Interest in the new thromboelastometry device, Clot Pro®, for predicting thrombocytopenia and hypofibrinogenemia during lung transplantation.

INTRODUCTION: Lung transplantation is associated with high proportion of transfusion. Monitoring of coagulopathy using viscoelastic tests could aid in the perioperative management of bleeding. The aim of the study was to assess the predictive cut-off values for thrombocytopenia and hypofibrinogenemia using the new thromboelastography analyzer, ClotPro. METHODS: We retrospectively enrolled 65 patients who underwent lung transplantation and were sampled for both viscoelastic assays and conventional coagulation assays simultaneously during the procedure. We characterized the correlation between the EX-test (extrinsic pathway) and platelet count as well as between the FIB-test (extrinsic pathway after platelet inhibition) and fibrinogen concentration. Then, we used ROC curve analysis to determine the optimal EX-test and FIB-test values for predicting thrombocytopenia and hypofibrinogenemia. RESULTS: All the amplitude values of the EX-test (A5, A10, A20, MCF) showed correlation with platelets count (Spearman's rank correlation coefficient ranging from 0.75 to 0.77, all p < 0.0001). We also observed a strong correlation between the amplitude values of the FIB-test (A5, A10, A20 and MCF) and the fibrinogen concentration (Spearman's rank correlation coefficient ranging from 0.68 to 0.71, all p < 0.0001). The AUCs of the EX-test values for thrombocytopenia <100 G/L and <80 G/L ranged from 0.80 to 0.93. Similarly, the AUCs of the FIB-test values for hypofibrinogenemia <1.5 g/L and <2 g/L ranged from 0.74 to 0.83. These results indicate that only the five-minute parameter of thromboelastometry is sufficient for detecting thrombocytopenia and hypofibrinogenemia in patients undergoing lung transplantation. The proposed cut off values for the EX-test to predict thrombocytopenia <80 G/L showed high sensitivity (>86 %), high specificity (>89 %) and high negative predictive value (>95 %). FIB-test cut off values predictive of fibrinogen below 1.5 g/L showed sensitivity (>78 %), specificity (>55 %) and negative predictive value (>88 %). CONCLUSIONS: Our study provided preliminary results that are useful for developing a ClotPro-based algorithm to guide transfusion in lung transplantation. Future interventional studies will be necessary to validate these cut-off values of ClotPro for guiding transfusion.

Comparison of two SARS-CoV-2 RT-PCR assays and implication of the instrument software on cycle threshold (Ct) value

The Cycle Threshold (Ct) value of SARS-CoV-2 RT-PCR are used as an indicator of viral load. Using a collection of 45 fresh nasopharyngeal samples collected on universal transport media, we compare the Ct value obtained with 2 RT-PCR assays, the Alinity M SARS-CoV-2 and the Alinity M RESP-4-Plex (Abbott Molecular, Des Plaines, Illinois, Etats-Unis) processed on an Alinity M device. The assays are highly correlated; however, the Ct values were in median lower of 4.54 with the Alinity M RESP-4-Plex. This difference could be attributed to earlier detection of positivity by the software of the Alinity M rather than a difference in RT-PCR performances. The Ct-value of SARS-CoV-2 RT-PCR should be interpreted with caution taking into account the clinical context, pre-analytical and analytical findings.

La valeur du cycle seuil (Ct) des RT-PCR positives pour le SARS-CoV-2 est utilisée pour évaluer si un patient est contagieux. Lors d'un changement de réactif, nous avons comparé les résultats de Ct obtenus pour 45 prélèvements positifs pour le SARS-CoV-2 avec 2 kits de réactifs : Alinity M SARS-CoV-2 et Alinity M RESP-4-Plex (Abbott Molecular, Des Plaines, Illinois, États-Unis) utilisée avec l'automate Alinity M. Les deux méthodes était corrélées mais les Ct étaient en médiane plus bas de 4,54 avec le réactif Alinity M RESP-4-Plex en comparaison du réactif Alinity M SARS-CoV-2. Cette différence semble liée à une détection plus précoce de la positivité par le logiciel de l'Alinity M qu'à une différence de performances. Nous alertons sur le fait que les valeurs de Ct doivent être interprétées avec prudence en prenant en compte le contexte clinique, les limites pré-analytiques et analytiques.

The Panbio COVID-19 Ag Rapid Test: Which Performances are for COVID-19 Diagnosis?

BACKGROUND: Rapid antigen detection assays are promising tools for the diagnosis of COVID-19. We assess the performances of the Panbio COVID-19 Ag Rapid Test. METHODS: The Panbio COVID-19 Ag Rapid test was compared to a reference RT-PCR performed on the same nasopharyngeal swab (NPS). Overall, 81 NPS were tested retrospectively and 330 healthcare workers (HCWs) were tested prospectively. RESULTS: Retrospective analyze. Of the 48 SARS-CoV-2 positive NPS, 19 (39.6%) were found positive with the Panbio COVID-19. There was no cross-reactivity with SARS-CoV-2 negative NPS. The Kappa value was 0.459. Prospective analyze. The prevalence of COVID-19 was 26.1% in symptomatic HCWs. The overall sensitivity and specificity of the Panbio COVID-19 were 47.2% and 100.0% respectively. The sensitivity was 55.2% and 14.3% in those tested within and after 4 days of diseases respectively. CONCLUSIONS: The Panbio COVID-19 Ag Rapid test displays low performance for the identification of SARS-CoV-2 infected patients.

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines.

