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Objectives: Advanced age is a well-established risk factor for severe coronavirus disease 2019 (COVID-19). Exacerbated inflammation affects multiple organs, among which hematopoiesis responds by increased output of various cells. We aimed to determine the association between COVID-19 progression and large immature cell (LIC) counts, changes in erythrocyte and platelet distribution widths (RDW, PDW) with reference to patients' age. Methods: A total of 755 patients with complete blood cell (CBC) analysis in the first 24 h of hospitalization were enrolled. Patients were divided into two groups: under and above 65 years of age. Results: The LIC counts were different in both groups (p < 0.003). However, only the senior patients had markedly different values of RDW and PDW (p < 0.001). The receiver operating characteristic (ROC) curve analysis provided increased LIC (AUC = 0.600), RDW (AUC = 0.609), PDW (AUC = 0.556), and platelet to LIC ratio (AUC = 0.634) as significant in discriminating outcome in the older group. Importantly, these results were not repeated in the younger patients. In the elderly, the progression was predicted with LIC cut-off at ≥ 0.305 × 109/L (OR = 3.166) and RDW over 12.15% (OR = 2.081). Discussion: Aging is characterized by a decline in immunological competence with a compromised control of inflammation leading to a proinflammatory state. This background together with the actions of pathogens may lead to emergency myelopoiesis. Conclusion: Our results point to the important differences between age groups regarding CBC-related parameters of stress hematopoiesis during severe infection. Higher LIC, RDW and PDW levels were reliable in the early identification of COVID-19 progression only in the elderly. [ABSTRACT FROM AUTHOR]

The primary immuna thrombocytopenia (ITP) is an acquired autoimmune disease characterized by isolated thrombocytopenia PLT < 100 x 109/L, and the absence of all conditions and diseases that can result in thrombocytopenia. The first-line therapy in ITP involves the use of corticosteroids, intravenous immunoglobulin or an immunoglobulin anti-D. The second-line treatment includes splenectomy, immunosuppressive drugs and agonists of thrombopoietin receptor (TPO-RA). To describe the treatment results with TPORA (eltrombopagin patients with ITP in the Clinic of Hematology UCC NIš. Between March 2018 and December 2023, at the Clinic of Hematology UCC Niš, 6 patients with ITP in which the previous treatment lines did not respond to the therapy or gave side effects were treated with TRO-RA. The indication for the TRO-RA therapy was chronic ITP. The period from the diagnosis to the initiation of the treatment with TRO-RA was on average 71,5 months. The analysis of the average number of platelets after TPO-RA therapy showed an upward trend. The TPO-RA does not show immunosuppression, they lead to an increase in platelet count, stopping bleeding and improving the quality of life. Therefore, TPO-RA are essential medicines for the treatment of ITP after the failure of the first and second - line therapy. [ABSTRACT FROM AUTHOR]

Introduction. In rare cases, chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma may transform into Hodgkin lymphoma, with about a hundred cases reported in the literature so far. We present a case of the Hodgkin variant of Richter transformation. Case report. After a oneyear watch and wait period, a 60-year-old male with CLL developed B symptoms, generalized lymphadenopathy, and splenomegaly. Upon initial staging (Binet B/Rai 3), he was started on fludarabine, cyclophosphamide, and rituximab (FCR) regimen. After the third cycle of treatment, the rightsided axillary lymphadenopathy persisted and became painful, while the dimensions of the remaining organs affected by the disease decreased. Upon the finalization of the final sixth FCR cycle, the painful right-sided axillary lymphadenopathy persisted (though partially decreasing in size), with the development of local redness and swelling. A biopsy of the residual axillary node was performed, which revealed disease transformation into Hodgkin lymphoma. Upon multislice computed tomography-based s taging ( IV E c linical stage) and prognostic assessment (unfavorable prognosis), it was decided that the treatment be continued with doxorubicin, vinblastine, dacarbazine (AVD) regimen. The presented patient died two months after the diagnosis of Hodgkin transformation (HT) was established during the initial cycle of AVD. Conclusion. Although CLL is an indolent malignancy, in rare cases of HT, the prognosis is largely dismal. The available treatment strategies demonstrate suboptimal results, although novel immunotherapies may change the landscape of HT therapy in the near future. [ABSTRACT FROM AUTHOR]

