Clinical pathology selected abstracts

Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Retrospective analysis of hemolytic disease of the fetus and newborn caused by anti-M antibodies

July 2023—Hemolytic disease of the fetus and newborn is caused by maternal immunoglobulin G crossing the placenta and binding to fetal RBC antigens. In severe cases, it results in fetal or neonatal anemia, edema, hepatosplenomegaly, and death. In China, antibodies to the ABO blood group system are the most common cause of hemolytic disease of the fetus and newborn (HDFN) and account for 85.3 percent of cases. This is followed by antibodies to the Rh blood group system, which account for 14.6 percent of HDFN cases. Other blood group systems, including Duffy, Kidd, and MNS, may also cause HDFN. Few studies have investigated anti-M-induced HDFN (anti-M-HDFN), and most case reports in the literature are from Japan, India, Taiwan, and other Asian countries. The authors conducted a study to summarize laboratory findings and clinical features of HDFN. They retrospectively analyzed the data on 17 infants who were diagnosed with anti-M-HDFN between June 2013 and May 2019. The authors compared the maternal history, neonatal diagnosis on admission, and laboratory test results for those 17 infants with those of 15 infants who had HDFN involving the ABO blood group system (ABO-HDFN), 15 infants who had HDFN involving the Rh blood group system (anti-D-HDFN), and a control group of 15 premature infants. Anti-M antibodies are common, unexpected RBC antibodies, with IgM antibodies representing the majority and 50 to 80 percent of cases combined with IgG. The results of the study showed that in the anti-M-HDFN group, 94.12 percent, 35.29 percent, and 17.65 percent of infants had free antibodies in plasma, a positive direct antiglobulin test, and a positive elution test, respectively. In 12 infants, the free antibody reactions were stronger at 4°C than at 37°C, and the antibody titers at 4°C ranged from one to 512. However, the anti-M titers were not high in two severe cases. All 17 of the infants with anti-M-HDFN developed anemia requiring treatment, and one of them died. One neonatal death following treatment also occurred in the ABO-HDFN, anti-D-HDFN, and premature infant cohorts. The authors noted that of the 39 pregnancies in anti-M-HDFN women, seven resulted in stillbirth or neonatal death, which was significantly higher than for ABO-HDFN (zero of 35) and anti-D-HDFN (one of 41). These results are consistent with other studies. In addition, the authors noted that the study findings suggest that the incidence and severity of anti-M-HDFN may be underestimated and that anti-M may be a cause of unexplained stillbirth, neonatal death, and other complications. They also found that anti-M-HDFN was associated with younger gestational age, lower birth weights, and higher incidences of respiratory distress than were other HDFN types. The findings suggest that the anti-M-HDFN pathogenesis mechanism may differ from that of other HDFNs and that this requires further research. Furthermore, since a low anti-M titer may lead to stillbirth and severe fetal anemia, clinicians should follow pregnant women with anti-M antibodies closely.

He Y, Gao W, Li Y, et al. A single-center, retrospective analysis of 17 cases of hemolytic disease of the fetus and newborn caused by anti-M antibodies. Transfusion. 2023;63:494–506.

Correspondence: Dr. Qiushi Wang at wangqs18@vip.126.com

Emergency department cotesting for HIV when testing for gonorrhea and chlamydia

The U.S. Department of Health and Human Services proposed an initiative, in 2019, to reduce new HIV infections in the United States by 90 percent by 2030. The plan was to increase HIV prevention and treatment strategies in the 50 local areas or counties and seven states that represented more than half of new HIV diagnoses. One of the areas with the highest new incidences of HIV infection was Cuyahoga County, Ohio. Cuyahoga County had 190 new HIV infections in 2020, a 27 percent increase from 2019 levels. The county also had an increase in syphilis cases and the highest number of chlamydia and gonorrhea cases in the state. The Nationwide Emergency Department Sample database showed a cotesting rate of only four percent for HIV when testing for gonorrhea and chlamydia (G/C) in the emergency department (ED). Because many people use the ED as a first point of contact for health care, the United States Preventive Services Task Force recommended that HIV testing be conducted in that department. In 2020, the Cleveland Clinic implemented an HIV screening approach in all of its EDs, which extended across Cuyahoga County. A multidisciplinary team evaluated current practices for HIV testing and obstacles to such testing during an ED encounter in which G/C testing was ordered. The Cleveland Clinic studied all G/C and HIV tests ordered from the health system’s 14 EDs during a two-year period to determine if testing in the ED may be an effective approach to reaching populations at highest risk for HIV. The authors collected EHR data from ED encounters for all G/C and HIV tests ordered from Jan. 1, 2019 to Dec. 31, 2021. The patients presented to the ED for sexually transmitted infection screening, with an emphasis on G/C screening. In October 2019, the Cleveland Clinic EDs implemented HIV rapid testing and G/C screening. To support the HIV screening program, the institution implemented a standardized EHR sexually transmitted infection screening order panel, with HIV testing education at staff meetings; rapid laboratory-based blood testing for HIV, with confirmed positive results sent to infectious disease personnel for follow-up; and periodic feedback to clinicians and ED directors about ordering patterns. ED providers were encouraged to discuss HIV testing and offer an HIV test to patients screened for gonorrhea and chlamydia in the ED. The overall rate of cotesting for HIV when a G/C test was ordered at the health system during the study period of 2019 to 2021 increased to approximately 30 percent, with some EDs screening at a rate of 60 percent. The authors showed that the G/C and HIV cotesting percentage was higher in locations that were hot spots for HIV infection. Seventy-eight (1.01 percent) of the 7,654 HIV tests conducted were reactive using rapid tests. Of those 78, 67 (86 percent) were positive using standard instrument-based laboratory testing followed by confirmatory testing, which yielded an overall rate of 0.87 percent true HIV positivity. The authors concluded that the Cleveland Clinic’s approach to testing for HIV in the ED is effective. Offering HIV testing at the time of G/C screening in the ED reduces resistance to HIV testing or reluctance to test since patients are already undergoing sexually transmitted infection screening.

Phelan MP, Panikkar V, Muir M, et al. Emergency department co-testing for human immunodeficiency virus when testing for gonorrhea and chlamydia: A readily available, missed opportunity for targeted HIV testing in emergency departments. Am J Clin Pathol. 2023;159:225–227.

Correspondence: Dr. Kamran Kadkhoda at kadkhok@ccf.org