Anaemia of chronic disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

mild to moderate anaemia (haemoglobin [Hb] 80 to 110 g/L [8 to 11 g/dL])

1st line – treatment of underlying disease and observation

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1st line –

treatment of underlying disease and observation

The level of anaemia correlates with the activity of the underlying disease, and treatment of the underlying disorder usually improves or abolishes the anaemia.

Patients with mild to moderate anaemia of chronic disease and an underlying condition that cannot be treated, or is not responsive to therapy, despite correction of iron deficiency, can usually be managed with simple observation.

underlying disorder not responsive to treatment and anaemia is symptomatic, or imposes additional risk

Consider – red blood cell transfusion

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Consider –

red blood cell transfusion

Additional treatment recommended for SOME patients in selected patient group

Transfusion is considered when the patient has symptomatic anaemia that significantly impairs their quality of life, or with comorbidities in which a mild to moderate anaemia imposes additional risk (e.g., heart failure, significant pulmonary disease, cerebral vascular disease).

The benefit of red blood cells (RBC) transfusion must always be weighed against its potentially significant risks, which include volume overload, transfusion reaction, acute haemolysis with shock, delayed haemolytic transfusion reaction, transfusion-associated acute lung injury, alloimmunisation, and iron overload.[62]

Guidelines for the treatment of anaemia in cancer and chronic kidney disease do not recommend routine, ongoing RBC transfusion principally because of the risks of iron overload.[62] However, it is reasonable to transfuse in cases of symptomatic anaemia.[63]

Consider – erythropoiesis-stimulating agents (ESAs)

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Consider –

erythropoiesis-stimulating agents (ESAs)

Additional treatment recommended for SOME patients in selected patient group

ESAs are considered when the patient has symptomatic anaemia that significantly impairs their quality of life, or with comorbidities in which a mild to moderate anaemia imposes additional risk (e.g., heart failure, significant pulmonary disease, cerebral vascular disease).

The decision to prescribe an ESA is made in consultation with a consultant and requires evaluation of the reported efficacy and adverse effects.

Red blood cell transfusion may be required until benefits of ESA therapy manifest. Absence of a response to ESA treatment should prompt a search for an additional cause of anaemia.

ESAs may be considered for patients with chronic kidney disease (CKD) not on dialysis who have haemoglobin (Hb) levels <10 g/dL. For patients with CKD on dialysis, ESA therapy may be used when Hb levels are between 9 and 10 g/dL, to avoid levels falling below 9 g/dL. Decisions about starting treatment and dosing should be individualised.[62]

Guidelines recommend considering ESAs for patients with chemotherapy-associated anaemia who have Hb levels <10 g/dL.[63][68][85] The Food and Drug Administration (FDA) stipulates that ESAs should not be used in patients receiving treatment with curative intent because of the potential risks of increased tumour progression and reduced survival; this is reflected in the US guidance.[63][68] If there are uncertainties about curative intent, RBC transfusion should be considered before ESA therapy.[63]

In patients with chemotherapy-induced anaemia, ESA therapy is effective in increasing Hb concentrations, improving haematological responses, reducing the need for blood transfusions, and improving health-related quality of life.[67][86] [ ] However, uncertainty remains about the risks.

For patients with CKD and cancer, use of ESAs may only be considered with caution and careful evaluation of the risks and benefits.[62] Patients receiving palliative chemotherapy may benefit from carefully dosed ESAs in preference to transfusion for the treatment of severe anaemia.[68] ESAs are not typically recommended for patients with CKD receiving curative cancer treatment, or with a history of cancer or stroke.[62]

There have been reports that ESAs reduce overall survival and, in some cancer patients, shorten time to tumour progression. Increased mortality and worsened outcomes have been reported with higher target Hb levels (>11 to 12 g/dL).[69] While some subsequent studies found no association between ESA use and increased mortality, uncertainty remains.[65][70][71][72][73]

ESA therapy is not recommended for patients with cancer who are not receiving chemotherapy or for those receiving non-myelosuppressive therapy.[63][68] However, selected patients with myelodysplastic syndrome may be an exception. See Myelodysplastic syndrome.

ESAs are associated with cardiovascular adverse effects, including increased thrombotic events and hypertension. Risk factors for venous thromboembolism should be evaluated and blood pressure controlled before treatment with an ESA. Pure red cell aplasia due to development of neutralising antibodies to erythropoietin has been reported rarely, but may be increased with some recombinant formulations.[68]

ESAs should be used at the lowest dose sufficient to reduce the need for RBC transfusions. Treatment should be discontinued in patients with chemotherapy-induced anaemia if there is no response to an ESA after 6 to 8 weeks. There is no benefit in switching to another ESA if the initial ESA has not been effective.[63]

Similar warnings have also been incorporated into European prescribing information for epoetin alfa and darbepoetin alfa. The European Medicines Agency recommends only treating patients with symptomatic anaemia and to not exceed an Hb target value of 120 g/L (12 g/dL).[85][89]

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly; if Hb has not increased by at least 1 g/dL after 4 weeks, dose may be increased to 60,000 units once per week if iron status satisfactory

darbepoetin alfa: 200 micrograms subcutaneously once every 2 weeks; may increase dose to 300 micrograms once every 2 weeks

Consider – supplemental iron

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Consider –

supplemental iron

Additional treatment recommended for SOME patients in selected patient group

Intravenous iron is preferred to oral iron because it is associated with a more rapid achievement of target Hb and decreased ESA requirement compared with oral iron.[53][54][55][56] Currently available intravenous iron formulations appear to be well-tolerated, with low risk of infusion reaction.[57][58][59][60]

One Cochrane review found evidence to suggest that intravenous ferric carboxymaltose may be more effective than intravenous iron sucrose for the treatment of iron deficiency in people with inflammatory bowel disease.[61]

