What must be done before blood or plasma may be donated, which requirements should a blood donation meet and in which ways can blood be donated?
Safety played a negligible role in the first blood transfusions. Between 1665 and 1670, particularly in France and England, experiments with blood transfusions were conducted. In England, Richard Lower was the first to be able to directly transfer blood from the artery of one animal to the vein of another. Meanwhile, the French doctor Jean-Baptiste Denys conducted pioneering research on blood transfusion in man. In 1667 and 1668, he tried to replace so-called ‘bad blood’ in patients with ‘fresh blood’, using the blood of lambs. A blood transfusion was assumed to cure madness and change human behaviour, and thought to make people younger and stronger. However, repeated administration of animal blood to humans resulted in all manner of complications. Denys’ experiments eventually even killed a patient, for which Denys was not prosecuted. The Paris municipal council did, however, prohibit all forms of blood transfusion under penalty of corporal punishment. It was not until the beginning of the nineteenth century that blood transfusions were carried out again. In 1818, after extensive animal experiments, the British obstetrician James Blundell began carrying out blood transfusions to humans. The patient and donor were laid side by side and the blood was transferred directly from the donor to the patient. After several successful transfusions, Blundell drew two fundamental conclusions that still apply: humans may only receive human blood and transfusions of human blood are only effective when given to replenish blood loss. These axioms earned Blundell the title of the ‘father of blood transfusion’.
Blood donor
Blood donors form the essential starting point of the supply of blood and blood products. After all, they supply the raw material for the production of blood components and medicines produced from blood. At every blood donation, safety is a priority. The protection of the donor and the safety of the patient who is treated with blood products are the main issues of donor-recruitment and donor selection procedures.
 | Blood donor
If the medical examination of the donor has revealed no irregulations, 500 ml of blood is collected. |
Our key principle is that we only use blood of voluntary, non-remunerated donors. In this way, we minimise the risk of contaminating the blood supply by only making use of blood that has been donated for altruistic reasons. Therefore, subjects who wish to be paid for a blood donation or are only interested in the results of tests for infectious-diseases are not permitted to donate blood.
Blood is not collected from people, who for medical reasons should not donate blood and people who run an increased risk of carrying infectious diseases that can be transmitted by blood.
The Sanquin Blood Banks manage the following aspects of the donation process:
- the medical examination of donors;
- the collection of donor blood;
- the determination of the AB0 blood group and Rhesus D factor of the donor;
- testing donor blood for the presence of infectious diseases that can be transmitted by blood;
- processing the blood, storage and distribution of the blood components to hospitals, and providing hospitals with recommendations on transfusion policy in general as well as for individual patients;
- conducting research.
We distinguish two groups of donors: first-time donors and repeat donors. First-time donors are subjects who have never donated blood or plasma at a Sanquin Blood Bank before, whereas repeat donors are those who have donated blood or plasma in the past.
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Medical examination of donors
Potential donors first undergo a thorough and specific medical examination before they can be accepted as a blood donor. The examination has two aims. Firstly, it serves to protect the potential donor, whose health may not be put at risk by giving blood. Secondly, we investigate whether the donation entails a risk for the recipient of the donated blood or its products.
Both first-time and repeat donors are all tested, each time before blood is given. The examination involves a medical questionnaire, a physical examination and blood tests. Specially trained blood bank employees conduct the donor tests and collect blood.
The physical examination takes place after the medical questionnaire has been completed. Blood pressure and pulse rate are measured, and the haemoglobin level is determined to exclude anaemia. The examining doctor discusses the medical questionnaire with first-time donors. For repeat donors the examination assistant discusses the questionnaire and the examining doctor will advise if necessary.
All donors are informed in detail about the background of blood collection, health guarantees and blood donation procedures. First-time donors do not donate blood after the first examination. Blood is only taken for blood group identification and infectious disease tests. If everything proves to be in order, blood may be donated during the next call and after an appropriate examination of the donor and used for the preparation of blood products.
Personal information is registered in accordance with the Dutch Personal Data Protection Act. The Sanquin Blood Banks apply their own privacy regulations. In addition, the processing of medical information falls under the realm of medical confidentiality. No information made available to the blood bank or data it has on file will be made available to third parties without the express written permission of the donor.
Blood donations are always anonymous, which means that the personal information of the donor is not indicated on the blood products. Only blood bank employees can trace this information by using the unique code attached to each donation. The patient in the hospital is not informed of the identity of the blood donor, and the blood bank (and donor) will not be informed about the identity of the recipient of the blood product.
