In an otherwise healthy person, symptoms do not develop from anemia until the hemoglobin level decreases below 7 g/dL. (Physiologic compensations include increased blood volume and cardiac output and decreased blood viscosity.) There is no universally accepted hemoglobin level that mandates blood transfusion. The patient's physiologic status and coexisting diseases must be factored into this highly subjective decision (Table 23-13: Types of Anemia).

1. Nutritional Deficiency Anemias
   1. Iron deficiency anemia may be an absolute deficiency caused by decreased oral intake of iron or a relative deficiency of iron caused by a rapid turnover of red blood cells (RBCs) (chronic blood loss, hemolysis). Severe iron deficiency produces microcytic anemia and may result in thrombocytopenia and neurologic abnormalities.
   2. Vitamin ₁₂ deficiency results in megaloblastic anemia and nervous system dysfunction (peripheral neuropathy secondary to degeneration of the lateral and posterior columns of the spinal cord manifesting as symmetric paresthesias with loss of proprioception and vibratory sensation, especially in the lower extremities). Prolonged exposure to nitrous oxide (inactivates the vitamin B₁₂ component of methionine synthetase) results in megaloblastic anemia and neurologic changes similar to those that occur in pernicious anemia.
   3. Folic acid deficiency (because of alcoholism, pregnancy, or malabsorption [phenytoin, methotrexate]) results in megaloblastic anemia, but peripheral neuropathy is not as common as with vitamin B₁₂ deficiency.
2. Hemolytic anemias reflect premature destruction (before 120 days) of RBCs.
3. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. It affects 400 million people worldwide and may confer malarial resistance.
   1. A deficiency of G6PD results in decreased levels of glutathione when erythrocytes are exposed to oxidants. This increases the rigidity of the RBC membrane (hemolysis) and accelerates clearance of erythrocytes from the circulation.
   2. A number of drugs may enhance the destruction of erythrocytes in patients with G6PD deficiency (Table 23-14: Drugs that Produce Hemolysis in Patients with Glucose-6-Phosphate Dehydrogenase Deficiency). Characteristically, the hemolytic episode begins 2 to 5 days after drug administration.
   3. Patients with G6PD deficiency are unable to reduce methemoglobin produced by sodium nitrate, so sodium nitroprusside should not be administered in these patients.
   4. Anesthetic drugs have not been implicated as hemolytic agents, but early postoperative evidence of hemolysis might suggest G6PD.
4. Hemoglobinopathies are diseases caused by genetic errors in hemoglobin synthesis and production. (These diseases convey survival protection in malaria-endemic areas.)
   1. Sickle cell disease (SCD) results from mutation of chromosome 11, which causes substitution of valine for glutamic acid. Whereas persons heterozygous for the sickle cell gene (HbSA) are usually asymptomatic, homozygous individuals (HbSS) have SCD.
   2. Clinical Manifestations (Table 23-15: Clinical Manifestations of Sickle Cell Disease). Acute chest syndrome (dyspnea, wheezing, chest pain, hypoxemia, pulmonary infiltrates) represents the single greatest threat to patients with SCD.
   3. Treatment of SCD is supportive and directed at early treatment of complications.
   4. Management of Anesthesia. Preparation of patients with SCD for surgery should be done in close collaboration with the SCD specialty service that provides the patient's routine care. Prevention of conditions that favor sickling is the basis of perioperative management.
      1. Supplemental oxygen is recommended during and after regional and general anesthesia.
      2. Circulatory stasis can be prevented with hydration and anticipation of intraoperative blood loss in order to avoid acute hypovolemia.
      3. Normothermia is desirable because hyperthermia increases the rate of gel formation, and hypothermia produces vasoconstriction that impairs organ blood flow.
      4. The use of a tourniquet or preoperative transfusion is controversial.
      5. Hemoglobin and hematocrit should be measured preoperatively and adequate oxygen-carrying capacity maintained by transfusion to keep the hematocrit near 30%.
      6. Drugs commonly used for anesthesia do not have significant effects on the sickling process, assuming arterial hypoxemia, vascular stasis, and reduced cardiac output are avoided. Regional anesthesia has been successfully used for surgery, labor and delivery, and pain management.

Rare Coexisting Diseases

1. Musculoskeletal Diseases
2. The Myotonias
3. Familial Periodic Paralysis
4. Myasthenia Gravis
5. Guillain-Barré Syndrome (Polyaradiculoneuritis)
6. Central Nervous System Diseases
7. Inherited Disorders
8. Anemias
9. Collagen Vascular Diseases
10. Skin Disorders