Affecting NF-κB cell signaling pathway in chronic lymphocytic leukemia by dendrimers-based nanoparticles.

The complex genetic diversity of chronic lymphocytic leukemia (CLL) makes it difficult to determine the effective and durable therapy beneficial to patients. During the several past years' significant insights in the biology of the disease and its treatment have been made, allowing for the identification of promising novel therapeutic agents. The investigation of signaling pathways to understand the biological character of CLL together with the development of molecular profiling is key in personalized approach in therapy for this disease. As it was already proven, maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers (PPI-G4) modulate BCR, TRAIL and WNT signaling pathway gene expression in CLL cells and strongly influence their survival by inducing apoptosis and inhibiting proliferation. The aim of this study was to evaluate the influence of PPI-G4-M3 dendrimers on NFκB pathway gene expression in CLL (MEC-1) cells with 60 K microarray, as it is one of the major factors in the pathogenesis of B-cell neoplasms. The findings were compared with those obtained with Fludarabine (FA) and the results indicate that PPI-G4-M3 dendrimers affect the expression of the examined genes and exert comparable effect on the CLL cells to FA. Dendrimers are one of the most potent groups of nanometer-sized macromolecules for closing the gap between the present ineffective treatment and the future effective personalized therapy due to their potential versatile biological properties.

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials.

Spleen tyrosine kinase (Syk) signaling is central to phagocytosis-based, antibody-mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on-treatment responses in a phase 2 ITP study. In two parallel, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks. The primary endpoint was stable response (platelets ≥50 000/µL at ≥4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16 000/µL; median duration of ITP was 8.5 years. Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/µL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006). Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%). Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti-motility agents). Fostamatinib produced clinically-meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.

Long-lasting extreme anemia during the therapy of acute lymphoblastic leukemia in a Jehovah's Witness patient.

BACKGROUND: The treatment of patients with acute leukemia, who due to their religious beliefs refuse to accept blood transfusion, is a great challenge for hematologists. CASE REPORT: We 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). RESULTS: During 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). CONCLUSION: We 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.

Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia.

Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD(+) patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 µg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 µg/kg platelet responses, defined as platelet count ≥ 30 × 10(9)/L and an increase in platelet count by > 20 × 10(9)/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.

[Correlations between ROTEM fibrinolytic activity and t-PA, PAI-1 levels in patients with newly diagnosed multiple myeloma]. / Ocena zaleznosci miedzy fibrynoliza mierzona przy uzyciu tromboelastometrii rotacyjnej ROTEM a stezeniami t-PA i PAI-1 u chorych na szpiczaka mnogiego w czasie rozpoznania.

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.

Immune thrombocytopenia in patients with chronic lymphocytic leukemia treated with cladribine-based regiments or chlorambucil--follow-up of PALG-CLL randomized trials.

OBJECTIVES: The relationship between treatments of chronic lymphocytic leukemia (CLL) with cladribine (2-CdA) or chlorambucil and immune thrombocytopenia (IT) has not been yet determined. METHODS: The records of 777 patients in two randomized Polish Adult Leukemia Group (PALG)-CLL programs treated with these agents were retrospectively analyzed. RESULTS: Immune thrombocytopenia occurred in 55 of 777 (7.1%) patients. No significant differences in IT prevalence were seen between patients on chlorambucil or 2-CdA-based regiments (P = 0.33). IT developed at a median time of 0.499 yr (0.06-4.8) from the start of CLL therapy. This time was significantly longer in patients treated with chlorambucil (2.03 yr, 95% CI: 0.06-4.22) in relation to patients treated with 2-CdA-based regiments (0.52 yr, 95%CI: 0.34-0.69, P = 0.049). Overall survival (OS) of patients with IT and those without IT were similar (2.65 yr vs. 3.2 yr P = 0.23) but the severity of bleeding was more pronounced in the 2-CdA group. The responses to IT therapy were 35%, 54% and 75% for steroids, chemotherapy and splenectomy, respectively. CONCLUSIONS: In this study, an unexpectedly high percentage of IT incidence was demonstrated in patients with CLL requiring chemotherapy. Although no marked differences were seen in IT frequency in patients treated with 2-CdA-based regiments compared to chlorambucil regimen, the clinical course of hemorrhagic diathesis was more severe in 2-CdA group. Also, the time elapsed from study screening to IT diagnosis was significantly shorter in the 2-CdA group than in the chlorambucil group suggesting a causative relationship. The appearance of IT did not influence the median time of OS.

