1. Is the administration of RhoGam indicated among Rh-negative women with vaginal bleeding during early pregnancy? Na Rae Ju PGY-3 August 28, 2013

2. 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.

3. 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

4. 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 μ g 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

5. 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

6. Visscher & Visscher (1972) Conclusions: –In early spont abortions, Rh isoimmunization rarely, if ever, occurs –Rh immune prophylaxis has not been proven to be necessary

7. 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

8. 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

9. 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

10. Kleihauer-Betke (KB) Test Used to measure amount of fetal hemoglobin transferred from fetus to mother’s bloodstream

11. 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

12. 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)

13. 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

14. Von Stein et al (1992) Limitations: –Observational study, no intervention performed –Did not actually assess development of auto-antibodies

15. 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

16. McSweeney et al (1998)

17. 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

18. McSweeney et al (1998) Limitations: –Retrospective study –Missing data –No control group –Results may not be applicable to our population

19. 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

20. 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

21. Hernandez-Andrade et al (2003) Results: –18/24 (75%) of cases had vaginal bleeding –5/24 (20%) of controls had vaginal bleeding

22. 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

23. 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

24. Hernandez-Andrade et al (2003) Limitations: –Retrospective study –Small study sample –Results may not be applicable to our population

25. 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.

26. Questions?

27. Indirect Coombs Test