Assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease: a European perspective.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Plasma collection and supply in Europe: Proceedings of an International Plasma and Fractionation Association and European Blood Alliance symposium.

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling-up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients' needs for plasma-derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non-profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.

Safety profile of plasma for fractionation donated in the United Kingdom, with respect to variant Creutzfeldt-Jakob disease.

Plasma-derived medicinal products (PDMPs) are life-saving and life-improving therapies, but the raw material is in short supply: Europe depends on importation from countries including the United States. Plasma from donors resident in the United Kingdom has not been fractionated since 1999 when a precautionary measure was introduced in response to the outbreak of variant Creutzfeldt-Jakob disease (vCJD). Cases of vCJD have been far fewer than originally predicted in the 1990s. Since the introduction of leucodepletion in 1999, and accounting for the incubation period, more than 40 million UK-derived blood components have been issued with no reports of TT vCJD. In February 2021, the UK Government authorized manufacture of immunoglobulin from UK plasma. Following separate reviews concluding no significant difference in the risk posed, the United States, Australia, Ireland and Hong Kong also lifted their deferrals of blood donors with a history of living in the United Kingdom. Other countries are actively reviewing their position. Demand is rising for PDMPs, and Europe faces a threat of supply shortages. Industry and patient groups are clear that using UK plasma would bring significant immediate benefits to patients and to the resilience of the European supply chain. From this scientific review, we conclude that UK plasma is safe for fractionation and urge blood regulators and operators to take account of this safety profile when considering fractionation of UK plasma, and to revise their guidelines on the deferral of donors who have lived in, or received a transfusion in, the United Kingdom.

The EHA Research Roadmap: Transfusion Medicine.

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research 1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including eleven sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.

The Presence of Fungal and Parasitic Infections in Substances of Human Origin and Their Transmission via Transfusions and Transplantations: Protocol for Two Systematic Reviews.

BACKGROUND: The European Union Directives stipulate mandatory tests for the presence of any infections in donors and donations of substances of human origin (SoHO). In some circumstances, other pathogens, including fungi and parasites, may also pose a threat to the microbial safety of SoHO. OBJECTIVE: The aim of the two systematic reviews is to identify, collect, and evaluate scientific evidence for the presence of fungal and parasitic infections in donors and donations of SoHO, and their transmission via transfusion and transplantation. METHODS: An algorithmic search, one each for fungal and parasitic disease, was applied to 6 scientific databases (PubMed, EMBASE, Web of Science, Scopus, Cochrane Library [trials], and CINAHL). Additionally, manual and algorithmic searches were employed in 15 gray literature databases and 22 scientific organization websites. The criteria for eligibility included peer-reviewed publications and peer-reviewed abstract publications from conference proceedings examining the prevalence, incidence, odds ratios, risk ratios, and risk differences for the presence of fungi and parasites in donors and SoHO donations, and their transmission to recipients. Only studies that scrutinized the donors and donations of human blood, blood components, tissues, cells, and organs were considered eligible. Data extraction from eligible publications will be performed independently by two reviewers. Data synthesis will include a qualitative description of the studies lacking evidence suitable for a meta-analysis and a random or fixed-effect meta-analysis model for quantitative data synthesis. RESULTS: This is an ongoing study. The systematic reviews are funded by the European Centre for Disease Prevention and Control, and the results are expected to be presented by the end of 2021. CONCLUSIONS: The systematic reviews will provide the basis for developing a risk assessment for fungal and parasitic disease transmission via SoHO. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020160090; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160090 ; PROSPERO International Prospective Register of Systematic Reviews CRD42020160110; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020160110. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25674.

Pathogen reduction of blood components during outbreaks of infectious diseases in the European Union: an expert opinion from the European Centre for Disease Prevention and Control consultation meeting.

Pathogen reduction (PR) of selected blood components is a technology that has been adopted in practice in various ways. Although they offer great advantages in improving the safety of the blood supply, these technologies have limitations which hinder their broader use, e.g. increased costs. In this context, the European Centre for Disease Prevention and Control (ECDC), in co-operation with the Italian National Blood Centre, organised an expert consultation meeting to discuss the potential role of pathogen reduction technologies (PRT) as a blood safety intervention during outbreaks of infectious diseases for which (in most cases) laboratory screening of blood donations is not available. The meeting brought together 26 experts and representatives of national competent authorities for blood from thirteen European Union and European Economic Area (EU/EEA) Member States (MS), Switzerland, the World Health Organization, the European Directorate for the Quality of Medicines and Health Care of the Council of Europe, the US Food and Drug Administration, and the ECDC. During the meeting, the current use of PRTs in the EU/EEA MS and Switzerland was verified, with particular reference to emerging infectious diseases (see Appendix). In this article, we also present expert discussions and a common view on the potential use of PRT as a part of both preparedness and response to threats posed to blood safety by outbreaks of infectious disease.

