INTRODUCTION:Proliferation of monocytes (MO) occurs in reactive conditions as well as in myeloid neoplasm with clonal monocytosis such as chronic myelomonocytic leukemia (CMML). CMML is a type of clonal hematopoietic disease characterized by a sine qua non condition: sustained peripheral blood monocytosis (absolute monocytes count from ≥1 X109/L, to ≥0.5 X109/L with monocytes accounting for ≥10% of the peripheral white blood cells), accompanied by overlapping changes in bone marrow of myelodysplasia and myeloproliferation, <20% blasts and presence pf clonality. In CMML, there is an inherent risk for leukemic transformation (15% over 3-5 years). The French-American-British (FAB) co-operative group, created in 1976, proposed a uniform system of classification and nomenclature of hemato-oncologic malignancies. Classification of hematopoietic neoplasms is essential for making proper evidence-based treatment decisions and accurately assessing prognosis.

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1–2. Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.

Background: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus. Objectives: To verify the efficacy of peripheral blood inflammatory markers (BIMs) in diagnosing preeclampsia and compare them with results from other studies. Methods: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis. Results: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did not succeed to differentiate between study and control groups. Conclusions: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

INTRODUCTION:Anemia is common and is an independent risk factor for morbidity and mortality, especially in pre- (30-40% of patients undergoing major surgery) or post-operative anemia (up to 80-90%). Using World Health Organization (WHO) criteria, in 2010 one quarter of the global population was anemic (1.9 billion people) and iron deficiency anemia (IDA( was and still remains the most common type of anemia worldwide, accounting for more than half of the total anemia burden. In a systematic analysis for the Global Burden of Disease Study 2016, IDA was the fourth leading cause of years lived with disability, particularly in women, thus highlighting prevention and treatment of IDA as a major public health goal. Red blood cells (RBC) transfusion is a common therapeutic intervention with considerable variation in clinical practice. More than 85 million units packed RBC (PRBC) are transfused annually worldwide. The principal indication for blood transfusion (BT) is anemia, yet a significant percentage of RBC transfusions are inappropriately overused. For many physicians and clinicians, across many different specialties, BT is still considered to be the first-line treatment when facing anemia. The Joint Commission along with the American Medical Association has included BT in a list of the five most overused therapeutic procedures in the United States. Restrictive blood transfusion (RBT) is an evidence-based policy, at least as effective, if not superior to the liberal policy of BT. Patient blood management (PBM) is a patient-centered systematic, evidence-based approach, supported by RBT. In this article we analyze the factors which influence the implementation of PBM.

INTRODUCTION:Acute appendicitis (AA) requires a prompt diagnosis. According to postoperative pathological results, a significant number of appendectomies are performed on a normal appendix (NA). The aim of this study is to evaluate the role of preoperative inflammatory markers in supporting and improving the clinical diagnosis of AA, extracting more information from CBC parameters.METHODS:The study is a retrospective one. The histopathological results of operated appendix from 102 patients, who underwent appendectomy for clinically suspected AA, were extracted from the Galilee Medical Center systems. Two patient groups (NA and true AA) were compared for neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and mean platelet volume (MPV). The obtained data were statistically analyzed, using the independent sample t test and Mann-Whitney test. Category data have been compared among groups with the chi-squared test. The primary endpoint of our research was to assess the predictive power of blood biomarkers.RESULTS:Patients with suspected AA, based on clinical picture and contrast enhanced computed tomography (CECT), and with MLR-value ≥0.3357 were 5.25 times more likely than normal to have AA. Patients with NLR-value ≥3.2223 were 7 times more likely than normal to have AA. The differences in PLR and MPV values were not statistically significant.CONCLUSIONS:The NLR and MLR biomarkers can assist in diagnosis of AA. This can be particularly helpful in cases where CECT is contraindicated, as in pregnant women or children.

