[Acute and chronic anticoagulation therapy in relation to joint replacements]. / Akutní a chronická antikoagulacní lécba u kloubních náhrad.

Thromboembolic disease (TED) is a considerable social and health problem. The solution evidently consists in the prevention of TED in clinical fields, not in the treatment itself. We can assume that effective prevention consequently reduces the cost of the following treatment. A lethal pulmonary embolism (PE) can be the first and the final clinical manifestation in patients with an asymptomatic deep venous thrombosis. This makes the systematic prevention of venous thromboembolism in higher risk patients necessary. Unfortunately, pharmacological prevention has been used less than would be needed. Inseparable from the TED prevention are physical methods. Pharmacological possibilities of the thromboembolic disease prevention were significantly extended within the past decade. To ensure the TED prevention after the total replacement (TEP) of hip and knee joints the following rules need to be observed: the TED prevention should be effected with LMWH, fondaparinux, dabigatran, rivaroxaban or apixaban for a period of 28-35 days after the hip joint replacement surgery and for 14 days after the knee joint replacement. The use of ASA, dextran and UFH as a thromboprophylaxis after the hip and knee joint TEP is not justified within the Czech Republic. Physical means (graduated compression stockings or IPC) can be used to support the recommended pharmacological treatment, they should not be used individually except in cases where pharmacological thromboprophylaxis is contraindicated.Key words: apixaban - dabigatran - LMWH - rivaroxaban - total hip and knee joint replacement - thromboembolic disease.

[Outpatient treatment of venous thromboembolic disease]. / Ambulantní lécba zilní plicní embolie.

Venous thromboembolic disease which includes both venous thrombosis and pulmonary embolism, is a frequent and potentially fatal disease. Based on the introduction of low-molecular-weight heparins (LMWH) into practice it has been proved that outpatient treatment of venous thrombosis is effective and safe for a large number of patients with VTE. The growing volume of data on LMWH outpatient treatment in recent years shows that up to 50 % of patients with clinically stable pulmonary embolism can be treated at home. In spite of these facts home treatment of pulmonary embolism has not been established as part of common practice as yet. If we were to summarize the conditions for home treatment, we would consider outpatient care for patients at low risk based on auxiliary criteria, free from hemodynamic instability (primarily without a shock state), free from right ventricular failure, prior chronic heart or lung disease, serious comorbidities (gastrointestinal tract disease, kidney disease, blood diseases, advanced cancers), at low risk of early thromboembolism recurrence, free from other indications for hospitalization (pain requiring parenteral analgesics, infections etc.), at low risk of bleeding and with guaranteed patients cooperation and well-organized home care.

Prevalence of hypercoagulable disorders in inflammatory bowel disease.

OBJECTIVE. Inflammatory bowel disease (IBD) can be associated with hypercoagulable disorders. Aim of this single-center, prospective study was an in-depth evaluation of acquired hypercoagulable states in IBD patients. METHODS. A total of 110 patients with Crohn's disease (CD) (aged 19-69; mean 40.5, median 38.5 years), 43 with ulcerative colitis (UC) (aged 17-72; mean 42, median 36 years), and 30 controls were enrolled. Full blood count, serum C-reactive protein (CRP), proteins C and S, activated protein C (APC) resistance, thrombin-antithrombin complex (TAT), F1+F2 fragments, tissue factor pathway inhibitor (TFPI) total and truncated, TFPI-factor Xa, tissue plasminogen activator (tPA) and PAI-I antigen were investigated in peripheral blood samples. RESULTS. Only 18 of 153 (11.8%) IBD patients had hemocoagulation parameters within normal range. Significant difference between IBD patients and controls was found in thrombocyte volume (p < 0.001), protein C (p = 0.025), protein S (p = 0.003), APC resistance (p < 0.001), F1+F2 fragments (p < 0.001), and tPA (p = 0.002). In CD patients who were divided into two subgroups according to serum CRP values (non-active disease: <5 mg/L; active disease ≥5 mg/L), thrombocyte count was significantly lower (p = 0.001), thrombocyte volume was significantly higher (p = 0.002), F1+F2 fragments were significantly lower (p = 0.007) and tPA was significantly higher (p = 0.038) in the subgroup with CRP <5 mg/L. In UC patients, no significant difference depending on CRP was found. CONCLUSIONS. Acquired hypercoagulable abnormalities in IBD patients are frequent. Patients with active CD, but not UC, displayed significantly different hemocoagulable parameters, when compared to non-active CD/UC subjects. In patients with active CD (with increased serum CRP concentration) and patients with active extensive UC found at endoscopy (despite low CRP values), prophylactic anticoagulation therapy should be considered.

