Heterophile antibodies and false-positive assays for human chorionic gonadotropin

2
Fetal neuromuscular blockade To the Editors: We thank Moise et al. for publishing their extensive experience in fetal surgery (Moise KJ, Carpenter RJ Jr., Deter RL, Kirshon B, Diaz SF. The use of fetal neuromuscular blockade during intrauterine proce- dures. AM J 0BSTET GYNECOL 1987; 157:874-9). We would like to ask Moise et al. these questions: 1. Does a 25-gauge needle leave skin dimpling or other cutaneous scars on the fetal thigh? 2. What gauge needle was used for cordocentesis? 3. Why did they choose to transfuse prenatally a 37- week, 3000 gm fetus (case l)? Delivery and neo- natal exchange transfusion seem to be preferable in a term baby. M. Mark Taslimi, MD C. Neil Herrick, MD Department of Obstetrics and Gynecology University of Tennessee-Chattanooga 921 East Third Street, Suite 400 Chattanooga, TN 37403 Reply To the Editors: These physicians asked if the 25-gauge needle used in the intramuscular injection of pancuronium or d-tubocurarine caused skin dimpling or other cuta- neous scars on the fetal thigh. In those neonates ex- amined in our series to date, there has been no evidence of cutaneous scarring whatsoever. In addition there was a question as to what gauge needle was used for cor- docentesis. We used either a 20- or 22-gauge needle for this procedure. Finally, there was a question as to why we elected to transfuse a 37-week, 3000 gm fetus described as case 1 in our article. This patient was re- ferred with uncertain menstrual dates. On her first visit an ultrasonogram was consistent with 32.7 weeks, at which time the patient was said to be 29 weeks' gestation by dates. Amniocentesis at 34.4 weeks' gestation re- vealed a lecithin/ sphingomyelin of 1.8, negative phos- phatidylglycerol, and results of foam test classified as immature. The patient underwent her first intrauterine transfusion at 34 5 /1 weeks' gestation. At 36 5 17 weeks' gestation it was elected to undertake the second intra- uterine transfusion. This was based on the fact that we thought it unlikely that this baby would be mature in view of uncertain menstrual dates and the known in- accuracy of late third-trimester ultrasonographic as- sessment of gestational age. Amniotic fluid obtained during the intrauterine transfusion revealed an leci- thin/ sphingomyelin of 3.3, phosphatidylglycerol 0.6 units, and foam transitional. 1598 CORRESPONDENCE In retrospect, amniocentesis probably was warranted before this transfusion. This patient was managed dur- ing the early course of our intravascular transfusion experience. Our protocol now entails the use of am- niocentesis after 35 weeks' gestation to assess fetal lung maturity. In consultation with our neonatalogists, we have elected to deliver fetuses affected by red blood cell alloimmunization only after pulmonary maturity has been documented. Fetal transfusions late in the third trimester are performed on the labor and delivery suite with preoperative preparations. Our experience with intravascular transfusions has indicated that the major complication associated with the procedure is fetal bradycardia. Our settings allow us to undertake emergency delivery by cesarean section if indicated. Kenneth]. Moise, Jr., MD Department of Obstetrics and Gynecology Baylor College of Medicine One Baylor Plaza Houston, TX 77030 Heterophile antibodies and false-positive assays for human chorionic gonadotropin To the Editors: In the January 1988 issue of The AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Check et al.' re- ported false-positive assays for serum human chorionic gonadotropin (hCG) in the range of 59 to 71 mIU/ml using an immunoradiometric assay. We have recently managed a similar case involving false-positive values in the 16 to 20 mIU /ml range using the same com- mercial assay kit. A 25 year-old woman, gravida 0, came to the Reproductive Endocrinology Service for evaluation of infertility. She was in her usual state of good health with regular menses until ap- proximately 1984 when she noted increasing menstrual irreg- ularity marked by intervals of amenorrhea of up to 3 months. Her evaluation in 1984 was unremarkable, and she remained in otherwise good health. In September 1987, she came to our clinic relating a history of 12 months of unprotected intercourse without pregnancy. Her last menstrual period was July 1987. Physical examination was unremarkable. A diagnosis of anovulation was made, and consideration was given to ovulation induction with clomi- phene citrate. Additional laboratory evaluation revealed a se- rum hCG concentration of 17 mIU I ml by immunoradiometric assay. The patient underwent serial hCG monitoring as listed in Table I. Additional studies included serum n-fetoprotein, CA 125, and carcinoembryonic antigen, which were negative. The patient was managed expectantly, and serum samples were reassayed with conventional radioimmunoassay tech- niques and a commercially available ftuorometric enzyme im- munoassay for hCG. Serum hCG concentrations with both assays were negative for all specimens assayed. Cross-reactivity was suspected, and serum samples were forwarded to Serono Laboratories, commercial supplier of the immunoradiometric assay. Analysis revealed the presence of heterophile antibodies reacting with the monoclonal antibodies used in the assay.