Several studies showed ethnic disparities in multiple myeloma (MM) incidence and prognosis. In order to compare prognosis and overall survival between different ethnic groups, a multicenter retrospective study was conducted in Northern Israel. A total of 145 patients suffering from MM were included (72% Jewish, and 28% Arabs) who were treated between 2008-2018. A difference was found in the stage of the disease at the time of diagnosis, patients of Arab origin were diagnosed at a more advanced stage (III), (53.7% vs. 33.7%, respectively). A mortality rate of 48.9% was found in the study, regardless of population ethnic origin. No significant differences in rates of MGUS, MM symptoms, treatments, or progression-free survival (PFS) and overall survival (OS) were observed between ethnic groups. This suggests that raising awareness of MM may result in an earlier diagnosis, especially among patients of Arab origin, preventing unnecessary suffering from these patients.

Cognitive impairment due to different types of anemia is well-known. We reviewed the links between different types of anemia and the mechanism of cognition impairment as well as the direct involvement of micronutrients such as iron, vitamin B12, folic acid, and copper on cognitive function. Anemia can lead to cognitive impairment, yet the current health policy usually requires patient involvement in the treatment decision-making. Therefore, can an anemic patient be a partner to shared decision-making concerning the recommended treatment?

Education is the key. Nelson Mandela

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naive patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax +/- anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels >= 80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2 dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy.

Background: Venous thromboembolism (VTE)—including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)—may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2. Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4–30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018–2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes. Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7–94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07–47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls. Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.

Introduction: The aim was to analyze the clinical and prognostic differences between patients with PE with home and hospital treatment. Methods: The RIETE registry included 18145 and 1166 PE patients treated at hospital and at home. The clinical features were compared according to the treatment regimen. Results: Patients with home therapy were younger than patients treated at hospital (59.0±16.4 vs 66.8±17.2 years, p<0.001), presented less immobilization (15% vs 19%, OR 0.75, 95%CI 0.64-0.88) and had less unprovoked PE (50% vs 55%, OR 0.80, 95%CI 0.71-0.90), had more subsegmental PE (17% vs 4.6%, OR 4.17, 95%CI 3.42-5.09) and less proximal PE (16% vs 43%), OR 0.26, 95%CI 0.21-0.31), and had less heart affectation (7.6% vs 19%, OR 0.36, 95%CI 0.21-0.62). More proportion of patients without admission had PESI<65 (36% vs 19%, OR 2.45, 95%CI 2.16-2.78). At 7 days, patients treated at home presented less major bleeding (0.1% vs 0.8%, OR 0.11, 95%CI 0.02-0.78), less mortality (0.1% vs 1.6%, OR 0.05, 95%CI 0.01-0.38) and less event composed by recurrent PE, major bleeding and death (0.3% vs 2.4%, OR 0.14, 95%CI 0.05-0.38). Risk factors for the composite event were history of myocardial infarction (HR 1.38, 95%CI 1.01-1.90), chronic heart failure (HR 1.51, 95%CI 1.12-2.04), recent bleeding (HR 2.16, 95%CI 1.35-3.44), active cancer (HR 1.47, 95%CI 1.13-1.92), having transient risk factors (HR 1.67, 95%CI 1.33-2.11) and hospital admission (HR 4.24, 95%CI 1.56-11.57). Conclusion: PE patients treated at home were younger, less severe and less complicated than patients treated at hospital. Risk factors for the composite event were heart disease, bleeding, cancer and hospital admission.

Background:Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death.Objectives:The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer.Methods:We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point.Results:From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups.Conclusions:In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.

The ideal duration of anticoagulation therapy in patients with autoimmune disorders and venous thromboembolism (VTE) is controversial. We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) database to compare the incidence rate of major bleeding during anticoagulation versus the incidence rate of VTE recurrences after its discontinuation. We included 1061 patients with autoimmune disorders and VTE followed‐up after discontinuing anticoagulant therapy: rheumatoid arthritis, 321; polymyalgia rheumatica, 159; ulcerative colitis, 134; Crohn’s disease, 111; systemic lupus erythematosus (SLE), 82; giant cell arteritis, 58; ankylosing spondylitis, 39; Behcet disease, 17; other vasculitides, 140. During anticoagulation (median, 183 days), 64 patients had major bleeding. After discontinuing anticoagulation (median, 190 days), 112 patients developed symptomatic VTE recurrences. In most subgroups, the incidence rate of major bleeding during therapy was similar to the incidence rate of VTE recurrences after its discontinuation. However, in patients with SLE (10.0 major bleeds, 95% confidence interval [CI] 4.07–20.9) per 100 patient‐years vs. 3.62 VTE recurrences, 95% CI 1.15–8.74) or ankylosing spondylitis (10.9 major bleeds [95% CI 3.47–26.3] vs. 4.69 VTE recurrences, 95% CI 1.19–12.8) the incidence rates of major bleeding during anticoagulation were over twofold higher than the incidence rates of VTE recurrences after its discontinuation.

