대한수혈학회지：제19권 제1호, 2008
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접수일：2008년 3월 5일, 승인일：2008년 4월 18일
책임저자：한 규 섭 110-744 서울시 종로구 연건동 28 서울대학교병원 진단검사의학과 TEL: 02) 2072-3519, FAX: 02) 762-9411, E-mail: [email protected]
항-N 항체에 의한 지연성용혈성수혈부작용 1예
서지원1ㆍ정미은2ㆍ이종원3ㆍ한규섭1
서울대학교병원 진단검사의학과1, 청주성모병원 진단검사의학과2, 신경외과3
= Abstract =
A Case of Delayed Hemolytic Transfusion Reaction due to Anti-N
Ji-Weon Seo1, Me-Eun Chung2, Jong-Won Lee3, Kyou-Sup Han1
Department of Laboratory Medicine, Seoul National University Hospital1,
Departments of Laboratory Medicine2 and Neurosurgery3, Cheong Ju St. Mary’s Hospital, Cheongju, Korea
지연성용혈성수혈부작용은 혈청학적으로 적합한 혈액을 수혈 받은 후 수일 후에 용혈이 나타난다. 저자 들은 용혈성수혈부작용을 거의 유발하지 않는 것으로 알려진 항-N 항체에 의해 발생한 지연성용혈성수 혈부작용 1예를 보고하는 바이다. 환자는 66세 남자로 두부외상으로 수술 중 3 단위의 적혈구를 수혈 받았다. 항체선별검사에서 적혈구 동종항체는 발견되지 않았고, 수혈 직후 별다른 증상이 없었다. 6일 후 혈색소가 10.9 g/dL에서 8.7 g/dL로, 합토글로빈이 2 mg/dL로 감소하였고, lactate dehydrogenase는 417 IU/L로 증가하였다. 직접 항글로불린 검사에서 양성을 보였고, 항-N 항체가 혈청검사에서 관찰되었다.
수혈 전 검체로 시행한 적혈구 항원검사에서 N 항원의 부재가 확인되었다. 항-N 항체는 수혈 전에는 발견되지 않아 기왕반응에 의한 것으로 판단된다. 경미한 임상증상만 있는 경우 검사소견이 용혈 발생의 유일한 증거가 될 수 있다. 따라서 혈색소나 헤마토크릿 감소의 발견 시 용혈의 감별을 위해 수혈로 인한 적혈구 동종항체의 생성유무를 확인하여야 한다. (Korean J Blood Transfus 2008;19:63-66)
Key words: Hemolytic transfusion reaction, Delayed hemolytic transfusion reaction, Anti-N antibody
Introduction
Delayed hemolytic transfusion reactions (DHTRs) are generally not recognized until 3 to 10 days after the transfusion of serologically compatible blood. DHTRs generally occur in patients who have been alloimmunized to red blood cell (RBC)
antigens by previous transfusion or pregnancy.1) The clinical symptoms and signs most frequently associated with DHTR include unexplained hemoglobin (Hb) level and hematocrit decreases, fever, and jaundice. The incidence of DHTR has been reported to be 1 in 5405 to 1 in 6715 transfused allogeneic RBC units.2,3) Antibodies
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Fig. 1. Progression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemo- globin (Hb) levels by day after hospitalization. The patient was transfused with three crossmatched units of RBCs on Day 0. On postoperative day 7 lactate dehydrogenase (LDH) was 417 IU/L and haptoglobin was 2 mg/dL.
directed against Rh and Kidd system antigens are most commonly implicated in DHTR.2-5) Here, the authors report a case of DHTR due to anti-N.
Only three cases of hemolytic transfusion reac- tions due to anti-N have ever been previously reported in the English literature.
Case Report
A 66-year-old male patient presented with disorientation two days after he had fallen from a bicycle. He had an abrasion on the right arm and a left leg swelling. Brain CT revealed a skull fracture and an intracranial hemorrhage. His labo- ratory findings were; Hb 9.5 g/dL, white blood cell (WBC) 6.89×109/L, platelet (PLT) 97×109/L, total bilirubin 1.3 mg/dL, aspartate aminotrans- ferase (AST) 58 IU/L, alanine aminotransferase (ALT) 24 IU/L, blood urea nitrogen (BUN) 9 mg/dL, and creatinine 0.6 mg/dL. His blood group was AB, D＋ and no unexpected antibody was found. Three units of serologically compatible RBCs were transfused during surgery undertaken to remove intracranial hematoma, and no adverse reaction was observed during or after the trans- fusion. His postoperative laboratory findings were;
Hb 10.9 g/dL, WBC 9.03 ×109/L, PLT 97×109/L, total bilirubin 1.4 mg/dL, AST 50 IU/L, ALT 22 IU/L, BUN 8 mg/dL, and creatinine 0.6 mg/dL.
