Importance of Lifetime Alerts in Electronic Medical Reporting Systems for Patients Who Test Positive for Antigens

With an estimated incidence of 6.2%, perioperative red blood cell (RBC) transfusions are common [1]. Although many patients undergoing lung lobectomy may require one or more perioperative red blood cell transfusions, a multicenter study by the College of American Pathologists surprisingly found that 9% of type and screening tests were not completed before the start of surgery. [2]. If compatible units are not available in the short term, an unexpected positive perioperative alloimmunization test result may jeopardize the continuation of the current surgery [2]. In such cases, non-compatible O-negative blood may be given to patients with a positive antigen screen after life-threatening hemorrhage. [3], but the benefit/risk balance of acute haemorrhage versus acute or delayed haemolytic transfusion reactions should be carefully assessed. Lifetime alerts in a hospital’s electronic medical record (EMR) system should be issued for patients with a positive history of antigen testing to help protect patients and prevent interruption or delays of surgery.

A 56-year-old woman seen in a preanesthesia clinic with an American Society of Anesthesiologists (ASA) class 3 physical status presented for elective right upper lung lobectomy via thoracotomy and mediastinal lymph node dissection. His medical history was notable for controlled hypertension, insulin-dependent type 2 diabetes mellitus, chronic obstructive pulmonary disease (COPD), class 2 obesity (body mass index of 36), former smoking for 30 years, controlled schizophrenia, gravida 11, para 11, and squamous cell carcinoma of the right upper lung lobe. No previous RBC transfusions had been received. Preoperative cardiac evaluation showed normal sinus rhythm and normal left ventricular ejection fraction. Pulmonary function tests confirmed COPD with persistent airflow limitations. Preoperative laboratory tests were unremarkable with a hemoglobin level of 11.9 g/dl and a hematocrit level of 36.9%. Preanesthetic physical examinations, including dental, cardiovascular, pulmonary, neurological, and abdominal status, were consistent with medical history. The Mallampati score was 2. A preoperative type and screening test, requested during the preoperative evaluation by the anesthesiology provider and performed one week before the procedure, revealed a positive blood type A with a screening of negative antibody.

On the day of surgery, a second type and a cross-sectional screen were performed. General anesthesia was provided with 2 mg midazolam, 20 mg etomidate, 50 mg propofol, 50 mcg fentanyl, 40 mg lidocaine, and 50 mg rocuronium. The patient was intubated with a left double lumen catheter and surgery was started without complications. After the surgical team freed the lung adhesions, profuse and continuous bloody oozing occurred with an estimated blood loss of 300ml. After discussion with the surgical team, the decision was made to request packed red blood cells from the blood bank in the event of further significant blood loss. The blood bank informed the anesthesiologist that the antibody test was positive with anti-U and only one unit of compatible blood was immediately available. The dissection and section of the branches of the right superior pulmonary artery and the right superior pulmonary vein having already been performed without hemorrhagic complications, the decision was made to continue the operation. Sectioning of the right upper lobe bronchus was uneventful. Hemodynamically stable for the remainder of the procedure and with no other significant blood loss, the patient did not require a blood transfusion. After switching from the double-lumen probe to the single-lumen probe, the intubated and analgesic patient is taken to surgical resuscitation.

A careful review of the patient’s previous medical records from other hospitals, which were not available during the preoperative evaluation, revealed a positive antibody screen two years prior showing anti-U.

Patients undergoing elective surgery may suddenly need a red blood cell transfusion. Thoracotomy with lobectomy carries a significant risk of perioperative hemorrhage. The Association for the Advancement of Blood and Biotherapies (AABB) guidelines recommend that type and screening tests should only be valid for a maximum of three days [4]. Finding compatible units for transfusion in a rare alloimmunization setting may require an extended lead time, up to several days, for additional cross-checking. A multicenter study by the College of American Pathologists showed that 25% of types and screens were drawn on the day of surgery and 9% were not completed before surgery began. Ideally, antibody screening should be completed before surgery begins. Positive antibody screens occurred in 2% of types and screens. Among positive antibody screens, 5.7% led to surgery being stopped or delayed [2].

