Summary
Introduction
The Belgian national External Quality Assessment Scheme performed a survey to assess the effect of the direct oral anticoagulant apixaban on the coagulation assays prothrombin ...time (PT), activated partial thromboplastin time (aPTT), fibrinogen and antithrombin as performed with a large number of reagent/instrument combinations.
Methods
Four lyophilized plasma samples spiked with apixaban (0, 41, 94 and 225 ng/mL) were sent to the 195 Belgian and Luxembourg clinical laboratories performing coagulation testing.
Results
PT and aPTT were barely influenced at the concentrations tested. At 225 ng/mL apixaban, PT and aPTT clotting times were only 1.15 times longer than at 0 ng/mL. Among PT reagents, RecombiPlasTin 2G® showed a slightly higher sensitivity with 225 ng/mL apixaban prolonging the PT clotting time 1.3‐fold. Among aPTT reagents, there was no appreciable difference in sensitivity.
Fibrinogen results were unaffected by the presence of apixaban, but antithrombin activity was considerably overestimated when measured with a FXa‐based assay. At 225 ng/mL apixaban, the median percentage increase in antithrombin level was 31% when measured with the Liquid Antithrombin® reagent and 44% with the Innovance Antithrombin® reagent.
Conclusion
Our data provide clinical laboratories with useful information on the impact of apixaban on their routine coagulation assays.
IntroductionHepatosplenic gamma/delta T-cell Lymphoma (HSTL) is a systemic extra-nodal lymphoma originating from cytotoxic T-cells expressing the gd receptor. We report clinical, morphologic and ...phenotypic characteristics of 3 patients with HSTL.Material and methodsAll patients were male and presented at a mean age of 23 years. One was treated with azathioprine for inflammatory bowel disease, the two others had no history of immunosuppression. All patients were admitted to the hospital with high fever and hepatosplenomegaly. Two presented severe abdominal pain and lymphadenopathy.Laboratory studies of the three patients were different:Case 1: thrombopenia and bone marrow infiltration with 69% of large lymphomatous blast cells and minimal peripheral blood infiltration.Case 2: pancytopenia without excess of blasts in the peripheral blood and moderate bone marrow infiltration in cytometry. Morphological and immune-phenotypical studies of the spleen (after splenectomy) showed a massive infiltration by lymphocytic small cells.Case 3: pancytopenia with 25% and 45% of blast cells in the peripheral blood and bone marrow aspirate respectively.Immuno-phenotyping showed a T lymphocytic population double negative (CD3pos CD4neg CD8neg to dim) with gamma-delta expression, CD1a- CD2 +CD5 CD7+CD56+CD57 in all 3 patients.Two patients underwent an initial treatment with Cyclophosphamide, Doxorubicin, Vincristine and Prednisone: the first died after 4 months, and there is no response to treatment in the second patient. Treatment was recently initiated in the third patient.Results and discussionsIn our series, HSTL confirmed a predilection to develop most often in young men with hepatosplenomegaly. Variable degrees of hematologic abnormalities were observed. Thrombocytopenia was the most striking finding in all. Bone marrow involvement is described in approximately two thirds of patients but was observed by immunophenotyping in our 3 cases. We show that immunophenotyping seems to be the best method for the rapid characterisation of the lymphoma cells morphologically heterogeneous and difficult to identify.ConclusionHSTL is an infrequent, rare aggressive tumour. The diagnosis is difficult. There is no treatment consensus and the prognosis remains poor.
Normal bone remodeling and pathological bone destruction have been considered to be osteoclast‐driven. Osteoclasts are able to attach to bare bone surface and produce an acidic subcellular space. ...This leads to acid dissolution of hydroxyapatite, allowing cathepsin K to degrade the organic type I collagen‐rich osteoid matrix under the acidic condition prevailing in Howship lacunae. Using a sting pH electrode, the interface membrane around a loosened total hip replacement prosthesis was found to be acidic. Confocal laser scanning disclosed irregular demineralization of the bone surface in contact with the acidic interface. Cathepsin K, an acidic collagenolytic enzyme, was found in interface tissue macrophages/giant cells and pseudosynovial fluid. Tissue extracts contained high levels of cathepsin K messenger RNA (mRNA) and protein. These observations suggest the presence of an acid‐ and cathepsin K‐driven pathological mechanism of bone resorption, mediated not by osteoclasts in subosteoclastic space, but rather by the uncontrolled activity of macrophages in extracellular space.