On sixth day after the operation, Hb dropped to 8.7 g/dL, and other laboratory findings were;
WBC 5.38×109/L, PLT 173×109/L, reticulocyte count 1.6%, total bilirubin 1.4 mg/dL, lactate dehydrogenase (LDH) 417 IU/L, haptoglobin 2 mg/dL, AST 46 IU/L, ALT 32 IU/L, and BUN
9 mg/dL. On postoperative day 9, AST and ALT had increased to 115 IU/L and 78 IU/L, respec- tively (Fig. 1). A peripheral blood smear showed macrocytic RBCs with autoagglutination. His direct antiglobulin test was positive, and the anti-N RBC antibody was identified in serum. An RBC antigen testing was done to find N antigen on his RBC, which revealed the antibody reacted with allogeneic RBC.
At this time, urinalysis showed yellow-colored urine with specific gravity of 1.020, 2＋ blood, 4＋
glucose, and 1＋ urobilinogen. Without further transfusion, Hb was found to have risen to 13.6 g/dL when the patient visited our OPD for a follow up check.
DHTR due to Anti-N
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Discussion
The presence of an unexpected posttransfusion decrease in Hb level and signs of hemolysis favor a diagnosis of DHTR, and an elevation in serum bilirubin or in serum creatinine, a reduction in serum haptoglobin from the pretransfusion level, hemosiderinuria, hemoglobinuria, hemoglobine- mia, an unexplained fever, and decreased urine output are considered evidence of clinical hemo- lysis.3,4) Positive direct and indirect antiglobulin tests also aid a diagnosis of DHTR.
In the described case, no unexpected antibody was identified by pretransfusion testing and no adverse reaction was observed after administering serologically compatible RBCs. However, six days later, blood Hb level decreased from 10.9 g/dL to 8.7 g/dL with an increased LDH level (417 IU/L) and a decreased haptoglobin level (2 mg/dL), which suggested hemolysis despite no patient's specific symptom about hemolysis. Posi- tive direct and indirect antiglobulin tests con- firmed what induced the hemolysis. Additional tests revealed that anti-N RBC alloantibody was guilty.
Unfortunately, there is no definite method of avoiding DHTR because it is related to an in- creased antibody production as a result of a secondary immune response. Although patient's previous transfusions were not evident, an anti-N RBC antibody was probably present with a low titer, which made it difficult for the antibody to be detected by pretransfusion test. Thus, it appears that the transfusion stimulated an amnestic res- ponse and subsequent anti-N production which
made it possible to reveal the cause of the hemo- lysis.
IgM is the most common type of an anti-N antibody, which is typically detected as weakly reactive cold agglutinins.6) It is noted that the anti-N antibody was a rare cause of alloimmuni- zation related to the transfusion. But, at least three cases of hemolytic transfusion reactions and one case of hemolytic disease of the newborn have been associated with anti-N.7-10)
In the present case of DHTR, the hemolysis was discovered 6 days after the transfusion. When clinical signs are mild or absent, laboratory evi- dence including a decrease in haptoglobin level and increased levels of bilirubin, LDH and BUN may provide the only indication of hemolysis.
Thus, when a decrease in Hb or hematocrit is noted, physicians must review the transfusion history to ascertain the presence of an alloanti- body produced by a secondary immune response.
Summary
Delayed hemolytic transfusion reactions are usually identified several days after the trans- fusion. We report here on a case of delayed hemo- lytic transfusion reaction that was due to anti-N, which is rarely related to a hemolytic transfusion reaction. A 66-year-old male presented with head trauma. Three units of red cells were transfused during the operation to remove a subdural hema- toma. No antibody was detected on the pretrans- fusion tests and no adverse reaction was observed during or after the transfusion. Six days later, the blood hemoglobin level decreased from 10.9 to
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RBC antigen testing revealed the absence of N antigen in his pretransfusion sample. The appe- arance of alloantibody after transfusion may be due to an anamnestic response. When the clinical signs are mild, laboratory tests may provide the only indication of hemolysis. Thus, when a de- crease in the hemoglobin level or hematocrit is noted, physicians must review the transfusion history to ascertain the presence of an alloan- tibody.
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