Heme unit 1

1.1 - anemia intro (w/o retic count and RPI); 1.1 - QA; 1.1 - iron metabolism/heme synthesis anemia; 1.2 - qualitative defects of Hgbopathies (in-progress)

What is hypervolemia?

increased plasma volume; Hgb/Hct falsely low

What is hypovolemia?

decreased plasma volume, Hgb/Hct falsely high or normal

What does Hgb look like during acute blood loss

Hgb is initially normal, but it falls as plasma re-expands

What can cause hypervolemia?

pregnancy, acute blood loss

What can cause hypovolemia?

dehydration

Up to what percent of decreased Hgb does the body tolerate in chronic anemia?

up to 50% below normal Hgb

Up to what percent of decreased blood volume can the body tolerate with acute loss?

up to 20% volume loss at rest

At what percentage of blood volume loss does the body experience shock?

30-40% volume loss

What are some physiological adaptations to anemia?

• increase in respiration rate/deeper inspiration

• increase in heart rate

• increase in cardiac output

• increase in circulation rate

• increase in 2,3-BPG in RBCs

• decreased oxygen affinity of Hgb in tissues

What does jaundice and dark urine suggest?

hemolytic process/anemia

What does splenomegaly/hepatomegaly suggest?

chronic hemolytic or infiltrative disease

What is koilonychia, and what does it suggest?

“spoon-shaped” upward/outward curved nails, instead of downward; suggest iron deficiency

What does a smooth tongue suggest?

megaloblastic anemia

What do bone deformities and expansion in children indicate?

chronic severe hemolytic anemia

What is pallor, and what does it indicate?

paleness in conjuctiva (behind/under eyelids), nail bed, palm, tongue; indicates anemia

What are some symptoms of anemia?

fatigue (most common) headache, vertigo, syncope, dyspnea, palpitations

What are follow-up tests of a CBC if you might suspect anemia, and what are they for?

retic count: indicates marrow response

peripheral smear: can see RBC morphology, inclusions, distribution

bilirubin: hemoglobin catabolism

urine and stool: test for occult blood, urobilinogen

What do microcytes and hypochromia indicate on a peripheral smear?

defective Hgb synthesis (iron deficiency, thalassemia, chronic disease anemia, sideroblastic)

What do macrocytes indicate on a peripheral smear?

impaired DNA synthesis (B12/folate) or reticulocytosis

What is the clinical significance of retic count?

It is the best indicator of marrow erythropoiesis.

What is immature retic fraction (IRF), and how can it be helpful?

it indicates the earliest sign of marrow response, because the IRF rises before retic count, Hgb, Hct, RBC count; useful after a marrow transplant or monitoring iron therapy; CLSI recommends to use IRF instead of RPI when possible

What is reticulocyte hemoglobin (Chr / RHT-He) indicate?

reflects the iron available over the last several days, can be an early indicator of response to iron therapy

How are anemia defects classified?

proliferation defect (decreased production), maturation defect (ineffective erythropoiesis), survival defect (increased destruction/loss)

What are laboratory indications of a proliferation defect?

normocytes/normochromia, decreased retics, RPI <2

What are laboratory indications of a survival defect?

increased retics, RPI >2, increased IRF

What is compensated hemolytic disease?

When there is hemolysis but the bone marrow keeps up pace, so no anemia develops

What is intrinsic hemolysis?

hereditary membrane, enzyme, or hemoglobin defects; usually extravascular hemolysis

What is extrinsic hemolysis?

acquired antibody, mechanical, chemical, or infectious injury to RBCs; extravascular or intravascular; DAT can be used for immune-mediated destruction

What is intravascular hemolysis?

hemolysis happening within the circulation

What is extravascular hemolysis?

hemolysis happening in the spleen, liver, or by bone marrow macrophages

What can cause intravascular hemolysis?

complement activation, mechanical trauma, toxic microenvironment

What can cause extravascular hemolysis?

antibody/complement-coated or damaged RBCs removed by phagocytes

What are laboratory indications of intravascular hemolysis?

• decreased haptoglobin

• increased Hgb

• hemoglobinuria

• hemosiderinuria

• very increased LDH

What are laboratory indications of extravascular hemolysis?

• increased indirect bilirubin

• increased urine and fecal urobilinogen

• slightly increased LDH

• increased expired CO

• is also more common than intravascular

What might you see a normal RDW (homogeneous)?

hypoproliferative anemia, chronic disease anemia, some hemoglobinopathies

When might you see an increased RDW (heterogeneous)?

nutritional deficiencies, early iron deficiency, chimerism, uncompensated hemolysis

True or False: bone marrow evaluation is usually a part of anemia evaluation.

False, only needed when a stem cell defect or marrow damage is indicated, or when blood work seemingly aligns with anemia but is inconclusive

What is the reference range for myeloid:erythroid (M:E) ratio?

1.5-3.3

What does a decreased myeloid:erythroid (M:E) ratio indicate?

hemolytic anemia (marrow compensating)

What does a increased myeloid:erythroid (M:E) ratio indicate?

proliferation defect (aplastic, infiltrative, chronic disease anemia)

When should you reject a coagulation specimen?

<90% of proper fill line, over-anticoagulated

What is the correction formula when the patient’s Hct is (falsely) over 55%?

