATISTICAL ANALYSIS: Data were presented as mean with standard deviation (SD). Repeated measures ANOVA with Tukey post-hoc test was performed for multiple comparisons. All analysis was done using GraphPAD Prism 8.0 software (GraphPad Software, San Diego, California, USA).  Results: In the case of PT and INR, no statistically significant difference was found between the mean values after thawing for 120 minutes when compared with the mean baseline value. However, the APTT showed a statistically significant difference (p = 0.0232) after 30 minutes of thawing when the sample was stored at -20°C. Furthermore, a statistically significance difference (p = 0.0001) was found after 60 minutes of thawing when the samples were stored at -80°C. CONCLUSION: Plasma samples for the PT and INR may be accepted for assessment up to 120 minutes, when stored at -20°C and -80°C for 24 hours. In the case of APTT, the plasma sample can be used for assessment up to 30 minutes after thawing when stored at -20°C and up to 60 minutes when stored at -80°C.

Isolated Prolongation of Activated Partial Thromboplastin Time: Not Just Bleeding Risk!

Activated partial thromboplastin time (aPTT) is a fundamental screening test for coagulation disturbances. An increased aPTT ratio is quite common in clinical practice. How the detection of prolonged activated aPTT with a normal prothrombin time is interpreted is therefore very important. In daily practice, the detection of this abnormality often leads to delayed surgery and emotional stress for patients and their families and may be associated with increased costs due to re-testing and coagulation factor assessment. An isolated, prolonged aPTT is seen in (a) patients with congenital or acquired deficiencies of specific coagulation factors, (b) patients receiving treatment with anticoagulants, mainly heparin, and (c) individuals/patients with circulating anticoagulants. We summarize here what may cause an isolated prolonged aPTT and evaluate the preanalytical interferences. The identification of the cause of an isolated prolonged aPTT is of the utmost importance in ensuring the correct diagnostic workup and therapeutic choices.

Congenital Factor X-Riyadh (Stuart-Prower) Deficiency With Isolated Prothrombin Time Prolongation: A Case Report.

Factor X (FX) deficiency is an extremely rare autosomal recessive inherited coagulation defect. We report a case of congenital Factor X-Riyadh deficiency discovered during a routine workup before a dental procedure. During routine work-up for dental surgery, prothrombin time (PT) and the international normalized ratio (INR) were prolonged. The prothrombin time (PT) was found to be 78.4 (normal 11-14 seconds) with an international normalized ratio (INR) of 7.83; the activated partial thromboplastin time (APTT) was 30.7 (normal 25-42 seconds). Specific coagulation factor assays confirmed an FX deficiency (<10 % of normal activity) and a mild factor VII deficiency 37% (normal 48%-124%). Molecular genetic analysis of the whole exome sequence (WES) confirmed the diagnosis of FX deficiency (homozygous pathogenic variant c. 271G>A p {Glu91Lys} chr13:113793685). The patient is currently on regular follow-up and is advised to take oral antifibrinolytic medications for any superficial or mucosal bleeding.

An Acute Need Inspiration: Autoneutralization of Lupus Anticoagulants in Affected Prothrombin Times (PT) and Activated Partial Thromboplastin Times (APTT).

Lupus anticoagulants are antibodies directed to phospholipids (PL) and in particular represent an in vitro phenomenon where these antibodies bind to PL in coagulation reagents creating an artificial prolongation of the activated partial thromboplastin time (APTT) and sometimes also prothrombin time (PT) clotting times. Prolongation of LA-induced clotting times is typically not associated with bleeding risk. However, the degree of prolongation may cause some trepidation for clinicians that will be performing delicate surgeries or those with high bleeding risks, so a mechanism to alleviate their anxiety may be prudent. As such, an autoneutralizing method to mitigate or eliminate the LA effect on the PT and APTT may be beneficial. In this document, the detailing of an autoneutralizing procedure to diminish the LA effect on the PT and APTT will be provided.

An Overview of Heparin Monitoring with the Anti-Xa Assay.

