scholarly journals Higher baseline lipid levels amplify the benefit of secondary prevention therapy with statins in Chinese patients with acute coronary syndrome

2020 ◽  
Vol 48 (11) ◽  
pp. 030006052096584
Author(s):  
Ling Zhu ◽  
Ying Liu ◽  
Wei Zhang ◽  
Zhu Zhang ◽  
Liqin Zhou ◽  
...  

Objective Statins are recommended as the first-line treatments for reducing the risk of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). The present study aimed to establish the baseline lipid levels associated with the greatest benefit from statin therapy in this population. Methods The study used a retrospective cohort methodology. In total, 636 patients with ACS were enrolled at Shaanxi Provincial People’s Hospital from 2011 to 2013. Participants were divided into four groups (group 1, hyperlipidemia with inconsistent statin use; group 2, no hyperlipidemia with inconsistent statin use; group 3, no hyperlipidemia with consistent statin use; and group 4, hyperlipidemia with consistent statin use). Results Patients in groups 3 (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.29–0.82) and 4 (HR = 0.21, 95% CI = 0.10–0.45) had lower risks of MACE than those in group 1. In subgroup analysis, patients in group 4 had a lower risk of MACE than those in group 3 (adjusted HR = 0.43, 95% CI = 0.21–0.89). Conclusion Sustained statin therapy is associated with a lower risk of adverse outcomes in patients with ACS, especially in those with higher baseline lipid levels.

2019 ◽  
Vol 5 (2) ◽  
pp. 156-160
Author(s):  
Md Mahboob Morshed ◽  
Md Joynul Islam ◽  
ATM Ashadullah ◽  
Khondker Shaheed Hussain ◽  
Mohammad Ahtashamul Haque

Background: Different risk factors may be related with the haemoglobin and CRP level among the acute coronary syndrome patients. Objective: The purpose of the present study was to see the association of haemoglobin and CRP level with different type of risk factors among the acute coronary syndrome patients. Methodology: This cross-sectional study was conducted in the Department of Cardiology at Mymensingh Medical College, Mymensingh, Bangladesh from December 2010 to November 2011 for a period of two (02) years. Patients of ACS who were presented within 12 hours of chest pain were included as study population. Study population were categorized in four groups according to the level of hemoglobin and C-reactive protein. Age, cardiovascular risks factor, history, family history of cardiovascular disease, treatment history and ECG were taken during admission. Blood sample was collected for baseline laboratory investigations like Troponin-I, Random Blood Sugar (RBS), Blood urea, Serum creatinine, lipid profile, Hemoglobin & CRP level. Sample were then send to standard laboratory/Biochemistry department of MMCH. Result: The mean age of the population was 52.18±8.88 years. Smoking was the highest percentage in Group 1 which was 54(50.0%) cases (P=0.001). Hypertension was found most common in group 1 (47.6%), Group 2 (33.3%), Group 3 (10.7%) and Group 4 (8.3%). Smoking (p=0.001) and hypertension (p=0.016) was found statistically significant. Diabetes was found in Group 1 (37.7%), Group 2 (43.5%), Group 3 (11.6%) and Group 4 (7.2%). Group 1 (50%) and Group 2 (50%) patients were dyslipidaemic. Family history of IHD was present group-1 (36.8%), Group 2 (44.7%), Group 3 (73.2%) and Group 4 (53%). Among the smoker patient 65.6% cases had CRP level ˃12 mg/l; 39.8% cases had CRP level ˂12mg/L. Among the nonsmoker 34.4% cases had CRP level ˃12mg/l and 60.2% cases had CRP level ˂12mg/L. The finding was statistically significant. Conclusion: In conclusion haemoglobin and CRP level is associated with different type of risk factors among the acute coronary syndrome patients. Journal of National Institute of Neurosciences Bangladesh, 2019;5(2): 156-160


2009 ◽  
Vol 3 ◽  
pp. CMC.S2289 ◽  
Author(s):  
Taysir S. Garadah ◽  
Salah Kassab ◽  
Qasim M. Al-Shboul ◽  
Abdulhai Alawadi

