Red blood cells in additive solution

Donated whole blood is collected into an anticoagulant (citrate) and nutrient (phosphate and dextrose) solution (CPD). Centrifugation removes virtually all of the associated plasma, and a solution of saline, adenine, glucose and mannitol is then added to provide optimal red cell preservation. The red cell concentrate is then run through a leucodepletion filter to reduce the white cells to a concentration of less than 5 × 10⁶/l. The final product has a haematocrit of 55–65% and a volume of approximately 300 ml. The blood cannot be sterilized, so that blood transfusion can transmit organisms not detected by donor screening. Red cell concentrates must be stored at +4°C ± 2°C.

Transfused blood must be ABO- and RhD-compatible with the recipient and transfused through a sterile blood administration set with an in-line macroaggregate filter, designed for the procedure. The set should be primed with saline and no other solutions transfused simultaneously. This product is indicated for acute blood loss and anaemia and is the most widely available form of red cells for transfusion.

Platelets

Platelet concentrates can be made either from centrifugation of whole blood or from an individual donor using apheresis. An adult dose is manufactured from four separate donations pooled together or one apheresis collection. In the UK it is advised that over 80% of platelets are procured by apheresis in order to minimize the number of donors a patient is exposed to. Platelets are currently concentrated in plasma rather than an optimal additive solution and carry a greater risk of bacterial contamination as they cannot be refrigerated but must be stored at 22°C ± 2°C. For this reason many platelet concentrates are now tested for bacterial contamination prior to release.

Platelets are infused through a standard blood-giving set over less than 30 minutes. As the concentrate contains some red cells and plasma, it should ideally be ABO- and RhD-compatible with the recipient. RhD-negative girls and women of child-bearing potential must receive RhD-negative platelets or, if only RhD-positive platelets are available, prophylactic RhD immunoglobulin should also be given. An adult dose should raise an adult platelet count by 20–40 × 10⁹/l.

Platelet concentrates are indicated in thrombocytopenia, when platelet function is defective, and in patients receiving massive blood transfusions when there is microvascular bleeding (oozing from mucous membranes, needle puncture sites and wounds).

Fresh frozen plasma (FFP)

Some 200–300 ml of plasma can be removed from a unit of whole blood and stored frozen at −30°C. FFP contains albumin, immunoglobulins and, most importantly, all of the coagulation factors. FFP can be stored at −30°C for a year and is thawed to 37°C before issue. FFP must be ABO-compatible with the recipient and should be transfused within 4 hours of thawing. The average adult dose is 3–4 units. Imported, virally inactivated plasma (treated with methylene blue or solvent detergent) is available for use in children up to the age of 16 years and patients who require repeated exposure to FFP, such as patients undergoing plasma exchange for thrombotic thrombocytopenic purpura.

FFP is used when there are multiple coagulation factor deficiencies (e.g. disseminated intravascular coagulation, DIC) associated with severe bleeding. It may be indicated in selected patients who are over-anticoagulated with warfarin, but there are now prothrombin complex concentrates which should usually be used in preference for this purpose. In the case of massive blood loss arising during or after surgery, the decision whether to use FFP and, if so, how much to use, should be guided by timely tests of coagulation. FFP should not be used to correct prolonged clotting times in patients who are not bleeding or who are not about to undergo immediate surgery.

Cryoprecipitate

A single unit of cryoprecipitate can be removed from 1 unit of FFP after controlled thawing. After resuspension in 10–20 ml plasma, the cryoprecipitate is frozen once more to –30°C, in which condition it can be stored for up to a year. It is enriched in high molecular weight plasma proteins such as fibrinogen, factor VIII, von Willebrand factor, factor XIII and fibronectin. A normal adult dose is 10 units. ABO-compatible units should be given, and the product infused as soon as possible after thawing. Cryoprecipitate is used when fibrinogen levels are low, as in DIC. However the pooling required to manufacture cryoprecipitate does lead to high donor exposure per dose and many countries do not produce this product, preferring instead to use higher volumes of FFP or fibrinogen concentrates to reverse hypofibrinogenaemia.

Human albumin

Albumin is prepared by fractionation of large pools of plasma that, at the end of processing, is pasteurized at 60°C for 10 hours. There are no compatibility requirements.

Solutions of 4.5 or 5% are used to maintain plasma albumin levels in conditions where there is increased vascular permeability, e.g. burns, and are sometimes used in acute blood volume replacement, although crystalloid or non-plasma colloid solution would be the recommended first-line volume expander. Randomized controlled trials on the use of albumin suggest that there is no clear advantage from the use of albumin solutions in the treatment of hypovolaemia over judicious use of saline or colloid solutions. Resuscitation with crystalloid requires volumes of fluid three times greater than with colloid (see chapter 7).

Twenty per cent albumin solutions can be used when hypoproteinaemia is associated with oedema or ascites which is resistant to diuretics (e.g. liver disease, nephrotic syndrome). Twenty per cent albumin is hyperoncotic, so that there is a risk of acutely expanding the intravascular space and precipitating pulmonary oedema.

Factor VIII and Factor IX concentrates

Factor VIII and IX concentrates have been widely used in the treatment of haemophilia. In the UK these have almost completely been replaced by recombinant products to reduce, inter alia, the vCJD transmission risk.

Prothrombin complex concentrates

These products contain factors II, IX and X, and may also contain factor VII (vitamin K-dependent clotting factors). Their use is indicated in the prophylaxis and treatment of bleeding in patients with single or multiple deficiencies of these factors, whether congenital or acquired. They are used to reverse the anticoagulant effect of warfarin when there is major bleeding. Care must be taken in patients with liver disease as this therapy may be thrombogenic.

Immunoglobulin preparations (90% IgG)

These are prepared from fractionation of large pools of plasma from unselected donors or from individuals known to have high levels of specific antibodies. Some products are administered intramuscularly. The indications for some of the more commonly used immunoglobulins are shown in Table 2.1 e.g. hyperimmune globulin against hepatitis B, herpes zoster, tetanus and RhD. Intravenous IgG was originally developed as replacement therapy for immunodeficiency states, but is also used to treat immune thrombocytopenia and other rare diseases such as Guillain–Barré syndrome.

Table 2.1 Indications and doses for the most commonly used specific immunoglobulins