Approach to Anemias Flashcards

1
Q

How can you tell if an erythrocyte is newly produced?

A

Do a DNA staining and look for granules containing DNA (which will still exist in young denucleated erythrocytes for 1-2 days after ejection from bone marrow). These classify the erythrocyte as a reticulocyte.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Daily turnover of erythrocytes

A

~1-2% destroyed by the spleen per day, ~1-2% produced by bone marrow per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Stress reticulocytes

A

Tend to be pushed out of the bone marrow early in times of hemorrhage or hemolytic anemia. Still blue from high RNA density, you don’t even need a special stain to see them.

High numbers of ‘bluish red cells’ is termed polychromatophilia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Anemias of erythrocyte loss

A

Hemoltyic or hemorrhagic

In hemolytic anemia, markers of erythrocyte and heme catabolism will be apparent in blood. This is not true for hemorrhagic anemia, but rather in hemorrhagic anemia iron is often scarce.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Haptoglobin

A

Free hemoglobin scavenger. Binds up free hemoglobin in plasma and brings it to macrophages for catabolism.

As a consequence, during hemolytic anemic processes, haptoglobin levels fall.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Classic pattern of hemolysis

A
  • Anemia
  • Increased reticulocytes
  • Elevated LDH and indirect bilirubin
  • Decreased haptoglobin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

If hemolytic anemia persists chronically, the patient may develop. . .

A

. . . a folate deficiency and bilirubin gallstones. These bilirubin gallstones may also impair secretion, leading to direct bilirubinemia on top of the pre-existing indirect bilirubinemia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Intravascular hemolysis

A

When hemolysis takes place within the ciruclatory system. In these cases, large amounts of hemoglobin will be secreted into plasma and haptoglobin will be completely consumed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

When haptoglobin cannot handle the hemoglobin load, as in intravascular hemolytic processes, . . .

A

. . . the remaining hemoglobin is filtered in the kidney, then reabsorbed and re-packaged as hemosiderin.

Chronically, hemoglobin and hemosiderin may be lost in urine, and in this case iron losses become significant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Extravascular hemolysis

A

Mediated primarily by macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Acute and chronic hemolysis summary

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Reasons one might have an erythrocyte production problem

A
  • Not enough EPO (renal failure)
  • Thalassemia (disorder of hemoglobin production)
  • Iron deficiency (iron deficiency anemia)
  • Folate or B12 deficiency (megaloblastic anemia)
  • Not enough stem cells (aplastic or hypoplastic anemia)
  • Fibrosis of marrow
  • Myeloma/leukemia/lymphoma/metastatic marrow cancer
  • Granulomas in marrow
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Normocytic anemia

A

Fewer erythrocytes, but erythrocytes look normal. Low BUN and creatinine levels indicating renal failure.

Results in insufficient EPO production, leading to anemia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Microcytic anemia

A

When hemoglobin synthesis is compromised or there is not sufficient iron available for synthesis (iron deficiency, thalassemia, anemia of chronic disease, sideroblastic anemia). Red cells are made smaller to preserve the concentration of hemoglobin within each cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Megaloblastic anemia

A

Affects myeloid and erythroid precursors. Precursors exhibit poor nuclear development and a high nuclear to cytoplasmic ratio. Erythrocytes are macrocytic and more ovular.PMNs with 6 lobes may also be seen in these anemias.

Caused by B12 or folate deficiency, or drug-induced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Aplastic or Hypoplastic anemia

A

There just aren’t enough stem cells in the bone marrow to meet demands. Red cells may be normocytic or macrocytic. PMNs also reduced, but not hyperlobed as in megaloblastic anemia.

Biopsy indicated to assess bone marrow cellularity.

17
Q

Myelophthisic anemia

A

Invasion of the marrow by a cancer, granuloma, fibrosing process, etc. Red cells usually normocytic, but may show an occasional ‘teardrop’ form. Immature precursors may also appear in peripheral circulation.

18
Q

Systematic approach to anemia Ddx

A
  1. Check reticulocyte count
    • If high, hemoltyic or hemorrhagic process
      • Hemolytic: Jaundice, ^ bilirubin, gallstones, ^ LDH, v haptoglobin
      • Hemorrhagic: Bleeding, low iron
    • If normal or low, insufficient production
      • Microcytic: Small erythrocytes
        • Iron deficiency
        • Hemoglobin processing problem
        • Anemia of chronic disease
      • Macrocytic: Large erythrocytes
        • Megaloblastic: Nuclear maturation problems, abnormal PMN nuclei. Folate or B12 deficiency, rarely drug-induced
        • Non-megaloblastic: Aplastic or hypoplastic anemia
      • Normocytic
        • ​Aplastic or Hypoplastic anemia: Often associated with other cytopenias. Bone marrow biopsy required
        • Myelophthisic: Often associated with other cytopenias. Bone marrow biopsy often required, teardrop cells can clue in, as can history of cancer or other signs of malignant process
        • Renal failure: Not enough EPO
        • Anemia of chronic disease: due to chronic inflammation
19
Q

Hereditary spherocytosis

A

Heritable hemolytic anemia with spherocytes on blood smear.

20
Q

A woman arrives for her first prenatal visit, appearing tired. She is well into her third trimester.

Without any additional information than the above and the lab results, what is the likely diagnosis?

A

Megaloblastic anemia due to pregnancy-related folate deficiency.

Treat by putting on a folate supplement.

21
Q

The primary indicator that distinguishes production problems from destruction/loss problems is ___.

A

The primary indicator that distinguishes production problems from destruction/loss problems is the reticulocyte count.

22
Q

Unconjugated vs conjugated bilirubin

A

Bilirubin is converted from unconjugated to conjugated bilirubin in the liver. So, if the anemia is hemolytic, you are likely to have high unconjugated bilirubin as opposed to high conjugated bilirubin.

23
Q

LDH

A

Lactate dehydrogenase

Abudant in erythrocyte cytoplasm