Tietz syndrome

Unexpected and confusing laboratory test results can occur if a blood sample is inadvertently collected following a blood transfusion. A potential for transfusion-acquired hemoglobinopathy exists because heterozygous individuals show no significant abnormalities during the blood donor screening process. Such spurious results are infrequently reported in the medical literature. We report a case of hemoglobin C passively transferred during a red blood cell transfusion. The proper interpretation in our case was assisted by calculations comparing expected hemoglobin C concentration with the measured value. A review of the literature on transfusion-related preanalytic errors is provided.

(Arch Pathol Lab Med. 1999;123:642-643)

It is well known that accuracy and reliability of laboratory tests can be greatly influenced by the quality of a patient sample. The complexities of preanalytic variations were described in detail elsewhere.1 One source of preanalytical variation is a blood transfusion, which can result in some degree of fluctuation in the levels of serum protein, electrolytes, and lactate dehydrogenase activity.l However, little attention has been given to test results that can be altered by a transfusion of blood containing abnormal or unexpected substances. If a blood sample is inadvertently collected after a blood transfusion, laboratory tests performed on such a sample can produce confusing results due to donor blood abnormalities. If the clinician interpreting the results is unaware of such a possibility, the potential for misdiagnosis and unnecessary diagnostic tests or procedures exists. We consider such incidents to be one type of preanalytic error.

Persons with abnormal hemoglobin may donate blood because heterozygous individuals show no significant abnormality detectable by the blood donor screening process. Such blood, when transfused, may cause aberrant results in the recipients. A literature review indicates that such a phenomenon is uncommonly recognized or reported. We report a case of transfusion-acquired hemoglobinopathy and suggest the utility of calculations to explain the origin of abnormal hemoglobin when the concentration is different from expected.

REPORT OF A CASE

A 46-year-old black woman was admitted to Saint Louis University Hospital, St Louis, Mo, with upper gastrointestinal tract bleeding and a 3-week history of fever and cough. Her family and past medical histories were unremarkable. Her initial hematology values were hemoglobin, 49 g/L; mean corpuscular volume, 60.9 fL; and mean corpuscular hemoglobin concentration, 289 g/L. After 3 units of red blood cells (RBCs) were given, the patient's posttransfusion hemoglobin level was 88 g/L. Later, pulmonary tuberculosis was diagnosed and the appropriate treatment was started. Because of the extreme microcytosis, a hemoglobin electrophoresis was also ordered to exclude hemoglobinopathy.

PATHOLOGIC FINDINGS

Hemoglobin electrophoresis in alkaline (pH 9.2) cellulose acetate gel showed a prominent band migrating in the region of hemoglobin C in addition to hemoglobin Al. The presence of hemoglobin C was confirmed by acid (pH 6.0) gel electrophoresis (Figure 1). Densitometry analysis showed 89.1% hemoglobin A and 10.9% hemoglobin C, an amount of hemoglobin C less than would be expected in a heterozygous individual. Dilution of hemoglobin C by the transfused units in a patient with hemoglobin C trait was initially proposed to explain the finding. However, an alternative hypothesis, that the patient had received blood from a heterozygous donor, was tested by performing a calculation. The calculation assumed that 1 unit of RBCs was received from a heterozygous individual with 40% hemoglobin C and that each transfused unit increased the patient's hemoglobin level by 13 g/L. Accordingly, the expected hemoglobin C concentration in the recipient was 5.7%. On the other hand, if a hemoglobin C heterozygote had received 3 RBC units from normal donors, a 22.7% hemoglobin C would be expected. The measured concentration was 10.9%, favoring the hypothesis that one of the donors was a hemoglobin C heterozygote. Hemoglobin electrophoresis performed on samples from attached segments from each donor unit identified 1 unit with a hemoglobin C level of 45.5% (Figure 2), confirming our suspicion. The affected donor was a healthy 19-year-old man of African-American and white parentage. He denied any knowledge of a family history of hemoglobin C and was referred to his personal physician for further counseling. He was not excluded from blood donation.

COMMENT

We are aware of only 3 case reports of abnormal hemoglobin electrophoresis results following RBC transfusions. In one case, hemoglobin migrating in the region of hemoglobin S was detected in a boy with hemolytic anemia.2 Additional tests excluded constitutional hemoglobinopathy, and the suggestion that hemoglobin S was present in the recently transfused RBC units was confirmed on subsequent testing. Another case of passive transmission of hemoglobin S was described in a woman with anemia.3 The transient nature and low concentration of abnormal hemoglobin in that case was puzzling and directed attention to a recent blood transfusion. Again, the donor was a hemoglobin S heterozygote. In the remaining reported case, hemoglobinopathy was suspected on the basis of an abnormal erythrocyte lysis pattern on an automated hematology analyzer.4 However, the presence of a small amount of hemoglobin C was shown by hemoglobin electrophoresis in a posttransfusion sample only and was determined to be acquired from a donor.