Recent studies indicated a high prevalence of hyperglycemia in non-diabetic patients presenting with acute coronary syndrome (ACS). However, the threshold of admission glucose (AG) as a predictor of adverse events in ACS is unclear. Objective The aim of this study was to assess the threshold of admission glucose (AG) as a predictor of adverse events including Major Acute Cardiac Events (MACE) and mortality, during the first week of admitting patients presenting with ACS. Material and Methods The data of 551 patients with ACS were extracted and evaluated. Patients were stratified according to their blood glucose on admission into three groups: group 1: <7 mmol/L (n = 200, 36.3%) and group 2: >7 mmol/L and <15 mmol/L (n = 178, 32.3%) and group 3: ≥15 mmol/L (n = 173, 31.4%). Stress hyperglycemia was arbitrarily defined as AG levels > 7 mmol/L (group 2 and 3). Patients with ACS were sub-divided into two groups: patients with unstable angina (UA, n = 285) and those with ST segment elevation myocardial Infarction (STEMI, n = 266) and data were analyzed separately using multiple regression analysis. Results The mean age of patients was 59.7 ± 14.8 years and 63% were males. The overall mortality in the population was 8.5% (5.4% in STEMI and 3.1% in UA) patients. In STEMI patients, the odds ratio of stress hyperglycemia as predictor of mortality in group 3 compared with group 1 was 3.3 (CI 0.99-10.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.75-8.07, P = 0.065) after adjustment for age and sex. Similarly, in UA patients, the odds ratio of stress hyperglycemia in group 3 compared with group 1 was 2.7 (CI 0.37-18.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.4-15.2, P = 0.344) after adjustment for age and sex. The incidence of more than 2 MACE in both STEMI and UA patients was higher in group 3 compared with the other two groups. Regression analysis showed that history of DM, high level of LDL cholesterol, high level of HbA1c, and anterior infarction were significant predictors of adverse events while other risk factors such as BMI, history of hypertension and smoking were of no significance. Conclusion This study indicates that the stress hyperglycemia on admission is a powerful predictor of increased major adverse events and hospital mortality in patients with acute coronary syndrome.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shao-Yuan Chuang ◽  
Jonathan Jiunn-Horng Chen ◽  
Chih-Cheng Wu ◽  
Wen-Harn Pan

Few studies examine the association between serum uric acid (SUA) and acute coronary syndrome (ACS). We aimed to investigate the association between SUA and ACS in a prospective study of ethnic Chinese. Enrolled were 128569 adults ≥ 20 yrs from 4 MJ Health Checkup Clinics in Taiwan during 1994 –1996, excluding those with heart disease, stroke, renal disease and cancer disease. All physical examination, biochemical test and structured questionnaire were executed in standardized central labs. ACS was defined by main ICD-9 of 410 – 414 from claim data of National Health Insurance for hospitalization and from Death certification registry. Cox proportional hazard model was used to estimate the hazard ratios (HRs) between levels of SUA and ACS events. A total of 2049 subjects (Men: 1239/Women: 810) developed ACS during the period from baseline to Dec.31.2002. Men had higher ACS incidence than women (2.84 vs. 1.61 per 1000 person-years [PY]; p < .0001). Independent risk factors of ACS unfolded from this study included age, male sex, waist circumference, body mass index, triglycerides, total-cholesterol, hypertension, diabetes, uric acid, and current smoking. The crude incidences of ACS were 1.27, 2.06, 3.27 and 4.61 per 1000 PY in that order for four consecutive SUA groups (group1: <5.0 mg/dl; group 2: 5.0 – 6.9 mg/dl; group 3: 7.0 – 8.9 mg/dl; group 4: ≥9.0 mg/dl) (p-value for trend <.0001). Compared to group1, the multi-variate adjusted HRs (95% Confidence intervals) were 1.14 (0.92, 1.42) for group 2, 1.38 (1.10, 1.72) for group 3 and 1.38 (1.10, 1.72) for group 4 among men, and 1.03 (0.87, 1.22), 1.30 (1.05, 1.62) and 1.43 (0.99, 2.05) among women after adjusting for age, systolic/diastolic BP, body mass index, triglycerides, total cholesterol, diabetes, smoking, alcohol drinking, physical activity, and occupation. One standard deviation increase in SUA corresponded to around 30% ACS risk increase in women (HR=1.33; 1.04 –1.70) and 60% in men (HR=1.59; 1.25–2.03). Baseline SUA level independently predicts the development of ACS and should be considered as a potential risk factor of ACS.