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Collection of donor blood
If the examination of the donor has revealed no irregularities, we collect 500 ml of blood. We call this a donation of whole blood. After a venepuncture, the plastic blood-collection bag will be filled. This bag contains anticoagulants to ensure that the blood remains fluid after donation. Three other plastic bags (satellite bags) are connected to the blood collection bag. Between two of these satellite bags there is a filter for the removal of leukocytes from the red blood cells (see below).
The blood collection bag together with the satellite bags is centrifuged at high speed, creating several layers of blood components in the collection bag. The heaviest cells – the red blood cells – collect at the bottom of the collection bag. On top of the red blood cells is the buffy coat, which is an intermediary layer consisting of platelets and white blood cells. Above the buffy coat we find the plasma (see illustration below).
Separation of blood cells and plasma
The centrifugation of blood created three layers of blood components. At the bottom are the red blood cells. On top of the red blood cells is the buffy coat (an intermediary layer comprising platelets and white blood cells). On top of the buffy coat, there is the plasma. |  |
In a separation apparatus the plasma and the red blood cells are each squeezed into a separate satellite bag. The satellite bag for the red blood cells contains storage fluid and nutrients, to keep the cells in good condition. The tubes of the plasma bag and the bag with red blood cells are then sealed, after which these bags are disconnected. The bag with the red blood cells is connected to the third satellite bag, in which the red blood cells are collected after passage through a filter. The collection bag with the buffy coat is connected with four other bags with buffy coat from other blood donations, and with one plasma unit (from one of the five donations), and subsequently the contents of these six bags is pooled into one collection bag. By centrifuging this collection bag at low speed the platelets are separated from the white blood cells.
In this way, a donation of whole blood is, within 24 hours, separated into components, namely red blood cells, plasma and, sometimes also, platelets. Thus, a single blood donation will benefit several patients.
One of the precautions to render red blood cell and platelet concentrates even safer, is to remove the white blood cells by filtration. The leukocytes in these concentrates serve no purpose and could cause detrimental transfusion side effects, such as immunological complications and transmission of disease. Leukocytes are routinely removed from red blood cells by passage through a filter between two satellite bags. Leukodepletion of platelet concentrates is done separately. We call this leukocyte depletion. In 2002 leukocyte depletion was also introduced for quarantined plasma.
A couple of hours after the blood donation, the blood volume in the donor’s body returns to normal. However, the replacement of red blood cells takes several weeks, primarily because the replenishment of the iron supply, which is required for the production of red blood cells takes several weeks. Men have higher iron reserves in their body than women. For this reason, men are allowed to donate whole blood up to a maximum of 5 times a year (every ten to eleven weeks) and women no more than 3 times a year (every seventeen weeks).
Each donation immediately is given an individual code to enable identification of the donor of the blood. The collected blood is examined, after each donation. In the laboratory the AB0 blood group and Rhesus D factor are identified and tests are conducted for the detection of infectious diseases which can be transmitted by blood.
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Identifying the AB0 blood group and Rhesus D factor of donor blood
The laboratory identifies the AB0 blood group and Rhesus D factor twice in order to ensure accurate test results. In addition, other blood groups on red blood cells may be identified, which is necessary if the patient receiving the blood has antibodies against certain blood groups.
Sometimes it is also necessary to identify blood groups on platelets or to test the donor blood for the presence of antibodies against platelet blood groups. Also tissue groups and their antibodies can be important factors in blood transfusion.
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Excluding infectious diseases, transmittable by blood – testing donor blood
We test all donor blood for the presence of micro-organisms that can be transmitted by blood and cause infectious diseases in the recipient (see illustration). The donated blood is tested for hepatitis B, hepatitis C, AIDS, syphilis and a rare form of leukaemia. The hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause hepatitis B and hepatitis C infections respectively. AIDS is caused by the human immunodeficiency virus (HIV), the most common types of which are HIV-1 and HIV-2. Syphilis is caused by infection with the bacteria Treponema pallidum and the rare form of leukaemia is a result of infection with the human T-cell leukaemia viruses HTLV-I and HTLV-II. Individuals infected with these pathogens are prohibited from donating blood.
In chapter 6 these diseases, which can be transmitted by blood, are discussed in more detail. During the initial period after infection, which can last from several weeks to several months, the presence of viruses such as HIV and the hepatitis viruses cannot always be traced by blood tests. For this reason, it is crucial to the safety of the recipients of the blood product that the donor accepts his / her responsibility and truthfully reports any chance of being infected to the examining doctor.