Gaucher disease (GD is a liposomal storage disease that is inherited in an autosomal recessive manner. The basis of the disease is a mutation of the gene that codes for the enzyme glucocerebrosidase. The clinical division of GB into type 1, 2 and 3 is based on the absence (type 1) or presence (type 2 and 3) of manifestations by the central nervous system. In order to establish a definitive diagnosis, the level of ß-glucose cerebrosidase in leukocytes and the value of chitotriosidase in the serum are determined. Genotype analysis is helpful in assessing the type and severity of the disease. Since 1991, Gaucher disease has been treated with enzyme replacement therapy (EST). We present the clinical characteristics of a patient with type 1 Gaucher disease diagnosed in November 2004 in the Hematology Clinic, UKC of Serbia. The patient was a heterozygous carrier of the N307S mutation. In February 2006, treatment was started with imiglucerase (CerezymeR) IV at a dose of 30 U/kg body weight every two weeks. After 24 months of imiglucerase therapy, a significant improvement in the patient's condition was registered, but she complained of nausea, an urge to vomit and pain in the epigastrium. MSCT of the upper abdomen was performed, and esophagogastroduodenoscopy with a biopsy of changes in the stomach. Pathohistological findings of biopsied changes in the stomach indicated the existence of gastric adenocarcinoma. A total gastrectomy with splenectomy and cholecystectomy was performed. PH finding was adenocarcinoma ventriculi intramucosum (early cancer). After the surgical intervention, the patient continued enzyme replacement therapy with imiglucerase. Patients with GD have an increased risk of developing malignant diseases, most often lymphoproliferative, although solid tumors (hepatocellular carcinoma) have also been described. In our case, to the best of our knowledge, the association of Gaucher disease with gastric cancer has been rarely reported in the literature. [ABSTRACT FROM AUTHOR]

Introduction/Aim. Hemophilia A is an antihemophilic factor deficiency which requires life-long treatment. The aim of this analysis was to present the effects of prophylactic non-factor replacement therapy in ten patients with hemophilia A. Patients and This retrospective analysis was conducted on ten male patients (4 children, 1 adolescent, and 5 adults) with severe hemophilia A and a history of antihemophilic factor replacement prophylaxis, prior to the initiation of emicizumab prophylaxis. A single adult patient developed inhibitors during the course of factor replacement prophylaxis. Four adult patients had already developed hemophilic arthropathy before the initiation of non-factor replacement prophylaxis. Two adult patients received emicizumab prophylaxis every four weeks, while others received emicizumab every two weeks. After a 14-month period (average) of non-factor replacement prophylaxis, we analyzed the number of breakthrough bleeding episodes, annualized bleeding rate, involvement of target joints, adverse drug reactions, and interviewed the patients regarding their satisfaction with the non-factor replacement treatment. Results. None of the patients on emicizumab prophylaxis experienced breakthrough bleeding or clinical worsening of the affected target joints during the period of emicizumab prophylaxis. Annualized bleeding rate was zero in all patients on emicizumab prophylaxis. No adverse drug reactions occurred in our patients during emicizumab prophylaxis. All patients reported greater treatment satisfaction compared to the replacement prophylaxis. Conclusion. By providing safety from bleeding events and potentially the stability of the affected joints, emicizumab prophylaxis enables greater activity and increases the quality of life of treated patients. [ABSTRACT FROM AUTHOR]

