Blood Transfusions

Why Are Transfusions Necessary?

All patients who undergo stem cell transplant will receive high doses of chemotherapy. One of the most important side effects of this chemotherapy is the suppression of bone marrow function. Bone marrow is the spongy substance inside the bones of vertebrae, ribs, pelvis, and skull. The bone marrow produces the various cells that circulate in the blood. These blood cells all have important functions. Red cells transport oxygen from the lungs to the tissues; too few red cells lead to anemia, tiredness, malaise, and pale skin. Platelets help stop bleeding by plugging holes in the blood vessel wall; patients with too few platelets bleed more easily and develop "petechiae", which are flea-bite size bleedings in the skin and may show up as small purple dots on the skin. White cells fight infections by eating and killing bacteria.

When patients receive high-dose chemotherapy, they develop low red cell levels (anemia), low white cell levels ("neutropenia"), and low platelet levels ("thrombocytopenia"). Therefore, such patients are at risk for tiredness, infection, and bleeding. This risk period starts a couple of days after the chemotherapy and may last only 1- 2 weeks (after autologous peripheral blood stem cell transplant) or many weeks (in some patients after allogeneic bone marrow transplant). During this risk period, patients need to be supported to prevent infection, bleeding, or anemia.

What Transfusions Are Used?

• White cells ("granulocytes" or "neutrophils"), which kill bacteria by "eating" them, live in the blood for only 6-12 hours. Therefore, replacing them in case of low levels is very difficult. Furthermore, such white-cell transfusions have additional drawbacks in the area of infection transfer, and by inducing transfusion resistance (allo-sensitization). Patients with very low white cells do not receive white-cell transfusions to prevent infections. Instead, they receive antibiotics (and sometimes antifungal and antiviral drugs) to prevent infections. White cell transfusions are used only rarely, and then exclusively to treat documented infections that do not respond to antibiotics.
• Platelets ("thrombocytes") survive in the blood stream for 6-10 days. Therefore, replacing them in case of low platelet levels can be more easily accomplished. In many patients, a platelet transfusion every third day will be sufficient to keep the platelets at a level that decreases their chance of bleeding. IBMT physicians try to keep the platelet level above 10,000/mm³ (> 10k) for patients who do not have signs of active bleeding; above 20,000/mm³ for patients with mild signs of bleeding; and above 50,000/mm³ for patients with significant bleeding or patients who need major surgery. Platelet transfusions take about one hour to infuse.

When platelets are obtained from whole blood, a number of units need to be combined to have enough platelets for transfusion. Usually, platelets from 6-8 units of blood are pooled into one platelet "concentrate". Such platelets are called "random" pooled platelets, since they originate from 6-8 different donors without any attempt to match them precisely with the patient. Alternatively, volunteer donors may be hooked up to an apheresis-machine. Platelets can then be collected, while very little plasma and few red cells are being removed. Thus, in a 1-2 hour procedure, a number of platelets similar to six units of random platelets can be collected. One such "pheresis platelet product" is sufficient for transfusion and should have the same effect as 6-8 units of random pooled platelets. IBMT physicians use platelets that have been leukocyte-depleted during the collection process or at the bedside (see below).

• Red cells circulate in the blood stream for 60-120 days. Therefore, unless a patient is bleeding, it does not take many transfusions to keep the red cell levels above a certain threshold. This threshold is mostly set with either the hemoglobin level (protein that is inside the red cells, and actually transports the oxygen) or the hematocrit (volume of red cells tightly packed together). IBMT physicians tend to keep the hemoglobin level above 8-9 g/dl. With the transfusion of 2 units of red cells every 1-2 weeks, the hemoglobin can usually be maintained in the desired range. Each unit of red cells is transfused over 1-2 hours.

Most blood donors donate about 450 cc of blood from their arm. This "whole blood" unit is divided by the blood center into different components: red cells, platelets, and plasma. One unit of red cells measures about 250 cc and contains the red cells from one unit of whole blood. IBMT physicians mostly use red cells originating from blood that has been collected in special bags with a filter to remove nearly all white cells prior to storage ("leukocyte depleted" red cells). If not available, they will use red cells collected in regular bags. A filter will then be used at the bedside to remove the white cells. Both methods of white-cell removal are effective and help to decrease the risk of transfusion reactions, production of antibodies against donor-specific proteins (allosensitization), and the transfer of some viruses.

What About Transfusion Risks?

All blood transfused by IBMT physicians, either inpatient or outpatient, comes from volunteer (non-paid) donors, and is extensively tested to prevent complications and transfer of disease. Nevertheless, complications can occur, and each patient should be aware of these possible complications.

• Transfusion reactions may occur. Most of these are relatively innocuous and are caused by the patient either being allergic to proteins in the blood of that particular donor (plasma reactions), or having antibodies against the white-cell type (tissue type) of the patient. Patients experiencing such reactions may develop fever, chills, and/or hives. Treatment consists of anti-allergy drugs such as Benadryl^®. To prevent reactions, the white cells can be removed prior to transfusion (leukocyte depletion) or Benadryl may be given. More serious transfusion reactions may occur if errors were made in the blood-group typing, or if the patient has antibodies which were unknown before the transfusion. Such transfusion reactions may cause kidney failure, low blood pressure, shortness of breath, and shock.
• Transfer of infectious diseases. All blood donors fill out a donor questionnaire, and all donor blood is tested for a wide variety of infectious agents. Tests are run to detect antibodies to HIV, to a number of hepatitis viruses, and to other viral and bacterial diseases. Although these precautions have greatly decreased the risk of transferring an infectious disease with blood transfusion, a small risk is still present. Donors may have been recently infected and not have made antibodies yet. An infectious agent for which a test may not be routinely performed or even exist, could be present. Human error during the testing is always possible. However small the risk of transferring an infection with blood transfusion has become, it definitely is not zero.

What Other Factors Are Important?

• Irradiated blood products. If a large number of fresh white cells remain in any blood product, these white cells may start growing inside the bone marrow of the patient, and thus form an inadvertent stem-cell graft. This happens only when the immune system of the patient is severely depressed and cannot "reject" these donor white cells. Patients with leukemia or lymphoma, or patients who have recently received a transplant, are at risk of such a complication, which is called "transfusion-induced graft-versus-host disease". Irradiation of the blood product will not kill the white cells, but will make it impossible for them to grow inside the patient. Therefore, IBMT irradiates the blood products administered to all transplant patients and to most patients with leukemia or lymphoma. If you would need a transfusion at another hospital or clinic, you must inform the personnel there that you should receive irradiated blood products. They should contact your IBMT physician or nurse. Blood products that need irradiation are red ells, platelets, and white cells. Fresh frozen plasma, cryoprecipitate and albumin do not need to be irradiated.
• CMV-negative blood products. Cytomegalovirus (CMV) is a virus that many people acquire during childhood or adolescence. In rural areas, about half the adults have been exposed to the virus; in urban areas often > 80% have previous exposure. In healthy people, the virus gives a flu-like illness or no symptoms at all. However, the virus stays alive in the body after infection, and can re-activate when the immune system is decreased. Thus, transplant patients are at high risk of reactivation of the virus. In such patients, CMV can cause very serious complications, with inflammation of lungs, bowel, kidneys, liver, and eyes. Blood from a healthy donor without symptoms can also transfer the virus to a transplant patient. The virus may be present in the white cells of the donor blood. Leukocyte-removal already decreases the risk of this transfer. IBMT has decided to take additional precautions for patients who are at the highest risk of serious CMV infection. Thus, patients who have never been exposed to CMV (CMV seronegative) and receive a stem-cell transplant from a donor (allogeneic transplant) are at very high risk of CMV infection. These high-risk patients will receive blood products that have been tested for CMV, and only products from CMV seronegative donors will be used.
• Change in blood type. Donors for allogeneic stem-cell transplantation are selected based on their HLA type (tissue type), and not on their blood type. Therefore, it is quite common that the donor and patient have different blood types. The blood type is determined by the red cells. After transplant and bone-marrow recovery the red cells will come from the donor and have the donor's blood type. As an example, if the patient is blood type A, and the donor is blood type O, the patient after transplant will become blood type O. The long-term outcome of an allogeneic stem-cell transplant is affected only to a small degree by the blood types of the donor and recipient. If an ABO difference exists, the transplant itself may create some technical difficulties, but these can be easily overcome. Red-cell recovery may be delayed after such transplants, and the patient may need support with red-cell transfusions for a prolonged period of time. More importantly, the patient should be aware that the blood type has changed or will change, and that old blood type cards are no longer valid. IBMT will provide you with a laminated card that indicates that your blood type may have changed. After your bone-marrow function has fully recovered, you may receive red cells of your new blood type. During the transplant process, usually red cells of blood type O are used, since these can be used for any patient (universal donor).

If you have questions or concerns about transfusions, or about blood donations from relatives and friends, we encourage you to discuss these with your physician, clinic nurses, or the transplant coordinator.