West Nile and Usutu Virus Infections and Challenges to Blood Safety in the European Union.

West Nile virus (WNV) and Usutu virus (USUV) circulate in several European Union (EU) countries. The risk of transfusion-transmitted West Nile virus (TT-WNV) has been recognized, and preventive blood safety measures have been implemented. We summarized the applied interventions in the EU countries and assessed the safety of the blood supply by compiling data on WNV positivity among blood donors and on reported TT-WNV cases. The paucity of reported TT-WNV infections and the screening results suggest that blood safety interventions are effective. However, limited circulation of WNV in the EU and presumed underrecognition or underreporting of TT-WNV cases contribute to the present situation. Because of cross-reactivity between genetically related flaviviruses in the automated nucleic acid test systems, USUV-positive blood donations are found during routine WNV screening. The clinical relevance of USUV infection in humans and the risk of USUV to blood safety are unknown.

One Health approach for West Nile virus surveillance in the European Union: relevance of equine data for blood safety.

West Nile virus (WNV) infection is notifiable in humans and equids in the European Union (EU). An area where a human case is detected is considered affected until the end of the mosquito transmission season (week 48) and blood safety measures have to be implemented. We used human and equine case notifications between 2013 and 2017 to define the WNV distribution in the EU and to investigate the relevance of using equine cases as a complementary trigger for blood safety measures. Adding areas with equine cases to the definition of an affected area would have a major impact on blood safety measures. Adding areas with equine cases where human cases have been reported in the past would increase the timeliness of blood safety measures with only a limited impact. Although the occurrence of human and/or equine cases confirms virus circulation in the EU, no evidence was found that occurrence of equine cases leads to human cases and vice versa. We conclude that information about equine data should contribute to raising awareness among public health experts and trigger enhanced surveillance. Further studies are required before extending the definition of affected areas to areas with human and/or equine cases.

Hepatitis E and blood donation safety in selected European countries: a shift to screening?

The public health implications of hepatitis E virus (HEV) in Europe have changed due to increasing numbers of hepatitis E cases and recent reports of chronic, persistent HEV infections associated with progression to cirrhosis in immunosuppressed patients. The main infectious risk for such immunosuppressed patients is exposure to undercooked infected pork products and blood transfusion. We summarised the epidemiology of HEV infections among blood donors and also outlined any strategies to prevent transfusion-transmitted HEV, in 11 European countries. In response to the threat posed by HEV and related public and political concerns, most of the observed countries determined seroprevalence of HEV in donors and presence of HEV RNA in blood donations. France, Germany, Spain and the United Kingdom (UK) reported cases of transfusion-transmitted HEV. Ireland and the UK have already implemented HEV RNA screening of blood donations; the Netherlands will start in 2017. Germany and France perform screening for HEV RNA in several blood establishments or plasma donations intended for use in high-risk patients respectively and, with Switzerland, are considering implementing selective or universal screening nationwide. In Greece, Portugal, Italy and Spain, the blood authorities are evaluating the situation. Denmark decided not to implement the HEV screening of blood donations.

Prioritizing of bacterial infections transmitted through substances of human origin in Europe.

BACKGROUND: Bacteria are the pathogens most frequently transmitted through substances of human origin (SoHO). The European Centre for Disease Prevention and Control (ECDC) organized an expert consultation, with the objective of developing a priority list of bacterial pathogens transmissible via SoHO. The list will be used to further assess risks and determine appropriate preventive measures. STUDY DESIGN AND METHODS: The 14 most frequently SoHO-transmitted bacteria identified through a scoping literature review were then prioritized during an expert workshop through a methodology based on multicriteria decision analysis. The selection of the prioritization method was based upon an ECDC framework for best practices in conducting risk-ranking exercises. Three transmission pathways, blood and blood components, tissues and cells, and organs, were considered in the ranking exercise. RESULTS: According to the ranking score (RS), bacteria were organized within each SoHO pathway into one of four risk tiers: Tier 1 (RS ≥ 0.70), Tier 2 (RS = 0.60-0.69), Tier 3 (RS = 0.40-0.59), or Tier 4 (RS < 0.40). The most consistently identified pathogens in the highest risk Tiers 1 and 2 of all three pathways were: Staphylococcus aureus, Klebsiella spp., Escherichia coli, ß-hemolytic streptococci, Pseudomonas spp., and Acinetobacter spp. CONCLUSION: Six bacteria were defined as being of the highest priority in respect of the threat to the safety of SoHO and will be the subject of subsequent in-depth risk assessments to be conducted by ECDC to identify measures to mitigate the risk posed by these bacteria.

