28 Sep 2020

8/27/20 Hereditary Spherocytosis

For Goldstein Report, PGY3 Christina Gainey presented a case of a 36 year old male with history of MSM on Truvada for PREP and H. pylori gastritis who presented from primary care clinic for abnormal labs and jaundice.  2 days prior to admission, the patient had onset of fever/chills and diffuse upper abdominal pain.  Pain is 5/10, epigastric without radiation, associated with nausea.  Also had night sweats, febrile to 102F.  He went to the PMD the following day and labs were sent.  Over the following day, urine started becoming darker, and noted that his skin and eyes were turning more yellow.  Abdominal pain and fevers subsequently improved.  Denies hematemesis, coffee ground emesis, hematochezia, melena and diarrhea.  Home medication includes Truvada and recently took 2 OTC pills from China for pain.  Other exposure history includes unprotected intercourse with 2 male partners in the last week, oral and anal receptive, recent binge drinking with 9 drinks consumed 6 days prior to admission.  No prior STIs though history of anal warts s/p removal.  Emigrated to US from China, currently works as a lawyer.

Physical exam with stable vital signs, mild sclera icterus, normal CV and pulm exam, mild hepatomegaly, palpable spleen tip, and minimal jaundice on skin.

CBC: WBC 2.8 > Hb 12.2/Hct 33 <Plt 113

Differential: 58% PMN, 35% lymphocytes, 0% eosinophils, 2% basophils

CMP:
Na 133/K 3.5/Cl 100/HCO3 23/BUN 11/Cr 1.03 <Glucose 104
ALP 127>T.protein 7/Albumin 4.5/AST 114/ALT 256/Tbili 20.3/Dbili 16.7

Coags:PT 14.6, INR 1.16, PTT 41.6

TSH 0.46 uIU/mL (normal 0.27-4.20)

APAP <5.0 mcg/mL

Infectious workup:

  • UA with 30 protein, large bilirubin, small blood (RBC 4-5), negative leuks (WBC 0-3)
  • Hep A Ab IgM neg
  • Hep A Ab total Reactive
  • Hep B Core Ab Nonreactive
  • Hep B Core IgM Nonreactive
  • Hep Bs Ag Nonreactive
  • Hep C Ab Nonreactive
  • HCV RNA Not detected
  • Hep E IgM Negative
  • Hep E IgG Negative
  • HIV Nonreactive
  • HIV RNA Not detected
  • RPR Nonreactive
  • CMV IgM <30 (negative), IgG 5.30 U/mL (>0.7 = positive), PCR not detected
  • EBV IgM 51.0 U/mL (H), IgG 236 U/mL (H), nuclear Ag Ab IgG >600 U/mL (H)

Autoimmune workup:

  • ANA negative
  • Actin Ab IgG <20 units
  • LKM-1 Ab <20 units
  • Mitochondrial Ab Negative
  • Cerruloplasmin 37 mg/dL (normal 18-36)
  • IgG 1068 mg/dL (normal 700-1600)
  • IgM 111 mg/dL (normal 40-230)

Hematology workup:

  • Reticulocyte percentage 7.37%
  • Iron panel
    • Iron 47 mcg/dL (normal 50-160)
    • TIBC 181 mcg/dL (normal 250-430)
    • Iron sat 26% (normal 15-50%)
    • Ferritin 947 ng/mL (normal 15-240)
  • LDH 440 U/L (normal 135-225)
  • Haptoglobin <10 mg/dL (normal 30-200)
  • Fibrinogen 505 mg/dL (normal 228-487)
  • Folate 8.4 ng/mL (normal >4.6)
  • B12 450 pg/mL (normal 232-1245)
  • G6PD 16.2 U/g (normal 7-20.5)
  • MCHC 36.9 g/dL (normal 32-35)
  • DAT negative
  • Peripheral smear shows spherocytes as well as nonspecific poikilocytes.  Some red cells lack central pallor and has a variable rim of unstained cytoplasm at one end. 

Abdominal US revealed advanced hepatic steatosis, splenomegaly and gallbladder sludge; no biliary dilatation.

MRCP revealed no evidence of choledocolithiasis, intra or extra-biliary ductal dilation, hepatic steatosis, and splenomegaly.

Treatment: Both hematology and hepatology consulted and after review of peripheral smear along with lab results, final diagnosis was hemolysis consistent with hereditary spherocytosis.  Liver enzymes steadily improved during the hospitalization without any further interventions.  Prior to discharge, team recommended the patient obtain an outpatient cholecystectomy.  The patient had the EMA binding test done outpatient and was positive.

Take home points:

  1.  Hereditary spherocytosis is one of the common causes of hemolytic anemia caused by a defect in red cell membranes.
  2. Common symptoms: hemolytic anemia with jaundice, splenomegaly, family history of gallstones at young age, gallstones (5 fold greater incidence of pigment gallstones)
  3. Lab findings: hemolysis (elevated LDH, indirect bilirubin, decreased haptoglobin, increased reticulocyte count), negative Coombs because non-immune, elevated MCHC (> 36 g/dL)
  4. Diagnosis: Osmotic fragility test (can also be positive in AIHA), EMA (eosin-5-maleimide) binding test is the preferred test of choice
  5. Treatment: supportive with folic acid and transfusions, severe cases can have splenectomy

Article:
NEJM CPC
Hereditary Spherocytosis

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