Bleeding Assessment Tools (BATs) are bleeding scoring systems used for screening and quantitative assessment of mild bleeding disorders. They consist of a standardized questionnaire and a scoring system that is used for the summation of the final score. In this review article, we have presented BATs that are applied in the area of hematology. The earlier BATs were designed to distinguish patients with von Willebrand disease (VWD) from healthy individuals. Later modifications of the original Vicenza-BAT were developed in order to improve its specificity, precision, and flexibility, as well as to shorten the administration time. The most significant of these modifications is the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool (ISTH-BAT), which is also validated for use in patients affected by hemophilia and inherited platelet disorders. ISTH-BAT score of = 6 in adult females, = 4 in adult males, and = 3 in children is considered abnormal. The WHO developed the first BAT for immune thrombocytopenia (ITP). However, more recently, the ITP International Working Group (IWG) designed the ITP-BAT. The IWG defines a severe or clinically relevant bleeding manifestation as an ITP-BAT SMOG index of S > 2 and/or M > 1 and/or O > 1. In 2016, a group of Chinese experts created a simple modification of the ITP-BAT, the ITP-2016. The values of the ITP-2016 Bleeding Score = 5 indicate severe immune thrombocytopenia. In the primary healthcare setting BATs serve as a valuable screening tool for discovering patients with bleeding disorders, who require further hematologic investigation. [ABSTRACT FROM AUTHOR]

Chronic neutropenia (CN) corresponds with absolute count of neutrophils below 1.8 × 109/L in last three months. Besides, neutropenia that persists more than three months and in absence of underlying diseases, chemical components, irradiation, use of particular drugs, inflammation, is defined as chronic idiopathic neutropenia (CIN). There are three types of CN - severe, moderate and mild, with or without extra-hematopoietic manifestations. The aim of this report was to define a stratified approach toward patient with hypothesis of CIN, including timely patient recognition with consequent follow-up and actions afterwards based on recommendation from EuNet INNOCHRON-European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias. Case presented a 40-year-old female who went to the Hematology Department of the University Clinical Center Niš for regular health condition and blood count control. Since she was 21, she has been monitoring neutropenia, which occurred immediately after first child birth. Laboratory parameters and peripheral blood smear values were within physiological range. Performed immune assays excluded the immune background of neutropenia. In the next step, we excluded viral infections as a cause of neutropenia with particular serological tests. Also, a bone marrow aspiration was performed with results in physiological range. Chronic neutropenia can be associated with serious health complications. The Severe Chronic Neutropenia International Registry (SCNIR) is a global organization dedicated to finding the causes, consequences and best treatments for severe CN. Similar to other European countries, we suggest the introduction of defined approach to diagnosis, registration and monitoring of chronic neutropenia patients in Serbia through Register. [ABSTRACT FROM AUTHOR]

Introduction. Bleeding scoring systems are used for predicting the risk of a specific primary outcome in a specific population.In this article, we present scoring systems frequently used in internist practice. Bleeding scoring systems for acute upper gastrointestinal bleeding. Are divided into clinical, endoscopic,and combined scoring systems, according to the type of variables included. Besides traditional systems (Rockall, Glasgow-Blatchford), we primarily present clinical scoring systems used for upper gastrointestinal bleeding. Bleeding scoring systems for patients with atrial fibrillation on anticoagulant therapy. We refer to the most significant scoring systems - ATRIA, HAS-BLED, and ORBIT. Since the prognostic performance of the existing scoring systems is less than satisfactory, medical organizations suggest they should be used for recognizing patients who deserve close monitoring during anticoagulant therapy. Bleeding scoring systems for patients with acute myocardial infarction treated with percutaneous coronary intervention. ACUITY-HORIZONS was proven to be superior to other scoring systems in predicting bleeding within 30 days in patients with a myocardial infarction treated with transradial percutaneous coronary intervention. Bleeding scoring systems for bleeding disorders. Scoring systems enable the detection of bleeding disorders before performing laboratory tests. Considering the frequency severity of symptoms, newer systems have been developed for the pediatric population and self-testing by modifying the original scoring system. Conclusion. Although medical organizations encourage the implementation of scoring systems in clinical practice, the development of newer and enhanced existing systems requires a comprehensive approach and critical analysis of the existing systems. [ABSTRACT FROM AUTHOR]

