Longitudinal SARS-CoV-2 Testing among the Unvaccinated Is Punctuated by Intermittent Positivity and Variable Rates of Increasing Cycle Threshold Values.

The coronavirus disease 2019 (COVID-19) pandemic is complicated by cases of vaccine breakthrough and reinfection and widespread transmission of variants of concern (VOCs). Consequently, the need to interpret longitudinal positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although diagnostic real-time reverse transcription (RT)-PCR tests yield values that are inversely correlated with RNA quantity, these tests are only approved for qualitative interpretation.

COVID-19 symptoms at time of testing and association with positivity among outpatients tested for SARS-CoV-2.

Introduction: Symptoms associated with SARS-CoV-2 infection remain incompletely understood, especially among ambulatory, non-hospitalized individuals. With host factors, symptoms predictive of SARS-CoV-2 could be used to guide testing and intervention strategies.

Methods: Between March 16 and September 3, 2020, we examined the characteristics and symptoms reported by individuals presenting to a large outpatient testing program in the Southeastern US for nasopharyngeal SARS-CoV-2 RNA RT-PCR testing.

Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion.

Background: Transfusion-associated circulatory overload (TACO) is the second leading cause of reported transfusion-related fatalities in the United States. While its occurrence has been previously investigated after red cell and plasma transfusion, no data are available regarding its association with platelet transfusion. Our goal was to determine the rate of platelet-associated TACO at our university medical centre.

Interferon-α is not elevated in idiopathic thrombotic thrombocytopenic purpura patients.

Idiopathic thrombotic thrombocytopenic purpura (TTP) patients have ADAMTS13 deficiency, which is usually caused by ADAMTS13 autoantibodies. However, the triggering factors for the autoantibody production remain unclear. Interferon-α (IFN-α) is a cytokine involved with many autoimmune processes such as inducing the activation of peripheral dendritic cells and stimulating T cells and B cells.

FVIIa as used pharmacologically is not TF dependent in hemophilia B mice.

Activated factor VII is approved for treating hemophilia patients with autoantibodies to their factor IX or FVIII; however, its mechanism of action remains controversial. Some studies suggest that FVIIa requires tissue factor (TF) for function and that the reason for the high dose requirement is that it must compete with endogenous FVII for tissue factor. Others suggest that FVIIa binds platelets where it activates FX directly; the high concentration required would result from FVIIa's weak affinity for phospholipids.

Performance of coagulation tests in patients on therapeutic doses of dabigatran: a cross-sectional pharmacodynamic study based on peak and trough plasma levels.

Background: Knowledge of anticoagulation status during dabigatran therapy may be desirable in certain clinical situations.

Objective: To determine the coagulation tests that are most useful for assessing dabigatran's anticoagulant effect.

Methods: Peak and trough blood samples from 35 patients taking dabigatran 150 mg twice daily, and one sample each from 30 non-anticoagulated individuals, were collected.

Major burn injury is not associated with acute traumatic coagulopathy.

Background: The pathophysiology and time course of coagulopathy after major burns are inadequately understood. Our study objectives were to determine whether acute traumatic coagulopathy (ATC) is seen in burn patients at admission and to determine the changes in international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count (PLT), and hemoglobin (Hgb) in the first 7 days after injury.

Methods: We conducted a retrospective study of patients with burn injury of at least 15% total body surface area who presented to the University of North Carolina.

Blood utilization in patients with burn injury and association with clinical outcomes (CME).

Background: Uncontrolled bleeding is an important cause of increased transfusion in burn victims; however, description of blood utilization patterns in the burn population is lacking.

Study Design And Methods: We conducted a single-institution, retrospective cohort study to measure blood utilization in 89 consecutive burn patients with 15% to 65% total body surface area (TBSA) burn within 60 days of injury. We also evaluated the relationship of blood product utilization with clinical variables including anticoagulant usage and mortality.

A sensitive venous bleeding model in haemophilia A mice: effects of two recombinant FVIII products (N8 and Advate(®)).

Haemostatic effect of compounds for treating haemophilia can be evaluated in various bleeding models in haemophilic mice. However, the doses of factor VIII (FVIII) for normalizing bleeding used in some of these models are reported to be relatively high. The aim of this study was to establish a sensitive venous bleeding model in FVIII knock out (F8-KO) mice, with the ability to detect effect on bleeding at low plasma FVIII concentrations.

