A new oral anticoagulant, dabigatran etexilate (DE, a prodrug of direct thrombin inhibitor (DTI) dabigatran), has been used clinically to prevent thrombosis. The assessment of dabigatran efficiency is necessary in some clinical cases, such as renal insufficiency, risk of bleeding, and drug interactions. However, a specific thrombin generation test (TGT) that is one of the most informative and sensitive to anticoagulant therapy (calibrated automated thrombinography (САТ)) shows a paradoxical increase of test parameters, such as endogenous thrombin potential (ETP) and peak thrombin, in patients receiving DE. The paradoxical behaviour of ETP and peak thrombin in these patients in the presence of DTIs is mostly caused by a decrease in the activity of thrombin in the α2-macroglobulin-thrombin complex that is used as a calibrator in CAT. For a correct estimation of the TGT parameters in patient’s plasma containing DTIs we proposed to use our previously described alternative calibration method that is based on the measurement of the fluorescence signal of a well-known concentration of the reaction product (7-amino-4-methylcoumarin). In this study, the validity of such approach was demonstrated in an ex vivo study in patients with knee replacement and two special patients with multiple myeloma, who received DE for thrombosis prophylaxis.

Introduction. Multiple myeloma (MM) in its early onset is complicated by myeloma nephropathy in 20-30% of patients, 10% of whom require haemodialysis. Early studies have shown that renal dysfunction has no adverse effect on melphalan pharmacokinetics. Auto-HSCT in some patients allows to restore renal function and to stop hemodialysis. Aim of the study. To assess the safety and efficacy of auto- HSCT in MM patients with dialysis-dependent renal failure. Materials and methods. During a period from May 2010 to December 2016 thirteen (3 males, 10 females) MM patients with dialysis-dependent renal failure aged 48 to 65 years (median 58) underwent auto-HSCT. The diagnosis was made according to IMWG criteria. In the onset of the disease, the median creatinine level was 1091 μmol /L, and GFR (CKD-EPI) ranged 3 to 10 ml / min / 1.73 m2 (median 3). Induction therapy included bortezomib-containing regimens in all patients, bendamustine was used in 5 (38.5%) patients, immunomodulatory drugs were used in 2 (15%) patients. HSC mobilization was performed according to the scheme: G-CSF 10 μg/kg. The median number of harvested CD34+ cells was 3.46x106/kg. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100-200 mg/m2), 12 patients underwent a single and one patient underwent a tandem auto-HSCT. On Day 100 after auto-HSCT, an antitumor response and renal response were assessed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10. Results. Before auto-HSCT CR was documented in 8 (61%) patients, VGPR was documented in 4 (31%) patients, PR was documented in 1 (8%) patient, with no renal response registered, GFR: 4-10 ml/min/1.73 m2 (median 5). The period of agranulocytosis after auto-HSCT was accompanied by infectious complications, cardiac and neurological dysfunctions (Table 1). The resulting complications were stopped; the mortality associated with transplantation (TRM) was 0%. At +100 days after auto-HSCT, the PR was confirmed in 9 (70%) patients and VGPR was confirmed in 4 (30%) patients. GFR: 5 - 17 ml/min/1.73 m2 (median 7). The minimal renal response was registered in 2 patients (15%), hemodialysis was stopped. After a median follow-up of 52 months 5-year progression-free survival (PFS) was 71%, and OS was 92%. Conclusion. Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, nevertheless, characterized by a high rate of early post-transplantation complications. Dialysis-dependent renal failure is not a contraindication for the use of high dosed melphalan followed by auto-HSCT. The probability of hemodialysis discontinuation after auto-HSCT was 15%. Survival rates are comparable to those in patients without renal impairment. Disclosures No relevant conflicts of interest to declare.

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Renal failure (RF) is detected in 20-30% of patients at the onset of multiple myeloma (MM), in 50% of patients during its progression. The advent of new, highly effective agents has considerably expanded the possibilities of treatment in MM patients. Unfortunately, patients with RF, especially those with severe RF, were not included in the majority of investigations. The available data are based on the results of treatment in small groups of patients generally without the morphological identification of nephropathies, with varying severity of RF, which explains significant differences in renal response rates. This review analyzes the results of the most important studies and gives recommendations for treatment in accordance with national and international standards.

Aim.Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy. Materials and methods.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission. Results.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN. Conclusion.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.