Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants?

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes.

Lactate dehydrogenase and hemolysis index to predict vaso-occlusive crisis in sickle cell disease.

Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder associated with chronic hemolysis. A major complication is vaso-occlusive crisis (VOC), associating frequent hospitalization, morbidity and mortality. The aim of this study was to investigate whether hemolysis biomarkers were able to predict VOC risk in adult patients with SCD requiring hospitalization within 1 year. This single-center prospective study included adult patients with SCD at steady state or during VOC. A total of 182 patients with SCD were included, 151 at steady state and 31 during VOC. Among the 151 patients at steady state 41 experienced VOC within 1 year (median: 3.0 months [2.0-6.5]). We observed an increase of lactate dehydrogenase (LDH) (p = 0.01) and hemolysis index (HI) (p = 0.0043) during VOC compared to steady state. Regarding patients with VOC requiring hospitalization, LDH (p = 0.0073) and HI (p = 0.04) were increased. In unadjusted logistic regression, LDH > median (> 260 U/L) (RR = 3.6 [1.29-10.88], p = 0.0098) and HI > median (> 8 UA/L) (RR = 3.13 [1.91-5.33]; p < 0.001) were associated with VOC. The association of LDH > 260 U/L and HI > 12 UA/L presented a sensitivity of 90%, and a specificity of 72.9% to predict VOC. The association of LDH and HI cut-off was able to predict VOC risk in SCD.

Endothelial Progenitor Cells in Autoimmune Disorders.

Circulating endothelial progenitor cells (EPCs) were first described in 1997 by Asahara et al. as "putative endothelial cells" from human peripheral blood. The study of endothelial progenitors is also intensifying in several pathologies associated with endothelial damage, including diabetes, myocardial infarction, sepsis, pulmonary arterial hypertension, obstructive bronchopneumopathy and transplantation. EPCs have been studied in several autoimmune diseases with endothelial involvement such as systemic lupus erythematosus, thrombotic thrombocytopenic purpura, antineutrophil cytoplasmic antibodies, vasculitis, rheumatoid arthritis, Goujerot-Sjögren and antiphospholipid syndrome. Factors involved in endothelial damage are due to overexpression of pro-inflammatory cytokines and/or autoantibodies. Management of these pathologies, particularly the long-term use of glucocorticoids and methotrexate, promote atherosclerosis. A lack of standardized assessment of the number and function of EPCs represents a serious challenge for the use of EPCs as prognostic markers of cardiovascular diseases (CVD). The objective of this review was to describe EPCs, their properties and their involvement in several autoimmune diseases.

Stability over time of immature platelet fraction and comparison between EDTA and citrated whole blood samples.

BACKGROUND: Immature platelets (IP) are the youngest circulating platelets, released from megakaryocytes, and demonstrating increased dimensions, significant RNA content, and enhanced activity. Immature platelet research focuses on a differential diagnostic help in patients with thrombocytopenia. The objectives of this study were to compare the variability of IP in citrate and EDTA samples, and to determine stability over time. METHODS: Fifty-six patients were included for comparison between EDTA and citrate whole blood sample collection. Among the patients, 28 had thrombocytopenia (platelet count < 150G/L). Platelet measurement impedancemetry and fluorimetry were performed with Sysmex XN-9000. The immature platelet fraction (IPF) and absolute immature platelet count (A-IPC) were determined with a fluorescent method. RESULTS: The mean value of platelet count with fluorescence was, in EDTA sample, 215 ± 171 and, in citrate sample, 153 ± 118 G/L. No significant difference was observed between IPF between EDTA and citrate (7.74 ± 6.68% vs. 8.45 ± 7.37%, p = 0.69), respectively. With the Bland-Altman analysis, the mean difference in the EDTA sample, between 1 and 24 h, was 8.06 ± 6.96% and 8.73 ± 7.12% for IPF, whereas in the citrate sample, between 1 and 6 h, it was 8.60 ± 7.29% and 7.54 ± 6.97%, for IPF. Comparing 1 h EDTA sample with 6 h citrate sample, the variance ratio was 0.974 (95% CI: 0.864-1.084) in IPF. CONCLUSIONS: We confirmed the potential to conduct IP measurements up to 24 h in the EDTA sample and IPF measurements in the citrate sample for up to 6 h. These results may be useful for the use of IPF, which is a promising parameter whose interest in clinical practice and standardization is not yet well defined.

