American Journal of Hematology 24:429-432 (1987)

Screening for Sickle Cell Trait: The Veterans Administration National Sickle Cel I Program Leo M. Meyer, Junius G. Adams 111, Martin H. Steinberg, Inez E. Miller, and Norma Stokes

VA Extended Care Center, St. Albans, New York; VA Medical Center and University of Mississippi School of Medicine, Jackson, Mississippi

Results of the Veterans Administration Sickle Cell Program for a period of 10 years are presented. We screened 370,250 patients; 404,341 attended educational sessions, and 38,347 had individual counseling sessions. Sickle cell trait was present in 6.4% of patients, and HbC trait was present in 1.8%. The clinically significant disorders HbSC disease, sickle cell anemia, and sickle fi thalassemia were present in 0.41 % of individuals screened. A large number of uncommon variants were detected. The program enhanced the awareness of and the approach to evaluation of hemoglobinopathies .

INTRODUCTION

The National Sickle Cell Anemia Act authorized the establishment of a national program for the diagnosis, control, treatment, and research in sickle cell anemia. Statutory authorization for the Veterans Administration comprehensive program for sickle cell screening, education, and counseling was part of this legislation. As an outgrowth of the VA cooperative study in sickle cell trait (HbAS) [l], the current program of screening, education, and counseling of all veterans likely to have HbAS was implemented. This report presents the data gathered over a period of 10 years.

Principal Investigators: A. Prasad (Allen Park, MI), L. Weatherbee (Ann Arbor, MI), C. Lutcher (Augusta, GA), A. Seiguer (Baltimore, MD), H. Friedman (Birmingham, AL), T. Muhlfelder (Bronx, NY), S. Rothenberg (Brooklyn, NY), W. Lawrence (Buffalo, NY), F.M. Brown (Charleston, SC), H. Kwaan (Chicago, IL), S. Schade (Chicago, IL), A. Muhleman (Cincinnati, OH), T.R. Spitzer (Cleveland, OH), R. Sheehan (Dallas, TX), J.B. Weinberg (Durham, NC), L. Howard (East Orange, NJ), 0. Iglesias (Fayetteville, NC), M.A. Savin (Hampton, VA), H. Messmore (Hines, IL), C. Waddell (Houston, TX), M. Steinberg (Jackson, MS; Reference Laboratory), A. Mansouri (Little Rock, AR), A. Lichtenstein (Los Angeles, CA), W. Lockwood (Louisville, KY), H.B. Neil1 (Memphis, TN), K. Tornyos (New Orleans, LA), H. Ballard (New York, NY), W.K. Smith (Richmond, VA), L.M. Meyer (St. Albans, NY; Administrative Office), J. Reimers (St. Louis, MO), A. Deisseroth (San Francisco, CA), F. Muniz (San Juan, PR), R.C. Hartmann (Tampa, FL), M.R. Osman (Temple, TX), J. M. Webber (Tuskegee, AL), G. Schechter (Washington, DC), R. Papac (West Haven, CT), and S. Hanson (Wilmington, DE). Received for publication September 18, 1986; accepted September 29, 1986. Supported in part by Research funds of the Veterans Administration and the VA Sickle Cell Program.

Address reprint request to Martin H. Steinberg, M.D. (151), VA Medical Center, Jackson, MS 39216.

0 1987 Alan R. Liss, Inc.

430 Brief Report: Meyer et a1

METHODS

All black and hispanic patients in hospsitals where they constituted an apprecia- ble proportion of admissions were approached for possible testing. In some hospitals all admissions were screened for thalassemia trait by examining the results of auto- mated CBCs for the presence of microcytosis. An educational film designed to present information on sickle cell trait and disease that was intelligible to laymen was shown on CCTV on frequent occasions throughout hospitals. Brochures, posters, and lantern slide presentations were available to all patients.

After obtaining informed consent, 5-7 ml of anticoagulated blood was obtained by venipuncture. A portion of this was used for detection of sickle cell trait and other hemoglobinopathies . Hemoglobin electrophoresis was performed on cellulose acetate membranes at pH 8.6 [2]. Samples showing a variant hemoglobin corresponding to sickle hemoglobin (HbS) were further evaluated using the dithionite solubility test and citrate agar electrophoresis. Other hemoglobins in addition to HbS and HbC were studied in the Reference Laboratory. This laboratory also served as a reference and proficiency testing center for the hospitals participating in the program.

When an individual was found to have sickle cell trait or one of the clinically significant sickle hemoglobinopathies, confidential genetic counseling was offered. Pre- and postcounseling questionnaires were used to assess the utility of counseling sessions.

