Aplastic anemia resident survival guide

Revision as of 00:45, 15 December 2013 by Chetan Lokhande (talk | contribs)
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Chetan Lokhande, M.B.B.S [2]


Definition

Aplastic Anemia is a condition where the bone marrow and the bone marrow cells are damaged. A deficiency of all the three cell types is seen which leads to pancytopenia. Decrease in red blood cells (Anemia) presents as pallor, fatigue, dyspnea and leg pain. Decrease in platelets (Thrombocytopenia) presents as mucosal bleeding, purpura and bruising. Decrease in white blood cells (Neutropenia) manifests as recurrent infection.

Causes

Idiopathic ( The most common cause - atleast 50% of the causes)

Drug History

  • Chemotherapy

Infection

Congenital /Family History

  • Fanconi's Anemia 98 % Autosomal recessive and 2 % X-linked recessive

===Radiation=== [2][3]


Miscellaneous

Investigations

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symptoms of dyspnea , fatigue , bleeding and recurrent infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check routine Labs,
CBC and smear
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pancytopenia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
{{{ }}}
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone Marrow Aspirate / Biopsy
 
 
 
 
 
 
 
 
 
1. Chest X-ray
2. Liver function tests
3. Vit B12 / Folate
 
 
 
 
 
 
 
 
 
Genetic / Cytology

1. Chromosomal breakpoint for Fanconi's Anemia
2. Mutational Analysis for Inherited Bone Marrow Failure Syndrome (IBMFS)
3. Flow cytometry for Paroxysmal Nocturnal Hemoglobinuria (PNH).
Check CD55 and CD59 expression on RBC for PNH.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
{{{ }}}
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
{{{ }}}
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypocellular
Diagnostic criteria of Aplastic Anemia includes
1. Increased fat / Stroma
2. No Malignant / Fibrotic infiltration
3. Normal Residual hematopoeitic cells with megaloblastic cells
Once diagnosed as Aplastic anemia rule out the common causes of Aplastic anemia.
 
 
 
 
 
 
 
 
 
 
 
Variable / Infiltrated / Hypercellular
Causes are :
1. Myelodysplastic Syndrome
2. Leukemia
3. Hodgkins
4. Storage disorder
5. Anorexia Nervosa
6. Nutritional deficiency
7. Myelofibrosis
8. Solid tumors
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Grading

 
 
 
 
 
 
 
 
 
 
Aplastic anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moderate
1. Bone marrow cellularity < 30 %
2. Absence of severe pancytopenia
3. Depression of atleast 2 / 3rd blood elements
 
 
 
 
 
Severe
1. Bone Marrow cellularity < 25 % OR
2. Bone Marrow cellularity < 50 % out of which < 30 % cells are hematopeotic and atleast 2 out of the following :
a. Absolute reticulocyte count < 40000 / ul.
b. ANC < 500 / ul
c. Platelet < 10,000 / ul
 
 
 
 
 
Very Severe
Same as Severe +
Absolute neutrophil count < 200 / ul
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Management

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Aplastic Anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematopoietic stem cell transplantation(HSCT)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunotherapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe and very severe Aplastic anemia
 
 
 
 
Patients < 40 yrs old
 
 
 
 
HLA match
 
 
 
 
 
 
 
 
Moderate Aplastic anemia
 
 
 
Patients > 40 Yrs old
 
 
 
HLA not matched hence not a candidate for HSCT
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
{{{ }}}
 


Drugs used in Immunotherapy

 
 
 
 
 
 
 
 
Immunotherapy in Aplastic anemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Horse ATG
( 20 mg / kg x 4 days )
+
Cyclosporine (CSA)
( 12 - 15 mg / kg in divided doses b.i.d x 6 months
 
 
 
 
Granulocyte colony-stimulating factor ( G-CSF)
(5 µg / kg/ day x 90 days)
 
 
 
 
For relapsing and in countries where ATG is unavailable
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide (CTX)
( 30 mg / kg IV x 4 days over 1 hr )
+
Cyclosporin (CSA)
(3 mg / kg / day )
Starting on day 11 to maintain trough and peak blood levels of 150 - 250 mg/ml and 700 - 1000 mg / ml respectively for 180 days
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Do's

  • Take detailed history of all patients presenting with anemia.
  • Have a high suspicion and look for any identifiable causes.
  • When treating with ATG keep the platelet count >20,000 / microL at all times. Keep platelets and leukoreduced irradiated blood products readily available.
  • Secure a central line which would help in blood drawing, infusing blood products and other fluids.
  • When treating with cyclosporine check levels regularly , renal function ( creatinine levels ), blood pressure and for signs of neurotoxicity. Cyclosporine should be given for six months but doasge should be tapered right from the first month to maintain levels of 200 to 250 ng/ml.
  • In previously untreated adults use horse ATG than rabbit ATG.

Don'ts

  • G-CSF should not be used as a primary therapy because that will only delay the onset of effective therapy (Immunosuppressive therapy) . There is an increased incidence of MDS/AML as well as poor outcome in relapsing patients who were treated with G-CSF.
  • There is no evidence to use high dose intravenous cyclophosphamide (total dose 200 mg/kg given over four days), with or without cyclosporine in the initial treatment of severe aplastic anemia (SAA) . However, this regimen can be used in patients who did not respond to immunosuppressive therapy.


References

  1. Goss, JA.; Schiller, GJ.; Martin, P.; Seu, P.; Stribling, R.; McDiarmid, SV.; Shackleton, CR.; Markowitz, JS.; Nuesse, BJ. (1997). "Aplastic anemia complicating orthotopic liver transplantation". Hepatology. 26 (4): 865–9. doi:10.1002/hep.510260410. PMID 9328306. Unknown parameter |month= ignored (help)
  2. Young, NS. (2002). "Acquired aplastic anemia". Ann Intern Med. 136 (7): 534–46. PMID 11926789. Unknown parameter |month= ignored (help)
  3. LANGE, RD.; WRIGHT, SW.; TOMONAGA, M.; KURASAKI, H.; MATSUOKE, S.; MATSUNAGA, H. (1955). "Refractory anemia occurring in survivors of the atomic bombing in Nagasaki, Japan". Blood. 10 (4): 312–24. PMID 14363312. Unknown parameter |month= ignored (help)
  4. Walport, MJ.; Hubbard, WN.; Hughes, GR. (1982). "Reversal of aplastic anaemia secondary to systemic lupus erythematosus by high-dose intravenous cyclophosphamide". Br Med J (Clin Res Ed). 285 (6344): 769–70. PMID 6810992. Unknown parameter |month= ignored (help)
  5. Nissen, C. (1991). "The pathophysiology of aplastic anemia". Semin Hematol. 28 (4): 313–8. PMID 1759172. Unknown parameter |month= ignored (help)