Haematological problems

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CHAPTER 10 HAEMATOLOGICAL PROBLEMS

Introduction 246
Anaemia in the critically ill 246
Indications for blood transfusion 246
Blood products in the UK 247
Administration of blood products 250
Major haemorrhage 251
Risks and complications of blood transfusion 252
Patients who refuse transfusion 254
Normal haemostatic mechanisms 255
Coagulopathy 258
Thrombocytopenia 262
Disseminated intravascular coagulation 263
Purpuric disorders 264
Thrombotic disorders 264
The immunocompromised patient 266

INTRODUCTION

Haematological problems are common in the ICU. Most are related to blood loss, the need for large volume blood transfusions and the development of coagulation disorders. Bone marrow failure and immunosuppression are also problems in some patients.

ANAEMIA IN THE CRITICALLY ILL

Anaemia is common in critically ill patients and often necessitates repeated blood transfusion. Anaemia may be the direct result of an underlying disease process, but more commonly is multifactorial. Common factors that may contribute to anaemia are listed in Box 10.1.

Box 10.1 Factors contributing to anaemia in the critically ill

Repeated blood sampling

Blood loss associated with repeated surgical procedures

Haemorrhage (especially GIT)

Anaemias of chronic disease (e.g. chronic renal failure)

Effects of underlying disease process

Haemolysis (e.g. drugs, antibodies, infection)

Bone marrow suppression

Relative iron/B12/folate deficiencies

Where possible, the underlying causes of anaemia should be addressed. Blood loss, including that from blood sampling, should be minimized.

INDICATIONS FOR BLOOD TRANSFUSION

There has been significant debate about the optimum haemoglobin level for critically ill patients and the level at which transfusions should be instituted (the so-called transfusion threshold). The following are key considerations:

image Oxygen carriage and delivery. The oxygen content of blood is given by Hb × SaO2 × 1.34. Raising haemoglobin is an effective way of improving oxygen content and delivery. (See Oxygen delivery and oxygen consumption, p. 68.)
image Myocardial function. Myocardial ischaemia and diastolic dysfunction may occur in the stressed heart when the haematocrit falls below 0.18. In the presence of coronary artery disease, the threshold is 0.24 or higher.
image Rheology. In vitro and probably in vivo, blood viscosity is reduced as haematocrit falls below 0.24 and rises above 0.3. This may have implications for perfusion of the microcirculation, particularly in critical illness and following vascular surgery. Recent evidence suggests that both very low and very high haematocrits are associated with impaired tissue perfusion. Haematocrit can be estimated from Hb (g / dL) × 3/100.
image Immunology. There is some evidence that transfusion induces a degree of immunosuppression, particularly massive transfusion. This is important following any major surgery, and especially so where surgery has been performed for malignant disease.
image Finite risks associated with each individual blood product transfused (see below).

Recent work suggests that restrictive transfusion strategies produce the best outcome in critically ill patients, and that the optimal level in most cases is Hb of 8–10 g / dL. Transfusion thresholds of around 7 g / dL are reasonable in most patients, with an aim to raise the haemoglobin to no more than 10 g / dL. The rate of transfusion will depend on the clinical circumstances, but for many ‘routine transfusions’ the blood can be given slowly over a number of hours to avoid rapid volume loading effects.

The blood volume of a patient will vary considerably with size and age, but is approximately 80 mL/kg, lean body mass.

BLOOD PRODUCTS IN THE UK

In the UK, blood is donated by unpaid volunteers, who undergo general health screening. Whole blood is collected into a citrate-based anticoagulant solution (chelating calcium to prevent clotting) and then further separated to yield individual blood components such as platelets, fresh frozen plasma (FFP) and cryoprecipitate.

All donations are serologically tested for HIV-1 and HIV-2, hepatitis B and C, syphilis and cytomegalovirus (CMV). CMV-free blood components are used for immunosuppressed patients and those under 1 year of age.

Recently, potential transmission of new variant Creutzfeldt–Jakob disease (vCJD) has become a concern. It is likely that in the near future screening of donors for vCJD will become available. Currently in the UK all blood products have white cells removed (leucodepletion) as a precaution against vCJD transmission (white cell count < 5 × 106). Continuing concerns regarding the potential for carriage and transmission of vCJD by the UK blood donor pool has resulted in some plasma products being sourced from outside the UK, principally from the USA.

