Patients undergoing some elective surgical procedures with a high probability for transfusion can donate their own blood for use during that surgery. Collection is usually started 4 to 5 weeks prior to the procedure. The patient is usually allowed to donate a unit as long as the hematocrit is at least 34% or hemoglobin at least 11 g/dL. A minimum of 72 h is required between donations to ensure plasma volume has returned to normal. With iron supplementation and erythropoietin therapy, at least 3 or 4 units can usually be collected prior to operation. Autologous blood transfusions probably do not adversely affect survival in patients undergoing operations for cancer. Although autologous transfusions likely reduce the risk of infection and transfusion reactions, they are not risk-free. Risks include those of immunological reactions due to clerical errors in collection, labeling, and administration; bacterial contamination; and improper storage. Allergic reactions can occur due to allergens (eg, ethylene oxide) that dissolve into the blood from collection and storage equipment.
CASE DISCUSSION A Patient with Sickle Cell Disease
A 24-year-old woman with a history of sickle cell anemia presents with abdominal pain and is scheduled for cholecystectomy. What is sickle cell anemia?
Sickle cell anemia is a hereditary hemolytic anemia resulting from the formation of an abnormal hemoglobin (HbS). HbS differs structurally from the normal adult hemoglobin (HbA) only in the substitution of valine for glutamic acid at the sixth position of the β chain. Functionally, sickle hemoglobin has less affinity for oxygen (P50 = 31 mm Hg) as well as less solubility. Upon deoxygenation, HbS readily polymerizes and precipitates inside RBCs, causing them to sickle. Sickle cell patients produce variable amounts (2–20%) of fetal hemoglobin (HbF), and it is likely that cells with large amounts of HbF are somewhat protected from sickling. The continuous destruction of irreversibly sickled cells leads to anemia, and hematocrits are typically 18% to 30% due to the extravascular hemolysis. RBC survival is reduced to 10 to 15 days, compared with up to 120 days in normal individuals. What is the difference between sickle cell anemia and sickle cell trait?
When the genetic defect for adult hemoglobin is present on both the maternally and paternally derived chromosomes (No. 11), the patient is homozygous for HbS and has sickle cell anemia (HbSS). When only one chromosome has the sickle gene, the patient is heterozygous and has sickle cell trait (HbAS). Patients with the sickle trait produce variable amounts of HbA (55–60%) and HbS (35–40%). Unlike those with HbSS, they are generally not anemic, are asymptomatic, and have a normal life span. Sickling occurs only under extreme hypoxemia or in low-flow states. Sickling is particularly apt to occur in the renal medulla; indeed, many patients with the sickle trait have impaired renal concentrating ability. Patients with HbAS may have renal medullary, splenic, and pulmonary infarcts.
Sickle cell anemia is primarily a disease of individuals of Central African ancestry. Approximately 0.2% to 0.5% of African Americans are homozygous for the sickle gene and approximately 8% to 10% are heterozygous. Sickle cell anemia is found less commonly in patients of Mediterranean ancestry. What is the pathophysiology?
Conditions favoring the formation of deoxyhemoglobin (eg, hypoxemia, acidosis, intracellular hypertonicity or dehydration, increased 2,3-DPG levels, or increased temperature) can precipitate sickling in patients with HbSS. Hypothermia may also be detrimental because of associated vasoconstriction (see below). Intracellular polymerization of HbS distorts red cells, makes them less pliable and more “sticky,” increasing blood viscosity. Sickling may initially be reversible but eventually becomes irreversible in some RBCs. Formation of red cell aggregates in capillaries can obstruct tissue microcirculation, and a vicious cycle is established in which circulatory stasis leads to localized hypoxia, which, in turn, causes more sickling. With what symptoms do patients with sickle cell anemia usually present?