ASPIRIN RESISTANCE IN NEUROVASCULAR DISEASES.

INTRODUCTION: The issue of resistance to antiplatelet therapy has raised many questions in the area of neurovascular diseases. The first objective of this work was to determine the prevalence of aspirin resistance in neurovascular patients with clinical non-responsiveness to aspirin treatment and a high-risk of atherothrombotic complications using two interpretable and independent methods (aggregation and PFA 100). The second objective was to find the correlation between both assays and to evaluate the results in groups at risk for various cerebrovascular diseases. MATERIAL AND METHODS: Laboratory tests of aspirin resistance were performed in 79 patients with clinical non-responsiveness to aspirin treatment suffering from neurovascular diseases. Patients were divided into the two groups: expected low risk for aspirin resistance due to the first manifestation of a neurovascular disease (n = 34) and expected high risk due to the second clinical manifestation of a neurovascular disease (n = 45). RESULTS: The prevalence of aspirin resistance in both groups combined as determined by the PFA-100 and CPG techniques were 50.6% and 17.7%, respectively. No correlation was found between the two techniques. CONCLUSIONS: No significant prevalence of aspirin resistance was demonstrated by either method despite the heterogeneous pathophysiological mechanisms. However, we are presently unable to provide an accurate opinion on the value of laboratory test result or routine monitoring in clinical neurology.

Fifteen years of single center experience with stem cell transplantation for multiple myeloma: a retrospective analysis.

INTRODUCTION: Autologous stem cell transplantation (ASCT) became standard of care for patients with multiple myeloma (MM) under the age of 65 years. We routinely perform ASCT for newly diagnosed MM since 1996 in our department. PATIENTS AND METHODS: We retrospectively analyzed all 285 transplants in 185 patients done for MM from January 1996 till December 2010. We analyzed overall survival (OS) and progression-free survival (PFS) regarding conditioning, stage, complete or very good partial remission (CR, VGPR) achievement, renal impairment, single vs. double transplant. RESULTS: Estimated 10-years survival of the whole set of patients is 39% (median survival 95 months). Patients with renal impairment show same OS as those without (p = 0.22). Patients show similar overall survival and event free survival regardless of type of transplant. We observed better outcome in terms of overall survival in patients treated with new drugs (p = 0.0014). Reaching CR or VGPR was not translated into better OS (p = 0.30) and EFS (p = 0.10). Also stage of the disease and whether single or double transplant was used did not make any significant difference in the outcome. CONCLUSION: Stem cell transplantation greatly improved outcome of patients with MM. Poor outcome of allogeneic transplantation in our group of patients is related to high transplant related mortality (20% vs. 0%) and unexpected high relapse rate. There is a trend towards better survival, when new drugs are incorporated at any time in the course of the disease. This fact supports hypothesis that use of these drugs with ASCT should translate into better long-term outcome.

Beneficial effect of plasma exchange in the treatment of toxic epidermal necrolysis: a series of four cases.

