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Management
Patients with aplastic anemia often come into recognition when symptoms of pancytopenia are present. It is
important to recognize the cytopenias because they may lead to life threatening events. Supportive management is
thus initiated rst to address the immediate problems associated with pancytopenia before proceeding with the
denitive management.
Supportive Management
The major consequences of cytopenias include decompensation in severe anemia haemorrhage resulting from
thrombocytopenia and infections due to leu!openia. The goals of supportive care are directed towards these
events. "nemia and thrombocytopenia are usually addressed with transfusions and broad spectrum antibiotics are
usually given for infections.
Transfusions with blood components such as red cells and platelets are given to maintain blood counts. The initial
goal of transfusion therapy for anemia should be to correct or avoid cardiopulmonary complications. #ed cell
transfusions are given to maintain a safe haemoglobin level of $%& g'l although this will depend on co(morbidities.
The goal of platelet transfusion should be to maintain a high enough platelet count to prevent spontaneous
bleeding. Prophylactic platelet transfusions are indicated when the platelet count is ) *& + *&, '- ) / + *&, '-0 or
) 1& + *&, '- in the presence of fever or infection. Prediction of bleeding is often a challenge and fatal
haemorrhage such as sudden cerebral haemorrhage can occur without warning and may even be the presenting
manifestation.
Problems may arise due to multiple transfusions sucha s alloimunisation and iron overload. Patients with aplastic
anaemia may develop alloimmunisation to leucocytes present in red cell and platelet transfusions by generating
2-" or non2-" minor histocompatibility0 antibodies. The use of leu!oreduced blood products is recommended to
prevent 2-" alloimmunisation. 3on(sensitized patients can receive random donor platelets while allo(sensitized
patients with platelet refracoriness should receive 2-"( and'or 2P"(matched platelet concentrates. 4lood products
should also be irradiated to prevent transfusion associated graft(versus(host disease reduction of sensitization to
2-" and non(2-" antigens from multiple transfusions. Iron overload can cause signicant problems in heavily
transfused patients. Iron chelation is generally e5ective in reducing iron burden in "". #eduction in serum ferritin is
a function of transfusional iron inta!e and dose of chelator such as desferro+amine or deferasiro+.
6rowth factors are an option for patients who need support for hematopoiesis but currently there are no e5ective
and safe haemopoietic growth factors to support red cell and platelet counts in patients with aplastic anaemia.
There is no standardized approach to antibiotic therapy in these patients. "s for all neutropenic patients fever mayrequire immediate hospitalisation and treatment before the results of bacterial investigations are available. "
combination of antibiotics must be employed wherein the e+act choice depends on local hospital microbiological
sensitivity'resistance patterns. It is recommended that systemic antifungal therapy is introduced into the febrile
neutropenia regimen early if fevers persist.
The ris! of infection is determined by the patient7s neutrophil and monocyte counts and on an individual basis as
some patients have repeated infections. Patients with aplastic anaemia are at ris! of bacterial and fungal infections.
Severely neutropenic )&./+*&8,'-0 patients should receive prophylactic antibiotics to help prevent 6ram(negative
sepsis with either a combination of two non(absorbable antibiotics such as neomycin and colistin or a quinolone
antibiotic such as cipro9o+acin. These patients are also at high ris! of fungal infection including "spergillus.
:luconazole provides no cover against "spergillus species. The drugs of choice are itraconazole and posaconazole.
Defnitive Management
Initially infection or uncontrolled bleeding should be treated rst before giving immunosuppressive therapy. This
also applies to patients scheduled for 4one ;arrow Transplant 4;T0 although it may sometimes be necessary to
proceed straight to 4;T in the presence of severe infection as a 4;T may o5er the best chance of early neutrophil
recovery. It is essential that before specic treatment is given the patient is stabilized clinically in terms of
controlling bleeding and treating infection. It is dangerous to give immunosuppressive therapy< since the presence
of infection is an adverse factor for outcome after stem cell transplantation. Prednisolone should not be used to
treat patients with aplastic anemia because corticosteroids are ine5ective they encourage bacterial and fungal
colonization and can precipitate 6I hemorrhage. Similarly hematopoietic growth factors such as 6(=S: and
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r2u>po should not be used on their own in newly diagnosed patients in the mista!en belief that they may cure the
disease. This would lead to a delay in giving specic treatment during which time the patient may become
infected or allo(immunised.
