Transfusion of blood and blood products

Immunological basis and indications

Blood transfusion is a treatment that must adapt to clinical and biological status of each patient. The indication of the total blood is exceptional (exanguino- transfusion). Whole blood is separated into blood derivatives in which there are:

– The labile blood derivatives with the red blood cell concentrates, platelet concentrates, leukocyte concentrates and plasma. These derived from the fractionation of whole blood can also be obtained from plasmapheresis or apheresis using cell separators in batch or continuous flow.

– Medicinal products derived from blood, from the plasma fractionation industry. They are considered drugs and their availability is assured by pharmacies. The treatment suffered by these products during their preparation actually secure products vis-à-vis the risk of transmission of viral diseases. They are used in particular for the correction of coagulation disorders associated with deficiencies of certain clotting factors (haemophilia …) or for the prevention or treatment of certain infectious conditions (immunoglobulin deficiency).

Immunological Basis:

A- Red blood cells:

They present on their surface antigenic structures to the origin of blood groups. More than 650 different antigens have been described. They are responsible for human polymorphism. The introduction of red blood cells in a recipient, a risk of alloimmunization to be taken into account in the subsequent selection of blood products.

1- ABO blood group system:

This system is characterized by the presence of two antigens, the antigens A and B. Their presence or absence on the red blood cell is at the origin of the four blood groups A, B, AB and O. The absence of antigen and (or) B of the red blood cell results in the production of specific antibodies in serum. These antibodies are called “natural” because they appear outside of any transfusion or gestation. They are developed later than the age of 1 year and their systematic presence is the cause of mandatory rules of compatibility in the ABO system. There transfusion compatibility rule that governs when packed red cells for transfusion or any blood product containing red blood cells (inset). When the plasma is transfused compatibility rule is contrary to the previous (box).

2- The other blood group systems:

Rhesus, Kell, Duffy, Kidd … They do not all have the same importance and they are distinguished by their antigenicity.It is their ability to induce the formation of a alloantibodies when transfused. The Rhesus system is a complex blood group system (tens of antigens) in which an antigen is systematically sought in determining blood grouping. This is antigen D. When present, the test is said blood Rhesus positive. When this antigen is absent, blood is Rhesus negative said. The Rhesus compatibility is respected (except in exceptional circumstances) as well as ABO compatibility because the risk of immunization varies from 50 to 75% if the Rh-positive blood is transfused to Rh negative recipient. Next to that antigen D, we must emphasize the importance (in transfusion and obstetrics) antigens C, c, E, e, which are among the most immunizing antigens. It may be necessary to prevent a vis-a-vis immunization of these antigens in some clinical circumstances. The Kell system is also an important blood group system because Kell (K) is the most immunizing antigen after the D antigen (Immunization risk = 35%). Immunization vis-à-vis this antigen will be prevented as the antigens D, C, c, E and e by using phenotyped blood. Despite the extreme diversity of antigens present on a red blood cell, compliance with only Rh and Kell phenotypes prevents 95% of red cell allo-immunization. Other antigens (Duffy, Kidd, MNSs) are less frequently involved in allo-immunization. Compatibility vis-à-vis these antigens will be respected in smaller clinical circumstances or when the corresponding antibodies will be present in the recipient. Some of these antigens are called public. They are observed in all individuals except few people who have none (phenotype “negative public”). The immunization risk is permanent. The risk of transfusion reaction is prevented by autologous transfusion (sampling and long-term preservation by freezing red blood cells of the person concerned) or through a rare blood bank (bank centralizing samples of people with a phenotype lacks a public antigen). The search for irregular antibodies (RAI), mandatory before any transfusion (must be older than 72 h) avoids transfusion reactions due to antibodies alloimmunization or natural. When there is a history of transfusion or pregnancy, the use of recorded blood (cross match) helps increase blood safety of the patients concerned.

B- Leukocytes:

They carry antigens on their membrane. There are common antigens to different cell types. These are antigens of histocompatibility, the HLA system. Antigenic polymorphism in this system is very important and the antigenicity of HLA A HLA B and systems is high. Anti-HLA immunizations are common. Repeated pregnancies are causing anti-HLA immunizations. Leukocytes present in cellular blood components play the same role. Polymorphonuclear also possess membrane antigens of their own (NA systems, … PN). these antigens may induce allo-immunization responsible incidents or accidents whose clinical transfusion intensity varies from simple ineffectiveness transfusion to pulmonary edema lesions. In an immunocompromised patient (originally acquired or inherited), donor lymphocytes can induce a response against the antigens of the recipient. This is the phenomenon of graft against the host (graft-versus-host disease). Leukocytes are also behind an immunomodulation which, in a tumor or surgical pathological context (eg intestinal surgery) may increase postoperative infections or tumor recurrence. Clinical data remain contradictory.

C- pads:

These cells bear the HLA antigens. The presence of anti-HLA antibody is responsible for clinical events (chills, rigors …) during the transfusion of non-HLA compatible platelets. These antibodies are also responsible for refractory state leading to a transfusion inefficiency. Refractory states represent a major problem in transfusion. Platelets also carry specific antigens combined in the HPA system (human platelet antigen) in which there is also a polymorphism. The specific anti-platelet immunizations are responsible for transfusion incidents similar to those observed with the anti-HLA antibodies. They are also responsible for Fetomaternal incompatibilities with neonatal thrombocytopenia.

D- Plasma:

Certain plasma proteins are capable of inducing the formation of antibodies in patients with selective deficiency of a protein. We must retain the possibility of vis-à-vis immunization of factor VIII in hemophilia. There are also immunizations vis-à-vis certain immunoglobulin classes (IgA) in IgA deficient patients. They are the cause of serious transfusion reactions.

Indications of blood derivatives:

A- blood erythrocyte Derivatives: packed red cells

These blood products are indicated in the correction anemic states.

1- standard globular concentrate:

The shelf life of the blood product is 42 days. Ongoing research give hope for this period is extended to 49 days. The red cell concentrate is obtained by transferring to a second pocket of the supernatant plasma after centrifugation of whole blood. The standard product must contain at least 45 g of hemoglobin per unit. The dose in mL is given by the following formula: Volume to transfuse = [(Hb desired – Hb patient) weight in kg T] T 2 This blood derivative contains a large amount of leukocytes and platelets from the donor.

2- globular concentrate leukodepleted:

In such packed cells, leukocytes are removed largely by filtration. Only globular concentrates which the number of residual leukocytes is less than 1 x 106 can be called globular leukodepleted concentrated. When the amount of residual leukocytes is greater than this value the blood product is said leukocyte depleted. The directions of these two products are distinct. The leukocyte depleted packed cells avoids transfusion reactions in patients with moderate anti-leukocyte immunization. When the anti-leukocyte immunization is intense or polyspecific, use of leukocyte-depleted blood is made compulsory. The amount of residual leukocytes present in packed red cells, leucocyte depleted significantly reduces the risk of anti-HLA primary immunization.

3- globular concentrate Washed:

Red blood cells are déplasmatisés by washing. The rate of extracellular proteins must be less than or equal to 0.5 g.This product is indicated when the vis-à-vis immunization of certain plasma proteins is responsible for transfusion accidents. This is usually anaphylactic shock induced by anti-IgA specific immunizations.

4- Concentrated erythrocyte phenotype:

This is not a specific package of red blood cells collected but an immunological selection. Immunohematological the qualification of these blood products is no longer limited to simple determination of blood group ABO and Rh. All these products are phenotyped at least in the Rhesus system (antigens C, c, D, E, e) and in the Kell (K antigens and k). The selection of packed red cells is made to avoid the introduction of one or Rhesus antigens and (or) Kell absent erythrocyte phenotype of the patient. The phenotype blood is used in two situations:

– Prevention of immunization; it is primarily female recipients still of childbearing age. This prevention regarding any subsequent transfusion risk. It also relates to the maternal-fetal risk. A transfusion-immunization may be the cause of a maternal-fetal incompatibility. The concentrates globular phenotyped are also indicated for multiple transfusions. The repetition of acts transfusion increases the frequency of immunizations. In some pathologies (eg hemoglobinopathies) compatibility phenotypes may affect other antigens such as Duffy antigens, Kidd and Ss;

– In already immunized patients, introducing a vis-à-vis antigen which the patient is immunized causes hemolytic transfusion reaction. The phenotype blood compatibility and respect the Rhesus and Kell antigens involved in the patient or other antibody (highlighted by a search for irregular antibodies).

The qualification déleucocytée:

Residual leukocytes <1.106 Re:

– Concentrated globular;

– Platelet concentrates (standard and apheresis). allows:

– Avoid transfusion reactions (shudder-hyperthermia) in immunized patients (HLA antibodies);

– Limit the risk HLA immunization in patients receiving multiple transfusions or awaiting transplantation.

The qualification phenotyped:

Concerns: red blood cells, leukocytes and platelets:

– For RBCs standard phenotype regards the Rhesus system (Ag C, c, D, E) and Kell (Ag K and k);

– For platelet concentrates HLA phenotype relates A and B antigens or specific platelet antigens (HPA) according to the origin of immunizations;

– For concentrated leukocyte phenotype relates to HLA antigens A and B. Allows:

– Avoid immunizations in patients at risk;

– Avoid transfusion reactions in immunized patients.

5- globular concentrate compatibilised:

This qualification can be applied to different categories of packed red cells already mentioned. It is an immunological selection blood products but it is personalized. Packed red cells are tested patient serum vis-à-vis. When the test is negative, packed red cells are presumed compatible. The validity of this assay is limited to 72 hours. Beyond this deadline could reappear antibodies in the serum of the recipient.

6- globular concentrate preserved by freezing:

All statements blood derivative are very limited. It is most often of autologous red blood cells corresponding to rare phenotypes (phenotypes “negative public” usually stored in the National Bank of scarce blood of the National Reference Centre on blood – CNRGS) or collected from patients polyimmunisation complex. This blood product is still phenotype. Thawing causes deleukocytation match the criteria of leukocyte-depleted blood.

7- irradiated blood cell concentrate:

This is a physical treatment of the blood product. The irradiation (between 25 and 45 G) makes lymphocytes donor unable to develop a graft against the host. This qualification is necessary in immunocompromised patients (eg .: after hematopoietic stem cells or neonatal).

B- platelet Derivatives: platelet concentrates

The blood product is indicated for the treatment of thrombocytopenia. The statements refer to the bleeding disorder associated with thrombocytopenia (80% of indications in hematology). The indication may also be preventive in a context aggravating (major thrombocytopenia accompanied by fever, splenomegaly or in a surgical context). The retention period for this blood product is currently 5 days.

1- standard platelet concentrate:

This product is obtained by the fractionation of whole blood. The treatment of thrombocytopenia requires the use of several standard concentrated. They are obtained by the mixture of 6 to 8 units. The dosage is determined depending on thrombocytopenia and patient context. This standard platelet concentrate is “contaminated” by a high number of white blood cells that may be responsible for transfusion reactions in immunized patients. The presence of HLA Class I antigens on platelets may also be responsible for a transfusion inefficiency in an immunized patient.

2. Concentrate apheresis platelets:

It is obtained from the sample from a single donor, using a cell separator. The alloimmunization risk HLA and viral risk are reduced. The blood product is indicated whenever we want to limit a patient risk of allo-immunization. It is also indicated in patients with a clinical response at the standard transfusion of platelet concentrates or in the presence of a transfusion inefficiency with standard concentrated.

3- concentrate platelets leukodepleted:

Leucocyte depletion can be performed on both concentrates Platelets as concentrates, apheresis platelets. The absolute number of residual leukocytes must be less than 1 x 106. This product helps prevent transfusion reactions of immunological origin (HLA immunization). It also prevents alloimmunization vis-à-vis these antigens. However, in 25% of cases, there is still transfusion reactions probably related to the release of mediators by certain leucocytes (the role of filtration?).

4- concentrate platelets phenotype:

This qualification concerns apheresis concentrates. The antigens concerned are usually HLA A and HLA B. They are then identical to those of the recipient or have said cross-react with these antigens. Immunological selection can also be done on specific platelet antigens (HPA). This is indicated as part of a maternal-fetal incompatibility with neonatal thrombocytopenia due to anti-HPA immunization 1. The transfusion should make platelets lacking the antigen-HLA compatibility 1. (cross match) can be performed as in globular concentrates. The test is then performed between the recipient’s serum and leucocytes or platelets of donor origin according to immunizations.

5- Concentrate Washed plate:

This is a product that should contain less than 0.5 g of protein. The indications are identical to those concentrates globular déplasmatisés such serious transfusion reactions due to selective immunizations vis-a-vis of plasma proteins (anti-IgA). Platelet concentrates (standard or apheresis) may be irradiated for identical to those directions of irradiation globular concentrates.

C- leukocyte Derivatives: concentrates of granulocytes

These blood products have very limited indications. They are accurate: infectious syndrome with hyperthermia> 38 ° C for 48 h, severe neutropenia (<100 per mm3 PN) and ineffectiveness of antibiotics with broad spectrum for 48 hours.They are, in most cases, patients in severe aplasia.

1- Granulocytes:

It is always obtained by apheresis. Concomitant fungizone and (or) plasma from female donors is strictly prohibited.

2- Granulocytes HLA phenotype:

The donor may be selected according to HLA antigens and (or) anti-HLA antibodies present in the recipient. The granulocyte concentrates are routinely irradiated given the clinical context in which they were prescribed.

Highlights to include:

• Blood transfusion is a selective therapy that must adapt to the patient’s pathology. Cell derivatives (red cells, leukocytes, platelets) carry immunization antigens responsible.

• The observed antibodies can cause transfusion reactions imposing an immunological selection of blood products.Globular concentrates from fractionation of whole blood are used in the treatment of constitutional or acquired anemias. Platelets prepared from whole blood or by apheresis, are used in the treatment of bleeding disorders thrombocytopenia. Leukocytes obtained by apheresis have precise information and very limited in severe neutropenia with infectious syndrome. Therapeutic plasma is used only in the treatment of coagulation factor deficiencies.

• Transfusion difficulties with alloimmunization are managed either by pretreatment products (eg. Removal of leukocytes by filtration) or by immunological selection.

Strong Points to remember:

• The reasons of economy of blood products (whose availability is sometimes difficult) and the need for therapeutic efficacy require the use of blood products adapted to the clinical and biological context of patients. In particular, the anemia is corrected by the red blood cell transfusion. There is no indication in adults justifying the use of a single red cells (that is in any case unnecessary transfusion).

• Transfusion incidents of immunological origin should be prevented by an immunological selection of blood products:

– Or by removing the offending cells: method of leukocyte depletion;

– Either by selection of cells lacking the antigens involved in the immunological reaction.