Determining the correct dosage of RHIG for immunoprophylaxis of feto-maternal hemorrhage (FMH)

A physician in Oregon wonders what practice other institutions follow with respect to recommending a dose of RHIG after quantification of feto-maternal hemorrhage (FMH) by flow cytometery or Kleihauer-Betke test. Specifically, she wants to know if laboratories recommend a dosage of RHIG along with the lab report quantifying the amount of FMH or merely report the result of testing (i.e., so many % fetal red cells seen) and leave the dosage calculation strictly to the clinician. Currently her laboratory reports the results of the FMH testing and recommends an RHIG dosage, but she is strongly considering discontinuing the dosage recommendation. She is concerned that by recommending a dosage the laboratory is "prescribing" a medication dose. Also, she is concerned about clinical variables that may impact the RHIG dose about which the laboratory is unaware.

The following comments have been received.

ADDENDA August 1, 2007

1. A transfusion medicine physician located at a major East Coast University hospital urges the physician in Oregon to maintain her laboratory's current practice of recommending a dose of RHIG based on the results of testing for FMH. The East Coast colleague points out that a recommendation for administration of RHIG is NOT the same as a prescription, and that practicing clinical physicians can hardly be expected to keep up with all developments in medicine. In his opinion, it is in the best interest of the patient if clinicians are given expert advice which the clinician may then choose to modify in light of the individual circumstances of each patient. In the absence of any recommendation, it is entirely possible that no RHIG would be given, which would be potentially detrimental to future pregnancies. Imagine if a pathology report of a biopsy that was suspicious for a malignancy failed to recommend further evaluation. At the East Coast colleague's institution, they report the Kleihauer-Betke findings and couple these with a recommended dose of RHIG. He concludes saying "Laboratories have much to contribute to patient care; we should not underestimate our value."
   
   
2. Dr. James AuBuchon at the Dartmouth-Hitchcock Medical Center in New Hampshire (attribution used with permission) comments that his laboratory's report provides the quantitative determination of the proportion of fetal cells in the maternal circulation by flow cytometry and the report suggests the corresponding RHIG dose calculated using the patient's weight (and thus blood volume). If the patient is in their center, the physician usually orders "RHIG" and leaves the calculation of the dosage to the Transfusion Service. (Similarly, they routinely calculate the dose for many components, including plasma (at 10 mL/kg), cryoprecipitate (based on patient weight and latest fibrinogen level, and many plasma derivatives that they handle.) This practice is well established in that institution and approved by the Transfusion Committee. Dr. AuBuchon adds that he would not regard the suggestion of an RHIG dose as "the lab practicing medicine" any more than he would regard a product insert's suggested dose of a drug as the pharmaceutical company practicing medicine. Once they have the data (% fetal cells), the lab is simply performing a calculation that the physician him/herself could also perform (but, in actuality, is more likely to get wrong!). Clinical judgment is required to be applied by a physician in all prescriptions, and the calculation (and its assumptions) need to be rectified with the clinical situation.
   
   
3. A transfusion medicine physician located at an academic center in Vermont reports that in his opinion the crux of the problem is the following AABB Standards for Blood Banks and Transfusion Services: AABB STD 5.20.3 "There shall be a process to ensure that an adequate dose of Rh immunoglobulin is administered." He comments that the choice to ensure compliance with this AABB Standard is to either report a recommended dosage in conjunction with the FMH report, or to review the number of doses of RHIG issued to confirm adequate dosing based on the FMH report. His laboratory reports the volume of the FMH in the hematology lab, but they do NOT report a recommended RHIG dosage. If asked by the OB/GYN service, the pathology resident will share with them the formula for calculating a RHIG dose verbally. The responding physician has confirmed with the OB/GYN service in the past that they are using the same formula. However, he does check and document that an appropriate dose of RHIG is given based on the Kleihauer-Betke test for patients with a positive fetal screen result in the Blood Bank. Whenever there is a positive fetal screen in Blood Bank, a reflex Kleihauer-Betke test is performed in Hematology, and the OB/GYN service is notified of the potential need for more than one dose of RHIG and that a Kleihauer-Betke test result is pending. Previously, the Blood Bank had not followed up on Hematology's Kleihauer-Betke test results to confirm appropriate RHIG dosing, but now they do, based on an AABB inspection that pointed out this area for improvement.
   
   
4. A transfusion medicine physician located at an academic medical center in the mid-Atlantic region of the East Coast is of the opinion that it is entirely appropriate to communicate dosage recommendation based on the calculated feto-maternal hemorrhage (they use the AABB Technical Manual as a reference). He adds that to suggest the dose of RHIG is certainly appropriate, because it is not a prescription-it is a calculation based on the information available to the laboratory. The patient's physician is free to incorporate this information with whatever else she/he considers pertinent. He concludes with the rhetorical question "If transfusion medicine physicians do not participate in this manner, why have physicians on the service at all?"
   
   
5. Dr. Mark Brecher at the University of North Carolina (attribution used with permission) reports that according to AABB Standards for Blood Banks and Transfusion Services (24th edition): 5.20.3 There shall be a process to ensure that an adequate dose of Rh Immune Globulin is administered. Based on this standard, at the University of North Carolina, investigation of a possible feto-maternal hemorrhage (FMH) in an Rh negative mother is a two-step process. All samples are initially screened with a rosette test, and if positive, quantification by flow cytometry is reflex ordered. The number of doses of RHIG is then calculated as described in the 15th edition of the AABB Technical Manual and the proper dose dispensed from the Transfusion Service. Dr. Brecher feels that the best way to ensure an adequate dose of RHIG is administered is to control the calculation of the dose. The procedure for calculating dose is reviewed annually by a Transfusion Medicine physician. The actual order for the administration of the RHIG is written by the patient's physician.
   