2019 ◽  
Vol 63 (1) ◽  
pp. 29-34
Author(s):  
Olesya V. Sagaydak ◽  
E. V. Oshchepkova

Introduction. Today there is no method to assess whether number of PCI-capable centers in Russia corresponds to the real needs. The aim of the study was to develop a PCI-capable hospitals necessity calculation algorithm. Material and methods. We used population densities, maximum/optimal distances (areas) to which delivery of patients with acute coronary syndrome by sanitary transport is possible and maximum/optimal areas where patients can be transported by ambulance transport. Then we calculated the density threshold values: Group 1: 53 persons/km2 or more; Group 2: 53-27 people/km2; Group 3: 27-18 people/km2; Group 4: 18-8 people/km2; Group 5: 8 persons/km2 and less. Results. Formulas were proposed for calculating the need for PCI-centers. For group 1: population/60000 people, for group 2: area/11,310 km2, group 3: area/31,416 km2, group 4 with functioning of sanitary aviation: area/70,686 km2 (additional strengthening of the prehospital medical care); in the absence of functioning sanitary aviation: area/31,416 km2 (also additional strengthening of the pre-hospital stage of medical care); for group 5: population/600,000 in large cities (in addition, the use of sanitary aviation, increased prehospital medical care, the organization of primary vascular departments). Discussion. The existing amount of percutaneous interventions in Russia is not enough to meet the real needs for this treatment. At the same time, simple multiplying of PCI-centers is not expedient. Conclusion. According to the developed algorithm, in Russia it is necessary to organize 239 PCI-centers 24/7. In regions with a high population density it is possible to combine several cathlabs in one center.


2020 ◽  
Vol 5 ◽  
pp. 16-21
Author(s):  
Dmytro Dziuba ◽  
Serhii Veremchuk ◽  
Oleh Loskutov

Percutaneous x-ray endovascular angioplasty is one of the most modern methods of treatment of severe forms of cardiovascular diseases. In the pathogenesis of acute coronary syndrome, a special place is occupied by the proinflammatory reaction of the body. The main “secondary” marker is interlekin-6. The peak of its production occurs on the first day of damage and correlates with its size. The aim of the study. To investigate the dynamics of interleukin-6 level in the perioperative period of coronary revascularization, depending on the presence of acute coronary syndrome. Materials and methods. This study included 68 patients with coronary artery disease. The patients were divided into three study groups. Group 1 and 2 patients were diagnosed with ACS, and they underwent emergency stenting of coronary vessels in order to recanalize occlusion of the coronary arteries. 3rd group patients did not have ACS and they were recanalized as planned. Results. Analyzing the results of the study, we found that the highest obtained values of IL-6 were in group 1 in comparison with the group of patients who were surgically treated as planned and after stent placement, the interleukin values were 24.8 % higher in group 1 than in group 2 and almost 4 times higher in group 3 (p<0.001). When comparing groups with acute coronary syndrome, interleukin-6 indices were significantly higher by 47.4 % before surgery in group 3 and by 24.9 % after stent placement, which once again confirms the severity of patients with acute myocardial infarction. Conclusions. Intraoperatively proinflammatory interlekin-6 after coronary artery stenting tends to increase in groups with acute coronary syndrome, while in the group with stable angina, these indicators are significantly higher by 22.8 % (p <0.001). The dynamics of Il-6 levels clearly correlates with the severity of the patient's condition and increases in the presence of acute coronary syndrome, especially in the presence of acute myocardial infarction.