[Evaluation of a diagnostic test for heparin-induced thrombocytopenia: validation of a delayed test time]. / Évaluation d'un test d'orientation diagnostique de thrombopénie induite à l'héparine : validation d'un délai différé de réalisation du test.

Heparin-induced thrombocytopenia (HIT) is a rare, iatrogenic condition, characterized by its potential severity and diagnostic difficulties. The diagnosis is based on a set of arguments allowing the calculation of a pre-test score pointing to HIT. There are rapid diagnostic tests for suspected HIT. Among these, the STic Expert® HIT has a good sensitivity to detect HIT. However, it must be performed within 2 hours after sampling. The aim of this study was to evaluate a delayed STic Expert® HIT test at 8 hours and in frozen plasma. Thirty-six patients were prospectively included for HIT testing between April 01, 2018, and July 1, 2022, at the University Rouen Hospital. For any request for HIT testing, an analysis by STic Expert® HIT was performed within 2 hours and 8 hours post-sampling. Any positive result was confirmed by a functional test, platelet aggregation with heparin, release of 14C-serotonin assay (SRA), and immunological assay by a research for anti-platelet factor 4 IgG antibodies. Twenty-three patients had a STic Expert® HIT. Sixteen presented platelet aggregations in the presence of heparin and had a positive anti-PF4 test, 17 had a positive SRA. Six patients had no HIT. For the test performed within 2 hours of collection, the Se = 100%, Sp = 68.42%, PPV = 73.91%, and NPV = 100%. The X2 = 18.21 with p < 0.001. For the test performed at 8 hours post sampling, the Se = 100%, Sp = 68.42%, PPV = 73.91% and NPV = 100%. The X2 = 18.21 with p < 0.001. In conclusion, we have demonstrated that the STic Expert® can be used to perform an HIT diagnostic test 8 hours after sampling and on thawed plasma. However, this study needs to be confirmed on a larger number of samples.

C-reactive protein and D-dimer in cerebral vein thrombosis: Relation to clinical and imaging characteristics as well as outcomes in a French cohort study.

Introduction: Cerebral venous sinus thrombosis (CVST) is a rare disease with highly variable clinical presentation and outcomes. Clinical studies suggest a role of inflammation and coagulation in CVST outcomes. The aim of this study was to investigate the association of inflammation and hypercoagulability biomarkers with CVST clinical manifestations and prognosis. Methods: This prospective multicenter study was conducted from July 2011 to September 2016. Consecutive patients referred to 21 French stroke units and who had a diagnosis of symptomatic CVST were included. High-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), D-dimer, and thrombin generation using calibrated automated thrombogram system were measured at different time points until 1 month after anticoagulant therapy discontinuation. Results: Two hundred thirty-one patients were included. Eight patients died, of whom 5 during hospitalization. The day 0 hs-CRP levels, NLR, and D-dimer were higher in patients with initial consciousness disturbance than in those without (hs-CRP: 10.2 mg/L [3.6-25.5] vs 23.7 mg/L [4.8-60.0], respectively; NLR: 3.51 [2.15-5.88] vs 4.78 [3.10-9.59], respectively; D-dimer: 950 µg/L [520-2075] vs 1220 µg/L [950-2445], respectively). Patients with ischemic parenchymal lesions (n = 31) had a higher endogenous thrombin potential5pM than those with hemorrhagic parenchymal lesions (n = 31): 2025 nM min (1646-2441) vs 1629 nM min (1371-2090), respectively (P = .0082). Using unadjusted logistic regression with values >75th percentile, day 0 hs-CRP levels of >29.7 mg/L (odds ratio, 10.76 [1.55-140.4]; P = .037) and day 5 D-dimer levels of >1060 mg/L (odds ratio, 14.63 [2.28-179.9]; P = .010) were associated with death occurrence. Conclusion: Two widely available biomarkers measured upon admission, especially hs-CRP, could help predict bad prognosis in CVST in addition to patient characteristics. These results need to be validated in other cohorts.

Point-of-Care Viscoelastic Hemostatic Assays in Cardiac Surgery Patients: Comparison of Thromboelastography 6S, Thromboelastometry Sigma, and Quantra.

