Blood chem Result Normal value Urea nitrogen 4.8 mmol/L 2.2-8.2mmol/L Creatinin 1.9 5-17 Phos Alk 32.8 10-35 SGPT 50.9 5-47
What are you impression?
Leukemia--- WBC increased in BM
Multiple Myeloma--- plasma cell increased in BM
Lymphoma(Hodgkins)--- Lymphocyte increased in BM
APLASTIC ANEMIA What happens when the bone marrow shuts down?
What is Aplastic Anemia ? - Aplastic Anemia is a bone marrow failure disease .
Aplastic anemia is a severe, life threatening syndrome in which production of erythrocytes, WBCs, and platlets has failed.
The disease is characterized by peripheral pancytopenia and accompanied by a hypocellular bone marrow.
Peripheral blood Smear Peripheral blood Smear
HYPOCELLULAR BONE MARROW IN APLASTIC ANEMIA
Aplastic Anemia patients
Aplastic Anemia patients have decreased amounts of: - Red Blood Cells
- White Blood Cells
Functions of Blood Cells
Red Blood Cells
Carry oxygen to all body organs
White Blood Cells
Fight infection and keep you healthy
Help control bleeding
Clinical Manifestations Symptoms caused by suppression of any or all bone marrow elements
Low Red Blood Cell
Fatigue, Headache, Inability to Concentrate, Dyspnea
Low White Blood Cell
Frequent or prolonged infections
Viral Infections, Bacterial Infections
Easy Bruising, Petichiae, Nosebleed and bleeding gums,Prolonged bleeding
Stem cell failure resulting from:
1-An acquired intrinsic stem cell defect
2-An environmental cause
Growth factor deficiency
Defects in the microenvironment
Pathophysiology of aplastic anemia
5-10 persons:10 6 per year
Aplastic anemia may occur in all age groups and both genders
Etiology : Hereditary
1-Schwacman – Diamond Syndrome
2-Fanconi’s anemia syndrome
Autosomal recessive disorder
congenital developmental anomalies
increase risk of malignancy
characterized by mucous membrane leukoplasia
dystrophic nails, reticular hyperpigmentation
development of aplastic anemia during childhood
2- Drugs: dose related idiosyncratic
3-Radiation- Damages DNA
5-Viruses- Hepatitis – most common
7-PNH ( Paroxysmal Nocturnal Hemoglobinuria )
8-Disorders of immune system- SLE.
Paroxysmal Nocturnal Hemoglobinuria
Defect in PIG-A gene which is required for the biosynthesis of cellular anchors, so partial or complete inability to construct Glycosylphosphatidylinositol(GPI) anchor for the attachment of CD55, CD59
Diagnosis: Ham’s test , sucrose hemolytic test , Flow cytometry using antibodies against cell surface antigens CD55, CD59 which are lacking in disease
Clinical manifestations of PNH
Hepatic vein most common
common cause of fatality
Cerebral vein thrombosis
sagittal sinus in particular
Pulmonary embolism unusual
Clinical manifestations of PNH
Relative/absolute bone marrow failure
present to some degree in all patients
decreased capacity to form myeloid colonies
Two stage model
somatic mutation in PIG-A gene
some cause for bone marrow failure
Diagnosis of AA: Lab findings Peripheral blood Smear Bone marrow biopsy
Normocytic-normochromic anemia (may be slightly macrocytic)
Low reticulocyte index
Empty fatty spaces
Few hematopoietic cells
Lymphocytes and plasma cells
Hypocellular bone marrow
CLASSIFICATION Designation Criteria PBS BM biopsy Severe aplastic anemia
-2 / 3 values-
Neutro < 500/ L
-Platelets < 20,000/ ul-
-Reticulocyte index < 1%
-Marked hypocellular < 25% cellularity -Moderate hypocellular <25-50% -normal cellularity with <30% of remaining cell hematopoietic Very severe aplastic anemia As above but neutrophils < 200/ L Infection present
Presentation of Anemia, Neutropenia and Thrombocytopenia Hemorrhagic lesion of the gums in a patient with aplastic anemia caused by infection with Capnocytophaga ochraceus; such lesions are easily confused with those of herpes simplex.
26-year-old woman with acute aplastic anemia and 1 day of facial pain/swelling. Mouth open involuntarily due to perioral edema. Needle aspirate of small purplish area near right alar revealed P. aeruginosa.
Aplastic anemia. Oral leukoplakia in dyskeratosis congenita.
Treatment Options Bone Marrow Transplant Growth Hormones Immune Suppressive Therapy Supportive Care
1-Withdrawal of the etiologic agent
transfusion of the blood products, CMV seronegative should be given transfusion from the family members should be avoided to prevent sensitization.
pooled donor platelets but leads to sensitization
in refractory cases need HLA matched transfusion
packed cells filtrated to remove leukocyte and platelets
iron overload : give chelating therapy deferoxamine
Staph. Aeureus * hospitalization * menses
This is the best therapy for the young patient with a fully histocompatible sibling donor
usually indicated for most patients with severe disease.
-Preferably from sibling
-Curative in 60-90% of patients
-Applicable only for a third of patients
Removal of the spleen
does not increase hematopoiesis but may increase neutrophil
increase platelet counts two- to threefold
improve survival of transfused red cells
platelets in highly sensitized individuals
Antithymocyte globulin(ATG) induces hematologic recovery (independence from transfusion and a leukocyte count adequate to prevent infection.
Cyclosporin + ATG
High dose cyclophosphamide
6. G-CSF/ GM-CSF/ EPO
**Response rate 50-70% Occurs 2-3 months post Rx.
*Mycophenolate mofetil (MMF) - cytotoxic to T cells
*Monoclonal Ab against IL-2 receptor which is present on activated lymphocytes