Test yourself: Blood transfusions

Case 1: Post-transfusion drop in hemoglobin level

A 23-year-old woman is hospitalized for surgical drainage of a tubo-ovarian abscess. She has thalassemia intermedia caused by homozygous ß-positive thalassemia and was transfusiondependent until she had a splenectomy at age 15 years. On physical examination, pulse is 110/min. She is pale, slightly jaundiced, and dyspneic at rest. Hemoglobin is 5.4 g/dL compared with her baseline value of 7.5 g/dL. Blood is type Group O, Rh positive, and the antibody screen is negative. She receives a transfusion of two units of type Group O, Rh-positive packed red blood cells that raises her hemoglobin to 7.6 g/dL. One week later, she has a low-grade fever, increased jaundice, recurrent dyspnea, and tachycardia. Hemoglobin is 6.0 g/dL. A repeated antibody screen is positive for anti-E antibody.

Which of the following is the most appropriate next step in the management of this patient's most recent decrease in hemoglobin?

A. Corticosteroids
B. Erythropoietin
C. Repeated transfusion
D. Intravenous immunoglobulin

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Case 2: Avoiding fetal loss in sickle cell disease

A 23-year-old woman at 8 weeks gestation is evaluated during a routine visit. Her history is significant for sickle cell disease for which she has had two hospitalizations for painful episodes. She also experienced a fetal loss 5 years ago during the third trimester of pregnancy. She is currently asymptomatic and performs all of the activities of daily living. The remainder of the history is noncontributory.

On physical examination, she is afebrile. Pulse rate is 88/min, respiration rate is 18/min, and blood pressure is 110/85 mm Hg. Pulse oximetry indicates oxygen saturation of 96% (room air). On cardiopulmonary examination, the lungs are clear, and a 2/6 early systolic murmur is heard over the left sternal border. The remainder of the examination is normal. Laboratory studies indicate a hemoglobin of 5.5 g/dL, which is her baseline value, and a mean corpuscular volume of 95 fL.

Which of the following is the most appropriate transfusion strategy for avoiding fetal loss in this patient?

A. Routine exchange transfusion to maintain the percentage of hemoglobin S <30%
B. Routine transfusion to maintain hemoglobin >10 g/dL
C. Routine transfusion to maintain hemoglobin >7 g/dL
D. No transfusion required at this time

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Case 3: Positive direct antiglobulin test

A 40-year-old man undergoes preoperative evaluation for trauma- induced aseptic necrosis requiring hip replacement. His medical history is noncontributory, and no lymphadenopathy or hepatosplenomegaly was noted on physical examination. Preoperative hemoglobin was 14.5 g/dL. The patient has type Group O blood, is Rh positive, and had a negative antibody screen. He received two units of autologous blood during surgery. The postoperative hemoglobin was 11.3 g/dL. Four days after surgery, a wound infection developed, for which he received a high-dose second-generation cephalosporin. At that time, the hemoglobin was 9.5 g/dL, serum haptoglobin was 140 mg/dL, reticulocyte count was 5.5% of erythrocytes, and serum lactate dehydrogenase was 170 U/L. A repeated antibody screen was negative, and the direct antiglobulin test (DAT test) was weakly positive for IgG but not complement. Elution studies performed by the blood bank were nonreactive.

Which of the following is most likely explanation for this patient's serologic findings?

A. Cold autoantibody reaction
B. Warm autoantibody reaction
C. Drug-dependent antibody reaction
D. Transfusion-related alloantibody reaction

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Case 4: No compatible blood units available

A 17-year-old woman is evaluated for a 3-week history of headache and exercise intolerance. The remainder of the medical history is noncontributory.

On physical examination, the patient is pale. Pulse rate is 100/min, and respiration rate is 14/min. There is no evidence of jugular venous distention or S3, and the lungs are clear to auscultation. A spleen tip is enlarged on abdominal examination.

Laboratory studies indicate a hemoglobin of 5.5 g/dL, and an absolute reticulocyte count of 605,000/μL (normal, 25,000/μL to 75,000/μL). The blood is type Group O, Rh-positive.

Warm autoimmune hemolytic anemia is diagnosed, and prednisone therapy is initiated at a dose of 1 mg/kg. Two days later, the patient is dyspneic at rest. Pulse rate is 135/min, respiration rate is 25/min, and blood pressure is 160/100 mm Hg. On cardiopulmonary examination, jugular venous distention and an S3 are present, and crackles are heard in both lungs. The hemoglobin has decreased to 4.6 g/dL, and the absolute reticulocyte count has increased to 900,000/μL. A chest radiograph shows evidence of heart failure.

The blood bank cannot find compatible units of blood for this patient, and it will be at least another day before the serologic evaluation will have been completed.

Which of the following is the most appropriate initial treatment for this patient?

