Anemia in Adults Overview

Anemia in Adults

• Evaluation of anemia in adults is a critical objective for healthcare professionals
• Objectives include reviewing cell lineage and function, metabolic and physiologic responses to anemia, types of anemia (microcytic, normocytic, macrocytic), and guidelines for hematology referral

Anemia as a Primary Diagnosis

• Annual office visits associated with anemia diagnosis: 2.8 billion
• Annual ED visits: 778,000
• Annual deaths: 5,380

Cell Lineage

• Erythrocytes develop from erythroblast precursors
• Platelets develop from megakaryocytes
• Leukocytes develop from myeloid stem cells (granulocytes and agranulocytes)
• The development of various types of leukocytes (eosinophils, basophils, neutrophils, monocytes, and lymphocytes) is detailed

Red Blood Cell Function

• RBCs transport oxygen from the lungs to the tissues
• RBCs transport carbon dioxide (CO2) from the tissues to the lungs
• RBCs carry electrolytes, hormones, vitamins, antibodies, heat, and immune cells

Normal Hematologic Parameters in Adults

• Hemoglobin levels differ between men and women
• Hematocrit levels differ between men and women
• RBC count, MCV, and MCHC values differ between men and women
• Range for each parameter is included

Anemia Definition

• Anemia is a reduction in the proportion of red blood cells
• Hemoglobin levels less than 13.5 g/dL in men, and less than 12.0 g/dL for women indicate anemia.

Microcytic Anemia

• This type of anemia is characterized by smaller RBCs
• RBCs often have decreased red coloration (hypochromic)
• Microcytosis is indicated by MCV <80 and hypochromic by MCHC<33

Causes of Microcytic Anemia

• Iron deficiency anemia
• Thalassemia
• Lead poisoning
• Sideroblastic anemia
• Inflammation
• Copper deficiency
• Hemolysis
• Anemia of chronic disease

Iron Deficiency Anemia (IDA)

• Iron is essential for blood production
• The body recycles and conserves iron
• IDA causes can be blood loss, malabsorption, or milk anemia (infants)
• Common symptoms include fatigue, headache, exercise intolerance, sore throat, shortness of breath, chest pain, pallor, and difficulty concentrating.
• Rare symptoms include pica, glossitis, cheilosis, koilonychia, and dysphagia

IDA Diagnosis

• CBC abnormalities (decreased Hgb/Hct), increased RDW, decreased MCV/MCH/MCHC
• Iron studies (decreased serum iron, increased TIBC, decreased % saturation)
• Decreased ferritin

IDA Treatment

• Consider oral ferrous sulfate
• IV iron
• Investigate the cause of iron deficiency

Thalassemia

• Group of genetic disorders involving abnormalities in alpha or beta globin chains, affecting red blood cell production
• Alpha Thalassemia Major: abnormality on chromosome 16, inability to produce hemoglobin a, resulting in severe anemia
• Alpha Thalassemia Minor: Loss of two alpha-globin genes, usually mild
• Beta Thalassemia Major: abnormality on chromosome 11, leading to a transfusion-dependent condition due to significant deficiency affecting red blood cell production
• Beta Thalassemia Intermedia/Minor: less severe than thalassemia major

Thalassemia Diagnosis

• CBC abnormalities, serum electrophoresis

Thalassemia Treatment

• PRBC transfusions, iron chelation therapy, folic acid supplementation, splenectomy, stem cell transplantation

Lead Poisoning

• Lead, a naturally occurring metal, binds to proteins and alters their function
• Lead competes with calcium for binding sites
• Lead causes impaired heme synthesis and increased rate of red blood cell destruction
• Sources like workplace exposure (paint, gasoline, bullets), drinking water, cosmetics, or herbal supplements can lead to lead exposure

Lead Poisoning Patient Presentation

• Symptoms may include abdominal pain, constipation, anorexia, joint pain, muscle aches, fatigue, sleep disturbances, or even severe central nervous system effects associated with high lead blood levels
• Anemia results from lead inhibiting enzymes critical to hemoglobin synthesis and causing red blood cell membrane fragility.

Lead Poisoning Diagnosis

• Elevated blood lead level (BLL)

Sideroblastic Anemia

• A group of blood disorders
• Defective maturation of developing erythroid cells; Iron accumulates in the mitochondria of RBC precursors which gives a ringed appearance to the nucleus.
• Causes can be congenital or acquired, including excess alcohol use, drugs (isoniazid, chloramphenicol, linezolid), copper deficiency, or hypothermia

Normocytic Anemia

• Circulating RBCs are normal in size, and color
• Normocytic: MCV 81-99, Normochromic: MCHC 33-37
• Causes: Acute anemia, Anemia of chronic disease/inflammation, Chronic renal insufficiency, Hypothyroidism, Bone marrow suppression, or Excessive alcohol

Acute Anemia

• A sudden drop in red blood cell count, resulting from acute blood loss, ruptured aneurysm, massive GI hemorrhage, ruptured ectopic pregnancy, or disseminated intravascular coagulation, or any cause of acute or chronic hemolysis

