Fresh Frozen Plasma and Cryoprecipitate
Standard fresh frozen plasma (FFP) is produced from both UK and non-UK donors; methylene blue FFP is available for children under the age of 16 years. The FFP is sourced from the USA as a precaution against variant Creutzfeldt–Jakob Disease (vCJD). FFP is frozen and stored at −30°C with a shelf-life of 24 months. If required FFP is rapidly thawed at 37°C before being issued. Once thawed, FFP should be transfused within 4 hours. However, if FFP is stored at 4°C after thawing, the transfusion can be completed within 24 hours. FFP may be indicated if the patient has a single factor deficiency for which there is no virus-safe fractioned product, severe bleeding, disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP) (BSCH 2004a). Table 14.2 shows the principles of selection of FFP.
Cryoprecipitate is a plasma product that contains clotting factors such as factor VIII, fibrinogen and factor XIII. The most common use for cryoprecipitate is to enhance fibrinogen levels in dysfibrinogenaemia and acquired hypofibrinogenaemia seen in massive transfusion and DIC. Treatment is usually indicated if plasma fibrinogen is less than 1 g/l. Cryoprecipitate once thawed should be transfused immediately. The use of FFP and cryoprecipitate should be guided by monitoring using laboratory coagulation screens.
Platelets
Platelets can be either pooled or apheresis. When pooled platelets are produced from the National Blood Service, donated whole blood is centrifuged to separate the red cells, platelets and plasma. Four donations of platelets are pooled to produce one adult unit of platelets. Apheresis platelets are collected from just the donor who only donates platelets. Red cells are not collected from this donor, although the platelets are in the plasma.
All platelets must be stored on a special agitator rack at 20–24°C to prevent clumping. Each unit of platelets has a shelf-life of 5 days from the date of donation. Platelet transfusions are indicated for the prevention and treatment of haemorrhage in patients with thrombocytopenia (low platelet count) or platelet function defects. The cause of thrombocytopenia should be established before a decision is made for a platelet transfusion (BSCH 2003). Risks associated with platelet transfusions include alloimmunisation, transmission of infection, allergic reactions and transfusion-related lung injury (TRLI).
IMPORTANCE OF PATIENT IDENTIFICATION
Serious hazards of transfusion reports (1996–2008) have identified that a patient identification band missing, defaced or hidden is a significant contributory factor to wrong blood incidents. All patients receiving a blood transfusion must wear a patient identification band (or a risk assessed to be equivalent). The minimum patient identifiers are last name, first name, date of birth and unique patient identification number. The information must be legible and accurate. In emergency situations the patient’s core identifiers may be unknown. In this situation, at least one unique identifier, usually a temporary identification number (e.g. accident and emergency number), and the patient’s gender (i.e. unknown male/female) must be used.
Patient identification should be checked and confirmed as correct at each stage of the transfusion process. The patient should, whenever possible, be asked to state full name and date of birth. This must match exactly the information on the patient’s wristband and any other associated paperwork required at that stage of the blood transfusion process. For patients who are unable to identify themselves, e.g. patients who are unable to respond competently, or are unconscious or confused, verification of the patient’s identification should be obtained from a parent or carer if present. If there are patient identification discrepancies at any stage of the transfusion process, the information must be verified and discrepancies investigated and corrected before proceeding to the next stage of the process.
DOCUMENTATION, TRACEABILITY AND EQUIPMENT
Documentation
Full and complete documentation is required at every stage of the blood transfusion process to provide an assured and unambiguous audit trail. Minimum documentation of transfusion episodes in the patient clinical records should include:
Pre-Transfusion
- Clinical indication for transfusion
- Pre-transfusion indices (e.g. full blood count, coagulation screen)
- Date of decision
- Date of transfusion (if known)
- Blood component to be transfused and volume
- Rate of transfusion
- Consent from patient (written consent not required)
- Special requirements (e.g. irradiated or cytomegalovirus [CMV]-seronegative components).
Administration
- Date and time component collected
- Date and time transfusion started
- The donation number of component transfused
- Volume administered
- Identification of staff who started the transfusion
- Observations before, during and after transfusion.
Post-Transfusion
- Date and time component completed
- Evidence of unit being fated
- An indication of whether transfusion achieved desired effect
- Documentation of any reactions that occurred.
