Final Diagnosis -- Acute Hemolytic Reaction Secondary to ABO Incompatible Platelet Transfusion


FOLLOW UP AND DISCUSSION:

The lab results clearly show that passive Anti-A antibodies were present in the patient's serum and on his red cells. These antibodies were acquired from the plasma present in the group O platelet units transfused to the patient. The acute drop in hemoglobin and rapid rise in bilirubin within 24 hours strongly suggested that acute hemolysis had occurred. Although urine hemoglobin and visible plasma hemoglobin were both negative at the time of testing, at least partial intravascular hemolysis was suspected. The significant drop in hemoglobin may have been due to hemolysis plus hemodilution from the transfusion of 4 pools of platelets (a total of 31 units with approximate total plasma volume of 2000 ml) within 18 hours. Since the half-life of free hemoglobin is only 2-4 hours, any intravascular free hemoglobin may have already been cleared by the time of testing (6 hours post-transfusion).

Because of the presence of Anti-A antibodies in the patient's serum, it was recommended that the patient be transfused with group O (+) red cells, if needed. It was also recommended that any future platelet transfusions or transfusion of plasma containing blood components be group A or AB. Later that day, he received two units of group O (+) packed RBC. His hemoglobin improved to 11.7 g/dl on the following day. Three days later, the patient's hemoglobin was 10.2 g/dl and total bilirubin had decreased to 1.4 mg/dl (near his baseline). His DAT, however, continued to show weak or microscopic positivity for several days. The patient recovered without sequelae from the hemolytic reaction and was discharged five days after the event. He continues to receive routine platelet transfusions as an outpatient.

Central Blood Bank was contacted to recall all blood component products (red cells and FFP) associated with the platelet concentrates transfused at the time of the reaction. It was recommended that these blood components be quarantined until an ABO titer could be performed on each of the units. Fresh frozen plasma associated with each of the units (total 16) was sent to the reference lab for ABO titers. The titers were performed at room temperature (RT) and antiglobulin (AHG) phases, both with 60 minutes incubation. One of the donors had a very high IgG anti-A titer:

Anit-A titer, 60 min RT  Anti-A titer, AHG
1:64 1:1024

The donor of this platelet unit was deferred permanently from blood donation. The other units were released from quarantine.

Due to limited supply of random platelet concentrates and the occasional need for HLA-matched or crossmatch-compatible single donor platelets for platelet refractoriness, the use of ABO incompatible platelets is often unavoidable. Since the small amount of incompatible donor plasma will be diluted in the relatively larger plasma volume of the recipient, the transfusion of ABO incompatible platelets is generally considered safe and clinically effective. Rarely though, the passively transfused antibodies may cause hemolysis of the recipient's red cells. This infrequent hemolytic reaction is usually associated with Group O single donor platelet apheresis products that can contain as much as 350 ml and have a high ABO antibody titer (greater than 1:1024 at AHG). (5,6) Although the volume of pooled platelet concentrates may be larger than with platelet apheresis products (6 to 10 random platelet concentrates with 50 to 70 ml each), the risk of hemolysis is less likely because the amount of plasma from a potential donor with a potent ABO antibody is smaller and will be diluted in the platelet pool.

An additional risk factor for potential hemolytic reaction is the transfusion of a large number and volume of ABO incompatible platelet products during a short time. This would allow for cumulative buildup of passively acquired anti-A1 and anti-B titers in the patient's plasma. In our patient, this buildup of ABO antibodies was probably a contributing factor since he received approximately 1450 ml of ABO incompatible plasma (or 35% of his plasma volume) within 18 hours. Also, although only one of the random donor platelet concentrates had a very high Anti-A titer of 1:1024, six additional donors had anti-A titers of 1:128 or higher at AHG phase.

Several cases of severe hemolysis after transfusion of platelets with ABO incompatible plasma have been reported. Some of these cases are summarized in the following table:

Hemolytic reactions after platelet transfusion
Reference Year Patient's ABO Donor's ABO Volume infused (ml) ABO titer- Saline ABO titer- AHG
Mcleod 1982 A O 200 1280 10,240
Pierce 1985 A O 200 512 32,000
Pierce 1985 B O 50 512 16,384
Murphy 1990 A O 448 256 1024
Larsson 1999 A O 371 16,384 NT

In all these cases, post-transfusion studies showed definitive evidence of acute intravascular hemolysis, negative antibody screens, positive direct anti-human globulin test, and anti-A or Anti-B antibodies present in the patient's serum or eluted from the patient's cells. All of the patients were critically ill at the time of platelet transfusion, and the intravascular hemolysis contributed to significant morbidity, and in one case, mortality.

