Question

Description

Homer Simpson, a 45 year old morbidly obese male has been admitted for anemia. He has a history of HT and chronic anemia.

Answer 1

Obesity is characterized by chronic, low‐grade, systemic inflammation, which, in turn, has been associated with anemia of chronic disease. Anemia is described as a reduction in the proportion of the red blood cells. Anemia is not a diagnosis, but a presentation of an underlying condition. Whether or not a patient becomes symptomatic depends on the etiology of anemia, the acuity of onset, and the presence of other commodities.

Etiology

The etiology of anemia depends on whether the anemia is hypo-proliferative (i.e., corrected reticulocyte count <2%) or hyperproliferative (i.e., corrected reticulocyte count >2%).

Hypoproliferative anemias are further divided by the mean corpuscular volume into microcytic anemia (MCV<80 fl), normocytic anemia (MCV 80-100 fl), and macrocytic anemia (MCV>100 fl).

1) Hypoproliferative Microcytic Anemia (MCV<80 fl)

• Iron deficiency anemia

• Anemia of chronic disease (AOCD)

• Sideroblastic anemia (may be associated with an elevated MCV as well, resulting in a dimorphic cell population)

• Thalassemia

• Lead poisoning

2) Hypoproliferative Normocytic Anemia (MCV 80-100 fL)

• Anemia of chronic disease (AOCD)

• Renal failure

• Aplastic anemia

• Pure red cell aplasia

• Myelofibrosis or myelophthisic processes

• Multiple myeloma

Macrocytic anemia can be caused by either a hypoproliferative disorder, hemolysis, or both. Thus, it is important to calculate the corrected reticulocyte count when evaluating a patient with macrocytic anemia. In hypoproliferative macrocytic anemia, the corrected reticulocyte count is <2%, and the MCV is greater than 100 fl. But, if the reticulocyte count is > 2%, hemolytic anemia should be considered.

3) Hypoproliferative Macrocytic Anemia (MCV>100 fL)

• Alcohol

• Liver disease

• Hypothyroidism

• Folate and Vitamin B12 deficiency

• Myelodysplastic syndrome (MDS)

  • Refractory anemia (RA)

  • Refractory anemia with ringed sideroblasts (RA-RS)

  • Refractory anemia with excess blasts (RA-EB)

  • Refractory anemia with excess blasts in transformation

  • Chronic myelomonocytic leukemia (CMML)

• Drug-induced

  • Diuretics

  • Chemotherapeutic agents

  • Hypoglycemic agents

  • Antiretroviral agents

  • Antimicrobials

  • Anticonvulsants

4) Hemolytic anemia: hemolytic anemia (HA) is divided into extravascular and intravascular causes.

• Extravascular hemolysis: red cells are prematurely removed from the circulation by the liver and spleen. This accounts for a majority of cases of HA

  • Hemoglobinopathies (sickle cell, thalassemias)

  • Enzyemopathies (G6PD deficiency, pyruvate kinase deficiency)

  • Membrane defects (hereditary spherocytosis, hereditary elliptocytosis)

  • Drug-induced

• Intravascular hemolysis: red cells lyse within the circulation, and is less common.

  • PNH

  • AIHA

  • Transfusion reactions

  • MAHA

  • DIC

  • Infections

  • Snake bites/venom

Patient, Mr Homer Simpson, a 45 year old morbidly obese male has been admitted for anemia has a history of HT and chronic anemia

The anemia of chronic disease is multifactorial anemia. Diagnosis generally requires the presence of a chronic inflammatory condition, such as infection, autoimmune disease, kidney disease, or cancer. It is characterized by a microcytic or normocytic anemia and low reticulocyte count. Values for serum iron and transferrin are typically low to normal, while the serum ferritin value can be normal or elevated. The treatment is to reverse the underlying disorder and in some cases, to give erythropoietin.

Etiology

The anemia of chronic disease occurs as part of a chronic inflammatory disorder, most often chronic infection, an autoimmune disease (especially rheumatoid arthritis), kidney disease, or cancer; however, the same process appears to begin acutely during virtually any infection or inflammation, including trauma or post-surgery. (See also Anemia of Renal Disease.)

Three pathophysiologic mechanisms have been identified:

• Slightly shortened RBC survival, thought to be due to increased hemophagocytosis by macrophages, occurs in patients with inflammatory diseases.

• Erythropoiesis is impaired because of decreases in both erythropoietin (EPO) production and marrow responsiveness to EPO.

• Iron metabolism is altered due to an increase in hepcidin, which inhibits iron absorption and recycling, leading to iron sequestration.

Reticuloendothelial cells retain iron from senescent RBCs, making iron unavailable for hemoglobin (Hb) synthesis. There is thus a failure to compensate for the anemia with increased RBC production. Macrophage-derived cytokines (eg, interleukin-1-beta, tumor necrosis factor-alpha, interferon-beta) in patients with infections, inflammatory states, and cancer contribute to the decrease in EPO production and the impaired iron metabolism by increasing hepatic hepcidin synthesis.

Diagnosis

• Symptoms and signs of the underlying disorder

• Complete blood count (CBC) and serum iron, ferritin, transferrin, and reticulocyte count

Clinical findings in the anemia of chronic disease are usually those of the underlying disorder (infection, inflammation, cancer). The anemia of chronic disease should be suspected in patients with microcytic or normocytic anemia who also have chronic illness, infection, inflammation, or cancer. If anemia of chronic disease is suspected, serum iron, transferrin, reticulocyte count and serum ferritin are measured. Hb usually is > 8 g/dL (> 80 g/L) unless an additional mechanism contributes to anemia, such as concomitant iron deficiency (see table Differential Diagnosis of Microcytic Anemia Due to Decreased RBC Production) or iatrogenic phlebotomy.

A serum ferritin level of < 100 ng/mL (< 224.7 pmol/L) in a patient with inflammation (< 200 ng/mL [< 449.4 pmol/L] in patients with chronic kidney disease) suggests that iron deficiency may be superimposed on anemia of chronic disease, because serum ferritin is usually elevated as an acute-phase reactant.

Treatment

• Treatment of underlying disorder

• Sometimes recombinant erythropoietin (EPO) and iron supplements

Treatment of the anemia of chronic disease requires treating the underlying disorder. Because the anemia is generally mild, transfusions usually are not required.

Recombinant EPO has been shown to be most useful in patients with chronic kidney disease. Because both reduced production of and marrow resistance to EPO occur, the recombinant EPO dose may need to be 150 to 300 units/kg subcutaneously 3 times a week. A good response is likely if, after 2 weeks of therapy, the Hb has increased > 0.5 g/dL (> 5 g/L) and the serum ferritin is < 400 ng/mL (< 898.8 pmol/L).

Iron supplements are required to ensure an adequate response to recombinant EPO. However, careful monitoring of Hb response is needed because adverse effects (eg, venous thromboembolism, myocardial infarction, death) may occur when Hb rises to > 12 g/dL (> 120 g/L).

Key Points

• Almost any chronic infection, inflammation, or cancer can cause anemia; hemoglobin usually is > 8 g/dL (> 80 g/L) unless an additional mechanism contributes.

• Multiple factors are involved, including shortened red blood cell survival, impaired erythropoiesis, and impaired iron metabolism.

• Anemia is initially normocytic and then can become microcytic.

• Serum iron and transferrin are typically decreased, while ferritin is normal to increased.

• Treat the underlying disorder and consider recombinant erythropoietin.