Patients with HbSS generally first develop symptoms in infancy, when levels of HbF decline. The disease is characterized by both acute episodic crises and chronic and progressive features (Table 51–7). Children display retarded growth and have recurrent infections. Recurrent splenic infarction leads to splenic atrophy and functional asplenism by adolescence. Patients usually die from recurrent infections or kidney failure. Chronic abdominal, bone, and joint pain is typical, often complicated by repeated, acutely painful sickling crises, and patients frequently require chronic opioid therapy. Because of issues related to analgesic tolerance and addiction, these patients often benefit from management by pain specialists. Crises are often precipitated by infection, cold weather, dehydration, or other forms of stress. Crises may be divided into three types:
How is sickle cell anemia diagnosed?
Vasoocclusive crises: Depending on the vessels involved, these acute episodes can result in micro- or macroinfarctions. Most painful crises are thought to be due to microinfarcts in various tissues. Clinically, they present as acute abdominal, chest, back, or joint pain. Differentiation between surgical and nonsurgical causes of abdominal pain is difficult. Most patients form pigmented gallstones by adulthood, and many present with acute cholecystitis. Vasoocclusive phenomena in larger vessels can produce thromboses resulting in splenic, cerebral, pulmonary, hepatic, renal, and, less commonly, myocardial infarctions.
Aplastic crisis: Profound anemia (Hb 2–3 g/dL) can rapidly occur when red cell production in the bone marrow is exhausted or suppressed. Infections and folate deficiency may play a major role. Some patients also develop leukopenia.
Splenic sequestration crisis: Sudden pooling of blood in the spleen can occur in infants and young children and can cause life-threatening hypotension. The mechanism is thought to be partial or complete occlusion of venous drainage from the spleen.
RBCs from patients with sickle cell anemia readily sickle following addition of an oxygen-consuming reagent (metabisulfite) or a hypertonic ionic solution (solubility test). Confirmation requires hemoglobin electrophoresis. What would be the best way to prepare patients with sickle cell anemia for surgery?
Optimal preoperative preparation includes the following: patients should be well hydrated, infections should be controlled, and the hemoglobin concentration should be at an acceptable level. Preoperative transfusion must be individualized for the patient and to the surgical procedure. Partial exchange transfusions before major surgical procedures are usually advocated, which decrease blood viscosity, increase blood oxygen-carrying capacity, and decrease likelihood of sickling. The goal of such transfusions is generally to achieve a hematocrit of 35% to 40% with 40% to 50% normal hemoglobin (HbA). Chronic management of sickle cell disease has been revolutionized by the introduction of hydroxyurea. Are there any special intraoperative considerations?
Conditions that might promote hemoglobin desaturation or low-flow states should be avoided. Every effort must be made to avoid hypothermia, hyperthermia, acidosis, and even mild degrees of hypoxemia, hypotension, or hypovolemia, and generous hydration and a relatively high (>50%) inspired oxygen tension are important. The principal compensatory mechanism for impaired tissue oxygen delivery in these patients is increased cardiac output, which should be maintained intraoperatively. GDFT may be useful. Mild alkalosis may help avoid sickling, but even moderate degrees of respiratory alkalosis may have an adverse effect on cerebral blood flow. Tourniquet use, other than brief, should be avoided. Are there any special postoperative considerations?
Most perioperative deaths occur in the postoperative period, and the same management principles applied intraoperatively should be utilized following surgery. Hypoxemia and pulmonary complications (particularly acute chest syndrome) are major risk factors. Supplemental oxygen; optimal hemodynamic, fluid, and pain and symptom management; and pulmonary physiotherapy with early mobilization all help minimize the risk of these complications. What is the pathophysiology of thalassemia?