Traceability
To ensure compliance with the Blood Safety and Quality Regulations (MHRA 2005) all blood components should be traceable from the donor to their final destination, whether this be a recipient, manufacturer or disposal. All organisations have a policy on how to achieve this by using electronic or manual methods. This information is then kept for 30 years.
Equipment
Intravenous Access
All blood components can be administered through standard peripheral intravenous cannulas according to manufacturer’s specifications. The size of the intravenous cannulas depends on the size and integrity of the vein as well as the speed at which the blood component is to be transfused. All blood components can be slowly infused through small-bore cannulas or butterfly needles, e.g. 21 gauge (G). For more rapid infusion, large-bore needles e.g. 14 G, are needed. Peripherally inserted long central catheters (PICC lines) with narrow lumen diameter may lead to slower rates. Many transfused patients have venous access established by the use of short-term or indwelling multi-lumen central lines. These are usually suitable for transfusion of blood components. One lumen should be reserved for administering blood components where possible.
Administration Set
Blood components must be administered only using a ‘blood administration set’ that has an integral 170–200 µm screen filter. It is now deemed unnecessary to prime the blood administration set with saline. The blood administration line should be changed at least every 12 hours and after completion of the prescribed blood transfusion to prevent bacterial growth. Platelets should not be transfused through an administration set that has been previously used for red cells or other components because this may cause aggregation and retention of platelets in the line.
Infusion Pumps
Electronic infusion devises may be used for the administration of blood and blood components if they are licensed to do so. Rapid infusion devices may be used when large volumes have to be infused quickly, as in massive haemorrhage. These typically have a range of 6–30 l/h and usually incorporate a blood-warming device. It is important to be familiar with the equipment and use it according to the manufacturer’s instructions.
Blood Warmers
Rapid infusion of red cells soon after their removal from blood storage refrigeration at 4°C can lead to hypothermia, arrhythmias, cardiac arrest or impaired blood clotting in surgical or trauma patients. This is also of concern when blood is rapidly infused through a central venous catheter terminating in or near the right atrium, or in neonates and small infants undergoing large-volume transfusions (BSCH 2004b). The National Institute for Health and Clinical Excellence (NICE 2008) recommends that, in all adults undergoing elective or emergency surgery under general or regional anaesthesia, all blood components should be warmed to 37°C.
Blood warmers should also be used in the transfusion of patients with clinically significant antibodies. Blood should only be warmed using CE-marked, specifically designed and regularly maintained blood-warming equipment with a visible thermometer and audible warning. Some blood warmers operate up to 43°C but are safe provided that they are used and serviced according to the manufacturer’s instructions. Blood must never be warmed in an uncontrolled way, such as in a microwave, in hot water or on a radiator.
MONITORING PRIORITIES IN A PATIENT RECEIVING A BLOOD TRANSFUSION
A blood transfusion should take place only when there are sufficient staff available to observe and monitor the patient. The patient should always be visually observed and monitored throughout the blood transfusion to ensure quick identification of any adverse reactions. This is particularly necessary if patients are unconscious because they are unable to complain of any transfusion reaction symptoms. A conscious patient should be made aware of the symptoms of a transfusion reaction and advised to inform health-care staff immediately should he or she experience one. Ensure that the patient’s ‘call bell’ is easy to reach.
Pre-Transfusion
Transfusion observations must be clearly distinguished from other routine observations and filed in the patient’s clinical notes. Immediately before collecting the first unit of blood component record the patient’s temperature, pulse rate, blood pressure and respiration rate. These should be taken no more than 60 minutes before the start of the transfusion. This is to provide baseline observations in case of a reaction during the transfusion. It also allows staff to assess the patient’s medical condition before starting the transfusion. If there are any concerns raised by the baseline observations, medical advice should be sought before collecting the unit of blood from the transfusion department. Equipment required for the blood transfusion should also be ready because a delay once the blood component has been collected could result in unnecessary wastage.
