Clinical Surgery in General - part 3 potx

7 5 PATIENT ASSESSMENT such as corneal grafts, do not normally evoke a cellular rejection. On the other hand, kidney, liver, heart, lung, pancreas, small bowel and bone marrow grafts induce rejection (see Ch. 25). Allografts are mainly cadaveric organs but there is increasing use of live related donors. Bone marrow allografts are from live donors and may be related or unrelated. Rejection of allografts is predominantly acute and cell-mediated early in the course of transplantation, unless the recipient has had prior contact with the donor tissues or is of a different blood group, in which case hyperacute rejection occurs. A slower onset of chronic Vascular' rejection, causing graft dysfunction and pro- gressive graft loss, is due to a variety of mechanisms, including cell- and antibody-mediated responses, physical effects, accelerated vasculopathy and immunosuppressive drug-induced effects. Tubular structures, such as blood vessels and biliary ducts, are affected by this process. Avoiding rejection 1. Except when transplanting the cornea, the donor and recipient tissues are matched for ABO blood groups and as closely as possible for human leucocyte antigens (HLA). In addition, the recipient's serum is cross-matched with the donor lymphoid cells to exclude preformed cytotoxic antibodies. 2. Except when transplanting between identical twins, the recipient is immunosuppressed, with agents selected from a variety of drugs, including corticosteroids, azathio- prine, mycophenolate mofetil, ciclosporin, tacrolimus and sirolimus. The anchors of current therapy are still ciclosporin and tacrolimus, whose action prevents the development of cytotoxic T cells; however, both are nephro- toxic. Antilymphocytic globulin (ALG) or antithymocyte globulin (ATG) are polyclonal antibodies preferably raised in rabbits, and may be used to increase immunosuppres- sion early in transplantation. Monoclonal antibodies such as OKT3 (CDS) or Campath 1 (CDw52) have been used to reverse acute rejection. Newer monoclonal antibodies react- ing with the IL-2 receptor (CD25) are effective at prophyl- actically reducing acute rejection episodes. 3. Graft versus host disease (GVHD) may develop if the graft contains competent T cells which react against the host cells that are incapable of rejecting them. This is most likely to develop following bone marrow transplantation. GVHD predominantly affects the skin, liver and gut. CANCER IMMUNOLOGY • The occasional but well documented spontaneous regression of tumours suggests that immunity may develop against cancers. • Immunosuppressed patients have a higher than normal risk of malignancy, especially skin cancers and lymphoid tumours. • Cancers are often infiltrated with lymphocytes and macrophages - this may be associated with an improved prognosis. • Latent cancers, especially of the thyroid and prostate glands, are often disclosed at postmortem examination, suggesting that the tumours develop but lie dormant for many years without clinical disease. This has been attributed to immune mechanisms. Tumour antigens Specific antigens can be found on the surface of tumour cells, especially those that are virally induced, without being present on normal cells of this type. Some tumour cells express antigens normally found only in fetal tissue, such as a-fetoprotein (AFP) and carcinoembry- onic antigen (CEA). These may be used as markers for some cancers or to monitor progress by measuring serum levels, but there is little evidence that they act as targets for the immune system. Radiolabelled monoclonal antibody to CEA may be used to localize residual bowel tumour. Malignant cells can overexpress proto- oncogenes on their surface, which contribute to malignant behaviour; these were identified by antibodies developed for the recognition of specific tumour types. Monoclonal antibodies that attach to receptors highly expressed in tumours can be labelled with isotopes such as m ln and 99m Tc. These can be identified by external scintigraphy. This is especially valuable in identifying residual tumour following treatment. Immunotherapy The identification of immune aspects of cancer has led to the search for therapeutic uses, especially for disseminated tumour cells beyond the scope of conventional treatment, or residual tumour following treatment. Antibodies alone are rarely cytotoxic to tumour cells and are largely restricted to haemopoietic malignancy. Monoclonal antibodies can be conjugated to radioiso- topes, immunotoxins or enzymes. Radiolabelled antibodies can target highly expressed epidermal growth factor receptors (GFRs) in lung and brain tumours and there is hope that monoclonal antibodies to GFRs will be effective in treating tumours. Monoclonal antibody to Her-Neu has proven effective in a minority of breast cancers express- ing this on the tumour. 88 IMMUNITY IN SURGERY / Summary • Do you understand that the immune system is composed of humoral and cellular elements and is made up of innate and adaptive mechanisms? • Are you aware that normally the immune system distinguishes self from non-self but autoimmunity may develop in predisposed individuals? • Do you recognize that immune deficiency arises from many causes, including operation, which predisposes to postoperative complications? • Are you aware that, except in specific circumstances, organ transplants must be protected from rejection by immunosuppressive drugs and other techniques? • Can you foresee the immunological aspects of cancer becoming increasingly valuable in identifying, monitoring and treating malignancy? References Kohler G, Milstein C 1975 Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256(5517): 495-497 Further reading Goldsby RA, Kindt T], Osborne BA, Kuby } 2003 Immunology, 3rd edn. W H Freeman, New York Janeway CA, Travers P, Walport M, Shlomchik M (eds) 2001 The adaptive immune response. In: Immunobiology, 5th edn. Churchill Livingstone, Edinburgh Medzhitov R, Janeway CA 2000 Innate immune recognition: mechanisms and pathways. Annual Review of Immunology 173: 89-97 Norman D, Turka L 2001 Primer on transplantation, 2nd edn. Blackwell Science, Oxford Stites DP, Terr AI, Parslow TG 1997 Medical immunology. Appleton & Lange, Stamford CT 89 7 blood component therapy C P. F. Taylor, A. B. Mehta Objectives Understand the need for preoperative detection of blood abnormalities which may affect the outcome of surgery and anaesthesia. Be aware of the range of blood components available for clinical use. Understand how to use blood components appropriately and the hazards associated with their use. Be aware of alternatives to allogeneic blood transfusion and know when they are appropriate. Understand the underlying mechanisms and management of excessive intra- or postoperative blood loss. INTRODUCTION This chapter outlines the investigation and management of patients undergoing surgery. It includes patients who have a prior abnormality of their blood count or blood plasma constituents and also discusses appropriate use of blood components in patients with no prior haematological problems. Anaemia and excessive bleeding are symptoms and not diagnoses. An accurate diagnosis is an essential step in the formulation of a management plan. In the majority of hospitals, a clinical haematologist will be available to advise you on optimum use of laboratory diagnostic facilities, interpretation of results and appropriate therapy. Make sure you discuss problems early, and take advice on the appropriate specimens to send and tests to order. If a result is puzzling, go and discuss it with the haematologist. PREOPERATIVE ASSESSMENT Growing pressure on hospital beds and increasing use of day surgery means that the preoperative assessment should, wherever possible, be performed prior to admis- sion. This allows for efficient use of hospital resources and limits the number of cancelled operations. The key aims are to assess a patient's fitness to undergo surgery and anaesthesia, anticipate complications, arrange for sup- portive therapy to be available perioperatively and to liaise with the appropriate specialists regarding non- surgical management. This assessment needs to take place at a presurgical clinic at least 1 month prior to the planned date of surgery. Preoperative planning Arrange for the patient to attend a preoperative clinic at least 4-6 weeks prior to operation, to: • Take a full history and examination, including previous surgical episodes and bleeding history • Arrange full blood count, group and antibody screen, routine chemistry, coagulation screen (if indicated) and tube for haematinics assessment (ferritin level for iron stores, vitamin B 12 and folic acid), which can be put on hold pending full blood count (FBC) results • Consider autologous predeposit if the patient is fit enough and there is a greater than 50% likelihood of significant blood loss requiring transfusion • Consider using erythropoietin (Greek erythros = red + poiesis - making), even with normal haemoglobin, at a dose of 600 units/kg weekly for 4 weeks preoperatively • Prescribe iron and folic acid supplement if there is any suspicion of iron deficiency • Establish whether the patient is taking regular aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) or warfarin and make necessary arrangements to stop this drug preoperatively • Consider a staged surgical approach in major surgery. After the clinic, ensure that all the results of the above tests are seen within a few days so that you can take necessary action. In addition, discuss with the anaesthetists whether acute normovolaemic haemodilution (ANH) or intraoperative cell salvage may be appropriate. 90 8 Haematological assessment and HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 8 Anaemia 1. Anaemia is defined as a reduction in haemoglobin concentration below the normal range after correction for age and sex (approximately 13-16 g dl" 1 in males, 11.5-15 g dH in females). The most common causes of anaemia in surgical patients are iron deficiency (from chronic blood loss) or anaemia of chronic disease. Both may be due to the underlying condition for which operation is required. 2. Every anaemic patient, that is those whose haemoglobin level is below their laboratory normal range, should have iron studies and ferritin levels performed sufficiently in advance of operation to allow for corrective measures to take effect. A subnormal ferritin indicates iron deficiency and the patient should be treated preoperatively with iron supplements orally or intravenously. Defer elective surgery until the maximum haemoglobin is attained. One should not use allogeneic blood unless there are no reasonable alternatives (Table 8.1). Key point • Anaemia in elective surgical patients should be assessed and appropriately treated preoperatively. 3. A normal or high ferritin level does not exclude iron deficiency (although it is less likely), as ferritin is an acute phase protein. Anaemia of chronic disease (ACD) may be present in many presurgical patients, including those with malignancy or joint disease requiring orthopaedic surgery. ACD is usually normochromic and normocytic, although it is sometimes slightly microcytic. Iron levels Table 8.1 Reasons to reduce blood exposure Immunological complications - Red cell alloantibodies: HTR - HLA antibodies: refractoriness - TRALI, FTP, TA-GvHD, etc. Errors and 'wrong blood' episodes Infections - bacterial, viral, ? prion Immunomodulation - infection, malignancy Litigation Resource HTR, haemolytic transfusion reaction; PTP, post- transfusion purpura; TRALI, transfusion-related acute lung injury; TA-GVHD, transfusion-associated graft versus host disease. are normal but iron-binding capacity is reduced (in contrast to iron deficiency where iron-binding capacity is raised). Ferritin (an intermediary in the absorption of iron from the gut) may be normal or raised. ACD may respond to erythropoietin therapy preoperatively. Although iron stores may be adequate, supplemental iron and folic acid may be required. Anaemia accompanied by thrombocytopenia or neutropenia may indicate a bone marrow disorder, a complex autoimmune condition or systemic disease, so seek the advice of a haematologist, and other specialists, without delay. A classification of anaemia is given below: • Decreased red cell production - Haematinic deficiency: Iron, vitamin B 12 , folic acid - Marrow failure: Aplastic anaemia, leukaemia, pure red cell aplasia. • Abnormal red cell maturation - Myelodysplasia - Sideroblastic (Greek sideros = iron) anaemia • Increased red cell destruction - Inherited haemolytic anaemia, such as sickle cell anaemia or thalassaemia (Greek thalassa = sea) - Acquired haemolytic anaemia: Immune (e.g. autoimmune) Non-immune (e.g. microangiopathic haemolytic anaemia, disseminated intravascular coagulation) • Effects of disease in other organs Anaemia of chronic disorder; renal, endocrine, liver disease. Examination of red cell indices provides important clues to the cause of anaemia. The following alterations in red cell indices offer a clue to the cause of anaemia. • Lowered mean cell volume (MCV), mean cell haemoglobin (MCH) - Iron deficiency - Thalassaemia trait - Homozygous thalassaemia - Hyperthyroidism • Raised MCV - Megaloblastic (Greek megalo = large) anaemia - Hypothyroidism - Liver disease - Reticulocytosis - Myelodysplasia - Aplastic anaemia - Paraproteinaemia - Alcohol abuse • Normochromic normocytic - Anaemia of chronic disease - Renal failure - Bone marrow infiltration - Haemorrhage. 91 8 PATIENT ASSESSMENT A reduction in MCV and MCH (microcytic hypochromic picture) is highly suggestive of iron deficiency. Nutritional deficiency or very slow chronic blood loss leads to a well- compensated anaemia of gradual onset. A raised MCV is highly suggestive of megaloblastic anaemia and malab- sorption (due to pernicious anaemia, coeliac disease, or after gastrectomy) or poor dietary intake are the commonest causes. The underlying cause of the anaemia should be specifically treated as far as possible and elective surgery delayed until this is achieved. Haemoglobinopathies These are a group of inherited disorders (autosomal recess- ive) of haemoglobin synthesis in which affected individuals (homozygotes) suffer a lifelong haemolytic anaemia. They are the commonest human inherited disorders. The carriers (heterozygotes) have a small degree of pro- tection against malaria; haemoglobinopathies are therefore common in all parts of the world where malaria is (or was) prevalent - southern Europe, Asia, the Far East, Africa, South America and immigrant populations in northern Europe and North America. Carriers are asymptomatic and have a normal life expectancy, but may have a mild degree of anaemia. Haemoglobinopathies are divided into two types: disorders affecting haemoglobin structure and disorders of haemoglobin synthesis. In the structural haemoglobin variants, a single deoxyribo- nucleic acid (DNA) base mutation leads to an amino acid substitution in haemoglobin to give rise to a variant haemoglobin, e.g. haemoglobin S (sickle haemoglobin, which leads to sickle cell anaemia). The variant haemoglobin may be functionally abnormal; thus, haemoglobin S tends to crystallize under conditions of low oxygen tension and this distorts red cell shape to cause 'sickling'. The second type of haemoglobinopathy is thalassaemia, where there is no change in the amino acid composition of the haemoglobin molecule but there is deficient synthesis of one of the globin chains (a or (3), leading to imbalanced chain synthesis and anaemia. Thalassa (Greek = sea) recognizes that the disease was discovered in countries bordering the Mediterranean sea. It is important to detect carriers of some haemoglobinopathies (e.g. sickle cell) prior to operation because anaesthesia and hypoxia can precipitate sickling. All patients of non-northern European origin should be screened prior to operation, for example in the pread- mission clinic, by haemoglobin electrophoresis and/or a sickle solubility test. Affected individuals (homozygotes) usually present in childhood but occasionally patients present incidentally. Patients with sickle cell disease (HbSS) should be managed jointly with a clinical haematologist. The consultant anaesthetist performing the case needs to know in advance of the sickle status of the patient because special anaesthetic precautions and prac- tices are required, including exchange transfusion prior to major surgery such as hip replacement. This involves venesection of the patient together with transfusion of donor blood (6-8 units) resulting in a postexchange haemoglobin S level of less than 30%. It can be performed manually or using a cell separator. Minor surgery such as dental procedures can be safely carried out without transfusion in the majority of patients. Intermediate procedures such as cholecystectomy can be performed following transfusion with 2-3 units of packed red cells to a haemoglobin level of 10 g H (Vichinsky et al 1995). Pay particular attention to the hydration of the patient, at least 3 litres per day, and to oxygenation during anaesthesia. Patients with some haemoglobinopathies, especially HbSC disease, are at increased risk of postoperative thrombosis, and appropriate prophylaxis with low molecular weight heparin is desirable unless there are contra- indications. Other inherited red cell disorders Deficiency of the red cell enzyme glucose-6-phosphate dehydrogenase (G6PD) is a sex-linked disorder affecting more than 400 million people worldwide. It results in a reduced capacity of the red cell to withstand an oxidative stress. Patients are asymptomatic in the steady state and have a near normal FBC, but may suffer haemolysis of red cells in response to an oxidative challenge. Common pre- cipitants are infection and drugs, principally antimalarials such as primaquine, pamaquine and pentaquine but not usually chloroquine or mefloquine, and sulphonamide antibiotics (Mehta 1994). Excessive bleeding 1. Preoperative assessment should allow us to anticipate problems. Many patients with an inherited or acquired defect of coagulation (Table 8.2) leading to peri- and postoperative complications cannot be detected preoperatively. However, take a careful history, which may reveal features such as excessive bleeding at times of previous surgery, bleeding while brushing teeth, nose bleeds, a family of history of bleeding disorders, spontaneous bruising, a history of renal or liver disease and a relevant drug history. 2. Request a coagulation screen, prothrombin time (PT), activated partial thromboplastin time (APTT) and throm- bin time (TT) and platelet count, in any patient with a sus- pected bleeding disorder, although disordered platelet function can be difficult to detect. A bleeding time is the best in vivo test of platelet function and involves a standard skin incision and timing of clot formation, provided the tester is expert and performs it regularly. Laboratory platelet function analyses may also be necessary. 92 HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 8 Table 8.2 Bleeding disorders associated with excessive bleeding which may cause peri- or postoperative complications Disorder type Cause Congenital Clotting factors Platelets Vessel wall Acquired Clotting factors Platelets - function Platelets - number Vessel wall Haemophilia A, B von Willebrand's syndrome Congenital platelet disorders Hereditary haemorrhagic telangiectasia Drugs (anticoagulants, antibiotics) Liver disease DIC (in sepsis) Drugs (aspirin, NSAIDs) Liver disease, renal disease, myeloproliferative disorders, paraproteinaemic disorders Autoimmune thrombocytopenia Hypersplenism Aplastic anaemia, myelodysplasia Drugs (steroids) Vasculitis Malnutrition DIC, disseminated intravascular coagulation; NSAIDs, non-steroidal anti-inflammatory drugs. 3. Ask advice from a haematologist specialising in haemostasis before elective operation on patients with coagulation and platelet abnormalities, since their preoperative management may be complex. A very common cause of excessive intra-operative bleeding due to platelet dysfunction is pre-operative ingestion of aspirin, clopi dogrel, NSAIDS, or warfarin. The need for these drugs must be assessed at the pre-operative clinic and low dose aspirin should be stopped 10 days prior to surgery, unless this is contraindicated. Platelets may be required to achieve haemostasis in bleeding patients, even with sat- isfactory platelet counts, if they have been taking aspirin within one week of surgery. Anticoagulation therapy 1. The dose of oral anticoagulants such as warfarin (named for Winconsin Alumni Research Foundation + coumarm) is adjusted to maintain the international nor- malized ratio (INR, which is a measure of the patient's PT to that of a control plasma) within a therapeutic range. The therapeutic range varies depending upon the indication for which the patient was warfarinized. 2. Heparin is a parenteral anticoagulant and may be given in either low molecular weight or unfractionated forms. Low molecular weight heparin (LMWH) is not usually monitored at prophylactic doses, but at therapeutic doses an anti-Xa assay is required for monitoring. Unfractionated heparin is monitored by measurement of the ratio of the patient's APPT compared to that of control plasma. The short half-life of unfractionated heparin allows safer management during the perioperative period. Key point • Always check the platelet count before starting heparin and every second day on treatment to detect heparin-induced thrombocytopenia (HIT). 3. For elective surgery in patients on oral anticoagulants, you must balance the risk of haemorrhage if the INR is not reduced against the risk of thrombosis if the INR is reduced for too long or by too great an amount. For minor surgery (e.g. dental extraction) it is normally suffi- cient to stop the oral anticoagulant for 2 days prior to the procedure and restart with the usual maintenance dose immediately afterwards. For high risk patients such as those with prosthetic heart valves, or for patients undergoing more extensive procedures, you must stop warfarin and substitute heparin, either subcutaneously or by continuous intravenous infusion, under close haematological supervision to provide thrombosis prophylaxis. Patients on warfarin who present for emergency surgery or who have bled as a result of anticoagulant therapy may need reversal of the anticoagulant. This can be done using vitamin K with either a concentrate of factors II, VII, IX and X or, if this is unavailable, fresh frozen plasma (FFP). ARRANGING INTRAOPERATIVE BLOOD COMPONENT SUPPORT Elective surgery 1. The standard red cell product is SAG-M blood, that is, red cells suspended in an optimal additive solution of saline, adenine, glucose and mannitol, with a citrate anticoagulant. Whole blood is not used in the UK, although it is available in some other countries in Europe, and plasma-reduced blood is available for specific multitransfused patients. All cellular products, such as platelets and red cells, are leucodepleted at the blood 93 8 PATIENT ASSESSMENT centres in the UK, and have been so since November 1999. There is therefore no role for an in-line white cell filter in these products. Special products, such as blood with extended red cell phenotyping or rare blood from the frozen blood bank, are available after discussion with laboratory staff and haematology consultants at the blood service. 2. Give the laboratory time to perform a 'group' and antibody screen on every patient before elective surgery. Although in most patients crossmatched blood can be provided, after the group and screen (G & S) in 1 hour, the 1-4% of patients with atypical red cell alloantibodies require extra laboratory time for antibody identification and to obtain compatible units of blood from the blood centre. For this reason, grouping and saving of blood is best performed at a preoperative clinic, even if this is several weeks in advance, and even though a new sample may then be required for crossmatching a day or two before operation, depending on local hospital policy. 3. If no atypical antibodies are present, many procedures can now be performed after grouping and saving alone, blood being provided only if it is required during or after operation. If the antibody screen has been performed already and is negative, blood can be issued on an immediate spin test taking 10 min. In some hospitals a so- called 'electronic' crossmatch allows blood to be issued without any further wet testing. 4. Most hospitals operate a standard, or maximum, blood order schedule (SBOS/MBOS) (British Committee for Standards in Haematology 1990). This agreed schedule for blood ordering improves efficiency within the blood bank and can also simplify the ordering process for junior doctors. An order can be placed prior to major vascular or hepatic operation, where there is a strong likelihood that FFP or platelets may be required, but the components are not usually issued until they are required; this avoids wastage. Discuss these arrangements preoperatively with a clinical haematologist and agree the procedures for regularly recurring events. Key point • Blood component therapy should be given after reviewing recent laboratory results, not on an empirical basis. 5. Elective surgery should be undertaken on patients with thrombocytopenia, or congenital and acquired disorders of coagulation, only after careful preoperative assessment, and under the direction of a haematologist. 6. Many patients can avoid allogeneic transfusion by normalization of haemoglobin preoperatively, using erythropoietin and iron therapy as appropriate, minimization of intra- and postoperative blood loss, and acceptance of a lower postoperative haemoglobin, such as 7-8 g dH. A blood loss of 1.5 litres is well tolerated by most patients who have a normal initial blood haemoglobin, without the need for red cell transfusion of any sort, provided they are given adequate volume support with crystalloid and colloids. Preoperative autologous transfusion There are three kinds of autologous (derived from the same individual) blood transfusion that are practised to varying degrees at hospitals in the UK. 1. Intra- and postoperative cell salvage 2. Acute normovolaemic haemodilution 3. Preoperative autologous deposit (PAD). Intra- and postoperative cell salvage A number of companies manufacture equipment that can be used to collect shed blood from intraoperative wounds and drains, and also postoperative drainage containers. Some of these return the blood as collected or they may be used to wash and process the blood to remove plasma constituents. If large volumes of shed blood are returned without processing, the patient may experience coagulation problems that can cause further bleeding. These cell salvage procedures have been evaluated by clinical trials in cardiac and orthopaedic surgery. There is definite evidence that salvage can reduce the proportion of patients who receive allogeneic red cell transfusion in orthopaedic surgery. In cardiac surgery, trials show only a slight reduction in transfusion of allogeneic red cells. The systems have also been used in liver surgery and liver transplantation and are increasingly used in other major vascular surgical procedures. Many clinicians believe from clinical experience that patients with major surgical blood losses do better if they are managed by reinfusing salvaged blood. These systems should not be used for 'dirty' wounds where there is risk of infection from bowel contents or abscesses. Great caution is also exercised over the use of this equipment in patients with malignancy. Acute normovolaemic haemodilution There is some controversy over the value of this procedure, in which the anaesthetist withdraws several packs of the patient's blood in the anaesthetic room immediately before surgery, replacing the volume straight away with crystalloid or colloid. The collected blood is then reinfused during or immediately after the operation. The blood must be taken into a clearly labelled blood pack containing standard anticoagulant and should remain 94 HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 8 with the patient until it is reinfused to avoid problems of transfusion to an inappropriate patient. Reinfusion must be completed before the patient leaves the responsibility of the anaesthetist. This procedure is most likely to be of benefit where the anticipated blood loss is greater than one litre and where the patient's haematocrit is relatively high. The degree to which the haematocrit can be lowered preoperatively depends on the status of the patient but patients who can tolerate a low haematocrit are likely to benefit most from this procedure. Preoperative autologous deposit (PAD) 1. It may be possible for the patient to make a preoperative donation of 2-4 units of red cells - typically 1 unit per week - for autologous transfusion at or after operation. This is suitable for patients undergoing major surgery likely to require transfusion, especially if there are red cell phenotypying problems or refusal to receive donated blood. Directed donations from family or friends are not recommended in the UK, primarily because of confidence in the general safety of donor blood and concern that coercion may inhibit voluntary withdrawal of unsuitable donors. 2. Autologous donations may not be given by patients with active infections, unstable angina, aortic stenosis or severe hypertension. A haemoglobin level of > 10 g dl" 1 is maintained with oral iron supplements. Trials have failed to demonstrate a consistent advantage from using recom- binant human erythropoietin (rhEPO) to accelerate haemopoiesis. Elective orthopaedic and gynaecological surgery are two areas where up to 20% of patients may be suitable for autologous donation. 3. A number of issues mitigate against the wider appli- cability of this procedure: a. Late cancellation of surgery can lead to waste. b. Relatively few patients are suitable for PAD because of age, drug therapy or comorbidity. c. Criteria for transfusion of donated units should be identical to those for ordinary units and not be relaxed simply because it is available. d. Many patients become more anaemic following PAD and the likelihood of receiving a transfusion increases, whether autologous or allogeneic. e. Current UK guidelines (British Committee for Standards in Haematology, Blood Transfusion Task Force 1993) stipulate that autologous units be tested for the same range of markers of transmissible disease as homologous donations, which increases costs and leads to ethical dilemmas if the results prove positive. f. Although some risks of transfusion are reduced by using autologous predeposit, errors in patient identification may still occur. It is possible that bacterial contami- nation is more likely than with standard donor blood. g. Hospitals need to operate secure laboratory and clinical protocols to ensure proper identification of autologous units and separation from homologous donation. h. The practice is likely to be associated with increased cost, and benefits are difficult to quantify. Emergency surgery 1. Patients who are clinically shocked, as from sepsis or haemorrhage, or actively bleeding, require preoperative clinical and laboratory assessment. If possible, stabilize the patient prior to operation unless there is immediate access to the operating theatre to stop the bleeding. Maintain blood pressure, circulating volume and colloid osmotic pressure. First priorities in treating acute blood volume depletion are to maintain blood pressure, circulating volume and colloid osmotic pressure and then to restore the haemoglobin level. The appropriate initial therapy is to give a synthetic plasma substitute and crystalloid. 2. Replace massive blood loss with red cells, FFP, platelets and cryoprecipitate, as indicated by results of testing for PT, APTT, TT, fibrinogen levels and platelet count. The thromboelastogram (TEG), which gives a global assessment of clotting efficiency, is used routinely in some hospitals. Maintain normothermia by transfusing all blood and fluids through a warming device. Even mild hypothermia can contribute to coagulopathy. 3. In an extreme emergency you may give uncrossmatched group O RhD negative blood, 'flying squad blood', immediately. As soon as a sample from the patient reaches the laboratory, group-compatible uncrossmatched blood may be issued within approximately 10 min. It requires 45-60 min for a full crossmatch. A retrospective crossmatch will always be performed on any uncrossmatched units transfused in an emergency. BLOOD COMPONENTS 1. The supply of blood components in the UK is based on unpaid volunteer donors. Over 99% of donor blood is separated into components, predominantly red cells in additive solution, fresh frozen plasma (FFP), platelets and cryoprecipitate. Cryosupernatant and buffy coats are also produced (Table 8.3). The collection, testing and processing of blood products is organised within the UK by the National Blood Service under the aegis of the National Blood Authority (NBA). Fractionated plasma products, produced by the Bio Products Laboratory (BPL) section of the NBA, are now produced entirely from imported USA plasma. This is because of fears about potential transmis- sion of variant Creutzfeldt-Jakob disease (vCJD) through the British blood supply. The fractionation process is used to produce intravenous immunglobulin (IVIg), albumin, specific immunglobulins and other products. 95 8 PATIENT ASSESSMENT Table 8.3 Blood constituents available for ciinicai use Whole blood* Blood components* Plasma products Red cells - plasma reduced - leucocyte poor - frozen - phenotyped Platelets White cells (buffy coat) Fresh frozen plasma Cryoprecipitate Human albumin solution Coagulation factor concentrate Immunoglobulin - specific - standard human *These products are not heat treated, and all may transmit microbial infection. 2. The hospital transfusion laboratory is concerned with grouping and antibody screening of patient samples, compatibility testing and issuing of appropriate components, together with running an appropriate and accurate documentation system. Remember that, unlike the rest of pathology, the transfusion laboratory, under the direction of its consultant haematologist, is offering a therapy for patients, not merely a testing service. Seek advice regarding the appropriate use of therapeutic components from the haematologist in change. 3. All the functions of the hospital transfusion laboratory require regulation and monitoring and both internal and external quality assurance schemes are performed regularly. Hospital laboratories have standard operating procedures for all the laboratory work carried out within them. Hospitals are also required by the Department of Health, via the Better Blood Transfusion initiative, to have a set of protocols and guidelines in place which are issued to all medical staff, detailing the range of components available together with procedures and indications for their use. The standard blood-ordering schedule is one of these, as men- tioned above. The Hospital Transfusion Committee (HTC) provides a forum whereby the clinical users of blood components can meet with the laboratory staff, the haematologist in charge of transfusion and the local transfusion specialists from the blood centre. The responsibilities of such a committee are to organize audit so that activity can be assessed against protocols, to provide information on use of resources, to monitor inappropriate use and adverse effects of transfusion and to provide a mechanism whereby the audit loop can be completed. Plans for education and training in blood transfusion may be drawn up by the HTC along with new protocols and initiatives to improve blood transfusion practice within the hospital. The HTC is directly accountable to the Chief Executive and once again this pattern of responsibility is now formally expected and monitored by the Department of Health. Serious adverse events in transfusion are reported to SHOT (Serious Hazards of Transfusion), which is a national reporting body that collates anonymized data nationwide on serious adverse events. An annual report is brought out and actions are drawn up to try and improve transfusion practice in hospitals nationwide. In the 5 years since this scheme began, nearly 70% of reports to SHOT have been in the category of 'incorrect blood component transfused'. Blood grouping and compatibility testing Red cells carry antigens, which are typically glycoproteins or glycolipids attached to the red cell membrane. Antibodies to the ABO antigens are naturally occurring. Antibodies to other red cell antigens, such as the Rh group (CDEce), Kell, Duffy and Kidd, appear only after sensitization by transfusion or pregnancy and may cause haemolytic transfusion reactions and haemolytic disease of the fetus and newborn. 1. Naturally occurring antibodies are usually IgM antibodies but may be IgG and are found in individuals who have never been transfused with red cells or who have not been pregnant with a fetus carrying the relevant red cell antigen. They are believed to be produced in response to exposure to substances that are found within the en- vironment, including the diet, which have similar structure to red cell antigens. Naturally occurring anti-A anti-B and anti-AB antibodies are reactive at 37°C and are com- plement fixing antibodies which cause intravascular lysis of ABO incompatible red cells. 2. Immune red cell antibodies are principally IgG, but can contain an IgM and/or an IGA component and these are formed as a result of exposure to foreign red cell antigens during transfusion or pregnancy. Frequency of these immune red cell alloantibodies is determined by the frequency of the antigen in the population and its immuno- genicity. Of these D is by far the most immunogenic, followed by Kell (K) and c. The concentration of the antibodies decreases over time if the individual is not exposed to further antigenic stimulus and they may become undetectable in the laboratory. Key point Report to the clinical haematologists and transfusion laboratory staff any patient with a history of a previous red cell alloantibody. 96 HAEMATOLOGICAL ASSESSMENT AND BLOOD COMPONENT THERAPY 8 3. In the blood transfusion laboratory all samples sent for 'group and screen' or 'group and save' have the ABO and RhD group determined using monoclonal antibodies, which cause direct agglutination of red cells at room temperature if the relevant antigen is present on those red cells. A screen for atypical red cell alloantibodies is performed in which the patient's serum is incubated with reagent red cells, usually three different ones, which between them carry all the commonest red cell antigens. Any antibodies present in the serum will coat the reagent red cells during the incubation period. The red cells are then washed to remove free antibody, and antihuman globulin (AHG) is added to cause visual agglutination of any red cells that are coated with antibody. This is known as the indirect antiglobulin test (IAT) or Coombs' test. If antibodies are detected using this test, a more extended red cell panel is used to identify which alloantibodies are present. These techniques may be carried out in glass tubes, in microtitre plates or in solid phase (Diamed) columns. ABO, Rh compatible blood may then be crossmatched, or a G & S sample can be held until blood is required. A lower threshold for crossmatching is necessary if a patient has alloantibodies as this may cause delay in finding compatible blood at short notice. Red cell transfusion Major indications for transfusion of red cells are bleeding, anaemia (if severe, and the cause has been established and cannot be treated with alternatives) and bone marrow failure. 1. The majority of red cells issued in the UK are resus- pended in optimum additive solution, most commonly SAG-M (sodium chloride, adenine, glucose and mannitol). The blood is anticoagulated with a citrate anticoagulant. The approximate volume of an SAG-M unit of red cells is 270 ml ± 50 ml. The haematocrit is between 0.5 and 0.7. All cellular components are leucodepleted in the UK and the white cell count per unit is less than 5 x 10 6 . There is therefore no indication for the use of a bedside in-line filter in the UK. 2. The blood has a shelf life of 35 days when stored between 2°C and 6°C. It can be out of controlled storage temperature for up to a maximum of 5 h before transfusion is completed. 3. During storage the concentration of the red cell 2,3- diphosphoglycerate (2,3-DPG) gradually falls, which increases the oxygen affinity and reduces the amount of oxygen the cells can deliver to tissues. Red cells in SAG- M are not usually used for exchange transfusion or large volume transfusion in neonates. An alternative product using citrate phosphate dextrose and adenine (CPDA) is used. 4. There is almost no whole blood issued to any hospital in the UK at present (less than 1 % of units are issued as whole blood), but alternative plasma-reduced products are sometimes available for multitransfused problem patients. 5. Red cells matched for extended phenotype are issued for patients who are transfusion dependent and at risk of producing multiple red cell alloantibodies. 6. There is a bank of frozen red cells available through the National Blood Service stored at Birmingham. These include rare units negative for specific common antigens, for use in patients with multiple red cell antibodies. These are made available for particular patients after discussion with the consultant haematologists in the National Blood Service. Indications 1. For the majority of patients undergoing elective or emergency surgery a transfusion trigger of 8 g dl" 1 is appropriate. Patients with known cardiovascular disease, previous myocardial infarction and the very elderly or infirm may require a higher haemoglobin perioperatively. A patient undergoing operation with a normal haemoglobin of approximately 14 g dl" 1 can afford to lose 1.5 litres of blood before red cell transfusion becomes necessary. Clearly the patient should not be allowed to become hypovolaemic or hypotensive and the volume lost must be replaced with colloids and crystalloid as appropriate. Except in an emergency, patients should not undergo operation if they are anaemic. At preoperative clerking clinics, iron deficiency anaemia or anaemia of chronic disease can be corrected using iron therapy or erythropoietin as appropriate. This reduces unnecessary use of a limited resource and exposure of patients to potentially risky blood products. 2. A recent large randomised clinical trial in critically ill patients demonstrated that a restrictive transfusion policy aimed at maintaining Hb in the range 7-9 g dl -1 was at least equivalent, and possibly superior, to a liberal policy maintaining Hb at 10-12 g dl -1 . A trigger haemoglobin of 7-8 g dl -1 is therefore appropriate even in the critically ill, except perhaps for those with unstable angina or acute myocardial infarction (MI). This leaves some margin of safety over the critical level of 4-5 g dl" 1 . At this level, oxygen consumption begins to be limited by the amount that the circulation can supply. 3. In those patients with abnormal bone marrow function from bone marrow failure resulting from drugs or marrow infiltration, it may be less appropriate to allow the haemoglobin to become so low; a maintenance trough level of 9 g dl -1 may be appropriate. There is now some evidence that patients receiving radiotherapy for malignancy have better outcomes if the haemoglobin is maintained at 97 [...]... Normal saline Normal saline + KCI 150 150 150 190 40 30 0 38 0 Normal saline + KCI 150 170 20 34 0 Hartmann's 5% dextrose 5% dextrose + KCI 131 111 5 40 40 280 280 36 0 20 20 32 0 5% dextrose + KCI 286 Dextrose saline 30 30 Dextrose saline + KCI 30 70 40 36 6 Dextrose saline + KCI 30 50 20 32 6 75 30 0 1000 167 75 30 0 Half normal saline Twice normal saline - Continuing loss Patients with continuing losses... with normal values Temp pH Pco2 P02 37 °C 7 .3 6-7 .44 (4 4 -3 6 nmol M) 4. 6-5 .6 kPa (3 5-4 2 mmHg) 10. 0-1 3. 3 kPa (7 5-1 00 mmHg) HCOi Tco2 SBC BE SBE O2 sat Hb 2 2-2 6 mmol 1-1 2 4-2 8 mmol 1-1 2 2-2 6 mmol 1-1 -2 to +2 mmol I-1 -3 to +3 mmol 1-1 >95% 11. 5-1 6.5gdl-1 9 temperature Blood gas machines are programmed to correct the gases if you tell the machine the patient's actual temperature However, there has been much... by succinylated gelatin (Gelofusin) Being relatively short acting, it is particularly useful as a holding measure until blood becomes available Gelofusin probably stays within the intravascular space for 6 0-9 0 min at most 3 In continuing hypovolaemia, hetastarch gives more prolonged expansion and its larger molecules are better retained in the circulation when the capillaries are leaky, e.g in septicaemic... liver disease Trends in Experimental and Clinical Medicine 8: 8-2 5 Ogden JE, MacDonald SL 1995 Haemoglobin based red cell substitutes: current status Vox Sanguinis 69: 30 2 -3 08 Vichinsky EP, Haberkern CM, Neumayr L et al 1995 A comparison of conservative and aggressive transfusion regimens in the peri-operative management of sickle cell disease New England Journal of Medicine 33 3: 20 6-2 13 Williamson L 1994... transfusion in a sheep Lancet 35 6: 99 9-1 000 Hunt BJ 1991 Modifying peri-operative blood loss Blood Reviews 5: 16 8-1 76 McClelland DEL, Phillips P 1994 Errors in blood transfusion in Britain: survey of hospital haematology departments BMJ 30 8:120 5-1 206 Mehta AB 1994 Glucose-6-phosphate dehydrogenase deficiency Prescribers Journal 34 : 17 8-1 82 Mehta AB, Mclntyre N 1998 Haematological changes in liver disease... ECF leading to a rise in albumin concentration and haematocrit B Loss of plasma leading to a rise in haematocrit but no change in albumin concentration 114 FLUID, ELECTROLYTE AND ACID-BASE BALANCE § Table 9.5 Changes resulting from three kinds of expansion and contraction of body fluids Acute change Example Change in ECF vol Change in ICF vol Change in [Na] Change in [Hct] Change in [protein] Loss... Dextran 70 in saline 0.9% or glucose 5% Macrodex Lomodex 70 Gentran 70 38 000 . Trends in Experimental and Clinical Medicine 8: 8-2 5 Ogden JE, MacDonald SL 1995 Haemoglobin based red cell substitutes: current status. Vox Sanguinis 69: 30 2 -3 08 Vichinsky EP, . transfusion-associated graft versus host disease. are normal but iron-binding capacity is reduced (in contrast to iron deficiency where iron-binding capacity is raised). Ferritin (an intermediary . disease - Reticulocytosis - Myelodysplasia - Aplastic anaemia - Paraproteinaemia - Alcohol abuse • Normochromic normocytic - Anaemia of chronic disease - Renal failure - Bone marrow infiltration -

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