questions 2

Paroxysmal Nocturnal Hemoglobinuria (PNH)

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Topic updated on 03/02/17 6:53pm

Snapshot
  • A 25-year-old pregnant woman presents with fatigue and abdominal pain in the emergency room. She reports feeling unwell for the past few days. Every morning, she notices that her urine is tea-colored, which slowly resolves throughout the day. She has a low-grade fever. On physical exam, her skin is jaundiced, her liver edge is palpable, and she has abdominal tenderness to palpation.  Her physicians are suspicious of Budd-Chiari syndrome.
Introduction

  • Clonal stem cell defect from mutation in hematopoietic stem cell
  • Pathogenesis
    • mutation in PIGA gene
    • defect in glycosylphosphatidylinositol (GPI) anchors CD55 (decay-accelerating factor) and CD59 on RBC membrane
      • these protect RBC from complement
      • DAF inhibits C3 convertase 
    • complement-mediated destruction of RBCs
  • "PNH Thrombosis"
    • Pancytopenia
    • with Nocturnal build up of dark urine
    • Coombs negative Hemolytic anemia (complement-mediated)
    • venous Thrombosis
  • Acute hemolysis often triggered by stress, infection, surgery, and other inflammatory states
  • May cause
    • aplastic anemia
    • myelodysplasia
    • acute leukemia
Presentation
  • Symptoms/physical exam
    • episodic dark urine with first urine of the day
      • caused by hemoglobin
    • hemolytic anemia: pallor, fatigue, tachycardia, jaundice, and gross hematuria
    • thrombocytopenia: mucosal bleeding, petechiae,and  ecchymoses
    • leukemia: infections
    • thrombosis
    • renal impairment
Evaluation
  • Flow cytometry – most accurate test
    • CD55/59-negative RBCs
  • Labs
    • anemia
    • thrombocytopenia
    • leukopenia
Differential Diagnosis
  • Aplastic anemia
  • Myelodysplasia
Treatment
  • Eculizumab
    • inactivates C5 in complement pathway
    • decreases red cell destruction
    • complement inhibitor
    • must vaccinate all against Neisseria due to increased risk
  • Allogeneic bone marrow transplant
  • Supportive therapy
    • folic acid
    • transfusions as needed
Prognosis, Prevention, and Complications
  • Prognosis
    • improved with use of eculizumab
  • Complications
    • renal insufficiency
    • thromboembolism
    • 5% develop myelodysplasia
    • 2.5% develop acute leukemias


  RATE CONTENT
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AVERAGE 4.0 of 4 RATINGS

Qbank (1 Questions)

TAG
(M1.HE.75) A 42-year-old male presents to his primary care physician with complaints of fatigue and occasionally darkened urine over the past 3 months. Upon further questioning, the patient reveals that he has regularly had dark, 'cola-colored' urine when he has urinated at night or early in the morning. However, when he urinates during the day, it appears a much lighter yellow color. Laboratory work-up is initiated and is significant for a hemoglobin of 10.1 g/dL, elevated LDH, platelet count of 101,000/uL, and leukopenia. Urinalysis, taken from an early morning void, reveals brown, tea-colored urine with hemoglobinuria and elevated levels of hemosiderin. Which of the following is responsible for this patient's presentation? Topic Review Topic

1. Deficiency of C1 esterase-inhibitor
2. Autosomal dominant deficiency of spectrin protein in the RBC membrane
3. Presence of a temperature-dependent IgG autoantibody
4. Deficiency of CD-55 and CD-59 cell membrane proteins
5. Autosomal recessive deficiency of platelet Glycoprotein IIb/IIIa receptor

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