Thalassemia is a hereditary defect in the production of one or more of the normal subunits of hemoglobin. Patients with thalassemia may be able to produce normal HbA but have reduced amounts of α- or β-chain production; the severity of this defect depends on the subunit affected and the degree to which hemoglobin production is affected. Symptoms range from absent to severe. Patients with α-thalassemia produce reduced amounts of the α subunit, whereas patients with β-thalassemia produce reduced amounts of the β subunit. The formation of hemoglobins with abnormal subunit composition can alter the red cell membrane and lead to variable degrees of hemolysis as well as ineffective hematopoiesis. The latter can result in hypertrophy of the bone marrow and often an abnormal skeleton. Maxillary hypertrophy may make tracheal intubation difficult. Thalassemias are most common in patients of Southeast Asian, African, Mediterranean, and Indian ancestry. What is the significance of sickle cell anemia and thalassemia in the same patient?
The combination of HbS and thalassemia, most commonly sickle β-thalassemia, has a variable and unpredictable effect on disease severity. What is hemoglobin C disease?
Substitution of lysine for glutamic acid at position 6 on the β subunit results in hemoglobin C (HbC). Approximately 0.05% of African Americans carry the gene for HbC. Patients homozygous for HbC generally have only a mild hemolytic anemia and splenomegaly and rarely develop significant complications. The tendency for HbC to crystallize in hypertonic environments is probably responsible for the hemolysis and characteristically produces target cells on the peripheral blood smear. What is the significance of the genotype HbSC?
Nearly 0.1% of African Americans are simultaneously heterozygous for both HbS and HbC (HbSC). These patients generally have a mild to moderate hemolytic anemia. Some patients occasionally have painful crises, splenic infarcts, and hepatic dysfunction. Eye manifestations similar to those associated with HbSS disease are particularly prominent. Women with HbSC have a high rate of complications during the third trimester of pregnancy and delivery. What is hemoglobin E?
Hemoglobin E is the result of a single substitution on the β chain and is the second most common hemoglobin variant worldwide. It is most often encountered in patients from Southeast Asia. Although oxygen-binding affinity is normal, the substitution impairs production of β chains (similar to β-thalassemia). Homozygous patients have marked microcytosis and prominent target cells, but are not usually anemic and lack any other manifestations. What is the hematologic significance of glucose-6-phosphate dehydrogenase (G6PD) deficiency?
RBCs are normally well-protected against oxidizing agents. The sulfhydryl groups on hemoglobin are protected by reduced glutathione. The latter is regenerated by NADPH (reduced nicotinamide adenine dinucleotide phosphate), which itself is regenerated by glucose metabolism in the hexose monophosphate shunt. G6PD is a critical enzyme in this pathway. A defect in this pathway results in an inadequate amount of reduced glutathione, which can potentially result in the oxidation and precipitation of hemoglobin in red cells (seen as Heinz bodies) and hemolysis.
Abnormalities in G6PD are relatively common, with over 400 variants described. Clinical manifestations are variable, depending on the functional significance of the enzyme abnormality. Up to 15% of African American males have the common, clinically significant, A− variant. A second variant is common in individuals of eastern Mediterranean ancestry, and a third in individuals of Chinese ancestry. Because the locus for the enzyme is on the X chromosome, abnormalities are X-linked traits, with males being primarily affected. G6PD activity decreases as RBCs age; therefore, aging red cells are most susceptible to oxidation. This decay is markedly accelerated in patients with the Mediterranean variant, but only moderately so in patients with the A− variant.
Most patients with G6PD deficiency are not anemic but can develop hemolysis following stresses such as viral and bacterial infections, or after administration of certain drugs (Table 51–8). Hemolytic episodes can be precipitated by metabolic acidosis (eg, diabetic ketoacidosis) and may present with hemoglobinuria and hypotension. Such episodes are generally self-limited because only the older population of RBCs is destroyed. Mediterranean variants may be associated with chronic hemolytic anemia of varying severity and may include the classic feature of marked sensitivity to fava beans.
Management of G6PD deficiency is primarily preventive, avoiding factors known to promote or exacerbate hemolysis. Measures aimed at preserving kidney function (see above) are indicated in patients who develop hemoglobinuria.