Hairy cell leukemia (HCL) is a rare, chronic lymphoid leukemia characterized by circulating lymphocytes with pale, hair-like cytoplasmic projections, pancytopenia, marked monocytopenia, and splenomegaly. Classic HCL displays distinct morphological, immunophenotypical, and genetic features. Classic HCL cells exhibit central nuclei, abundant cytoplasm with hair-like projections, and expression of CD20, CD22, CD11c, CD103, CD25, CD123, TBX21, annexin A1 (ANXA1), FMC7, CD200, and weak cyclin D1 (CCND1). While the vast majority of classic HCL cases harbor the BRAF V600E somatic mutation, rare examples have been reported without splenomegaly, with bulky lymphadenopathy, or with an atypical morphology, immunophenotype or genotype. This review analyzes the atypical clinical, morphologic, immunophenotypic, and genetic presentations associated with classic HCL. PubMed, Web of Science, and Google Scholar were searched for articles of hairy cell leukemia, including atypical morphology, atypical immunophenotype, atypical genotype, and rare symptoms. Publications from October 2004 to December 2024 were reviewed, with additional relevant studies obtained by reviewing references from selected articles.

Introduction: Targeting factor XII (FXII) is a new concept for safe thrombosis prophylaxis. Global hemostasis tests offer promise in terms of the laboratory monitoring of FXII inhibition. The present study examines selected parameters of rotational thromboelastometry (ROTEM) in patients with FXII deficiency. The objective of this study was to assess the impact of FXII deficiency on selected parameters of ROTEM, which can be significant in the laboratory monitoring of FXII inhibition. Material and methods : The study included 20 patients with FXII deficiency ≤40% and 21 volunteers free of it. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF), and maximum lysis (ML) were recorded in ROTEM. Results: For the INTEM test, CT and CFT readings were markedly higher in FXII deficient patients than in controls. No marked differences in relation to MCF and ML were found. Conclusion: The results of ROTEM show that FXII deficiency has a great impact on the initiation and amplification of coagulation. This was confirmed by a number of marked correlations between FXII activity and certain ROTEM parameters. ROTEM tests merit further investigation as treatment control strategies in the context of FXII inhibition.

Introduction: Contemporary technological development make the cytological analysis of megakaryocytes (MKs) a valuable tool for supporting differential diagnosis of myeloproliferative neoplasms’ (MPNs) early stages. Aim: The aim of the study was to identify megakaryocyte’s cytological differences between chronic myelogenous leukemia (CML), polycythemia vera (PV) and essential thrombocythemia (ET), as well as to assess the usefulness of this analysis in differential diagnosis of the aforementioned MPNs. Materials and methods: Bone marrow aspirate smears were obtained from 20 patients with CML, 15 patients with PV and 12 patients with ET. The control included bone marrow biopsies from 15 patients without any hematological disorder. The following megakaryocyte’s parameters were examined: cell diameter, cytoplasmic area, nuclear area, nuclear-cytoplasmic ratio and nuclear lobulation. Results: Cytological analysis revealed a significantly decreased megakaryocytes’ size and the prevalence of cells with hypolobulated nuclei in CML patients comparing to other groups. MKs in ET were found to have characteristic staghorn-like hyperlobulated nucleus, whereas polycythemia vera showed the predominance of cells with multilobulated nuclei (4-7 lobes) and a tendency to hyperlobulation. However, there were no significant differences in mean values for cytoplasmic and nuclear area among these two groups of patients. Conclusion: Characteristic megakaryocytes’ cytological differences in CML patients may be useful in differential diagnosis of the CML’s early stage. MKs’ size and nuclear-cytoplasmic ratio are not useful in differentiation between polycythemia vera and essential thrombocythemia.

