Approach to anemia (underproduction): Clinical sciences

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Introduction0:00–0:28

Anemia is a condition characterized by a decrease in healthy red blood cells indicated by low levels of hemoglobin and hematocrit or red blood cell count.
Anemia can be caused by red blood cell sequestration, destruction or underproduction of red blood cells. Now, if you suspect anemia, you should first perform an ABCD E assessment to determine if the patient is unstable or stable.

Unstable Patient0:28–1:10

If the patient is unstable, stabilize the airway, breathing and circulation. Next, obtain IV access, give IV fluids and if necessary, consider blood products such as packed red blood cells if needed, provide supplemental oxygen.
And don't forget to put your patient on continuous vital sign monitoring including BP, heart rate and pulse oximetry. Now that we're done with unstable patients, let's go back to the ABCD E assessment and look at the stable ones.

Stable Patient1:10–3:34

In this case, obtain a focused history and physical examination and order labs including CBC with indices and a reticulocyte count.
The history could reveal fatigue, malaise palpitations and dyspnea while physical exam might show tachycardia and conjunctival pallor.
However, these findings are nonspecific. So you need to check labs.
If the labs reveal low hemoglobin and hematocrit only, then can you diagnose anemia? Here's a clinical pearl.
After confirming that your patient has anemia, you need to find what's causing it by looking at additional clues in the lab results.
Here. Our approach is based on assessing reticulocyte count first followed by the M CV.
Some people instead start from the M CV. Both approaches are valid.
The important thing is to use a reliable approach that will make sure you consider all the appropriate causes and help you narrow your differential, then assessed the reticulocyte count.
Reticulocytes are young red blood cells. And if their count is above the reference range, it suggests that the body is actively producing new red blood cells to compensate for the loss.
In this case, the underlying cause of anemia is the loss of red blood cells either through destruction such as hemolysis or sequestration in the spleen.
On the other hand, if the reticulocyte count falls within or below the reference range, diagnose anemia due to the underproduction of red blood cells.
The next step is to classify the anemia based on the size of the red blood cells using the mean corpuscular volume or M CV.
For short, depending on the value of the M CV, you can classify anemia as either microcytic normocytic or macrocytic. First, let's focus on a patient with an MCV.

Microcytic anemia3:34–5:09

Under 80 we call this microcytic anemia because the red blood cells are smaller than normal to investigate the cause. Order iron studies check the levels of serum iron and ferritin to assess iron availability in the blood.
Next, check transferrin saturation or TSAT to evaluate the iron binding sites on transferrin and serum total iron binding capacity or T IBC.
To determine if the body is trying to compensate by capturing any available iron. Let's take a look when the studies reveal low serum iron ferritin and TSAT levels along with a high serum T IBC.
In this case, you should consider iron deficiency or lead poisoning as potential diagnoses to determine which one it is.
Order a blood lead level test and a peripheral blood smear if the blood lead level test is negative and the peripheral blood smear shows microcytic and hypochromic red blood cells.
The diagnosis is iron deficiency anemia. Remember iron deficiency is the most common cause of microcytic anemia.
On the other hand, if the blood lead level test is positive and the peripheral blood smear shows basophilic stippling of the red blood cells diagnose anemia due to lead poisoning also be sure to keep an eye out for hints in the patient's history such as potential occupational or environmental lead exposure.

Iron deficiency/Lead poisoning5:09–5:46

Here's a high yield fact, lead poisoning can cause microcytic anemia via two mechanisms. The first one can clinically resemble iron deficiency because lead interferes with the iron absorption in the intestines.
While the second mechanism involves the inhibition of enzymes that are involved in heme synthesis resulting in sideroblastic anemia.

Sideroblastic anemia5:46–6:38

Speaking of sideroblastic anemia, let's go back to the iron studies and take a look at a patient with high serum iron ferritin and TSAT levels and a normal serum TIBC.
In this case, you should consider sideroblastic anemia. So make sure to order a peripheral blood smear as well as a bone marrow aspirate with prussian blue staining if the peripheral smear shows basophilic stippling of the red blood cells.
And the aspirate reveals erythrocytes with a ring of iron around the center known as ringed sideroblasts. You can confirm the diagnosis of sideroblastic anemia.
The most common causes include chronic alcohol use and heavy metal poisoning such as arsenic or even lead. Lastly, let's say iron studies show low levels of serum iron TS AT&T IBC and high ferritin levels.

Anemia of chronic disease6:38–7:39

If that's the case, consider anemia of chronic disease, also known as anemia of chronic inflammation. This type of anemia occurs when the inflammatory response in chronic disease prevents iron release from its stores.
So serum iron levels are low while ferritin is high because iron stores are full to confirm your suspicion. Take a closer look at the history and look for an underlying chronic condition.
Some examples include infections, malignancy and rheumatologic diseases. Here's a clinical pearl.
Keep in mind that anemia of chronic disease may initially present as normocytic and over time becomes microcytic if the underlying condition isn't resolved.
Speaking of normocytic anemia, let's turn our attention to those with normal M CV, which ranges from 80 to 100 in such cases, diagnosed normocytic anemia, meaning that despite being anemic, the size of red blood cells is within the normal range to determine the cause.

Normocytic anemia7:39–8:03

You need to revisit the patient's history. One of the most important causes you should consider is chronic kidney disease or CKD.