INTRODUCTION: Toxic epidermal necrolysis (TEN) is a rare, life-threatening disease with a high mortality rate that is linked to drug toxicity. There is a lack of data about the underlying pathophysiologic mechanisms and treatment options. The only widely accepted treatment of TEN is withdrawal of the offending drug followed by supportive care. The potential roles of corticosteroids, intravenous immunoglobulin (IVIG) and plasmapheresis (TPE) remain controversial. AIMS: We present four patients with severe TEN (all with >80% involvement of body surface) who were treated with TPE following unsuccessful treatment with corticosteroids/IVIG. METHODS: TPE was performed using a COBE Spectra blood cell separator. ACD-A was used as anticoagulant fluid and the target-washed plasma volume was one body volume. Plasma was replaced by a 5% solution of human albumin + Ringer's lactate. RESULTS: The mean number of TPE sessions was 5.25 ± 2.22 (range 3-8). Drugs were implicated as an etiologic agent in each case. TPE led to prompt improvement of acute condition and general health as well as halting of disease progression. Additionally, the restoration of the epithelium began in all four patients. CONCLUSION: Plasmapheresis should be considered as an alternative treatment modality for patients with the most severe form of TEN if initial treatment with other agents, including corticosteroids and/or IVIG, fails. Drugs were suspected to be the cause of TEN in all four cases.

Experience with extracorporeal elimination therapy in myasthenia gravis.

We describe our experience with plasma exchange (PE) and immunoadsorption in patients with myasthenia gravis. The group of 27 patients consists of 21 patients treated with PE and 6 patients who received immunoadsorption. PE therapy led to stabilization in 20 patients. In patients treated with immunoadsorption, therapy could be discontinued in 2 patients after 13 months of therapy, and the other 4 patients were stabilized without myasthenic crises after 6-9 years of therapy. Extracorporeal elimination therapy through PE or immunoadsorption is effective and sometimes life saving and is safe in the hands of an experienced team (6% complication rate).

Significant change in ZAP-70 expression during the course of chronic lymphocytic leukemia.

INTRODUCTION: It is widely accepted that expression of ZAP-70 in chronic lymphocytic leukemia (CLL) remains stable in time. However, data supporting this notion are surprisingly scarce. Therefore, we assessed expression of ZAP-70 in serial samples taken during the course of the disease. PATIENTS AND METHODS: We studied 44 patients with CLL diagnosed according to NCI-WG criteria (34 men, 10 women, median age 62, range, 36-81). A total of 104 samples were examined; all patients had at least two measurements. Median interval between the first and the second sample was 13 months (range, 2-36). ZAP-70 expression was detected by flow cytometry using phycoerythrin-conjugated monoclonal antibody clone 1E7.2 and negative isotype control. Twenty percent of positive cells were considered as the threshold of positivity. RESULTS: Significant change in ZAP-70 expression (i.e. from positivity to negativity and vice versa) was detected in 15/44 patients (34%). Interestingly, 7/8 patients whose ZAP-70 expression converted to positivity had unmutated IgVH genes. In addition, the conversion was accompanied by clinical progression or relapse in all but one patient. On the other hand, 5/7 patients with loss of ZAP-70 had stable clinical course. One patient became ZAP-70-negative during treatment with prednisone for autoimmune hemolytic anemia. CONCLUSIONS: In contrast to commonly accepted opinion, significant change in ZAP-70 expression in time was detected in a substantial proportion of our patients with CLL. While the conversion to ZAP-70 negativity was found predominantly in patients with stable disease, change to positivity was typical in patients with unmutated IgVH genes at the time of progression or relapse. Based on our pilot results, repeated assessment of ZAP-70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP-70-negative.

