Algorithm of differential diagnosis of anemia involving laboratory medicine specialists to advance diagnostic excellence.

Objectives: Anemia is a severe global public health issue. Testing practices for anemia suggest overuse of screening laboratory tests and misinterpretation of studies even in "easy-to-diagnose" underlying causes, leading to late diagnoses and missed treatment opportunities. We aimed to develop a complete and efficient algorithm for clinical pathologists and laboratory medicine physicians for the differential diagnosis of anemia.

An international study on activated partial thromboplastin time prolongation. Part 2: Interpretative commenting.

Background: Providing evidence-based interpretative comments (IC) is an integral task of clinical laboratory professionals. It may be of special relevance for coagulation testing, where pathological first-line tests could trigger more specialized tests. Our aim was to evaluate the quality of ICs provided to the physician in two samples with activated partial thromboplastin time (APTT) prolongation.

An international study on activated partial thromboplastin time prolongation. Part 1: Analytical results.

Background: Unexpected prolongation of first-line coagulation tests, including activated partial thromboplastin time (APTT), should trigger further work-up by performing mixing tests to elucidate the underlying cause, direct further specific testing and clarify their possible clinical impact. The aim of our study was to assess whether methodological diversity has any impact on the APTT mixing test results and their interpretation.

Material And Methods: Two lyophilized plasma samples (case 1: heparin contamination [0.

[Immune response against the severe acute respiratory syndrome coronavirus 2].

Coronavirus disease 2019 (COVID-19) displays tremendous inter-individual variability, ranging from asymptomatic infections to life-threatening illness. Although more studies are needed, a picture has begun to emerge that variability in the immune system components is a main contributor to the heterogeneous disease courses. Here, we provide a concept for the interaction of the innate and adaptive immune systems with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to link the observations that have been made during the first two years of the pandemic.

Antibody and T Cell Responses against SARS-CoV-2 Elicited by the Third Dose of BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) Vaccines Using a Homologous or Heterologous Booster Vaccination Strategy.

In the present study, antibody and T cell-mediated immune responses elicited by BBIBP-CorV and BNT162b2 vaccines were compared 6 months after the two-dose immunization of healthy individuals. Additionally, antibody and T cell responses after the third dose of BBIBP-CorV or BNT162b2 were compared using a homologous or heterologous vaccination strategy. The third dose was consistently administered 6 months after the second dose.

Comparison of antibody and T cell responses elicited by BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) vaccines against SARS-CoV-2 in healthy adult humans.

In the present study, humoral and T cell-mediated immune responses elicited by BBIBP-CorV (inactivated virus) and BNT162b2 (mRNA-based) vaccines against SARS-CoV-2 virus were compared. Convalescent volunteers were also investigated to evaluate adaptive immunity induced by live virus. Although both vaccines induced antibody- and T cell-mediated immune responses, our analysis revealed significant quantitative and qualitative differences between the two types of challenges.

[Encephalitis following COVID-19 disease].

Shortly after that COVID-19 appeared it became clear, that although the disease mainly characterized by respiratory symptoms, other signs frequently appeared, which showed involvation of other organs. There are several new publications which report about neurological complications. According to data developing of encephalitis could be relatively frequent among these.

Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM).

Background Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods In 2013-2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen).

[Laboratory aspects of novel oral anticoagulant treatment].

The introduction of novel oral anticoagulants (NOAC) have long been expected drugs and they quickly became used widespread as their clinical effectiveness was as good as, or even better than the previously used only oral anticoagulant drug, the coumarins. Thus, the direct thrombin inhibitor dabigatran and the activated factor X inhibitors (rivaroxaban, apixaban, edoxaban) have become the part of daily therapeutic practice. Their permeation was facilitated by the guideline which suggested that no laboratory monitoring was required during NOAC treatment and this was very convenient for both patients and doctors.

Factor XIII levels and factor XIII B subunit polymorphisms in patients with venous thromboembolism.

Background: The association of plasma factor XIII (FXIII) level with venous thromboembolism (VTE) is still controversial and the effect of sex and FXIII B subunit (FXIII-B) polymorphisms in this respect have not been explored.

Objectives: 1/ To determine FXIII activity and antigen levels in patients with a history of VTE and how they are influenced by sex and FXIII-B polymorphisms. 2/ To explore the association of FXIII levels and FXIII-B polymorphisms with the risk of VTE.

Toward harmonization of interpretive commenting of common laboratory tests.

Interpretive commenting (IC) is an integral part of postanalytical activities of laboratories when the clinical interpretation of laboratory results in the context of the clinical situation of a patient is provided. Harmonizing practices in IC can be an approach to ensure high-quality comments, which if followed by adequate clinical actions has a great potential in improving patient outcomes. This paper reviews basic work prior to harmonization of IC of common laboratory test results.

A pragmatic approach to sample acceptance and rejection.

