Test 4: Hypoproliferative anemias Flashcards by Sarah King

What are the mechanisms of bone marrow failure?

-destruction of stem cells due to drugs, chemicals, radiation, viruses, or autoimmune mechanisms
-Premature apoptosis of stem cells due to mutations
-Ineffective Hematopoiesis due to B12 or folate deficiencies
-Disruption of marrow microenvironment
-decreased production of growth factors
-Loss of normal hematopoietic tissue due to infiltration of marrow space with abnormal cells

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This marrow disorder is characterized by a reduction in the number or function of multipotential stem cells (CD 34)

Aplastic anemia

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Characteristic feature of aplastic anemia

Pancytopenia

Also, ridiculo cytopenia, bone marrow hypocellularity, and depletion of hematopoietic stem cells (Increase fat cell infiltration)

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Is aplastic anemia acquired or inherited?

-most common is acquired (95%)
(Idiopathic)
-Inherited accounts for 30% of cases in children

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Is acute or chronic aplastic anemia more common?

Acute (rapidly fatal) is most common

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Aplastic anemia is most frequent in what age range?

Individuals 10 to 25 years and those over 60

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Diagnosis of aplastic anemia is made when two of the three peripheral blood values are found. What are the three?

-WBC less than 500 cells
-Platelet count less than 20×10 to the 3rd µL
-Retic count less than one percent

(Pancytopenia definition)

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How does the bone marrow appear in aplastic anemia?

Few cells, lots of fat

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Acquired aplastic anemia can be further classified as ______________ When cause is unknown and ____________ When cause is known

Idiopathic 70%, Secondary

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Secondary causes of aplastic anemia are usually related to what?

Drug related. Benzene, sulfa drugs, penicillin, tetracycline and chemotherapeutic agents

Can be reversible or irreversible
90% of cases are due to idiosyncratic reaction to drug/chemicals

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What are the clinical characteristics of acquired aplastic anemia?

-Bleeding from thrombocytopenia
-Increase susceptibility to infection due to leukopenia
-All the symptoms of anemia
-Absence of splenomegaly
-Iron overload from repeated transfusions and decreased need of iron for erythropoiesis

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What is the pathophysiology of acquired aplastic anemia?

Due to a qualitative and quantitative deficiency of the hematopoietic stem and progenitor cell population by a direct or indirect mechanism

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What is the pathophysiology of a quired aplastic anemia that is direct?

A cytotoxic drugs, chemical, radiation, or virus damages the DNA of stem and progenitor cells

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What is the pathophysiology of acquired aplastic anemia that is indirect?

-Exposure to certain drugs or chemicals that produces an auto immune T cell attack that destroys the stem and progenitor cells
-Elevated levels of growth factor in serum including EPO (Despite this, growth factors are unsuccessful in correcting the cytopenia’s)
-failure of cell growth could result from excessive suppression of hematopoiesis byT lymphs or macrophages

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A type of primary inherited aplastic anemia, congenital problem originates within bone marrow itself as an autosomal recessive disorder

Inherited aplastic anemia Fancini’s syndrome

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Caused by mutation in one of seven different genes
Presents with skin pigmentation, short stature, hypogonadism, malformation of fingers, toes, and organs

Inherited aplastic anemia Fancini’s syndrome

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Characterized by major chromosomal abnormalities Like breaks, gas, and Jean rearrangement
Peripheral blood abnormality show up in early childhood: Anemia, neutropenia, thrombocytopenia

Inherited aplastic anemia Fancini’s syndrome

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What is the prognosis for Inherited aplastic anemia Fancini’s syndrome ?

Prognosis is still very poor, even with cytokines and androgen in therapy

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Inherited aplastic anemia Fancini’s syndrome:

Death usually occurs from…

Overwhelming hemorrhage or infection before age 30 (This is the most common cause of death in any aplastic anemia)

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What is a commonly use therapy for Inherited aplastic anemia Fancini’s syndrome?

Bone marrow transplant commonly used however patient still pre-disposed to other malignancies due to widespread chromosomal damage.

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What are the peripheral blood findings for aplastic anemia?

• Anemic, neutropenic, AND thrombocytopenic
• Normocytic, normochromic anemia (or macrocytic)
• Decreased retic count and RPI
No immature cells present*
• Predominant WBC is lymphocyte (“lymph”)
• Toxic granulation of neutrophils may be observed

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Other disorders that cause pancytopenia, such as leukemia, are associated with the presence of many…..

Immature cells

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It is normal to see toxic granulation in…..

Infections

(Darker and more pronounced granules)

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In aplastic anemia, serum iron and percent transferrin saturation are ___________.

Increased due to decreased use of iron for erythropoiesis

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Bone marrow for aplastic anemia is….

Hypocellular or is a dry tap

Approximately 30% of patients with aplastic anemia develop…

Paroxysmal Nocturnal Hemoglobinuria (PNH) * sensitive to complement

Paroxysmal Nocturnal Hemoglobinuria (PNH): Acquired stem cell mutation results in the hemolysis of RBCs by _____________

Complement. • PNH erythrocytes are deficient in membrane regulators of complement (PIGA gene), and are subject to chronic hemolysis in vivo • Disease characterized by attacks of intravascular hemolysis and hemoglobinuria that occur chiefly at night while the patient is asleep.

Paroxysmal Nocturnal Hemoglobinuria (PNH): Flow cytometry shows decreased ______ and ________.

CD55 and CD59

Paroxysmal Nocturnal Hemoglobinuria (PNH): Positive _________ test (acidified serum lysis) Complement-Dependent Hemolysis.

Ham

What is the treatment for aplastic anemia?