Antithrombin Deficiency Is Associated with Prothrombotic Plasma Fibrin Clot Phenotype.

BACKGROUND: Deficiency of antithrombin increases risk of venous thromboembolism. We hypothesized that antithrombin deficiency affects fibrin clot structure and function. METHODS: We evaluated 148 patients (age: 38 [32-50] years; 70% women) with genetically confirmed antithrombin deficiency and 50 healthy controls. Fibrin clot permeability (Ks) and clot lysis time (CLT) along with thrombin generation capacity were assessed before and after antithrombin activity normalization in vitro. RESULTS: Antithrombin-deficient patients had lower antithrombin activity (-39%) and antigen levels (-23%) compared with controls (both p < 0.01). Prothrombin fragment 1 + 2 levels were 26.5% higher in patients with antithrombin deficiency than in controls along with 94% increased endogenous thrombin potential (ETP) and 108% higher peak thrombin (all p < 0.01). Antithrombin deficiency was associated with 18% reduced Ks and 35% prolonged CLT (both p < 0.001). Patients with type I (n = 65; 43.9%) compared with type II antithrombin deficiency (n = 83; 56.1%) had 22.5% lower antithrombin activity (p < 0.001) and despite similar fibrinogen levels, 8.4% reduced Ks, 18% prolonged CLT, and 30% higher ETP (all p < 0.01). Reduced Ks was associated with lower antithrombin antigen level (ß = - 6.1, 95% confidence interval [CI]: -1.7 to -10.5), while prolonged CLT was associated with lower antithrombin antigen (ß = - 69.6, 95% CI: -9.6 to -129.7), activity (ß = - 2.4, 95% CI: -0.3 to -4.5), higher PAI-1 (ß = 12.1, 95% CI: 7.7-16.5), and thrombin-activatable fibrinolysis inhibitor levels (ß = 3.8, 95% CI: 1.9-5.7). Addition of exogenous antithrombin reduced ETP (-42%) and peak thrombin (-21%), and improved Ks (+8%) and CLT (-12%; all p < 0.01). CONCLUSION: Our study suggests that enhanced thrombin generation and prothrombotic plasma fibrin clot phenotype can contribute to increased risk of thrombosis in patients with antithrombin deficiency.

Increased Oxidative Stress in Acute Myeloid Leukemia Patients after Red Blood Cell Transfusion, but Not Platelet Transfusion, Results Mainly from the Oxidative/Nitrative Protein Damage: An Exploratory Study.

Chronic oxidative stress (OS) can be an important factor of acute myeloid leukemia (AML) progression; however, there are no data on the extent/consequence of OS after transfusion of packed red blood cells (pRBCs) and platelet concentrates (PCs), which are commonly used in the treatment of leukemia-associated anemia and thrombocytopenia. We aimed to investigate the effects of pRBC/PC transfusion on the OS markers, i.e., thiol and carbonyl (CO) groups, 3-nitrotyrosine (3-NT), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGE), total antioxidant capacity (TAC), SOD, GST, and LDH, in the blood plasma of AML patients, before and 24 h post-transfusion. In this exploratory study, 52 patients were examined, of which 27 were transfused with pRBCs and 25 with PCs. Age-matched healthy subjects were also enrolled as controls. Our results showed the oxidation of thiols, increased 3-NT, AGE levels, and decreased TAC in AML groups versus controls. After pRBC transfusion, CO groups, AGE, and 3-NT significantly increased (by approximately 30, 23, and 35%; p < 0.05, p < 0.05, and p < 0.01, respectively) while thiols reduced (by 18%; p < 0.05). The PC transfusion resulted in the raise of TBARS and AGE (by 45%; p < 0.01 and 31%; p < 0.001), respectively). Other variables showed no significant post-transfusion changes. In conclusion, transfusion of both pRBCs and PCs was associated with an increased OS; however, transfusing the former may have more severe consequences, since it is associated with the irreversible oxidative/nitrative modifications of plasma proteins.

