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Prevention of Rh immunization after transfusion with Rh-positive blood
Prevention of Rh immunization
after transfusion
with Rh-positive blood THOMAS
G.
WILLIAM Flemington
McELRATH,
Q. and
ASCARI,
Raritan,
M.D. M.D.
New
Jersey
A nulliparous Rh-negative woman received a#firoximately 500 ml. of Rh-positive blood following acute blood loss associated with an incomplete abortion. Twenty vials of Rh-immune globulin were administered to her in divided doses within 72 hours after transfusion. This was followed by the development of a passive anti-Rh titer of I :I 6 and the disappearancs of the transfused Rh-positive cells from her circulation ouer a 12 day period. No adverse reaction was experienced by the patient and an eight-month follow-up indicates no evidence of active Rh immunization.
R H -IM M u N E suppression with Rhimmune globulin represents one of the most recent developments in disease prevention. Whereas the success in preventing maternal Rh immunization after Rh-incompatible term pregnancies has been remarkable, only variable success has been achieved in case of massive fetal maternal hemorrhage and Rhincompatible transfusions. In theory, the technique of Rh-immune suppression should work even for large volumes of Rh-positive blood entering the circulation of Rh-negative individuals. In January, 1970, we had the opportunity of testing the safety and efficacy of Rh-immune globulin in preventing Rh immunization after an accidental transfusion of one unit of 500 C.C. of Rh-positive blood in an Rh-negative woman, as the following case illustrates.
cervical OS. The protruding products of conception were removed with a sponge stick and the patient was treated with bed rest and Syntocinon” in an intravenous infusion of glucose in water. Blood tests on admission revealed a hematocrit of 30 per cent with a hemoglobin of 9.5 Cm. per cent. Two hours later, the patient was observed to be in shock with evidence of peripheral vascular constriction and a blood pressure of 90/50. Her hemoglobin had fallen to 7.6 Gm. per cent. The patient was re-examined and additional placental tissue was removed from the cervix and vagina following which the bleeding became minimal. A request for blood transfusion was made and the patient was typed as Group 0, Rh positive. One unit of suitably cross-matched blood was provided and administered. Three hours later, a second unit of whole blood was requested. This time
Case reporf A gravida ii, para 0 woman was hospitalized in approximately her twentieth week of gestation with a history of passing a small fetus at home and profuse vaginal bleeding of several hours’ duration. Physical examination showed cervical dilatation of 3 cm. with portions of the umbilical cord and placental tissue visible at the From the Gynecology, Flemington, Research, Foundation,
the
patient
was
typed
as
Croup
0,
Rh
negative. In view of this discrepancy, the original specimen of the patient’s blood was retyped and the results were as follows: Group 0, rh’(C) negative, Rho(D) negative, rh”(E) negative. hr’( c) positive, DU negative. Her probable genotype was rr (cde/cde). The direct and indirect Coombs tests were negative. Typing of the first unit administered in transfusion revealed it to be Group 0, rh’( C) positive, R&(D) positive, rh”( E) positive, hr’( c) positive, hr” (e) positive. The probable genotype of the donor was R,R, (CDe/cDE) . Because of the risk to this childless woman’s
Department of Obstetrics and Hunterdon Medical Center, and the Division of Clinical Diagnostics, Ortho Research Raritan.
*Trademark J~~XY.
309
of
Sandoz
Pharmaceuticals,
Hanr~~,
New
310
McElrath
and
Ascari
Table I. Laboratory
results on patient’s
Post
Pretransfusion specimen
Rho (D) antigen Indirect Coombs test Direct Coombs test Anti-Rho (D) titer Haptoglobin level (mg. %) Bilirubin (mg. %) *N.D.,
Analysis
blood
2 days
1 3 days
/ 5 days
N.D.”
t 120
t +
t +tt
+ CD”) +++
t
-
I:1 119
ttt I:16 N.D.
I:16 N.D.
1:16
0.1
N.D.
N.D.
0.3
N.D.
+t+-
days
I12 days / 25 days I.52 days / 88 days / 242
-
-
-
119
+ 1:1(C) N.D.
N.D.
113
0.2
N.D.
N.D.
