Bone Marrow

What is Hematopoiesis?

A continuous renewal, proliferation, differentiation, and maturation of all blood cell lines

What is the role of the hematopoietic stem cell?

It produces all other stem cells and therefore all other blood cells

What are the 2 main bone marrow samples collected?

Aspirate and Biopsy

What are the 4 types of bone marrow specimens collected?

• Aspirate smears

• Crush smears

• Touch preps

• Clot samples

What are you assessing during a bone marrow examination?

• Cell differentials

• M:E ratio

What is an M:E ratio?

A measure of the balance between myeloid cells (which become white blood cells like granulocytes) and erythroid cells (which become red blood cells) in the bone marrow

What is a normal M:E ratio?

3:1

What are the advantages and disadvantages of marrow aspirate smears?

Advantage: fast, no need to decalcify specimen

Disadvantage: may not represent all cells

What are the advantages and disadvantages of marrow core biopsy?

Advantages: ability to analyze both cells and stroma

Disadvantages: slow processing

What is Prussian blue staining for?

Evaluating iron stores for deficiency or excess iron

What is H&E stain used for?

Used to evaluate cellularity and hematopoietic cell distribution

What is the definition of bone marrow failure?

The reduction of blood forming cells in the bone marrow, affecting one or more cell lines

Bone marrow failure often leads to what?

Pancytopenia (a condition where the blood count of all three major types of blood cells—red blood cells, white blood cells, and platelets—is lower than normal)

Abnormal changes in the body caused by bone marrow failure

• Destruction of stem cells

• Disruption of bone marrow micro environment (cells aren’t released)

• Premature aging and increased apoptosis

• Ineffective hematopoiesis

What is aplastic anemia?

The bone marrow stops producing enough blood cells because the stem cells of marrow microenvironment is defective or damaged and fails to produce enough blood cells to serve the body’s needs

What are the characteristic features of aplastic anemia?

• Pancytopenia

• Reticulocytopenia

• Bone marrow hypocellularity

Idiopathic acquired aplastic anemia has….

No known cause and make up 70% of the cases

Secondary acquired aplastic anemia has….

Specific causes with 10-15% of the cases

What lab finding is found in both Idiopathic and Acquired aplastic anemia?

Macrocytic Anemia

What causes secondary Aplastic Anemia?

• Some drugs, chemicals, radiation, or infections

• EBV, HIV, hepatitis, human parvovirus

Pathophysiology of Acquired AA

• deficiencies of the hematopoietic stem cell

• Stromal cells are functionally normal

• Increased serum erythropoietin, thrombopoietin, and granulocyte colony stimulating factor

What are the lab findings for acquired aplastic anemia?

• Pancytopenia

• Leukopenia

• Thrombocytopenia

• HGB <100g/L

• Serum iron is elevated reflecting a decrease in iron utilization during erythropoiesis

What is needed to diagnose aplastic anemia with a bone marrow sample

• Hypocellular marrow

• Erythroid, megakaryocytic, or granulocytic cells are reduced or absent

• Biopsies required for accurate diagnosis of AA

What is the treatment for acquired aplastic anemia?

• Discontinue the causative agent

• Blood and platelet transfusion as needed

• Hematopoietic stem cell transplant for severe forms and those under 40yrs with identical HLA match

• Immunosuppressive therapy for people >40 years

How does immunosuppressive therapy work to treat acquired aplastic anemia?

Anti-thymocyte globulin decreases the number of T-lymph’s and cyclosporine inhibits T-cell function. Together this suppresses the autoimmune reaction against the stem cells (won’t attack stem cells)

What is Fanconi Anemia?

An inherited chromosome instability disorder

What are the symptoms of Fanconi Anemia?

• Physical abnormalities

• Aplastic anemia

• Cancer susceptibility

• Genetic abnormalities

What is the first detected abnormality of Fanconi anemia in the lab?

Macrocytic anemia

How is Fanconi anemia diagnosed?

Chromosomal breakage analysis test is done and confirmed my testing for gene mutations and deletions

What is the treatment for Fanconi anemia?

• transfusions for treatment of cytopenia(s)

• HSCT with an identical HLA match is only curative treatment

What is Pure Red Cell Aplasia?

A disorder of erythropoiesis characterized by selective destruction of RBC precursors in the bone marrow

What are the symptoms of Pure Red Cell Aplasia?

• Normocytic but severe anemia

• Reticuloytopenia

• Bone marrow relatively normal

What cell populations are NOT affected by Pure Red Cell Aplasia?

WBCs and PLTs

What is Congenital Dyserythropoietic Anemia (CDA)?

A rare, inherited group of blood disorders where immature red blood cells (erythrocytes) don't mature properly, leading to a shortage of functional red blood cells (anemia) and iron overload in the body

CDA 1

• Macrocytic and RBC,

• Interneuclear chromatin bridges

• Inclusions

• <5% binucleated erythroblasts

CDA 2

• Most common

• Normocytic with RBC inclusions

• 10 - 35% binucleated forms

CDA 3

• Lease common

• Macrocytic anemia with inclusions

• Megaloblastic changes

• Giant Erythroblasts (up to 12 nuclei)

What is Myelophthisic Anemia?

Infiltration of abnormal cells into the bone marrow causing destruction and replacement of normal hematopoietic cells

What are the symptoms of Myelophthisic anemia?

• Metastatic solid tumour cells for in a variety of areas in the body leading to the release of immature cells

• Stem and progenitor cells leave BM and goes to the Liver causing it to enlarge

What are the lab findings of Myelophthisic anemia?

• Severe anemia

• Reticulocytopenia

• Teardrop cells

• NRBCs

• Immature myeloid cells

What is the cause of Anemia of Chronic Kidney Disease?

• Mainly due to inadequate erythropoietin in the kidney

• Also caused by Uremia (increase in urea in the blood stream) because it inhibits erythropoiesis and increases RBC fragility

How does Anemia of Chronic Kidney disease appear on a blood smear?

• Normocytic

• Normochromic

• Reticulocytopenia

• Burr cells in cases of uremia