Phase 2 multiple-dose study of an FcRn inhibitor, rozanolixizumab, in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is a predominantly immunoglobulin G (IgG)-autoantibody-mediated disease characterized by isolated thrombocytopenia. Rozanolixizumab, a subcutaneously infused humanized monoclonal anti-neonatal Fc receptor (FcRn) antibody, reduced serum IgG in healthy volunteers. In this phase 2, multicenter, open-label study, patients with persistent/chronic primary ITP received 1 to 5 once-weekly subcutaneous infusions of rozanolixizumab (cumulative doses, 15-21 mg/kg). Primary objectives were safety and tolerability, and secondary objectives were clinical efficacy (change in platelet count) and pharmacodynamic effect (change in IgG). In all, 51 (77.3%) of 66 patients reported 1 or more adverse events (AEs), all mild-to-moderate, most commonly headaches (26 [39.4%] of 66), of which 15 were treatment related. Four patients had serious AEs, but none were treatment related. No AEs resulted in discontinuation of the study drug. No serious infections occurred. Platelet counts of ≥50 × 109/L were achieved at least once at any time after multiple infusions (5 × 4, 3 × 7, or 2 × 10 mg/kg: 35.7%, 35.7%, and 45.5% of patients, respectively) or single infusions (15 or 20 mg/kg: 66.7% and 54.5% patients, respectively). Minimum mean IgG levels and maximum mean platelet counts both occurred by day 8 in the higher (15 and 20 mg/kg) single-dose cohorts and maximum platelet count occurred by day 11 onward in the multiple-dose cohorts. No clinically meaningful changes occurred in IgA, IgM, IgE, or albumin levels. In patients with persistent/chronic primary ITP, rozanolixizumab demonstrated a favorable safety profile and rapid, substantial platelet increases concordant with substantial IgG reductions, especially with single doses. By day 8, in the 15 and 20 mg/kg single-dose cohorts, >50% patients achieved clinically relevant platelet responses (≥50 × 109/L), coinciding with the lowest mean IgG levels. These data support phase 3 development of rozanolixizumab in persistent/chronic primary ITP. This trial was registered at www.clinicaltrials.gov as #NCT02718716.

Six molecular patterns leading to hemophilia A phenotype in 18 females from Poland.

INTRODUCTION: Female hemophilia is an intriguing rare disorder and few larger reports on its genetic etiology are available. While historically the diagnosis was satisfactorily reached by factor VIII activity assays, the clinical and potentially therapeutic heterogeneity of female hemophilia calls for comprehensive molecular diagnosis in each case. Currently, the genetic investigations are not a part of routine, state-funded, diagnostics in Poland, and thus molecular epidemiological data are missing. AIM: We set out to perform a comprehensive genetic analysis of Polish females with hemophilia A. PATIENTS/METHODS: Eighteen females with hemophilia A (including 2 with severe and 5 with moderate hemophilia phenotype) consented for genetic diagnostics. To establish F8 mutations, we used next-generation sequencing of a panel of genes associated with hematological disorders, standard assays for recurrent intragenic F8 inversions and MLPA when deletions were suspected. When appropriate we also used karyotyping, genomic microarrays and X chromosome inactivation assays. RESULTS: While abnormally skewed X-chromosome inactivation combined with a F8 variant on the active allele was, as expected, the most common genetic etiology, a number of other genetic scenarios were unraveled. This included: misdiagnosis (molecular diagnosis of vWd), Turner syndrome, compound heterozygosity and androgen insensitivity syndrome (a phenotypical 46,XY female with a novel androgen receptor gene mutation). We report 3 novel F8 mutations. CONCLUSION: Every case of female hemophilia warrants full genomic diagnostics, as this may change the diagnosis or reveal broader morbidity than a coagulation disorder (Turner syndrome, androgen insensitivity, or cardiovascular morbidity that we described previously in a SHAM syndrome carrier).