For ESA-treated patients with cancer, the US guidelines recommend: consideration of intravenous iron for chemotherapy-associated anaemia, given regardless of the iron status, with baseline and periodic iron studies; and consideration of intravenous iron in patients with functional iron deficiency (ferritin 30 to 500 ng/mL and transferrin saturation <50%).[63][68]

A trial of intravenous iron is recommended for patients with chronic kidney disease who are receiving ESA therapy.[62]

Iron supplementation, alongside ESA treatment, may improve haemoglobin response and reduce RBC transfusion requirements. Baseline and periodical iron studies are recommended.[63]

Supplemental iron is not recommended for patients with anaemia of chronic disease who have normal or high ferritin levels (except in certain cases of functional iron deficiency).[17] Iron supplementation is relatively contraindicated in the setting of active infection.[58][62][85]

Test doses may need to be given before starting therapy.

Primary options

sodium ferric gluconate complex: consult specialist for guidance on dose

iron sucrose: consult specialist for guidance on dose

iron dextran: consult specialist for guidance on dose

severe (Hb <80 g/L [<8 g/dL]) or life-threatening (Hb <65 g/L [<6.5 g/dL]) anaemia

1st line – treatment of underlying disease and red blood cell (RBC) transfusion

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1st line –

treatment of underlying disease and red blood cell (RBC) transfusion

Commencing treatment for the underlying condition is important as the level of anaemia correlates with disease activity, and its treatment usually improves or abolishes the anaemia.

RBC transfusion may be effective in severe or life-threatening anaemia, depending on comorbid conditions and rate of anaemia development.[17]

Likely benefits of transfusion need to be balanced against possible risks (e.g., volume overload, transfusion reaction, acute haemolysis with shock, delayed haemolytic transfusion reaction, transfusion-associated acute lung injury, alloimmunisation, iron overload).[62]

The use of a restrictive haemoglobin concentration of 7 to 8 g/dL decreases the proportion of patients exposed to RBC transfusion.[92] Transfusion guidelines suggest using a restrictive transfusion strategy, initiating transfusion at Hb levels <7 g/dL.[93]

Decisions about starting treatment should be individualised; some patient sub-groups may benefit from RBC transfusion to maintain higher haemoglobin concentrations.[68]

2nd line – treatment of underlying disease and erythropoiesis-stimulating agents (ESAs)

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2nd line –

treatment of underlying disease and erythropoiesis-stimulating agents (ESAs)

Important pre-emptive therapy in patients who may require transfusions urgently but for whom they may be unacceptable, unavailable, or carry excessive risk (e.g., Jehovah's Witnesses, those with rare blood types, or those with multiple allo-antibodies).

Concurrent supplemental intravenous iron should also be considered.

The decision to prescribe an ESA is made in consultation with a consultant and requires evaluation of the reported efficacy and adverse effects.

Red blood cell transfusion may be required until benefits of ESA therapy manifest. Absence of a response to ESA treatment should prompt a search for an additional cause of anaemia.

ESAs may be considered for patients with chronic kidney disease not on dialysis who have Hb levels <10 g/dL. For patients with CKD on dialysis, ESA therapy may be used when Hb levels are between 9 and 10 g/dL, to avoid levels falling below 9 g/dL. Decisions about starting treatment and dosing should be individualised.[62]

Guidelines recommend considering ESAs for patients with chemotherapy-associated anaemia who have Hb levels <10 g/dL.[63][68][85] The FDA stipulates that ESAs should not be used in patients receiving treatment with curative intent because of the potential risks of increased tumour progression and reduced survival; this is reflected in the US guidance.[63][68] If there are uncertainties about curative intent, RBC transfusion should be considered before ESA therapy.[63]

ESA therapy is not recommended for patients with cancer who are not receiving chomotherapy or for those receiving non-myelosuppressive therapy.[63][68] However, selected patients with myelodysplastic syndrome may be an exception. See Myelodysplastic syndrome.

Primary options

epoetin alfa: 40,000 units subcutaneously once weekly; if Hb has not increased by at least 1 g/dL after 4 weeks, dose may be increased to 60,000 units once per week if iron status satisfactory

darbepoetin alfa: 200 micrograms subcutaneously once every 2 weeks; may increased dose to 300 micrograms once every 2 weeks

Consider – supplemental iron

Back

Consider –

supplemental iron

Additional treatment recommended for SOME patients in selected patient group

A trial of intravenous iron is recommended for patients with CKD who are receiving ESA therapy.[62]

Iron supplementation, alongside ESA treatment, may improve haemoglobin response and reduce RBC transfusion requirements. Baseline and periodical iron studies are recommended.[63]

Supplemental iron is not recommended for patients with ACD who have normal or high ferritin levels (except in certain cases of functional iron deficiency).[17] Iron supplementation is relatively contraindicated in the setting of active infection.[58][62][85]

Test doses may need to be given before starting therapy.

Primary options

sodium ferric gluconate complex: consult specialist for guidance on dose

iron sucrose: consult specialist for guidance on dose

iron dextran: consult specialist for guidance on dose

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Anaemia of chronic disease

Treatment algorithm

mild to moderate anaemia (haemoglobin [Hb] 80 to 110 g/L [8 to 11 g/dL])

treatment of underlying disease and observation

red blood cell transfusion

erythropoiesis-stimulating agents (ESAs)

Primary options

supplemental iron

Primary options

severe (Hb <80 g/L [<8 g/dL]) or life-threatening (Hb <65 g/L [<6.5 g/dL]) anaemia

treatment of underlying disease and red blood cell (RBC) transfusion

treatment of underlying disease and erythropoiesis-stimulating agents (ESAs)

Primary options

supplemental iron

Primary options