Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin.

BACKGROUND: The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels. OBJECTIVES: To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670). METHODS: We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization (n = 39); G2, cardiothoracic intensive care unit (ICU) after CPB (n = 35); G3, medical ICU (n = 53); G4, other medical inpatients (n = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model. RESULTS: We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs. 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran-patient group interaction (p < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups (p = 0.0302). CONCLUSION: The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated.

A French single-center experience on allogeneic stem cell transplant cryopreservation during severe acute respiratory syndrome coronavirus 2 pandemic.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for chemo-resistant hematological malignancies. Because of transport restriction imposed by the coronavirus disease 2019 pandemic, regulatory bodies and societies recommended graft cryopreservation before recipient conditioning. However, the freezing and thawing processes, including washing steps, might impair CD34+ cell recovery and viability, thereby impacting the recipient engraftment. Over 1 year (between March 2020 and May 2021), we aimed to analyze the results of frozen/thawed peripheral blood stem cell allografts in terms of stem cell quality and clinical outcomes. METHODS: Transplant quality was evaluated by comparing total nucleated cells (TNCs), CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM)/kg numbers as well as TNC and CD34+ cell viabilities before and after thawing. Intrinsic biological parameters such as granulocyte, platelet and CD34+ cell concentrations were analyzed, as they might be responsible for a quality loss. The impact of the CD34+ cell richness of the graft on TNC and CD34 yields was evaluated by designing three groups of transplants based on their CD34 /kg value at collection: >8 × 10 6/kg, between 6 and 8 × 106/kg and <6 × 106/kg. The consequences of cryopreservation were compared in the fresh and thawed group by evaluating the main transplant outcomes. RESULTS: Over 1 year, 76 recipients were included in the study; 57 patients received a thawed and 19 patients a fresh allo-SCT. None received allo-SCT from a severe acute respiratory syndrome coronavirus 2-positive donor. The freezing of 57 transplants led to the storage of 309 bags, for a mean storage time (between freezing and thawing) of 14 days. For the fresh transplant group, only 41 bags were stored for potential future donor lymphocyte infusions. Regarding the graft characteristics at collection, median number of cryopreserved TNC and CD34+ cells/kg were greater than those for fresh infusions. After thawing, median yields were 74.0%, 69.0% and 48.0% for TNC, CD34+ cells and CFU-GM, respectively. The median TNC dose/kg obtained after thawing was 5.8 × 108, with a median viability of 76%. The median CD34+ cells/kg was 5 × 106, with a median viability of 87%. In the fresh transplant group, the median TNC/kg was 5.9 × 108/kg, and the median CD34+ cells/kg and CFU-GM/kg were 6 × 106/kg and 276.5 × 104/kg, respectively. Sixty-one percent of the thawed transplants were out of specifications regarding the CD34+ cells/ kg requested cell dose (6 × 106/kg) and 85% of them would have had this dose if their hematopoietic stem cell transplant had been infused fresh. Regarding fresh grafts, 15.8% contained less than 6 × 106 CD34+ cells /kg and came from peripheral blood stem cells that did not reach 6 × 106 CD34+ cells /kg at collection. Regarding the factor that impaired CD34 and TNC yield after thawing, no significant impact of the granulocyte count, the platelet count or the CD34+ cells concentration/µL was observed. However, grafts containing more than 8 × 10 6/kg at collection showed a significantly lower TNC and CD34 yield. CONCLUSIONS: Transplant outcomes (engraftment, graft-versus-host disease, infections, relapse or death) were not significantly different between the two groups.

[Antiphospholipid syndrome in nephrology. Kidney damage and practical aspects of the management]. / Le syndrome des antiphospholipides en néphrologie. Atteinte rénale et aspects pratiques de la prise en charge.

The antiphospholipid syndrome is a thrombophilia characterized by the combination of arterial and/or venous thrombotic events or obstetric clinical events, associated with persistent presence of antiphospholipid antibodies. In this syndrome, thromboses may affect all of the vascular tree, renal damage is frequently associated with a specific antiphospholipid syndrome nephropathy. We propose in this review to provide updated recommendations on the management of antiphospholipid syndrome in nephrology. Treatment is based on long-term anticoagulant therapy with or without antiplatelet agents according to clinical events. The use of a conventional nephroprotection must not be forgotten (strict control of blood pressure with drugs blocking the renin-angiotensin-aldosterone system). Catastrophic antiphospholipid syndrome is an extremely severe complication which can threaten the vital prognosis of the patient. This justifies particular surveillance, as well as prevention in high-risk situations. We also illustrate the difficulties of long-term management in these patients, both in dialysis or kidney transplantation.