As seen in the above cases, hemolysis occurs when the donor(s) have high titer ABO antibodies against the recipient ABO blood group. However, hemolysis following ABO-incompatible platelet transfusion is quite uncommon. In a 5 year review during which time nearly 1000 single donor ABO incompatible plateletpheresis products were transfused to bone marrow transplant recipients, Shanwell et al. noted positive direct antiglobulin tests caused by passively absorbed anti-A and/or anti-B from the donor plasma, but found no cases of hemolysis. (7) In addition, a retrospective review by Mair and Benson showed no significant decrease in hemoglobin, as evidence of hemolysis, with transfusion of ABO incompatible plateletpheresis products in 24 non-group O bone marrow transplant patients. (8) At two separate large institutions, the incidence of hemolytic reaction from transfusion of ABO incompatible single donor apheresis products was only 0.01% over a 9 to 10-year period. (5,8)

Although the transfusion of ABO incompatible platelets is infrequently associated with overt hemolysis, the transfusion service staff and clinicians should be cognizant of the potential risk. Several ways to help minimize the risk may include: (1) limiting the quantity of platelet transfusions to what is clinically necessary; (2) continually evaluating those patients receiving large volumes of platelets; (3) whenever possible, transfusing ABO compatible platelets; and (4) reducing the volume of incompatible plasma transfused for group A, B, or AB patients who must receive ABO incompatible platelet products, particularly in children and patients with small plasma volume. (6, 8) Volume reduction for emergent platelet transfusions may be impractical, though. And, one must keep in mind that concentrating platelets can be associated with some platelet loss. (8)

Unfortunately, the degree of volume reduction that would prevent immune hemolysis has not been established. The reported volume of infused ABO incompatible plasma that has resulted in hemolytic reactions has ranged from 50 to 500 ml. (5) Probably more important, as was noted in our patient, is the total volume of incompatible plasma that may be infused over a short time period (i.e. 24 hours). Thus, the most practical policy would be to transfuse group-specific platelets whenever possible and to minimize minor ABO incompatible platelet transfusions, especially for children who have smaller plasma volumes and for adult patients who will receive large volumes of plasma as a result of multiple transfusions.

References

  1. Petz LD, Swisher SN, Keinman S, et al. Clinical Practice of Transfusion Medicine. 3rd ed. New York, NY; Churchill Livingstone Inc; 1996:320, 397-399, 720.
  2. McLeod BC, Sassetti RJ, Weens JH, Vaithianathan T. Haemolytic transfusion reaction due to ABO incompatible plasma in a platelet concentrate. Scand J Haematol. 1982 Mar;28(3):193-6.
  3. Pierce RN, Reich LM, Mayer K. Hemolysis following platelet transfusions from ABO-incompatible donors. Transfusion. 1985 Jan-Feb;25(1):60-2.
  4. Murphy S. ABO blood groups and platelet transfusion. Transfusion. 1988 Sep-Oct;28(5):401-2.
  5. Larsson LG, Welsh VJ, Ladd DJ. Acute intravascular hemolysis secondary to out-of-group platelet transfusion. Transfusion. 2000 Aug;40(8):902-6.
  6. McManigal S, Sims K L. Intravascular hemolysis secondary to ABO incompatible platelet products: an underrecognized transfusion reaction. Am J Clin Pathol 1999;111:202-206.
  7. Shanwell A, Ringden O, Wiechel B, Rumin S, Akerblom O. A study of the effect of ABO incompatible plasma in platelet concentrates transfused to bone marrow transplant recipients. Vox Sang. 1991;60(1):23-7.
  8. Mair B, Benson K. Evaluation of changes in hemoglobin levels associated with ABO-incompatible plasma in apheresis platelets. Transfusion. 1998;38:51-55.

Contributed by Muammar Arida, MD, Kathleen Puca, MD




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