Selection strategies for newly registered blood donors in European countries.

BACKGROUND: Two selection strategies for newly-registered blood donors are available: a single-visit selection called the standard selection procedure (SSP), and a two-stage selection named predonation and donation screening (PDS). This study reviews the selection strategies for newly-registered donors currently applied in European countries. MATERIAL AND METHODS: We collected data on donor selection procedures, blood donation, laboratory screening and HIV, HCV and HBV positive donors/donations from 2010 to 2013 in 30 European countries by using questionnaires. We grouped the countries according to the applied selection strategy, and for each country, we calculated the 4-year prevalence of confirmed positive results indicating the presence of overall and recent HIV, HCV and HBV infections among first-time and repeat donations and among newly-registered donors. RESULTS: Most of the 24 countries (80%) apply the SSP strategy for selection of newly-registered donors. Twenty-two countries (73.3%) employ a nucleic acid amplification testing in addition to the mandatory serological screening. The survey confirms a higher overall prevalence of HIV, HCV and HBV infections among first-time donations and newly-registered donors than among repeat donations. In contrast, the prevalence of recently acquired HIV and HCV infections was lower among first-time donations and newly-registered donors than among repeat donations, but higher for recent HBV infections (6.7/105 vs 2.6/105 in the SSP setting and 4.3/105 vs 0.5/105 in one country using PDS). The relatively low numbers of infected donors selected by PDS impeded accurate assessment of the prevalence of recent infections in first-time donations. DISCUSSION: The data from European countries provide inconclusive evidence that applying PDS reduces the risk of donations being made in the diagnostic window of first-time donors. The impact of PDS on the risk of window-period donations and blood donor management needs further investigation.

Hepatitis E virus: Assessment of the epidemiological situation in humans in Europe, 2014/15.

BACKGROUND: Hepatitis E virus (HEV) is endemic in EU/EEA countries, but the understanding of the burden of the infection in humans is inconsistent as the disease is not under EU surveillance but subject to national policies. STUDY: Countries were asked to nominate experts and to complete a standardised questionnaire about the epidemiological situation and surveillance of HEV in their respective EU/EEA country. This study reviewed surveillance systems for human cases of HEV in EU/EEA countries and nominated experts assessed the epidemiology in particular examining the recent increase in the number of autochthonous cases. RESULTS: Surveillance systems and case definitions across EU/EEA countries were shown to be highly variable and testing algorithms were unreliable. Large increases of autochthonous cases were reported from Western EU/EEA countries with lower case numbers seen in Northern and Southern European countries. Lack of clinical awareness and variability in testing strategies might account for the observed differences in hepatitis E incidence across EU/EEA countries. Infections were predominantly caused by HEV genotype 3, the most prevalent virus type in the animal reservoirs. CONCLUSION: Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV.

Climate change projections of West Nile virus infections in Europe: implications for blood safety practices.

BACKGROUND: West Nile virus (WNV) is transmitted by mosquitoes in both urban as well as in rural environments and can be pathogenic in birds, horses and humans. Extrinsic factors such as temperature and land use are determinants of WNV outbreaks in Europe, along with intrinsic factors of the vector and virus. METHODS: With a multivariate model for WNV transmission we computed the probability of WNV infection in 2014, with July 2014 temperature anomalies. We applied the July temperature anomalies under the balanced A1B climate change scenario (mix of all energy sources, fossil and non-fossil) for 2025 and 2050 to model and project the risk of WNV infection in the future. Since asymptomatic infections are common in humans (which can result in the contamination of the donated blood) we estimated the predictive prevalence of WNV infections in the blood donor population. RESULTS: External validation of the probability model with 2014 cases indicated good prediction, based on an Area Under Curve (AUC) of 0.871 (SD = 0.032), on the Receiver Operating Characteristic Curve (ROC). The climate change projections for 2025 reveal a higher probability of WNV infection particularly at the edges of the current transmission areas (for example in Eastern Croatia, Northeastern and Northwestern Turkey) and an even further expansion in 2050. The prevalence of infection in (blood donor) populations in the outbreak-affected districts is expected to expand in the future. CONCLUSIONS: Predictive modelling of environmental and climatic drivers of WNV can be a valuable tool for public health practice. It can help delineate districts at risk for future transmission. These areas can be subjected to integrated disease and vector surveillance, outreach to the public and health care providers, implementation of personal protective measures, screening of blood donors, and vector abatement activities.