Best treatment is to treat the symptoms, and if possible, find the cause of suppression Blood transfusions given as needed Long-term survival in patients who receive stem cell transplant from HLA identical sibling

What is the most common peripheral blood findings in severe aplastic anemia?

Macrocytosis, thrombopenia & neutropenia

A rare disorder characterized by a selective and severe disease in erythrocyte precursors and otherwise normal bone marrow

Pure red cell aplasia (PRCA)

Pure red cell aplasia (PRCA): Can be Acquired or congenital, But most common is…

Acquired due to acute or chronic illness

Pure red cell aplasia (PRCA): Patients present with…

Severe anemia, reticulocytopenia, and normal WBC and platelet count

Extremely rare, inherited disorder involving EPO resistant stem cells of unknown cause

Diamond-Blackfan anemia

What is the morphology in Diamond-Blackfan anemia?

Normocytic (Or macrocytic), Normochromic anemia, reticulocytopenia, but normal wbc and playlets

What hemoglobin is increased in Diamond-Blackfan anemia ?

Hemoglobin F**** Poor prognosis, Half of cases Present with physical abnormalities

Diamond-Blackfan anemia: Bone marrow biopsy is cellular, but with marked decrease in…

Erythrocytes (Normal myeloid cells and megakaryocytes)

Half of Diamond-Blackfan anemia pts present with what abnormalities?

physical abnormalities

Diamond-Blackfan Anemia will have increased hgb ____.

How common is Acquired Pure Red Cell Aplasia?

-rare -occurs more in adults than children

Is Acquired Pure Red cell Aplasia acute or chronic?

could be either -May be idiopathic or autoimmune related

Acquired Pure Red Cell Aplasia: > 50% cases occur in patients with concurrent _________.

thymoma (cancer cells in thymus)

Acquired Pure Red Cell Aplasia: characterized as ____-, ______- anemia, but WBCs and plt. counts are normal.

normo-, normo-

Acquired Pure Red Cell Aplasia: Bone marrow shows mostly normal cellularity, but with severe decrease in which precursors?

erythroblasts

Acquired Pure Red Cell Aplasia: When found in children, it is referred to as...

transient erythroblastopenia of childhood -Patients have history of viral infection

Acquired Pure Red Cell Aplasia: Anemia is normocytic and Hgb-F levels are ________.

Normal

What is the standard therapy for Acquired Pure Red Cell Aplasia?

 Transfusions  Disorder is usually transient

Congenital Dyserythropoietic Anemias: -Refractory (not responsive to therapy) -Can cause _______ nuclei

multiple

Group of rare disorders characterized by refractory anemia (unresponsive to therapy), reticulocytopenia, and hypercellular bone marrow with markedly ineffective erythropoiesis

Congenital Dyserythropoietic Anemias

Congenital Dyserythropoietic Anemias: True or false? Megaloblastoid features are not due to vitamin B12 or folate deficiency (gene expression)

True

Characteristically include multinucleated forms and internuclear chromatin bridges or nuclear strands between two erythroblasts (nuclear bridging)

Congenital Dyserythropoietic Anemias

Diamond-Blackfan anemia differs from inherited aplastic anemia in that in the former: A. Retics are increased B. Hb F is decreased C. Only erythropoiesis is affected D. Congenital malformations are absent

C. Only erythropoiesis is affected

The infiltration of abnormal cells into the bone marrow and subsequent destruction and replacement of normal hematopoietic cells.

Myelophthisic Anemia

Myelophthisic Anemia: Premature release of immature cells from bone marrow and _________ hematopoietic sites occur.

extra-medullary

Myelophthisic Anemia is common in...

pts. with metastatic carcinoma ("space-occupying lesions") or in leukemia/lymphoma -Degree of anemia correlates with tumor burden

Lab results with Myelophthisic Anemia?

Normocytic, normochromic erythrocytes, reticulocytosis, with varying degrees of maturation found in peripheral blood.

What can be seen on blood smear with Myelophthisic anemia?

Teardrop erythrocytes*, nRBCs, and immature myeloid cells, megakaryocyte fragments, and giant platelets are seen on smear

How is Myelophthisic Anemia distinguished from Aplastic Anemia?

by teardrop RBCs, a leukoerythroblastic blood picture, and abnormal cells in the bone marrow

Anemia that occurs in patients w/ end-stage renal disease

Anemia of Chronic Renal Insufficiency (Anemia of Chronic Renal Disease)

Anemia of Chronic Renal Insufficiency: There is a general correlation between the severity of the anemia and the degree of elevation of the ______>

BUN

Anemia of Chronic Renal Insufficiency: When BUN is > 100 mg/dL, the Hct is usually < ____%

What is the primary cause of Anemia of Chronic Renal Insufficiency?

decreased production of EPO

What causes increased hct with Anemia of Chronic Renal Insufficiency?

-decreased plasma volume (due to decreased [plasma protein] & thus tissue edema) -increased due to relative erythrocytosis – but this may be counterbalanced by the absolute anemia due to the lack of EPO!

What morphology is associated with Anemia of Chronic Renal Insufficiency?

 Normo- normo-, with normal or decreased reticulocytes  Burr cells (renal disease), and shistocytosis

Anemia of Chronic Renal Insufficiency: Generally shortened RBC survival; uremia causes RBC p.m. defects such as?

Burr cells -Uremia also causes decreased plt. function, & resulting chronic bleeds = more anemia!

Anemia of Chronic Renal Insufficiency: What lab values correlate with the severity of uremia?

increased BUN & creatinine

What is the treatment for Anemia of Chronic Renal Insufficiency?

 Recombinant erythropoietin injections are effective  Iron therapy given if levels are too low for recombinant EPO to be effective