###Acute Anemia Patient Presentation

• Symptoms often include dizziness, shortness of breath, chest pain, pallor, symptoms specific to the source of blood loss

Acute Anemia Treatment

• Establish an accurate diagnosis of the source of blood loss
• Implement supportive care

Anemia of Chronic Disease (ACD)

• Immune-mediated dysregulation of iron homeostasis, with hepcidin produced by the liver as a major iron regulator
• Cytokines induce hepcidin and causes increased macrophage iron uptake and reduced RBC production
• ACD is associated with various underlying conditions, such as infections, inflammatory diseases, or malignancies

ACD Causes

• Inflammatory disease (such as systemic lupus erythematosus, vasculitis), malignancies, or chronic disorders (such as Chronic Obstructive Pulmonary Disease (COPD) or Chronic Heart Failure (CHF))

ACD Diagnosis

• CBC abnormalities (typically mild to moderate anemia), decreased retic count, normal/uniform RBCs, no evidence of hemolysis
• Iron studies (increased ferritin, decreased serum iron, and decreased TIBC)
• Inflammatory markers (increased ESR, elevated CRP)

ACD Patient Presentation

• Common symptoms include fatigue, shortness of breath and pallor
• Symptoms of underlying disease often mask those of anemia

ACD Treatment

• Prioritize addressing the underlying disorder.
• Concurrent causes of anemia are also investigated and treated as necessary

Anemia in Chronic Renal Insufficiency (CRI)

• Decreased production of red blood cells due to insufficient erythropoietin
• Red blood cells are coated with waste products which kidneys do not excrete.

CRI Anemia Patient Presentation

• Fatigue, weakness, dyspnea, pallor, headaches, and cold intolerance may be observed.

CRI Anemia Treatment

• ESO stimulation agent, dependent on severity and stage of CRI.

Bone Marrow Suppression: Aplastic Anemia

• Decreased bone marrow activity leading to decreased production of RBCs, neutrophils, and platelets
• Causes can include viruses, radiation, chemotherapy, exposure to toxic chemicals, medications or autoimmune disorders

Aplastic Anemia Patient Presentation

• Common symptoms include fatigue, shortness of breath, tachycardia, and frequent or prolonged infections
• Symptoms may include unexplained bruising, bleeding, skin rash, dizziness, and headache

Aplastic Anemia Treatment

• Identification of the cause and prompt treatment is crucial
• Supportive care may be needed

Anemia and Hypothyroidism

• Bone marrow depression and decreased erythropoietin may result from comorbid diseases and concomitant iron/B12/folate deficiencies

Hypothyroidism Anemia Patient Presentation

• Common symptoms include fatigue, exercise intolerance, weight gain, pallor, and unexplained bruising

Anemia and Hypothyroidism Treatment

• Address the underlying hypothyroidism
• Rule out or address concurrent causes

Causes of Macrocytic Anemia

• B12/folate deficiency
• Liver disease
• Excess alcohol
• Medications
• MDS

Macrocytic Anemia

• Large RBCs
• Macrocytic: MCV >100, Hyperchromic: MCHC <37

B12 Deficiency (Cobalamin)

Water-soluble vitamin essential for RBC formation, cell metabolism, nerve function, and DNA production

• Intrinsic factor produced by parietal cells in stomach

B12 Deficiency Causes

• Malabsorption (ileal dysfunction, transcobalamin deficiency), gastric resection, or presence of intrinsic factor autoantibodies

Folate Deficiency (Folate)

Essential for DNA synthesis and absorbed in the jejunum.

Folate Deficiency Causes

• Dietary restrictions
• Excessive alcohol use
• Increased requirements during pregnancy
• Medications that impair folate metabolism
• Loss during hemodialysis

B12/Folate Deficiency Anemia Patient Presentation

• Common symptoms include fatigue, SOB, GI complaints, glossitis, pallor or yellow/waxy appearance, and neurological signs like neuropathy

B12/Folate Deficiency Anemia Diagnosis

• Decreased B12 levels, increased MMA, decreased folate levels, Hgb/Hct decrease, increased RDW and increased MCV/MCH/MCHC.

B12/Folate Deficiency Anemia Treatment

• B12 supplementation (oral or intramuscular)
• Folic acid supplementation

Liver Disease and Excess Alcohol

• Alcohol is often implicated in the pathogenesis of chronic liver disease
• Excessive alcohol use or liver disease impacts red blood cell production.

Myelodysplastic Syndrome (MDS)

• Clonal hematopoietic stem cell disorder
• Cells in the bone marrow do not mature, leading to various degrees of bone marrow failure in presentation and many subtypes

Medications That Cause Macrocytic Anemia

• Several medications can cause macrocytic anemia - including antineoplastic agents and certain antibiotics and anti-inflammatories

"Shotgun" Approach to New Onset Anemia

• Initial labs for new onset anemia analysis include CBC, CMP, B12/folate, MMA, LDH, reticulocyte count, haptoglobin, indirect bilirubin, ESR, CRP, and erythropoietin.