Transcript of Heterophile antibodies and false-positive assays for human chorionic gonadotropin

Page 1: Heterophile antibodies and false-positive assays for human chorionic gonadotropin

Fetal neuromuscular blockade To the Editors:

We thank Moise et al. for publishing their extensive experience in fetal surgery (Moise KJ, Carpenter RJ Jr., Deter RL, Kirshon B, Diaz SF. The use of fetal neuromuscular blockade during intrauterine proce­dures. AM J 0BSTET GYNECOL 1987; 157:874-9).

We would like to ask Moise et al. these questions: 1. Does a 25-gauge needle leave skin dimpling or

other cutaneous scars on the fetal thigh? 2. What gauge needle was used for cordocentesis? 3. Why did they choose to transfuse prenatally a 37-

week, 3000 gm fetus (case l)? Delivery and neo­natal exchange transfusion seem to be preferable in a term baby.

M. Mark Taslimi, MD C. Neil Herrick, MD

Department of Obstetrics and Gynecology University of Tennessee-Chattanooga 921 East Third Street, Suite 400 Chattanooga, TN 37403

Reply To the Editors:

These physicians asked if the 25-gauge needle used in the intramuscular injection of pancuronium or d-tubocurarine caused skin dimpling or other cuta­neous scars on the fetal thigh. In those neonates ex­amined in our series to date, there has been no evidence of cutaneous scarring whatsoever. In addition there was a question as to what gauge needle was used for cor­docentesis. We used either a 20- or 22-gauge needle for this procedure. Finally, there was a question as to why we elected to transfuse a 37-week, 3000 gm fetus described as case 1 in our article. This patient was re­ferred with uncertain menstrual dates. On her first visit an ultrasonogram was consistent with 32.7 weeks, at which time the patient was said to be 29 weeks' gestation by dates. Amniocentesis at 34.4 weeks' gestation re­vealed a lecithin/ sphingomyelin of 1.8, negative phos­phatidylglycerol, and results of foam test classified as immature. The patient underwent her first intrauterine transfusion at 34 5/1 weeks' gestation. At 36 517 weeks' gestation it was elected to undertake the second intra­uterine transfusion. This was based on the fact that we thought it unlikely that this baby would be mature in view of uncertain menstrual dates and the known in­accuracy of late third-trimester ultrasonographic as­sessment of gestational age. Amniotic fluid obtained during the intrauterine transfusion revealed an leci­thin/ sphingomyelin of 3.3, phosphatidylglycerol 0.6 units, and foam transitional.

1598

CORRESPONDENCE

In retrospect, amniocentesis probably was warranted before this transfusion. This patient was managed dur­ing the early course of our intravascular transfusion experience. Our protocol now entails the use of am­niocentesis after 35 weeks' gestation to assess fetal lung maturity. In consultation with our neonatalogists, we have elected to deliver fetuses affected by red blood cell alloimmunization only after pulmonary maturity has been documented. Fetal transfusions late in the third trimester are performed on the labor and delivery suite with preoperative preparations. Our experience with intravascular transfusions has indicated that the major complication associated with the procedure is fetal bradycardia. Our settings allow us to undertake emergency delivery by cesarean section if indicated.

Kenneth]. Moise, Jr., MD Department of Obstetrics and Gynecology Baylor College of Medicine One Baylor Plaza Houston, TX 77030

Heterophile antibodies and false-positive assays for human chorionic gonadotropin

To the Editors: In the January 1988 issue of The AMERICAN JOURNAL

OF OBSTETRICS AND GYNECOLOGY, Check et al.' re­ported false-positive assays for serum human chorionic gonadotropin (hCG) in the range of 59 to 71 mIU/ml using an immunoradiometric assay. We have recently managed a similar case involving false-positive values in the 16 to 20 mIU /ml range using the same com­mercial assay kit.

A 25 year-old woman, gravida 0, came to the Reproductive Endocrinology Service for evaluation of infertility. She was in her usual state of good health with regular menses until ap­proximately 1984 when she noted increasing menstrual irreg­ularity marked by intervals of amenorrhea of up to 3 months. Her evaluation in 1984 was unremarkable, and she remained in otherwise good health.

In September 1987, she came to our clinic relating a history of 12 months of unprotected intercourse without pregnancy. Her last menstrual period was July 1987. Physical examination was unremarkable. A diagnosis of anovulation was made, and consideration was given to ovulation induction with clomi­phene citrate. Additional laboratory evaluation revealed a se­rum hCG concentration of 17 mIU I ml by immunoradiometric assay. The patient underwent serial hCG monitoring as listed in Table I. Additional studies included serum n-fetoprotein, CA 125, and carcinoembryonic antigen, which were negative. The patient was managed expectantly, and serum samples were reassayed with conventional radioimmunoassay tech­niques and a commercially available ftuorometric enzyme im­munoassay for hCG. Serum hCG concentrations with both assays were negative for all specimens assayed. Cross-reactivity was suspected, and serum samples were forwarded to Serono Laboratories, commercial supplier of the immunoradiometric assay. Analysis revealed the presence of heterophile antibodies reacting with the monoclonal antibodies used in the assay.