2ematopoietic stem cell transplantation( 4one marrow transplantation is potentially curative and is the treatment of
choice for treatment for children and young adults age ) ?& years0 with Severe "plastic "nemia who have an 2-"(
matched sibling donor. "n advantage of 4;T over the standard Immunosuppressive therapy IST0 is a mar!ed
reduction both in the ris! of relapse and the evolution of late clonal disorders such as ;@S and P32.=yclophosphomide with or with antithymocyte globulin "T60 is commonly used for conditioning before 4;T in
patients with S"". "lthough this regimen is non(myeloablative the immunosuppression is suAcient to allow
engraftment in most cases. "voidance of total body irradiation T4I0 and busulfan mar!edly reduces transplant(
related complications such as mucositis 6B2@ second malignancies and infertility.
Treatment "lgorithm for 3ewly @isgnosed Severe ""
=ompared with 4;T another highly e5ective treatment for S"" is "ntithymocyte globulin "T60 and =yclosporine "
=s"0 Immunosuppressive therapy IST0 and is generally rst(line therapy for S"" patients who lac! matched
sibling donors or are not good candidates for 4;T. The hematopoietic response rate after "T6'=s" is C&(D&E and
the probability of survival at / years ranges from C& to %/E. 2owever up to F&E eventually relapse.
In a prospective randomized controlled trial of the IST for 3on(severe "plastic "nemia showed that the combination
of "T6 and =s" resulted in a signicantly higher median hemoglobin level and platelet count at C months.
Treatment "lgorithm for 3ewly @iagnosed 3on(Severe ""
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Tacrolimus as an alternative to =s" has been investigated in children with S"" and found to have comparable
response rates %% vs %/E0 with a more favorable side e5ect prole.
The decision whether to use "T6 in older patients can be diAcult and requires careful assessment and discussion of
the ris!s with the patient. :or older patients the response rate and survival rate are lower compared to younger
patients. Glder patients aged $ C& years0 also have a higher ris! of serious cardiac events after "T6.
Reerences:
https://www.ebmt.org/Contents/Resources/Library/Slieban!/""C#$vent%ov&'(&/Documents/""')*Su
pportiveCare*Schre+enmeier,inal.p
http://aphcon.org/aplastic-anemia-treatment-guielines.html
http://www.bcshguielines.com/ocuments/"plast*anaem*bh*une&'('.p
http://www.ncbi.nlm.nih.gov/pmc/articles/MC)()01&0/
https://www.ebmt.org/Contents/Resources/Library/Slidebank/AACQEventNov2012/Documents/AA03_SupportiveCare_SchrezenmeierFinal.pdfhttps://www.ebmt.org/Contents/Resources/Library/Slidebank/AACQEventNov2012/Documents/AA03_SupportiveCare_SchrezenmeierFinal.pdfhttp://aphcon.org/aplastic-anemia-treatment-guidelines.htmlhttp://www.bcshguidelines.com/documents/Aplast_anaem_bjh_june2010.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138728/http://aphcon.org/aplastic-anemia-treatment-guidelines.htmlhttp://www.bcshguidelines.com/documents/Aplast_anaem_bjh_june2010.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138728/https://www.ebmt.org/Contents/Resources/Library/Slidebank/AACQEventNov2012/Documents/AA03_SupportiveCare_SchrezenmeierFinal.pdfhttps://www.ebmt.org/Contents/Resources/Library/Slidebank/AACQEventNov2012/Documents/AA03_SupportiveCare_SchrezenmeierFinal.pdf