Hereditary Spherocytosis

Snapshot

A 25-year-old pregnant woman presents to her obstetrician reporting yellow eyes, yellow skin, and dark urine. She reports having a family history of “jaundice,” and some of her relatives have undergone splenectomy. She states she has had periodic jaundice throughout her life, but now that she is pregnant, she is constantly jaundiced. A peripheral smear shows spherocytes.

Introduction

Overview
- hereditary spherocytosis is a hereditary disorder characterized by small, round red blood cells (RBCs) without central pallor, resulting in premature removal by the spleen and hemolytic anemia
  - treatment is usually splenectomy
Epidemiology
- incidence
  - most common cause of hereditary hemolytic anemia in patients of northern European descent
Pathogenesis
- mechanism
  - intrinsic defect in RBC membrane proteins leading to decreased RBC membrane surface area and increased fragility
  - abnormal RBCs are lysed by the spleen, resulting in extravascular hemolysis
Genetics
- inheritance pattern
  - autosomal dominant
- mutations
  - multiple mutations implicated, leading to variety of clinical manifestations, ranging from asymptomatic to fulminant hemolytic anemia
  - most commonly caused by spectrin deficiency
less commonly caused by ankyrin mutation

Presentation

History
- may have family history of relatives who have undergone splenectomy
- may have a history of intermittent scleral icterus, jaundice, and dark urine color, often associated with viral infections
Symptoms
- clinical severity varies
  - onset may occur in neonatal period, or in adulthood in the context of environmental stress
  - cholelithiasis may be the presenting sign
    - gallstones are pigmented
- common symptoms
  - colicky abdominal pain
Physical exam
- inspection
  - splenomegaly
  - jaundice
    - may be triggered by stress, fatigue, pregnancy, or infection
  - pallor
dark urine

Studies

Osmotic fragility test
- increased fragility
Serum labs
- normocytic anemia
- ↑ reticulocyte count
- ↑ bilirubin
- ↑ mean corpuscular hemoglobin concentration (MCHC)
Peripheral blood smear
round RBCs (spherocytes) without central pallor

Differential

Autoimmune hemolysis
- key distinguishing factor
  - may also present with spherocytes but is Coombs positive
Gilbert syndrome
- key distinguishing factors
  - may also present with jaundice intermittently, but patients often also have abdominal cramps, fatigue, and malaise
laboratory studies show normal reticulocyte count and peripheral blood smear

Treatment

Medical
- folic acid supplementation
  - indications
    - folic acid is required for continued erythropoiesis
    - folic acid deficiency can result in megaloblastic crisis
- RBC transfusion
  - indication
    - aplastic crisis
Surgical
- splenectomy
  - indications
    - definitive treatment
    - can be deferred in patients with mild HS (hemoglobin > 11 g/dL)
patients must undergo vaccination against pneumococcus and H influenzae prior to splenectomy

Complications