Heparin remains a critical therapy in hospitalized patients requiring anticoagulation. Unfractionated heparin (UFH) mediates its therapeutic effect by binding to antithrombin (AT) and inhibiting thrombin and FXa, as well as other serine proteases. Because of its complex pharmacokinetics, monitoring UFH therapy is required, which is usually achieved with either the activated partial thromboplastin time (APTT) or the anti-factor Xa (anti-Xa) assay. Low molecular weight heparin (LMWH) is fast replacing UFH, as it has a more predictable response, negating the need for routine monitoring in most cases. When required, the anti-Xa assay is used for monitoring of LMWH. The APTT has many notable limitations when used for heparin therapeutic monitoring, including biologic, preanalytical, and analytical issues. With its increasing availability, the anti-Xa assay is appealing as it is less affected by patient factors (e.g., acute-phase reactants, lupus anticoagulants, consumptive coagulopathies), known to interfere with the APTT. The anti-Xa assay has shown additional benefits, such as faster time to achieve therapeutic levels, more consistent therapeutic levels, less dose adjustments, and, overall, less tests performed during therapy. However, poor interlaboratory agreement has been observed among anti-Xa reagents, highlighting that further work needs to be done to standardize this assay for use in patient heparin monitoring.

Genetic Polymorphisms Associated with Prothrombin Time and Activated Partial Thromboplastin Time in Chinese Healthy Population.

(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (p < 1 × 10−5). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10−19) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10−5). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10−6), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10−6) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10−6) were significantly correlated with APTT (p < 1 × 10−5). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation.

A Recurrent Neural Network Model for Predicting Activated Partial Thromboplastin Time After Treatment With Heparin: Retrospective Study.

BACKGROUND: Anticoagulation therapy with heparin is a frequent treatment in intensive care units and is monitored by activated partial thromboplastin clotting time (aPTT). It has been demonstrated that reaching an established anticoagulation target within 24 hours is associated with favorable outcomes. However, patients respond to heparin differently and reaching the anticoagulation target can be challenging. Machine learning algorithms may potentially support clinicians with improved dosing recommendations. OBJECTIVE: This study evaluates a range of machine learning algorithms on their capability of predicting the patients' response to heparin treatment. In this analysis, we apply, for the first time, a model that considers time series. METHODS: We extracted patient demographics, laboratory values, dialysis and extracorporeal membrane oxygenation treatments, and scores from the hospital information system. We predicted the numerical values of aPTT laboratory values 24 hours after continuous heparin infusion and evaluated 7 different machine learning models. The best-performing model was compared to recently published models on a classification task. We considered all data before and within the first 12 hours of continuous heparin infusion as features and predicted the aPTT value after 24 hours. RESULTS: The distribution of aPTT in our cohort of 5926 hospital admissions was highly skewed. Most patients showed aPTT values below 75 s, while some outliers showed much higher aPTT values. A recurrent neural network that consumes a time series of features showed the highest performance on the test set. CONCLUSIONS: A recurrent neural network that uses time series of features instead of only static and aggregated features showed the highest performance in predicting aPTT after heparin treatment.

Assessment of Stability of Prothrombin Time, International Normalized Ratio, and Activated Partial Thromboplastin Time Under Different Storage Conditions in Human Plasma.