Biological prognostic markers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most frequent leukemic disease of adults in the Western world. It is remarkable by an extraordinary heterogeneity of clinical course with overall survival ranging from several months to more than 15 years. Classical staging sytems by Rai and Binet, while readily available and useful for initial assessment of prognosis, are not able to determine individual patient's ongoing clinical course of CLL at the time of diagnosis, especially in early stages. Therefore, newer biological prognostic parameters are currently being clinically evaluated. Mutational status of variable region of immunoglobulin heavy chain genes (IgVH), cytogenetic aberrations, and both intracellular ZAP-70 and surface CD38 expression are recognized as parameters with established prognostic value. Molecules regulating the process of angiogenesis are also considered as promising markers. The purpose of this review is to summarize in detail the specific role of these prognostic factors in chronic lymphocytic leukemia.

Long-term health outcome and mortality evaluation after invasive coronary treatment using drug-eluting stents: HOME DES registry.

AIM: To assess the occurrence of late clinical events after the discontinuation of dual antiplatelet treatment in patients with drug-eluting stent implantation, complex coronary artery disease and high clinical risk profile. METHODS: Between January 2004 and December 2005, 2080 patients underwent percutaneous coronary intervention, including 276 patients (13%) who were treated with drug-eluting stents. At the 6-month follow-up, 273 patients remained event-free and of these, 171 completed the 12-month and 18-month follow-ups and have been enrolled in the analysis. Dual antiplatelet treatment was administered for 6 months in all patients. RESULTS: At the 18-month follow-up, stent thrombosis had occurred in 10 patients (5.8%), resulting in five sudden deaths and five target-vessel nonfatal myocardial infarctions. The majority (80%) of the events had developed within 7-12 months. The larger stent area and left main interventions were significantly associated with stent thrombosis (P=0.031 and P=0.001, respectively). CONCLUSIONS: Our study confirmed worrisome results concerning drug-eluting stent thrombosis after the discontinuation of dual antiplatelet treatment. The rate of stent thrombosis-related events in our high-risk cohort of patients reached almost 6% with a 50% mortality. The majority (80%) of the events occurred within the months 7-12.

Safety and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia.

The aim of this work is to arbitrate the incidence of side effects and tolerability of long lasting LDL-apheresis in familial hyperlipoproteinemia. 1200 procedures were performed and the last 463 of them were evaluated. An immunoadsorption method of LDL-apheresis was used (continuous blood cell separator Cobe Spectra; secondary device: automated adsorption-desorption ADA, Medicap; absorption columns: Lipopak). As a whole, 6.26% adverse events were found and subsequently resolved by standard symptomatic therapy. Vaso-vagal reactions (symptoms of neurovegetative lability) were the most common adverse effects, presented as malaise, weakness, slight and short-term drop in blood pressure or other general signs. They were all well controlled by symptomatic therapy. We conclude that LDL-apheresis in the hands of experienced personnel is a safe procedure. An acceptable procedure duration limit, balancing the possibility to achieve a targeted cholesterol level while still maintaining an acceptable patient tolerance, was confirmed to be 4 hours.

Addition of rituximab significantly improves outcomes in patients with diffuse large B-cell lymphoma--a single-center, retrospective study.

CHOP chemotherapy has been used as a standard first-line treatment for diffuse large B-cell lymphoma since the 1970s. Phase III trials have shown that the addition of rituximab (R) to CHOP chemotherapy leads to significant improvements in response rate, progression-free survival and overall survival. This single-center, retrospective study was performed to evaluate the role of the addition of R to chemotherapy (CHT) in a real-world clinical setting. Outcomes were assessed in 85 patients with newly diagnosed DLBCL treated with CHT alone (n=38) and R-CHT (n=47). Complete response (CR) rates were significantly higher after R-CHT than CHT (93 % vs. 73 %; p=0.02). The relapse rate was significantly higher after CHT compared with R-CHT (38 % versus 12 %; p=0.01). Progression-free survival was significantly extended by the addition of R (median not reached versus 26.1 months; p=0.04). These data bring further support for rituximab-based immunochemotherapy as a standard first-line therapy for patients with DLBCL.

Monoclonal gammopathies in a series of 1743 plasma donors.