OBJECTIVES: Viscoelastic tests allow a reduction in blood product transfusion. Three modern devices are currently available (rotational thromboelastometry [ROTEM] sigma, thromboelastography [TEG] 6S, and Quantra). No study has compared the performances of these 3 devices simultaneously. DESIGN: An observational, nonrandomized cohort study. SETTING: A single-center of cardiac surgery in a university hospital. PARTICIPANTS: A total of 30 consecutive measurements from at least 10 adult patients presenting significant bleeding in the intensive care unit after cardiac surgery INTERVENTION: Viscoelastic tests using ROTEM sigma, TEG 6S, and Quantra were performed concomitantly with conventional coagulation measurements MEASUREMENTS AND MAIN RESULTS: The authors included 16 patients with 31 blood samples. After the exclusion of missing values, 27 samples were analyzed. Correlation with platelet count was as follows: ROTEM, r = 0.84 [0.66-0.93], p < 0.0001; Quantra, r = 0.83 [0.64-0.92], p < 0.0001; TEG 6S, r = 0.64 [0.29-0.83], p = 0.001. Correlation with fibrinogen (Clauss assay) was as follows: ROTEM, r = 0.85 [0.68-0.93], p < 0.0001; Quantra, r = 0.88 [0.74-0.95], p < 0.0001; TEG 6S, r = 0.79 [0.55-0.91], p < 0.0001. No difference was observed for the detection of residual circulating heparin (anti-Xa activity >0.1), with 87% of correct identification for Quantra and 80% for both ROTEM and TEG 6S (p = 0.3). Time to first results after the beginning of the test was shorter for Quantra than ROTEM and TEG 6S (136 [126-152] seconds v 205 [176-221] seconds, p = 0.003 and v 450 [372-516] seconds, p < 0.0001 respectively). CONCLUSION: ROTEM sigma, TEG 6S, and Quantra performed similarly for exploring platelet count or residual circulating heparin. Thromboelastography 6S presented a weaker correlation with fibrinogen Clauss.

Anticoagulation Monitoring with Activated Partial ThromboPlastin Time and Anti-Xa Activity in Intensive Care Unit Patients: Interest of Thrombin Generation Assay.

Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between 0.3 and 0.7 U/mL. Correlation among aPTT, anti-Xa activity, and thrombin generation was determined by measuring endogenous thrombin potential (ETP), with the inflammatory response evaluated. C-reactive protein (CRP) was used as a marker of inflammatory response. The plasma of 107 samples from 30 ICU patients was analyzed. The correlation between aPTT and anti-Xa activity was 0.66, CI95% [0.54;0.76] (p < 0.0001). Although thrombin generation, aPTT, and anti-Xa were correlated with inflammatory responses, the correlation was higher with thrombin generation and anti-Xa activity compared to aPTT. When aPTT was in a therapeutic range, a low thrombin generation was observed but was 50% inhibited when anti-Xa was in a therapeutic range. Coagulation testing with aPTT, anti-Xa correlated with thrombin generation. A 50% decrease in thrombin generation was observed when anti-Xa was within a therapeutic range. Further work is needed to evaluate coagulation biomarker responses and clinical outcomes in specific ICU populations.

Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease.

Introduction: Sickle cell disease (SCD) is an inherited hemoglobinopathy disorder. The main consequence is synthesis of hemoglobin S leading to chronic hemolysis associated with morbidity. The aim of this study was to investigate Thrombin Generation Assay (TGA) to assess hypercoagulability in SCD and TGA parameters as biomarkers of vaso-occlusive crisis (VOC) risk and hospitalization within 1 year. Materials and methods: We performed TGA in platelet poor plasma (PPP) with 1 pM of tissue factor and 4 µM of phospholipid-standardized concentration, in duplicate for patients and controls. We measured thrombomodulin (TM), soluble endothelial Protein C Receptor and Tissue Factor Pathway Inhibitor (TFPI). Results: A total of 113 adult patients with SCD, 83 at steady state and 30 during VOC, and 25 healthy controls matched on age and gender were included. Among the 83 patients at steady state, (36 S/S-1 S/ß0, 20 S/Sα3.7, and 19 S/C-7 S/ß+) 28 developed a VOC within 1 year (median: 4 months [2.25-6]). We observed an increase of peak and velocity associated with a shortening of lagtime and time to peak (TTP) and no difference of endogenous thrombin potential (ETP) in patients compared to controls. TFPI (p < 0.001) and TM (p = 0.006) were significantly decreased. TGA confirmed hypercoagulability in all SCD genotypes and clinical status. The association of ETP > 1,207 nM.min and peak >228.5 nM presented a sensitivity of 73.5% and a specificity of 93.9% to predict VOC development within 1 year. Conclusion: We have demonstrated a hypercoagulable state in SCD associated with chronic hemolysis. These preliminary findings suggest that TGA parameters, as ETP and peak, could be used to predict VOC development within 1 year.

