EpistemisParoxysmal hemoglobinuria
Specialty: Hematology.
Why it occurs
- Paroxysmal nocturnal hemoglobinuria (acquired clonal deficiency of the PIG-A gene that prevents the synthesis of the glycosylphosphatidylinositol anchor, leaving blood cells vulnerable to lysis mediated by the complement membrane attack complex during the physiological acidosis of sleep)
- Paroxysmal refrigerant hemoglobinuria (autoimmune hemolytic anemia due to cold antibodies of the IgG type or biphasic Donath-Landsteiner antibody, which binds to red blood cells at low temperatures and fixes the complement, lysing them when the blood is rewarmed)
- Severe microangiopathic hemolytic anemia (hemolytic uremic syndrome or thrombotic thrombocytopenic purpura with mechanical destruction of red blood cells)
- Clostridium perfringens infection or Plasmodium falciparum malaria (blackwater fever, with direct massive destruction of erythrocytes)
- Hemoglobinuria of walking or extreme exertion (mechanical destruction of erythrocytes in the capillaries of the soles of the feet due to repetitive trauma against hard surfaces).
Initial workup
High sensitivity flow cytometry in peripheral blood to quantify the absence or decrease of GPI-bound proteins (CD55 and CD59) in erythrocytes, monocytes and neutrophils (absolute reference method); biochemical analysis of intravascular hemolysis (extreme elevation of lactate dehydrogenase - LDH, drastic decrease or abolition of serum haptoglobin levels, elevation of indirect bilirubin); microscopic examination of fresh urine to differentiate hematuria (presence of intact erythrocytes in the sediment) from hemoglobinuria (clean sediment with dipstick highly positive for blood); determination of hemosiderin in urine (hemosiderinuria, marker of chronic intravascular hemolysis); positive Donath-Landsteiner test (to diagnose paroxysmal refrigerant hemoglobinuria).
red flags
Presence of diffuse and oppressive abdominal pain associated with dysphagia, erectile dysfunction in men and restrictive dyspnea of acute onset (symptoms of smooth muscle spasm mediated by the depletion of free nitric oxide due to the massive release of circulating free hemoglobin); progressive oliguria or anuria accompanied by marked elevation of serum creatinine and potassium (acute renal failure due to hemoglobin cast nephropathy and acute tubular necrosis); intense bilateral lumbar pain associated with fever, arterial hypotension and chills (massive intravascular hemolytic crisis with risk of distributive shock and multiple organ failure).
Standard management
- Eculizumab — humanized recombinant IgG monoclonal antibody that specifically binds to the complement protein C5, blocking its cleavage to C5a and C5b and preventing the formation of the membrane attack complex; almost immediately stops intravascular hemolysis and its complications in patients with PNH
- Ravulizumab — second-generation monoclonal antibody directed at C5 with a long half-life that allows its administration intravenously every 8 weeks
- Pegcetacoplan — complement inhibitor directed at C3, administered subcutaneously, indicated for patients who maintain residual extravascular hemolysis under treatment with C5 inhibitors
- Prednisone (oral glucocorticoid useful in acute phases of paroxysmal refrigerated hemoglobinuria to mitigate the autoimmune response mediated by antibodies).
Educational guidance for study. It is NOT a prescription recommendation. The actual choice depends on the cause, the patient, and current guidelines.
- Area
- Hematology
- Listed causes
- 5
- Treatment options
- 4