Background In this study, we aimed to determine the effects of storage time and temperature on commonly performed coagulation tests such as prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) in human plasma. Methodology Whole blood samples from 100 patients were collected in a 3.2% sodium citrate vacutainer. The blood was centrifuged within two hours of collection at 2,000 g for 10 minutes, and the platelet-poor plasma (PPP) obtained was analyzed for PT, INR, and APTT tests at zero hours (baseline) and repeated at 12 hours, 24 hours, and 36 hours on a fully automated coagulation analyzer at various storage conditions (room temperature, refrigerator, and freezer). The results were categorized into two groups: group 1 comprised results with normal coagulation profile and group 2 comprised results with abnormal coagulation profile. The percentage change of the results from baseline (zero hours) for PT, INR, and APTT tests was also studied. A percentage change of more than ±10% from baseline was considered as a clinically significant change. Results In this study, a total of 95 PPP samples were evaluated. The median age of all patients was 44 years (range: 19-65 years). The male-to-female ratio was 0.9:1. The baseline PT, INR, and APTT values were 12.1 seconds, 1.06, and 26.5 seconds, respectively, in group 1, whereas the baseline PT, INR, and APTT values were 19.1 seconds, 1.80, and 36.0 seconds, respectively, in group 2. In the freezer, the samples were stable for PT, INR, and APTT tests at 12 hours, 24 hours, and 36 hours showing a change of <10% from baseline at all three time-points. In the refrigerator, the samples were stable for PT and INR tests for up to 24 hours showing a change of <10% from baseline. In comparison, the samples for the APTT test were not stable at 12 hours, 24 hours, and 36 hours showing a change of 12.1%, 15.5%, and 17.9%, respectively, from the baseline (zero hours). Finally, at room temperature, the samples deteriorated at 12 hours for all coagulation parameters (PT, INR, and APTT). Conclusions The patient plasma samples for PT, INR, and APTT tests could be safely stored for up to 36 hours in the freezer. In the refrigerator, samples for PT and INR tests could be safely stored for up to 24 hours while the samples for APTT deteriorated at 12 hours. All patient samples for PT, INR, and APTT tests deteriorated at 12 hours at room temperature.

Comparison of capillary and venous blood sampling for routine coagulation assays.

OBJECTIVES: Capillary blood samples are generally assumed as unsuitable for coagulation testing since it is recognized that contamination with tissue factor and dilution with tissue fluid affects the coagulation assay. However, limited data is available about coagulations assays in which capillary blood sampling is compared to the standard venous blood withdrawal method. The aim of this study was to perform a method comparison between capillary and venous blood sampling for routine coagulation assays. METHODS: Both venous and capillary (finger stick) blood samples were collected from 188 healthy volunteers and patients. In citrate plasma, International Normalized Ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, and D-dimer were measured according to routine protocols using the ACL-TOP 750 LAS (Werfen) coagulation analyzer. Regression analysis was performed and the mean relative difference between capillary and venous sampling was reflected to the total allowable error (TEa). RESULTS: Strong correlations and acceptable variations, using the TEa as decision limit, were found for INR, PT, TT, fibrinogen, and D-dimer between capillary and venous sampling. However, capillary sampling resulted in significant shorter APTT values when using the standard APTT-SP Liquid reagent with a mean bias of -10.4% [95% CI -12.4 to -8.4]. CONCLUSION: Based on these results, capillary blood sampling proved to be an alternative blood withdrawal method for routine coagulation assays, with the exception of APTT, if a venipuncture is unavailable or undesired.

Could a Haematoma Be Due to an Acquired Phenomenon?

Acquired hemophilia, as opposed to congenital hemophilia, develops in individuals with no previous history of bleeding disorder with almost similar numbers of males and females affected. It is predominantly a disease of the elderly. It is an autoimmune disorder and occurs when the immune system produces antibodies that mistakenly attack healthy tissue, specifically the clotting factors, in particular clotting factor VIII. As a result, affected individuals develop abnormal uncontrolled bleeding into the muscles, soft tissues, and the skin and it can occur spontaneously during surgery, or following trauma, and potentially cause life-threatening bleeding complications in severe cases. The affected individuals may remain undiagnosed or be misdiagnosed, making it difficult to determine the actual frequency of the disorder in the general population. The clinical presentation should suspect it with confirmation by an abnormal coagulation test. Typical laboratory results with a recent onset of abnormal bleeding and an isolated prolongation of the activated partial thromboplastin time (APTT), especially in the elderly and peri- and post-partum women, should raise eyebrows. We present two cases following different symptomatology and emphasize the clinical challenges for junior medical doctors who receive patients on the front end. We hope to emphasize understanding simple coagulation blood results followed by a meaningful discussion with the hematology team towards appropriate and timely management of the bleeding diathesis. We hope this case series report will help junior medical doctors manage patients appropriately and consult with their hematology colleagues.

Higher admission activated partial thromboplastin time, neutrophil-lymphocyte ratio, serum sodium, and anticoagulant use predict in-hospital COVID-19 mortality in people with Diabetes: Findings from Two University Hospitals in the U.K.