BACKGROUND: There is a small amount of immunological data on COVID-19 heterologous vaccination schedules in humans. We assessed the immunogenicity of BNT162b2 (Pfizer/BioNTech) administered as a second dose in healthcare workers primed with ChAdOx1-S (Vaxzevria, AstraZeneca). METHODS: 197 healthcare workers were included in a monocentric observational study in Foch hospital, France, between June and July 2021. The main outcome was the immunogenicity measured by serum SARS-CoV-2 IgG antibodies. RESULTS: 130 participants received the ChAdOx1-S/BNT vaccine and 67 received the BNT/BNT vaccine. The geometric mean of IgG antibodies was significantly higher in the BNT/BNT vaccine group compared to the ChAdOx1-S/BNT vaccine group, namely 10,734.9, 95% CI (9141.1-12,589.3) vs. 7268.6, 95% CI (6501.3-8128.3), respectively (p < 0.001). However, after adjustment for time duration between the prime and second vaccinations, no significant difference was observed (p = 0.181). A negative correlation between antibody levels and time duration between second dose and serology test was observed for the BNT/BNT vaccine (p < 0.001), which remained significant after adjustment for all covariates (p < 0.001), but not for the ChAdOx1-S/BNT vaccine (p = 0.467). CONCLUSIONS: Heterologous and homologous schedules of ChAdOx1-S and BNT vaccines present robust immune responses after the second vaccination. The results observed were equivalent after adjustment for covariates and emphasize the importance of flexibility in deploying mRNA and viral vectored vaccines. Nevertheless, applying the ChAdOx1-S schedule vaccination for the heterologous second dose of BNT was associated with decreased IgG antibody levels compared to the homologous BNT/BNT vaccination.

SARS-CoV-2 screening of asymptomatic health care workers: experience of a General hospital.

Health care workers (HCWs) are at major risk to be infected by SARS-CoV-2 and transmit the virus to the patients. Furthermore, travels are a major factor in the diffusion of the virus. We report our experience regarding the screening of asymptomatic HCWs returning from holidays, following the issue of a national guideline on 08/20/2020. The organization of the occupational health department and the clinical laboratory was adapted in order to start the screening on August, 24, 2020. All HCWs tested for SARS-CoV-2 the week before and 4 weeks after the implementation of the screening were included. The mean number of tests was analyzed per working day and working week. Overall, 502 (31.4%) HCWs were tested for SARS-CoV-2 during the study period. The mean number of HCWs tested per working day was 27.1. HCWs accounted for 36.9% (n = 167) and 11.2% (n = 84) of the tests performed in the 1st and the 4th week following the implementation of the guidelines. The number of tests performed each week in HCWs increased by at least 20-fold after the implementation of the guidelines. No asymptomatic HCW was tested positive. Screening of asymptomatic HCWs was poorly effective in the context of low circulation of the virus. We suggest giving priority to infection prevention and control measures and screening of symptomatic subjects and asymptomatic contacts.

Pain assessment and factors influencing pain during bone marrow aspiration: A prospective study.

Although bone marrow aspiration (BMA) is still considered a painful procedure, pain level remains poorly documented. We therefore conducted a prospective study intended to evaluate pain level in adult patients undergoing BMA at the sternal or iliac crest site to identify factors associated with pain. We enrolled a total of 448 patients who underwent 461 BMA and asked those patients to score their pain intensity after BMA using numerical pain rating scale (NPRS). The following factors: level of anxiety, quality of the information given to the patient, operator's experience, and bone texture were recorded using a standardized questionnaire. The median NPRS score was 3.5 (IQR [2.0; 5.0]) the sternal site (n = 405) was associated with an increased median NPRS score (3.5 [2.0; 5.0]) compared to the iliac crest (n = 56, 2.5 [1.0; 4.0]; p<0.0001). For those patients who underwent sternal BMA, the median NPRS score was significantly lower when using lidocaine infiltration (p = 0.0159) as compared with no anesthetic use. Additionally there was no significant effect of anesthetic cream found. After multivariate analysis, the model of NPRS score at the sternal site included patient anxiety (p<0.0001) and the use of lidocaine infiltration (0.0378). This study underlines the usefulness of a comprehensive management including pain relief and efforts to reduce anxiety including appropriate information given to the patient during BMA.

Vitamin K antagonism impairs the bone marrow microenvironment and hematopoiesis.

Vitamin K antagonists (VKAs) have been used in 1% of the world's population for prophylaxis or treatment of thromboembolic events for 64 years. Impairment of osteoblast function and osteoporosis has been described in patients receiving VKAs. Given the involvement of cells of the bone marrow microenvironment (BMM), such as mesenchymal stem cells (MSCs) and macrophages, as well as other factors such as the extracellular matrix for the maintenance of normal hematopoietic stem cells (HSCs), we investigated a possible effect of VKAs on hematopoiesis via the BMM. Using various transplantation and in vitro assays, we show here that VKAs alter parameters of bone physiology and reduce functional HSCs 8-fold. We implicate impairment of the functional, secreted, vitamin K-dependent, γ-carboxylated form of periostin by macrophages and, to a lesser extent, MSCs of the BMM and integrin ß3-AKT signaling in HSCs as at least partly causative of this effect, with VKAs not being directly toxic to HSCs. In patients, VKA use associates with modestly reduced leukocyte and monocyte counts, albeit within the normal reference range. VKAs decrease human HSC engraftment in immunosuppressed mice. Following published examples that alteration of the BMM can lead to hematological malignancies in mice, we describe, without providing a causal link, that the odds of VKA use are higher in patients with vs without a diagnosis of myelodysplastic syndrome (MDS). These results demonstrate that VKA treatment impairs HSC function via impairment of the BMM and the periostin/integrin ß3 axis, possibly associating with increased MDS risk.