Assessment of Reticulocyte and Erythrocyte Parameters From Automated Blood Counts in Vaso-Occlusive Crisis on Sickle Cell Disease.

Sickle cell disease is a complex genetic disease involving cell adhesion between red blood cells, white blood cells, platelets and endothelial cells, inducing painful vaso-occlusive crisis (VOC). We assessed reticulocyte and erythrocyte parameters in a cohort of confirmed SCD patients, and investigated whether a combination of these routine laboratory biomarkers of haemolysis could be used to predict VOC development. Reticulocyte and erythrocyte parameters were evaluated using the Sysmex XN-9000 analyser. A total of 98 patients with SCD were included, 72 in steady state and 26 in VOC. Among the 72 patients in steady state, 22 developed a VOC in the following year (median: 3 months [2-6]). The following parameters were increased in SCD patients with VOC development compared to SCD patients without VOC development in the following year: reticulocyte count (94.6 109/L [67.8-128] vs. 48.4 109/L [24.9-87.5]), immature reticulocyte count (259 109/L [181-334] vs. 152 109/L [129-208]) reticulocyte/immature reticulocyte fraction (IRF) ratio (6.63 109/(L*%) [4.67-9.56] vs. 4.94 109/(L*%) [3.96-6.61]), and medium fluorescence reticulocytes (MFR) (19.9% [17.4-20.7] vs. 17.1% [15.95-19.75]). The association of a reticulocyte count of >189.4 109/L and an MFR of >19.75% showed a sensitivity of 81.8% and a specificity of 88% to predict VOC development in the following year. Based on our findings, a combination of routine laboratory biomarkers, as reticulocyte count, immature reticulocyte count and fluorescent reticulocyte fraction at steady state, could be used to predict VOC development in SCD.

Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study.

BACKGROUND: Thrombosis is frequent during COVID-19 disease, and thus, identifying predictive factors of hemostasis associated with a poor prognosis is of interest. The objective was to explore coagulation disorders as early predictors of worsening critical conditions in the intensive care unit (ICU) using routine and more advanced explorations. MATERIALS: Blood samples within 24 h of ICU admission for viscoelastic point-of-care testing, (VET), advanced laboratory tests: absolute immature platelet count (A-IPC), von Willebrand-GPIb activity (vWF-GpIb), prothrombin fragments 1 + 2 (F1 + 2), and the thrombin generation assay (TGA) were used. An association with worse outcomes was explored using univariable and multivariable analyses. Worsening was defined as death or the need for organ support. RESULTS: An amount of 85 patients with 33 in critical condition were included. A-IPC were lower in worsening patients (9.6 [6.4-12.5] vs. 12.3 [8.3-20.7], p = 0.02) while fibrinogen (6.9 [6.1-7.7] vs. 6.2 [5.4-6.9], p = 0.03), vWF-GpIb (286 [265-389] vs. 268 [216-326], p = 0.03) and F1 + 2 (226 [151-578] vs. 155 [129-248], p = 0.01) were higher. There was no difference observed for D-dimer, TGA or VET. SAPS-II and A-IPC were independently associated with worsening (OR = 1.11 [1.06-1.17] and OR = 0.47 [0.25-0.76] respectively). The association of a SAPS-II ≥ 33 and an A-IPC ≤ 12.6 G/L predicted the worsening of patients (sensitivity 58%, specificity 89%). CONCLUSIONS: Immature platelets are early predictors of worsening in severe COVID-19 patients, suggesting a key role of thrombopoiesis in the adaption of an organism to SARS-CoV-2 infection.