Acute Myeloid Leukemia with Platelet-Derived Growth Factor Receptor β (PDGFRβ) Rearrangement Successfully Treated with Intensive Chemotherapy in Combination Withimatinib- A Case Report. Archives Clinical Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal stem cell malignancy. Several subgroups of AML have been identified based on multiple genomic and proteomic aberrations; these demonstrate different clinical features, response to treatment and prognosis. Rearrangements in the platelet-derived growth factor receptor β ( PDGFRβ ) gene result in greater constitutive enzymatic activity (tyrosine kinase) and deregulation gene rearrangements are infrequent entities, which are mostly diagnosed in patients presenting with atypical CML, chronic myelomonocytic leukemia (CMML), myelodysplastic/myeloproliferative disorders (MDS/MPN) or juvenile myelomonocytic leukemia (JMML). PDGFRβ positive AML is extremely rare, accounting for well below 1% of all cases. In this article, we present the case of a 31-year-old woman with AML and abnormal karyotype with PDGFRβ rearrangement, who was treated with intensive chemotherapy combined with low-dose imatinib. Complete remission (CR) was achieved and imatinib was used as maintenance treatment. The patient remains in CR with disease-free survival (DFS) of 41 months.

AbstractThe preparation of patients with hemophilia before surgical operations and dental procedures constitutes a significant clinical challenge. This article presents the implantoprosthetic rehabilitation of a patient with severe hemophilia B (factor IX activity <1%). The patient was prepared for the surgical procedure with recombinant factor IX concentrate (Rixubis) during the clinical surgery study. Tooth extraction and the implantation of four dental implants in the mandible were planned: one dental implant of 3.7 mm diameter and 10 mm length in the place of tooth 35, and another of 3.2 mm diameter and 10 mm length in the place of tooth 37. The next two implants were implemented 1 month later: one implant 3.7 mm in diameter and 10 mm in length in the place of tooth 46, and another implant 3.2 mm in diameter and 10 mm in length in the area of tooth 44. Appropriate substitution of the missing coagulation factor, together with the use of local hemostatic therapy, allowed dental implantation to be performed without excessive blood loss in this patient with severe hemophilia B.

Patients with multiple myeloma (MM) are at increased risk of thrombosis. Growing evidence indicates that oxidative and nitrative modifications of proteins, including fibrinogen, may lead to changes in hemostasis. The study compares samples from patients with MM at diagnosis and healthy volunteers with regard to the oxidative/nitrative modifications of proteins, ROTEM and thrombin-catalyzed fibrin polymerization. The content of carbonyl groups in plasma proteins of patients with MM was significantly higher than in controls (2.981 vs. 1.807 nmol/mg of protein, p = 0.005), while no differences were seen in the concentrations of nitrated proteins. Maximum clot firmness readings were significantly higher in the samples of patients than in controls according to FIBTEM test (23.5 vs. 15 mm, p = 0.006). The lag time of the fibrin polymerization process and the velocity of clot lysis (V Lys) were found to be significantly higher in the group of MM patients than controls. In contrast, no marked differences were identified between studied groups in reference to maximal velocity of fibrin polymerization process (V max), maximal absorbance (A max) and plasmin amidolytic activity values. In conclusion, our study demonstrates that at the time of diagnosis, patients with MM demonstrated greater oxidative stress than healthy volunteers, which is reflected in a higher amount of carbonylated proteins. Some prothrombotic features found in ROTEM tests in MM patients were not confirmed by turbidimetry.