   
6. The director of a large donor center in Cincinnati, Ohio concurs with the physician in Oregon regarding discontinuing recommending a dosage of RHIG on their FMH report. In the responding physician's opinion, it is the laboratory's duty to give a test result and the clinicians' duty to prescribe therapy if indicated. He comments that the laboratory should not be prescribing a specific dosage. On the other hand, if a transfusion medicine consultation is obtained, this is a different matter. In this case assuming a dialogue between physicians, the consultant can recommend a dose to the prescribing physician. In summary, he would not add a dosage recommendation on every FMH report sent from the laboratory.
   
   
7. The medical director of a transfusion service at an academic medical center in California replies that the educational role of the transfusion service's expertise should not be underestimated. At his institution pathology residents are called with the results of Kleihauer-Betke tests. The residents are responsible to contact the primary team with RHIG dose recommendations. Over the years, resident involvement has lead to numerous opportunities to correct physician misconceptions about RHIG administration. In the last year alone, this has included appropriate timeframe for administration, need to treat the mother (as opposed to the baby), and futility of treating already alloimmunized mothers.

ADDENDA August 2, 2007

8. The Oregon physician who initiated this discussion adds that CLSI (formerly NCCLS) document H52-A recommends "report results only in terms of the fetal RBC percentage for the tested maternal blood sample with or without the calculated FMH size... and avoid making RhIG dose recommendations". This recommendation is based on the variability of therapy (i.e. intravenous vs. intramuscular injections) and the geographic variability and lack of an international consensus for RhIG dosing. (see page 17 of CLSI document H52-A).

ADDENDA August 3, 2007

9. A transfusion medicine physician in Chicago reports that at his lab, the detection of FMH is tested by flow and the % fetal cells and mL of fetal RBCs (based on 5L blood volume) are reported in chart and to blood bank. Then the blood bank reviews results and recommends extra dosage if needed to clinician (based on AABB Technical Manual formula). In cases of large hemorrhages, the blood bank physician may refine the dose using the patient's actual weight (i.e., blood volume) and hematocrit. For example, he reports that they had a recent case in which the fetal RBC % was 1.5%, for a calculated dose of 3 vials. (There was no risk factor for the excess hemorrhage.) They found that the patient's weight was 100 kg estimated post-delivery, for an actual blood volume of ~7000 mL. However, her postpartum Hct was 30%; total RBCs 2100 mL x 1.5% = 32 mL fetal RBCs. So the 3-vial dose was still OK (15 mL pure RBCs per vial), but her blood volume was actually much larger than the standard model. If her Hct had been 45%, she would have had about 48 mL of fetal RBCs present, and they would have added another vial.
   
   
10. A transfusion medicine physician in New York comments that they report the size of a feto-maternal bleed in milliliters and calculate a suggested dosage of RHIG that has a factor of 2 cushion, and report that as well. Since the protocol for these calculations is well accepted by those in immunohematology/transfusion medicine and obstetrics, and it is an SOP signed off by the laboratory director, he is of the opinion that there is no problem in prescribing a medication dose. It's a suggestion not a requirement. The attending OB may choose to administer zero doses of RHIG. In any case, the prescribing is done by the attending OB or other physicians at the bedside. The New Yorker's concern about not reporting out a recommended dose of RHIG is that many clinicians do not have experience in calculating these doses and the chance for misadventure is greater. He would suggest making sure one's chief of obstetrics is comfortable with what is being done and that one's technical staff are proficient, and keep doing what one is doing, as it's in the patient's best interest. He concludes saying that if the OB people don't want the suggested dose reported, by all means let them do the calculation.

ADDENDA August 5, 2007

11. A transfusion medicine physician who is located at several hospitals in a major metropolitan area in California reports that the transfusion services for which he consults will calculate the dose and distribute the RHIG (not the pharmacy). So, he acknowledges that his service is "prescribing" the medication. Their approach is to automatically give the patient a dose of RHIG at the time of delivery if they are Rh negative with a Rh positive baby. Additional doses are given based if the fetal screen is positive according to the results of the Kleihauer-Betke (K-B) test. He comments that although the total number of deliveries is fairly high for all of his facilities, the number of positive fetal screens with a positive K-B is pretty small (just a few per year). Because of this, he would feel uncomfortable counting on the 300 or so obstetricians scattered over all of the centers making an appropriate calculation for a case that he/she may personally have once in > 5 years.

ADDENDA August 10, 2007

12. A technical specialist and Tranfusion Medicine attending in blood banking located at a major academic center in Baltimore report that their current practice is to screen for excess FMH using a rosette test method. A sample with a positive rosette test is forwarded to hematology for quantitation using a Kleihauer-Betke staining technique. Hematology enters the % FMH into the pathology data system without any calculations or recommendations regarding RhIG dosage. Transfusion Medicine uses the %FMH to calculate the RhIG dosage based on the AABB Technical Manual guidelines and their SOP. The patient data and calculations are recorded on a worksheet that is reviewed and signed by the on call Transfusion Medicine attending physician. The Transfusion Medicine attending physician and/or Resident contacts the patient's physician regarding the recommended dosage, and ultimately the patient's physician places the order for RHIG. In their opinion, the Transfusion Medicine attending physician has the knowledge and experience necessary to recommend RHIG dosage in excess FMH cases; the recommendation should be discussed with the patient's physician, and ultimately the patient's physician should prescribe the RHIG.

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