Gonadotropins as novel active partners in vascular diseases: Insight from angiogenic properties and thrombotic potential of endothelial colony-forming cells.

BACKGROUND: The impact of estrogen and testosterone on atherosclerotic cardiovascular disease is well known, but the role of the gonadotropins follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) to some extent remain less studied. OBJECTIVES: To explore the angiogenic potential of gonadotropins on endothelial colony-forming cells (ECFCs). METHODS: We examined the effects of various doses of gonadotropins on ECFCs obtained from cord blood by assessing colony number, proliferation, migration, and sprouting ability. Moreover, we studied thrombin generation in ECFCs exposed to gonadotropins by performing a thrombin generation assay. Finally, we determined the levels of circulating gonadotropins in 30 men, to exclude the effect of estrogen, with lower extremity arterial disease (LEAD), in comparison with age- and sex-matched controls. RESULTS: Exposure to FSH, LH, or PRL resulted in an increase in ECFC migration but showed no effect on proliferation or ECFC commitment from cord blood mononuclear cells. Using a three-dimensional fibrin gel assay, we showed that ECFC sprouting was significantly enhanced by gonadotropins. Exposure to FSH also increased the thrombin generation of ECFCs exposed to FSH. Finally, FSH and LH levels in men with LEAD were higher than those in controls. CONCLUSION: Gonadotropins increase ECFC-related angiogenesis and may be involved in thrombin generation in cardiovascular disease. Gonadotropins may act as biomarkers; moreover, we hypothesize that gonadotropin-blocking strategies may be a novel interesting therapeutic approach in atherosclerotic cardiovascular disease.

Factor XII deficiency evaluated by thrombin generation assay.

INTRODUCTION: Coagulation factor XII (FXII) plays a role in thrombin generation, fibrinolysis, inflammation, angiogenesis, chemotaxis and diapedesis. FXII deficiency is not associated with bleeding risk unlike other coagulation factors. MATERIALS/METHODS: We investigated thrombin generation assay (TGA) profile modification in FXII deficiency and the correlation with TGA and deficiency severity. TGA was performed in platelet poor plasma (PPP) with tissue factor (1 pmol/L) and phospholipid (4 µmol/L) standardized concentration. Thrombin generation profiles were compared in 54 patients with FXII deficiency, 25 healthy controls and 23 patients with hemophilia A (factor VIII (FVIII) deficiency. Patients with FXII deficiency were classified in three groups based on FXII activity (30-50%, 10-29%, <10%). FVIII deficiency was included as a bleeding control group. RESULTS: As expected, we found a correlation between FXII deficiency and activated partial thromboplastin time (aPTT). A decrease of thrombin generation was observed in healthy controls and all FXII deficiency groups. A decrease of endogenous thrombin potential (ETP), peak and velocity was observed in patients with FVIII deficiency compared to FXII deficiency. A decrease of thrombin generation was noted in patients with FXII deficiency and bleeding history compared to patients with FXII deficiency and thrombosis history. CONCLUSION: In this study, thrombin generation profiles were not sensitive to FXII deficiency. TGA could distinguish bleeding and thrombotic tendency in FXII deficiency. Our results should therefore be considered as exploratory and deserve confirmation.

Evaluation of thrombin generation assay in factor XI deficiency.