During Transfusion
Many serious reactions occur in within 30 minutes of commencement of the transfusion of a blood component unit (Serious Hazards of Transfusion or SHOT scheme 2006), so close observation during this period is essential. Pulse rate, blood pressure, temperature and respiration rate should be taken and recorded 15 minutes after the start of each component transfusion. For rapid infusion more frequent observations may be required. Assessment should be made for signs of a transfusion reaction, in particular pyrexia, hypo- or hypertension and tachycardia. The National Confidential Enquiry into Patient Outcome and Death (NCEPOD 2005) reported that, in critically ill medical patients, the respiratory rate is an early and important indicator of deterioration. Difficulty in breathing and rapid respiration may both be features of serious transfusion reactions. Possible signs and symptoms of a blood component transfusion reaction include:
- Pyrexia
- Tachycardia
- Change in blood pressure
- Breathlessness or rapid breathing
- Coughing
- Haemoglobinuria
- Nausea
- Vomiting
- Diarrhoea
- Skin flushing/rash
- Rigors
- Collapse
- Chest, abdominal, bone, muscle or loin pain
- Headache
- Restlessness, agitation or confusion.
If a transfusion reaction is suspected, inform the doctor or nurse in charge immediately. Stop the transfusion and check that the correct patient details are on the blood component and the right blood has been given to the right patient. Development of any symptoms suggesting a transfusion reaction should prompt more frequent observations of temperature, pulse, blood pressure, respiratory rate, oxygen saturation levels and urine output. The doctor may request the transfusion to be discontinued due to the transfusion reaction or adverse event. In these cases the blood component, along with the giving set, should be removed and sealed per organisational policy and sent to the hospital transfusion department for further investigations.
Post-Transfusion
After each blood component has been transfused, record the post-transfusion pulse rate, blood pressure and temperature. If these measurements have altered significantly from any previous observations, respiratory rate should also be taken. Any routine observations should be continued, particularly if the patient is critically ill.
The SHOT (2008) report emphasises that, on occasion, transfusion reactions can occur many hours after the transfusion is completed and recommends that patients are observed during the subsequent 24 hours. For transfusions administered as day cases, continued direct observation is not possible. Such patients should be counselled about the possibility of late adverse reactions and organisations should ensure that mechanisms are in place that give patients access to clinical advice at all times.
ADVERSE REACTIONS TO A BLOOD TRANSFUSION
It is often difficult to distinguish which type of reaction is taking place because the signs and symptoms of these reactions are very similar and are detailed below. The most important transfusion reactions are:
- Acute haemolytic transfusion reactions
- Infusion of a bacterially contaminated unit
- TRALI
- Severe allergic reaction or anaphylaxis
- Post-transfusion purpura (PTP)
- Transfusion-associated graft-versus-host disease.
In all cases expert medical advice can be sought from a haematologist and the blood transfusion department must be informed as soon as possible, who may need to inform the National Blood Service or the Medicines and Healthcare products Regulatory Agency.
Acute Haemolytic Transfusion Reactions
This often occurs when patients are transfused with incompatible red cells, and is when the patient’s own anti-A or anti-B antibodies cause an acute severe clinical reaction. Acute haemolytic transfusion reactions are most commonly due to errors in obtaining or labelling group and antibody screen samples, collecting the wrong blood for the wrong patient, or failure to carry out the required bedside checks before the unit is administered. Signs and symptoms of an acute transfusion reaction are:
- Pain at cannulation site
- Pain in chest, back or abdomen
- Hypotension/Hypertension
- Tachycardia
- Pyrexia
- Bleeding
- Collapse
- Haemoglobinuria.
Acute haemolytic transfusion reactions can lead to acute renal failure and DIC, which can be fatal. Management of haemolytic transfusion reactions would consist of stopping the transfusion immediately but maintaining venous access and seeking more expert advice from a haematologist. Return the blood component to the blood transfusion department with any extra samples requested. Administer intravenous saline via a new giving set. The patient will need to be monitored closely so it is suggested that the patient be admitted onto a critical care unit if possible.
Infusion of a Bacterially Contaminated Unit
The signs and symptoms of this type of reaction may be similar to acute haemolytic reactions or severe acute allergic reactions. Bacterial contamination of blood components are rare, but it is more often reported with infusion of platelets, which are stored at a higher temperature of 22°C than red cells which are stored at 4°C. If a blood component is bacterially contaminated, most probably it will have discoloration, a smell or a Gram stain. The most common signs of infusion of a bacterially contaminated unit are:
- Acute reaction with rigors
- Pyrexia
- Hypo-/hypertension
- Tachycardia
- Collapse.
