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Department of Anesthesiology - Residents Section

Anesthesia Knowledge - Hemotologic Disorders and Anesthesia

Anemia

    ACUTE:
  • Blood loss
  • hemolysis
    CRONIC:
  • Nutritional/consumptive:
    • Iron deficiency anemia
    • Vitamin B 12 deficiency
    • Folate deficiency
  • Hemoglobinopathies:
    • Sickle cell disease
    • Thallasemia
  • Hemolytic anemias:
    • G6PDH-deficiency
    • Immune mediated (cold/warm agglutinine)
    • Drug-induced autoimmune
    • Pyruvate kinase deficiency
    • Spherocytosis

Nutritional/consumptive

  • iron deficiency anemia (nutritional deficiency exceedingly rare, usually chronic blood loss, chronic infection, malignancy)
  • Vitamin B12 deficiency (typically megaloblastic anemia in atrophic gastritis, can be associated with neuropathy: symmetric loss of proprioception in lower extremities - consider before administering regional anesthesia)
  • Folate deficiency (alcoholism, pregnancy, malabsorption, not associated with neuropathy)
  • Chronic blood loss may lead to extreme anemia, the other forms of nutritional or consumptive anemia usually present as a moderate degree anemia thus the main anesthetic consideration is the maintenance of sufficient oxygen carrying capacity
  • Nitrous oxide inhibits B12-dependent methionin-synthetase (needed for DNA-synthesis) prolonged exposure can cause a picture similar to B 12 - deficiency) however, there is no good evidence that there is significant effects from clinical use

Hemoglobinopathies

Sickle cell disorder

Underlying genetic defect: one aminoacid exchanged in the beta-chain of the hemoglobin Molecule (remember: 4 different globin-chains: alpha, beta, delta, gamma, normal adult Hemoglobin comprises of 2 alpha and 2 beta chains, HbF: 2 alpha, 2 gamma)

Pathophysiology: deoxygenation of HbS causes it to assume a gel-type consistency which leads to sickling of the erythrocyte if there is enough HbS (dependent on the genetic make up of the patient, see below), sickling and subsequent hemolysis (> anemia) starts at PO2 50 and becomes pronounced at PO2 20, local factors are important: systemic PO2 May be normal but regional perfusion may lead to locally low PO2, acidosis aggravates tendency to sickling, once sickling is initiated a vicious cycle begins with vasoocclusion leading to more Deoxygenation and so forth - prevention of crisis is easier than treating it.

Forms: several hundred hemoglobinopathies, 3 most common forms are variants of sickle cell disorder SA: sickle cell trait (heterozygote), 8-10% of African-Americans, 10-40% of Hb is HbS, under physiologic conditions not enough to cause the erythrocyte To sickle, however under extreme circumstances these patients are at risk for sickling, no overt anemia SC: HbS and HbC (another abnormal type of Hb): high levels of HbS but HbC is somewhat protective, patients less likely to have crisis, degree of anemia usually not as severe (Hb 10-11 g/dl) SS: homozygote form, 1:400 amongst African-Americans, 70-98% HbS, life expectancy 40-50 years, complications: auto- splencectomy by multiple infarctions at Age 6 with increased risk for infections, cholelithiasis, CNS-dysfunction due to microinfarction, renal insufficiency, priapism, Acute chest syndrome (crisis with lung infarction, often requires exchange transfusion)

Perioperative anesthetic considerations: PREVENT SICKLING
  • avoid excessive premedication with ventilatory depression (> hypoxemia)
  • adequate hydration and anticipation of intraoperative fluid loss (prevent increases of blood viscosity by hemoconcentration)
  • maintain normothermia (hypothermia actually prevents sickling, only because it causes vasoconstriction it has to be avoided, do not induce hyperthermia as it promotes sickling)
  • tourniquet only if critical for the success of the operation
  • transfuse to reduce fraction of HbS thus reducing the likelihood of sickling, usually not to increase Hb, SS-patients are often adapted to Hct around 20, decision should be made dependent on patients general status and planned procedure
  • volatile anesthetics promote sickling in vitro, in practice maintenance of perfusion and oxygenation is more important
  • all precautions should also be applied to the patient with sickle cell trait