Despite these and other measures, there remain risks associated with the use of all blood products. Although the most commonly reported major transfusion-related injury results from the wrong blood being transfused into the wrong patient, even when errors such as this are eliminated, there are finite risks associated with infection, immunological and idiosyncratic reactions. Therefore, you should not undertake transfusion of blood products lightly. In many cases, conservative management may be more appropriate. (See Risks and complications of blood transfusion, p. 252.)

The following component blood products are available.

Red cells

Whole blood was traditionally used for the replacement of blood loss. Whole blood is now rarely available. Red cell concentrates are usually used. The plasma component of whole blood is removed by the National Blood Transfusion Service (removes clotting factors and albumin) and the red cells are suspended in an additive solution prior to their issue to hospital transfusion laboratories. The two commonly used additive solutions are:

image citrate, phosphate, dextrose and adenosine (CPDA)
image sodium chloride, adenosine, glucose and mannitol (SAGM).

The blood products potentially available for red cell replacement are shown in Table 10.1.

TABLE 10.1 Red cell products

image

Fresh frozen plasma

Fresh frozen plasma (FFP) may be from a single donor or recovered from pooled donors. The volume of units provided therefore varies from 150 to 500 mL. FFP contains both labile and stable factors, including albumin, gamma globulin, fibrinogen and factor VIII. Usually 2–4 units are given when required for coagulopathy (prolonged PT). Plasma products should be ABO compatible.

Recent concerns regarding virus transmission have resulted in treated plasma products becoming available. There are currently two: methylene blue treated and solvent detergent treated. The characteristics of available plasma products are compared in Table 10.2.

TABLE 10.2 Fresh frozen plasma products

image

Recent reports of procoagulant complications with solvent detergent-treated FFP are thought to be due to relative protein S deficiency. This, together with the problems associated with pooled donors (1000 donors per batch), may limit its widespread use. However, the field is moving forward all the time. There is much current interest in production of a universal (ABO independent) pathogen inactivated plasma that would be safe for use in all blood groups, thereby eliminating the risk of ABO incompatibility and major transfusion reactions.

As with all blood products, the need for fresh frozen plasma should be critically assessed in every case. Although it is well established that fresh frozen plasma corrects coagulopathy and has a self-evident effect on the bleeding, there are no randomized controlled trials showing clinical benefit from the use of fresh frozen plasma. Nevertheless, solvent detergent and methylene blue treated plasma remain licensed in Europe and are an attractive option for patients needing massive or repeated transfusion. (See Major haemorrhage, p. 251.)

Cryoprecipitate

Cryoprecipitate is provided as one to six single donations per pack, suspended in 10–20 mL plasma. It contains fibrinogen and factor VIII. It is used to correct coagulopathy where fibrinogen levels are depleted. Six units generally raise fibrinogen levels by approximately 1 g/L.

Platelets

Platelets may be single donor, or pooled (five or six donors). Six units typically raise the platelet count by approximately 10–20 × 109/L. Platelets should ideally, but not necessarily, be ABO compatible. Platelet transfusion should only be used when absolutely necessary. Apart from all of the other risks of blood transfusion, platelets are kept at room temperature and can rarely give rise to overwhelming bacterial infection due to infusion of infected product. Although this is very rare, it is catastrophic, and is often fatal.

ADMINISTRATION OF BLOOD PRODUCTS

The complications of blood transfusion are discussed below. The biggest cause of major ABO incompatibility reactions is human error. Most commonly these result from failure to follow approved procedures. The following notes are applicable to all blood products.

Requesting blood products

image Ensure that you follow national / locally agreed procedures and guidelines.
image Ensure blood samples are carefully labelled and that the accompanying request forms are accurately completed.
image Ensure that blood products are appropriately prescribed.

Check recipient identity

Before administering any blood product, it is essential that the product is matched to the intended recipient. The product label always states the nature of the contents (e.g. whole blood, FFP), its storage temperature, expiry date and time, ABO and RhD grouping, donation or batch number and details of the patient against whom it has been cross-matched. These details must be verified against the wrist band of the patient who is the intended recipient.

image When possible, ask the patient to confirm his or her identity and that the details on the identification band are correct.
image Ensure that the patient’s name and identification number on the wristband match those on the intended blood product.
image Ensure that the ABO blood group, rhesus blood group and unit identification number are all correct.

image In some hospitals, a form accompanies blood products, identifying the units issued; this is intended as a record to be placed in the patient’s notes. These forms are not intended to be used as part of the checking procedure, and do not help to ensure that the correct unit of blood is given to the correct patient. The only acceptable checking process is to confirm that the patient details on the product label and those on the patient’s wrist band are the same.

