Venous thromboembolism in antiphosholipid syndrome.

Antiphosholipid syndrome (APS) is defined by the presence of clinical and laboratory criteria, it means by presence of antiphospholipid antibodies. Venous thromboembolism belongs to the most frequent clinical manifestation of this syndrome. Here we summarised basic pathophysiological mechanisms of venous thrombosis and lung embolism development, epidemiology of APS, and also the situations when this syndrome should be considered. The possible difficulties of laboratory diagnosis and their therapy involvement are mentioned.

Hemorrhagic shock and treatment of severe bleeding.

Hemorrhagic shock is a severe complication of conditions that are accompanied by massive bleeding and is associated with high mortality and morbidity. The authors summarize the recent knowledge in the pathophysiology of coagulopathy in the course of its development and some options in treatment strategy.

Systemic inflammatory response with high CRP values as the dominant symptom of multiple myeloma.

A man aged 60 years was examined for intense inflammatory response, night sweats, subfebrile and later febrile temperatures and a weight loss of 18 kg in 7 months. CRP was 270 mg / l, i.e. more than 20 times the upper limit of the physiological range. Reactive leukocytosis (10 × 109/l), thrombocytosis (530 × 109/l), increased fibrinogen (greater than 7 g/l), and anemia with hemoglobin of 80 g/l were present. No infection or systemic autoimmune disease has been proven. The patient had normal renal function and had no osteolytic deposits detectable by FDG-PET/CT. The procalcitonin level was not elevated. The bone marrow examination revealed a 30-40% infiltration of proplasmacyte type with admixture of plasmablasts, expressing light chains λ. Monoclonal immunoglobulin IgA λ was at a low concentration of about 8 g/l and the ratio of free light chains κ/λ was 0.13. The extent of bone marrow infiltration and anemia met the criteria for the diagnosis of symptomatic multiple myeloma. Following initiation of the combination therapy using thalidomide, bortezomib and dexamethasone, the maximum decrease in the concentrations of monoclonal immunoglobulin, free light chains and CRP was observed already after the first 2 cycles of treatment. Later, during the following two 2 cycles, the disease began to progress again. The patient underwent successful stem cell collection after the application of cyclophosphamide 2.5 g/m 2 and leukocyte growth factor (G-CSF), and high-dose chemotherapy (melphalan 200 mg/m 2) with the support of stem cell transplantation. At 2 months following high-dose chemotherapy, CRP levels of the physiological range decreased, the blood count was normalized, and monoclonal immunoglobulin was not detectable. Conclusion: The chronic inflammatory response may be due to plasmocytary bone marrow infiltration even if there are no other symptoms of multiple myel-oma present, except for anemia which, however, also involves the inflammatory reaction. In this case, the systemic inflammatory reaction with high CRP levels signalled aggressive behaviour of the disease. Key words: CRP - multiple myeloma - procalcitonin - systemic inflammatory response.

[The current role of warfarin]. / Postavení warfarinu v soucasné dobe.

Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.

[Splanchnic vein thrombosis]. / Splanchnická zilní trombóza.

Splanchnic vein thrombosis (SVT) represents an unusual manifestation of venous thromboembolism. The etiological factors for SVT can be divided into local and systemic, frequently found concurrently. SVT can be the first presenting symptom in myeloproliferative neoplasms. SVT puts the patients affected in jeopardy of developing the intestinal infarction, impairing the liver function and portal hypertension development with the risk of potentially life-threatening gastrointestinal bleeding. The current guidelines emphasise the role of anticoagulation in acute splanchnic thrombosis. Considering the potentially fatal complications it is necessary to tailor the anticoagulant treatment individually. The duration of anticoagulant therapy is strongly dependent upon the risk evaluation of thrombosis recurrence. The article deals with the causes, diagnostic methods and aspects influencing the therapeutic strategy.Key words: anticoagulation - liver cirrhosis - portal hypertension - prothrombotic state - splanchnic vein thrombosis.

[New - direct oral anticoagulants: actual review]. / Nová - prímá perorální antikoagulancia: aktuální prehled.

In recent years the options of anticoagulant/antithrombotic therapy have extended with new - direct oral anticoagulants, comprising direct thrombin inhibitors (dabigatran etexilate) and direct factor Xa inhibitors (rivaroxaban, apixaban). These agents represent another progress towards "the ideal antithrombotic drug", and thus towards a safe and effective antithrombotic therapy. The following article provides actual review and recommendations for clinical practice, including laboratory assessment and management of emergency situations. The approval of idarucizumab as a specific antidote for dabigatran has marked an important step in safety of this treatment.Key words: apixaban - dabigatran - DOAC - NOAC - rivaroxaban.

Very rare near-haploid acute lymphoblastic leukemia resistant to immunotherapy and CAR-T therapy in 19-year-old male patient.

Near-haploid acute lymphoblastic leukemia is rare subgroup of the disease, which is very important due to very poor prognosis and resistance to treatment including novel monoclonal antibodies and CAR-T therapy.

Increasing procoagulant activity of circulating microparticles in patients with Philadelphia-negative myeloproliferative neoplasms: a single-centre experience.