Patients with essential thrombocythemia suffer from thrombotic complications that are the main source of mortality. Due to its complex pathogenesis, no existing single laboratory method is able to identify the patients at highest risk for developing thrombosis. Twenty patients with essential thrombocythemia at diagnosis, 15 healthy volunteers and 20 patients treated with hydroxyurea were compared with regard to certain rotation thromboelastometry parameters. Clotting time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF) were assessed by using the INTEM, EXTEM, FIBTEM, and NATEM tests. Patients with essential thrombocythemia at diagnosis demonstrated significantly higher mean platelet count and markedly lower mean red blood count than controls. CT and CFT readings were found to be markedly lower in essential thrombocythemia patients at diagnosis than in the control group according to the EXTEM test. Patients at diagnosis had markedly lower CT values (EXTEM, FIBTEM) than patients on hydroxyurea therapy. Alpha angle values were markedly higher in essential thrombocythemia patients at diagnosis than in controls, according to the EXTEM, FIBTEM and NATEM tests. MCF readings were significantly higher in essential thrombocythemia patients at diagnosis than in controls according to EXTEM, INTEM, FIBTEM, and NATEM tests. Patients on hydroxyurea therapy had markedly lower MCF values according to EXTEM test than patients at diagnosis. Patients with essential thrombocythemia demonstrate a prothrombotic state at the time of diagnosis, which is reflected in changes by certain rotation thromboelastometry parameters. The hydroxyurea therapy induces downregulation of the prothrombotic features seen in essential thrombocythemia patients at diagnosis.

BACKGROUND:Congenital fibrinogen disorders (CFD) are rare fibrinogen deficiencies which may be quantitative or functional. The clinical course of hypofibrinogenemia (hypoFI) or dysfibrinogenemia (dysFI) is unpredictable and cannot be determined by the application of standard hemostasis tests.OBJECTIVES:The main aim of this study was to assess ROTEM parameters in CFD patients.MATERIAL AND METHODS:Nine patients with CFD were studied. The fibrinogen concentration was measured functionally and antigenically. EXTEM, INTEM, FIBTEM and APTEM tests were used to measure selected ROTEM parameters, including maximum clot firmness (MCF). Fibrin plasma polymerization, clot lysis and plasmin amidolytic activity were determined by spectrophotometric methods.RESULTS:Incorporating the antigenic, ELISA method, to the diagnostic workup allowed the initial diagnosis to be switched from hypoFI to dysFI in 3/7 patients. MCF readings (the most important parameter describing fibrin polymerization capacity) were significantly lower in patients than in controls according to all ROTEM tests. Cases with hypoFI demonstrated markedly lower readings of MCF according to all ROTEM tests than cases with dysFI. All patients demonstrated disturbances of fibrin polymerization process assessed by turbidimetry. In contrast, no marked differences were identified between studied groups in reference to plasmin amidolytic activity.CONCLUSIONS:Our data suggests that ROTEM and fibrin plasma polymerization according to the turbidimetric method have a high sensitivity towards detection of different CFD. Although ROTEM MCF assessment may help discriminate patients with hypoor dysfibrinogenemia, this finding has to be confirmed on larger groups of patients.

HaemophiliaVolume 22, Issue 5 p. e449-e451 Letter to the Editor Acquired haemophilia A in a Jehovah's Witness K. Chojnowski, K. Chojnowski Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorM. Robak, M. Robak Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorW. Nowak, W. Nowak Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorJ. Treliński, Corresponding Author J. Treliński jacek.trelinski@umed.lodz.pl Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland Correspondence: Jacek Treliński, Department of Hemostasis, Medical University of Łódź, ul. Ciołkowskiego 2, 93-510 Łódź, Poland. Tel.: +48 42 689 5191; fax: +48 42 689 5192; e-mail: jacek.trelinski@umed.lodz.plSearch for more papers by this author K. Chojnowski, K. Chojnowski Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorM. Robak, M. Robak Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorW. Nowak, W. Nowak Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, PolandSearch for more papers by this authorJ. Treliński, Corresponding Author J. Treliński jacek.trelinski@umed.lodz.pl Department of Hemostasis, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland Correspondence: Jacek Treliński, Department of Hemostasis, Medical University of Łódź, ul. Ciołkowskiego 2, 93-510 Łódź, Poland. Tel.: +48 42 689 5191; fax: +48 42 689 5192; e-mail: jacek.trelinski@umed.lodz.plSearch for more papers by this author First published: 24 June 2016 https://doi.org/10.1111/hae.12992Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, Issue5September 2016Pages e449-e451 RelatedInformation