0.1
it+
not done.
reproductive potential, it was decided to attempt the prevention of Rh immunization. Twenty vials of RhoGAM* Rh, (D) immune globulin (human) were obtained, 10 of which were administered intramuscularly 60 hours after her incompatible transfusion and additional 10 vials were administered 72 hours after transfusion. During this period, a completion dilatation and curettage was performed. During the postoperative period, the patient’s hemoglobin stabilized at 9.7 Gm. per cent. She was discharged from the hospital on the sixth postoperative day and was followed serologically for a period of eight months postabortally. Table I summarizes the values obtained after transfusion to assess the effect of the Rh-immune globulin in clearing the mismatched cells from patient’s circulation. Comment Keith and associates1 have summarized the published experience to date with Rhimmune suppression after extraordinarily large fetomaternal hemorrhages and transfusion accidents. From their analysis of the case reports, the incident of success is roughly correlated with a ratio of antibody (in micrograms) to antigen (milliliters of whole blood) of 6: 1 or greater. In the present case, 6,000 pg of (300 pg per vial) antiRh,( D) were administered to the patient after approximately 500 ml. of Rh-positive blood which yields a 12 : 1 antibody:whole blood ratio. The 20 vials of Rh-immune globulin administered gave a passive antiRh, (D) titer of 1: 16 in the patient’s serum. The Rh-incompatible cells remained weakly detectable by the D” test as long as 12 days after transfusion. “Tradema.k
transfusion
of Ortho
Diagnostics,
Raritan.
New
Jersey.
The patient tolerated the course of Rhimmune suppression with no apparent adverse reaction except for the local tenderness at the sites of intramuscular injection. Chemically, no fall was observed in haptoglobin levels and the maximum bilirubin level obtained was 0.3 mg. per cent. In the present case, the decision to employ 20 vials of Rh-immune globulin was predicted on previous experiences with at least 12 similar cases in which one of us (W. Q. A.) was asked to consult. There is no known hazard to overtreatment; however, inadequate therapy, i.e., insufficient antibody relative to the volume of circulating antigen, can lead to enhancement of the likelihood of Rh immunization.” Twenty (20) vials of RhoGAM probably represent a somewhat excessive dose after 500 ml. of Rh-positive blood, but our intention was to err on the conservative side. Certainly every Rh-negative recipient of Rh-positive blood, regardless of the volume, will not become immunized. In our patient, even a small risk left untreated would be intolerable since she has no living offspring and her husband is homozygous Rh positive. The absence of Rh,(D) in her circulation eight months after transfusion and passive immunization is fair assurance that she has escaped lifelong active Rh immunization. The ultimate test will be an uneventful subsequent pregnancy.
REFERENCES
1. Keith, L., Cuva, A., Houser, K., and Webster, A.: Transfusion 10: 142, 1970. 2. Pollack, W., Gorman, J. G., and Freda, V. J.: Progr. Hematol. 6: 121, 1969.
after transfusion
with Rh-positive blood THOMAS
G.
WILLIAM Flemington
McELRATH,
Q. and
ASCARI,
Raritan,
M.D. M.D.
New
Jersey
A nulliparous Rh-negative woman received a#firoximately 500 ml. of Rh-positive blood following acute blood loss associated with an incomplete abortion. Twenty vials of Rh-immune globulin were administered to her in divided doses within 72 hours after transfusion. This was followed by the development of a passive anti-Rh titer of I :I 6 and the disappearancs of the transfused Rh-positive cells from her circulation ouer a 12 day period. No adverse reaction was experienced by the patient and an eight-month follow-up indicates no evidence of active Rh immunization.
R H -IM M u N E suppression with Rhimmune globulin represents one of the most recent developments in disease prevention. Whereas the success in preventing maternal Rh immunization after Rh-incompatible term pregnancies has been remarkable, only variable success has been achieved in case of massive fetal maternal hemorrhage and Rhincompatible transfusions. In theory, the technique of Rh-immune suppression should work even for large volumes of Rh-positive blood entering the circulation of Rh-negative individuals. In January, 1970, we had the opportunity of testing the safety and efficacy of Rh-immune globulin in preventing Rh immunization after an accidental transfusion of one unit of 500 C.C. of Rh-positive blood in an Rh-negative woman, as the following case illustrates.
cervical OS. The protruding products of conception were removed with a sponge stick and the patient was treated with bed rest and Syntocinon” in an intravenous infusion of glucose in water. Blood tests on admission revealed a hematocrit of 30 per cent with a hemoglobin of 9.5 Cm. per cent. Two hours later, the patient was observed to be in shock with evidence of peripheral vascular constriction and a blood pressure of 90/50. Her hemoglobin had fallen to 7.6 Gm. per cent. The patient was re-examined and additional placental tissue was removed from the cervix and vagina following which the bleeding became minimal. A request for blood transfusion was made and the patient was typed as Group 0, Rh positive. One unit of suitably cross-matched blood was provided and administered. Three hours later, a second unit of whole blood was requested. This time
Case reporf A gravida ii, para 0 woman was hospitalized in approximately her twentieth week of gestation with a history of passing a small fetus at home and profuse vaginal bleeding of several hours’ duration. Physical examination showed cervical dilatation of 3 cm. with portions of the umbilical cord and placental tissue visible at the From the Gynecology, Flemington, Research, Foundation,
the
patient
was
typed
as
Croup
0,
Rh
negative. In view of this discrepancy, the original specimen of the patient’s blood was retyped and the results were as follows: Group 0, rh’(C) negative, Rho(D) negative, rh”(E) negative. hr’( c) positive, DU negative. Her probable genotype was rr (cde/cde). The direct and indirect Coombs tests were negative. Typing of the first unit administered in transfusion revealed it to be Group 0, rh’( C) positive, R&(D) positive, rh”( E) positive, hr’( c) positive, hr” (e) positive. The probable genotype of the donor was R,R, (CDe/cDE) . Because of the risk to this childless woman’s
Department of Obstetrics and Hunterdon Medical Center, and the Division of Clinical Diagnostics, Ortho Research Raritan.
