Blood transfusions and blood substitutes in surgical practice
C. C. ENTWISTLE
GENERAL PRINCIPLES
Blood lost due to surgery or trauma does not necessarily require replacement by transfusion. Circulating fluid is readily replaced from extravascular reserves, protein is regenerated in days and, in an otherwise healthy person, red cells are replaced over the next few days or weeks.
Transfusions may be warranted where blood loss is considerable, and especially if it is rapid, when further blood loss or imminent major surgery is likely, if the patient is suffering from symptomatic anaemia or if absorption of haematinics is impaired.
Blood to be transfused comes from donations, each bag from a single donor, and despite rigorous screening, each carries a small risk. Every recipient therefore requires individual assessment, and should only be transfused where the balance of risks is in favour of transfusion being performed.
PATIENT NEEDS
A minimum preoperative haemoglobin level of 100 g/1 is no longer regarded as essential since many patients with lower haemoglobin levels tolerate surgery and seem to recover just as well.
Operative blood loss should be measured if at all possible. The patient initially requires restoration of blood volume. For small losses (under 20–25 per cent blood volume) simple fluids such as saline solution are adequate, safe, and inexpensive replacements, even though their renal excretion is rapid. Greater losses (up to 30–35 per cent blood volume) are better countered by infusion of colloid plasma substitutes such as solutions of modified starch, gelatin, or dextrans. All are widely available commercially, are much less expensive than plasma-derived equivalents, and are ready for use at ambient temperatures for any patient regardless of blood group, (though samples for blood grouping and compatibility tests should be taken before some dextrans are given). Because these products have molecular weights of 30 to 70 kDa they remain in the circulation to maintain plasma oncotic pressure for much longer than simple electrolyte solutions. They are only slowly metabolized or excreted over a period of about 2 days and are excellent stop gap agents for use while red cell products are awaited. They have no procoagulant activity.
When losses involve about 50 per cent of blood volume (or less in the elderly or patients with respiratory insufficiency), and especially if this loss is rapid, effective replacement of oxygen carrying capacity, as well as volume replacement, is vital. Blood, commonly now supplied as red cell concentrates, is necessary. Replacement of plasma proteins and coagulation factors is rarely indicated when blood loss is less than about one blood volume, even though there is little of either in red cell products. Extravascular fluids provide a large protein reservoir and coagulation usually remains unaffected even when levels of clotting factors are only one-third of normal: these factors are regenerated within hours except in patients with pre-existing liver disease.
Patients suffering massive blood loss need to be provided with sufficient appropriate products, which may include fresh frozen plasma and cryoprecipitates: platelet concentrates are required to counter platelet depletion from haemodilution and to correct for any functional impairment of circulating platelets.
MECHANICS OF PROVIDING BLOOD
Patient and sample identification
Clinicians contemplating transfusion should have a working knowledge of transfusion medicine, and be familiar with local facilities and practices. Blood request forms are legal documents; they must give unambiguous patient identification (date of birth is very useful), and state clearly what is required and by when. A brief prior visit to the local blood bank can promote good future communication. Blood samples for grouping, antibody screening, and compatibility testing (cross-matching) must be adequately labelled, and this is best done as the sample is taken. Mistakes in identification and in mislabelling of samples are among the most common causes of fatal transfusion reactions.
Grouping, antibody screening, and crossmatching
Blood groups are determined by antigens on cells, and can be shown as an agglutination reaction induced by reference antisera (Fig. 1) 53. Such tests are performed either manually, on slides or in tubes or microwell systems, or by automated methods. Antibody screening involves testing the patient's serum for the presence of any rhesus, Kell, or other minor blood group antibodies which cause agglutination of a well-characterized panel of cells.
Compatibility testing consists of excluding in vitro antibody activity against donor cells, which if given, would provoke a transfusion reaction.
This is performed by adding serum in a 2 : 1 ratio to 3 per cent donor cells suspended either in low-ionic strength saline or normal saline; the mixture is then incubated at 37°C for 15 min (low ionic strength saline) or 45 min (normal saline), following which it is examined for agglutination, or even haemolysis, which indicate incompatibility. No single procedure detects all clinically important antibodies, but as a minimum, the indirect antiglobulin test should always be performed if possible. In this, an antiglobulin reagent (of animal or monoclonal origin) is added to cells which have been incubated as above; any cells coated with patient's antibody will then agglutinate, again indicating incompatibility. Recommended technical details are published elsewhere.
Anticipated requirements
The possible need for blood should always be anticipated. One or 2 per cent of patients carry atypical blood group antibodies, present either naturally or as a consequence of previous pregnancy, transfusion, or transplantation, and provision of compatible blood for these patients can sometimes prove difficult. For patients likely to require a transfusion a clotted blood sample should be grouped, screened for atypical antibodies and, where appropriate, special blood obtained and full compatibility tests done. At least a day's notice should be allowed for routine requests to be assimilated into the busy laboratory workload.
In emergencies, time may only allow shortened cross-matching, and even unmatched blood may have to be provided within 5 to 10 min. Unmatched blood can be of the same ABO group as the patient, or of Group O since Group O cells will not react with either anti-A or anti-B antibodies (Table 1) 39; it must also be rhesus D negative if the recipient is a female of potentially child-bearing age. If Group O blood is given to patients of Group A, B, or AB, concentrated cells are preferable since the donor plasma and its anti-A and anti-B antibodies are largely removed (although even if given they would be rapidly diluted in the recipient's circulation and most would cause little if any clinically significant problem). These measures may be life-saving but errors are more likely to be made, patient antibodies to other groups may be missed, and transfusion reactions are more common. Whatever blood is given, it should never be ABO incompatible, for example, A Group to a Group O patient, since immediate, severe, and sometimes fatal intravascular haemolysis can follow, depending on the strength of that patient's antibodies. Incompatibility involving other blood group systems (e.g. rhesus, Kell, Duffy) leads to reticuloendothelial sequestration of mistransfused cells rather than to immediate lysis, and is a much less severe clinical result.
Maximum surgical blood ordering schedules
To make the best use of the group and screen system, both to minimize hazards to patients from avoidable urgent blood requests and wastage of laboratory resources on blood not then used, blood banks are increasingly being encouraged through active clinical audit to use maximum surgical blood ordering schedules. Under these schedules, compatibility tests are only performed based upon ongoing review of previous blood usage by given surgeons for essentially similar clinical situations.
PRODUCTS AVAILABLE
Homologous blood
Almost all transfusion services are based upon blood collected from healthy unpaid volunteer donors. Because of national demands for self-sufficiency in blood and plasma-derived products, notably factor VIII for haemophilics, the use of whole blood is rapidly giving way to red cell preparations, supplied either as concentrates or as suspensions in optimal additive solutions, the plasma being removed for fractionation. Red cells in optimal additive solutions have excellent viability and the suspension viscosity is comparable to that of whole blood.
Whole blood may still be preferable for paediatric patients and blood transfused into babies should have been stored for less than 7 days and also be known to be cytomegalovirus antibody negative. There is no convincing evidence that ‘donor fresh’ blood has any magic haemostatic properties; perioperative haemorrhagic states, exclusive of surgical causes, are often attributable to platelet deficiency or malfunction and should be corrected appropriately. In some countries, though not in the United Kingdom, so-called ‘directed’ blood donations are used, usually from close family members, especially parents for their own children. Although such donations are better than no blood, they offer little advantage over conventional supplies and indeed may not always be quite as safe.
Autologous blood
A patient's own blood can be collected and reinfused, thus eliminating some of the hazards of homologous transfusions. A preoperative deposit of up to about four donations (450 ml blood each) can be made by basically healthy patients within the 5 weeks prior to planned (e.g. orthopaedic) surgery. Patients as young as 8 to those over 80 can predonate blood, provided that the necessary local facilities are available. Case selection should minimize the taking of blood unlikely to be needed. Where ‘cross-over’ of untransfused units into the routine blood bank is practised the patient-donor and blood must satisfy safety standards for homologous donations.
Intraoperative haemodilution is another means of providing autologous blood. Two units of blood are drawn in the anaesthetic room and replaced with crystalloid solution or plasma substitute: that fresh and platelet-rich blood is then immediately available if needed. The patient's blood viscosity is also lowered, which aids tissue perfusion and oxygenation—this is particularly valuable in vascular surgery.
Peroperative salvage may also be practised: shed blood is collected, and the red cells are washed and filtered ready for reinfusion, usually within minutes. Peroperative salvage is most cost-effective where substantial blood loss is predicted.
Some other blood products
Platelet concentrates
These are made from individual donations but are rarely needed in routine surgery. In patients suffering major blood loss, and particularly during cardiac surgery with prolonged bypass, in those with renal failure, and those taking aspirin or other antiplatelet drugs, circulating platelets may be deficient in number (under 100 × 10&sup9;/1), function, or both, making active platelet support essential. Patients with haematological disorders may need prophylactic platelet transfusion as well as replacement, for example to cover insertion of a Hickman line, splenectomy, and of course for intercurrent surgery. In all these situations a haematologist should be consulted and reasonable notice given to obtain appropriate products.
Fresh frozen plasma
This is essentially normal plasma containing citrate anticoagulant and its use is indicated when massive blood loss (over one blood volume) occurs, or when there is mixed coagulation impairment, for instance due to warfarin overdose, liver disease, or as part of disseminated intravascular coagulation. The last occasionally complicates prostatic or chest surgery and some obstetric situations. Fresh frozen plasma should then be given (1 litre initially) to supplement other transfusions. In such cases, haematological advice should be sought. Fresh frozen plasma should not be used as a volume expander; safer products are available.
Cryoprecipitates
These concentrates, which include factor VIII, fibrinogen, von Willebrand factor and some other factors are also made from individual donations. While most cryoprecipitates are given to patients with haemophilia A (see below), or von Willebrand's disease, they can provide a source of fibrinogen in patients with disseminated intravascular coagulation, and act as a substrate for ‘fibrin glue’, activated by thrombin for sealing large raw surfaces (pleura, liver etc.), for patients undergoing vascular surgery, and many other applications.
Clotting factor concentrates
These are best provided purified from plasma pools and subjected to viral inactivation to prevent transmission of HIV, etc. These concentrates and cryoprecipitates are critical in the proper management of surgery in haemophilics, but should always be given in collaboration with the local haemophilia service to ensure that adequate and correct treatment is given and monitored.
TRANSFUSION COMPLICATIONS
Immediate
Sites of vascular access may become inflamed, thrombose, or become dislodged; if so, resiting is indicated.
Over-transfusion, particularly in the elderly, can be avoided by accurate fluid balance control. Overhydration is treated by judicious use of diuretics and digoxin and reduced fluid input.
Allergic reactions, predominately cutaneous, are commonly attributed to unidentified foreign proteins in donor blood. These reactions are usually uncomfortable for the patient rather than serious, although severe anaphylactic reactions can occur. Treatment with antihistamines and intravenous hydrocortisone is usually effective.
Non-haemolytic febrile transfusion reactions are common. Some are associated with patient alloimmunization to HLA, platelet (HPA), or granulocyte-specific antigens following previous pregnancy, transfusion, or transplantation. These reactions are rarely serious and resolve either spontaneously after discontinuation of the offending unit, or with administration of antipyretics and symptomatic measures. In-line microaggregate, or the more effective though expensive white cell removal filters, reduce the incidence and severity of non-haemolytic febrile transfusion reactions in patients who react repeatedly.
Haemolytic reactions due to red cell incompatibility are similar to non-haemolytic febrile transfusions reactions, with the addition of rigors and perhaps loin pain and collapse. Such reactions should be exceedingly rare provided there have been no clerical or laboratory errors. Treatment is as for non-haemolytic reactions but the possible occurrence of intravascular lysis and complement activation make critical observation of renal function essential; dialysis may be necessary.
Delayed
Poorly sustained haemoglobin level (overt or occult bleeding excluded) may be due to elimination of transfused blood near the end of its shelf-life or accelerated destruction due to an anamnestic antibody response after previous pregnancy or transfusion; mild jaundice with elevated unconjugated serum bilirubin can occur.
An immunosuppressive ‘transfusion effect’ may follow transfusions of homologous blood. This results in depression of humoral and cellular immune responses which persists for many months. Renal graft survival may be improved but metastatic spread of certain tumours (particularly colorectal) may be potentiated and susceptibility to wound and other postoperative infections is increased.
Transmitted infections are the most serious complication. Despite routine virological donor screening, about one donation in every million carries low levels of hepatitis B virus or is HIV positive, despite a negative antibody test (especially in the early ‘window’ stages of infection). Hepatitis C virus is present in up to 1 in 500 of some donor populations, is readily transmissible through transfusion, and accounts for almost all cases of non-A, non-B hepatitis. Up to one-half of the recipients become chronic carriers and later develop chronic hepatitis, and perhaps cirrhosis and even hepatoma. Routine screening of donors for hepatitis C virus antibodies should reduce the incidence of these complications.
Cytomegalovirus is ubiquitous, although more endemic in some populations than others. While cytomegalovirus causes little more than a brief glandular fever-like illness for most patients and is a recognized cause of a similar postcardiotomy syndrome, it can cause serious morbidity and mortality in premature babies and immunosuppressed patients such as transplant recipients. Depending on local populations and facilities, blood negative for cytomegalovirus antibody can be provided or alternatively, virus-carrying white blood cells can be largely filtered out.
Rarely blood and its products can become contaminated with bacteria; some Gram-negative organisms proliferate even during storage at 4°C. Transfusion of such blood very rapidly leads to severe, often irreversible, endotoxin shock.
SUMMARY
Transfusions form an integral part of overall patient care, demanding definition of specific needs and complementary treatment. While careful surgical technique will minimize blood loss, particular aspects must be addressed, such as large raw areas, prolonged bypass, pre-existing coagulation problems, and platelet deficiency. Supplementary measures may be helpful, including use of fibrinolytic inhibitors during surgery and haematinics afterwards. Knowledge of the blood products given and monitoring of progress are essential to ensure anticipated effects are achieved and that adverse complications are expeditiously treated. Patients undoubtedly benefit from transfusion, but like any other prescribed medication, this must only be given when justified.
FURTHER READING
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British Committee for Standards in Haematology Blood Transfusion Task Force. Guidelines for implementation of a maximum surgical blood ordering schedule. Clin Lab Haematol, 1990; 12: 321–7.
British Society for Haematology and British Blood Transfusion Society. Guidelines for compatibility testing in hospital blood banks. Clin Lab Haematol, 1987: 9: 333–41.
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Goldfinger D. Controversies in transfusion medicine: directed donations (pro). Transfusion, 1989; 29: 70–4.
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Page PL. Controversies in transfusion medicine: directed donations (con). Transfusion 1989; 29: 65–70.
Simpson MB. Platelet transfusion in selected clinical situation. In: Platelets. American Association of Blood Banks, 1988: 129–65.
Sirchia G, Wenz B, Rebulla P, Parravicini A, Carnelli V, Bertolini F. Removal of white cells from red cells by transfusion through a new filter. Transfusion, 1990; 30: 30–3.
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