BACKGROUNDThe treatment of patients with acute leukemia, who due to their religious beliefs refuse to accept blood transfusion, is a great challenge for hematologists.CASE REPORTWe present a case of acute pre‐T‐lymphoblastic leukemia in a Jehovah's Witness who did not accept blood transfusion during chemotherapy. Standard induction and consolidation chemotherapy was used (according to the PALG ALL‐6 regiment).RESULTSDuring consolidation cycles, darbepoietin alfa, intravenous iron, and total parenteral nutrition was administered. Extreme (Hb < 5 g/dL), long‐lasting (41 days) anemia was observed with the lowest Hb concentration amounting to 1.3 g/dL (lasting 7 days).CONCLUSIONWe believe this to be the lowest Hb value observed, particularly one that persisted for such a long period of time and resulted in the patient surviving without consequences. The patient remains in complete remission for more than 2 years after diagnosis.

BACKGROUND:Rivaroxaban (Xarelto) does not require routine coagulation monitoring; however, in certain clinical situations (overdose, drug accumulation, urgent surgery) measurement of its plasma concentration is highly recommended. Currently, there is no single hemostasis test that shows a direct correlation between rivaroxaban plasma levels and anticoagulant efficacy.OBJECTIVES:This study was intended to assess the value of ROTEM in determining rivaroxaban administration.MATERIAL AND METHODS:Thirteen patients with venous thromboembolism and 13 healthy volunteers were compared with regard to certain ROTEM parameters and anti-FXa activity. The tests were done before the administration of 20 mg rivaroxaban (i.e. 24 h after previous administration) and 2.5 h afterwards.RESULTS:The study group demonstrated residual activity of rivaroxaban in plasma (20 ± 11.3 ng/mL) 24 h following the previous administration, which did not cause marked changes in clotting assays compared to controls. In the group, 2.5 h after rivaroxaban administration, prolongation of PT (PTratio 1.51 ± 0.22), APTT (APPTratio: 1.30 ± 0.14) and ROTEM CT (CTratio - EXTEM: 2.45 ± 1.06, CTratio -INTEM:1.32 ± 0.21) were observed. The cut-off values for particular tests were created to determine if the patient had achieved desirable anticoagulant effect after rivaroxaban administration. The mean anti-FXa values were significantly lower in patients before rivaroxaban dosing than after.CONCLUSIONS:PT demonstrated better diagnostic value than APTT in rivaroxaban administration. The ROTEM clotting time (CT) according to EXTEM may be used to determine the anticoagulation effect of rivaroxaban, but is not sensitive enough to measure the residual activity of this drug.

The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM‐1, VEGF, MMP‐9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years. The group consisted of patients with multiple myeloma (26) and lymphoma (8). The mobilization procedures comprised chemotherapy and then G‐CSF. Blood samples were collected before chemotherapy (N = 34) and on the day of the first apheresis (N = 26). Cytokines were evaluated with ELISA assay. We observed significant increase in VCAM‐1 levels during mobilization. On contrary, VEGF and SDF levels decreased during mobilization procedure. The levels of MMP‐9 were stable during mobilization. We divided patients according to baseline cytokines levels below and above median into “low” and “high” expressors. The group of VEGF “low” expressors had longer median time of G‐CSF treatment before first apheresis than ‘high’ expressors. Baseline VEGF levels correlated adversely with duration of G‐CSF treatment before first apheresis. Patients were also divided according to median cytokines levels at apheresis into “low” and “high” expressors. “High” VCAM‐1 expressors had higher CD34+in peripheral blood as well as higher CD34+numbers collected during first apheresis than “low” expressors. In conclusion, the levels of niche cytokines change significantly during mobilization in patients with hematopoietic malignancies. Baseline VEGF can influence timing of mobilization. Higher VCAM‐1 corresponds with higher mobilization efficacy. J. Clin. Apheresis 30:247–251, 2015. © 2014 Wiley Periodicals, Inc.

