A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome.

We report a very high factor V inhibitor affecting the measurement of all coagulation factors besides fibrinogen, all these factors being dramatically decreased. This inhibitor could be linked to antibiotic use. The patient died of massive hemorrhage before a plasma exchange could be initiated.

Does Decreased Diffusing Capacity of the Lungs for Carbon Monoxide Constitute a Risk of Decompression Sickness in Occupational Divers?

Long-term alterations of pulmonary function (mainly decreased airway conductance and capacity of the lungs to diffuse carbon monoxide (DLCO)) have been described after hyperbaric exposures. However, whether these alterations convey a higher risk for divers' safety has never been investigated before. The purpose of the present pilot study was to assess whether decreased DLCO is associated with modifications of the physiological response to diving. In this case-control observational study, 15 "fit-to-dive" occupational divers were split into two groups according to their DLCO measurements compared to references values, either normal (control) or reduced (DLCO group). After a standardized 20 m/40 min dive in a sea water pool, the peak-flow, vascular gas emboli (VGE) grade, micro-circulatory reactivity, inflammatory biomarkers, thrombotic factors, and plasmatic aldosterone concentration were assessed at different times post-dive. Although VGE were recorded in all divers, no cases of decompression sickness (DCS) occurred. Compared to the control, the latency to VGE peak was increased in the DLCO group (60 vs. 30 min) along with a higher maximal VGE grade (p < 0.0001). P-selectin was higher in the DLCO group, both pre- and post-dive. The plasmatic aldosterone concentration was significantly decreased in the control group (-30.4 ± 24.6%) but not in the DLCO group. Apart from a state of hypocoagulability in all divers, other measured parameters remained unchanged. Our results suggest that divers with decreased DLCO might have a higher risk of DCS. Further studies are required to confirm these preliminary results.

Complicated atazanavir-associated cholelithiasis: a report of 14 cases.

Fourteen human immunodeficiency virus (HIV)-infected patients receiving an atazanavir (ATV)-based antiretroviral regimen developed complicated cholelithiasis. ATV was found in biliary calculi in 8 of 11 cases: infrared spectrometry analysis of calculi revealed that ATV made up a median of 89% (range, 10%-100%) of the total calculus composition. Development and management of ATV-associated cholelithiasis are discussed.

Evaluation of beta-2 microglobulin, erythropoietin and tobacco use in polycythemic cases.

In the 2016 WHO classification, hemoglobin and hematocrit thresholds for diagnosing polycythemia vera (PV) have been lowered, increasing the number of consultations for polycythemia investigations. In PV, beta-2 microglobulin (B2m) levels are reportedly increased, whereas erythropoietin (EPO) levels are usually low. Most secondary polycythemia cases (SP) are caused by tobacco use. We decided to analyze the relevance of these three parameters in all patients seen for polycythemia investigations to help differentiate PV from SP cases. A cohort of 257 patients (123 PV; 134 SP) was identified. The median B2m level was higher for PV patients (3.16 vs 1.98 mg/l, p < 0.0001). Increased B2m levels were observed in 83.7% of PV patients (11.9% in SP). The median EPO level was lower in PV patients (4.4 vs 12.3 UI/l, p < 0.0001). Tobacco was used by 42.8% of SP patients (8% in PV, p < 0.0001). Increased B2m, low EPO and no tobacco exposure was predictive of PV (specificity and positive predictive value = 100%). Normal B2m, normal EPO and tobacco exposure was predictive of SP (positive predictive value = 100%). These simple and inexpensive parameters could be used to rapidly differentiate PV from SP cases, before prescribing time-consuming JAK2 V617F mutation analysis by specialists.

A case of IgE myeloma transformed into IgE-producing plasma cell leukaemia.

This is a case report of a challenging diagnosis of IgE monoclonal gammopathy of undetermined significance, which transformed into myeloma, then transformed into IgE-producing plasma cell leukaemia in a 71-year-old male who was followed in Brest, France, from 2015 to 2019. The IgE-producing variant is the rarest sub-type of multiple myeloma, and plasma cell leukaemia is considered to be the rarest and the most aggressive of human monoclonal gammopathies. In November 2015, hypogammaglobulinemia was detected during a systematic check-up. A kappa light chain monoclonal gammopathy was first diagnosed due to an increase of the free kappa/lambda light chains ratio. No monoclonal immunoglobulin was detected by either serum protein electrophoresis (Capillarys 2, Sebia, Issy-les-Moulineaux, France) or immunofixation (Hydrasys 2, Sebia, Issy-les-Moulineaux, France). In June 2018, a blood smear led to the diagnosis of plasma cell leukaemia. A monoclonal peak was detected and identified as IgE-kappa. Analysis of an archival sample taken three years earlier, revealed the presence of a monoclonal IgE, which had been missed at diagnosis. Chemotherapy with bortezomib and dexamethasone was introduced. The patient survived 10 months after the diagnosis of leukaemia. This case shows that an abnormal free light chain ratio should be considered as a possible marker of IgE monoclonal gammopathy even in the absence of a solitary light chain revealed by immunofixation. In addition, the use of an undiluted serum may increase the sensitivity of the immunofixation for the detection of IgE monoclonal gammopathies compared to the 1:3 dilution recommended by the manufacturer.