Hemophilia A is the most common congenital bleeding disorder caused by a deficiency in coagulation factor VIII activity, characterized by a marked bleeding tendency. It is inherited recessively. The most common complication of the disease is chronic arthropathy. In the prophylactic treatment regimen, the subjects receive preventative F VIII infusions every second day or three times a week. In an on-demand regimen, bleeds are treated as they occur. Analysis of the frequency and degree of chronic hemophilic arthropathy in patients with moderate and severe hemophilia A. Analysis of involvement of individual joints, and their score values by the treatment regimen (prophylaxis vs. on-demand treatment.) The study included 23 patients - 15 patients on „on-demand" regimen and 8 patients who had prophylaxis, all being treated at the Clinic of Hematology and Clinical Immunology, Clinical Center Niš. In the assessment of frequency of complications we used descriptive statistics: the number, proportion and mean. The comparison of arithmetic means of the two samples was performed using the t-test. The comparison of frequency values was performed using the chi-square test or Fisher's test. In the group without prophylaxis, the knee and hip were the most commonly affected sites (73.33% and 53.33%), and in the group with prophylaxis, the elbow joint was mostly affected (37.50%). The knee was statistically more often affected in patients without prophylaxis compared to those on prophylaxis. The knee score had the highest value in both groups. It was statistically significantly higher in patients without prophylaxis compared to those on prophylaxis. The hip score was the second highest value in the examined groups, the third was the elbow joint score, followed by the ankle score, and the lowest score was observed for the shoulder joint. Elbow and ankle scores were statistically significantly higher in patients without prophylaxis compared to those on prophylaxis. Chronic arthropathy is the most common complication in patients with severe and moderate Haemophilia A, with maximum involvement of the knee joint in both groups of patients (with or without prophylaxis), but with a statistically significantly higher score in patients without prophylaxis. [ABSTRACT FROM AUTHOR]

Background/Aim. The platelet aggregation, as a laboratory test for assessment of platelet function, is very efficient for optimal antiplatelet treatment and also to identify individuals who have suboptimal response to antiplatelet drugs, such as aspirin and clopidogrel. The aim of this study was to determine the level of inhibition of platelet aggregation using impedance aggregometry in the patients receiving different preparations of acetylsalicylic acid (ASA) in a dose of 100 mg per day. Methods. The examination included 215 patients (110 men and 105 women), treated with one of three different ASA preparations after acute myocardial infarction, as a single therapy or with clopidogrel. Among them, 89 patients were on Aspirin protect® (Bayer, Germany) - Group 1 and 66 patients were on Cardiopirin® (GL Pharma GMBH, Austria) - Group 2, while 60 patients were taking Andol® (Pliva, Croatia) - Group 3. The groups were equal in the presence of factors that can influence platelet aggregation (age, gender, smoking, diabetes, taking other drugs). The platelet function was measured using the impedance aggregometer Multiplate (Multiplate Platelet Function Analyzer, Roche) in the blood samples with heparin for the platelet aggregation activated by the arachidonic acid (ASPI) and by thrombin (TRAP) tests [the area under the aggregation curve (AUC) was used to express the aggregation response over the measured time (AU*min)]. Results. Efficacy of ASA preparations showed statistically significant differences among the three investigated groups (XKW2 = 46.279; p < 0.001), and it was also observed separately in the patients undergoing single therapy (XKW2 = 26.344; p < 0.001) and dual therapy (XKW2 = 23.498; p < 0.001). It was found that the patients who were taking Aspirin protect® obtained significantly better antiplatelet efficiency compared to the patients receiving Cardiopirin® (Z = 5.472; p < 0.001) and Andol® (Z = 5.387; p = 0.022). There is reduced efficiency of all ASA preparations in smokers, while patients receiving Aspirin protect® were 10.5 times more likely to be responders. Conclusion. Different ASA preparations observed in this study showed different efficiency on the platelet function as measured by the method of impedance aggregometry. [ABSTRACT FROM AUTHOR]