In the last decade, peripheral blood was the main source of hematopoietic stem cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms of HSC mobilization are still not clear and the efficacy of the procedure is hardly predictable. Ligand-receptor interactions of adhesion molecules, such as SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of HSC in the hematopoietic niche. There is some evidence that disruption of the ligand-receptor complex leads to the egress of HSCs to the peripheral blood. The aim of the present study was the evaluation of constitutive polymorphism of genes encoding cytokines and receptors present in the HSC niche and their impact on the efficacy of mobilization of HSCs in patients with hematological malignancies. We enrolled 110 patients (60 females and 50 males) in the study. The median age of the patients was 55 (range, 22 to 69) years. The group consisted of patients with multiple myeloma (n = 74), non-Hodgkin lymphoma (n = 19), Hodgkin lymphoma (n = 15), or acute myeloid leukemia (n = 2). The mobilization procedures comprised chemotherapy and subsequent granulocyte-colony stimulating factor (G-CSF) at a dose of 10 μg/kg daily. The poor mobilizers group was defined according to Italian National Bone Marrow Transplant Registry criteria: patients with peak CD34(+) in the peripheral blood < 20/μL or total yield < 2 × 10(6) CD34(+) cells/kg body weight in maximum 3 aphereses. Genotyping was performed using standard PCR-based assays. The group of patients (N = 108) who achieved minimal threshold for collections (CD34(+) at least 10/μL) proceeded to apheresis. The median total yield of CD34(+) in this group was 5.6 × 10(6) cells/kg body weight, whereas the median number of cells collected during the first apheresis was 3.3 × 10(6) cells/kg body weight. Median number of days of G-CSF treatment before first apheresis was 10. Fifteen patients fulfilled the criteria for poor mobilizer. The group of poor mobilizers had higher frequency of TT genotype in rs13347 (CD44) gene (CC+ CT versus TT P = .047). Patients homozygous for T allele had a lower total yield of CD34(+) cells/kg body weight than the group with allele C (median, 3.7 × 10(6)/kg versus 5.8 × 10(6)/kg; P = .019) and a lower number of CD34(+) cells gathered during first apheresis (.95 × 10(6)/kg versus 3.3 × 10(6)/kg, P = .04). Multivariate logistic regression analysis revealed that the CD44 TT genotype was the only factor associated with 5-fold higher risk of poor mobilization (P = .037). Polymorphic variants of CXCR4 and VCAM-1 did not significantly influence the efficacy of HSCs mobilization in our group of patients. In conclusion, our results indicate that among investigated single nucleotide polymorphisms (SNPs), only CD44 rs13347 has an impact on the efficacy of HSCs mobilization in patients with hematologic malignancies. CD44 SNPs analysis may be helpful for predicting the poor mobilizers population who may benefit from newer modalities using adhesion molecules inhibitors.

Introduction Patients with multiple myeloma (MM) have an increased risk of thromboembolic events (TEE). Due to the complex nature of the prothrombotic state in MM, no single laboratory test has been designed to identify patients with the highest risk of developing TEE. Hence, this study is intended to assess the feasibility of using global hemostasis test rotation thromboelastometry (ROTEM) in MM patients to identify the presence of changes indicating hypercoagulability. Materials and Methods The study included 26 patients with MM at the time of diagnosis and 20 healthy volunteers. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF) and maximum lysis (ML) were among the most important parameters recorded during the NATEM, INTEM, EXTEM, FIBTEM and APTEM tests. Results For the NATEM test, CT and CFT readings were markedly lower in MM patients than in controls (524 s v. 753 s; p = 0.0006 and 136 s v. 242 s; p = 0.02 respectively). However, no marked differences concerning these parameters were observed in the INTEM, EXTEM, FIBTEN or APTEM tests. α-angle values were significantly higher for MM samples according to the NATEM, EXTEM, FIBTEM and APTEM tests (64° v. 48.5°, p = 0.02; 77° v. 74°, p = 0.02; 80° v.69.5°, p = 0.00007; 77° v. 74°, p = 0.01 respectively). MCF readings were significantly higher in the FIBTEM test (22 mm v. 15.5 mm, p = 0.0003) in MM patients. Also, the NATEM test revealed a trend toward higher MCF values in MM samples (56 mm v. 49.5 mm, p = 0.055). No marked differences were seen in the INTEM, EXTEM and APTEM tests. ML readings were markedly lower (0 % v. 4.5 %, p = 0.0008) in MM samples than in controls according to the FIBTEM test. The studied clot lysis parameters did not differ markedly between analyzed groups in other tests. Marked negative correlations were noted between IgG concentration and CT (EXTEM, FIBTEM) and CFT (INTEM), as well as a significant positive correlation between IgG concentration and MCF (INTEM, FIBTEM) and α (INTEM) in MM IgG patients. Conclusions Our results suggest that patients with MM display changes in ROTEM tests at the time of diagnosis that may indicate a prothrombotic state.

