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Bone Marrow failure is associated with the failure to replace the damaged cells, which are damage because of normal
apoptosis or hemolysis. BM failure also has the reduction or cessation of the production of cells (mostly Erythroid lineage but
still can affect WBCs and Platelets)
Patients with Bone Marrow Failure will always have Pancytopenia occurring.
Destruction of hematopoietic stem cells (could be because due to injury or exposure to drugs or chemicals)
Premature senescence and apoptosis of hematopoietic stem cells (there might be mutation that is happening
for that specific cell)
Ineffective hematopoiesis (may be because of the deficiency of Vitamin B12 and Folate)
Disruption of the bone marrow microenvironment (reversible at sometimes through bone marrow transplant)
Decrease production of hematopoietic growth factors or related hormones
Loss of normal hematopoietic tissue (because the malignant/ abnormal cells are able to infiltrate the bone
marrow)
3 GENERAL TYPES OF ANEMIA (Aplastic Anemia, Pure Red Cell Aplasia, Myelophthisic Anemia)
A. APLASTIC ANEMIA
Either Acquired or Inherited - (Most common is acquired)
General View of Aplastic Anemia:
Anemia
Neutropenia
Thrombocytopenia
*The term aplastic anemia is misleading because we think the problem is the Anemia, but the primary problem is the
Neutropenia and Thrombocytopenia. If there is Neutropenia there is a recurrent bacterial infection while having
Thrombocytopenia is a possibility of having hemorrhage
Aplastic Anemia is characterized by:
Pancytopenia
Hypoplastic or Aplastic BM (underdevelopment of the Bone Marrow or reduction of cells in the organ or tissue)
According morphology: Normocytic, Normochromic
Decreased Reticulocyte Count and RPI (Reticulocytopenia)
*Reticulocyte Normal Value: 0.5-2% for Adults
Absence of Immature Cells (BM is unable to compensate) and Absence of Splenomegaly
*If the patient is having Anemia, Splenomegaly, and Lymphadenopathy then you could rule out Aplastic Anemia
(because AA has no Splenomegaly and Lymphadenopathy)
PRIMARY: Inherited or Congenital (Fanconi’s Anemia)
SECONDARY: Acquired
Pathogenesis of Aplastic Anemia:
Defective CFU-S Stem Cell Population
*CD-34 expresses hematopoietic stem cells, individuals with AA has decrease CD-34 Values
*Also having an increase number of FAS Receptor - which mediates apoptosis in the cell which result to increased
number of premature cell death thus leadingto anemia
Altered microenvironment for normal stem cell production (still reversible through BM transplant)
Absent humoral and cellular stimulators for hematopoiesis
Excessive suppresion of hematopoiesis by T-Lymphocytes (particularly the T-Suppresor Cells)
Immunologic mechanisms that suppresses hematopoiesis
*Administering immunosuppresive drugs may alleviate the problem
Premature senescence and apoptosis causes increased FAS Receptors
*BM Aspirate/Biopsy as the sample from the posterior iliac crest as the common site, sometimes from the sternum.
Needles used: Jamshidi Bone Marrow Aspiration Needle and Illinois Sternal/Illiac Aspiration Needle
*Bone Marrow Aspirate - To get the cells from the bone marrow by making a smear
*Bone Marrow Core Biopsy/ Trephine Biopsy - To get a 1-2 cm intact bone marrow in which is reflective of the cellularity of
the BM
*Myeloid:Erythroid (M:E) Ratio - Numerical expression of demonstrating or comparing the relative number of granulocytic
precursors with the erythroid precursors
Normal Reference Values = 2:1-4:1; Average = 3:1 (3:1 because granulocytic precursors to erythroid precursors)
CLINICAL PRESENTATION
*Aside from striking hypoplastic marrow
Pancytopenia Hemorrhage (from Thrombocytopenia)
Pallor, wekaness, fatigue Lack of palpable spleen (absence of Splenomegaly)
Decreased Neutophil (recurrent bacterial infection)
LABORATORY FINDINGS
Peripheral Blood Smear:
Decreased total Leukocytes Normal Red Cell Morphology (Normocytic and
Lymphocyte is normal to slightly decreased (SD when Normochromic)
administering immunosuppressive drug) Decreased Reticulocyte count in PB
No Immature Cells in PB
Bone Marrow:
Hypoplastic/Aplastic No increase number of immature cells
Lymphocyte and Plasma Cells are present With patchy areas of cellularity
Megakaryocytes are absent
CLINICAL FINDINGS
Short stature Microcephaly (causing retardation)
Brown skin pigmentation Low Birth weight
Hypogonadism (Failure to develop secondary sexual Internal Strabismus
characteristic) Increased levels of Fetal Hemoglobin and small “i”
Malformation of organs antigen (iAg)
Mental Retardation
Fanconi’s Anemia (Phenotype)
Growth retardation and Abnormal development 1000 Fold Risk of Cancer
Stem Cell Failure
*FA is a chromosomal instability disorder which mean there is random breakage of chromosome; Culture cells (from patient with FA) are
challenged with the addition of Alkylating/DNA Cross Linking Agent (2 most common types: Mitomycin and Diepoxybutane [DEB]); They
observed chromosomal breakage when the agents were added
*15 reported genes that are associated in FA (15 Genes are found in Rodak’s)
Remember: Most common gene present in FA is the FANCA Gene or known as Fanconi’s Anemia Complement Group A Gene
LABORATORY FINDINGS
Pancytopenia (Thrombocytopenia precedes other Macrocytic RBCs (First detected abnormality)
Cytopenia) Increased HbF and iAg
Reticulocytopenia Chromosomal Breakage
Hypoplastic BM Increase OFT and ESR result
Treatment: Due to Hypogonadism, it is administered with Androgen and Corticosteroid to stimulate Hematopoiesis
Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome)- Characterized by Mucocutaneous abnormalities, BM failure, and
Pancytopenia. It is a rare, inherited BM failure
Triad of Clinical Findings: Abnormal Skin Pigmentation (other references: Reticulated skin hyperpigmentation), Dystrophic
Nails, Oral Leukoplakia (whitish patch in the tongue, can’t be removed
- Patient is predisposed to Epithelial malignancies and Acute Myeloid Leukemia
Laboratory Findings: Macrocytic RBCs, Pancytopenia, Increase HbF
*This is differentiated from FA which has chromosomal breakage; DC has none
*Shwachman-Bodian-Diamond Syndrome - Combination of Pancreatic enzyme insufficiency and Neuropenia (or
Endocrine-Pancreatic insufficiency and Neuropenia)
- Hypopituitarism - the pituitary controls the adrenal gland, gonads, and thyroid. So if there is a problem it causes hypothyriodism and there would
be no production of the hormones: Growth Hormone, Thyroxine, and Prolactin (directly stimulate Erythropoiesis) so there is no stimulation of
Erythropoiesis
- Adrenal Abnormalities (Decreased Plasma Volume)
- Hypergonadism (Low Androgen: Low Testosterone thus there would be no stimulation of Erythropoiesis)
- Poikilocyte observed is Acanthocyte
ANEMIA OF PREGNANCY
- Relative anemia
- Starting at 8th Week of Gestation, increasingly slowly stable at 32 to 34th week
- Dilutional effects
*During pregnancy there would always be expansion of RCM and PV
*RCM expands because it is a protective mechanism of females because there is a chance for blood loss during childbirth or delivery
*PV is still anemia because PV expansion is more prominent/pronounced causing dilutional effect