Altered thrombin generation with prothrombin complex concentrate is not detected by viscoelastic testing: an in vitro study.

Background: Bleeding guidelines currently recommend use of viscoelastic testing (VET) to direct haemostatic resuscitation in severe haemorrhage. However, VET-derived parameters of clot initiation, such as clotting time (CT) and activated clotting time (ACT), might not adequately reflect a clinically relevant interaction of procoagulant and anticoagulant activity, as revealed by thrombin generation assays. The aim of this study was to evaluate the ability of CT and ACT to indicate thrombin generation activity.

TaqMan Array Card real-time polymerase chain reaction panel to detect pathogens in whole blood of febrile inpatients in northern Tanzania, 2016-2019.

Background: Acute febrile illness is a common reason for seeking healthcare in low- and middle-income countries. We describe the diagnostic utility of a TaqMan Array Card (TAC) real-time polymerase chain reaction (PCR) panel for pathogen detection in paediatric and adult inpatients admitted with febrile illness.

Methods: In this prospective cohort study, we screened medical admissions for a tympanic temperature ≥38.

Effect of Unfractionated Heparin Dose on Complement Activation and Selected Extracellular Vesicle Populations during Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) provides critical support for patients with severe cardiopulmonary dysfunction. Unfractionated heparin (UFH) is used for anticoagulation to maintain circuit patency and avoid thrombotic complications, but it increases the risk of bleeding. Extracellular vesicles (EVs), nano-sized subcellular spheres with potential pro-coagulant properties, are released during cellular stress and may serve as potential targets for monitoring anticoagulation, particularly in thromboinflammation.

Circulating endothelial extracellular vesicle signatures correspond with ICU requirement: an exploratory study in COVID-19 patients.

Extracellular vesicles (EVs) represent nanometer-sized, subcellular spheres, that are released from almost any cell type and carry a wide variety of biologically relevant cargo. In severe cases of coronavirus disease 2019 (COVID-19) and other states of systemic pro-inflammatory activation, EVs, and their cargo can serve as conveyors and indicators for disease severity and progression. This information may help distinguish individuals with a less severe manifestation of the disease from patients who exhibit severe acute respiratory distress syndrome (ARDS) and require intensive care measures.

Concentration-effect relationship for tranexamic acid inhibition of tissue plasminogen activator-induced fibrinolysis in vitro using the viscoelastic ClotPro® TPA-test.

Background: Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women.

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study.

Purpose: Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission.

Use of Recombinant Activated Factor VII in Bleeding Lung Transplant Patients Undergoing Perioperative ECMO Therapy.

Background: Hemostasis in critically ill patients represents a fragile balance between hypocoagulation and hypercoagulation, and is influenced by various factors. Perioperative use of extracorporeal membrane oxygenation (ECMO)-increasingly used in lung transplantation-further destabilizes this balance, not least due to systemic anticoagulation. In the case of massive hemorrhage, guidelines recommend considering recombinant activated Factor VII (rFVIIa) as an ultima ratio treatment only after several preconditions of hemostasis have been established.

Characterization of 2 Different Prothrombin Complex Concentrates by Different Hemostatic Assays in an In Vitro Hemodilution Model.

Background: Viscoelastically guided coagulation factor concentrate-based algorithms for the treatment of trauma-induced coagulopathy include the administration of prothrombin complex concentrates (PCCs). However, the exact role of PCC preparations in this context is a matter of debate. Particularly, the ideal diagnostic trigger for their administration and potential differences between heparin-containing and heparin-free preparations remain unclear.

Pharmacogenetic testing for NAT2 genotypes in a Tanzanian population across the lifespan to guide future personalized isoniazid dosing.

Despite updated recommendations for weight-based isoniazid dosing in children with drug-susceptible tuberculosis (TB) and higher dose isoniazid in regimens for adults with drug-resistant TB, individual pharmacokinetic variability can lead to sub-target isoniazid exposure. Host pharmacogenetics and isoniazid exposure remain understudied, especially in the East African population. We therefore employed a real-time polymerase chain reaction (qPCR) assay system to test genomic DNA extracted from saliva samples targeting the NAT2 gene responsible for isoniazid metabolism to describe the frequency of human single nucleotide polymorphisms in NAT2 within populations of children and adults in Tanzania, ascribe those polymorphisms to acetylator phenotype, and correlate to serum isoniazid exposures.

Subcutaneous Enoxaparin for Systemic Anticoagulation of COVID-19 Patients During Extracorporeal Life Support.

