American Society of Hematology

Case Study: 32 Year-Old Female with Anemia and Confusion

A board-style question with an explanation and a link to a relevant article is a recurring feature of TraineE-News. The goal of the case study is to clarify specific and timely teaching points in the field of hematology. The following case study focuses on a 32-year-old woman, with no significant past medical history, who presents to the emergency department with several days of worsening confusion. The complete blood count shows a hemoglobin concentration of 9.8 g/dL and platelet count of 34 x 109/L. Creatinine is 3.1 mg/dL and the LDH is 448 IU/L. Review of the peripheral blood smear shows numerous schistocytes. ADAMTS13 level is measured and found to be 68 percent without evidence of a detectable inhibitor. The patient is diagnosed with atypical hemolytic-uremic syndrome and eculizumab is started.  

Which of the following vaccinations should be administered as soon as possible after initiating eculizumab?

  1. Seasonal influenza
  2. Varicella zoster virus
  3. Hepatitis B
  4. Meningococcus
  5. Tetanus

Answer

  1. Meningococcus

Explanation

Meningococcal (Neisseria meningitides) infections have occurred in patients receiving eculizumab, and patients receiving eculizumab should be vaccinated. The patient has evidence of a thrombotic microangiopathy with anemia, schistocytosis, and elevated LDH. When combined with thrombocytopenia and renal failure along with an ADAMTS13 level > 10 percent, the clinical picture suggests atypical hemolytic-uremic syndrome. While similar to thrombotic thrombocytopenic purpura (TTP), it is not due to a deficiency of ADAMTS13, but rather mutations in the genes for C3, Factors H, B, and I, as well as membrane cofactor protein. The monoclonal antibody eculizumab inhibits the terminal portion of the complement cascade and is approved by the FDA to treat atypical HUS as well as paroxysmal nocturnal hemoglobinuria (PNH). The drug carries an FDA black-box warning about the risk of meningococcal disease and the product insert includes a recommendation to vaccinate patients against meningococcus as well as provide education and counseling. Ideally, the vaccine should be administered at least two weeks prior to initiation of eculizumab in order to allow sufficient immune response. For patients requiring immediate initiation of treatment with eculizumab, vaccination against meningococcus should be done as soon as possible. Should a patient develop evidence of meningoccocus, eculizumab therapy should be stopped.

Case study submitted by Nathan Connell, MD, Brown University, Providence, RI, Trainee Council Member.

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