[Prevention of venous thromboembolism: generally accepted guidelines]. / Prevence zilní tromboembolické nemoci: obecne platná pravidla.

This article summarizes the published data on the prevention of venous thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It is recommended to sort patients according the thrombosis risk and to make use of the standard prophylactic modes. In low risk patients, no specific thromboprophylaxis is needed. Patients with moderate risk levels are candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression. At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people after major orthopaedic surgeries and with a history of heparin induced thrombocytopenia over the past three months. An alternative to the administration of LMWH even after the end of the hospitalization can be warfarin in certain situations. The sole use of acetylsalicylic acid or Rheodextran is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis.

[Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology]. / Prevence zilní tromboembolické nemoci v chirurgii, v laparoskopické chirurgii, v cévní chirurgii a v urologii.

The article summarizes published data regarding the prophylaxis of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology. In surgical patients with low risk, no specific thromboprophylaxis is needed. Patients with moderate risk levels are the candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3 400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression (IPC). At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration (LDUH) over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people with a history of heparin induced thrombocytopenia over the past three months. The sole use of acetylsalycilic acid is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC is indicated only in those patients who undergo laparoscopic surgeries and who moreover display the additional thrombosis factors. Patients with additional risk thrombosis factors undergoing major venous reconstructions require prophylaxis with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low risk urologic surgery require no specific thromboprophylaxis. If they undergo a major intervention and/or they display additional risk thrombosis factors, they require the administration of LMWH or LDUH. Elastic panty-hose and/or intermittent pneumatic compression have the same indication as in abdominal surgeries.

[Hemorrhagic complications during warfarin treatment]. / Krvácivé komplikace pri lécbe warfarinem.

Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice.

[Heparin induced thrombocytopenia]. / Heparinem indukovaná trombocytopenie.

This article describes the pathogenesis, diagnostics, treatment and prevention of heparin induced thrombocytopenia (HIT). Although HIT is considered to be a hematological diagnosis, every physician who treats patients with heparin can encounter it in daily practice. It is even more probable that surgeons of any specialisation will meet with HIT patients. A section of them elude diagnostic detection. There are two forms of HIT - HIT I and HIT II. HIT I is caused by a direct pro-aggregation effect of heparin. It has no clinic significance. HIT II is an antidote mediated adverse reaction to heparin. Antidotes will generate only after the exposure to heparin. They are targeted against the platelet factor 4 and they act only at the presence of heparin. They may lead to the aggregation of thrombocytes in the vascular system (there is a decrease in thrombocyte count). This event can be accompanied by a development of venous or arterial thrombosis that can have a rapid and even fatal course. This fact clarifies the importance of HIT II diagnostics. Diagnosis of HIT II is based on recognizing of the typical decrease in thrombocyte count usually 1 day after heparin administration is initiated. Clinical manifestations are more likely in patients with already damaged endothelium. If thrombocyte count decrease is not connected with clinical manifestations, it is the so called isolated HIT II and in patients who display the signs of thrombosis, it is HIT II associated with thrombosis. The goal of this article is apart from implementing the recommendations of the 7th conference of the American Respiratory Society in real life also the exploration of the diagnostic and therapeutic limits (availability) in the Czech Republic.

A contribution to examination of propidium iodide and annexin V plasma cells indices in multiple myeloma.

The aim of this study was a contemporaneous measurement and a mutual comparison of plasma cells proliferative activity and grade of apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS) and various phases of MM i.e. smoldering (SMM), stable/plateau and active (progression/relapse) forms of this disease. The analyzed group of 197 patients consisted of 30 MGUS, 21 SMM, 82 patients examined at the time of MM diagnosis and 64 patients analyzed during various phases of the disease after previous chemotherapy. Plasma cell proliferative activity was measured by means of a propidium iodide index (PC-PI) examined by flow cytometry using a DNA/CD138 double staining technique. For detection of plasma cells entering apoptosis (PC-AI) flow cytometry method with annexin V FITC and MoAb CD138 was used. The individuals with MGUS, SMM and stable/plateau form of MM had overall low levels of PC-PI (M-1.8, 1.7% and 2.1%) and relatively high levels of PC-AI (M-9.1, 10.8 and 9.0%). The correlation between PC-PI and PC-AI was in all the groups mutually highly statistically significant (p=0.000). Analysis of plasma cells proliferative activity (PC-PI) was statistically significant in comparison of MGUS or SMM and versus: patients examined at the time of MM diagnosis (p=0.018 or 0.016); patients evaluated during various phases of MM after previous chemotherapy (p=0.021 or 0.019); stable/plateau MM phase in the cohort of all patients (p=0.017 or 0.040); in the plateau phase after chemotherapy (p=0.008 or 0.024) but insignificant in comparison of MGUS and SMM and with the stable group examined at the time of MM diagnosis. Analysis of the apoptotic process revealed significant differences when comparing PC-AI of SMM but not MGUS group versus all cohort of stable/plateau MM patients (p=0.045); there were also insignificant differences in comparison of MGUS and SMM groupsand versus the stable form of MM measured at the time of MM diagnosis or plateau phase after chemotherapy. There was observed a statistically significant difference in the PC-AI in comparison of SMM group versus group of all patients examined at the time of MM diagnosis (p=0.001) or in various phases of this disease (p=0.015) and the group of MGUS patients compared with patients evaluated at the time of MM diagnosis (p=0.03). Very significant statistical differences of plasma cell proliferative (PC-PI) and apoptotic (PC-AI) activity were found when comparing the levels of both the indices of MGUS, SMM and stable/plateau MM group versus the active (progression/relapse) form of MM marked by a higher level of PC-PI (3.2%, p=0.000) and PC-AI (4.8%, p=0.000) in the whole cohort of MM patients, but also in comparison with both the active forms at the time of MM diagnosis or active forms evaluated during various phases of the disease after chemotherapy. Highly significant inverse relationship between PC-PI versus PC-AI was also revealed in the group of patients in the active (progression/relapse) phase of MM (p=0.000). These results revealed importance of measurement not only of proliferative but also of apoptotic plasma cells indices for a complex evaluation of the cells kinetics of plasma cells compartments in patients with MGUS or MM. This study confirmed the initial hypothesis of a common 'inverse relationship between the proliferative (PC-PI) and the apoptosis activity (PC-AI) in plasma cells compartments in patients with MGUS, smoldering, stable/plateau and active (progression/ relapse) forms of MM'.