We carried out a retrospective analysis on a series of 1743 plasma donors during the period from January 1999 to February 2004 to determine the frequency of monoclonal gammopathies occurrence. In the whole group, we observed 0.68% occurence and in the subgroup of donors over 40 years of age even 1.18% occurrence of the serum paraprotein. We have presented our recommendations for the screening of monoclonal gammopathies in blood donors.

Analysis of thrombotic complications after catheter ablation.

INTRODUCTION: Thromboembolic complications are described in about 1% of the patients undergoing radiofrequency catheter ablation (RFA). The aim of this study was to analyze thrombotic complications after RFA and to determine prothrombotic states in patients with thrombotic complications. METHODS: We analyzed data from 400 patients (212 females) who underwent 453 RFA procedures for supraventricular tachycardias. Transthoracic echocardiography was performed one day before and after RFA in all patients. We evaluated the clinical and laboratory (in patients with thrombotic complications after RFA) risk factors of thromboembolism. RESULTS: We observed thrombotic complication in 7 (1.75%) patients (6 females), thrice flail thrombus in the right atrium, flail thrombus in the inferior vena cava, femoral vein thrombosis with massive pulmonary embolism, femoral vein mural thrombus and upper extremity digital arteries embolization; four of them were asymptomatic. As a prothrombotic state we identified factor V Leiden mutation in one case and the use of oral contraceptives in two cases. Two other patients had a positive history of thromboembolic events. In a subgroup of females the use of oral contraceptives (p = 0.13) or a positive history of thromboembolism (p = 0.21) were not identified as important risk factors. CONCLUSION: Echocardiographic detection of asymptomatic thrombotic complications contributed to the higher percentage of these complications in our study. Although we can identify the risk factor (laboratory or clinical) in a majority of patients with a thromboembolic complication, occurrence of these complications is unpredictable.

Chronic thromboembolic pulmonary hypertension after the first episode of pulmonary embolism? How often?

BACKGROUND: Surviving pulmonary embolism (PE) brings a risk of thromboembolic disease chronicity. Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a result of one or multiple pulmonary embolic events. It is an incapacitating long-term complication of thromboembolic disease with a negative impact on the patient's quality of life and prognosis. Contemporary pharmacological and especially surgical treatment possibilities offer hope for the patient's full recovery, but an early diagnosis is crucial for success. METHODS: In a prospective study cohort of 97 consecutive patients with a proven diagnosis of PE as the first documented thromboembolic event we tried to estimate the incidence of CTEPH during a 2-year follow-up. RESULTS: Four individuals from our study population developed CTEPH, which represents an incidence of 4.2%. CONCLUSION: Chronic thromboembolic pulmonary hypertension in pulmonary embolism survivors is a not uncommon complication deserving the attention of clinicians. Patients at risk of CTEPH can be identified for effective follow-up according to echocardiographic finding of elevated pulmonary artery systolic pressure and NT-proBNP levels at the time of hospital discharge.

Is radioiodine administration in patients with papillary thyroid multifocal microcarcinoma unnecessary?

UNLABELLED: Radioiodine (RAI) has played a crucial role in differentiated thyroid cancer treatment for more than 60years. However, the use of RAI administration in patients with papillary thyroid microcarcinoma (even multifocal) is now being widely discussed and often not recommended. In accordance with European consensus, and contrary to the American Thyroid Association (ATA) guidelines, we recently performed RAI thyroid remnant ablation in a patient with differentiated papillary multifocal microcarcinoma. The post-therapeutic whole-body scan and SPECT/CT revealed the real and unexpected extent of disease, with metastases to upper mediastinal lymph nodes. This finding led to the patient's upstaging from stage I to stage IVa according to the American Joint Committee on Cancer/International Union Against Cancer criteria. LEARNING POINTS: (131)I is a combined beta-gamma emitter, thus allowing not only residual thyroid tissue ablation but also metastatic tissue imaging.RAI remnant ablation omission also means post-treatment whole-body scan omission, which may lead to disease underestimation, due to incorrect nodal and metastatic staging.RAI should be considered also in "low-risk" patients, especially when the lymph node involvement is not reliably documented.Lower administered RAI activity (30mCi, 1.1GBq) may be a workable compromise in low-risk patients, not indicated for RAI remnant ablation according to ATA guidelines.