UNLABELLED:Multiple myeloma (MM) is associated with the increased risk of thrombosis. Hypofibrinolysis is among the various identified abnormalities in the hemostasis system that may cause a prothrombotic state. The aim of the study was intended to evaluate the association between certain rotational thromboelastometry (ROTEM) parameters with tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) levels and myeloma proteins in patients with MM and in controls.MATERIAL AND METHODS:The study included 21 patients with MM at the time of diagnosis and 15 healthy volunteers. Maximum clot lysis (ML), clot lysis index at 30, 45 and 60 minutes (LI 30, LI 45, LI 60 respectively), t-PA and PAI-1 activity were among the parameters studied.RESULTS:According to the FIB TEM test, ML readings were markedly lower (1% v. 3%, p = 0.04) while LI 45, LI60 parameters were significantly higher (p = 0.01 and p = 0.04) in MM group than in controls. Also median, MCF readings (22 mm v. 16 mm, p = 0.01) and alpha-angle values (80 degrees v 74, p = 0.002) were significantly higher in MM according to the FIBTEM assay. Statistically significant higher median values of PAL-1 levels were observed in the MM group than in controls. In MM patients correlations between PAI-1 a LI 45-FIBTEM (r = - 0.65) and between t-PA a LI60- EXTEM (r = 0.45) were discovered. In MM IgG group correlation between IgG protein concentration and MCF-FIBTEM (r = 0.62) was shown.CONCLUSIONS:Changes in ROTEM parameters and PAI-1 levels which may indicate a hypofibrinolytic state were found to occur in patients with MM at the time of diagnosis. There are correlations between t-PA, PAI-1 and some ROTEM parameters.

Thromboembolic events (TEE) are a serious clinical problem in multiple myeloma (MM) patients receiving thalidomide (T). Thirty-one MM patients were tested on diagnosis and after 2 and 4 weeks of therapy with T alone, or T in combination with dexamethasone (TD). Closure time (CT) in PFA-100 and P-selectin expression were assessed, as well as plasma levels of thrombin-antithrombin complexes (TAT), D-dimer (DD), soluble thrombomodulin (sTM) and von Willebrand factor antigen (vWF:Ag), along with the activity of coagulation factor VII and factor VIII. The concentration of vascular endothelial growth factor and its type 1 and 2 receptors were also assayed. On diagnosis, significantly prolonged median CT with both used cartridges, elevated P-selectin expression, DD concentration, TAT, vWF:Ag and factor VIII and factor VII activity were seen in the patient group as compared to controls. Therapy with these regimens caused marked shortening of CT with both cartridges. Treatment with TD leads to the significant increase in CD62P expression on platelets. Median TAT value increased significantly in relation to baseline after therapy with both regimens. Factor VIII activity exceeded 150 % in all patients after 2 weeks of TD therapy and was markedly elevated compared to baseline. One month of TD therapy significantly increased sTM concentration. These results demonstrate the enhanced platelet and coagulation system activation already present in MM patients on diagnosis, which is further increased by antimyeloma therapy. These changes are more pronounced after TD therapy and may promote TEE. Tested angiogenesis marker levels are elevated already on diagnosis, do not change after therapy and have no significant impact on the coagulation system in patients with MM.