The introduction of imatinib, as a type of targeted molecular therapy, has profoundly changed the treatment outcome of chronic myeloid leukaemia (CML). The aim of this study was to assess and compare treatment outcome among patients who achieved complete cytogenetic response (CCgR) within or after one year following initiation of imatinib therapy. A group of 42 adult patients with early chronic-phase Philadelphia-positive CML treated with imatinib mesylate therapy has been studied. In the study group CCgR has been achieved in 36/42 (85.71%) analysed patients, while in 3/42 (7.14%) patients the absence of cytogenetic response has been noted. Early CCgR has been achieved by 25/36 (69.44%) patients with response at median time of 6.9-1.9 months, while late CCgR has been achieved by 11/36 (30.56%) patients at median time of 18.75-2.4 months. Univariate analysis has identified prognostic factors for achieving early and late CCgR. Analysis of remission duration of treatment responders has shown that 21/25 (84%) patients in the group with early CCgR and 9/11 (81.81%) patients from the group with late CCgR still maintained stable remission on last cytogenetic control. The estimated 5-year survival rate was 85% for early responders and 74% for late responders. In conclusion, these results demonstrate that there are no differences in the treatment outcome, i.e. level of response, of patients with CML in relation to whether the CCgR was achieved within or after one year of imatinib therapy. [ABSTRACT FROM AUTHOR]

Background/Aim. Despite the introduction of new oral anticoagulants (dabigatran, rivoroxaban, apixaban), vitamin K antagonists (VKA), such as warfarin and acenocoumarol are still the most widely used oral anticoagulants for the treatment of nonvalvular atrial fibrillation (NVAF). The time in therapeutic range (TTR) represents a measure of the quality of the anticoagulant effect of these drugs, and it is considered that the lower value of TTR is associated with the adverse effects of therapy. The aim of this study was to evaluate of the effectiveness of VKA therapy in patients with NVAF and to identify factors affecting the anticoagulation efficacy. Methods. A retrospective study was conducted on a population of 725 outpatients with NVAF, treated with VKA and followed in the Blood Transfusion Institute of Niš, Serbia, from January to December 2017. Laboratory control of the INR was done from capillary blood of patients on Thrombotrack Solo (Axis Shield, Norway) and Thrombostat (Behnk Elektronik, Germany). Targeted therapeutic INR was between 2.0 and 3.0. For each patient all available INR values were evaluated to calculate the individual TTR according to the Rosendaal method. Results. The study included a total of 725 patients with NVAF which had 6,105 INR measurements, what was 8.13 ± 2.47 INR measurements per patient. The mean value of TTR and was 60.15 ± 17.52%, but 49.72% of patients had T TR l ess t han 6 0%. P atients were at high risk of thrombosis in 6.15% of time (INR < 1.5) and high risk of bleeding in 2.2% of time (INR > 4.5). The most significant independent factors affecting the quality of VKA therapy were gender, arterial hypertension, diabetes mellitus and the use of amiodarone and antiplatelet drugs (aspirin, clopidogrel). Conclusion. The TTR is undoubtedly useful indicator of the VKA treatment effectiveness. The most important predictors of poorer efficacy of VKA therapy are: arterial hypertension, diabetes mellitus, patients' gender and the use of amiodarone and antiplatelet drugs (aspirin, clopidogrel). To improve the quality of VKA therapy, education of patients and better collaboration with them, as well as a successful teamwork of clinicians are also imperative. [ABSTRACT FROM AUTHOR]

