Blood Transfusion and Blood Products

Over 250 different antigens have been found on the surface of red blood cells but the most important of these belong to the ABO system. A and B antigens are important because patients who lack one or both of the antigens form antibodies against the absent antigen(s). These circulating antibodies can fix complement and produce intravascular haemolysis. They are naturally occurring without earlier antigenic stimulation. In this way group A patients produce anti-B antibodies, group B patients produce anti-A antibodies and group O produce both anti-A and anti-B antibodies.

Whilst the majority of AB patients produce no circulating antibodies and can receive any blood group, the situation is complicated by the existence of group A1 and A2 subgroups. A1 equals approximately 80% of the entire A blood type population, and A2 makes up the remaining 20%.¹ Group A2/A2B patient form A1 antibodies.²

Five major antigens in the Rh system are D, C, c, E and e and of these the RhD antigen is highly immunogenic and thus clinically significant. 15% of the population is Rh-ve and they are at risk of an immune-mediated transfusion reaction.

There are a large number of other blood groups identified but the Kell antibodies and Kidd antibodies are amongst those known to be associated with transfusion reactions.

Before receiving their blood transfusion, patients are typed for ABO and Rh and and the patient's serum is screened for antibodies to other non ABO blood groups. If agglutination occurs, serum is tested further to identify antibodies present.
Increasingly, new technology is being used to crossmatch blood which utilises DNA genotyping. This enables a much wider range of antigens to be tested for, enabling the identification of rarer blood groups. This is particularly significant for compatibility testing.

Before being transfused to a patient, donor red cells are mixed with patients serum and if no reaction occurs the unit is considered compatible. In an extreme life-threatening situation there may not be enough time to perform this, in which case it is permissable to use group O Rh-ve red cells until testing is possible.

Whole blood

In most circumstances, blood component therapy has replaced the use of whole blood. However, whole blood is still occasionally used for massive transfusion in circumstances in which rapid correction of acidosis, hypothermia and coagulopathy is required. This mainly occurs in military situations for trauma patients who require resuscitation.³

Red blood cells

Red blood cells are prepared from whole blood by removal of most of the plasma. They are indicated in both acute haemorrhage and chronic anaemia. Red cell units have a haematocrit of 70% (Citrate Phosphate Dextrose adenine solution CPDA-1) or 55-60% (additive solutions, AS) with a shelf life of 35 days and 42 days respectively when refrigerated at 1-6°C. A decision to give a transfusion should be reached both on the patient's clinical situation and laboratory findings, not on Hb alone.^4,5 Transfusion is often not considered until Hb <7g/dl but patients with unstable angina or acute MI may require transfusion at Hb <10g/dl. Single unit of red blood will typically increase Hb by 1g/dl.Other red blood cell products include leucocyte-reduced components, which can reduce febrile reactions and are an alternative to CMV seronegative components and prevent HLA alloimmunisation. Also, washed components (RBC and platelets) remove harmful plasma antibodies.

Platelets

Each unit of platelets is prepared from a single whole blood collection by differential centrifugation and contain at least 5.5 x 10¹⁰ platelets in 50 ml of plasma. They are stored at 20-24°C in plastic containers under agitation and have a shelf life of 5 days. Each unit can raise platelet count by 5-10x10⁹/l. Alternatively platelets are prepared by apheresis (a process of filtration), contain >3x 10¹¹ platelets suspended in 200 ml plasma, and are equivalent to 6 random donor platelet units. Platelets are not usually crossmatched with the recipient, but ABO type-specific platelets should be provided where possible as, otherwise, the increment is 10-20% less in platelet count. Platelets are given to patients with thrombocytopenia who are bleeding or those with severe thrombocytopenia as a precaution. Patients rarely bleed spontaneously when platelet count is >20x10⁹/l and patients receiving chemotherapy can often tolerate counts of 5-10x10⁹/l.

Granulocytes

Mainly given to neutropenic cancer patients developing bacterial sepsis unresponsive to conventional antibiotic therapy for at least 24-48 hours. Preparations collected from normal donors by apheresis contain at least 1x10¹⁰ neutrophils/unit, but the concentration can be increased by using donors stimulated by steroids and/or growth factors. Granulocyte preparations can only be stored for 24 hours at 20-24°C. They need to be crossmatched with the recipient's serum because of the large number of red cells they contain and need to be irradiated because of the large number of lymphocytes present.
Granulocytes are only usually considered for patients with an absolute neutrophil count <0.5x10⁹/l and a good chance of marrow recovery. They need to be given usually daily until patients can maintain an absolute neutrophil count >0.5x10⁹/l without transfusion or until the infection has resolved. Patients frequently have a febrile reaction to granulocytes and these are more severe when amphotericin is infused at around the time of the granulocyte infusion.

Fresh frozen plasma

Fresh frozen plasma is produced by centrifugation of one donation of whole blood, and collecting the supernatant liquid.⁶ The plasma is frozen within 8 hours of collection in order to maintain the activity of factor V and factor VII. The main indication for fresh frozen plasma is deficiency of multiple coagulation factors found in liver disease and disseminated intravascular coagulation (DIC). It is also often used for urgent reversal of warfarin anticoagulation. Because of the large volume that would be required, FFP is not generally used to replace individual clotting factors. In these situations specific factors are given (see below).
Cryoprecipitate is made by thawing FFP at 1-6°C and is generally used for patients with von Willebrand's disease or severe hypofibrinaemia. A commercial preparation of solvent/detergent treated frozen human plasma called Octoplas is available but needs ABO compatibility checks. Uniplas is a human plasma product which has been shown to be independent of ABO compatibility, but it is not yet widely used in the UK.⁷
Plasma-transfused patients need to be observed for circulatory overload.⁷ The main side effects include fever,⁸ chills,⁸ bronchospasm,⁶ and adult respiratory distress syndrome.⁹

Albumin

This is available as 5 or 25% solution for the treatment of hypovolaemia and hypoalbuminaemia. The cost-benefits of albumin in the treatment of hypovolaemia is controversial, and it is largely being replaced by non-plasma colloidal solutions. It does however still have a place in the management of liver disease and ascites.¹⁰ It is tested for hepatitis C virus (HCV) RNA and virally inactivated, and not considered as a risk factor for viral transmission. Its use has now largely been superseded by non-plasma colloidal solutions.

Immunoglobulin

Intravenous immunoglobulin is used in the treatment of immuno-thrombocytopenia, Guillain-Barre syndrome and autoimmune haemolytic anaemias. RhD immunoglobulin is used to prevent exposure to D-positive red cells causing rhesus sensitisation in D-negative patients. This is usually given in pregnancy and immediately after birth to prevent haemolytic disease of the newborn in future babies.

Antithrombin III concentrate

This is prepared from human plasma and used to treat congenital deficiency of antithrombin III. This condition presents as thromboembolic phenomena at an early age.¹¹ Side effects of concentrate transfusion may include flushing, nausea, headache, and rarely fever and allergic reactions.⁶ There may be a place for antithrombin III concentrate in the management of acquired deficiency (e.g. heparin resistance, cirrhosis with coagulation disorders).^12,13

Drotrecogin Alfa (Activated)

This is recombinant activated protein C. In cases of severe sepsis, the protein C pathway regulates thrombin production, preventing the formation of the microvascular thrombosis which can lead to multiple organ failure.¹⁴ Caution needs to be used in patients with bleeding diatheses, co-morbidity leading to, or medication causing, increased bleeding tendency.^6,15 The preparation is contraindicated in cases of internal bleeding, cerebral herniation, intracranial neoplasm, chronic severe hepatic disease, and thrombocytopaenia.^15,6 There is little safety data concerning pregnancy or breastfeeding, so the drug should only be given if there is a definite indication.¹⁵ A study in 477 paediatric patients did not show any benefit,¹⁵ although there are isolated reports that it promotes improvement in selected cases.¹⁶ Adverse effects include headache,⁶ bleeding,¹⁷ pain,⁶ and ecchymoses.¹⁵

Factor VIIa (Recombinant)

This is used in patients with inhibitors to factors VIII and IX. It is indicated in patients with haemophilia A and B,¹⁸ and in uncontrolled bleeding in a number of clinical situations.¹⁹ Theoretical concerns about an increased risk of DVT and pulmonary embolus²⁰ have not been borne out in randomised trials.²¹

Factor VIII fraction, dried

Also known as human antihaemophilic fraction, this is prepared from human plasma by a suitable fractionation technique and indicated for the treatment and prophylaxis of haemorrhage in haemophilia A. Large or frequently repeated doses in patients with blood groups A.B or AB can lead to intravascular haemolysis. This is less likely to occur with high potency purified concentrates. Side effects include allergic reactions,²² including chills and fever.⁶

Factor VIII inhibitor bypassing fractions

This is prepared from human plasma. It is indicated for the control of spontaneous bleeding episodes or to cover surgical interventions in hemophilia A and hemophilia B patients with inhibitors.²³ It has also been used in non-haemophiliac patients with acquired inhibitors to Factors VIII, XI and XII.²⁴ Intravascular coagulation is the main adverse effect.²²

Dried factor IX fraction

This is prepared from fractionating human plasma, and may also contain factors II, VII, and X. It is used for the treatment of haemophilia B (congenital factor IX deficiency)⁶ or acquired haemophilia.²⁵ The risk of thrombosis has largely been obviated by increasing the purity of the product.⁶ Disseminated intravascular coagulation is the main contraindication.²⁶ Side effects include allergic reactions, chills and fever, but these are usually infrequent and mild.²⁷

Factor XIII dried

This is also known as Human Fibrin-stabilising Factor, Dried, is indicated for congenital factor XIII deficiency.⁶ It has also been used to promote the healing of anastomoses in gastrointestinal surgery.²⁸ Adverse effects, which include allergic reactions and fever, are rare.⁶ Recombinant factor XIII has shown to be a safe and effective alternative in trials.²⁹

Protein C concentrate

This is prepared from human plasma. It is indicated in congenital protein C deficiency, a congenital disorder characterised by an increased tendency to coagulation.^6,30 It has also been used for the treatment of sepsis and severe shock.³¹Caution should be used in patients hypersensitive to heparin.⁶

See related article - Blood Transfusion Reactions