Administration

Blood products are stored under carefully controlled conditions in the blood bank. Once removed from controlled storage they must be used within set time frames as indicated on the pack, typically as shown in Table 10.3.

TABLE 10.3 Storage and use of blood products

image

Blood should ideally be given through a large cannula (minimum 18 gauge) to avoid haemolysis. Standard giving sets with 170 μm filters are adequate. Microaggregate filters are not necessary and must never be used when giving platelets. If blood is given through the same set as other fluids, calcium-containing solutions should be avoided. Consider the use of a blood warmer.

MAJOR HAEMORRHAGE

A significant risk in managing major haemorrhage is the non-availability of appropriate blood when needed. Clear communication, sending blood samples to the laboratory in a timely fashion and prioritizing preparations (calling help, preparing blood warmers, cell savers and rapid infusion devices) all reduce the risk of disaster.

image Where possible, control the source of the bleeding, for example by direct pressure.
image Ensure adequate vascular access: at least 2 × 14-gauge peripheral lines or single large-bore cannula such as 8.5-Fr introducer sheath. This need not necessarily be inserted into a central vein; a peripheral vein may well be easier to cannulate in an emergency, and just as adequate.
image Continue background or maintenance fluids to provide free water, glucose and electrolyte requirements.
image Commence initial volume replacement with a crystalloid or simple colloid such as modified gelatin (e.g. Gelofusine or Haemaccel).
image Continue with packed cells to maintain a haematocrit of 0.26–0.32.
image After 5 units of blood, consider changing to whole blood if available and / or giving FFP to minimize the effects of dilutional coagulopathy.
image Recheck FBC, U&Es, clotting and thromboelastogram (TEG) if available.
image Ensure adequate treatment of coagulopathy. In particular, keep the ionized calcium above 0.85 mmol / L. Maintain normothermia with active warming of the patient if necessary.
image After 10 units, recheck clotting. Consider cryoprecipitate, platelets and further FFP (see Coagulopathy below).

The successful management of major haemorrhage usually depends on surgical control of the bleeding. Therefore as soon as significant haemorrhage is identified or suspected inform your consultant and the senior members of the relevant clinical team directly. Notifying the most junior member of other teams, and waiting for him / her to make a decision and refer the matter to more senior members of the team, is likely to waste valuable time. If available, consider the use of a cell saver, to reduce the need for ‘bank’ blood.

RISKS AND COMPLICATIONS OF BLOOD TRANSFUSION

Complications of blood transfusion include fluid overload, hypothermia, hypocalcaemia, acidosis and dilutional coagulopathy. ARDS and multiple organ failure are also considered to be complications of massive transfusion. Bacterial contamination of blood occurs rarely and is usually fatal (platelet transfusion carries the greatest risk because of the need to store at room temperature).

Recent figures for risk of transmission of viral infection suggest the risk of HIV transmission is around 0.14 per million donor exposures and the risk of hepatitis B and C are a little higher 1.7 and 0.8 per million respectively.

Acute transfusion reactions are relatively uncommon. They include:

image haemolytic (75% due to ABO incompatibility)
image anaphylactic (antibodies to IgA in IgA-deficient patients)
image febrile white cell reactions (antibodies to leucocyte antigens)
image transfusion-related acute lung injury (antibodies to leucocyte antigens)
image urticaria (1–2% of transfusions).

Severe haemolytic reactions due to ABO incompatibility are rare and usually result from the wrong blood being given. Febrile reactions are less common with leucocyte-depleted blood but may still occur.

Management of acute transfusion reactions

Minor febrile / urticarial transfusion reactions may settle following hydrocortisone 100 mg and chlorphenamine 10 mg and it may be possible to cautiously continue the transfusion. Major transfusion reactions require transfusions to be discontinued. Blood bags should be returned to the transfusion laboratory, together with a sample of the patient’s blood, for further evaluation. Seek the advice of the haematology department.

Transfusion-related acute lung injury (TRALI)

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