Red cells and marrow

Haemolysis

Approach

Confirm anaemia with reticulocytosis and biochemical evidence: raised bilirubin/LDH, low haptoglobin and blood-film changes. Determine intravascular versus extravascular and inherited versus acquired causes.

  • Haemolysis = premature red cell destruction (lifespan under 120 days). It is compensated if the marrow keeps up, uncompensated if anaemia develops (1).
  • Extrinsic (usually acquired): immune (autoimmune, drug-induced, transfusion reaction), infection (malaria, Babesia, Clostridium toxin), mechanical (microangiopathic, prosthetic valve, march haemoglobinuria), hypersplenism, toxins, burns. Intrinsic (usually inherited): membrane (hereditary spherocytosis), enzyme (G6PD deficiency), haemoglobin (sickle cell, thalassaemia); PNH is the acquired membrane defect (1).
Assessment

Jaundice, dark urine, pain, infection, drugs, transfusion, prosthetic valve, family/ethnic history and autoimmune disease. Examine for splenomegaly and thrombosis.

  • Drugs reported to cause immune haemolysis include quinine/quinidine, beta-lactams, methyldopa, co-trimoxazole and fludarabine; oxidant haemolysis with dapsone (1).
  • Intravascular haemolysis can cause haemoglobinuria (red-brown urine), back/abdominal pain and shock (1).
Emergencies

Transfusion reaction, severe symptomatic anaemia, haemoglobinuria with AKI, sickle crisis, TTP/HUS or rapidly falling haemoglobin requires urgent senior/haematology review.

  • Fragments on the film with low platelets suggest microangiopathy (TTP, HUS, DIC): TTP is fatal if untreated but survival is over 95% with prompt plasma exchange plus steroids and rituximab (2). Do not transfuse platelets in TTP unless life-threatening bleeding (3).
  • Warm autoimmune haemolysis with reticulocytopenia can be fatal (4).
Investigations

FBC/film, reticulocytes, bilirubin, LDH, haptoglobin, DAT, UEC and urinalysis; then targeted G6PD, haemoglobin studies or other tests.

  • Peripheral smear and reticulocyte count are the most important tests. Then indirect bilirubin, LDH and haptoglobin; a direct antiglobulin (Coombs) test or haemoglobinopathy screen (e.g. HPLC) to find the cause (1).
  • DAT positive = immune: warm antibody (IgG, usually extravascular) vs cold agglutinin disease (reacts below 37 degrees C) (4).
  • G6PD levels can be falsely normal during or just after a haemolytic episode.
Management

Treat cause, stop culprit drugs, support with transfusion when indicated and use folate in chronic haemolysis. Immune haemolysis and microangiopathy require specialist-directed therapy.

  • Warm AIHA (idiopathic): glucocorticoids first-line, often with rituximab; refractory cases may need IVIG, azathioprine/mycophenolate/cyclophosphamide or splenectomy (4).
  • Cold agglutinin disease: avoid cold, warm blood before transfusion, treat the underlying disorder; sometimes rituximab or complement inhibitors (4).
  • Drug-induced: withdraw the drug (4). Give folate for ongoing long-term haemolysis (4).
  • TTP: plasma exchange with glucocorticoids and rituximab; caplacizumab can speed platelet recovery (2).
References
  1. Merck Manual Professional: Overview of hemolytic anemia
  2. Merck Manual Professional: Thrombotic thrombocytopenic purpura
  3. National Blood Authority: PBM Guidelines Module 3 (Medical), Quick Reference Guide
  4. Merck Manual Professional: Autoimmune hemolytic anemia

Last updated from Sen’s notes on 9 October 2026.