2025 – PAGE 284 – HEMATOLOGY & ONCOLOGY

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

Look for the keywords “dark colored urine in the mornings” to possibly indicate a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). This is a complement-mediated hemolysis, which means there are NO antibodies involved. Thus, it is a COOMBS NEGATIVE autohemolytic anemia. Diagnose by using either flow cytometry analysis of CD59 expression on the cells, a DF assay, or a Ham’s test (which checks for fragility with exposure to mild ascetic acid).

MNEMONIC: pnH = pnHam. Alternatively, consider having a Paroxysmal Nocturnal HAM EATING CONTEST – a ham-eating contest that happens every once in a while (paroxysmal) at night from 5 – 9 PM (CD59).

SICKLE CELL ANEMIA

• PRESENTATION: The signs or symptoms of sickle cell anemia could include the following:
  • APLASTIC CRISIS: This will be due to Parvovirus B19.
  • SEQUESTRATION CRISIS(AKA SPLENIC SEQUESTRATION CRISIS): Look for abdominal pain, splenomegaly, and signs of SHOCK. Cells get trapped in the organ (usually the spleen, sometimes the liver). The pooling of the blood results in a lower effective volume of circulating blood, which results in SHOCK. Emergently transfuse!
    • PEARL: If given an option of IVF or PRBCs, go with what is FASTEST to bring up the blood pressure: IVF!
  • ACUTE CHEST SYNDROME: Look for the triad of PAIN + INFILTRATE + HYPOXIA. If there’s any doubt about the O₂ saturation, confirm with an ABG. Treatment is dictated by the hemoglobin level. LOW = TRANSFUSION. HIGH = EXCHANGE transfusion.
  • VASOOCCLUSIVE CRISIS: Look for acute pain! If the crisis is severe, it can cause ischemia, infarction of bone, stroke, or dactylitis(swelling of the hands or feet). Initial supportive therapy may include IV fluids and pain control. Definitive treatment is with a blood transfusion (low volume of 5 ml/kg PRBCs due to the potential for hyperviscosity syndrome). For suspected STROKE, get an MRI. Regarding transfusions, ONLY transfuse if there is evidence of a crisis AND there is anemia.
    • IMAGE: www.pbrlinks.com/SICKLECELL1
    • IMAGE: www.pbrlinks.com/SICKLECELL2
  • OSTEOMYELITIS: Salmonella osteomyelitis is MORE common than Staphylococcus aureus in sickle cell patients. Staph only accounts for about 25% of the cases in sickle cell patients. Don’t get distracted by trying to resolve conflicting statements about whether Staph or Salmonella is more frequent in sickle cell patients; just know that Salmonella is a major cause (www.pbrlinks.com/SICKLEOSTEO).
    • PEARLS: Remember that sickle cell patients can present with sepsis due to encapsulated organisms. Again, choose Salmonella over Staphylococcus for osteomyelitis in children with sickle cell anemia.
    • (DOUBLE TAKE) MNEMONIC: A complete list of encapsulated organisms can be recalled by remembering that “Some Nasty Killers Have Some Capsule Protection”: Streptococcus pneumoniae, Neisseria meningitidis, Klebsiella pneumoniae, Haemophilus influenzae, Salmonella typhi, Cryptococcus neoformans, and Pseudomonas aeruginosa. Bruton’s agammaglobulinemia and sickle cell patients are especially susceptible to encapsulated organisms.
  • DILUTE URINE: Due to renal damage, the urine may be dilute as evidenced by a low specific gravity. This is also known as HYPOSTHENURIA.
    • MNEMONIC: HYPOsthenURIA
• DIAGNOSIS of sickle cell anemia is done by HEMOGLOBIN ELECTROPHORESIS, which will show hemoglobin F and S (no hemoglobin A). The results might be shown as SF. The hemoglobin S develops due to a single “Glu→Val” amino acid substitution (glutamic acid replaced by valine) in the beta chain. Consider these patients as being functionally asplenic. Give penicillin prophylaxis through 5 years of age. Look for Howell-Jollybodies on the smear (indicating poor spleen function).
• PEARL: The RBCs contain hemoglobin with the Glu→Val swap that predisposes them to sickle, but they are of NORMAL size, so this is a NORMOCYTIC anemia. Thus, any macrocytosis or microcytosis has to be accounted for by an additional diagnosis! B12 or folate deficiency? Iron deficiency? Concomitant thalassemia?
• PEARL: If the electrophoresis results come back with Hgb SA, the patient has the sickle cell trait. Hemoglobin SC and S-beta thalassemia can result in a palpable spleen at the age of 6, but SF (AKA SS) causes the spleen to shrivel up by then. So, a palpable spleen in an 8-year-old is NOT due to sickle cell anemia.
• IMAGE: www.pbrlinks.com/SICKLECELL3 (Howell-Jolly bodies)
• MNEMONIC: Sickle cell anemia results in HOWell-JOLLY bodies. Have you ever noticed HOW JOLLY these patients get once they are given morphine?
• MNEMONIC: Regarding the Glu-Val swap mutation, there’s a mnemonic in there somewhere about a SICKLED CELL splattering over a BED (beta) on a WALL with GLUE on it. Thoughts?