*Trademark J~~XY.
309
of
Sandoz
Pharmaceuticals,
Hanr~~,
New
310
McElrath
and
Ascari
Table I. Laboratory
results on patient’s
Post
Pretransfusion specimen
Rho (D) antigen Indirect Coombs test Direct Coombs test Anti-Rho (D) titer Haptoglobin level (mg. %) Bilirubin (mg. %) *N.D.,
Analysis
blood
2 days
1 3 days
/ 5 days
N.D.”
t 120
t +
t +tt
+ CD”) +++
t
-
I:1 119
ttt I:16 N.D.
I:16 N.D.
1:16
0.1
N.D.
N.D.
0.3
N.D.
+t+-
days
I12 days / 25 days I.52 days / 88 days / 242
-
-
-
119
+ 1:1(C) N.D.
N.D.
113
0.2
N.D.
N.D.
0.1
it+
not done.
reproductive potential, it was decided to attempt the prevention of Rh immunization. Twenty vials of RhoGAM* Rh, (D) immune globulin (human) were obtained, 10 of which were administered intramuscularly 60 hours after her incompatible transfusion and additional 10 vials were administered 72 hours after transfusion. During this period, a completion dilatation and curettage was performed. During the postoperative period, the patient’s hemoglobin stabilized at 9.7 Gm. per cent. She was discharged from the hospital on the sixth postoperative day and was followed serologically for a period of eight months postabortally. Table I summarizes the values obtained after transfusion to assess the effect of the Rh-immune globulin in clearing the mismatched cells from patient’s circulation. Comment Keith and associates1 have summarized the published experience to date with Rhimmune suppression after extraordinarily large fetomaternal hemorrhages and transfusion accidents. From their analysis of the case reports, the incident of success is roughly correlated with a ratio of antibody (in micrograms) to antigen (milliliters of whole blood) of 6: 1 or greater. In the present case, 6,000 pg of (300 pg per vial) antiRh,( D) were administered to the patient after approximately 500 ml. of Rh-positive blood which yields a 12 : 1 antibody:whole blood ratio. The 20 vials of Rh-immune globulin administered gave a passive antiRh, (D) titer of 1: 16 in the patient’s serum. The Rh-incompatible cells remained weakly detectable by the D” test as long as 12 days after transfusion. “Tradema.k
transfusion
of Ortho
Diagnostics,
Raritan.
New
Jersey.
The patient tolerated the course of Rhimmune suppression with no apparent adverse reaction except for the local tenderness at the sites of intramuscular injection. Chemically, no fall was observed in haptoglobin levels and the maximum bilirubin level obtained was 0.3 mg. per cent. In the present case, the decision to employ 20 vials of Rh-immune globulin was predicted on previous experiences with at least 12 similar cases in which one of us (W. Q. A.) was asked to consult. There is no known hazard to overtreatment; however, inadequate therapy, i.e., insufficient antibody relative to the volume of circulating antigen, can lead to enhancement of the likelihood of Rh immunization.” Twenty (20) vials of RhoGAM probably represent a somewhat excessive dose after 500 ml. of Rh-positive blood, but our intention was to err on the conservative side. Certainly every Rh-negative recipient of Rh-positive blood, regardless of the volume, will not become immunized. In our patient, even a small risk left untreated would be intolerable since she has no living offspring and her husband is homozygous Rh positive. The absence of Rh,(D) in her circulation eight months after transfusion and passive immunization is fair assurance that she has escaped lifelong active Rh immunization. The ultimate test will be an uneventful subsequent pregnancy.
REFERENCES
1. Keith, L., Cuva, A., Houser, K., and Webster, A.: Transfusion 10: 142, 1970. 2. Pollack, W., Gorman, J. G., and Freda, V. J.: Progr. Hematol. 6: 121, 1969.