Synopsis
Use the absolute reticulocyte response and a coherent haemolysis profile to distinguish red-cell underproduction, loss and destruction, then select immune, membrane, enzyme or mechanical testing.
- Use the absolute reticulocyte count, not the percentage alone. A percentage can appear high simply because the circulating red-cell denominator is low.
- Ask whether the response is appropriate for the depth and duration of anaemia. Reticulocytes take time to rise, and severe iron, B12 or folate deficiency can limit a response despite haemolysis.
- A typical haemolysis pattern combines raised indirect bilirubin and LDH, low haptoglobin, reticulocytosis and film change, but inflammation, liver disease, ineffective erythropoiesis and recent transfusion can alter individual markers.
- Intravascular haemolysis releases free haemoglobin into plasma and urine and may lower haptoglobin markedly; extravascular haemolysis occurs mainly in spleen and liver and often produces spherocytes and splenomegaly.
- The direct antiglobulin test identifies immunoglobulin or complement on red cells. It supports immune coating but must be interpreted after recent transfusion, medicines and laboratory specificity.
- Schistocytes with thrombocytopenia suggest a thrombotic microangiopathy or DIC pathway; preserved coagulation supports TTP but does not replace ADAMTS13 and urgent specialist assessment.
- A low reticulocyte response directs attention to marrow suppression, renal erythropoietin deficiency, nutrient lack, infection, inflammation or infiltration rather than assuming occult bleeding.
- Recent red-cell transfusion mixes donor and patient cells, modifies indices and haemolysis tests, and can create alloimmune reactions; record unit timing before interpreting the panel.
Key red flags
Back or abdominal pain, dark urine, haemoglobinaemia, marked haptoglobin depletion and acute kidney or potassium disturbance suggest red-cell destruction within the circulation.
Anaemia, thrombocytopenia, schistocytes, high LDH and organ ischaemia raises TTP, HUS, DIC or severe hypertension and requires immediate mechanism-directed assessment.
Investigation priorities
Measure effective marrow erythroid output in relation to the anaemia.
Management branches
Haemoglobin is falling or jaundice, dark urine, splenomegaly or a regenerative count suggests red-cell destruction.
- First-line testing is FBC, absolute reticulocytes, film, bilirubin fractions, LDH, haptoglobin, DAT, renal profile and urinalysis, alongside observations and a bleeding assessment.
- Check prior counts, transfusion and medicine timing, liver disease, infection, pregnancy and prosthetic valves; an alternative diagnosis is blood loss when reticulocytosis occurs without a convincing destructive profile.
- Escalate shock, symptomatic rapid anaemia, hyperkalaemia, renal injury, transfusion reaction or thrombocytopenic fragmentation for immediate specialist and transfusion support.
The haemolysis profile is supported and the patient is physiologically stable enough for cause-directed testing.
- Use DAT pattern, film and clinical context as the preferred branch: IgG-associated spherocytosis suggests warm AIHA, complement and agglutination suggests cold disease, and fragments suggest mechanical injury.
- When DAT is negative, assess oxidant triggers, family and ethnic history, haemoglobinopathy, membrane disease, parasites, valves and microangiopathy; specialist enhanced DAT testing is an alternative when immune disease remains likely.