Is the administration of RhoGam indicated among Rh-negative women with vaginal bleeding

during early pregnancy?

Na Rae Ju

PGY-3

August 28, 2013

References

• Visscher RD, Visscher HC. Do Rh-negative women with an early spontaneous abortion need Rh immune prophylaxis?. Am J Obstet Gynecol. 1972;113:158–165.

• Von Stein GA, Munsick RA, et al. Fetomaternal hemorrhage in threatened abortion. Obstetrics & Gynecology. 1992;79(3):383–386.

• McSweeney E, Kirkham J, Vinall P, et al. An audit of anti-D sensitization in Yorkshire. Br J Obstet Gynaecol. 1998;105:1091–1094.

• Hernández-Andrade E, Ahued-Ahued JR. Transvaginal bleeding during pregnancy associated with Rhesus-D isoimmunization. Salud Pública de Méx. 2003;45(6):492–496.

Visscher & Visscher (1972)

• Only RCT - included in 2013 Cochrane Review

• ID’ed 57 Rh-negative mothers who had spontaneous miscarriage b/t 8-24 weeks’ gestation over 32 mo period

• 48 participated in double-blind study

Visscher & Visscher (1972)

• 19/57 treatment group: 14/19 D&C & 5/19 spontaneous miscarriage

• 29/57 control group: 25/29 D&C & 4/29 spontaneous miscarriage

• Coded ampules containing 300 μg of Rh immune globulin & 1 mL of placebo were randomly allocated to participants w/in 72 hrs after spontaneous complete miscarriage or operative termination of incomplete miscarriage

Visscher & Visscher (1972)

• Results:– At 6 months, all 19 from treatment group &

all 29 from control group were non-sensitized by indirect Coombs’ test

– Subsequent 9 Rh-positive pregnancies (6/19 from treatment group & 3/29 from control group) showed no evidence of Rh alloimmunization

Visscher & Visscher (1972)

• Conclusions:– In early spont abortions, Rh

isoimmunization rarely, if ever, occurs– Rh immune prophylaxis has not been

proven to be necessary

Visscher & Visscher (1972)

• Limitations:– Small sample size– Uncertain length of f/u period– Not clear how sequence of code on vials

generated & how randomization of participants done

Von Stein et al (1992)

• Case control study• ID’ed pregnant pts at <20 weeks’ gestation who

presented to ED w/ vaginal bleeding w/o cervical dilatation or passage of tissue– Excluded women w/ cervicitis, cervical polyps, other

obvious cervical lesions, ectopic pregnancy, missed abortion, or septic abortion

• Pregnant control population consisted of women of similar gestational ages who presented for elective abortion– Excluded women w/ h/o antepartum bleeding

Von Stein et al (1992)

• Determined incidence of fetomaternal hemorrhage using Kleihauer- Betke (KB) acid elution test– Nonpregnant, age-matched control group

used to establish baseline + KB value

Kleihauer-Betke (KB) Test

• Used to measure amount of fetal hemoglobin transferred from fetus to mother’s bloodstream

Von Stein et al (1992)

• Results:– 10/89 (11%) subjects w/ threatened abortion had

e/o transplacental hemorrhage– 4/94 (4%) of pregnant controls had e/o

transplacental hemorrhage– 1/66 (2%) of nonpregnant controls had positive KB

Von Stein et al (1992)

• Results:– Diff b/t threatened abortion & pregnant control

group was not statistically significant (P=0.13)– Diff b/t pregnant & nonpregnant control group was

not statistically significant (P=0.49)– Diff b/t threatened abortion & combined control

group was statistically significant (P<0.05)

Von Stein et al (1992)

• Conclusions:– There is increased incidence of

transplacental hemorrhage in pts w/ threatened abortion

– This may indicate that Rh-negative women w/ threatened abortion should receive RhoGam

Von Stein et al (1992)

• Limitations:– Observational study, no intervention

performed– Did not actually assess development of

auto-antibodies

McSweeney et al (1998)

• Retrospective observational study

• ID’ed 147 cases of RhD sensitization from 15 obstetric units from 1988-91 in Yorkshire region

• Only 129 cases (or 312 pregnancies) were included in study, since data lacking in other 18 cases

McSweeney et al (1998)

McSweeney et al (1998)

• Conclusions:– Increased compliance w/ RhoGam for

published recommendations is necessary– In particular, RhoGam should be

administered following potentially immunizing events during first 20 wks of pregnancy; however, further research needs to be done to determine dosing

McSweeney et al (1998)

• Limitations:– Retrospective study– Missing data– No control group– Results may not be applicable to our

population

Hernandez-Andrade et al (2003)

• Retrospective case control study• ID’ed 3722 Rh-negative pts who received care at

Mexico’s National Perinatology Institute from 1995-2001

• Cases: 24 non-immunized pregnant women w/ positive anti-D ab seroconversion during pregnancy or early postpartum period

• Controls: 24 non-immunized pregnant women, enrolled after each case, w/ similar clinical characteristics, but w/o anti-D ab seroconversion

Hernandez-Andrade et al (2003)

• No differences in clinical characteristics b/t both groups

• All pts had newborns who were Rh-positive & did not receive RhoGam

• Any episodes of vaginal bleeding were recorded

Hernandez-Andrade et al (2003)

• Results:– 18/24 (75%) of cases had vaginal bleeding– 5/24 (20%) of controls had vaginal

bleeding

Hernandez-Andrade et al (2003)

Threatened abortion

Bleeding after amniocentesis

Retroplacental hematoma

Low insertion of placenta

Preterm uterine activity

VB before 20 wks gestation

VB after 20 wks gestation

VB at any stage of pregnancy

Frequency of risk factors & odds ratios

for Rh antigen isoimmunization

during pregnancy

Causes of VB

Hernandez-Andrade et al (2003)

• Conclusion:– Prophylaxis w/ RhoGam should be given to

all non-immunized Rh-negative pregnant women w/ vaginal bleeding at any stage of pregnancy

Hernandez-Andrade et al (2003)

• Limitations:– Retrospective study– Small study sample– Results may not be applicable to our

population

HUPism

• The evidence for or against RhoGam for vaginal bleeding in early pregnancy is lacking. However, until there is more definitive data against the administration of RhoGam, it should continue to be given in Rh-negative patients who present with vaginal bleeding in early pregnancy.

Questions?

Indirect Coombs Test