Sample rejection due to preanalytical errors is very common in many medical laboratories worldwide, though the decision when and how to refrain from analyzing such samples is handled very heterogeneously. As a rational, it is mostly stated that it is done to prevent the patient from being harmed by wrong medical decisions based on such values. But when thinking of the consequences of laboratory results instead of their quality being important per se, the rejection of preanalytically altered samples might be harming the patient by the need of re-collection and timely delay.

Regulation of plasma factor XIII levels in healthy individuals; a major impact by subunit B intron K c.1952+144 C>G polymorphism.

Background: The regulation of plasma factor XIII (FXIII) levels in healthy individuals has been only partially explored. The identification of major non-genetic and genetic regulatory factors might provide important information on the contribution of FXIII to the risk of cardio/cerebrovascular diseases.

Objectives: To determine the effect of age, smoking, BMI, fibrinogen concentration on plasma FXIII activity, complex FXIII antigen (FXIII-AB) and total FXIII-B subunit (tFXIII-B) level, to correlate FXIII-B level with the other two FXIII parameters and to assess the variation of FXIII levels in carriers of major FXIII subunit polymorphisms.

Adding Value in the Postanalytical Phase.

Apart from maintaining the highest quality of analytical test results, laboratories are now getting more focused on how to achieve the greatest impact of laboratory results on their patient's outcome. Laboratory professionals are now in the learning phase of implementing new practices at different steps of the extra-analytical phases of the testing process where laboratories used to contribute seldom, only sporadically. Recently, the achievable levels of harmonization and responsible contributors at various steps of the testing process have also been proposed.

Is D-dimer used according to clinical algorithms in the diagnostic work-up of patients with suspicion of venous thromboembolism? A study in six European countries.

Introduction: Clinical algorithms consisting of pre-test probability estimation and D-dimer testing are recommended in diagnostic work-up for suspected venous thromboembolism (VTE). The aim of this study was to explore how physicians working in emergency departments investigated patients suspected to have VTE.

Materials And Methods: A questionnaire with two case histories related to the diagnosis of suspected pulmonary embolism (PE) (Case A) and deep venous thrombosis (DVT) (Case B) were sent to physicians in six European countries.

An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation.

Background: An unexpectedly detected prolonged activated partial thromboplastin time (APTT) can be a harmless laboratory finding, but can also reflect a thrombotic tendency or a bleeding disorder. The assistance of laboratory professionals in the interpretation of an unexpectedly detected prolonged APTT (uAPTT) is often required. The way in which uAPTTs are evaluated in laboratories was assessed in this international study with the aim of determining whether laboratory professionals are able to fulfill this need.

Effect of the Gas6 c.834+7G>A polymorphism and the interaction of known risk factors on AMD pathogenesis in Hungarian patients.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. Numerous genetic factors contribute to the development of the multifactorial disease. We performed a case-control study to assess the risk conferred by known and candidate genetic polymorphisms on the development of AMD.

Interpretation and management of INR results: a case history based survey in 13 countries.

Introduction: Standardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care.

Methods: Two case histories were distributed to physicians in 13 countries.

Distribution of CFTR mutations in Eastern Hungarians: relevance to genetic testing and to the introduction of newborn screening for cystic fibrosis.

Background: The aim of this study was characterization of an updated distribution of CFTR mutations in a representative cohort of 40 CF patients with the classical form of the disease drawn from Eastern Hungary. Due to the homogeneity of the Hungarian population our data are generally applicable to other regions of the country, including the sizeable diaspora.

Methods: We utilized the recommended "cascade" CFTR mutation screening approach, initially using a commercial assay, followed by examination of the common "Slavic" deletion CFTRdele2,3(21kb).

Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients.

Purpose: Recent studies strongly support the role of genetic factors in the aetiology of age-related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors.

Methods: In a case-control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls.

Assessment of thrombotic risk factors predisposing to thromboembolic complications in prosthetic orthopedic surgery.

Background: Congenital thrombophilia is responsible for thromboembolic complications despite prolonged low-molecular-weight heparin (LMWH) prophylaxis following hip and knee endoprosthesis surgery.

Methods: A series of 86 patients with hip or knee endoprosthesis surgery were assessed 1 year after operation. Antithrombin III, protein C, and protein S were determined, and the activated protein C sensitivity ratio was measured.

Severe bleeding complications caused by an autoantibody against the B subunit of plasma factor XIII: a novel form of acquired factor XIII deficiency.

Acquired factor XIII (FXIII) deficiency due to autoantibody against FXIII is a very rare severe hemorrhagic diathesis. Antibodies directed against the A subunit of FXIII, which interfere with different functions of FXIII, have been described. Here, for the first time, we report an autoantibody against the B subunit of FXIII (FXIII-B) that caused life-threatening bleeding in a patient with systemic lupus erythematosus.