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    Special Conditions in Venous Thrombembolism - Case Series
    (Macedonian Academy of Sciences and Arts/Walter de Gruyter GmbH, 2019-10-01)
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    Klincheva, Milka
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    Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.
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    Rare blood groups in ABO, Rh, Kell systems – biological and clinical significance
    (2022)
    Ristovska, Elena
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    Hristova Dimceva, Anita
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    Todorovski, Bojan
    Background: The frequency of ABO, Rh and Kell blood group antigens differs among populations of different ethnic ancestry. There are low-frequency antigens (<1%) and high-frequency antigens (>90%). A rare blood group is defined as the absence of a high-frequency antigen in the general population, as well as absence of multiple frequent antigens within a single or multiple blood group systems. Aim: To perform red blood cell typing and to calculate the antigen and phenotype frequencies, in order to identify rare blood group donors within the clinically most important АВО, Rh and Kell systems. Material and Methods: АВО, Rh (D, C, E, c, e) and Kell (K) antigen typing was performed using specific monoclonal sera and microplate technique, while Cellano (k) typing was performed with a monoclonal anti-k, antihuman globulin and column agglutination technique. Weak ABO subgroups were determined using the absorption elution method or molecular genotyping (PCR-SSP). Results: ABO antigen frequency is: A (40.89%), O (34.22%), B (16.97%), AB (7.92%) and weak ABO subgroups (0, 009 %). The established genotypes were AxO1 (0, 0026%) and AxB (0, 001%). Rh antigen frequency is: D (85.79%), C (71.7%), c (76.0%), E (26.0%) and е (97.95%). The most common Rh phenotype is the DCcee (32.7%) while the rarest phenotype is the DCCEE phenotype (0. 003%). The prevalence of K and k antigen is 7.5% and 99.94%, respectively. The frequency of the rare phenotype K+k- is 0.06%. Conclusion: Large scale phenotyping of blood group antigens enables the identification of blood donors with rare blood groups for patients with rare phenotypes or with antibodies to high-frequency antigens and to frequent antigens within one or more blood group systems.
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    Имунохематолошка дијагностика и менаџмент на алосензибилизациите во тек на бременост кон антигените од Rh-крвногрупниот систем
    (2015)
    Вовед: Алоимунизација на мајката, т.е имунизација во текот на бременост се дефинира како присуство на нерегуларни антиеритроцитни алоантитела во крвта на бремена жена, кои теоретски можат да предизвикаат HBFN. Кога еднаш ќе се создат антитела, со текот на времето тие можат да станат невидливи, но при ново изложување на антигенот, имунолошкиот систем ќе реагира со рапидно зголемување на количината на антителата. Цел: Цел на оваа студија е да се дефинира епидемиологијата на анти-D алоимунизацијата во тек на бременоста и одредување на нејзината преваленца. Да се одреди предиктивната вредност на количината и типот на антиеритроцитните антитела од Rh крвногрупниот систем и нивна корелација со клиничката слика на фетусот/новороденото. Да се предложи препорака за национална стратегија за фреквенцијата и дозирањето на антенаталната профилакса, во согласност со одредувањето на количината на фетоматерналната хеморагија (FMH) со проточна цитометрија. Да се предложи протокол за имунохематолошки испитувања кај алосензибилизирани бремени жени кон еритроцитните антигени и детекција на RhD статусот на фетусот со PCR фетална DNK. Материјал и методи: Во студијата ретроспективно и проспективано опфатени сe 22009 бремени жени, кандидати за имунохематолошки испитувања во тек на 10 години, од 2004 -2014 година. Проспективно се опфатени: 250 новородени, на RhD-негативни мајки,200 биолошки татковци на фетус/плод на RhD-негативни жени. Kaj 80 RhD-негативни бремени жени е детектирана и квантифицирана FMH со проточна цитометрија, а кај 30 е детектиран RhD статусот на плодот со PCR техника, од плазма на мајката. Тестирањата се изведуваа од серумот, плазмата и еритроцитите од венска крв, без антикоагуланс и/или EDTA, не постара од 24 часа. За новороденчината тестирањата се изведуваа од венска и од папочна крв без антикоагуланс и/или EDTA, не постара од 24 часа. Кај сите испитаници во студијата изведувани се имунохематолошки тестирања: o крвногрупна типизација на еритроцитните антигени, o скрининг на ирегуларни антиеритроцитни антитела (индиректен антихуман глобулински тест, ензимски тест и директен антихуман глобулински тест) Кај испитаниците кај кои скрининг тестовите покажаа позитивен резултат, беа извршени додатни имунохематолошки тестирања: o идентификација на антитела со повеќе комерцијални панели, o елуција на антитела, o квантитативно одредување на антиеритроцитните антитела со метода на титрација, o одредување на субкласата на анти-D антителата, o одредување на RhD статусот на фетусот со PCR фетална DNK. FMH беше одредена со метода на проточна цитометрија Добиените податоци се анализирани и обработени со помош на повеќе статистички методи. Резултати: Од вкупно 22009 бремени жени, антиеритроцитни антитела кон антигените од Rh системот беа детектирани кај 205 бремени жени, со идентификација на вкупно 237 антиеритроцитни антитела. Од нив, кај 169 беше идентифицирана сензибилизација само кон RhD антигенот, кај 1 кон С, с 1 и Е 1; кај 36 бремени беа присутни мултипли антитела, анти: -D+C 26, - D +Е 3, D+С+К 2, -D+ Jkb 1 и D+ Lea 1. 65,35% од сензибилизираните кон RhD антигенот не пимиле рутинска антенатална анти-D профилакса (ААДП), не е спроведена профилакса после сензитизирачка атака и абортус или е несоодветно спроведена профилакса во тек на бременоста. Кај 17.07% бремени не е спроведена постпартум профилакса, а кај 9.26% се детектирани анти-D антителата пред 28 г.н. FMH се забележува кај: 5% од жените за време на првото тромесечие од бременоста, кај 15% за време на второто тромесечие, кај 45% за време на третото тромесечие и кај 60% од родиликите. Во студијата беа испитани примероци од 45 новороденчиња на сензибилизирани бремени жени со анти-D антитела. Од 15 новородени со детектирани IgG1 антитела, 7 покажаа интензивна, 8 HBFN од среден или слаб сепен без терапија. IgG1 зедно со IgG3 беше детектирано кај 25 бремени жени. Од нив16 новороденчиња развија тешка HBFN, 9 беа со симптоми на HBFN од среден степен. Во 3 случаи каде беше детектирано само IgG3 анти- D антитело, новородените развија клиничка слика на HBFN од послаб или среден степен. Во два случаи бременоста заврши со мртов плод. Кај 22,91% новородени немаше симптоми на HBFN или тие беа со многу слаба симптоматологија. Од нив 8 беа со титар 8-32, 2 со титар 32-512 и само 1 со титар над 512. 54.16% новородени беа со симптоми на средно тешка HBFN, од кои 21 со титар на антитела во серумот на мајката до 32 и 5 со титар 32-512. Тешка HBFN се појави кај 22,91% новородени, 3 со титар до 32, 5 до 512, 2 над 512 и 1 заврши како фетална смрт, со титар над 1000. Вкупно 30 RhD-негативни бремени жени, од 12 г.н. до 31 г.н., беа тестирани со Real time PCR. Биолошкиот татко беше фенотипизиран како хетерозиготен на RhD антигенот. Резултатите покажа дека 30% од фетусите се RhD-негативни, а 70% се RhD-позитивни. Заклучок: Преваленцата на алосензибилизацијата во текот на бременоста кон Rh еритроцитните антигени изнесува 6,09%, а кон RhD 4.74%. Етиологијата на сензибилизацијата кај најголем дел од сензибилизираните е не почитување на RhIG профилаксата. Потребно е изготвување на Национална програма за RhD имунизацијата во бременоста, со ревизија на постоечките протоколи за RhD профилакса во тек на бременоста и по породувањето.
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    Protocols for detection and prevention of RhD alloimmunisation during pregnancy
    (SHMSHM / AAMD, 2015)
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    Ismaili A
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    Useni S
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    Dejanova-Ilijevska V
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    Mitevska L
    Mother’s alloimmunisation during pregnancy, also known as isoimmunisation, is defined as a presence of irregular Red Blood Cells (RBC’s) alloantibodies in blood of pregnant woman that can lead to Hemolytic Disease of the Fetus and Newborn (HDFN) or in severe cases to fetal demise. Aim: to evaluate the RhD alloimmunisation during pregnancy among women in R. Macedonia and to propose protocols that will improve healthcare and women safety during pregnancy. Material and method: for 22.009 pregnant women in the period of 2004-2014, were done immunohematology analyses: ABO blood group and Rh type, screening of RBC’s alloantibodies, Indirect Antiglobulin Test (IAT) with 5 panels of RBC’s antigens, enzyme test (two panels of RBC’s antigens), identification of RBC’s antibodies (Coombs and enzyme panels), quantification of antibodies and blood group phenotypisation. Results: total of 3.838 (17.42%) pregnant women were RhD negative. RBC’s alloantibodies were detected among 205 women, out of which 169 had sensitization toward RhD antigen and 36 pregnant women had multiple antibodies. The prevalence of allosensibilisation in R. Macedonia is 4.74%; 112 (54.62%) RhD sensitized pregnant women didn’t receive antenatal prophylaxis. Symptoms of HBFN didn’t show 50.93% of newborns, mild or strong intensity had 36.11% and 12.5% had fetal demise. Conclusion: The most often reason for RhD sensitization of pregnant women in R. Macedonia is the lack or inappropriate antenatal prophylaxis. It is expected that the wide use of a proposed new protocols will decrease the percentage of women’s RhD sensitization and the morbidity and mortality of newborns with HDFN.
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    Epidemiology of RhD alloimmunization in pregnancy in R Macedonia
    (Medical Faculty, Ss. Cyril and Methodius University in Skopje, 2015)
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    Violeta Dejanova-Ilijevska
    The most of the cases of the hemolytic disease of the fetus and the newborn occur in RhD positive newborns, born from RhD negative mothers. If RhD prophylaxis is not implemented, the mother often creates antiD antibodies as a result of small fetal-maternal bleedings during pregnancy and after delivery of the first RhD positive newborn Aim:To present the reasons of the RhD alloimunisation of the woman in pregnancy Material and methods: In the study retrospectively and prospectively are covered 14790 pregnant women, 200 newborns of RhD-negative mothers, 117 fathers of the fetuses/newborns of sensitized RhD-negative women. Tests were done in serum and in erythrocytes from venous blood, no more than 24 hours. From examined 14790 pregnant women, red blood cell antibodies to RhD antigen were detected in 117 pregnant women, with identification of 141 red cell antibodies. Out of these,87 were identified with sensitization only to RhD antigen, whilst in 21 pregnant multiple antibodies were present The analyses of data on the causes for sensitization to the RhD antigen in 117 pregnant women can be grouped into several related groups: 4 pregnant women with routine antenatal anti D profilaksis (ААDP),without history of potential sensitization attack during pregnancy; 15 pregnant women developed antibodies despite conducted postpartum prophylaxis; 21 pregnant women with non-implementation of prophylaxis after sensitizing attack and abortion; 29 pregnant women who did not receive AADP; 7 pregnant women without AADP and postpartum prophylaxis; 19 pregnant as a result of inadequate prophylaxis; 12 pregnant developed sensitization till 28 g.w in the current pregnancy; 10 pregnant with incomplete data. Conclusion: There are special reasons when sensitization occurs in pregnant women: Not recognizing the sensitizing condition during pregnancy, as well as errors in treatment, inability or error in determination of fetomaternal hemorrhage, lack of or disagreement with the existing norms for antenatal and postpartum prophylaxis.
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    Clinical Futures and Analysys Of Survival in Sample of Patients Infected with SARS-COV-2 in the Spesialised Hospital for Geriatric and Palliative Medicine ”November 13”-Skopje
    (Scientific Foundation Spiroski, 2022)
    Veterova Miljkovic L
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    Ljatif Petrusovska S
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    Jordanovski L
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    Ivanovska M
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    Bundaleska O
    BACKGROUND: New worldwide intensive studies of a new virus called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) have shown that in its clinical manifestations, the virus has an extremely different expression in different population groups, with age being found to be one of the most common and significant variables. AIM: The objective of this study is to categorize the difference between clinical and laboratory parameters of a sample of patients infected with SARS-COV-2 in the Specialized Hospital for Geriatric and Palliative Medicine “November 13” – Skopje, between survived and deceased patients, impact on the number and severity of comorbidities on the severity of the clinical picture and the survival rate. MATERIALS AND METHODS: In our study, we analyzed data from a sample of 113 patients hospitalized in our institution. The study is cross-sectional and observational, and in the methodology, we analyzed demographic data by gender and age groups, analysis of comorbidities, functional and nutritional status of patients, and risk factors for mortality and survival rate. For this purpose, we used several geriatric scores: Cumulative Illness Rating Scale scale–Geriatric (CIRS-G), degree of functional ability (Bartel), and the Geriatric Nutritional Index (GNRI) score. RESULTS: The deceased patients had a significantly higher CIRS-G score, while no significant difference in functional (Bartel) and GNRI scores was found. Multivariate regression analysis showed that lymphocytopenia and low saturation were high-risk factors for death in the geriatric population. CONCLUSION: Providing hospital-level care for the elderly with SARS-COV-2 contributes to a lower mortality rate.
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    Development of Transfusion Medicine in Republic of North Macedonia
    (2022)
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    Dejanova-Ilijevska, Violeta
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    Ristovska, Elena
    Transfusion medicine has been successfully practiced in North Macedonia for 76 years. Since its foundation, the Transfusion Medicine Unit is constantly growing and developing through the experiences of a large number of professional medical workers who left a lasting mark and paved the way toward modern transfusion activity. The Institute for transfusion medicine of North Macedonia constantly follows the latest world achievements in the field of transfusion medicine and they invest their energy in constant education, new technologies, and appropriate practices that ensure a high level of health services for donors and patients. This manuscript presents the journey of transfusion medicine in the Republic of North Macedonia covering various topics like the History, changes in legislation over time, blood donation activity ,other services and the future directions for the field of transfusion medicine in the country.
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    Noninvasive Antenatal Diagnosis of Fetal RhD Status
    (2018-10-25)
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    Dijana Plaseska-Karanfilska
    Introduction: Fetal cell-free nucleic acids within the blood stream of a pregnant woman come from fetal genetic material which can be acquired by simple venipuncture that reduces any risk to a minimum. Fetal cell-free DNA can be detected in the mother's blood stream in the 5th gestation week at the earliest. That enables fetal genotyping at the earliest possible stage of pregnancy which is best done in the 12th gestation week. Aim: To determine fetal RhD status at RhD negative pregnant women where the father is a heterozygote, Dd. Materials and Methods: The research includes 1540 RhD negative pregnant women, out of which at 30 of them the RhD fetal status had been detected by a PCR technique from the mother’s plasma. The RhD fetal status was confirmed after delivery by serologic analysis at 27 newborn babies. All research patients were submitted to serologic immunohematology testing: blood group typing of red blood cell antigens, screening of irregular anti-red blood cell antibodies. Fetal RhD status was determined by the plasma of RhD negative pregnant women using the real-time PCR technology in the period from the 12th gestation week until the 31 gestation week. The biological fathers of all 30 fetuses were phenotyped as heterozygote to the RhD antigen. The results showed that 30% of the fetuses are RhD negative, and 70% are RhD positive. Conclusion: The noninvasive fetal RhD genotyping is not only one precious tool in the management of RhD alloimmunised pregnancies, but it also allows antenatal anti-D immunoglobulin prophylaxis exclusiveness for only non-immunized RhD pregnant women carrying RhD positive fetus. Taking into consideration that 30% of the RhD negative pregnant women that carry a RhD negative fetus receive antenatal RhIG prophylaxis with no absolute need for it. At RhD alloimmunised pregnant women the noninvasive genotyping of the fetal blood group enables an easy and safe method in determination of a fetal risk from a hemolytic disease, and at the same time evading a vast laboratory and clinical monitoring of RhD antigen-negative fetal cases.
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    The Significance of Imunohematology Research in Relation to Menagement of Hemolitical Diseases of the Newborn in Republic of Macedonia
    (Scientific foundation Spiroski, 2014)
    Intorduction: The hemolytic disease of the fetus and the newborn (HBFN) is a clinical syndrome at which the basic patho-physiological disorder represents a hemolytic anemia of the fetus or the newborn. Besides the RhIG prophylaxis it still represents one of the reasons for morbidity and mortality of the fetus and the newborn. Goal: Prompt discovery of allosensibilisation to RBC antigens during pregnancy and successful management of HBFN, in order to decrease morbidity and mortality of the fetus and the newborn. Materials and methods: The study comprises in total 23 800 patients, 14 858 pregnant women and 8 842 newborn babies. The screening and identification of anti RBC’s antibodies detected in total 216 alloantibodies, out of which 81% (175) had a clinical significance. Out of the above mentioned 164 alloantibodies (65,9%) belong to the Rh system. The most often reason for a severe hemolytic disease is the anti-D antibody. The HBFN symptoms of mild and moderate degree demonstrated 32,5%, and 18,9% had symptoms of severe fetal suffering, and almost half of them (48%) were with or with mild HBFN and had no need of therapy. In 15% it was about alloantibodies of other Rg antigens: anti-C, anti-E and anti-c, at which in most cases there were no signs of HBFN, or it showed weak symptoms (89%), just one case of anti-c ended with intrauterine death. Conclusion Anti D antibody represents the most often reason for severe HBFN and displays a need of intrauterine transfusion and exsangvino transfusion. Anti-c is the only antibody that demonstrated the same potential for severe HBN as the anti-D. The most often reason for alloimmunisation of the mother is the lack of RhIG prophylaxis (97,8): postnatal, antenatal and in case of possible sensible conditions during pregnancy. Thus, there is a need and an outmost importance of elaboration and adoption of the National programe for RhIG prophylaxis in Republic of Macedonia.