Systematic overestimation of human serum albumin by capillary zone electrophoresis method due to monoclonal immunoglobulin interferences.

BACKGROUND: The capillary zone electrophoresis method of albumin measurement is frequently used in monoclonal gammopathy patients but some studies suggest poor performances of the method in this population. The aim of this study was to analyse the impact of serum monoclonal immunoglobulins on human serum albumin determination by capillary zone electrophoresis method compared to other available methods. METHOD: We prospectively measured albumin in 100 freshly collected non-frozen serum samples in a monoclonal gammopathy patients population, by using four different methods: the capillary zone electrophoresis method, the bromocresol purple dye method, the nephelometric method and the turbidimetric method. Differences in albumin values between the different methods were analysed with respect to serum monoclonal immunoglobulin concentration. These differences were further investigated by measuring albumin levels in human serum samples spiked with exogenous monoclonal immunoglobulins. RESULTS: Human serum albumin difference values between capillary zone electrophoresis compared to immunonephelometry method are significantly correlated with increasing monoclonal immunoglobulins concentrations: regression analyses revealed a correlation coefficient r2 = 0.60 and a slope of 0.14 (0.12-0.17, 95% confidence interval). The capillary zone electrophoresis method overestimated serum albumin levels by up to 67% (12 g/L) when monoclonal immunoglobulin level was 63 g/L. The determination of albumin levels in human serum samples spiked with exogenous monoclonal immunoglobulins showed an overestimation of human serum albumin measurement by the capillary zone electrophoresis method proportional to the amount of monoclonal immunoglobulin added in the serum with a slope of 0.19 (0.18-0.20, 95% confidence interval). CONCLUSION: Monoclonal immunoglobulins directly interfere with serum albumin measurement by the capillary zone electrophoresis method leading to a systematic overestimation of serum albumin concentrations proportional to the serum monoclonal immunoglobulin level.

Is capillary zone electrophoresis a suitable method for estimating serum albumin: A comparison of four methods.

BACKGROUND: The capillary zone electrophoresis method of albumin measurement is frequently used for oncologic and haematologic patients but few data exist about the agreement between the albumin measurements performed by capillary zone electrophoresis and other methods. The aim of this study was to analyse the agreement between human serum albumin measurements by capillary zone electrophoresis and by the nephelometry, bromocresol purple and turbidimetry methods. METHOD: We prospectively measured 100 freshly collected non-frozen patient serum samples, by using four different methods: the capillary zone electrophoresis method performed with a CAPILLARYS 2 instrument, the bromocresol purple dye method performed with an Advia XPT analyser, the nephelometric method performed with a BN ProSpec analyser and the turbidimetric method with reagents from DiAgam and performed with the Advia XPT analyser. RESULTS: A bias towards higher values in the lower range of albumin concentrations was observed with capillary zone electrophoresis compared to immunonephelometry: correlation coefficient r2 = 0.925; slope of 0.86 (0.82-0.89, 95% confidence interval), which is significantly different from 1; and an intercept of 4.94 g/L (3.67-6.16, 95% confidence interval). Similar results were observed when comparing capillary zone electrophoresis to the bromocresol purple and immunoturbidimetry methods. The capillary electrophoresis method overestimated low albumin levels by up to 25% (5 g/L). CONCLUSION: Compared to the nephelometry, turbidimetry and bromocresol purple methods, the capillary zone electrophoresis method tends to overestimate human serum albumin concentrations for levels below 30 g/L. This discrepancy could lead to an overestimation of the nutritional status, an inappropriate scoring of the disease and a delay in nutritional treatment.

The presence of monoclonal gammopathy in Ph-negative myeloproliferative neoplasms is associated with a detrimental effect on outcomes.

Many case reports have indicated the occurrence of monoclonal gammopathy of uncertain significance (MGUS) or multiple myeloma (MM) in patients with Ph-negative myeloproliferative neoplasms (MPN), but few cohorts of patients have been published. This study concerns 667 patients newly diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) who were tested for monoclonal (M) protein at diagnosis (13.9% of patients). The overall survival of patients with M protein was dramatically lower than that of patients without M protein (12.7 versus 22.4 years; p = .0132). Univariate analysis identified the presence of M protein as a potential risk factor for the secondary occurrence of myelofibrosis (p = .02), myelodysplastic syndrome (p = .043), and MM/Waldenstrom macroglobulinemia (p < .0001). Our cohort shows that the presence of M proteins in patients with PV or ET leads to a poor prognosis. We believe that testing for M protein could help practicians to identify such patients.