Background: Mean platelet volume (MPV), an essential component of the complete blood count (CBC) indices, is underutilized in common practice. In recent years, MPV has drawn strong interest, especially in clinical research. During inflammation, the MPV has a higher value because of platelet activation. Objectives: To verify whether high MPV values discovered incidentally in healthy naive patients indicates the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. Methods: A cohort study was used to assess the diagnostic value of high MPV discovered incidentally, in naive patients without any known cause of an abnormal high MPV, greater than upper limit of the normal range, such as active cardiovascular diseases and metabolic syndrome). Results: The mean MPV value in the patient group was 12.3 femtoliter. There was a higher incidence of metabolic syndrome in our research group than in the general population and a non-significant tendency; of pre-diabetes. Family doctors more frequently meet naive patients with high MPV than a hospital doctor. The results of our study are more relevant for him, who should know the relevance of such a finding, and search for a hidden pre-diabetes or metabolic syndrome. Conclusions: High MPV values discovered incidentally in healthy naive subjects suggest the development or the presence of cardiovascular risk factors, particularly metabolic syndrome and pre-diabetes. No statistically significant association was found between MPV and the presence of cardiovascular disease.

Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, BNT162b2, an mRNA COVID-19 vaccine with a high efficacy of 95% in immunocompetent individuals, was introduced. We investigated the safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with CLL from nine medical centers in Israel, Overall 400 patients were included, of whom 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, an antibody response was detected in 43% of the cohort. Among these CLL patients, 61% of the treatment-na ve patients responded to the vaccine, while responses developed in only 18% of those with ongoing disease, 37% of those previously treated with a BTK inhibitor and 5% of those recently given an anti-CD20 antibody. Among patients treated with BCL2 as monotherapy or in combination with anti-CD20, 62% and 14%, respectively, developed an immune response. There was a high concordance between neutralizing antibodies and positive serological response to spike protein. Based on our findings we developed a simple seven-factor score including timing of any treatment with anti-CD20, age, treatment status, and IgG, IgA, IgM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the BNT162b2 mRNA COVID-19 vaccine was found to be safe in patients with CLL, but its efficacy is limited, particularly in treated patients.

BACKGROUND:Red blood cell transfusion (RBCT) is a therapeutic procedure with important and undesirable secondary effects. Inappropriate overuse of RBCT is significant, and a significant percentage of physicians prescribe RBCT unnecessarily. Patient involvement in treatment decision-making is poor worldwide. Shared (with the patient) transfusion decision-making (TrDM) can temper a "quick finger on the trigger" of blood transfusion (BT). The objective of this study was to determine patients' preferences surrounding their involvement in the TrDM process as well as physicians' willingness to involve the patient in TrDM. The study also determined the role of patient age, gender, ethnicity, and schooling years in the TrDM process.METHODS:This cross-sectional study was conducted in a variety of departments, with 123 patients over 18 years old, who received a BT for the first time. The patients completed an anonymous questionnaire which included demographic characteristics (age, gender, ethnicity, and schooling years) and 2 questions linked to potential willingness to participate in the decision to transfuse.RESULTS:The questionnaire response rate was 100%. The data showed that 60% of patients (especially younger patients), independent of ethnicity, preferred a passive role in TrDM and 40% preferred to share the decision.CONCLUSIONS:The majority of patients, especially younger patients, prefer a passive role in TrDM, possibly due to insufficient information about the need for BT and its significance. We feel that active involvement on the part of the patient can provoke a more judicious thought process about the real need of BT on the part of the physician and have a positive influence on patient blood management.

To assess the usefulness of proton MR-spectroscopy (1H-MRS) and diffusion-weighted MRI (DW-MRI) sequences in the follow-up of CLL-patients with chemotherapy treatment.