(1.85 × 10^-3) x (100 - Hct) x V = C

C = sodium citrate (mL)

V = whole blood (mL)

Hct = pt Hct%

How often is QC ran for coag tests?

every 8 hours

What is Bull’s testing algorithm/X-B moving average?

The analyzer calculates the average RBC indices for each group of 20 specimens, and alerts if the moving average is outside of the acceptable range (indicating possible analyzer issue)

How is the acceptable range for the moving average calculated?

You determine the RBC indices on 500 consecutive pt specimens, then the acceptable range is ±3% of the mean of each indice.

What is the rule of three in hematology?

RBC ct x 3 = Hgb

Hgb x 3 = Hct

What can cause false increase of Hgb?

lipemia, icterus, hemolysis

How do you correct a falsely increased Hgb by corrected calculation?

Mix well, aliquot the whole blood, and centrifuge

Perform Hgb determination on supernatant/plasma

corrected Hgb = Hgb (on original whole blood specimen) - Hgb (supernatant/plasma)

then recalculate MCH and MCHC using the corrected Hgb and RBC and Hct of original specimen

How do you correct a falsely increased Hgb by saline?

Mix well, aliquot the whole blood, and centrifuge

Remove the plasma, noting the amount there was

Replace with equal amount of saline, mix well

Perform Hgb determination

How can cold agglutinins impact hematology results?

decreased RBC count

increased MCV

decreased Hct (calculated from measured MCV)

increased MCHC (>36 g/dL)

What conditions can interfere with coag tests?

lipemia, icterus, hemolysis

What form of iron is in heme, red meat, and is absorbed more efficiently?

ferrous (Fe2+)

What form of iron is in vegetables/whole grains and needs to be converted in order to be absorbed?

Ferric (Fe3+)

What is ferritin?

short-term storage of iron

What is ferroportin?

exports iron in the gut

What is transferrin?

transports iron

How does the intestine regulate iron absorption?

It increases absorption when erythropoiesis is increased and when iron stores are depleted.

What are factors that can decrease the availability of iron in the body?

diet, macrophage recycling

What are intraluminal factors that can decrease the absorption of iron in the body?

inflammatory bowel disease (IBD), parasites, toxins, intestinal motility, decreased absorptive surface area

What are systemic conditions that can decrease the absorption of iron in the body?

inflammation, infection

What are factors that can both increase and decrease iron absorption in the body?

Hematopoetic/erythropoietic activity of bone marrow, tissue iron stores

What are factors that can increase absorption of iron in the body?

low Hgb concentration, hypoxia

What can cause an increase in total iron-binding capacity (TIBC)?

the liver producing more transferrin in response to low iron stores

What can cause a decrease in total iron-binding capacity (TIBC)?

high iron stores and inflammation

How is total iron-binding capacity calculated?

serum iron + UIBC (unsaturated, which is tested) = TIBC

What is the reference range for ferritin in males?

20-300 mcg/L

What is the reference range for ferritin in females?

12-200 mcg/L

What is the reference range for serum iron in males?

65-180 mcg/dL

What is the reference range for serum iron in females?

50-180 mcg/dL

What is the reference range for RBCs?

4-6 × 10⁶/uL

What is the reference range for Hgb?

12-18 g/dL

What is the reference range for MCV?

76-100 fL

What is the reference range for MCH?

26-34 pg

What is the reference range for MCHC?

32-36 g/dL

What is the reference range for RDW?

11.5-14.5%

What is the reference range for absolute retics?

20-115 × 10³/uL

What is the reference range for relative retics?

0.5-2.5%

What is the reference range for platelets?

150-450 × 10³/uL

What is the calculation for Hct?

Hct% = (MCV x RBC)/10

What is the manual calculation for MCV?

MCV = (Hct% x 10)/RBC

What is the calculation for MCH?

MCH = (Hgb x 10)/RBC

What is the calculation for MCHC?

MCHC = (Hgb x 100)/Hct

What is the calculation for RDW-CV?

RDW-CV = (RDW-SD x 100)/MCV

What is indicated if ferritin is <12 mcg/L?

depletion of iron stores

What is indicated if ferritin is >1000 mcg/L?

iron overload

What is serum transferrin receptor (sTfR)?

extracellular portion of transferrin released into the plasma

What is the reference range for serum transferrin receptor (sTfR)?

8.7-28.1 nmol/L

What is the reference range for TIBC?

250-450 mcg/dL

What is zinc protoporphyrin (ZPP)?

zinc is incorporated into heme when iron is unavailable, and reflects iron supply during recent erythropoiesis; indirect measure of iron

What is the reference range of zinc protoporphyrin in males?

1-27 mcg/dL

What is the reference range of zinc protoporphyrin in females?

11-45 mcg/dL

What is the calculation for transferrin saturation?

% = (serum iron/TIBC) x 100

What is the reference range of transferrin saturation for males?

20-45%

What is the reference range of transferrin saturation for females?

15-45%

What is hemosiderin?

“long-term storage,” partially degraded ferritin in macrophages

When should you see hemosiderin in bone marrow macrophages?

normal or increased iron stores

Where is iron primarily stored?

the liver

True or False: serum ferritin reflects total body iron stores.

True, except during inflammation

What is hepcidin?

a hormone produced by the liver that binds/degrades ferroportin

How does increased hepcidin affect iron absorption and serum iron?

decreases intestinal absorption, decreases serum iron