Case 117 summary

This week we discussed a case of a young gentleman with pancytopenia.

Initial investigations for the cause of pancytopenia were undertaken and these included

  • Repeat FBC
  • Blood film
  • Reticulocyte count
  • Haematinics
  • Liver function
  • Viral studies- cmv, hepatitis, HIV, parvo, hepatitis, EBV
  • Autoantibody screen –  as during our case this has its own limitations and needs to be interpreted appropriately within clinical context.
  • Reviewing medications – gold/chloramphenicol/carbamazepine/phenytoin
  • Review family history
  • Bone marrow aspirate and trephine- incl FISH for cytogenetics
  • HbF% in children for prognostication
  • Peripheral blood chromosomal breakage analysis for Fanconi anaemia
  • flow cytometry for PNH
  • CXR- useful at presentation to exclude infection
  • X-rays of hands and feet if inhertited BMfs suspected
  • HRCT if Dyskeratosis congenita suspected or RUNX1 BMFs

Aplastic anaemia is defined as pancytopenia with a hypocellular marrow in the absence of abnormal infiltrate or marrow fibrosis

Diagnosis

Two of the following criteria must be met:

  1. Hb <100g/l
  2. Platelet count <50
  3. Neutrophil count <1.5

There is a biphasic distribution of 10-25 and 60+

Assessing severity:

Severe – marrow cellularity <25%, plus at least 2 is the following

    Neuts <0.5
    Plts<20
    Retics <20

 

Very severe – neuts <0.2

 

Supportive treatment

    Transfusional support- phenotype matched red cells (Rh and Kell). Platelet transfusion to keep plts >10, or if fever/sepsis >20
  • Prophylactic antibiotics and antifungals for patients who are severely neutropenia
  • Antivirals for patients receiving immunosuppressive therapy
  • Regular mouth care including antiseptic mouthwash
  • Food of low bacterial contant
  • Irradiated blood products should be used for patients receiving ATG/HSCT/alemtuzumab/granulocyte infusions/HLA matched platelets
  • Iron chelation should be considered on an individual patient basis
  • Granulocyte transfusions – irradiated – can be used in life threatening infection related to severe neutropenia (although data regarding effetiveness of granulocyte infusions is limited.

 

PNH

All patients should be screened for PNH

  1. using flow cytometry on perioheral blood to detect a deficiency in GPI anchored proteins – i.e. CD 14, CD16, CD24 and using FLAER for white blood cells and CD55/CD59 for red cell analysis
  2. if negative  test 6 monthly for 2 years.  If test becomes positive, check 3 mohtly for the first 2 years and reduce frequency if the proportion of PNH cells remains stable
  3. presence of small of moderate clones does not influence choice of treatment
  4. new PNH patients should be referred to the PNH national service

 

ATG

  • Provide prophylactic antiviral, antibiotic and antifungal treatment alongside ATG
  • Exclude platlet refractoriness prior to commencing treatment
  • Risk of anaphylaxis therefore test dose should be given
  • admisnter via central venous catheter
  • each dose should be preceded by methyl pred/chlorphenamine and plt transfusion to keep plts>20
  • commnece steroids on day after ATG is completed at 1mg/kg/day for 2 weeks followed by a rapid tapering
  • ciclosporing comenced as prednisolone dose is tapered at a dose of 5mg/kg/day aiming for trough levels of 100-200 micrograms/l.  slowly taper ciclosporin after at least a further 12 months of therapy
  • side effects – fever, rash, rigors, hypo/hypertension/fluid retention/pulmonary oedema/ARDS/anaphylaxis/serum sickness (treated with IV hydrocortisone 100mg QDS)
  • Response is delayed, starting at approx 3-4 months.  70% response rate at 6 months follwoing horse ATG.  Response to a second course will be further reduced
  • other immunosupressives may be considered if transplant is not an option

 

Transplantation

Current BCSH guidelines

image

However, data is suggesting that upfront transplant in young patients with severe aplastic anaemia has better outcomes, therefore if the timeline allows MUD/haplo transplant this may have better outcomes.

References

Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment.  George E. Georges, Kris Doney and Rainer Storb. 

Guidelines for the diagnosis and management of aplastic anaemia.  BSH guidelines.  Killick, S, B.

 

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