With the permission of the counselee, some counseling sessions were tape recorded and reviewed by a committee of three (two experienced counselors and the chief of the program) to determine adherence to the prescribed format. When sickle cell trait was detected in a patient, the spouse was offered the opportunity to be tested and participate in the counseling session.

RESULTS

Our data do not permit us to determine the number of individuals offered testing but who declined to participate. There were 404,341 individuals who attended edu- cation sessions, 370,250 were screened, and 38,347 received individual counseling sessions.

Table I shows the common abnormal hemoglobin genotypes detected. A number of other less common hemoglobin variants and abnormal electrophoretic patterns were detected. These are shown in Table II.

Rare variants detected included Hb Gun Hill [l], Hb Hope [l], Hb I [2], Hb N [3] , Hb 0 Arab [ 11, Hb Alamo [ 11 , and Hb Hasharon [ 11.

The percent errors obtained in the proficiency testing program were as follows: 1976-0.46%;1977-1.41%; 1978-1.28%; 1979--1.47%; 1980-0.77%; 1981-

TABLE I. Common Hemoglobinopathies Detected in Screening Black Veterans

Hemoglobin genotype No. Percent of patients screened

Sickle cell trait 23,706 6 .4 HbC trait 6,663 1.8 HbSC disease 652 0.18 Sickle cell anemia 540 0.14 HbS-0-Thalassemia 336 0.09 Heterozygous 0-Thalassemia 680 0.18

Brief Report: Screening for Sickle Cell 431

TABLE 11. Uncommon Variants and Electrophoretic Patterns Observed

Variant No.

HbA + HbF’ 294 114

HbG (a-globin variant) 32 HbJ 28 HbA2 variants 66 HbE 4 HbC Harlem 6 HbCCC 102 “Fast” variantd 20 Hb Lepore 6

aThis category includes heterocellular and pancellular hereditary persistence of HbF and Go-thalassemia. HbF levels ranged from 2 % to 25 % . bThese were defined as nonsickling variants with the electrophoretic migration of HbS, that were present at about a 40% concentration and were not associated with a variant HbA2. ‘HbCC + HbC with elevated HbF. dunidentified variant with rapid electrophoretic mobil- ity other than HbJ.

Hb “D*>b

0.58%; 1982-0.05%; 1983-0.19%; 1984-0.73%. Of these errors, 22.1% were found to be clerical.

DISCUSSION

Screening for HbS heterozygotes has two major purposes: 1) to inform carriers of any possible health consequence of this condition, and 2) to identify couples at risk of having offspring with a severe sickle hemoglobinopathy so that they may be informed of the likelihood of having affected children. The value of a screening program based upon either of these premises is unproven.

About 9% of our patients screened had an abnormality by hemoglobin electro- phoresis, but less than 0.5% had a clinically significant hemoglobinopathy. This is not unexpected given the highly selected population examined. A surprising finding is the substantial number of patients detected who had HbSS, HbSC disease, or HbS- P-thalassemia. The frequency of this diagnosis approximated that expected for the black adult population in general. It is highly unlikely that this is the true incidence of these disorders in the veteran population. More plausible is that patients with serious hemoglobinopathies have been tested on multiple occasions and often in more than a single institution.

The prevalence of HbAS appears to be lower than expected on the basis of previous studies [1,3]. This might be influenced by the low prevalence of Hb AS in certain black population, as well as by the inclusion of Caucasians screened for P thalassemia trait in some programs.

A large number of uncommon and rare hemoglobin abnormalities were found. Most of these variants have previously been detected in blacks and few were associ- ated with hematologic disease. Excluding individuals whose sole abnormality was an

432 Brief Report: Meyer et al

elevated HbF level (0.07%), these abnormalities were seen in 0.10% of the patients screened.

In general, the purposes of the program were fulfilled since the educational and screening procedures were available to all who expressed an interest. No attempt was made at any time to influence the patient or spouse as to what course of action to take regarding family planning. This decision was always left with the patient. Importantly, the participants in the program felt that its presence enhanced the awareness of and the approach to the diagnosis of inherited disorders of hemoglobin structure and synthesis.

ACKNOWLEDGMENTS

cooperation and Connie Palmer for preparing the manuscript. The authors acknowledge with thanks Dr. Charles F. Whitten for his continued

REFERENCES

1. Heller P, Best WR, Nelson RB, Bechtel J: Clinical implication of sickle cell trait and G-6-PD

2. Honig GR, Adams JG 111: “Human Hemoglobin Genetics.” New York: Springer-Verlag, 1986. 3. Motulsky AG: Frequency of sickling disorders in U.S. blacks. N Engl .I Med 288:31-33, 1973.

deficiency in hospitalized black patients. N Engl J Med 300:lOOl-1005 1979.