CKD8:03–8:57

Normally, the kidneys produce erythropoietin or epo which in turn signals the bone marrow to produce red blood cells. But in CKD, the kidneys can't make enough epo leading to insufficient red blood cell production and anemia.
Patients may already have a confirmed diagnosis of CKD or may present with suggestive symptoms like hypertension or edema to confirm your diagnosis.
Check the estimated glomerular filtration rate or egfr if it's less than 60 has remained below 60 for three months or more, you can diagnose CKD.

Pure Red Blood Cell Aplasia8:57–10:17

Finally, let's consider pure red blood cell aplasia. Say your patient presents with a history of infection like parvo virus B 19.
Certain neoplasms such as Thymomas and lymphoid neoplasms like lymphomas or leukemias or a history of exposure to certain medications such as rifAMPin or Phenytoin.
In this case, if lab reveals a reticulocyte count below the normal reference range with normal white blood cell and platelet counts consider pure red blood cell aplasia.
The next step is to obtain a bone marrow aspirate if it reveals normal cellularity with isolated erythroid hypoplasia, diagnose a pure red blood cell aplasia.
Here's another clinical pearl anemia is common among patients over 50 it is often caused by nutritional or vitamin deficiencies or anemia of chronic disease.
However, a subset of elderly patients develop normocytic anemia without an obvious underlying cause. This is referred to as unexplained anemia of the elderly.
Let's take another step back and have a look at an M CV, greater than 100. In such cases, you should diagnose macrocytic anemia, meaning that red blood cells are larger than normal.

Macrocytic anemia10:17–10:42

Next, obtain a peripheral blood smear to further classify it into megaloblastic and nonmegaloblastic. Let's take a look at megaloblastic anemia.

Megaloblastic anemia10:42–12:14

If the blood smear shows hypersegmented neutrophils together with the macrocytic red blood cell count, diagnose megaloblastic anemia.
This can be caused by deficiency of vitamin B12, also known as cobalamin or B nine, commonly called folate. So check their serum levels.
If you find low B12 and normal folate levels, diagnose vitamin b12 deficiency anemia. On the other hand, if there's normal b12 and low folate levels, diagnose folate deficiency anemia.
Now, here's a high yield fact, if the levels of B12 or folate are borderline, you should check methylmalonic acid or M MA and homocysteine levels.
Vitamin B12 plays a role in converting mm A to succinyl coenzyme A and homocysteine to methionine. So in case of B12 deficiency, you will notice elevated levels of both mm A and homocysteine.
On the other hand, folate is only necessary for converting homocysteine to methionine. Therefore, in folate deficiency, you'd find normal M MA levels with elevated levels of homocysteine only.
Finally, let's take a look at nonmegaloblastic anemia if there's no hypersegmented neutrophils. But instead, you only observe macrocytic red blood cells, diagnose nonmegaloblastic anemia.

Non-megaloblastic anemia12:14–12:38

Next, check the CBC for white blood cell and platelet counts. Let's take a look at chronic alcohol use liver disease and hypothyroidism.

Chronic alcohol use/Liver disease/Hypothyroidism12:38–14:24

If both white blood cells and platelets fall within the reference range, consider anemia due to chronic alcohol use liver disease or hypothyroidism.
That's because alcohol is toxic to the bone marrow. While liver disease affects the metabolism of cholesterol and fossil lipids.
So, these substances end up accumulating on red blood cell membranes in excess. Lastly, hypothyroidism can lead to anemia via an adaptive change to a decrease in cellular metabolism to confirm the diagnosis, assess for a history of chronic alcohol use or liver disease.
And order labs like FTS and TSH. If there's a positive history or elevated FTS, especially if AST is more than twice as high as alt, then you can confirm the diagnosis of chronic alcohol use and liver disease.
On the other hand, elevated TSH is highly suggestive of anemia due to hypothyroidism. Here's a high yield.
Fact, patients with chronic alcohol use liver disease or hypothyroidism can also develop folate or B12 deficiency due to a combination of inadequate dietary intake, impaired intestinal absorption and decreased hepatic uptake, ultimately presenting as megaloblastic anemia.
Now, let's take a look at aplastic anemia and myelodysplastic syndrome. Lastly, if labs reveal low white blood cells and platelets.

Aplastic anemia / Myelodysplastic syndrome14:24–15:03

You should obtain a bone marrow aspirate to assess the hematopoietic stem cells. If the aspirate reveals a dry tap, meaning hypocellularity without any myelodysplastic morphology, diagnose aplastic anemia on the flip side.
If there's hypocellularity with myelodysplastic morphology, diagnose myelodysplastic syndrome. All right, as a quick recap.

Review15:03–16:25

Once you diagnose anemia, assess the reticulocyte count to determine the underlying cause if it's normal or below the reference range, diagnose anemia due to underproduction of red blood cells.
Next check the M CV. And if it is 80 or below, assess for causes of microcytic anemia, including iron deficiency, lead poisoning, sideroblastic anemia and anemia of chronic disease.
If the M CV is between 8100, assess for causes of normocytic anemia, including anemia of chronic disease, D and pure red blood cell aplasia.
Finally, MCV, greater than 100 points to macrocytic anemia. In this case, obtain a peripheral blood smear to differentiate between megaloblastic anemias, which can be caused by B12 and folate deficiencies and nonmegaloblastic anemias, which can be associated to chronic alcohol use liver disease, hypothyroidism, aplastic anemia and myelodysplastic syndrome.