[Therapeutic results and changes in prognosis in patients with multiple myeloma in central and northern Moravia over the past 40 years]. / Výsledky lécby a zmena prognózy nemocných s mnohocetným myelomem v období predchozích 40 let v oblasti strední a severní Moravy--rozbor souboru 562 nemocných.

OBJECTIVE: The objective of the investigation is evaluation of therapeutic results and the development of the prognosis of patients with multiple myeloma (MM) as a result of consecutive changes of therapeutic procedures in patients of central and northern Moravia in the course of the last 40 years. METHODS AND RESULTS: The analyzed group of 562 patients with MM was concentrated at the Ist and IIIrd Medical Clinic of the Faculty Hospital Olomouc in 1959 - 2000, median age 63 (28-91) male/female ratio 1.1: 1.0. From analysis of Kaplan-Meier survival curves and the results of statistical analysis (log rank test p = 0.0000) ensued that during the evaulated period a very substantial change of prognosis occurred with improvement of theraupeutic results and a significant prolongation of survival in general. The first " turning point" was the introduction of chemotheraphy with alkylating substances with Prednisone (1963-1975), leading as compared with the period of symptomatic treatment alone (1959-1063) to a significant prolongation of the media value of general survival (M) from 8 to 19 months (p = 0.0031) and 3-year survival from 4 to 23 % patients, whereby 10-year survival was only 0 % and 1 %. The second "turning point" was the period from 1976 - 1980 with introduction of systematic chemotherapy using conventional doses of polychemotherapeutic (CP) regimes with better opportunities of supporting treatment (M = 40 months, p = 0.0000; 3-year and 10-year survival 55% and 5.5% patients). The therapeutic results acheived during the subsequent 15 years were however an unsatisfactory advance. During the interval between 1976-1995 in a group of 295 patients divided into 5-year sub-periods remission was acheived (R = < 25 % of the baseline value of M-protein) in 10-24 % patients, an inadequate response (NR) = persistence in > 50 % M-protein) in 55-28 %, prolongation of the median of total survival in 232 of the accessble patients for 44 months and long-term survival of 5 - 10 years after establisment of the diagnosis increased from 25 to 36 % and from 5.5 to 16.5 % patients. The third "turning point" was 1996 characterized by the introduction of high-dosage chemotheraphy with transplantation of autologuos peripheral haematopoietic cells ("HD" therapy with ASCT) leading ina group of so far only 33, assessable patients under 65 years to acheived remission in 71 %, to decline of NR in 10 % only and 5 -year suvival so far in 91 % patients ( p = 0.0037). Improvement of therapeutic results and prognosis of the disease as compared with 1976 - 1995 occurred in the whole group of patients also in 1996 - 2000 (CP and "HD"-therapy with ASCT) characterized by remission in 36 %, NR IN 33 % and 5 -year survival in 57 % (p = 0.030). It was reveled that the application of "HD" theraphy with ASCT led in 1995-2000 to the acheivement of more favorable therapeutic results (R - 71 % NR - 10 %. 5-year survival after the interval which elapsed so far 91 %), as compared with 2 similar groups of subjects under 65 years meeting the criteria of "HD" theraphy with ASCT, but treated only by conventional polychemotheraphy (1991 - 1995 and 1996 - 2000: R - 24 and 32 %, NR - 42 and 23 %, 5-year survival 46 and 68 % of the patients). In the group of 148 patients from the period of 1991-2000 the patients had as regards remission (R) more favourable results as compared with patients with NR concerning the prognosis [M 63 vs.22 months, 5-year and 10-year survival 53 vs. 17 % and 17 vs. 0 % of patients (p = 0.0000)]. CONCLUSION: From the submitted analysis ensured that during the period form 1959 - 2000 in patients with mutiple myeloma in central and northern Moravia as a result of the application of modern methods of chemotheraphy and supporting treatment a significant improvements of results of conventional treatment occurred with a more than 5 fold prolongation of so far assessable median values of survival (8 - 44 months) and long-term 10-year survival of almost one sixth of the patients. The real asset of "HD" theraphy with transplantation of ASCT will be revealed by analyses made after a longer time interval.