Optimization of the therapeutic procedure during LDL-apheresis--a computerized model.

UNLABELLED: LDL-apheresis is a very effective method for the treatment of resistant hypercholesterolemia when other therapy (dietary, or medication) fails. To maximize the efficacy of the LDL-absorbers we aimed to create a computerized model. PATIENTS AND METHODS: The therapeutic technique of immunoadsorption was used, applying a pair of columns, the Lipopak, Pocard, Russia. Plasma was separated by a continuous-flow plasma separator, the Cobe Spectra, USA; adsorption was controlled by adsorption-desorption equipment, ADA, Medicap, Germany. 494 LDL-apheresis procedures (treatment interval 17.5+/-1.6 days) were used to treat nine patients with primary hypercholesterolemia followed during the consecutive 3.6+/-0.5 years. Metabolism of LDL-cholesterol is known to be multicompartmental and dynamic, but for the short-time period of the procedure it can be simplified and one can calculate the procedure as a continuous filtration. We developed a program for procedure planning, using Microsoft Excel for Windows. Inputs inserted into the program include only basic patient data (mass, height, sex and initial plasma LDL level in mmol/l). RESULTS: The results show a very promising match between our planning of the procedures and the real laboratory results. The drop in calculated vs real plasma LDL-cholesterol level differ no more than +/-10%. CONCLUSIONS: Although our software does not take into account many well known details about the metabolism of cholesterol, in given conditions it can provide a fairly precise prediction of procedure parameters. It is also suitable for practical use, because it requires only a few commonly used and readily available input values. Immunoadsorption with Pocard absorbers is a potent and safe method of therapy in indicated patients.

Plasma concentrations of vascular endothelial growth factor and basic fibroblast growth factor in lymphoproliferative disorders.

Angiogenesis plays a major role in the development and progression of haematological malignancies. In our study we measured plasma concentrations of key angiogenic activators vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) using comercially available sandwich enzyme-linked immunosorbent assay (ELISA) in 37 patients with lymphoid malignancies and 20 healthy donors. We found a statistically significant increase in bFGF concentrations in patients with B-cell chronic lymphocytic leukemia (B-CLL, n=18) compared to the control group (median 118.8 vs. 9.3 pg/ml, p<0.001). However, we didn't find any significant difference in VEGF concentrations between B-CLL patients and the control group. There was also no significant increase in bFGF or VEGF in patients with multiple myeloma (n=7) and non-Hodgkin's lymphoma (n=12). Our pilot study shows that measurement of angiogenic activators in plasma is a feasible and reproducible method of angiogenesis assessment. Larger studies are needed for correlation between serum and plasma concentrations and detailed statistical evaluation including the impact on patients' survival.

Transplantation of bone marrow derived progenitor cells in acute myocardial infarction. The first results.

The intracoronary administration of autologous bone marrow cells (BMCs) has been shown to improve the left ventricle function in the course of acute myocardial infarction. Therefore we have started a clinical trial using transplantation of BMCs in the acute phase of myocardial infarction. The aim of our study is to assess the feasibility and safety of this procedure, and effect on the left ventricle function of these patients. We describe the first experience in two patients with acute myocardial infarction reperfused using direct stenting. The aspiration of bone marrow from the sternum provided sufficient amount of the cells for transplantation. No serious ischemia and no changes in coronary artery patency were detected after intracoronary infusion. The left ventricle ejection fraction was increasing throughout the time of three-month follow-up. No other complications (ventricular arrhythmias, reinfarction, thrombus formation) were detected.