A blood banker reports that at their hospital a patient with ITP received intravenous anti-D immune globulin. The patient needed a RBC transfusion, and the antibody screen was positive due to the infused anti-D. The inquiring blood banker wants to know if the donor RBC unit should be Rh positive or Rh negative. At present, the inquiring blood banker's hospital does NOT have a policy covering this situation, and they decide on the Rh type of the donor RBCs on a case by case basis. In the case example, the technologist automatically set up Rh negative blood. However, in the past when the ordering physician was been consulted on other patients, in one case they used Rh negative RBCs and in another case they used Rh positive. The inquiring blood banker wants to know what policy, if any, is followed by other members of the e-network forum for selection of donor RBCs when transfusing an Rh positive individual with ITP, whose antibody screen is positive due to infusion of anti-D via the IV route?

In reply to the above, the following responses were submitted.

1. A blood banker from a major university in New York commented that regarding the selection of Rh positive versus Rh negative RBCs for transfusion of a patient who is receiving intravenous anti-D for treatment of ITP, this is a situation where the ordering physician should be consulted, case-by-case. In the opinion of the New Yorker, if the anti-D treatment requires a sufficient volume of Rh Positive RBC's to be circulating in the patient's blood stream for the anti-D to be effective, the transfusion decision should be to give Rh Positive RBCs. However, if the patient has become so anemic due to the action of the anti-D therapy that they have become deficient in oxygen transport capacity and if the transfused red cells are needed to survive, give Rh Negative RBCs. That is a judgment that the treating clinician must make whenever red cells are ordered.

2. A blood banker from Boston reported that at her hospital, when a patient has received IV anti-D and it is detectable in the antibody screen, their policy is to give Rh negative RBCs. This is probably more of a convenience for the Blood Banker as it will be easier to get a compatible crossmatch.

3. A blood banker in Washington DC reports that regarding the question concerning Rh-positive or Rh-negative RBCs after IV anti-D, this matter should be a medical decision based on the following factors, not a blood bank policy. If the platelet count has not yet increased to the targeted "safe" level, Rh-positive RBCs should be transfused since the primary treatment objective remains reversal of thrombocytopenia. Any transfused Rh-positive RBCs that are eliminated by circulating IV anti-D contribute to quicker realization of the full therapeutic effect of the dose of IV anti-D. In contrast, if the desired increase in platelet count has been achieved, for example immediately post-splenectomy, but there is symptomatic anemia, the primary goal is correction of the anemia. In this case, Rh-negative RBCs should be selected. This issue is discussed briefly in Savasman CM, Sandler SG: Serological aspects of treating immune thrombocytopenic purpura using intravenous Rh immune globulin. Immunohematology 2001; 17:106-110. (http://www2.redcross.org/pubs/immuno/).

ADDENDA May 3, 2002

4. A blood banker in Milwaukee reports that in this situation their policy is to dispense crossmatch "compatible" blood, when RBCs are ordered for transfusion. In the setting of a patient who is Rh positive but who displays anti-D, they call the requesting physician in order to determine if the antibody is passive anti-D used to treat ITP. In that case, they dispense compatible (thus D-negative) RBCs, but also make notes in their records that the D-negative requirement is to be honored only for as long as passive anti-D is detectable (but not for all time as you would for an individual producing allo-anti-D.) The Milwaukee blood banker is not aware that diluting a patient's Rh D positive red cells with a unit of D negative cells is demonstrated to affect the response to ITP therapy, and they prefer policy of dispensing compatible blood whenever possible.

ADDENDA May 6, 2002

5. With all due respect for the various protocols above that suggest one should transfuse Rh positive blood products to ITP patients with hemolyis being treated with IV anti-D, a blood banker familiar with the most current package insert of IV anti-D had the following to report: "Based on a recent assessment of adverse events following administration of IV anti-D to immune thrombocytopenic purpura (ITP) patients positive for Rho(D) antigen (D-positive), we have revised the package insert to state that Rho(D) positive ITP patients treated with IV anti-D should be monitored for signs and/or symptoms of intravascular hemolysis (IVH), clinically compromising anemia, and renal insufficiency."