2018 ◽  
Vol 33 (2) ◽  
pp. 21-25
Author(s):  
E. I. Tsoi ◽  
E. V. Vyshlov ◽  
V. B. Trusov

The article shows the results of the study using drug Ropren in the patients with acute coronary syndrome. Ropren is  a plant drug containing polyprenols — dolichol precursors which take part in dolichol phosphate pathway. The pathology in this pathway leads to disbalance and glycoprotein deficiency. This is the reason of large group of diseases. This study is randomized double blind placebo controlled (No. NCT03122340 at ClinicalTrials.gov). Patients (n=68) with ACS taking standard therapy including atorvastatin 40 mg/day were randomized into to 2 groups: group 1 (n=34) took Ropren  8 drops 3 times per day for 3 week, then 5 drops 3 times per day for 5 weeks; group 2 (n=34) took placebo in the same dose regimen. After two — month therapy there was a positive dynamic (decreasing) in the level of interleukin-6 in the study group whereas in the control group there was no statistically significant change: 4.36 (2.61, 8.95) and 5.5 (3.3; 8.4) pg/ml, respectively (p<0.05). In the group of patients taking Ropren the reduction or cessation of statin was required significantly less than in the placebo group: 3 (8.8%) vs 9 (26.5%), respectively. One patient from the first group had a side effect in the form of gravity in the right hypochondrium. That is why the administration of Ropren in addition to standard therapy is reasonable in patients with ACS.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 719-719
Author(s):  
Madiha Naseem ◽  
Manwah Yeung ◽  
Suruthi Senthilvel ◽  
Pooya Dibajnia ◽  
Doshina Naila ◽  
...  

719 Background: Patients with locally advanced rectal cancer (LARC) undergo surgery at 6-8 weeks after neoadjuvant chemoradiation based on standard protocol. However, the optimal time to undergo surgery remains debatable. The goal of this study was to identify associations between time to surgery and additional variables with overall survival (OS) and recurrence rates in LARC patients. Methods: A retrospective chart review was conducted for 80 LARC patients with T3 or node positive disease, who have undergone neoadjuvant chemoradiation and surgery at St. Michael’s Hospital from January 1st 2005-December 31st 2015. Patients were divided into 4 groups based on time to surgery: 4-6 weeks (group 1), 6-8 weeks (group 2), 8-10 weeks (group 3), and > 10 weeks (group 4). Cox proportional hazards model was used to find associations with recurrence and OS. Results: Of the 80 patients, 67.5% (n = 54) were male and 32.5% (n = 26) were female. Median age at diagnosis was 59 years (range, 28-80 years). Median follow-up was 4.84 years. Recurrence occurred in 29% (n = 23) of patients. Incidence of death was 11% (n = 9). Pathologic complete response (pCR) was achieved in 15% (n = 12) of patients. Statin use during chemoradiation was prevalent in 25% (n = 20) of patients. Compared to group 1, patients in group 2 had a 14% reduction in the risk of recurrence (hazard ratio (HR): 0.86, 95% CI: 0.252.91); group 3 had a 69% reduction (HR: 0.31, 95% CI: 0.081.22) and group 4 had a 55% reduction (HR: 0.45, 95% CI: 0.073.08). There was no statistically significant difference in OS between the 4 groups. Furthermore, patients who took statins during chemoradiation had improved OS (HR: 5.42, 95% CI: 39.27.48, p < 0.019) with no difference in pCR rate. Conclusions: This study shows that surgery at 8-10 weeks after chemoradiation offers the best disease-free survival outcome. It also highlights a mortality benefit conferred by statin use during chemoradiation. This could be attributed to the radiosensitizing effects of statins, which allow tumor stem cells to undergo enhanced autophagy. Further prospective studies are warranted to investigate this therapeutic benefit.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Nakazawa ◽  
H Arashi ◽  
Y Inagaki ◽  
H Otsuki ◽  
J Yamaguchi ◽  
...  

