Fibrinolysis is a critical aspect of the hemostatic system, with assessment of fibrinolytic potential being critical to predict bleeding and clotting risk. We describe the method for a novel low-plasma-volume assay of fibrinolytic capacity utilizing the euglobulin fraction (the “modified mini-euglobulin clot lysis assay [ECLA]”), its analytic sensitivity to alterations in key fibrinolytic substrates/regulators, and its initial applications in acute and convalescent disease cohorts.
The modified mini-ECLA requires 50 μL of plasma, a maximal read time of 3 h (with most results available within 60 min), and is entirely performed in a 96-well microplate. Assay measurements were obtained in a variety of commercial control and deficient plasmas representing clinically relevant hypo- and hyperfibrinolytic states, and in three distinct adolescent cohorts with acute or convalescent illness: critically ill, following endotracheal intubation; acute COVID-19-related illness; and ambulatory, 3 months following a venous thromboembolic event.
In 100% and 75% deficient plasmas, hypofibrinolysis for plasminogen-deficient, fibrinolysis for alpha-2-antiplasmin-deficient, and hyperfibrinolysis for plasminogen activator inhibitor-1-deficient plasmas were observed.
The modified mini-ECLA Clot Lysis Time Ratio (“CLTR”) demonstrated moderate-strength correlations with the Clot Formation and Lysis (CloFAL) assay, is analytically sensitive to altered fibrinolytic states in vitro, and correlates with clinical outcomes in preliminarily-studied patient populations.
G20210A (c.*97G>A) prothrombin gene variant, found in white population has been associated with an increased risk of venous thromboembolism (VTE). Other rare polymorphisms in F2 gene (C20209T) have been reported, more rare and touching black people, but its potential association with VTE remain uncertain.
About a 69 years-old Caucasian woman presenting an unprovoked deep venous thrombosis of the leg, we analyzed retrospectively 25.000 thrombophilia tests on a 11-year period of time (2007–2018), at Nice and Marseille University Hospitals, and performed extensive review of the literature.
Genetic determination included a similar PCR protocol and sequencing. Twenty-one heterozygous cases out of 25.585 determinations (0.08%) was found. The C20209T mutation detected in our Caucasian patient is rare, with a frequency that differed from what was reported in the previous literature, mainly in non-Caucasian patients (Africans, Africans-Americans, and Caribbeans). One hundred and thirteen patients with this mutation have been described in the literature, of which only one homozygous.
This study is the most important on C20209T mutation performed at present, allowing to precise its frequency and its potential role in venous thromboembolism.
Reticulocyte count and novel derived parameters provide insight into the effectiveness of erythropoiesis and may be useful tools in the classification and diagnosis of anemias. However, there is no standardisation, so we consider it necessary that each laboratory evaluates the parameters according to its own methodology and instrumentation and establishes its own reference ranges. Our aim was to establish the reference intervals (RIs) of reticulocyte profile provided by the Beckman Coulter DxH 900 haematological autoanalyzer in our reference population.
One hundred and seventy-five healthy adults (18 to 62 years) were included. Subjects were collected from the blood donation centre of the Hospital Clínico San Carlos (Madrid, Spain) upon informed consent. Whole blood was collected and assayed for 14 haematological parameters on the Beckman Coulter DxH 900 analyzer in the haematology laboratory of the Clinical Analysis Department. RIs were established as per Clinical and Laboratory Standards Institute EP28-A3c guidelines using three different statistical approaches.
RIs estimated using the non-parametric method and the Harrell-Davis bootstrap method were very similar. RIs estimated by the robust method were narrower. Gender partitioning was required for two haematological parameters (low haemoglobin density (LHD) and microcytic anaemia factor (MAF)). The rest of the parameters did not need to be partitioned according to Lahti's method.
RIs have been established for 14 hematologic parameters of the reticulocyte profile for the Beckman Coulter DxH 900 haematology analyzer using a healthy cohort of adult subjects.
Bone marrow necrosis (BMN) is a clinically and pathologically poorly-defined and readily-overlooked entity. The current facts and guidelines pertaining to this entity are scarce, and there exist controversies. Upon reviewing the literature, we present the facts, analyze these controversies, and discourse on future prospects.
Haematological parameters have been used for a long time for clinical evaluations, however the dynamics of these parameters has not been studied at length, in healthy populations. We aim to understand the dependence of haematological parameters on human physiotypes.
Using an age and gender restricted healthy human (male) population (n = 100), we attempt to analyse the dynamics of haemoglobin and red blood cells, with reference to age, height and weight of individuals. Using advanced generalised additive modelling and classical hierarchical structural analysis we aim to establish relationships between these parameters and human physiotypes.
We demonstrate that definitive relationships can be established for number of red blood cells, haemoglobin levels, RDW-CV, RDW-SD and weight, height and age of individuals.
This study provides a proof of principle, that haematological parameters are dependent on physiotypic variation, within the normal ranges in a healthy population. It may also be noted that there is a definitive influence of height, weight and age on normal ranges and stratification by these factors might therefore make reference intervals narrower, in turn, possibly allowing more precise clinical decisions based on the complete blood count (CBC).
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