There are reports indicating that other unexpected laboratory results can be seen after blood transfusions. Two of the reported cases include passively acquired hepatitis B antibodies.56 There are also 2 reports of confirmed passive transfer of anti-D alloantibodies.'8 The notion that such reports have only historical significance, since donors are now screened for hepatitis antibodies and alloantibodies, is incorrect. In one case, anti-D alloantibody was missed on the donor screening.7 In many of the cases cited, diagnostic confusion and additional extensive testing resulted from unsuspected posttransfusion findings. However, the following case illustrates the potential seriousness of unrecognized transfusion-acquired test results. A fresh frozen plasma transfusion from a pregnant donor produced a false-positive test result for human chorionic gonadotropin in the recipient? This result prompted invasive diagnostic procedures (including dilation and curettage) to evaluate for unrecognized pregnancy. The most unusual case involved misleading normal results of cytogenetic evaluation of stimulated peripheral blood culture showing a normal karyotype in a premature neonate who received nonirradiated blood.lo The patient was later diagnosed with Downs syndrome complicated by transient myeloproliferative disorder. The false-negative result delayed the proper diagnosis and was thought to be due to analysis of donor leukocytes.

We conclude that the possibility of transfusion-acquired abnormal hemoglobin should be considered whenever the relative amount of the detected abnormal hemoglobin is not typical or cannot be explained by dilution. Simple calculations like the one used here could guide further testing. Several factors may account for less than perfect results of these calculations and may include inaccuracy of the densitometry, unequal contribution by each of the transfused units, or individual variation in abnormal hemoglobin concentration in heterozygous individuals. alphaThalassemia should also be considered when interpreting unusual hemoglobin C and S concentrations. Our case may reflect a not uncommon occurrence in the United States owing to the high prevalence of hemoglobin C heterozygosity.

References

1. Young DS, Bermes EW. Specimen collecting and processing, sources of biological variation. In: Burtis CA, Ashwood ER, eds. Tietz Textbook of Clinical Chemistry 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994:58-102.

2. Rechavi G, Brok-Simoni F, Ben-Bassat I, Ramot B. Spurious haemoglobinopathy [letter]. Lancet. 1986;1(8488):1035.

3. Gibaud A, Braconnier F, Garel MC, Cohen-Solal M, Gidaud H, Rosa J. Sur une hemoglobine "S" acquise de I'adulte. Nouv Presse Med.1974;3:2013-2014.

4. Strobel SL, Panke TW, Zelensky K. Hemoglobin C acquired via blood transfusion: detection by automated blood counter. Arch Pathol Lab Med. 1987;111: 565-568.

5. Carta JR. Presumed transfer of hepatitis antibody by blood transfusion to chronic hemodialysis patients. Am J Infect Control. 1982;10:34-36.

6. Devine P, Taswell HF, Moore SB, Gilchrist GS, Jacobson TM. Passively acquired antibody to hepatitis B surface antigen: pitfall in evaluating immunity to hepatitis B viral infection. Arch Pathol Lab Med. 1989;113:529-531.

7. Harrison CR, Evans C. Transient presence of an anti-D alloantibody. Arch Pathol Lab Med. 1985;109:1042-1043.

8. Callahan J, Faragher BS. Passive anti-D [letter]. Med J Aust. 1982;1:290. 9. Kruskall MS, Owings DV, Donovan LM, Pacini DG, Costello Ti. Passive transfusion of human chorionic gonadotropin from plasma donated during pregnancy. Vox Sang.1989;56:71-74.

10. Druce M, Cohen IJ, Naor N, Shohat M. Late diagnosis of Down syndrome due to incorrect cytogenetic diagnosis and extreme prematurity. Clin Genet. 1 995;48:1 92-194.

Accepted for publication January 22, 1999. From the Department of Pathology, St Louis University, St Louis, Mo (Drs Suarez, Polski, and Johnston), and Blood Services, American Red Cross, St Louis, Mo (Dr Grossman).

Reprints: Marilyn F. M. Johnston, PhD, MD, Department of Pathology, Division of Transfusion Services, St Louis University Hospital Health Sciences Center, 3635 Vista Ave, St Louis, MO 63110.

Copyright College of American Pathologists Jul 1999
Provided by ProQuest Information and Learning Company. All rights Reserved