Background/Aim. Preparation of platelet concentrate (PC) from a unit of whole blood is a method dependent on a number of factors, which alone or together, can have a significant impact on the quality of the final product. Quality of PCs is determined with criteria defined in the Guide to the preparation, use and quality assurance of the Council of European Committee for Blood Transfusion. The aim of the study was to analyze the quality of PCs prepared from buffy coat (BC) and to allocate the factors of improvement and standardization of the quality of PCs. Methods. The study included a total of 80 PCs prepared from BC according to the standard procedure in the Blood Transfusion Institute Niš. The quality of PCs was determined according to the product volume and laboratory testing on the first (PC1), the third (PC3) and the fifth day (PC5) of the PC storage. The following parameters were determined: platelets, residual erythrocytes and leukocytes count, gas analysis [partial pressure of oxygen, carbon dioxide (pO2, pCO2)], pH, sterility and platelet aggregation triggered by using 3.2, 6.4 and 9.6 µg collagen/mL (impedance aggregometry). Results There were significantly lower platelet count, pO2, pCO2 and pH in the PC3 and PC5 samples (p < 0.001). Except for the fulfillment of the criteria for platelet count, all the other quality parameters were in accordance with recommended criteria. Platelet aggregation for all the concentrations of collagen showed a decrease during the storage period, with statistically significant differences for PC3 and PC5 as compared to PC1 (p < 0.01). There was statistically significant decrease in activity of PCs triggered with higher concentrations of collagen (6.4 and 9.6 µg collagen/mL) in comparison with lower concentration of collagen (3.2 µg collagen/mL). Conclusion. Platelet count, evaluated biochemical parameters and the platelet function were significantly changed during the storage period. In order to improve the quality of PCs it is important to store the products under proper conditions, change the type of plastic bag for PC storage and use platelet additive solutions (PAS) instead of plasma. [ABSTRACT FROM AUTHOR]

Dabigatran, a new generation anticoagulant, is a direct thrombin inhibitor, which has a rapid onset of action and relatively wide therapeutic scope, with no need for monitoring of efficacy, as is the case with vitamin K antagonists. However, there are certain emergency situations that require immediate assessment of the effectiveness of dabigatran. The aim of this study was to determine whether the aPTT as a screening coagulation test, can be reliably used to assess the anticoagulant effect of dabigatran. The study included 32 patients with non-valvular atrial fibrillation who received dabigatran (Pradaxa, Boehringer Inhelheim) in a single dose of 110 mg or 150 mg twice a day. In all patients screening coagulation (PT, aPTT, INR) was done before the treatment. aPTT was performed 4 hours, 8 hours and 12 hours after taking the drug. There was a statistically significant prolongation of aPTT after 4 hours and 8 hours of taking the drug in patients who were treated with 150 mg of dabigatran compared to 110 mg, while after 12 hours there was no statistically significant difference in aPTT between these two groups. There was a strong correlation between the control values of aPTT and the total increase in aPTT after dabigatran administration (r = 0.96 for a dose of 150 mg IR = 0.83 for a dose of 110 mg). aPTT is a useful test for assessing the effect of dabigatran and can be used as a screening test in patients who urgently need to determine the efficacy of the drug. [ABSTRACT FROM AUTHOR]

Background/Aim. Low birth weight (LBW) is a result of preterm birth or intrauterine growth retardation, and in both cases is the strongest single factor associated with perinatal and neonatal mortality. It is considered that socioeconomic factors, as well as mothers bad habits, play the most significant role in the development of LBW, which explains notable number of researches focused on this particular problem. The aim of this study was to characterize socioeconomic factors, as well as smoking habits of the mothers, and their connection with LBW. Methods. The questionnaire was carried out among mothers of 2 years old children (n = 956), born after 37 gestational weeks. The characteristics of mothers who had children with LBW, defined as < 2 500 g, (n = 50), were matched with the characteristices of mothers who had children ≥ 2 500 g, (n = 906). For defining risk factors, and protective factors as well, we used univariant and multivariant logistic modeles. Results. As significant risk factors for LBW in an univariant model we had education level of the mothers, smoking during pregnancy, smoking before pregnancy, the number of daily cigarettes, the number of cigarettes used during pregnancy, paternal earnings and socioeconomic factors. In a multivariant model the most significant factors were socioeconomic factors, education level of the mothers, paternal earnings and mothers smoking during pregnancy. Conclusion. Smoking during pregnancy and socioeconomic factors have great influence on LBW. Future studies should be carried out in different social groups, with the intention to define their influence on LBW and reproduction, as well. This should be the proper way of adequate health breeding planning for giving up smoking, the prevention of bad habits and melioration of mothers and children health, as the most vulnerable population. [ABSTRACT FROM AUTHOR]