Anaemia is common in palliative care patients. In this context, it is often caused by chronic inflammation (chronic disease), although iron deficiency from blood loss and bone marrow failure from malignant infiltration are also quite commom problems. It is often hard to differentiate symptoms of anaemia from symptoms of advanced cancer and this makes decisions regarding treating anaemia more difficult. Given that treatment of profound anaemia (e.g. with a blood transfusion) can bring about a significant improvement in symptoms and quality of life, it is always worth considering treatment in such patients if they are not imminently dying.
Pathogenesis and Epidemiology
Anaemia is extremely common in palliative care patients, especially in cancer patients. The aetiology is usually complex and multifactorial and often includes the following:
- Chronic inflammatory state (chronic disease)
- Bone marrow infiltration with cancer
- Poor nutrition
- Blood loss (e.g. due to the cancer or due to medications such as NSAIDs and anti-coagulants)
- Medications (such as cytotoxics)
A chronic inflammatory state is often a key reason for anaemia. The body reacts to cancer through the release of cytokines such as IL-1, IL-6 and TNF-alpha. These inhibit erythropoietin synthesis and uptake of iron for erythropoiesis.
In some cases, the cause of anaemia is self-evident, however if there is any uncertainty it is worth investigating further to ensure the most appropriate treatment is given.
In a patient with complete cessation of red cell production, the haemoglobin usually falls by about 10 per week. Falls of greater than this suggest there must also be destruction of blood or loss of blood.
The World Health Organization (WHO) grades anaemia in cancer as follows:
|Mild (Grade 1)||Hb > 100|
|Moderate (Grade 2)||Hb 80-100|
|Severe (Grade 3)||Hb 65-80|
|Life-threatening (Grade 4)||Hb < 65|
Full blood count
A full blood count (FBC) may also be known as a complete blood count (CBC) or complete blood exam (CBE) and includes
- Red blood cell indices including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC)
- Platelet count
- White cell count and differential
The MCV is a particularly useful indicator of aetiology. A normal range is approximately between 80-96. It is usually low in iron deficiency and normal in chronic inflammatory states. A more extensive list is found below.
|Low MCV (microcytic)|
|Chronic disease (uncommon; usually normocytic)|
|Other causes - thalassaemia, sideroblastic anaemia|
|Normal MCV (normocytic)|
|Chronic disease such as cancer|
|Chronic renal failure|
|Bone marrow suppression from malignant infiltration a medication side effect (e.g. cytotoxics) or aplastic anaemia|
|Acute blood loss|
|Other causes - haemolytic anaemia|
|High MCV (macocytic)|
|Vitamin B12 deficiency|
|Other causes - haemolytic anaemia with a reticulocytosis|
White cell count and differential
A low white cell count (leucopaenia) (or pancytopaenia) in anaemic patients may be caused by
- Bone marrow suppression (e.g. malignant infiltration or cytotoxics)
- Vitamin B12 deficiency
- Folate defiency
Circulating precursor white and red cells are common in bone marrow infiltrated with cancer (leucoerythroblastic picture).
A high white cell count (leuocytosis) might occur in:
- Unconnected to the anaemia - e.g. an acute infection or steroid use
- Malignancy with a leukaemoid-typed response
- Acute myeloid leukaemia
In patients who are anaemic, a pancytopaenia (or a thrombocytopaenia) may indicate:
- Bone marrow suppression
- B12 deficiency
- Folate deficiency
Bleeding secondary to low platelets may be involved in the aetiology of the anaemia.
A high platelet counts may indicate
- A systemic inflammatory state (e.g. cancer)
- Iron deficiency
- A myeloproliferative disorder
Some centres will automatically perform a manual blood smear when there are abnormalities, whereas others will not, and thus this may need to be specificially requested.
Neutrophil hypersegmentation (i.e. neutrophils with more than 5 lobes) occurs in many patients with megaloblastic anaemias (B12 or folate deficiency).
Features of iron deficiency
Typical features of iron deficiency include anisocytosis (different size red cells) and poikilocytosis (different shaped red cells). Often in severe deficiency there are pencil-shaped red cells.
Nucleated red blood cells and a leucoerythroblastic picture
Nucleated red cells are not normally present in the blood. Their presence may indicate bone marrow infiltration with malignant cells. Nucleated red cells also are found in various other conditions such as thalassaemia, myelofibrosis and severe sepsis. In hospitalized patients (not specifically palliative care patients) the presence of nucleated red cells is a bad prognostic marker.
Likewise precursor white cells such as myelocytes and promyelocytes are not normally found in blood and their presence may indicate bone marrow infiltration with cancer. The presence of precursor white cells and erythroblasts is known as a leucoerythroblastic blood picture.
Reticulocytes are early or precursor red cells circulating. Both the absolute reticulocyte count and the relative (percentage) give evidence as to the cause of anaemia.
|High reticulocyte count = increased red cell production|
|Low reticulocyte count = deficient red cell production|
|Anaemia of chronic disease|
|Bone marrow suppression due to malignant infiltration or medications (e.g. cytotoxics)|
|Vitamin B12 deficiency|
Iron stues can be very useful in distinguishing between anaemia due to iron deficiency and chronic disease.
|Iron deficiency||Chronic disease|
|Transferrin (iron-binding capacity)||Increased||Decreased|
LDH and haptoglobin
If the film shows fragmented red cells (schistocytes) or spherocytes if there is a reticulcytosis, consider investigating for haemolysis with
A raised LDH and a reduced haptoglobin is almost diagnostic of haemolysis.
In advanced cancer, disseminated intravascular coagulation with associated haemolysis sometimes occurs.
An alternative mechanism of haemoyltic anaemia that rarely occurs in cancer (usually haematological malignancies) is autoimmune haemolytic anaemia. The blood film will typically show spherocytes.
In patients with a suspected autoimmune haemolytic anaemia (e.g. normocytic anaemia, reticulocytes, spherocytes, raised LDH) consider investigating with a Coombs' test. This is the test for antibodies (IgG) or complement (C3d) on the surface of red cells that are associated with autoimmune haemolytic anaemia.
Vitamin B12 and folate
Fasting levels of B12 and red cell folate levels are decreased in vitamin B12 and folate deficiency respectively.
Many palliative care patients have anaemia and deciding upon when to intervene or not may be difficult, especially since intervention usually means blood transfusions. This is especially the case when the anaemia is recurrent. Different physicians and units have different philosophical approaches. A reasonable approach is:
- Fatigue (or dyspnoea, diziness or chest pain) in the context of a haemoglobin of less than 70 is very likely to respond to a transfusion
- When the haemoglobin is from 70-100 it is less clear that anaemia is the main contributor, but it might be.
- If the anaemia is thought to be symptomatic and there is no other better treatment, then a transfusion is appropriate unless a patient is imminently dying.
- If the patient's symptoms resolve with a transfusion, then repeat transfusions are also reasonable
If transfusions are being required on more than a weekly basis (e.g. on an almost daily basis) then further transfusions are probably not appropriate.
Prior to transfusing, other options for treatment of anaemia should be carefully considered.
If renal failure is thought to be a significant contributing factor then:
- Eryhtropoetin or darbepoetin
- Supplemental iron
If blood loss and iron deficiency is thought to be a significant contributing factor then:
- Consider if further investigations would be helpful or needed (e.g. an endoscopy)
- Aim to stop any blood loss (e.g. stop NSAIDs, add a proton pump inhibitor, irradiate the bleeding source)
Consider supplemental iron
If vitamin B12 or folate deficiency is present:
- Consider if further investigations would be helpful
- Replacement vitamin B12 and/or folate