The influence of allogeneic platelet gel on the morphology of human long bones.

The aim of this study is to analyze the morphologic and functional change of human bone defect after its grafting with mixture of platelet gel and autologous cancellous bone. For one year, we have prospectively studied nine consecutive pa- tients, aged 25-73 y, with pseudoarthrosis of long bones, after unsuccessful initial surgeries. We have harvested can- cellous bone from patients' iliac crests and mixed with the ABO compatible allogeneic platelet rich plasma (PRP) gel. That mixture has been inserted in the bone defect, and surgically fixated. Radiologically, the defects achieved the bone morphology (the appearance of hazy callus) between 6th and 24th week. The time of functional recovery was varied, be- tween 12 and 40 weeks for partial weight bearing, and between 16 and 48 weeks for free limb mobility and full function of the limb. The overall healing of bone defect was 16 to 36 weeks. Two patients had complications of poor graft ingrowth and one with a reversible postsurgical nerve paresis. On the X-ray scans, solid and fast restoration of bone structure was notable, with excellent bone ingrowth, suitable for full weight bearing. The allogeneic platelet gel had no adverse effects. This method can be used for treating of long bone defects, because of its strong influence on restoration of normal bone morphology. Further investigation is required to establish efficiency relative to other methods.

Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: In an open-label blinded study, we compared intracoronary and transendocardial CD34(+) cell transplantation in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: Of the 40 patients with dilated cardiomyopathy, 20 were randomized to receive intracoronary injection and 20 received transendocardial CD34(+) cell delivery. In both groups, CD34(+) cells were mobilized by filgrastim, collected via apheresis, and labeled with technetium-99m radioisotope for single-photon emission computed tomographic imaging. In the intracoronary group, cells were injected intracoronarily in the artery supplying segments of greater perfusion defect on myocardial perfusion scintigraphy. In the transendocardial group, electroanatomic mapping was used to identify viable but dysfunctional myocardium, and transendocardial cell injections were performed. Nuclear single-photon emission computed tomographic imaging for quantification of myocardial retention was performed 18 hours thereafter. At baseline, groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number of CD34(+) cells was also comparable (105 ± 31 × 10(6) in the transendocardial group versus 103 ± 27 × 10(6) in the intracoronary group, P=0.62). At 18 hours after procedure, myocardial retention was higher in the transendocardial group (19.2 ± 4.8%) than in the intracoronary group (4.4 ± 1.2%, P<0.01). At 6 months, left ventricular ejection fraction improved more in the transendocardial group (+8.1 ± 4.3%) than in the intracoronary group (+4.2 ± 2.3%, P=0.03). The same pattern was observed for the 6-minute walk test distance (+125 ± 33 m in the transendocardial group versus +86 ± 13 m in the intracoronary group, P=0.03) and N-terminal pro-brain natriuretic peptide (-628 ± 211 versus -315 ± 133 pg/mL, P=0.04). CONCLUSIONS: In patients with dilated cardiomyopathy, transendocardial CD34(+) cell transplantation is associated with higher myocardial retention rates and greater improvement in ventricular function, N-terminal pro-brain natriuretic peptide, and exercise capacity compared with intracoronary route. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01350310.

Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up.

RATIONALE: CD34+ transplantation in dilated cardiomyopathy was associated with short-term improvement in left ventricular ejection fraction and exercise tolerance. OBJECTIVE: We investigated long-term effects of intracoronary CD34+ cell transplantation in dilated cardiomyopathy and the relationship between intramyocardial cell homing and clinical response. METHODS AND RESULTS: Of 110 dilated cardiomyopathy patients, 55 were randomized to receive CD34+ stem cell transplantation (SC group) and 55 received no cell therapy (controls). In the SC group, CD34+ cells were mobilized by granulocyte colony-stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and cells were injected in the artery supplying segments with the greatest perfusion defect. At baseline, 2 groups did not differ in age, sex, left ventricular ejection fraction, or N-terminal B-type natriuretic peptide levels. At 5 years, stem cell therapy was associated with increased left ventricular ejection fraction (from 24.3 ± 6.5% to 30.0 ± 5.1%; P=0.02), increased 6-minute walk distance (from 344 ± 90 m to 477 ± 130 m; P<0.001), and decreased N-terminal B-type natriuretic peptide (from 2322 ± 1234 pg/mL to 1011 ± 893 pg/mL; P<0.01). Left ventricular ejection fraction improvement was more significant in patients with higher myocardial homing of injected cells. During follow-up, 27 (25%) patients died and 9 (8%) underwent heart transplantation. Of the 27 deaths, 13 were attributed to pump failure and 14 were attributed to sudden cardiac death. Total mortality was lower in the SC group (14%) than in controls (35%; P=0.01). The same was true of pump failure (5% vs. 18%; P=0.03), but not of sudden cardiac death (9% vs. 16%; P=0.39). CONCLUSIONS: Intracoronary stem cell transplantation may be associated with improved ventricular function, exercise tolerance, and long-term survival in patients with dilated cardiomyopathy. Higher intramyocardial homing is associated with better stem cell therapy response.