Abstract Background This study aimed to elucidate whether high-density lipoprotein cholesterol (HDL-C) at 3-month follow-up for patients receiving contemporary lipid-lowering therapy after acute coronary syndrome (ACS) could predict cardiac events. Methods The HIJ-PROPER study was a multicenter, prospective, randomized trial comparing intensive lipid-lowering therapy (pitavastatin + ezetimibe) and conventional lipid-lowering therapy (pitavastatin monotherapy) after ACS. For the present analysis, the entire cohort was divided into three groups according to HDL-C levels at 3-month follow-up (Group 1, HDL-C ≤43 mg/dL; Group 2, 43–53.6 mg/dL; Group 3; HDL-C ≥53.6 mg/dL). Baseline characteristics and the incidence of the primary endpoint (a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, or ischemia-driven revascularization) were compared among the three groups. Results The primary endpoint was reported in 34.8%, 30.1%, and 24.6% of patients in Groups 1, 2, and 3, respectively. The incidence of the primary endpoint was significantly higher in Group 1 than in Group 3 (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.19–1.9; p=0.001). Irrespective of the treatment regimen, Group 1 had a significantly higher rate of the primary endpoint than Group 3 (pitavastatin + ezetimibe therapy: HR, 1.6; 95% CI, 1.12–2.22; p=0.01 and pitavastatin monotherapy: HR, 1.4; 95% CI, 1.05–1.98; p=0.02). These trends remained even after adjustment for baseline characteristics and lipid profiles. Conclusions Lower levels of HDL-C at 3-month follow-up are associated with higher incidence of the cardiovascular events in patients with acute coronary syndrome receiving contemporary lipid-lowering therapy. HDL-C levels and Cardiovascular events Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Gao ◽  
Jing-Yu Liu ◽  
Peng-Ju Lu ◽  
Jian-Yong Xiao ◽  
Ming-Dong Gao ◽  
...  

Background: Several studies have demonstrated that using a higher dose of statin can easily induce liver injury and myopathy. Low-density lipoprotein cholesterol (LDL-C) is a well-established modifiable risk factor for cardiovascular disease; however, the large majority of Chinese patients cannot meet the target level of LDL-C recommended by the Chinese expert consensus. Evolocumab has been demonstrated to reduce LDL-C by approximately 60% in many studies. Nevertheless, whether combined evolocumab and moderate-intensity statin is as effective in lowering LDL-C and decreasing incidence of MACE in Chinese patients presenting with the acute phase of acute coronary syndrome (ACS) remains unknown. Therefore, the “Evolocumab added to Moderate-Intensity Statin therapy on LDL-C lowering and cardiovascular adverse events in patients with Acute Coronary Syndrome” (EMSIACS) is conducted.Methods: The EMSIACS is a prospective, randomized, open-label, parallel-group, multicenter study involving analyzing the feasibility and efficacy of evolocumab added to moderate-intensity statin therapy on lowering LDL-C levels in adult Chinese patients hospitalized for acute phase ACS. The sample size calculation is based on the primary outcome, and 500 patients will be planned to recruit. Patients are randomized in evolocumab arm (evolocumab 140mg every 2weeks plus rosuvastatin 10mg/day or atorvastatin 20mg/day) and statin-only arm (rosuvastatin 10mg/day or atorvastatin 20mg/day). The primary outcome is the percentage change in LDL-C in weeks 4 and week 12 after treatment. The secondary outcome is the occurrence of MACE after 12weeks and 1year of treatment.Discussion: If the EMSIACS trial endpoints prove statistically significant, the evolocumab added to moderate-intensity statin therapy will have the potential to effectively lower subjects’ LDL-C levels, especially for the Chinese patients with acute phase ACS. However, if the risk of MACE is not significantly different between the two groups, we may extend follow-up time for secondary outcome when the clinical trial is over.Clinical trial registration: The study is registered to ClinicalTrials.gov (NCT04100434), which retrospectively registered on November 24, 2020.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3782-3782
Author(s):  
Nan Xinyu ◽  
Srivastava Pallavi ◽  
Mamta Puppala ◽  
Sai Ravi Pingali ◽  
Ibrahim Ibrahim ◽  
...  

