Anemia is defined as a decrease in red blood cells (RBC), leading to less oxygen carrying capacity and delivery to end organs.

Normal hemoglobin in adult males is 14–18 g/dL and in adult females 12–16 g/dL.

Normal Hct in adult males is 40–52% and in adult females is 35–47%.

Anemia may be caused by disorders of bone marrow production, red cell maturation, increased destruction, and iron deficiency. Anemia is subclassified into microcytic, normocytic, and macrocytic (Table 16.1). Clinical symptoms of anemia are fatigue and decreased exercise tolerance.

Ferritin: marker of iron stores (also an acute phase reactant).

TIBC (total iron binding capacity): indirect measure of transferrin saturation levels.

Transferrin: protein which transports iron within the blood.

Reticulocyte: immature erythrocyte (new RBC that is usually 1–1.5 days old).

Reticulocyte count: fraction of RBCs consisting of reticulocytes that indirectly indicates the bone marrow activity of the erythrocyte line; expressed as a percentage; normal value 1%.

Etiology is the decreased synthesis of heme. Iron deficiency anemia is the most common cause of anemia in the United States of all ages and both genders.

Increase in RBC size, commonly caused by either Vitamin B₁₂ or folate deficiency.

Most common cause of Vitamin B₁₂ deficiency is pernicious anemia (decrease in intrinsic factor due to autoimmune destruction of gastric parietal cells).

Most common cause of folate deficiency is alcoholism.

Vitamin B₁₂ is found in meat, eggs, and dairy products.

Folate is found in green vegetables and animal proteins.

Characteristic difference between Vitamin B₁₂ and folate deficiency: neurologic disease (seen in Vit B₁₂ deficiency but not folate deficiency).

Lab findings in both: decreased Vitamin B12 or folate, increased homocysteine, pancytopenia and hypersegmented PMNs (PMN with more than five lobes).

Other less common causes of macrocytic anemia: chemotherapy, hemolysis, liver disease, myelodysplastic syndromes, hypothyroidism

Most common anemia in hospitalized patients.

Common causes: chronic inflammation (rheumatoid arthritis, tuberculosis), alcoholism, malignancy.

Caused by decreased synthesis of heme.

Lab findings: decreased iron, TIBC and iron saturation; increased ferritin

ACD is microcytic 10–30% of the time.

This may occur due to external causes (trauma, peptic ulcers) or internal causes (ruptured abdominal aortic aneurysm) and results in signs of volume depletion such as hypotension and tachycardia.

Aplastic anemia is a bone marrow disorder.

There are many causes of aplastic anemia and morbidity is high as only 10% of cases make a full recovery.

In general, there is a destruction of multipotent myeloid stem cells with inadequate production of differentiated cell lines.

The majority of cases are idiopathic; the most common known causes are drugs, commonly chemotherapy drugs (alkylating agents, antimetabolites).

Other causes include chemical toxins (insecticides, benzene, parathion), viral infection (EBV, CMV, parvovirus B19, non-A and non-B hepatitis), and whole body radiation therapy.

Lab findings: pancytopenia, low reticulocyte count (hallmark), hypocellular bone marrow.

Clinical findings: fatigue, malaise, pallor, mucosal bleeding, petechia, infection.

Treatment: withdrawal of offending agent, RBC and platelet transfusion, bone marrow transplant.

Extravascular hemolysis due to the excessive destruction of RBCs by the liver and the spleen by autoantibodies against foreign RBC antigens.

Warm type (70%) associated with IgG antibodies.

Cold type (30%) associated with IgM antibodies.

SLE (systemic lupus erythematosus) is the most common cause of AIHA.

The direct antihuman globulin test (DAT or Coombs test) is the most important marker for AIHA.

An autosomal dominant RBC membrane defect.

Intrinsic membrane defect of ankyrin or spectrin that causes extravascular hemolysis due to loss of RBC membrane and formation of spherocytes (small, round RBCs with no central pallor).

Lab findings: increase in MCHC, RDW, RBC osmotic fragility (diagnostic for hereditary spherocytosis); normocytic anemia with spherocytes.

Clinical findings: jaundice (due to increased unconjugated bilirubin), increased incidence of gallstones (due to increased conjugated bilirubin), splenomegaly.

Treatment: splenectomy (Howell-Jolly bodies present after splenectomy).

Autosomal recessive disorder – intrinsic defect causing a hemoglobinopathy that causes extravascular hemolysis of sickled RBCs.

Most common hemoglobinopathy in patients of African descent.

SCA is a missense point mutation where valine is substituted for glutamic acid at the sixth position of the beta-globin chain of Hb; this mutation causes sickling of RBCs.

Key pathologic processes in SCA: severe hemolytic anemia and vaso-occlusive crises (Table 16.2). Management is based on symptoms. Fluid hydration, pain management (PO or IV), oxygen therapy (O₂ < 92%), and steroids.

Treatment: hydroxyurea (increases HbF which prevents sickling) and bone marrow transplant.

Leukemia is a disease of the mesenchymal cells of the blood in which there is an abnormal proliferation or an increased lifespan of myeloid or lymphoid cells.

In the simplest form, all blood cells originate from a pluripotent stem cell, which can then differentiate into a myeloid (bone marrow) precursor or lymphoid (lymphatic tissue) precursor. Therefore, leukemias are classified as either myeloid or lymphoid and then subclassified as acute or chronic depending on its characteristics.

Myeloid cells form – erythrocytes, polymorphonuclear lymphocytes (PMNs), macrophages/monocytes, platelets, eosinophils, and basophils.

Lymphoid cells form – plasma cells (B cells), T cells, or natural killer (NK) cells.

Pathogenesis of leukemias – block in stem cell differentiation leading to proliferation of neoplastic leukemic cells.

In myeloid leukemias, there is a somatic gene mutation resulting in the loss of control at one level of production which then leads to increased, decreased, or normal production of the cells of that line.

The production of the other cells in that cell line is then indirectly disturbed. This disturbance, which can be quantitative or qualitative, causes crowding or suppression within the bone marrow.

Therefore a common characteristic of myeloid leukemias is their infiltration of the bone marrow with a decreased number of normal myeloid cells of poor function.