An indirect Coombs test, also called indirect antiglobulin test, antibody screening, or crossmatch, is used to detect antibodies to foreign red blood cells in a patient’s serum or plasma before a blood transfusion. The indirect Coombs test is a two-step test. In the first step, the patient’s serum is incubated with a wide range of washed foreign red blood cells of known antigenicity to include a full range of surface antigens. In the second step, the red blood cells are washed three or four times with an isotonic saline solution, then incubated with an anti-human globulin, known as Coombs’ reagent, to distinguish the presence or absence of immunoglobulins to the surface of red blood cells. If the antibodies have bound to the surface antigens of the red blood cells in the first step, the red blood cells will agglutinate with Coombs’ reagent in the second step. The indirect Coombs test will then be declared positive. [5].

There are many reasons for false negative indirect Coombs test results. These include insufficient amount of antibody on red blood cells, improper incubation temperature (including during transport to external laboratories), undercentrifugation, delay in adding Coombs’ reagent, or addition of expired Coombs reagent, incorrect amount of Coombs reagent, inappropriate antigen/antibody ratio, and elution of low avidity antibodies from red blood cells during washing [6]. Buchta et al. showed that antibody testing produces 0.16% false negative results [7].

It is important to note that once a single antibody screen is positive, the patient should be considered positive, even if subsequent type and screening tests are negative. In our case, the patient’s medical history from other hospitals with a positive anti-U antibody screen was not available during the preoperative evaluation. We relied entirely on our own type and screening which was negative before the procedure, but apparently false negative, which we didn’t know. Once the crossmatch during the procedure revealed the positive antibody screen and the blood bank informed us of the multiple hour-long delays in receiving good blood, we had to make the difficult decision to put the test on hold. operation or to carry out a possible need for transfusion and the consequent risk of acute or delayed haemolytic transfusion reactions. To avoid such scenarios, it is crucial to set up a lifetime medical alert in the hospital’s EMR reporting system for patients with at least one positive type and one screening result. If the old antibody screening had been known in our case, we could have prevented such a scenario. Friedberg’s study showed that 9% of types and screenings are not completed before surgery begins and carry the risk of stopping or delaying surgery once a positive result is shown. [2]. If an alert similar to an allergy alert in the EMR system existed, a positive antigen screening surprise would be avoided. After this incident, our hospital introduced such an alert in our electronic medical reporting system for patients who screened positive for antibodies.

Unmatched type O negative blood may be given to patients who screen positive for antibodies and who have emergent intraoperative hemorrhage. The benefit/risk balance of acute haemorrhage versus acute or delayed haemolytic transfusion reactions should be carefully assessed. If appropriate units are not available, the benefit of blood transfusion should be weighed against the risk of alloimmunization, and a restrictive transfusion policy should be applied. The lower the amount of the patient’s native blood that remains in circulation, the lower the risk of a transfusion reaction. [3]. Garratty and Petz recommend considering transfusion of unpaired type O negative blood in patients with positive screening tests and life-threatening anemia [8].

Although very rare, alloimmunization with anti-U antibodies can cause hemolytic transfusion reactions [9]. Only 24 cases of anti-U immunization have been reported in the literature. All reported cases were pregnant women from sub-Saharan African ethnic groups [10]. The pathophysiology of anti-U antibodies, similar to Rh isoimmunization, follows pregnancy or a previous blood transfusion (in 1.2% of people of African descent). The U antigen is nearly universal in the Caucasian population, resulting in limited availability of compatible blood for transfusion in patients with anti-U antibodies [11].

Perioperative transfusions of red blood cells are common. Transfusion of red blood cells requires prior antigen screening. False negative results can lead to acute and delayed hemolytic transfusion reactions leading to increased morbidity and mortality. This case report highlights the importance of lifetime alerts in hospital EMR systems for patients who screen positive for antigens.