Aplastic Anemia

 

Aplastic CrisisPreviously, the Ped EM Morsels have requested that we remove the phrase “it’s just a virus” from our lexicons. One simple reason is that viruses can lead to significant illness also (ex, myocarditis, Guillain-Barre). While ordering a million tests and admitting everyone is not the answer, remaining vigilant can help you find subtle, ominous clues (ex, Derm Exam). That odd rash in the setting of fatigue may lead you to diagnose an Aplastic Anemia.

 

Aplastic Anemia: Basics

  • The diagnosis, evaluation, and treatment of aplastic anemia varies between institutions. [Williams, 2014]
  • “Aplastic Anemia” = tri-lineage peripheral blood cytopenia due to reduced or absent production of hematopoietic cells without cellular infiltration. [Barone, 2015]
    • Bone marrow failure leads to:
      • Severe anemia
      • Thrombocytopenia
      • Neutropenia
  • Mortality rates have improved with improved supportive care and anti-microbial management.
  • Majority of cases are idiopathic (~70-80%), but can be due to inherited conditions.
    • Fanconi Anemia is the most common inherited bone marrow failure syndrome
    • Dyskeratosis congenita and Schwachmai-Diamond Syndrome also cause aplastic anemia.
  • Can be acquired from:
    • Viral illness (ex, EBV, Hepatitis)
    • Graft-vs-host disease
    • Systemic lupus erythematous
    • Radiation exposure
    • Chemical exposure

 

Aplastic Anemia: Severity

  • Based on  [Barone, 2015]
  • Non-Severe
    • Neutrophils > 0.5 x10^9/L, but < 1.0 x10^9/L
    • Marrow cellularity < 30%
  • Severe
    • At least 2 of the following:
      • Neutrophils < 0.5 x10^9/L
      • Platelets < 20 x10^9/L
      • Reticulocytes < 20 x10^9/L
    • Marrow cellularity < 30%
  • Very Severe
    • Neutrophils < 0.2 x10^9/L

 

Aplastic Anemia: Evaluation

  • Family history is important
    • Can help distinguish patients with an inherited condition
    • Ask about family history of:
      • Bleeding disorders
      • Malignancy
      • Congenital abnormalities
      • Consanguinity
  • Drug and Environmental Exposure history can also offer clues, even if you aren’t a toxicologist!
    • Some offending drugs:
      • Linezolid, Chloramphenicol
      • Indomethacin, naproxen, sulfasalazine, diclofenac
      • Phenytoin, carbamazepine
      • Chloroquine
      • Thiazide diuretics, allopurinol
  • Thorough (and purposeful) physical exam can also find clues!
    • Physical findings may help alert us to the presence of aplastic anemia:
      • Pallor, petechiae
      • Tachycardia, hepatomegaly, systolic flow murmur
    • Physical findings can also highlight possible inherited condition:
      • Ex, dystrophic nails, oral leukoplakia, and reticular skin pigment consistent with congenital dyskeratosis
        • 2nd most common inherited cause of bone marrow failure
      • Cafe au last spots, microcephaly, hypogonadism, mucosal abnormalities? [Barone, 2015]
  • Lab Tests useful in the Emergency Department:
    • CBC with Differential
      • Usually shows normochromic, normocytic anemia
      • In early stages, only one or two cell lines may be effected (usually thrombocytopenia).  [Barone, 2015]
    • Reticulocyte Count
      • Always reduced.  [Barone, 2015]
    • Blood Type and Crossmatch
    • Peripheral Smear
      • Presence of dysplastic cells or blast cells may suggest leukemia instead!

 

Aplastic Anemia: Treatment

  • Non-severe cases may not require transfusions. Discuss with hematologist.
  • Transfuse Packed Red Blood Cells
    • Transfuse indications:
      • Symptomatic anemia
      • Asymptomatic anemia with Hgb < 8 g/dL [Barone, 2015]
    • Need to be leukoreduced and CMV-negative
    • Consult hematologist prior to transfusing. A period of observation is often used first.  [Barone, 2015]
  • Transfuse Platelets
    • Need to be leukoreduced and CMV-negative
    • Indications:
      • Platelet count < 10,000/microL
      • Platelet count < 20,000 /microL in setting of fever, sepsis, or bleeding
  • Consider bacterial infections, especially if neutropenic!
    • Empiric antibiotics should be given if patient is febrile and neutropenic.
    • Often regimen to include anti-pseudomonal coverage in addition to gram-negative and gram-postivive coverage.
    • If persistent fevers, consider fungal coverage.
  • Other disease specific regimens:
    • Immunosuppressants
    • Matched unrelated donor Stem Cell Transplant

 

References

Barone A1, Lucarelli A2, Onofrillo D3, Verzegnassi F4, Bonanomi S5, Cesaro S6, Fioredda F7, Iori AP8, Ladogana S9, Locasciulli A10, Longoni D5, Lanciotti M7, Macaluso A11, Mandaglio R12, Marra N13, Martire B14, Maruzzi M9, Menna G13, Notarangelo LD15, Palazzi G16, Pillon M17, Ramenghi U18, Russo G19, Svahn J7, Timeus F20, Tucci F21, Cugno C22, Zecca M22, Farruggia P11, Dufour C23, Saracco P18. Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis. 2015 Jun;55(1):40-7. PMID: 25976466. [PubMed] [Read by QxMD]

Williams DA1, Bennett C, Bertuch A, Bessler M, Coates T, Corey S, Dror Y, Huang J, Lipton J, Olson TS, Reiss UM, Rogers ZR, Sieff C, Vlachos A, Walkovich K, Wang W, Shimamura A. Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): an initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatr Blood Cancer. 2014 May;61(5):869-74. PMID: 24285674. [PubMed] [Read by QxMD]

Young NS1, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19. PMID: 16778145. [PubMed] [Read by QxMD]

Guinan EC1. Aplastic anemia: management of pediatric patients. Hematology Am Soc Hematol Educ Program. 2005:104-9. PMID: 16304366. [PubMed] [Read by QxMD]

Sean Fox

I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renown educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.

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3 Responses

  1. Ellen says:

    Hi SEAN FOX,

    Great post! Thank you so much for sharing this very educative article. This is very helpful. Keep on posting significant articles. Thanks!

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