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Testing donor blood
All donor blood is tested for bloodgroup identification and for the presence of micro-organisms that can be transmitted by blood |
In the blood bank laboratory each donation is tested for the presence of antibodies to HIV-1, HIV-2, HCV, HTLV-I, HTLV-II and Treponema pallidum. We also test for the presence of a specific protein (surface antigen) found on HBV. This surface antigen is abbreviated as HBsAg (hepatitis B surface antigen). In addition to tests for the presence of antibodies against HCV and HIV, blood banks test all blood donations (usually in minipools of 48 donations) also for the presence of the viruses themselves using the nucleic acid amplification test (NAT), which reveals the genetic material (RNA) of HCV and HIV. The test is based on the polymerase chain reaction (PCR), a technique that increases the amount of genetic material (DNA or RNA) and which enables us to detect even minute quantities of genetic material and thus the micro-organisms. The great advantage of these sensitive tests is that they reveal nearly all cases of HCV and HIV infection. In addition, they considerably reduce the period between the moment of infection and the moment at which the virus is detected – the window period or window phase.
The table below indicates the number of donors infected with a virus (namely HIV, HBV, HCV and HTLV) and the number of donors infected with Treponema pallidum in the Netherlands in 2000 and 2001. These figures are reported in absolute numbers and calculated per 100,000 donors. The numbers reveal that viral infections among Dutch blood donors are rare, but that they are not totally absent. Viral infections occur more frequently among first-time donors (subjects who donate blood, or are tested, for the first time) compared to repeat donors (subjects who have donated blood before).
The numbers for first-time blood donors give information concerning the prevalence of infection in the population from which the donors are recruited. In this case, the numbers approximate the quality of the blood of the Dutch population, while those for repeat donors indicate the incidence of infection among the repeat donor population, which is a measure of blood safety.
Table: The number of viral and bacterial infections among donors in 2000 en 2001
| The number of viral infections (HIV, HBV, HCV en HTLV) en bacterial infections (Treponema pallidum) among first-time and repeat Dutch donors, respectively, in 2000 (source: 2000 Sanquin Annual Report) and 2001 (Source: 2001 Sanquin Annual Report) |
| Number of donors tested positive in the Netherlands in 2000 | Total number of donors and donations in the Netherlands in 2000 |
First-time donors | Repeat donors | Registered donors | 612,00
584,000 whole-blood donors and
28,000 plasmapheresis donors |
 | absolute | per 100.000 donors | absolute | per 100.000 donors |
| HIV 1/2 | 2 | 3.4 | 1 | 0.2 |
| HBV | 26 | 44.1 | 8 | 1.4 | Number of donations | 875,000
773,000 whole-blood donors and
102,000 plasmapheresis donors |
| HCV | 10 | 16.9 | 0 | 0.0 |
| HTLV-I/II | 2 | 3.4 | 1 | 0.2 |
| Treponema pallidum | 10 | 16.9 | 82 | 0.4 |
| Number of donors tested positive in the Netherlands in 2001 | Total number of donors and donations in the Netherlands in 2001 |
First-time donors | Repeat donors | Registered donors | 614,000
572,000 whole-blood donors and
42,000 plasmaferesedonors |
 | absolute | per 100.000 donors | absoluut | per 100.000 donors |
| HIV 1/2 | 0 | 0.0 | 3 | 0.5 |
| HBV | 23 | 37.7 | 7 | 1.3 | Number of donations | 872,000
750,000 vol bloeddonaties en
122,000 plasmapheresis donors |
| HCV | 5 | 8.2 | 1 | 0.2 |
| HTLV-I/II | 3 | 4.9 | 1 | 0.2 |
| Treponema pallidum | 13 | 21.3 | 8 | 1.4 |
It is neither useful nor possible to conduct laboratory tests for all infectious diseases that may be transmitted by blood, for example malaria. It is essential that donors always report potential infectious risks. In cases of travel to a malaria endemic area, donors are usually temporarily deferred from donating blood.
Malaria is caused by parasites that are transmitted by mosquitoes in (sub) tropical regions. These parasites (Plasmodium parasites) specifically infect the red blood cells. Tests intended to trace the malaria parasite in donor blood are not very reliable. Donors who have visited regions with an increased risk of malaria must always report this. Even if the donor used malaria prophylactics (medication against malaria) or have taken other protective measures against mosquitoes (including mosquito repellents and wearing trousers and clothes with long sleeves), they still are deferred from donating blood for seven months.
Since 1995, donors are questioned regarding exposure to the (classic form of) Creutzfeldt-Jakob (CJD) disease – a brain disease that may be accompanied by a form of dementia, muscle contraction and paralyses. CJD is an extremely rare disease that usually manifests itself between the ages of 55 and 75. While this disease may occur spontaneously, it has also, in the past (before 1986) been inadvertently transmitted by medication (hormones) derived from human brain tissue. The involved medicines were produced from the pituitary glands, which originated from persons who died of CJD. In 1986, treatment with these hormones, including growth hormones and thyroid-stimulating hormones, prepared from cadavers, was stopped. In addition, CJD has been inadvertently transmitted by cornea and dura mater transplants. Subjects who have received such medicines or those who have undergone a cornea or dura mater transplantation are not permitted to donate blood. People with CJD and their family members are not permitted to donate blood.
A connection is made between a variant of Creutzfeldt-Jakob Disease (variant Creutzfeldt-Jakob Disease or vCJD) and the occurrence of mad cow disease (Bovine Spongiform Encephalopathy or BSE). vCJD is considered to be caused by the consumption of BSE-contaminated beef and beef products containing brain, spinal cord material or central nerve tissue derived from BSE-infected cows. Unlike the classic form of CJD, vCJD primarily affects people under forty years of age. The incubation period (the period before one becomes ill) for vCJD is possibly shorter than for the classic form of CJD. Both CJD and vCJD are frequently fatal within two years. The pathogens that are suspected of causing BSE and vCJD are called prions (see the section below), which are infectious protein-like particles that can be transmitted through brain tissue (including hormones from the pituitary gland), spinal marrow, eyes, small intestine and ganglia. It needs to be established to what extent CJD or vCJD can be transmitted by blood products. The above-mentioned leukocyte depletion is an additional precautionary measure believed to prevent the unknown risk of transmitting vCJD.
| In 1982, the American neurologist Stanley Prusiner introduced the term ‘prion’, which is derived from ‘proteinaceous infectious particle’. Just like viruses and bacteria, these particles can cause diseases. However the agent is believed not to contain DNA or RNA. The prion protein is not inherently pathogenic. A ‘normal form’ is found in all mammals, including humans. The aetiology and function of prions are not fully understood. Problems arise if a prion folds itself in an abnormal way (helix structure), and becomes pathogenic. According to one theory, the pathogenic prion forces healthy prions in the brain to adapt to its own abnormal structure. The abnormal structure of the prion cannot be restored by the body and amasses in the brain and nerve tissue, which are subsequently damaged. The deteriorated brain tissue accumulates rapidly, as a result of which the patient experiences kinetic disorders and dementia. Patients often die within two years. An additional problem is that the body does not recognise pathogenic prions as being foreign and, consequently, produces no antibodies, enabling the prions to continue unabated. Well-known prion diseases include CJD, Kuru and the Gerstmann-Sträussler-Scheinker syndrome (in humans), BSE (in cows) and scrapie (in sheep). |
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Plasmapheresis
A donation of whole blood involves collecting all the components usually found in the blood (including blood cells and plasma). However, it is also possible to extract only a specific blood component. For example, by plasmapheresis we obtain only plasma from the donor. A similar process can be used for platelets (thrombocyta-pheresis) and red blood cells (erythrocytapheresis). In this way, we only extract the blood component that is needed.
Plasmapheresis is performed at the blood bank. During plasmapheresis, the donor blood is separated into plasma and blood cells. The blood cells are immediately returned to the donor, enabling us to extract a larger quantity of plasma in one session without endangering the health of the donor. A whole blood donation supplies approximately 250 ml of plasma, while plasmapheresis provides up to 650 ml. In addition, a donor can safely give plasma much more frequently (every two to four weeks) as compared to whole-blood donation. This is due to the fact that red blood cells take longer to be replaced by the body than other constituents.
Plasmapheresis requires four steps. After a venepuncture, the blood enters the apheresis apparatus via a tube, where the blood is separated into cells and plasma. The plasma is then collected in a plastic collecting bag, while the blood cells are returned to the donor via the same tube (see illustration).
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| Diagram of the plasmapheresis |
Plasmapheresis is particularly suitable for obtaining hyperimmune plasma, with a high concentration of antibodies to a specific pathogen. Some plasmapheresis donors have these specific antibodies because in the past they have been infected with the pathogen in question or have been vaccinated against it. Hyperimmune plasma is a good source of specific immunoglobulins to the hepatitis B virus (hepatitis B), Varicella zoster virus (chicken pox), Clostridium tetani toxins (tetanus) or the Rhesus D factor on red blood cells (see Plasma fractionation). The specific immunoglobulins directed against the hepatitis B virus, the Varicella zoster virus and tetanus toxin are administered to patients who may have been infected with either of these pathogens. Anti-Rhesus D immunoglobulins are administered to Rhesus D-negative women, who have delivered or will deliver a Rhesus D-positive baby.
We also use plasmapheresis to obtain plasma for the preparation of specific clotting factors, including factor VIII, which are administered to patients who lack these clotting factors. For example, a lack of clotting factor VIII (haemophilia A) or clotting factor IX (haemophilia B) has serious consequences from bleeding during injury, operations or after accidents. Clotting factors are primarily derived from plasma obtained from whole-blood donations. However, plasmapheresis is an option if the need for clotting factors is greater than can be obtained from whole blood.
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