Aplastic anemia resident survival guide

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

Aplastic Anemia

Drug History 50% of the cases

Radiation

Infection

Idiopathic

Congential / Family history Fanconi's Anemia 98 % Autosomal recessive 2 % X-linked recessive

Bone Marrow suppressing drugs Chloramphenicol carbamazepine Felbamate Phenylbutazone Quinine Phenytoin

Chemotherapy

Viral hepatitis

Parvovirus B19 in children

Investigations

Aplastic anemia

Check routine Labs, CBC and smear

Pancytopenia

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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.

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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

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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