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Hematology - Anemia - Fast Facts | NEJM Resident 360

Anemia is a common presentation in all medical practice settings. Symptoms are related to poor oxygen-carrying capacity. Anemia is defined as reduced red-cell mass quantitated by hemoglobin (Hb) and hematocrit (Hct) levels and red blood cell (RBC) count. The differential diagnosis of the etiology and type of anemia is broad. The following factors must be considered when determining the severity and type of anemia:

• Chronicity is based on the clinical manifestations of the anemia (tachycardia, hypotension, dyspnea, fatigue, decreased level of consciousness, angina) and whether the patient is experiencing active blood loss and in need of acute repletion.

• Reticulocyte count (See a reticulocyte index calculator)

• • A high reticulocyte index indicates either blood loss or destruction of RBCs (see hemolytic anemia below) with marrow that is able to respond.

  • A low reticulocyte index is more common and requires evaluation of mean corpuscular volume (average volume of red cells).

• Mean corpuscular volume (MCV)

• Macrocytic anemia (MCV >100 femtoliters [fL]) can be either megaloblastic or nonmegaloblastic:

• • Megaloblastic anemia results from impaired DNA synthesis during RBC production due to vitamin B₁₂ deficiency, effects of certain drugs (e.g., zidovudine, methotrexate, hydroxyurea), and rarely from folate deficiency or inherited disorders.

  • Nonmegaloblastic anemia causes include alcohol use disorder, liver disease, hypothyroidism, and bone-marrow disorders (including myelodysplasia).

• Normocytic anemia (MCV ≥80 fL and ≤100 fL) can occur with increased reticulocytes due to blood loss or hemolysis. Low reticulocytes suggest anemia of chronic disease, iron deficiency combined with a macrocytic disorder, or a bone-marrow disorder (infiltration, red-cell aplasia, aplastic anemia). Early iron-deficiency anemia can be normocytic but is more likely to be microcytic as the severity worsens.

• Microcytic anemia (MCV <80 fL) is most often caused by iron deficiency or thalassemia. These two etiologies can be differentiated by the red-cell distribution width (RDW), which is a measure of anisocytosis. RDW is elevated in iron deficiency and is usually normal in thalassemia. Other causes of microcytic anemia to consider include chronic disease, lead poisoning, and sideroblastic anemia.

The following flowchart summarizes the basic approach to the workup of anemia:

(Source: Harrison’s Principles of Internal Medicine. 20th Edition. McGraw-Hill Education, Inc. 2020.)

Aplastic Anemia

Aplastic anemia is a form of hypoproliferative anemia often caused by autoimmune destruction of red-cell lineage cells with hypoplastic marrow. The cause of the damage can be acquired or inherited (see table below). Patients with aplastic anemia are at risk of developing acute myeloid leukemia (AML).

Diverse Pathophysiological Features That Lead to a Common Pathologic Process in Bone-Marrow Failure

Replacement of hematopoietic cells by fat is the distinctive pathologic feature of aplastic anemia. A hypocellular marrow can result from chemical or physical damage; the most frequent causes are iatrogenic, such as after cytotoxic chemotherapy or irradiation and exposure to benzene, usually in industry. In certain constitutional genetic defects that affect hematopoietic stem-cell function and the immune system, marrow failure and a hypocellular marrow are prominent. The disease immune aplastic anemia results from destruction, mainly by T cells, of hematopoietic stem cells and progenitor cells. Treatments are different for marrow damage, genetic defects that produce multiorgan effects, and the immune disease.
(Source: Aplastic Anemia. N Engl J Med 2018.)

A comprehensive review of aplastic anemia can be found here.

Hemolytic Anemia

Hemolytic anemia results from shortened survival of RBCs due to premature destruction. Causes are usually classified as acquired or hereditary.

(Source: Case 20-2013 — A 29-Year-Old Man with Anemia and Jaundice. N Engl J Med 2013.)

Evaluation of hemolytic anemia requires careful review of the patient’s history, physical examination, and the following key laboratory tests:

• complete blood count (CBC)

• red-cell indices

• peripheral-blood smear

• reticulocyte count (percent and absolute)

• liver function tests (including direct and indirect bilirubin)

• lactate dehydrogenase (LDH) and haptoglobin

• direct antiglobulin (Coombs) test (DAT)

Clinically significant acute hemolysis is essentially ruled out if the patient’s laboratory results do not show an appreciable elevation in the indirect bilirubin, aspartate transaminase (AST), and LDH level. Haptoglobin is a very sensitive marker for intravascular hemolysis, but even miniscule amounts of hemolysis usually depletes haptoglobin. Therefore, the degree of hemolysis cannot be determined from a low haptoglobin level alone.

If intravascular hemolysis is suspected, consider measuring free plasma/urinary hemoglobin or urinary hemosiderin as part of the workup.

Treatment of hemolytic anemias depends on severity and etiology and is often aimed at treating the underlying condition.

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