Abstract Vascular calcifications (VCs) are important predictors of cardiovascular mortality in patients with chronic kidney disease (CKD). We have shown previously that osteoprotegerin (OPG), a ...potential early biomarker for VC, was an independent predictor of mortality in CKD patients. The aim of our study was to follow longitudinally coronary and aortic VCs. VCs were measured using Siemens 16 detector CT in a group of predialysis and hemodialyzed patients before and after a follow-up of 4 years. Some of these patients were transplanted in the meantime. Renal function, calcium, phosphate, iPTH, hs-CRP (high sensitive protein C reactive), and OPG serum levels were also compared. VCs progressed in predialysis, hemodialyzed, and transplanted patients but the progression was not the same in all arterial beds. A progression of coronary calcifications was observed in predialysis and transplanted patients, while aortic calcifications worsened significantly only in hemodialyzed patients. OPG serum levels and hs-CRP were significantly lower among transplanted patients. We concluded that VC depends on the severity of the kidney disease. Transplanted patients are not protected from VC, yet their OPG serum levels were significantly lower, suggesting that there is no link between between OPG levels and severity of VC. Longer follow-up of these patients would be necessary to assess whether a decline in OPG correlates with better survival.
Background: Detection of anticardiolipin antibodies (ACA) is an independent laboratory criterion for diagnosis of antiphospholipid syndrome (APS). Alternative methods to ELISA were recently developed ...such as automated chemiluminescence immunoassay (CLIA).
Patients and methods: We compared a CLIA to an ELISA kit for the detection of IgG isotype of ACA. 87 routine samples from 75 patients suspected of having APS were tested using each method. Cut-off values were calculated in our laboratory for each test using 99
th
percentile of 50 normal controls.
Results: Cut-off values were > 20 GPL for ELISA and > 2 GPL for CLIA. Overall agreement (OA), agreement for positive (AP) and agreement for negative (AN) cases were 56.3%, 49.2% and 77.2% respectively. Most discrepant results were positive with ELISA and negative with CLIA. However, OA, AP and AN increased to 82.1%, 84.6% and 80% respectively when CLIA was compared to the repeated ELISA performed at least 12 weeks later. When correlated with APS-related clinical background, CLIA showed lower sensitivity, higher specificity and higher likelihood ratio (LR) as compared to first ELISA whereas these parameters were similar to those of the repeated ELISA. No association was found between any test results and APS-related clinical background of the patients. Using our own cut-off value (> 2GPL), sensitivity, specificity and LR of CLIA to identify patients with APS were respectively 100%, 72.3% and 3.6. A ROC curve showed that at 7.5 GPL cut-off value, specificity and LR improved to 91.1% and 11.25 respectively, without affecting sensitivity. A strong correlation was observed between CLIA results and APS (χ
2
= 12.25; p < 0.001).
Conclusion: The performance of CLIA is as good as a repeated ELISA test to detect IgG ACA in suspected APS patients. It is fully automated, which represents several advantages over semi-manual ELISA techniques for its implementation in a routine laboratory.
2 We present a case of a 49 years-old male on long-term oral anticoagulation because of positive antiphospholipid antibodies and clinical history of multiple arterial thrombotic events, who consulted ...a nephrologist for progressive renal failure. Since 1985, he complained of progressive bilateral claudication of buttocks and thighs as well as impotence.
Pagetic osteoclasts are greatly increased in number and size and have increased numbers of nuclei per cell compared to normal osteoclasts. The mechanisms responsible for enhanced osteoclast formation ...in Paget's disease are unknown. We have used our recently described model system for pagetic osteoclast formation to evaluate culture media conditioned by these atypical multinucleated cells (MNC) to determine if pagetic osteoclasts produce an autocrine or paracrine factor that enhances osteoclast formation. Conditioned media from long-term bone marrow cultures from patients with Paget's disease stimulated osteoclast-like MNC formation in normal marrow cultures. At least part of this activity could be ascribed to interleukin 6 (IL-6). In contrast, conditioned media from normal marrow cultures contained lower levels of IL-6 and did not stimulate formation of osteoclast-like MNC. 7 of 8 bone marrow plasma samples taken from involved bones and 18 of 27 peripheral blood serum samples from Paget's patients had high levels of IL-6. Normal marrow plasma and peripheral blood serum had no or very low levels of IL-6. These results suggest that IL-6 produced by marrow and/or bone cells in patients with Paget's disease may be an autocrine/paracrine factor for pagetic osteoclasts.
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