Thallasemia

Underlying defect: failure to produce enough alpha- or beta-globin (alpha-, beta-thallasemia), to compensate abnormal globin- chains (delta, Gamma) are produced, thus abnormal hemoglobin with a tendency for hemolysis is comprised, homozygote patients (Thallasemia major, Cooley-anemia) usually do not reach adulthood, anesthetic considerations include extramedullary hematopoiesis (facial bones: difficult airway, spine: extradural cord compression), iron toxicity from multiple transfusions (cardiomyopathy, hepatic dysfunction) heterozygote patients (more common: beta-thallasemia) have often only mild anemia, prevalent in the Mediterranean, Middle East, India, South East Asia

Hemolytic Anemias

G6PDH-deficiency: most common enzyme-defect: 400 million people afflicted worldwide, 1% of African-American population X-chromosomal - only men affected Underlying defect: enzyme-defect leads to insufficient production of NADPH, thus leaving the erythrocyte without enough reducing agent to fight oxidative stress, subsequent hemolysis usually self-limited because only erythrocytes toward the end of their life-span (120 days) are vulnerable, crisis begins 2-5 days after inducing drug administration (not immediately perioperatively)

Inducing drugs: antibiotics (Penicillin, Chloramphenicol, Sulfonamides), INH, Antimalaria drugs, Methylen blue

Anesthetic considerations
  • avoid inducing drugs including methylen blue
  • patients cannot reduce methemoglobin: prilocain and nitroprusside are contraindicated (one of the treatments for cyanide- toxicity from nitroprusside is induction of methemoglobinemia by sodium nitrate as methemoglobin is able to bind cyanide and reduce its cellular toxicity)

Immune hemolytic anemia

Autoimmune hemolysis: cold agglutinine: associated with autoimmune diseases, neoplasias (lymphoma), auto-antibodies cause hemolysis when the temperature falls below a certain threshold

Anesthetic considerations:
  • Meticulously avoid hypothermia
  • Remove antibodies by plasmapheresis if the patient has to undergo prolonged procedures or CPB

Drug induced hemolytic anemia: drugs causing alterations of red cell membrane rendering it subject to immunologic reaction with subsequent hemolysis, drugs that can cause immune-hemolytic anemia: methyl-dopa, Penicillin, INH, sulfonamides, hydralazine, HCTZ

Alloimmune hemolysis: Rh-incompatibility: Rh-positive fetus in Rh-negative mother who has previously been exposed to Rh- positive blood, can cause fetal hemolysis only because antibodies cross the placenta (as opposed to ABO-antibodies which cannot cross the placenta)

Pyruvate Kinase Deficiency

Impaired ATP-synthesis in the red blood cell with subsequent membrane changes leading to chronic hemolysis, mild to more severe forms exist

Spherocytosis

Membrane defect leads round shaped red cells and increased vulnerability to hemolysis, often not severe, most of these patients undergo splenectomy

Summary:

  • Acute anemia is typically caused by excessive blood loss, the degree of anemia can reach from mild to most severe, patients are not adapted, main concern is maintenance of oxygen carrying capacity
  • Chronic anemia is most commonly caused by nutritional deficiencies, chronic disease or chronic blood loss, nutritional deficiencies and chronic diseases often cause mild to moderate degrees of anemia, chronic blood loss (bleeding ulcer, gynecological blood loss) can also cause most severe anemia, these patients are more or less adapted to anemia, nonetheless oxygen carrying capacity is the main concern especially if there are other conditions present
  • Rarer causes of chronic anemia are hemoglobinopathies, enzyme deficiencies and membrane defects, besides the usually marked anemia there are numerous concerns in the patient with SS-disease (hemoglobinopathy), they are directed towards prevention of sickle crisis the patient with G6PDH-deficiency will most likely not undergo surgery while having an acute crisis, thus main concern is avoiding the agents that can exacerbate the condition
  • Immune mediated hemolytic anemia can be caused by auto-antibodies, certain drugs and blood transfusion, main concern is to keep the possibility in mind