Microparticles are small membrane fragments with dimension between 0.1 and 1 µm, which are released during cell activation or apoptosis, exposing the phospholipid phosphatidylserine and membrane antigens typical for cellular origin. Philadelphia-negative myeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis. Data from literature suggest an association between thrombosis and the procoagulant activity of microparticles. Association between the procoagulant activity of microparticles and the incidence of thrombosis was assesed in a group of 126 patients with Philadelphia-negative MPNs. Measurement of microparticles procoagulant activity was performed using a functional assay, namely the Zymuphen MP-activity (Hyphen Biomed, Neuville-sur-oise, France). A total of 539 samples were analysed within this group of patients, regardless of patients' state of health. A significantly higher circulating microparticles procoagulant activity was found in MPN patients as compared with the control group (P < 0.001). A pathological level of procoagulant activity was observed more frequently in patients with polycythaemia vera (88%, P = 0.002) than groups of patients with essential thrombocythaemia (73.2%) and primary myelofibrosis (68.3%); the same result was confirmed in patients with a history of venous thrombosis in comparison with patients without thrombosis (84.7 vs. 73.2%, P = 0.029). Patients without cytoreductive treatment had a higher activity of microparticles (P = 0.010). Furthermore, presence of JAK2 V617F mutation was associated with an increased procoagulant activity (P = 0.007), as well as the higher JAK2 V617F allele burden (P = 0.001). Further prospective clinical studies will be necessary to evaluate the clinical relevance of microparticles in the prediction hypercoagulable state in these patients.

Increased mean platelet volume and immature platelet fraction as potential predictors of thrombotic complications in BCR/ABL-negative myeloproliferative neoplasms.

BCR/ABL-negative myeloproliferative neoplasms (MPNs) are considered to be acquired thrombophilic conditions. Persistently enhanced platelet activation has been described in polycythaemia vera and essential thrombocythaemia (ET), and shown to contribute to a higher risk of arterial and venous thrombotic complications. Recent studies have shown that mean platelet volume (MPV) and immature platelet fraction (IPF) can serve as useful markers of platelet activation and increased risk of thrombosis. The aim of the present study was to investigate the relationship between these parameters and thrombotic events in BCR/ABL-negative MPN. MPV values in patients with BCR/ABL-negative MPN were significantly higher than MPV values of healthy individuals (P < 0.001). No significant difference in MPV or IPF was observed between groups of patients with and without thrombotic complications (P = 0.441; P = 0.110); the difference in IPF values was close to the significance level for patients with ET (P = 0.073). Higher values of IPF were more frequently detected in patients with JAK2 V617F positivity (P = 0.030). These patients had higher MPV more frequently than others, and this difference was close to the significance level (P = 0.056). Further studies should validate the use of platelet parameters to identify patients at high risk.

Second malignancies in philadelphia-negative myeloproliferative neoplasms-single-center experience.

AIM: The aim of this work was to retrospectively analyze patients with Philadelphia-negative myeloproliferative neoplasms through evaluation of frequency and characteristics of second malignancies (other than acute leukaemia and myelodysplastic syndrome). PATIENTS AND METHODS: Records of 172 patients were reviewed; an analysis was performed on data from 66 patients treated with hydroxyurea, 105 patients treated with other cytoreductive therapy, and 25 patients without treatment. RESULTS: A higher occurrence of second malignancies was found in the group treated with hydroxyurea (7.6%; other cytoreduction: 1.2%; without therapy: 0). After a median follow-up of 89 months in the hydroxyurea group, 13 patients developed second cancer during hydroxyurea therapy, located on the skin (68.75%) and other sites (31.25%). CONCLUSION: The incidence of second malignancies during hydroxyurea therapy in our cohort patient was significantly higher than the incidence of malignancies in the Czech population of corresponding age.

Generation of antigen-loaded dendritic cells in a serum-free medium using different cytokine combinations.

Dendritic cells (DCs) are antigen-presenting cells that play a critical role in the induction of cytotoxic T-lymphocytes. An optimal method for the generation of DC for clinical use remains to be established. The aim of our study was to find an optimal cytokine combination for DC generation from peripheral blood stem cells (PBSC) and peripheral blood mononuclear cells (PBMC) in serum-free conditions. Serial immunophenotyping enabled us to observe changes in DC content during the culture as well as the development of maturation and activation markers. As a source for DC culture, we used PBSC from patients with multiple myeloma after stem cell mobilization using cyclophosphamide and G-CSF, or PBMC from healthy donors without mobilization. The cells were cultured in a serum-free medium with different cytokine combinations including GM-CSF, TNF-alpha, Flt-3, CD40L, IFN-gamma, IL-1alpha, IL-6, PGE1, and IL-4. The cell cultures were evaluated by immunophenotyping. For PBMC, interleukin-12 assay was performed. For PBSC, the yield of DC as determined by CD83+ cell count ranged from 0. 6 x 10(5) to 30.1 x 10(4) (mean: 9.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated nucleated cells from apheresis. This yield corresponded to (0.3-19.1) x 10(5) (mean: 4.3 x 10(5)) per 1 x 10(6) of CD34+ cells in the apheresis products. For PBMC, the yield was (0.4-24.8) x 10(4) (mean: 2.4 x 10(4)) of DC generated per 1 x 10(6) of initially plated mononuclear cells from venous blood. The cultured cells expressed the mature immunophenotype. No significant differences in cell yield or immunophenotype were detected when comparing different cytokine combinations.