Substitution of a heparin correlation value for activated partial thromboplastin time in heparin nomograms.

PURPOSE. Use of nomograms based on the "heparin correlation value" (HCV)-a value that corresponds to measured activated partial thromboplastin time (aPTT) and that removes the need to revise nomograms in response to a change in the aPTT reagent or coagulometer used-was evaluated as an alternative to traditional aPTT-based anticoagulation nomograms. SUMMARY.

Overexpression of the cell cycle inhibitor p16INK4a promotes a prothrombotic phenotype following vascular injury in mice.

Objective: Age-associated cellular senescence is thought to promote vascular dysfunction. p16(INK4a) is a cell cycle inhibitor that promotes senescence and is upregulated during normal aging. In this study, we examine the contribution of p16(INK4a) overexpression to venous thrombosis.

Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time.

Background: In an effort to improve interlaboratory agreement in the monitoring of unfractionated heparin (UFH), the College of American Pathologists (CAP) recommends that the therapeutic range of the activated partial thromboplastin time (APTT) be defined in each laboratory through correlation with a direct measure of heparin activity such as the factor Xa inhibition assay. Whether and to what extent this approach enhances the interlaboratory agreement of UFH monitoring has not been reported.

Objectives: We conducted a cross-validation study among four CAP-accredited coagulation laboratories to compare the interlaboratory agreement of the anti-FXa-correlated APTT with that of the traditional 1.

Overview of murine thrombosis models.

There are a myriad of options on where and how to perform thrombosis studies in mice. Models have been developed for systemic thrombosis, larger and smaller vessels of both the arterial and venous systems as well as several different microvascular beds. However, there are important differences between the models and investigators need to be careful and thoughtful when they choose which model to use.

The heparin-binding exosite of factor IXa is a critical regulator of plasma thrombin generation and venous thrombosis.

The role of the factor IXa heparin-binding exosite in coagulation was assessed with mutations that enhance (R170A) or reduce (R233A) stability of the protease-factor VIIIa A2 domain interaction. After tissue factor (TF) addition to reconstituted factor IX-deficient plasma, factor IX R170A supported a 2-fold increase in velocity index (slope) and peak thrombin concentration, whereas factor IX R233A had a 4- to 10-fold reduction relative to factor IX wild-type. In the absence of TF, 5 to 100 pM of factor IXa increased thrombin generation to approach TF-stimulated thrombin generation at 100% factor IX.

Serpins (serine protease inhibitors).

Serpins are a class of proteins involved in the regulation of serine and other types of proteases. In humans, the majority of serpins regulate the functions of proteases involved in the body's response to injury. This includes roles in coagulation, fibrinolysis, inflammation, wound healing, and tissue repair.

Coagulation activation and inflammation in sickle cell disease-associated pulmonary hypertension.

Background: Pulmonary hypertension (PHT) is common in sickle cell disease (SCD). The purpose of this study was to determine whether markers of coagulation activation and inflammation are associated with PHT in SCD.

Design And Methods: This cross-sectional study was performed using a cohort of patients followed at an adult Sickle Cell Clinic.

Essential thrombin residues for inhibition by protein C inhibitor with the cofactors heparin and thrombomodulin.

Background: Protein C inhibitor (PCI) and antithrombin (AT) are serine protease inhibitors (serpins) that inhibit a wide array of blood coagulation serine proteases including thrombin.

Objective: Fifty-five Ala-scanned recombinant thrombin mutants were used to determine thrombin residues important for inhibition by PCI with and without the cofactors heparin and thrombomodulin (TM) and compared with the prototypical serpin, AT.

Results: Residues around the active site (Tyr50 and Glu202) and the sodium-binding site (Glu229 and Arg233) were required for thrombin inhibition by PCI with and without cofactors.

Molecular mapping of the thrombin-heparin cofactor II complex.

We used 55 Ala-scanned recombinant thrombin molecules to define residues important for inhibition by the serine protease inhibitor (serpin) heparin cofactor II (HCII) in the absence and presence of glycosaminoglycans. We verified the importance of numerous basic residues in anion-binding exosite-1 (exosite-1) and found 4 additional residues, Gln24, Lys65, His66, and Tyr71 (using the thrombin numbering system), that were resistant to HCII inhibition with and without glycosaminoglycans. Inhibition rate constants for these exosite-1 (Q24A, K65A, H66A, Y71A) thrombin mutants (0.