Background: Extracorporeal membrane oxygenation, with an inherent requirement for anticoagulation to avoid circuit thrombosis, is a key element in the treatment of respiratory failure associated with COVID-19. Anticoagulation remains challenging, the standard of care being intravenous continuous administration of unfractionated heparin. Yet regimens vary.

Enteropathogen spectrum and effect on antimycobacterial pharmacokinetics among children with tuberculosis in rural Tanzania: a prospective cohort study.

Background: Enteropathy is prevalent in tuberculosis-endemic areas, and it has been shown to impair intestinal absorptive function; therefore, enteropathogen burden might negatively affect antimycobacterial pharmacokinetics, particularly among malnourished children. We sought to quantify enteropathogen burden among children initiating tuberculosis treatment in rural Tanzania and determine the effect of enteropathogen burden on serum antimycobacterial pharmacokinetics.

Methods: We performed a prospective cohort study at one site in rural Tanzania as an exploratory substudy of a large multicountry cohort study.

Anti-factor Xa Activity Is Not Associated With Venous Thromboembolism in Critically Ill Patients Receiving Enoxaparin for Thromboprophylaxis: A Retrospective Observational Study.

Background: Anti-factor Xa activity has been suggested as a surrogate parameter for judging the effectiveness of pharmacological thromboprophylaxis with low molecular weight heparins in critically ill patients. However, this practice is not supported by evidence associating low anti-factor Xa activity with venous thromboembolism.

Methods: We performed a retrospective observational study including 1,352 critically ill patients admitted to 6 intensive care units of the Medical University of Vienna, Austria between 01/2015 and 12/2018.

Whole genome sequencing-based drug resistance predictions of multidrug-resistant isolates from Tanzania.

Background: Rifampicin- or multidrug-resistant (RR/MDR) complex (MTBC) strains account for considerable morbidity and mortality globally. WGS-based prediction of drug resistance may guide clinical decisions, especially for the design of RR/MDR-TB therapies.

Methods: We compared WGS-based drug resistance-predictive mutations for 42 MTBC isolates from MDR-TB patients in Tanzania with the MICs of 14 antibiotics measured in the Sensititre™ MycoTB assay.

Comparison of the New Viscoelastic Coagulation Analyzer ClotPro® With ROTEM® Delta and Conventional Coagulation Tests in Critically Ill Patients With COVID-19.

Viscoelastic coagulation testing has been suggested to help manage coagulopathy in critically ill patients with COVID-19. However, results from different viscoelastic devices are not readily comparable. ClotPro® is a novel thromboelastometry analyzer offering a wider range of commercially available assays.

Effect of scheduled antimicrobial and nicotinamide treatment on linear growth in children in rural Tanzania: A factorial randomized, double-blind, placebo-controlled trial.

Background: Stunting among children in low-resource settings is associated with enteric pathogen carriage and micronutrient deficiencies. Our goal was to test whether administration of scheduled antimicrobials and daily nicotinamide improved linear growth in a region with a high prevalence of stunting and enteric pathogen carriage.

Methods And Findings: We performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial in the area around Haydom, Tanzania.

Population Pharmacokinetics and Significant Under-Dosing of Anti-Tuberculosis Medications in People with HIV and Critical Illness.

Critical illness from tuberculosis (TB) bloodstream infection results in a high case fatality rate for people living with human immunodeficiency virus (HIV). Critical illness can lead to altered pharmacokinetics and suboptimal drug exposures. We enrolled adults living with HIV and hospitalized with sepsis, with and without meningitis, in Mbarara, Uganda that were starting first-line anti-TB therapy.

Can Heparin-Coated ECMO Cannulas Induce Thrombocytopenia in COVID-19 Patients?

Extracorporeal membrane oxygenation (ECMO) is often used in the management of COVID-19-related severe respiratory failure. We report the first case of a patient with COVID-19-related ARDS on ECMO support who developed symptoms of heparin-induced thrombocytopenia (HIT) in the absence of heparin therapy. A low platelet count of 61 G/L was accompanied by the presence of circulating HIT antibodies 12 days after ECMO initiation.

Effect of Goal-Directed Crystalloid versus Colloid Administration on Perioperative Hemostasis in Partial Hepatectomy: A Randomized, Controlled Trial.

The use of colloids may impair hemostatic capacity. However, it remains unclear whether this also holds true when colloids are administered in a goal-directed manner. The aim of the present study was to assess the effect of goal-directed fluid management with 6% hydroxyethyl starch 130/0.

Pathogens That Cause Acute Febrile Illness Among Children and Adolescents in Burkina Faso, Madagascar, and Sudan.

Background: The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood.

Methods: Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens.