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SPECIAL COMMUNICATION
Year : 2022  |  Volume : 7  |  Issue : 1  |  Page : 71-76

Development of Transfusion Medicine in the Republic of North Macedonia


Institute for Transfusion Medicine of Republic of North Macedonia, Skopje, North Macedonia

Date of Submission28-Mar-2021
Date of Decision01-Apr-2022
Date of Acceptance05-Apr-2022
Date of Web Publication29-Apr-2022

Correspondence Address:
Dr. Ema Velkova
Institute for Transfusion Medicine of Republic of North Macedonia, Skopje
North Macedonia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/gjtm.gjtm_27_22

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  Abstract 


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.

Keywords: Developmenet, public of North Macedonia, Transfusion Medicine


How to cite this article:
Velkova E, Makarovska-Bojadzieva T, Dejanova-Ilijevska V, Petkovic E, Ristovska E, Drakulevska S, Mitevska L. Development of Transfusion Medicine in the Republic of North Macedonia. Glob J Transfus Med 2022;7:71-6

How to cite this URL:
Velkova E, Makarovska-Bojadzieva T, Dejanova-Ilijevska V, Petkovic E, Ristovska E, Drakulevska S, Mitevska L. Development of Transfusion Medicine in the Republic of North Macedonia. Glob J Transfus Med [serial online] 2022 [cited 2022 Sep 25];7:71-6. Available from: https://www.gjtmonline.com/text.asp?2022/7/1/71/344334



The Republic of North Macedonia is located in Southeast Europe, in the central part of the Balkan Peninsula, bordering Bulgaria to the east, Greece to the south, Serbia and Kosovo to the north, and Albania to the west. Extending on over 25,713 square kilometers, the Republic of North Macedonia is a territory inhabited by almost two million inhabitants. The capital is Skopje with about half a million inhabitants. It is a multiethnic and multicultural society with different religions. The official language is Macedonian. In the Republic of North Macedonia, apart from Macedonians, there are also many ethnic groups – Albanians, Turks, Serbs, Vlachs, Roma, and others. Two-thirds of the population are Orthodox Christians, others are Muslims, Catholics, so one can expect a wonderful mix of architectural and ethnic heritage. A natural paradise of mountains, lakes, and rivers, where life moves to a different rhythm, North Macedonia is blessed with outstanding natural beauty. It is dotted with beautiful Orthodox churches, monasteries, and Ottoman mosques.

The Institute for Transfusion Medicine of North Macedonia is a supreme and unique medical institution that links healthy and sick people and is committed to provide optimal amounts of safe blood and blood components for the needs of the citizens of their country. From its establishment until today, the mission of this institution is to encourage and nurture humanity by promoting voluntary blood donation, as well as enable donated blood reach those that need it the most.

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.


  History of Transfusion Medicine in North Macedonia Top


The first transfusion (direct blood donation from the vein of a healthy person into the vein of a sick person) in the annals of the Macedonian medicine was recorded in 1935, performed by a young surgeon. This act can be considered a kind of prehistory of transfusion activity in the country. The true history or the official beginning of the activity is connected to the constitution of the country after its liberation. On June 1, 1946, by decision of the Ministry of Health, the first blood transfusion service (BTS) unit was established, located in the basement of the Surgery Clinics in Capital town, Skopje. The first donors were fighters from the XV-Corps of (National Liberation War). For the next 3 years, a total of 206 L of blood was collected. The development and promotion of blood donation in next few years rapidly increased to 3765 units. March 17, 1953, BTS together with the Central Committee organized the first field action with a mobile team. During that period, transfusion service units in three bigger towns in Macedonia were opened. In the summer of 1952, the transfusion service unit in Skopje was renamed into “Institute for Transfusion Medicine” (ITM). In 1955, the Institute moved to a separate building within the Clinical Center. During this time, the testing of the Rh factor in donors was introduced. Until 1962, the number of blood units collected from 5572 in 1958 increased to 17.266, which was three times more than in the previous period. In the next period, immunohematology testing was developed with the first studies related to the presence of blood groups in our population. From 1965, we introduced component therapy, the process of lyophilizing the plasma, and the production of proprietary antiserums and reagents.[1]

Until 1966, most of the blood donation was paid and therefore unsafe. Hence, cooperation with the Red Cross was intensified with the intention to popularize blood donation, following the example of some developed countries. In the 70s of the last century, transfusion service units were opened in many cities around the country with the doctors who soon became specialists in the field of transfusion medicine. The need for the development of hematology as a separate branch imposed the necessity for additional space, so on May 24, 1968, a new joint building for the ITM was passed into use and even a long period in the autumn 1980, the two basic activities transfusion and hematology were separated, and each continued to develop independently. The seventies of the last century were years of intensive development in transfusion activities in Macedonia, both from the aspect of human resources and premises. In addition to this, equipment modernizing and expansion of the scope of work were also considered as the laboratory of hemostasis and thrombosis, which soon became a reference for the Medical Faculty of the University “Cyril and Methodius,” the laboratory for the control of transfusion transmissible infections (TTI) among blood donors, development of the department for human leukocyte antigen (HLA) typing, which actively participated in the team for transplants of tissues and organs from 1977 when the first kidney transplant was established. One year later, in 1981, the production of human albumin with ion-exchange chromatography was introduced (which successfully exists for 20 years), and the production of blood components was promoted. Following the new trends in the world in 1986, the use of plastic bags for the preservation of the blood sample was introduced, thus raising the quality of blood components and extending the period of blood storage. The number of collected blood units obtained exclusively voluntarily and donated without compensation increased continually. In this period, Pharmaceutical Department within the ITM was extremely active, producing parenteral solutions for the main clinical center in the country and functioned without interruption until the beginning of this century, when its activity slowly dimmed. The period from 1989 to 1996 was marked by the introduction of two new activities: automated donor and therapeutic plasmapheresis in patients, hemodynamic examination Doppler ultrasound (1994). In 1999 by the decision of the Ministry of Health, the center for hemophilia was established, which significantly improved the quality of life of people with hemophilia.[1]

In 2000, the institute actively participated in performing the first transplantation of stem cells in hematology patients.

A telemedicine network for transfusion medicine has been established in this past 7 years all over the country, thus overcoming the shortage of specialists of transfusion medicine.

With a fully automated system in immunohematology testing of donors and patients and TTI of donors with direct data transfer in e-system, we obtained a significant improvement of the quality and safety of blood products in the country.


  Legislation Improvements Top


After a long period of preparation, the network of Southeast Europe project “EFS 2005–2008 for development of the legislative measures for blood safety” was realized in cooperation with the French government. In the year 2007, the “Law for safety in blood supply in RM” was introduced,[2] which met the EU Directive 2002/98/EC,[3] to improve the quality work in transfusion activities. The by-laws took time to be defined harmonizing with EU legislatives Dir (2002/98/EC, 2004/33/EC).[4] After the adoption of the Law on safety in the blood supply and use of blood and blood components all over the country, from January 1, 2011, transfusion service was integrated as a single institution-Institute for Transfusion Medicine of the Republic of Macedonia (ITM of RM). Organization of the ITM of RM consists of 1 Institute of Transfusion Medicine in the Capital-Skopje, 3 Regional Blood Centers, and 18 BTS in the bigger cities of the country [Figure 1].
Figure 1: Organogram of the institute for transfusion medicine of North Macedonia

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With the Instrument for Pre-accession Assistance (IPA), funding a project on “Strengthening of the Blood Safety System” was implemented within the framework of IPA TAIB 2009 (Transition Assistance and Institution Building Component), in the year 2013–2014. EU supported the strengthening of the capacity of the (national institute of transfusion medicine [NITM]) in terms of significant improvement of quality and safety of blood products in the country and effective functioning of the blood transfusion system. The IPA is the means by which the EU supports reforms in the “enlargement countries” with financial and technical help. The training of qualified health professionals and specialists in transfusion medicine, biologists, biochemists, medical laboratory technicians was performed by experts of Transfusion Medicine from the Netherlands, Slovenia, and Serbia. The participants of the project were trained in blood-related issues and quality management system and had great opportunity to visit very well-developed transfusion centers in Amsterdam and Ljubljana. The standard operation procedures for all the methods we use in transfusion medicine were made and the EU Guide to the preparation, use and quality assurance of blood components (17th edition) was translated and adopted.[5],[6] Standardization of the equipment for the BTSs in the whole country was provided within the framework of this project. In the next 2 years (2014–2015), the department of transplantation immunology and molecular biology was fully equipped according to the “European society of workers in the field of immunogenetics, histocompatibility testing and transplantation” European Federation for Immunogenetics (EFI) standards to create a registry for HLA and blood group type platelet donors. In 2016, the Institute introduced a national information system for the registration of data from voluntary blood donors as well as processes related to processing, testing, and distribution of blood products. Since 2015, the Institute has been certified according to ISO 9001:2008, which meets the European/world standards for quality management. Due to good collaboration with the European Directorate for Quality of Medicines and healthcare (EDQM) external audit was performed at NITM), in the year 2016, known as Blood Quality Management Program. The Blood Proficiency Testing Scheme (B-PTS) is a form of external assessment of quality control management systems that use inter-laboratory comparisons to determine the performance of blood transfusion screening laboratories responsible for testing individual blood donations. This scheme supplements each laboratory's own internal quality control procedures by providing an external measure of their testing capabilities. The EDQM designs and organizes the B-PTS according to “ISO/IEC 17043:2010 Conformity Assessment-General Requirements for proficiency testing.”[7] In the year 2016, the NITM was performed B-PTS029 ABO Rhesus, extended phenotyping, and irregular antibodies external control. This practice continues in the year 2017, when the external control was performed at laboratory for testing the blood donor samples for TTI. The other project was “E-Donor project,” realized in cooperation with the Health Insurance Fund (HIF). With this project, an electronic database was created for donors who have more than ten blood donations.

It was directly related to the (HIF) system and the blood donor's electronic health card, to release the blood donor from paying co-payments.

The “South EU project” with Germany, Germany provided equipment for the Department for blood donors (scales-mixers, beds for donors, etc.) improving the quality and safety of blood. In that period, ITM-Skopje provided an interesting project with NLB technology for the assessment of health status of blood donors before blood donation by monitoring 120 parameters (biochemical values) by bloodless method. The first Balkan seminar on “Quality Management for European Blood Establishments” from September 27, 2016, to September 30, 2016 was held at the University “St Cyril and Methodius”- Medical Faculty in Skopje, for doctors from Bosnia and Herzegovina, Montenegro, Kosovo, Serbia, and Macedonia, with a total of 27 participants, of which 12 were from the Institute of Transfusion Medicine of R. Macedonia. The seminar was organized by the EDQM, an integral part of the Council of Europe and co-financed by the European Union. Institute of Transfusion Medicine was a host for students in the Erasmus + Program (2014–2020). The Institute is a training base for students with the cooperation of the Medical University in Sofia, Bulgaria, mobility of individuals-Students, placements in enterprises, training centers, and other organizations. Students were guided and monitored during the placement program by mentors designed by the host organization which was recognized by Medical University, Sofia. The area of interest was public health policies and their implications to quality of care and patient safety. Students worked on the preparation of their final report related to benefits of their observations and practices at the end of the placement program. Since 2019, the Institute has been certified according to certification ISO 9001:2015. Every year we have audit from EDQM and recertification.[8]


  Education Top


Unfortunately, although transfusion has been the educational basis of the Faculty of Medicine since 1969, in 1975, the subject Transfusion became optional. The situation changed even in 2008 when the subject transfusion became a regular subject at the medical faculty in the curriculum for students of general medicine, later as a subject on for the Faculty studies for Nurses and Faculty for Engendering for medical and laboratory diagnosis. The specialization for transfusion medicine is 5 years practice, learning, and ends with an examination with a three-member professorial commission. There is also postgraduate study for Transfusion Medicine (PhD study lasts 3 years) in the University “Cyril and Methodius” Medical faculty-Skopje, Republic of North Macedonia.


  Blood Donation Top


The current population of the Republic of North Macedonia is 2,082,658. Annual blood donation is around 51,000 donations, which is quite enough to meet all needs of the public and private health care all over the country. We can say that blood donation with 24 donations/1000 inhabitants is self-sufficient for N. Macedonia. ITM of RNM performs the collection, testing, processing, and distribution of blood and blood components.

The data presented in [Table 1] for 4 years, before pandemic COVID-19, show the real situation with blood donation in North Macedonia. There are more than 99% voluntary and nonremunerated (VNR) blood donations; unfortunately, the first-time donations are still in low percentage, as well as the women blood donors. The young population is represented by 16% average, and we are in process to improve it [Table 1].
Table 1: Blood donors in the Institute for Transfusion Medicine of North Macedonia

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In 2021 for improving the quality and safety of the donor, blood donation and the donate blood, the process of donation is automatically transferred from the mixer for blood to the donor database – e Delphyn. In that way, we have more data about: technician who performed the venipuncture, time of donation, duration of donation, quantity of donated blood, occurrence of any problems during the donation process.

Almost 100% of the blood is separated into blood components (red blood cell [RBC] concentrate, leukodepleted and filtered, fresh frozen plasma, cryoprecipitate, and platelet concentrate).

ITM-Skopje performs donor apheresis for plasma and platelet as well as for therapeutic purpose of the patients. We still have not established centers for plasmapheresis and have not enough plasma for fractionation. There is a project with the Ministry of Health, in process, for developing these activities.

The testing of donor blood consists of blood grouping, screening of RBCs antibody, and TTI. All tests are performed on with fully automated system with automatic transfer to the donor database.

Every blood unit is test on blood group ABO, Rh phenotyping, screening of irregular antibody on BioRad microplatelet assay on fully automated system Techno and IHA-500 with automatic data transfer to the e-system.

The Macedonian national legislative mandates the examination of HBV, HIV, HCV, and Treponema pallidum (TP). Serological laboratory testing has been introduced in the 1950s for Syphilis and HBsAg, in the 1980s for HIV, and in the 1990s for HCV.

At present, every blood unit is screened for HBsAg, anti-HIV (p24 antigen and HIV-1/2 antibodies), anti-HCV, and anti-TP using serological assay CMIA-Architect system-Abbot. There is an algorithm in accordance with the European Council directives and EDQM guidelines for retesting of the initially reactive blood samples and donor deferral, donor information, and counseling. Repeatedly, reactive samples are retested with confirmatory assays such as Vidas HBsAg Ultra for HBV and Immunoblot Deciscan HCV Plus for HCV.

With the introduction of the donor database – e Delphyn in 2017, the TTI prevalence was calculated according to the number of blood donors instead previous calculation according to the annual number of blood donations. During 2017–2019, there are not any significant changes in the rates of HBV and HCV positivity, but there is a slightly increasing rate of HIV positivity [Table 2]. The TTI prevalence in first-time donors versus repeat donors was also calculated, as it is shown in [Table 3] and [Table 4], respectively. According to epidemiological data reporting, TTI prevalence is higher among repeat donors than in first-time donors.
Table 2: Prevalence of transfusion transmissible infections markers in blood donors

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Table 3: Epidemiological data reporting transfusion transmissible infections prevalence in first time donors

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Table 4: Epidemiological data reporting transfusion transmissible infections prevalence in repeat blood donors

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The fact that blood donation in our country is VNR, regularly and there are no family/replacement donors in the past few years, donor selection and deferral criteria are permanently revised contributes to the low prevalence of TTIs in our donor population as well as to the blood safety.

At present, we are also in the process of implementing nucleic-acid testing (NAT) as a complement to traditional serology testing, to fully optimize the safety of their blood supplies.


  Outpatient Departments Top


The department has an ambulance for pick up and examining patients and also a laboratory for hemostasis.

In 2014, a software called “My appointment” was implemented by the Ministry of Health in the Outpatient Department for patients with thrombosis. All specialists of transfusion medicine have terms in the system. Patients with peripheral and deep vein thrombosis are diagnosed and treated in the outpatient department, patients, and pregnant women with thrombophilia as well. Regular checkup of INR from capillary blood samples for those patients on oral anticoagulant therapy also is performed in the outpatient department.


  Centre for Hemophilia Top


Hemophilia care in the Republic of North Macedonia is based on collaboration between three institutions: Centre for Hemophilia in the Institute of Transfusion Medicine, Department of Hematology in the University Children Clinic, and University Clinic of Hematology. According to European Hemophilia Consortium and European Association for Hemophilia and Allied Disorders, Centre for Hemophilia is recognized as European Hemophilia Comprehensive Care Centre. Centre for Hemophilia collaborates closely with educated team members of multidisciplinary team for bleeding disorders from many specialties, such as hematologists, pediatricians, dentists, oral surgeons, orthopedic surgeons, physiatrists, physiotherapists, psychologists, social workers, gynecologists, and biologists. The center is responsible for laboratory diagnosis of bleeding disorders, registration of people with bleeding disorders in the National Registry, regular periodical checkup for people with bleeding disorders and recommendations for prophylaxis, as well as treatment for adults with bleeding disorders and social/psychology counseling.[8]

Laboratory tests for the diagnosis of bleeding disorders and thrombosis in our outpatient departments are the following: screening hemostasis (Plt, PT, activated partial thromboplastin time, TT), deficiency of factors I, II, V, VII, VIII, IX, X, XI, XII, and XIII by quantitative coagulation method, detection of inhibitors by Bethesda coagulation method, Ristocetin cofactor activity assay (von Willebrand Factor Assay) and VWF Ag, Ristocetin-induced platelets aggregation, Adenosine Diphosphate (ADP) and Collagen-induced platelets aggregation. This department provides tests, diagnosis, and therapy for ambulatory patients and hospitalized patients in public hospitals all over the country.

There is a special laboratory (waiting for the document from MH to be named as Referral Laboratory of immunohematology) that works by the algorithm in accordance with the European Council directives and EDQM guidelines for retesting of the initially reactive blood samples for irregular antibody in donors and patients. Furthermore, this laboratory is in charge for solving all discrepancies about blood groups, screening identification of irregular RBCs antibody, posttransfusion reactions, autoimmune hemolytic anemia. Immunohematology tests in pregnant women, hemolytic disease of the fetus, and newborn as well as counseling are performed in this laboratory.

The department of transplantation immunology and molecular biology are involved in the transplantation of organs (kidney, heart), equipped by the EFI standards (The European Federation for Immunogenetics). The HLA typing for platelet registry and molecular typing for cardiovascular disease and thrombophilia in pregnant women, sterility, and patients with thromboembolic events are performed in the same laboratory, as well.

The Department for Quality Assurance and Quality Control is included in the preparation of the documentation, working procedures, collecting and analysis of nonconformities, performs internal audits and is included in external audits by EDQM. Quality control of the blood components is performed only in the Institute for Transfusion Medicine in Skopje: residual leukocytes count in leukocyte-depleted blood components, red cells, hemoglobin, hematocrit, hemolysis, platelet content, pH, factor VIII, fibrinogen, and factor von Willebrand.


  Future Top


The project for fractionation of plasma in North Macedonia in collaboration with the Ministry of Health is nearing completion, which includes the organization of plasmapheresis centers in a few towns of the country.

There is procedure documentation for the referral laboratory for immunohematology. The laboratory is unique in the country and has 6 years of positive assessment external controls from EDQM.

Furthermore, there is procedure documentation for referent laboratory for transplantation immunology and molecular biology, with 8 years of positive assessment external controls from EFI.

Employees of the Institute for transfusion medicine of North Macedonia constantly follow 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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Official Gazette of the R. of Macedonia, September 14, No. 110; 2007. p. 47. https://www.refworld.org/pdfid/5b3f3e5c4.pdf [Last accessed 2022 Mar 20].  Back to cited text no. 1
    
2.
Velkova E, Blagoevska M, Makarovska Bojadzieva T, Andonov G. Monograph, 70 Years Transfusion Medicine in Macedonia, Institute for Transfusion Medicine of RSM; 2016.  Back to cited text no. 2
    
3.
Directive 2002/98/EC of the European Parliament and of Council of 27 January 2003 Setting Standards of Quality and Safety for the Collection, Testing, Processing, Storage and Distribution of Human Blood and Blood Components and Amending Directive 2001/83/EC. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/directive-2002/98/ec-european-parliament-council-27-january-2003-setting-standards-quality-safety-collection-testing_en.pdf. [Last accessed on 2022 Mar 20].  Back to cited text no. 3
    
4.
Commission Directive 2004/33/EC of March 2004 Implementing Directive 2002/98/EC of the European Parliament and of the Council as Regards Certain Technical Requirements for Blood and Blood Components. Available from: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/commission-directive-2004/33/ec-22-march-2004-implementing-directive-2002/98/ec-european-parliament-council-regards-certain-technical-requirements-blood-blood-components_en.pdf. [Last accessed on 2022 Mar 20).  Back to cited text no. 4
    
5.
Jovicic M, Primoz R, Resnik H. Manuel and Instructions for Safety and Quality of Blood and Blood Components, IPA Funded Project “Strengthening of the Blood Safety System.” MOH; 2014.  Back to cited text no. 5
    
6.
ISO/EC 17043:2010 Conformity Assessment General Requirements for Proficiency Testing. Available from: https://www.iso.org/obp/ui/#iso:std:iso-iec:17043:ed-1:v1:en [Last accessed on 2022 Mar 20].  Back to cited text no. 6
    
7.
Implementation and Certification a Quality Management System ISO 9001under the Institute for Accreditation of the Republic North Macedonia. Available form: https://iarm.gov.mk/wp-content/uploads/2021/03/Report-IARM-2012.pdf. [Last accessed on 2022 Mar 20].  Back to cited text no. 7
    
8.
Dejanova Ilijevska V. Quality of Life in Adults with Hemophilia Treated with and Without Prophylaxis. Dissertation. Skopje, North Macedonia: Medical Faculty Skopje; 2019. p. 18 20.  Back to cited text no. 8
    


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