Page 2: Heterophile antibodies and false-positive assays for human chorionic gonadotropin

Volume 159 Number 6

Regardless of the immunoassay used, false-positive results for serum hCG remain a perplexing, albeit in­frequent, clinical problem. Bock et al.2 reported false­positive results for hCG of 32 to 55 IU IL caused IgM antibodies using an immunoenzymatic assay (Tan­dem E hCG assay, Hybritech Inc., San Diego, Calif.). The recent report of Check et al. 1 and our case describe false-positive results caused heterophile anti­bodies (IgG) using an immunoradiometric assay (hCG MAIAclone, Serono Laboratories, Norwell, Mass.). Such antibodies have been well characterized and their interference in immunoassays well described.3

•4 Various

laboratory techniques have been used to reduce assay interference, including the addition of nonspecific im­munoglobulins. 5

Given the sensitivity and specificity of most com­mercially available assay kits for hCG, false-positive re­sults are indeed rare but should be considered in the differential diagnosis in those patients in whom con­sistently low levels of hCG are not in agreement with clinical presentation. The data of the present case sug­gest that in such clinical circumstances, serial sampling and testing for hCG with the use of alternate assay techniques may be warranted before intervention is considered. Timely consultation with appropriate lab­oratory personnel and the commercial distributor proved invaluable in our management and should be incorporated, when clinical conditions permit, in the evaluation of patients with persistently low levels of serum hCG.

Major Gerard S. Letterie, MC, USA Captain Scott Rose, MC, USA

Colonel Kunio Miyazawa, MC, USA Department of Obstetrics-Gynecology Tripler Army Medical Center Honolulu, HI 96859-5000

REFERENCES

I. Check JH, Nowrooz K, Chase JS, Lauer C, Elkins B, Wu CH. False-positive human chorionic gonadotropin levels caused by a heterophile antibody with the immunoradio­metric assay. AM J 0BSTET GYNECOL 1988;158:99-100.

2. BockJL, FurqiueleJ, Wenz B. False-positive immunometric assays caused by antiimmunoglobulin antibodies: a case re­port. Clin Chim Acta 1985;147:241-6.

3. Boscato LM, Stuart MC. Incidence and specificity of inter­ference in two-site immunoassays. Clin Chem 1986;32: 1491-5.

4. Thompson RJ, Jackson AP, Langlois N. Circulating anti­bodies to mouse monoclonal immunoglobulin in normal subjects-incidence, specificity and effects on a two-site assay for creatine-kinase-MB isoenzyme. Clin Chem 1986; 32:476-81.

5. Boscato LM, Stuart MC. Heterophilic antibodies: a prob­lem for all immunoassays. Clin Chem 1988;34:27-33.

Pediatric cardlology To The Editors:

In the report of Yagel et al. (Yagel S, Hochner­Celnikier D, Hurwitz A, Patti Z, Gotsman MS. AM J

Correspondence 1599

Table I. Serial hCG monitoring with immunoradiometric assay

Date

91 I /87 9/8/87

9115/87 9/28/87

10/15/87 10/16/87 10/26/87

{3-hCG (m!Ulml)

17 18 17 19 16 14 16

OBSTET GYNECOL 1988; 158:272-7), some of the cardiac descriptions were not precise. In the discussion of the patient with "complete atrioventricular canal," the au­thors conclude by describing a "complete endocardial cushion defect." In pediatric cardiology there are sev­eral schools of anatomic nomenclature, and generally, one chooses a particular classification and uses one set of terms consistently. The lesion to which the authors refer may be described as a complete atrioventricular canal, endocardial cushion defect, or atrioventricular septal defect depending on the particular system of nomenclature.

The authors described a mitral and tricuspid valve in this patient with common atrioventricular canal. In this lesion, there is a common atrioventricular valve without distinct mitral and tricuspid valves. In addition, the authors described a "perimembranous" ventricular septal defect. The ventricular communication in this lesion might be described as a "canal-type" or "inlet" ventricular septal defect.

In another case, the authors state that the parallel great arteries are "indicative of transposition of the great vessels." Although this characteristic view is often seen with dextrotransposition, the identity of each great vessel (and all cardiac structures) is based on the de­tection of specific anatomic characteristics (for example, the aorta gives rise to the head and neck vessels, the main pulmonary artery gives rise to two branch pul­monary arteries) rather than their location.

Medical Genetics West Penn Hospital Pittsburgh, PA 15224

Angela E. Lin, MD

The fimbrial biopsy In Chlamydia trachomatls pelvlc inflammatory disease

To the Editors: Endocervical samples are routinely used for diag­

nosis of gynecologic Chlamydia trachomatis infection by culture or direct immunoftuorescent staining. Fallopian tube swabs and small biopsies did not increase the de­tection of C. trachomatis in pelvic inflammatory disease.'

During laparoscopy in severe pelvic inflammatory disease, 3 by 2 mm fimbrial biopsies were performed with a Frangenheim forceps (Storz). All bleeding