[Disseminated intravascular coagulation in abdominal aortic aneurysm--case report]. / Rozsiane krzepniecie sródnaczyniowe w przebiegu tetniaka aorty brzusznej--opis przypadku.

Disseminated intravascular coagulation (DIC) constitutes a rare presentation form of aortic aneurysms. In majority of cases, DIC is asymptomatic and has chronic course, but in 0.5-4% of patients it is clinically overt. Very seldom DIC leads to diagnosis of previously unknown aortic aneurysm. The authors describe a case of 84 years old man referred to hospital due to haemorrhagic diathesis with laboratory results consistent with overt DIC. A CT scan demonstrated abdominal aortic aneurysm (AAA) as an underlying disorder. The patient was treated with fresh frozen plasma and enoxoparine. After reaching the clinical and laboratory improvement he was proposed with placing an endoluminal stent graft, but he did not agree for operation. The multidisciplinary management of this patient is presented and some issues concerning the epidemiology, treatment and coagulation assessment of AAA patients with DIC are discussed.

Genetic and clinical characterization of congenital fibrinogen disorders in Polish patients: Identification of three novel fibrinogen gamma chain mutations.

INTRODUCTION: Congenital fibrinogen disorders are poorly explored in Slavic populations. The aim of this study was to characterize the genetic background and clinical manifestations of fibrinogen disorders in the Polish case series. MATERIALS AND METHODS: In 27 unrelated patients (mean [SD] age, 30.4 [19.2] years, 30% men) with fibrinogen concentration (von Clauss method) < 1.8 g/L, exons and intron-exon junctions of the fibrinogen alpha chain (FGA), fibrinogen beta chain (FGB), and fibrinogen gamma chain (FGG) genes were analyzed using polymerase chain reaction (PCR) amplification followed by sequencing. RESULTS: At enrollment, 15 (55.6%) and 2 (7.4%) of patients experienced bleeding and thrombotic events, respectively, and the remainder were asymptomatic. The following congenital fibrinogen disorders were identified: 1A. afibrinogenemia, n = 1; 2A. severe hypofibrinogenemia, n = 2; 2B. moderate hypofibrinogenemia, n = 4; 2C. mild hypofibrinogenemia, n = 6; 3A. dysfibrinogenemia, n = 12; 3B. thrombotic related-dysfibrinogenemia, n = 1; 4C. mild hypodysfibrinogenemia, n = 1. Eight dysfibrinogenemic patients (62%) were carriers of hotspot mutations. Fifteen patients were heterozygous and one (afibrinogenemia) homozygous for known causative mutations. Three new heterozygous mutations were detected, all affecting splicing in FGG: fibrinogen Poznan II, a 177 bp deletion eliminating parts of intron 6 and exon 7 in a dysfibrinogenemic woman with recurrent bleeding; fibrinogen Zakopane, (intron 2 acceptor splice site) and fibrinogen Belchatow (intron 1 donor splice site), found in hypofibrinogenemic patients. During follow-up (median 60, interquartile range 10-60 months), bleeding episodes, mainly menorrhagia and easy bruising were reported in 15 (55.6%) patients. One thromboembolic event was observed. CONCLUSION: This study of the largest cohort of Slavic patients with congenital fibrinogen disorders has enabled the identification of 3 new FGG mutations and shows a high prevalence of bleeding manifestations with recurrences.