Effects of intracoronary stem cell transplantation in patients with dilated cardiomyopathy.

BACKGROUND: We investigated clinical effects of intracoronary transplantation of CD34+ cells in patients with dilated cardiomyopathy (DCM). METHODS: Of 55 patients with DCM, 28 were randomized to CD34+ transplantation (SC group), and 27 patients did not receive stem cell therapy (controls). In the SC group, peripheral blood CD34+ cells were mobilized by granulocyte-colony stimulating factor and collected via apheresis. Patients underwent myocardial scintigraphy and CD34+ cells were injected in the coronary artery supplying the segments with reduced viability. RESULTS: At baseline, the 2 groups did not differ in age, gender, left ventricular ejection fraction (LVEF), or NT-proBNP levels. At 1 year, stem cell therapy was associated with an increase in LVEF (from 25.5 ± 7.5% to 30.1 ± 6.7%; P = .03), an increase in 6-minute walk distance (from 359 ± 104 m to 485 ± 127 m; P = .001), and a decrease in NT-proBNP (from 2069 ± 1996 pg/mL to 1037 ± 950 pg/mL; P = .01). The secondary endpoint of 1-year mortality or heart transplantation was lower in patients receiving SC therapy (2/28, 7%) than in controls (8/27, 30%) (P = .03), and SC therapy was the only independent predictor of outcome on multivariable analysis (P = .04). CONCLUSIONS: Intracoronary stem cell transplantation could lead to improved ventricular remodeling, better exercise tolerance and potentially improved survival in patients with DCM.

Association of CYP2C9 gene polymorphism with bleeding as a complication of warfarin therapy.

The aim of this study was to determine the association of bleeding as a complication of warfarin therapy with polymorphism of CYP2C9 gene (alleles 1, 2 and 3). The CYP2C9 is the main enzyme for warfarin metabolism. Study included 181 patients receiving warfarin for at least one month. Allele 1 of CYP2C9 gene (in 94.5%) and genotype *1/*1 (57.5%) prevailed. Allele 3 was found in 12.7% patients. Bleeding side-effects occurred in 18 patients (10%). Patients with allele *1 needed significantly higher maintenance warfarin dose (p=0.011). Those with allele *3 had significantly lower maintenance warfarin dose (p=0.005) and higher prothrombin time (PT) at induction (p=0.034). Bleeding occurred significantly more often in those with lower maintenance warfarin dose (p=0.017). Patients with allele *3 had increased risk of bleeding, with marginal significance (p=0.05). Polymorphism of CYP2C9 could determine dose of warfarin therapy and thus it could be related to the risk of bleeding complications. Allele *3 carriers need lower warfarin dose. Therefore, initially reduced warfarin induction dose in allele *3 carriers could avoid more prolonged PT and decrease the risk of bleeding complication.

Anti-inflammatory effects of exercise training in the early period after myocardial infarction.

The aim of this investigation was to determine the effect of exercise training on the levels of plasma cytokines and acute phase reactants in the early post acute myocardial infarction (AMI) period. Sixty patients were enrolled into this three-week cardiac rehabilitation study. The mean time from AMI was 7.08 +/- 1.60 days, and the patient mean age was 60 +/- 10 years. Subjects were randomly assigned to one of the two groups: the control group treated with standard measures, and the group with additional regular moderate-intensity exercise training. Physical activity was based on the ergospirometry test results. Apart from clinical follow-up and routine laboratory analysis we determined the levels of plasma cytokines: tumor necrosis factor (TNF-alpha), soluble TNF-alpha receptor 1 (TNF-alphaSR1), interleukin (IL)-8, IL-10, and acute phase reactants: high sensitivity C-reactive protein (hsCRP) and fibrinogen. The obtained results confirmed the hypothesis that the early post AMI period is an inflammatory state the intensity of which gradually decreases with standard treatment during the first month after AMI, while including patients into early exercise training improves their inflammatory profile by decreasing the level of acute phase reactant and TNF-alphaSR1.