6. This is what a blood banker had to say about the package insert for IV anti-D: The circular was revised in January 2000 to state: "Following administration of WinRho SDF™, Rho(D) positive ITP patients should be monitored for signs and/or symptoms of IVH, clinically compromising anemia, and renal insufficiency. If patients are to be transfused, Rho(D) negative packed red blood cells (PRBCs) should be used so as not to exacerbate ongoing IVH. Platelet products may contain up to 5.0 mL of red blood cells (RBCs); thus caution should likewise be exercised if platelets from Rho((D) positive donors are transfused." (FDA/MedWatch)

7. A blood banker in Detroit reported that due to the (rare) occurrence of hemolysis, the manufacturer of IV anti-D (WinRho - Cangene/Nabi) has recommended that these patients be transfused with Rh negative RBCs.  They changed their policy based on this recommendation. Prior to this, the Michigan blood banker had been considering these cases on an individual basis. However, after consultation with the hematology/oncology physicians caring for these patients, it was decided that, since this recommendation was part of the public record, it would be most prudent to follow it in all of these cases.

8. The blood banker in Washington DC, who submitted reply #3, adds that regarding RBC transfusions after IV anti-D, blood bankers may be correct when citing the manufacturer's package insert as the basis for selecting only Rh(D)-negative RBCs after infusing IV anti-D. However, that text reads, "If patients are to be transfused , Rho(D) negative red blood cells (PRBCs) should be used SO AS NOT TO EXACERBATE ONGOING IVH (intravascular hemolysis)." The Washington DC blood banker, who is an advocate of using Rh(D)-positive RBCs if thrombocytopenia persists, interprets the manufacturer to be referring to the preceding sentence about the rare complication of "IVH, clinically compromising anemia and renal insufficiency" and not as a general guidance for all post-WinRho infusion situations.

ADDENDA May 7, 2002

9. A blood banker from Texas reports that in his experience, IV RhIG, even at 75ug/kg (adult ~5000ug) is not associated with significant hemolysis, and when it is, most of the hemolysis is extravascular. According to his calculation, 5000 ug will at the most hemolyse ~225 mL RBCs (300ug for 15 mL RBC). He reports having seen only one child who dropped their Hgb from 12 to 9g/dL in the last 5 years. Furthermore, he is not convinced that it makes any difference if one transfuses Rh positive or Rh negative RBC units to an Rh positive patient who has ongoing hemolysis due to IV RhIG, so long as the patient has an active marrow that is producing Rh positive red cells. His transfusion service has always transfused Rh positive RBC units in such a scenario, if needed, which has been only once or twice for significant drop in Hgb without the patient being symptomatic due to anemia. The Texan agrees with the Washington DC blood banker about the rationale of transfusing Rh positive units to maintain the efficacy of IV RhIG.

9. A blood banker from a university in Austria reports that in his experience the use of anti-D in ITP is a treatment modality that needs to be given only to very selected patients, refractory to any other treatments. To quote "There is experience that it also is effective in Rhesus-negative individuals, suggesting that its effects are not only due to an overload of the monocyte/macrophage system with RBC that need to be removed from the circulation, and thus the monocyte/macrophage system is "fed-up" with these latter cells and cannot deal with the Ig-coated platelets from the ITP. Indeed, all platelets anyway bind Ig and the Ig-load is a simplistic way to consider ITP-platelets as targets of the monocyte/macrophage system. In brief, the activity of anti-D simply attributed only to the coating on RBC, autologous or transfused. Further, if a patient is anemic and the respiratory system requires RBC substitution, this substitution needs to be effective for oxygen transportation, and cannot be allowed to be hemolysed by whatever medication the patients has recieved in the past. Therefore, an individual that needs RBC transfusion needs to get the best compatible RBCs, in this case Rh-negative RBC."

10. The Washington DC blood banker who submitted replies #3 and #8 has yet another comment. "When editing correspondence, the Editor has substituted 'anti-D' wherever this correspondent, and possibly others, wrote 'WinRho.' Anticipating the likely approval of other manufacturers' products, which may have different formulations, we should consider using only the product's brand name, as we do to distinguish among antihemophilic factor concentrates. If that's not acceptable, a more precise text would use the product's generic name "Rho (D) Immune Globulin Intravenous (Human)," abbreviated to IV RhIG. The lingo "anti-D," frequently used by clinicians is imprecise and gives the impression of pharmaceutical purity and consistency that may be misleading to technologists who may find anti-C, -E, -G, -V or Fya in post-WinRho infusion plasma or eluates (see Rushin J et al Detection of multiple passively acquired alloantibodies following infusions of IV Rh immune globulin Transfusion 2000;40552-4)."

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator