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Blood and blood products
Essentials
- 1
The decision to transfuse packed red cells should ultimately be based on the knowledge that the patient’s oxygen carrying capacity has dropped to an unacceptably low level.
- 2
The administration of blood products carries substantial risk. The emergency physician should always ensure that potential benefits outweigh potential risks and communicate these risks and benefits in order to obtain informed consent where possible.
- 3
Rigorous risk management of administrative and clinical processes minimizes the risk of serious adverse reaction from the transfusion of blood products.
Introduction
Blood is living tissue composed of blood cells suspended in plasma; it transports nutrients and oxygen and facilitates temperature control. An average 70-kg male has a blood volume of about 5 L. The cellular elements comprise red blood cells, white blood cells and platelets and make up about 45% of the volume of whole blood. Plasma, which is 92% water, makes up the remaining 55%.
Early attempts at blood transfusion were thwarted by adverse reactions. In 1900, Karl Landsteiner demonstrated the ABO blood group system and explained many of the observed severe incompatibility reactions ( Table 13.5.1 ). He won the Nobel Prize for medicine in 1930 and went on to discover the rhesus factor in 1940. The next major advance in transfusion medicine occurred with the development of long-term anticoagulants, such as sodium citrate, which allowed extended preservation of blood. The development of refrigeration procedures enabled the storage of anticoagulated blood. The addition of a citrate-glucose solution extended the viability of collected blood to several days. The ability to preserve blood for longer than a few hours paved the way for the establishment of the first blood bank in a Leningrad hospital in 1932.
Table 13.5.1
The ABO group system
| ABO blood group | Antigens on red cells | Antibody in serum |
|---|---|---|
| O | None | Anti-A, anti-B |
| A | A | Anti-B |
| B | B | Anti-A |
| AB | A, B | None |
Transfusion of blood and blood products is now routine and vital to the practice of emergency medicine. As with any prescribed treatment, these products are associated with potential hazards as well as advantages. The hazards are more likely to be encountered with blood products used during emergencies. The blood products available in most Australian emergency departments (EDs) are packed red blood cells, platelets, fresh frozen plasma (FFP), cryoprecipitate, activated factor VII, prothrombin complex concentrates, and other factor concentrates.
In the Australian urban hospital setting, 50% of packed red cells are used for the treatment of anaemia, 22% pre- or perioperatively and 13% for abnormal, excessive or continued bleeding. Medical oncology uses 78% of all platelets. Approximately 41% of all FFP is used to correct coagulopathy associated with surgery, 27% to correct coagulopathy in bleeding, 16% to reverse haemostatic disorders in patients having massive blood transfusion, 11.5% for reversal of warfarin effect and the remaining 4.5% for a number of miscellaneous conditions, including liver disease and disseminated intravascular coagulation (DIC).
In the ED setting, blood products are most often administered to patients with acute rather than chronic blood loss. In trauma centres, severely injured patients are the major consumers of blood products; in non-trauma centres, patients with gastrointestinal haemorrhage account for the majority of transfusions. In these settings of acute blood loss, transfusion may be required rapidly and in large quantities. However, as short-stay units are developed, non–time critical transfusions of blood products for other medical indications are increasingly the responsibility of ED staff.
Packed red blood cells
Packed red blood cells are produced from whole blood collections by removing most of the plasma by centrifugation and then resuspending the red cells in citrate-based anticoagulant/preservative solution to prolong storage time. Each unit of packed cells contains approximately 200 mL of red cells. Transfusion of one unit can be expected to raise the haematocrit by 3% and the haemoglobin by 10 g/L provided that there is no ongoing blood loss.
Packed red cells are the blood product most commonly prescribed in the ED, the usual indication being the replacement of acute blood loss. Transfusion of packed red cells is indicated where the patient’s oxygen-carrying capacity is so impaired that control of bleeding alone, if indeed it can be readily achieved, is regarded as insufficient to prevent tissue hypoxia. In patients with primary haematological conditions, failure of erythropoiesis or a haemolysis, the indication for transfusion is usually the same as for haemorrhage: a severe reduction in oxygen-carrying capacity. In patients with associated complex multi-system failure, such as DIC or septic shock, red cell transfusion may be lifesaving by improving the oxygen debt in tissues ( Box 13.5.1 ).
Box 13.5.1
Potential indications for red cell transfusion
Haemorrhage
Dilutional anaemia following severe burns
Iron deficiency anaemia
Megaloblastic anaemia
Anaemia of chronic disorders
Chronic renal failure
Failure of erythropoiesis
Sickle cell disease
Septic shock
Disseminated intravascular coagulopathy
The indication for transfusion in haemorrhagic shock has been traditionally defined as persistent haemodynamic instability despite a small volume fluid challenge. However, two further patient factors must be considered. First is the concept of hypotensive resuscitation, which states that prior to definitive cessation of bleeding, relative hypotension may stabilize clots and reduce further bleeding. Clinician must therefore alter their thresholds of haemodynamic instability. Patient factors must be borne in mind, including the cardiovascular co-morbidities and the presence of head injuries. Second, both high-volume crystalloid and blood transfusion have been associated with adverse outcomes. This suggests that both should be limited rather than focusing resuscitation efforts on the management of coagulopathy and early surgical management of haemorrhage.
Transfusion is not indicated when alternative haematinic therapy is deemed safe and appropriate. A moderately anaemic patient who is asymptomatic and not bleeding, with some reserve oxygen-carrying capacity, does not require blood transfusion. A haemoglobin of 7 g/dL is sometimes taken as the failsafe point in the decision regarding whether to transfuse, although of course the patient’s unique circumstances must be taken into account: in other words, treat the patient, not the number. It should be also considered that, in an acutely bleeding patient, the initial haemoglobin result, measured at a time of volume contraction, may be an inaccurate representation of circulating oxygen-carrying capacity. The National Health and Medical Research Council together with the Australasian Society of Blood Transfusion have published transfusion guidelines for red blood cells and other products ( Table 13.5.2 ).
Table 13.5.2
Guidelines for transfusion of blood components
Modified from the National Health and Medical Research Council and Australasian Society Clinical Practice Guidelines on appropriate use of blood components. https://transfusion.com.au/transfusion_practice/patient_blood_management_guidelines .
| Indications | Considerations |
|---|---|
| Red blood cells | |
| Hb | |
| <70 g/L | Lower thresholds may be acceptable in patients without symptoms and/or where specific therapy is available. |
| 70–100 g/L | Likely to be appropriate during surgery associated with major blood loss or if there are signs or symptoms of impaired oxygen transport. |
| >80 g/L | May be appropriate to control anaemia-related symptoms in a patient on a chronic transfusion regimen or during marrow suppressive therapy. |
| >100 g/L | Not likely to be appropriate unless there are specific indications. |
| Platelets | |
| Bone marrow failure | At a platelet count of <10 × 10 9 /L in the absence of risk factors and <20 × 10 9 in the presence of risk factors (e.g. fever, antibiotics, evidence of systemic haemostatic failure). |
| Surgery/invasive procedure | To maintain platelet count at >50 × 10 9 /L. For surgical procedures with high risk of bleeding (e.g. ocular or neurosurgery), it may be appropriate to maintain at 100 × 10 9 /L. |
| Platelet function disorders | May be appropriate in inherited or acquired disorders, depending on clinical features and setting. In this situation, platelet count is not a reliable indicator. |
| Bleeding | May be appropriate in any patient in whom thrombocytopaenia is considered a major contributory factor. |
| Massive haemorrhage/transfusion | Use should be confined to patients with thrombocytopaenia and/or functional abnormalities who have significant bleeding from this cause. May be appropriate when the platelet count is <50 × 10 9 /L (<100 × 10 9 /L in the presence of diffuse microvascular bleeding). |
| Fresh frozen plasma | |
| Single factor deficiencies Warfarin effect | Use specific factors if available. Use in the presence of life-threatening bleeding. Use in addition to vitamin K–dependent concentrates. |
| Acute DIC | Indicated where there is bleeding and abnormal coagulation; not indicated for chronic DIC. |
| TTP | Accepted treatment. |
| Coagulation inhibitor deficiencies | May be appropriate in patients undergoing high-risk procedures. |
| Following massive transfusion or cardiac bypass | Use specific factors if available May be appropriate in the presence of bleeding and abnormal coagulation. |
| Liver disease | May be appropriate in the presence of bleeding and abnormal coagulation |
| Cryoprecipitate | |
| Fibrinogen deficiency | May be appropriate where there is clinical bleeding, an invasive procedure, trauma or DIC. |
DIC, Disseminated intravascular coagulation; TTP, thrombocytopaenia purpura.
Prior to any blood product transfusion, informed consent should be sought, obtained and documented except in emergent cases, where the delays may result in substantial adverse effects. The following sections discuss the risks of red cell transfusion.
Effect of storage on red blood cells
Although it makes intuitive sense that blood loss should be replaced by blood products, there is evidence that the immediate observed benefit is from volume replacement rather than improved oxygen carriage. Red blood cells may not be fully functional until 2 to 6 hours after transfusion, because storage affects the oxygen-carrying capacity of blood. This is probably due to decreased intracellular 2,3-diphosphoglycerate (2,3-DPG), loss of red cell viability, decreased red cell deformability, relative acidosis and potassium leakage.
Storage reduces 2,3-DPG levels, leading to a leftward shift of the oxyhaemoglobin dissociation curve and increased affinity of oxygen binding. The transfused red cell does regenerate 2,3-DPG to normal levels, but this can take 6 to 24 hours post-transfusion. With increasing age of stored red cells, levels of 2,3-DPG progressively fall, such that by 5 to 6 weeks the level is only 10% of normal. It is still uncertain whether this abnormality is physiologically important, even in critically ill patients. In addition, hypocalcaemia, cell lysis, release of free haemoglobin, changes in nitric oxide levels, alterations in pH and increases in lipids, complement and cytokines are other effects of red cell storage. These changes are accompanied by increased membrane fragility, which can compromise microcirculatory flow and lead to increased red cell–endothelial cell interaction and inflammatory cytokine release. Such changes may explain recent findings associating the age of red blood cells with adverse outcomes and may be particularly disadvantageous to critically ill patients with a higher mortality risk.
When red cells are transfused, some of the cells are removed from the circulation within a few hours, with the rest surviving normally; as the storage time increases to 42 days, more cells are removed immediately after transfusion. This loss of viability is highly dependent on the anticoagulant/preservative solution used.
Potassium gradually leaks out of stored red cells, and this raises the plasma potassium by approximately 1 mEq/L/day. Citrate toxicity results when the citrate in the transfused blood begins to bind calcium in the patient’s body, resulting in hypocalcaemia. Clinically significant hypocalcaemia does not usually occur unless the rate of transfusion exceeds 1 unit every 5 minutes or so. Citrate metabolism is primarily hepatic; therefore hepatic disease or dysfunction can cause this effect to be more pronounced.
Choice of red cell product
The choice of red cell product is determined by time and safety considerations. O-negative red cells, the universal donor group, are readily available in most major hospitals. Supplies of O-negative blood are limited, and the product should be used with care. O-negative blood is generally reserved for transfusion immediately during patient reception and the initial stages of resuscitation, with a switch to cross-matched blood as soon as it is available. It is preferable that blood be collected prior to transfusion so as to characterize the recipient’s blood group serology. Premenopausal female patients should be given group O Rh-negative, Kell-negative blood in an emergency situation in order to avoid sensitization and the possibility of haemolytic disease of the newborn in subsequent pregnancies. Male patients, however, can be transfused with either Rh-positive or negative blood. The incidence of adverse reaction using this type of blood is approximately 3%. By contrast, the provision of group-specific blood requires matching a blood sample to the major (ABO) and Rh-D compatibility groups only. Group-specific blood can be available for transfusion within 35 minutes, depending on the logistic support and staffing levels within the haematology laboratory. It has an incidence of adverse reactions similar to O-negative blood. As O-negative blood is usually in short supply, it is preferable, where possible, to infuse group-specific blood. A more comprehensive cross-match where there are no atypical antibodies identified in the initial screening can take 30 minutes or more and the incidence of adverse transfusion reaction is then reduced to 0.01%.
Precautions when cross-matching and transfusing blood
Although most patients do not require transfusion in the ED, it is often appropriate to ‘group and hold’ or cross-match the patient while in the department. Many hospitals have written protocols detailing the anticipated requirements for a given surgical procedure. Documentation should be meticulous. It should be mandated that the person drawing the blood for cross-matching should also fill in and sign the laboratory request form. Most severe incompatibility reactions to blood transfusion result not from exposure to unusual antigens but from administrative errors. Any systematic change in documentation protocols—for example, the adoption of an electronic record—must be accompanied by obsessive risk-management strategies.
The checking of the compatibility details of blood to be transfused must be meticulous. Blood products should not be left lying around workbenches. Universal precautions must be observed by staff setting up transfusions. Rapid or large transfusions should be given via a blood warmer. Blood should be transfused intravenously through sterile giving sets containing 170-μm filters. Alternative routes (arterial, intraperitoneal or intraosseous) should be used in exceptional circumstances. Lines for transfusion should be dedicated lines; drugs and other additives should be administered at separate sites. Normal saline is compatible with all blood components.
Pulse, blood pressure and temperature are measured at regular intervals and particular attention is paid to the patient during the first 25 minutes of the transfusion. The transfusion is started slowly. The rate at which it continues depends on clinical urgency. As a general rule, the faster the anaemia has developed, the more rapidly it must be corrected. Rapid infusion techniques may be indicated in patients who appear to be exsanguinating, but an overly rapid infusion may precipitate cardiac failure in the elderly. Hypothermia may be a problem if a blood warmer is not used.
Adverse reactions to transfusion
The principal adverse reactions to blood transfusion are listed in Table 13.5.3 . Serious adverse reactions are relatively rare ( Table 13.5.4 ), although some are more likely to occur when blood is administered urgently.
Table 13.5.3
Adverse effects of blood transfusion
| Immunological transfusion reactions | Transmission of infection |
|---|---|
| Immediate | Bacterial |
| Febrile non-haemolytic reactions | Brucella |
| Acute haemolytic transfusion reactions | Pseudomonas |
| Allergic reactions and anaphylaxis | Salmonella |
| Transfusion-related acute lung injury | Treponema pallidum |
| Delayed | Parasites |
| Delayed haemolytic transfusion reactions | Babesia |
| Alloimmunization | Plasmodium |
| Transfusion-associated graft-versus-host disease | Toxoplasma |
| Hypothermia | Trypanosoma |
| Dilutional coagulopathy | Viruses |
| Volume overload | Cytomegalovirus |
| Hepatitis B and delta agent | |
| Hepatitis A | |
| Hepatitis C | |
| Other hepatitis, ‘non-A, non-B’ | |
| HIV-1 and HIV-2 | |
| HTLV-1 and HTLV-2 | |
| Parvovirus |
HIV, Human immunodeficiency virus; HTLV, human T-cell lymphotropic virus.
Table 13.5.4
Incidence of adverse transfusion reactions (per unit packed red cells transfused)
Modified from Australian Red Cross website: https://transfusion.com.au/adverse_events_overview . Accessed February 2017.
| Adverse transfusion reaction | Incidence | Mortality |
|---|---|---|
| Bacterial sepsis | 1 in 40,000–500,000 | 1 in 4–8 million |
| Acute haemolytic reaction | 1 in 12,000–38,000 | 1 in 600,000–1.5 million |
| Delayed haemolytic reaction | 1 in 1,000–12,000 | 1 in 2.5 million |
| Anaphylaxis | 1 in 20,000–50,000 | |
| Transfusion-related acute lung injury | 1 in 5,000–100,000 | 1 in 5 million |
| Fluid overload | 1 in 100–700 | |
| Transfusion-associated graft-versus-host disease | Rare | 90% fatality |
Immunological transfusion reactions
Immunological transfusion reactions may be immediate or delayed in onset.
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