Makindo Medical Notes

Related Subjects: |Sideroblastic Anaemia |Splenectomy |Paroxysmal Nocturnal Haemoglobinuria |Pernicious anaemia |Normocytic anaemiaa |Pyruvate Kinase deficiency |Blood Products - Platelets |Von Willebrand Disease

🩸 Paroxysmal Nocturnal Haemoglobinuria (PNH) is a rare, acquired, and potentially life-threatening blood disorder. It is characterised by:
– Intravascular haemolysis (red cell destruction)
– Thrombosis (venous clots in unusual sites)
– Bone marrow failure (cytopenias, aplasia)

🔎 About

• Caused by loss of the GPI-anchor that attaches protective proteins to blood cells.
• Absence of CD55 & CD59 → unchecked complement activation → red cell lysis.
• Classified as a bone marrow failure syndrome.

🧬 Aetiology

• Somatic mutation in a haematopoietic stem cell (not inherited).
• All lineages affected: RBCs, WBCs, and platelets.
• May coexist with aplastic anaemia or myelodysplasia.
• Symptoms often worsen with infection, surgery, or physiological stress.
• Diagnosis: flow cytometry showing ↓ or absent CD55/CD59.

📂 Types of PNH

• Classical PNH: haemolysis + thrombosis.
• PNH with marrow disorders: seen with aplastic anaemia / MDS.
• Subclinical PNH: small clone, no overt haemolysis or thrombosis.

🩺 Clinical Features

• Chronic haemolytic anaemia (fatigue, pallor, jaundice).
• Thrombosis in unusual sites – e.g. Budd–Chiari syndrome, cerebral venous sinus thrombosis, splenic/abdominal vein clots.
• Dark “cola-coloured” urine in the morning 🌙 (nocturnal haemoglobinuria).
• Bone marrow aplasia → pancytopenia.

🧪 Investigations

• FBC: Anaemia, ± leukopenia / thrombocytopenia.
• Haemolysis markers: ↑ LDH, ↓ haptoglobin, haemoglobinuria, haemosiderinuria.
• Flow cytometry: diagnostic – absence of CD55/CD59 on RBCs.
• Historical (rarely used): Ham test, sucrose lysis test.

💊 Management

• Eculizumab: anti-C5 monoclonal antibody; reduces haemolysis & transfusion needs.
• Supportive: folate & iron supplementation.
• Steroids: may reduce haemolysis, but toxicity limits long-term use.
• Stem Cell Transplant: only curative option (reserved for severe cases).
• Anticoagulation: prophylaxis/treatment for thrombosis (warfarin or DOAC if specialist-approved).

💡 Key Exam Pearls: – Think PNH in a young patient with unexplained haemolysis + thrombosis in hepatic/abdominal veins. – Flow cytometry for CD55/CD59 is diagnostic. – Eculizumab dramatically improves prognosis, but bone marrow failure may still require transplant.

📚 References

• Paroxysmal Nocturnal Haemoglobinuria – Blood Journal

Cases — Paroxysmal Nocturnal Haemoglobinuria (PNH)

• Case 1 — Haemoglobinuria 🌑: A 32-year-old man reports passing dark, cola-coloured urine in the mornings. He also complains of fatigue and dyspnoea. Bloods: Hb 8.5 g/dL, reticulocytosis, raised LDH, low haptoglobin. Flow cytometry: absence of CD55/CD59 on RBCs. Diagnosis: PNH with intravascular haemolysis. Managed with eculizumab and folate supplementation.
• Case 2 — Thrombosis 🩸: A 40-year-old woman presents with abdominal pain and ascites. Imaging: hepatic vein thrombosis (Budd–Chiari syndrome). Bloods: anaemia with evidence of haemolysis. Flow cytometry confirms PNH. Diagnosis: PNH presenting with venous thrombosis. Managed with anticoagulation and complement inhibitor therapy (eculizumab/ravulizumab).
• Case 3 — Bone marrow failure 🧬: A 27-year-old man presents with recurrent infections and mucosal bleeding. FBC: pancytopenia. Bone marrow: hypocellularity. Flow cytometry: CD55/CD59 deficient clone. Diagnosis: PNH associated with aplastic anaemia. Managed with immunosuppression, complement inhibitors, and consideration of allogeneic stem cell transplant.

Teaching Point 🩺: PNH is an acquired stem cell disorder caused by a PIGA gene mutation → deficiency of CD55/CD59 → RBCs susceptible to complement-mediated lysis. Classic triad: intravascular haemolysis, cytopenias, and thrombosis. Treatment includes eculizumab/ravulizumab, anticoagulation, and sometimes bone marrow transplantation.