A. Increased prednisone dosage
B. Intravenous immunoglobulin administration
C. Immediate transfusion of Group O blood
D. Albumin infusion
E. Emergent splenectomy

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Answers and commentary

Case 1

Correct answer: C. Repeated transfusion

This patient is experiencing a delayed hemolytic transfusion reaction. Immediate re-transfusion is needed to treat her continued symptoms, and antigen-negative blood must be used to avoid further hemolysis. No other intervention is required in handling a delayed hemolytic transfusion reaction except for avoidance of the incompatible antigen. Alloantibodies often become undetectable over time in the absence of continued antigenic challenge, only to return after re-exposure to a detectable titer. Once this patient stopped growing, her need for an expanded erythrocyte volume ceased, and she no longer required transfusion. Her alloantibody to the E antigen had diminished to an undetectable level by the time of her surgery. After the hemolytic reaction was identified, the patient's pretransfusion sample was found to be negative for the E antigen, but both transfused units were tested and found to be E positive. The anti-E antibody caused extravascular hemolysis of the incompatible blood in this patient.

Corticosteroids might be useful in controlling autoantibodies, but they have no proved role in treating alloimmunity. Thalassemia is responsible for the underlying ineffective erythropoiesis that has already caused elevated levels of erythropoietin and marked erythroid hyperplasia in this patient. Although supraphysiologic doses of erythropoietin might result in some increase in erythropoiesis, achieving this response would take several weeks and would not address her immediate need for transfusion. Intravenous immunoglobulin is useful in treating autoantibodies but has little effect on alloimmune destruction unless extremely high doses are used, and then, only when antigen- negative, compatible blood is not available for transfusion.

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Key point

  • No other intervention is required in handling a delayed hemolytic transfusion reaction except for avoidance of the incompatible antigen.

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Case 2

Correct answer: D. No transfusion required at this time

Routine blood transfusion during pregnancy in patients with sickle cell disease is not necessary unless mandated by other high-risk conditions. Especially in underserved areas, fetal wastage and intrauterine growth retardation can be significant problems for many pregnant patients with sickle cell disease, which had previously been attributed to the effects of the anemia on the integrity of the fetal–placental unit.

These problems have been linked to poor nutrition, such as iron or folate deficiency, or to a higher rate of other complications, such as preeclampsia, rather than to the direct effects of the anemia. Just as it does in cases of acute pain crises, transfusion may have deleterious effects on blood viscosity in the microvasculature and should be reserved for use in raising oxygen carrying capacity.

Exchange transfusion is now used for acute events, such as chest syndrome, or to prevent recurrent stroke. Although pregnancy increases plasma volume—often disproportionately to

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Key point

  • Routine blood transfusion during pregnancy in patients with sickle cell disease is not necessary unless mandated by other high-risk conditions.

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Case 3

Correct answer: C. Drug-dependent antibody reaction

This patient's antibody screen (indirect antiglobulin test) identifies serum antibodies capable of reacting with reagent red blood cells. The direct antiglobulin test (Coomb's direct test) identifies globulins already on the surface of the patient's erythrocytes. These serologic findings are indicative of a drugdependent antibody in this patient. One of the most common mechanisms of drug-induced antibody, often producing a positive direct antiglobulin test, occurring with the use of cephalosporins, causes alteration of the erythrocyte membrane and results in nonspecific deposition of IgG and other serum proteins. This mechanism does not cause hemolysis nor complement activation. The serologic findings in this patient are indicative of a drug-dependent antibody.

Cold reactive autoantibodies are IgM antibodies and are not a cause of a positive IgG antibody test. Many cold autoantibodies are merely cold agglutinins and only react at room temperature or lower but can cause hemolysis if they react at temperatures closer to 37°C. In this case, the direct antibody test would be positive for complement but not IgG. Warm reactive autoantibodies are IgG antibodies and cause a positive direct antiglobulin test because IgG reacts with the red blood cells, and can occasionally cause complement activation. Warm autoantibodies that are recovered by elution from direct antiglobulin test–positive red blood cells will react with all cells tested rather than be nonreactive. Drug-dependent antibodies recovered in a eluate will only be detected if the drug is used in the test system.

This patient has never received donor blood and therefore has not been sensitized to develop alloantibodies against donor red blood cells. During a hemolytic transfusion reaction, the direct antibody test may be positive for IgG, but the antibody is present on the repeated antibody screen, and elution would show reactivity with antigen-positive cells. In the absence of hemolysis, the elevated reticulocyte count probably reflects this patient's response to surgical blood loss that was incompletely corrected by only two autologous units of blood. Other causes of the lower hemoglobin include ongoing bleeding and/or blood loss from continued phlebotomy for laboratory testing.

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Key point

  • Patients with a drug-induced antibody reaction do not have indications of hemolysis or evidence of complement activation on direct antibody testing.

Case 4

Correct answer. C. Immediate transfusion of Group O blood

This patient has high-output heart failure and is at risk for cardiovascular collapse. The prednisone has not slowed the hemolysis, and the patient requires rapid correction of her oxygen- carrying capacity. Transfusion of incompatible blood may accelerate the hemolysis and perhaps worsen the symptoms, but it is the best option because withholding blood in this setting confers even more risk of cardiovascular compromise. She has no history of pregnancy or past transfusion and little likelihood of having an alloantibody antigen that would require transfusion with antigen-negative blood. Waiting an additional day for the results of serologic evaluation provides no practical improvement in the risk of transfusion. Increasing the dose of prednisone to >1 mg/kg has no proved benefit and may be harmful.

Key point

  • Patients with heart failure and hemolysis require immediate transfusion, even when only incompatible blood is available, to avoid cardiovascular collapse.