[Pseudohypobicarbonatemia in a patient with a kappa IgA monoclonal gammapathy]. / Pseudohypobicarbonatémie chez une patiente atteinte d'une gammapathie monoclonale à IgA kappa.

Paraprotein interferences assays are known but rather unusual in clinical chemistry.we here report a paraprotein interference with a bicarbonate assay in a IgA kappa-type myeloma patient. Serum bicarbonate level was assessed by the enzymatic method of a multiparametric chemistry analyzer (Advia 1800, Siemens) as well as a specific electrode assay on a blood gas analyzer (GEM 4000, IL). Paraprotein interference with the enzymatic assay was evidenced by an abnomally low bicarbonate level measured by the enzymatic method in contrast with usual levels obtained by using the gas analyzer and with the clinical status of the patient. Therefore, gammapathy has to be taken into consideration when interpreting biological data.

[Comparative study of parathormone and vitamin D measurements by three automats: ADVIA Centaur XP® (Siemens), ISYS® (IDS) and Liaison® (Diasorin)]. / Étude comparative des dosages de parathormone et de vitamine D sur 3 automates : Advia Centaur XP (®) (Siemens), Isys(®) (IDS) et Liaison(®) (Diasorin).

Vitamin D (Vit.D) and parathormone (PTH) measurements are usually prescribed for phosphocalcic metabolism assessment and, especially for Vit.D, more and more frequently for other pathologies. In order to step up to automated techniques for these analysis in our laboratory, we tested 3 devices: ADVIA Centaur XP(®) (Siemens), ISYS(®) (IDS) and Liaison(®) (Diasorin), which allow to simultaneously quantify Vit.D and PTH. The aim of this study was to evaluate the fidelity of these methods as well as study the correlation between them and the radioimmunological techniques previously used in our laboratory : « ELSA PTH ¼ (Iba Cisbio International) and « 25-OH D ¼ (IDS). The comparison of PTH analysis was performed on a population of chronic renal failure patients undergoing haemodialysis. According to our study, the 3 devices show acceptable analytical performances; anyway the measurements realized on the ISYS analyzer are the ones showing the best results in terms of fidelity, and the closest results to those obtained with the RIA reference techniques.

Lipid parameters, lipid lowering drugs and the risk of venous thromboembolism.

BACKGROUND: Besides their effects on atherogenesis, lipids and lipoproteins could contribute to the development of venous thromboembolism (VTE). This association has been investigated in a few studies with conflicting results. METHODS: Plasma levels of total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, apolipoprotein A-I and apolipoprotein B were measured in 467 patients with a first unprovoked VTE event diagnosed between May 2000 and December 2004 and in 467 age and sex matched controls. The association between these parameters and VTE was determined in non-users of lipid lowering drugs (LLD), in statin users and in fibrate users in a quartile-based analysis. We repeated this stratified analysis within each stratum of men and women. RESULTS: The median age of patients was 73 years [interquartile range 58-80], 41.5% were men. Among the 934 patients of the study, 100 were treated with statin, 91 with fibrate and 743 were not receiving LLD. Among non users of LLD, high levels of apolipoprotein B were associated with VTE (OR 1.82, 95% CI 1.19-2.79) after adjustment for age and body mass index. Elevated LDL-cholesterol levels were associated with VTE only in men (OR 2.32, 95% CI 1.07-5.01). High levels of LDL/HDL-cholesterol and apolipoprotein B/apolipoprotein A-I ratios were associated with VTE (OR 2.76, 95% CI 1.69-4.50 and OR 1.86, 95% CI 1.16-2.97 respectively) but this effect was mainly observed in men. There was no association between lipid parameters and VTE in statin users and in fibrate users. CONCLUSION: Our results are in line with the new concept of a global cardiovascular disease combining atherosclerosis and VTE.

The hook effect in calcitonin immunoradiometric assay: a case report.

UNLABELLED: The hook effect, which has long been detected and documented for immunoradiometric assays (IRMA) such as those measuring prolactin or thyroglobulin, occurs when the serum antigen level is extremely high, thus inducing a bias in the methodology of measurement. RESULTS: We report the case of an 80-year-old man with confirmed medullary thyroid carcinoma (MTC). In the case reported here, the clinical status of the patient contrasts with his tumor antigen, serum calcitonin (CT), concentrations. The measured increased CT concentrations revealed the presence of a hook effect. This phenomenon occurs due to an excess of antigen during the one-step IRMA where the signal antibodies, bound to the non-captured antigens, are washed out during the measurement, inducing the loss of signal. Aiming to prevent the "hook effect", successive dilutions of the same sample of serum were done. CONCLUSIONS: Previous studies have shown when one-step IRMA reveals high concentrations of a tumor serum antigen (i.e. prolactin or thyroglobulin), a two-step IRMA or a systematic 1:10 dilution of the serum sample prevents the formation of the "hook effect". In our case report, the CT "hook effect" formation was prevented by performing serial dilutions of the serum sample.