Abstract Background: Hyperleukocytosis is complication of leukemia and is defined as peripheral white blood cell (WBC) count greater than 100, 000/mm^3. The high WBC count can increase blood viscosity and lead to leukostatsis, which is a medical emergency most commonly seen in acute leukemias. The use of Leukapheresis, is controversial and there are few guidelines. We performed a retrospective review of outcomes in patients with hyperleukocytosis who received leukapheresis in Houston Methodist Hospital between 2006 and 2015. Methods: The patient data was queried from METEOR (Methodist Environment for Translational Enhancement and Outcomes Research), a clinical data warehouse and analytics environment that integrates existing business data warehouse with internal and external research databases and national registries to support clinical research and outcome studies for improving patient care cost-effectively. METEOR data warehouse contains records dating back to January 1, 2006 with over 1 million unique patients and over 4 million unique patient encounters. We queried for the diagnosis of leukemia and those that received at least one course of leukapheresis and also obtained baseline demographics, and overall outcomes. Results: We reviewed 5585 of whom 42 patients who meet the criteria-patients, 29 of them have diagnosis of AML, 6 with CLL, 4 with ALL, and 3 with CML. The baseline demographics included 29 males and 13 females, whose median age was 52.5; 19 were Caucasians while 10 were African Americans, 5 Hispanic, 5 Asian and 3 reportedly as others. As shown in Table 1, the population is divided into 3 groups according to WBC before leukapheresis. Group 1 has 7 patients with WBC <100,000, median of 80.460. Group 2 has 17 patients with WBC range from 100,000 to 200,000, median of 150,740. Group 3 has 18 patients with WBC above 200,000, median of 252,200. In group 1, the average leukostatsis symptom grade is 1.43, average % decrease of WBC is 34.54%, ( blast-84%). In group 2, the average leukostatsis symptom grade is 1.88, average % decrease of WBC is 48.25%, ( blast- 69%). In group 3, the average leukostatsis symptom grade is 1.06, average % decrease of WBC is 42.81%, (blast-59.5%). In terms of complications, in group 1, 42.86% presented with acute kidney injury (AKI), 28.57% with tumor lysis syndrome, 28.57% with disseminated intravascular coagulation (DIC), 28.57% with sepsis, 14.29% with pneumonia, 42.86% with respiratory failure, 14.29% and with acute coronary syndrome (ACS). In group 2, 17.65% presented with AKI, 47.06% with TLS, 47.06 % with DIC, 23.53% with sepsis, 11.76% with pneumonia, 41.18% with respiratory failure, and 5.88% with acute coronary syndrome. In group 3 11.10 % presented with acute kidney injury, 44.44% with TLS, 38.89 % with DIC, 22.22% with sepsis, 11.11% with pneumonia, 27.78 % with respiratory failure, and 5.56 % with ACS. The 4 weeks mortality rate are 42.86% for group 1, 29.41% for group 2, and 22.22% for group 3. Conclusions: We have validated the Hyperleukocytosis grading schema and usefulness of leukapheresis. Our data indicates comparable mortality in pts with WBC between 100 -200,000 and > 200,000. Further statistical review of this data set will be presented at the ASH Meeting, Orlando 2015 Table 1. Group 1 Group 2 Group 3 WBC range <100,000 100,000 to 200,000 >200,000 Number of patients 7 17 18 Average leukostasis symptom grade 1.43 1.88 1.06 % Lymphoid leukemia 14.29% 17.65% 33.33% Median WBC before leukapheresis 80,460 150,740 252,200 Average % decrease of WBC 34.54% 48.25% 42.81% Median % of blast before leukapheresis 84% 69% 59.5% Average % change in %blast 5.35% 11.23% -6.55% Average Creatinine after Leukapheresis 2.39 1.47 1.38 Average uric acid after leukapheresis 8.77 6.52 6.75 Average Fibrinogen after leukapheresis 424.25 336.78 300.56 % Acute kidney injury 42.86% 17.65% 11.10% % Tumor lysis syndrome 28.57% 47.06% 44.44% % DIC 28.57% 47.06% 38.89% % Sepsis 28.57% 23.53% 22.22% % Pneumonia 14.29% 11.76% 11.11% % Respiratory failure 42.86% 41.18% 27.78% % Acute Coronary Syndrome 14.29% 5.88% 5.56% % 4 weeks Mortality 42.86% 29.41% 22.22% References: 1. Novotny JR, Müller-Beissenhirtz H, Herget-Rosenthal S, Kribben A, Dührsen U. Grading of symptoms in hyperleukocytic leukaemia: a clinical model for the role of different blast types and promyelocytes in the development of leukostatsis syndrome. Eur J Haematol 2005:74:501-510 Disclosures No relevant conflicts of interest to declare.


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