INTRODUCTION: Factor XI (FXI) deficiency is characterized by a lack of correlation between FXI plasma levels and the occurrence of hemorrhagic events. The main objective of our study was to determine whether thrombin generation assay (TGA) could be used to assess the hemorrhagic phenotype of patients with FXI deficiency. MATERIAL AND METHODS: All patients had confirmed laboratory measurement of FXI < 50% in two plasma samples. Relevant bleeding history was evaluated by a senior physician. TGA was performed with Calibrated Automated Thrombography, in platelet poor plasma, from patients and healthy controls. The assay was performed with PPP low reagent (1 pM of human tissue factor). RESULTS: Seventy-six patients with FXI deficiency were included between 2011 and 2020. Among them, eight patients had severe deficiency (FXI < 15%). Mean age was 34 years [range: 9-77]. Endogenous thrombin potential (ETP) was significantly lower in patients with FXI deficiency and bleeding (573 nM·min [225-1214]) or no bleeding (732 nM·min [222-1435]), compared to healthy controls (1184 nM·min [933-1518]). No difference was observed for ETP and peak between patients with FXI deficiency and bleeding and patients with FXI deficiency and no bleeding. No difference was observed for ETP (923 nM·min [377-1497] vs 1063 nM·min [252-2529]), peak (82 nM [28-154] vs 131 nM [20-330]) or velocity (13.7 nM/min [3.6-29.6] vs 26.5 nM/min [2.5-90]) in women with (n = 4) and without history (n = 17) of post-partum bleeding. No difference of thrombin generation was observed in pregnant women with FXI deficiency (ETP: 1395 nM·min [351-2529]; peak: 154 nM [26-330]; velocity: 29.6 nM/min [4.1-90.0]), compared to healthy controls and a control group of healthy pregnant women. CONCLUSION: In conclusion, under our experimental condition, a non-significant decrease of thrombin generation was observed in plasma samples of patients with FXI deficiency and bleeding. Our results suggest an increase of coagulation parameters during pregnancy in women with FXI deficiency. A larger sample size or other experimental conditions are required to evaluate the use of TGA in FXI deficiency.

Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study.

Antiphospholipid syndrome (APS) is associated with thrombotic events (tAPS) and/or obstetrical morbidity (oAPS), with persisting antiphospholipid antibodies (aPL). Despite an update of aPL in 2006, several patients had typical clinical events without the classical biological criteria. The aim of our study was to evaluate the hypercoagulability state with both thrombin generation (TG) profiles and activated protein C resistance (aPCR) in different types of APS. METHODS: We retrospectively included 41 patients with Sydney criteria classification (tAPS, oAPS) and no clinical manifestation of APS with persistent aPL (biological APS). A thrombin generation assay was performed with a Fluoroskan Ascent fluorometer in platelet-poor plasma (PPP). Activated protein C resistance was measured as a ratio: ETP+aPC/ETP-aPC × 100. RESULTS: Thrombotic APS and oAPS had an increase of global thrombin generation (ETPcontrol = 808 nM.min (756-853) vs. 1265 nM.min (956-1741) and 1863 nM.min (1434-2080), respectively) (Peakcontrol = 78 nM (74-86) vs. 153 nM (109-215) and 254 nM.min (232-289), respectively). Biological APS had only a lag time increase (Tcontrol = 4.89 ± 1.65 min vs. 13.6 ± 3.9 min). An increased aPCR was observed in tAPS (52.7 ± 16.4%), oAPS (64.1 ± 14.6%) as compared to the control group (27.2 ± 13.8%). CONCLUSION: Our data suggest an increase of thrombin generation in thrombotic and obstetrical APS and no hypercoagulable states in patients with biological APS. The study of a prospective and a larger controlled cohort could determine the TGA useful for APS monitoring and could confirm an aPCR evaluation in PPP.

Investigation of Coagulation Biomarkers to Assess Clinical Deterioration in SARS-CoV-2 Infection.

Since December 2019, a pandemic caused by a new coronavirus has spread to more than 170 countries around the world. Worsening infected patients requiring intensive care unit (ICU) admission associated with 30% of mortality. A part of worsening is induced by hemostasis deregulation. The aim of this study was to investigate the association of coagulation activation in COVID-19 progression. Thirty-five of the 99 patients got clinically worse. The final model of the logistic regression analysis revealed that O2 requirement (RR = 7.27 [1.50-19.31]), monocytes below 0.2G/L (RR = 2.88 [1.67-3.19]), fibrinogen levels (RR = 1.45 [1.17-1.82] per g/L increase), prothrombin fragments 1+2 higher than 290 pM (RR = 2.39 [1.20-3.30]), and thrombin peak (RR = 1.28 [1.03-1.59] per 50 nM increase) were associated with an increased risk of clinical worsening. A fibrinogen level threshold of 5.5 g/L, a thrombin peak measurement threshold of 99 pM, and O2 requirement associated with clinical outcome in more than 80% of our cohort. In conclusion, we identified fibrinogen and thrombin peak at admission as coagulation biomarkers associated with an increased risk of ICU admission or death. This finding allows initiating steroids and triage for worsening patients. Our results should therefore be considered as exploratory and deserve confirmation.