Suggested treatment would be to stop the transfusion immediately and seek medical advice, and contact a microbiologist for expert advice. Intravenous antibiotics should be administered that cover both Gram-positive and Gram-negative bacteria. Return blood component to the blood transfusion department with any samples requested.
Transfusion-Related Lung Injury
TRALI is mostly associated with transfusion of plasma containing white cell antibodies, which will react with the patient’s own white cells. Symptoms usually occur within 6 hours of transfusion, which are:
- Breathlessness
- Non-productive cough
- Loss of circulatory volume
- Hypotension
- Acute dyspnoea
- Hypoxia
- Neutropenia.
The chest radiograph characteristically shows bilateral nodular infiltrates in a batwing pattern, typical of acute respiratory distress syndrome (ARDS). It may be difficult to distinguish TRALI from other non-cardiogenic pulmonary oedema or cardiac failure; therefore it may be necessary to seek advice from a critical care specialist as well as a haematologist. Treatment should be the same as for patients with ARDS. High concentration oxygen or mechanical ventilatory support may be needed.
Allergic Reactions or Anaphylaxis
Allergic reactions or anaphylaxis to blood units usually occur at the start of transfusion. They are normally associated with rapid transfusion of plasma. Anaphylaxis occurs when a patient who is pre-sensitised to an allergen producing IgE antibodies is again exposed to the antigen. Patients who are deficient in IgA can develop antibodies to IgA and cause anaphylaxis if exposed to IgA in transfusion. Symptoms may include:
- Hypotension
- Bronchospasm
- Chest pain
- Abdominal pain
- Dyspnoea
- Nausea
- Vomiting
- Urticaria
- Periorbital and laryngeal oedema
- Redness of skin
- Conjunctivitis.
In severe anaphylaxis stop transfusion and call for medical advice immediately. Consider giving intravenous chlorpheniramine.
Post-Transfusion Purpura
This is a rare complication of transfusion that most often occurs in female patients. It is caused by platelet-specific alloantibodies. The main symptoms are an extremely low platelet count typically 5–9 days after transfusion. The patient may also develop bruising or bleeding.
Treatment of post-transfusion purpura is a high-dose intravenous immunoglobulin. Platelet transfusions may be necessary if the patient is at high risk of bleeding.
Transfusion-Associated Graft-Versus-Host Disease
Transfusion-associated graft-versus-host disease (TA-GvHD) is caused when white cells present in the blood component recognise the recipient’s HLA antigens as foreign which leads to engraftment. The skin, gut, liver, spleen and bone marrow are affected, commonly within 2–3 weeks of transfusion, and are usually fatal. There is no effective treatment and expert advise from a haematologist is recommended. High-risk groups, such as patients who are immunocompromised, should be given irradiated blood products only to prevent this from happening. This is when blood components are treated with 25 gray (Gy) gamma irradiation to inactivate lymphocytes that could cause TA-GvHD.
CONCLUSION
Blood transfusions should be carried out only when the risks to the patient are balanced against the benefits. Once a decision has been made to transfuse, full and complete documentation must be completed at every stage of the blood transfusion. Patients should also be monitored throughout their blood transfusion to ensure quick identification of any adverse reactions. All blood components should be traceable from the donor to its final destination.
REFERENCES
British Committee for Standards in Haematology Blood Transfusion (2001) The clinical use of red cell transfusion. British Journal of Haematology, 113, 24–31
British Committee for Standards in Haematology Blood Transfusion (BSCH) (2003) Guideline for the use of platelet transfusions. British Journal of Haematology, 122, 10–23.
British Committee for Standards in Haematology Blood Transfusion (2004a) Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. British Society for Haematology, 126, 11–28.
British Committee for Standards in Haematology Blood Transfusion (2004b) Transfusion guidelines for neonates and older children. British Journal of Haematology, 124, 433–453.
MHRA (2005) Statutory Instrument 2005/50. London: The Stationery Office.
National Confidential Enquiry into Patient Outcome and Death (2005) An Acute Problem. London: NCEPOD.
National Institute for Health and Clinical Excellence (2008) Clinical Practice Guideline: The management of inadvertent perioperative hypothermia in adults. London: NICE.
Serious Hazards of Transfusion (SHOT) scheme (1996–2008) SHOT Annual reports 1996–2008. Manchester: SHOT Office.