Abstract:

This lesson provides an overview of paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired blood condition. It details the pathophysiology, focusing on the PIGA gene mutation and subsequent deficiency in GPI-anchored proteins like CD55 and CD59, leading to complement-mediated hemolysis. The video discusses the epidemiology, clinical features (hemolytic anemia, bone marrow suppression, thrombosis, hemoglobinuria), diagnostic methods (flow cytometry), and treatment options (eculizumab, anticoagulation, and in some cases, hematopoietic stem cell transplantation).

Summary of Proximal Nocturnal Hemoglobinuria

• 0:06 Definition: PNH is an acquired blood condition affecting hematopoietic stem cells, not inherited, causing deficiency of GPI anchor proteins like CD55 and CD59 due to an acquired PIGA gene mutation.
• 0:30 Pathophysiology:
  • PIGA deficiency leads to red blood cells lacking GPI anchor protein CD55 and CD59.
  • Without this protein, red blood cells cannot repel complement, leading to abnormal complement activation and intravascular hemolysis.
• 0:35 Epidemiology:
  • Rare condition affecting 1-10 per million.
  • Onset in 3rd-4th decade of life.
  • Associated with aplastic anemia.
• 0:39 Proximal Nocturnal Hemoglobinuria: Episodes irregularly occur at night, causing hypoxemia and more destruction (hemolysis) of red blood cells. Hemoglobin in urine causes red/pink coloration.
• 0:52 Hemolytic Anemia: The complement-mediated hemolysis results in normochromic normocytic anemia (normal cell size and hemoglobin content) with increased reticulocyte count, LDH, and bilirubin, and decreased free haptoglobin. Scleral icterus (jaundice) may be visible.
• 0:59 Bone Marrow Suppression: Can lead to pancytopenia (decreased levels of all blood cell types).
• 0:59 Thrombosis Risk: Increased risk of arterial and venous thrombi (clots), particularly in abdominal and cerebral veins, due to complement activation.
• 1:06 Clinical Features: Red or pink urine in the morning that clears as the day goes on, fatigue, dyspnea, abdominal and chest pain, headaches. Depletion of vascular nitric oxide can lead to dysphagia, erectile dysfunction, renal insufficiency, and pulmonary hypertension. Risk of transformation to other blood conditions like aplastic anemia or leukemia.
• 2:52 Diagnosis: Flow cytometry is key, showing CD55 and CD59 negative cells. Other lab findings include hemolytic anemia markers.
• 2:54 Treatment:
  • Eculizumab (key treatment)
  • Anticoagulation (to prevent thrombosis).
  • Hematopoietic stem cell transplantation (in some cases).