[Quality of life and tolerance of maintenance therapy in patients with multiple myeloma]. / Kvalita zivota a tolerance udrzovací lécby u pacientu s mnohocetným myelomem. Ceska myelomova skupina.

Questionnaires on the quality of life and tolerance of different parts of maintenance treatment were sent to a total of 83 patients with multiple myeloma. All patients were for more than one year on maintenance treatment which involved either interferon alpha monotherapy (I), 3 million u. three times per week till signs of relapse developed or sequence administration of interferon alpha and dexamethazone 40 mg on day 1 to 4, 10 to 13 and 20 to 23 and then after a four-week interval again interferon alpha, again till progression of the disease occurred. The patients evaluated the presence or absence of different undesirable effects of treatment during the first two weeks of treatment and throughout the year and listed their intensity into four categories defined in the questionnaire. The quality of life was evaluated by means of a basic module of the questionnaire of the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30). The results of the questionnaire are to a certain extent surprising as from the patients' answers ensues that this maintenance treatment is associated with more numerous undesirable effects than the physicians realized when in contact with the patient. In this summary we can list only the most frequent effects (deterioration of eyesight, impaired sleep, depressions, irritability and unrest, chill, pain in muscles and joints, general weakness and dyspnoea). From the questionnaires on the quality of life ensues a markedly poorer quality of life of these patients as compared with the healthy population. There are however no basic differences between individual groups. The questionnaires were handed only to patients who had maintenance treatment for more than one year and thus patients were eliminated where maintenance treatment was discontinued because of undesirable effects. To give a general idea of the tolerance of the above maintenance treatment the authors mention that to the date of Aug. 31, 2001 113 patients were randomized into one of the branches of maintenance treatment. Maintenance treatment had to be discontinued in 6% patients (in two instances on account of severe hypothyroidism, in one case on account of hallucinations, in three instances on account of severe mental depression caused by this treatment). Reduction of interferon doses in 20% patients usually because of cytopenia but also on account of psychic problem. To the question what length of prolongation of life compensates the undesirable effects of maintenance treatment the following replies were obtained from patients receiving ID, possibly I: 3 months--47.6 and 38.3%, 6 months--4.3 and 10.6%, 9 months--0 and 4.3%, 12 months--47.6 and 46.8% of the addressed patients. In reply to the question whether the patients would prefer, assuming equal effectiveness, a maintenance monotherapy with interferon alpha or dexamethazone more patients preferred interferon to dexamethasone. For practice ensues from this article informing on undesirable effects of maintenance treatment and the effect of maintenance treatment on the quality of life: 1. the necessity of thorough knowledge of physicians of all possible undesirable effects as only a doctor knowing possible undesirable effects of treatment can recognize them, 2. regular monitoring not only of the activity of the basic disease, but also undesirable effects of maintenance treatment and the influence of treatment on the patients' quality of life, 3. the necessity to assess the quality of life in clinical trials as an important parameter for deciding on the way of treatment.

[Autologous transplantation of peripheral hematopoietic cells and subsequent maintenance therapy with interferon alpha or interferon alpha and dexamethasone in patients with multiple myeloma--results from the 4W randomized clinical trial of the Czech Myeloma Group]. / Autologní transplantace periferních hemopoetických bunek a následná udrzovací terapie interferonem alfa nebo interferonem alfa a dexamethasonem u nemocných s mnohocetným myelomem--prubezné výsledky randomizované klinické studie 4W Ceské myelomové skupiny.

In the clinical 4W study patients with newly diagnosed multiple myeloma are included where the state of the disease calls for treatment, while high dose chemotherapy is not contraindicated. Treatment according to protocol 4W comprises induction chemotherapy VAD, mobilization of haematopoietic cells (cyclophosphamide 5 g/m2). This is followed by autologous transplantation (as a conditioning regime melfalan 200 mg/m2 is administered). The patients are randomized into two groups, the first one is given interferon alpha as maintenance treatment, in the second group alternates cyclically interferon alpha and dexamethasone treatment. So far between 1996 and Aug. 31 2000 in the 4W clinical study 167 patients were included. 113 patients after transplantation were evaluated incl. 13 (12%) who achieved complete remission of the disease (absence of paraprotein, negative immunofixation), 63 patients (56%) with remission of the disease (decline of paraprotein, by more than 75%). Another 24 patients (21%) achieved partial remission (decline of paraprotein by more than 50% but less than 75%). The peritransplantation mortality is 2.67%. So far there is no significant difference between the two groups on maintenance treatment as regards the mean period before a relapse of the disease (p = 0.567). The median of the mean survival was not reached so far. The authors describe the results of the internal analysis of data incl. statistical processing.