AIMS: To create and compare survival models from admission laboratory indices in people hospitalized with coronavirus disease 2019 (COVID-19) with and without diabetes. METHODS: Retrospective observational study of patients with COVID-19 with or without diabetes admitted to Sheffield Teaching Hospitals from 29 February to 01 May 2020. Predictive variables for in-hospital mortality from COVID-19 were explored using Cox proportional hazard models. RESULTS: Out of 505 patients, 156 (30.8%) had diabetes mellitus (DM) of which 143 (91.7%) had type 2 diabetes. There were significantly higher in-hospital COVID-19 deaths in those with DM [DM COVID-19 deaths 54 (34.6%) vs. non-DM COVID-19 deaths 88 (25.2%): P < 0.05]. Activated partial thromboplastin time (APPT) > 24 s without anticoagulants (HR 6.38, 95% CI: 1.07-37.87: P = 0.04), APTT > 24 s with anticoagulants (HR 24.01, 95% CI: 3.63-159.01: P < 0.001), neutrophil-lymphocyte ratio > 8 (HR 6.18, 95% CI: 2.36-16.16: P < 0.001), and sodium > 136 mmol/L (HR 3.27, 95% CI: 1.12-9.56: P = 0.03) at admission, were only associated with in-hospital COVID-19 mortality for those with diabetes. CONCLUSIONS: At admission, elevated APTT with or without anticoagulants, neutrophil-lymphocyte ratio and serum sodium are unique factors that predict in-hospital COVID-19 mortality in patients with diabetes compared to those without. This novel finding may lead to research into haematological and biochemical mechanisms to understand why those with diabetes are more susceptible to poor outcomes when infected with Covid-19, and contribute to identification of those most at risk when admitted to hospital.

Noninvasive evaluation of ovarian endometriosis: a single-center experience.

BACKGROUND: To investigate the relationships of cancer antigen (CA) 125, CA 19-9, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen (FIB), and D-dimer values with ovarian endometriosis (OEM), and to explore the validation of biomarkers for noninvasive preoperative evaluation of patients with severe OEM. METHODS: This retrospective case-control study included 413 women with OEM (of whom 143 cases were stage I to II, 139 cases were stage III, and 131 cases were stage IV, respectively) and 158 women without OEM as controls. Subjects' serum CA-125 and CA19-9 levels, and coagulation test results (serum PT, aPTT, and D-dimer values) were evaluated. RESULTS: The serum CA-125, aPTT, FIB and D-dimer levels were statistically different between OEM patients in the stages I to (and) II group and those in the stages III and IV group (P<0.05). However, a statistical difference in CA 19-9 levels and TT was only found between patients with stages III and IV OEM. In receiver operating characteristic (ROC) curve analysis of single indexes, the area under the ROC curve values for CA-125, CA19-9, aPTT, TT, FIB, and D-dimer were 0.953, 0.512, 0.66, 0.576, 0.573, and 0.624, respectively, for diagnosing stage III and stage IV OEM. In ROC curve analysis of combined indexes, the AUC values for aPTT + D-dimer, CA-125 + D-dimer, CA-125 + aPTT and CA-125 + D-dimer + aPTT were 0.672, 0.954, 0.958, and 0.961, respectively. CONCLUSIONS: The combined index of CA-125, aPTT, and D-dimer is a valid noninvasive preoperative method for the evaluation of moderate and severe OEM, and may help to decrease the interval between the first complaint and a definitive diagnosis.

The Effect of Sugammadex on Prothrombin and Activated Partial Thromboplastin Time.

Sugammadex is routinely used as an effective neuromuscular blockade reversal agent. Several studies have indicated that it may prolong the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). This review gathers the relevant in vivo studies to accumulate knowledge on the subject. Nine studies were included. According to the results, sugammadex seems to lead to a transient increase in aPTT and PT values, compared to standard care. However, the clinical impact seems to be trivial. Nevertheless, the trials' findings reveal great heterogeneity, preventing a meta-analysis. Therefore, more well-designed studies are needed to lead to prudent conclusions.