[Thrombotic thrombocytopenic purpura in pregnancy. A case report]. / Zakrzepowa plamica maloplytkowa w ciazy--opis przypadku.

Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. About 10-20% of TTP cases are associated with the pregnancy. Preterm delivery and intrauterine fetal death are frequent pregnancy complications of TTP. The following paper presents the case of a 32-year-old woman with TTP relapse at 10 weeks of her second pregnancy. Despite regular fresh frozen plasma transfusions, intrauterine fetal death occurred at 21 weeks of gestation. Current views on TTP management during pregnancy have been presented in the article as well.

[The assessment of platelet function in patients with essential thrombocythemia]. / Ocena czynnosci plytek krwi u chorych na nadplytkowosc samoistna.

UNLABELLED: Essential thrombocythemia (ET) is associated with an increased risk of both thromboembolic and bleeding complications. Changes in platelet count and function are crucial but leukocyte activation is also suspected. The aim of the study. The study was designed to assess platelet function by optical and impedance platelet aggregometry and also PFA-100 analyser in ET patients at the time of diagnosis MATERIAL AND METHODS: The tests were performed in 32 ET patients. In each patient platelet aggregation tests by optical (in platelet rich plasma) and impedance methods (in whole blood) after stimulation with ADP, collagen, epinephrine were done. The platelet function was also assessed by PFA-100 method. The control group consisted of 20 healthy volunteers. RESULTS: In optical platelet aggregometry different platelet function abnormalities were seen in 31 patients (97%). The most frequent was decreased aggregation (19/32) with all used agonists but especially with epinephrine. Spontaneous aggregation was observed in 10 cases and in one we observed hyperaggregation. In whole blood platelet aggregometry abnormal results concerned 23 patients (72%). The most typical (14/32) was hyperactivity of platelets (especially after ADP). In this method we noted spontaneous aggregation in patients and in 4 patients' diminished aggregation. Mixed aggregation disturbances were observed in 6 patients. The closure time in the cohort of patients was significantly prolonged with both cartridges in comparison to control group and was outside reference ranges in 25/32 patient. No significant correlation between values of platelet aggregation in platelet rich plasma and in whole blood was found. No significant differences were observed between ET patients with and without clinical symptoms of bleeding/thrombosis although closure time with both cartridges was longer in patients with bleeding. CONCLUSIONS: In majority of ET patients different platelet function abnormalities are present. The platelet aggregation results depend on environment in which tests are performed. The PFA-100 seems to be a good method for detection of platelet defects in ET.

Blockage of Wnt/ß-Catenin Signaling by Nanoparticles Reduces Survival and Proliferation of CLL Cells In Vitro-Preliminary Study.

The Wnt/ß-catenin signaling pathway is shown to play a significant role in the control of the survival, proliferation, and differentiation of hematopoietic cells. Studies have confirmed that aberrant activation of canonical Wnt signaling occurs in various forms of leukemia, and is crucial for chronic lymphocytic leukemia (CLL) pathogenesis. The aim of the study is to evaluate the influence of maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers (PPI-G4) on Wnt/ß-catenin pathway gene expression in CLL (MEC-1) cells and to compare these findings with those obtained with fludarabine (FA). Microarray data analysis reveals seven of 19 Wnt/ß-catenin pathway genes whose expression changes significantly during dendrimer and FA treatment: WNT10A, WNT6, and CDH1 among others. PPI-G4-M3 is already known to influence MEC-1 cell apoptosis and proliferation. The obtained results suggest that the reduction in cell survival under the influence of glycodendrimers and FA may be due to loss of Wnt signaling.

Assessment of rotation thromboelastometry parameters in patients with essential thrombocythemia at diagnosis and after hydroxyurea therapy.

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.