Autoimmune Hemolytic Anemia:
Controversies re: Transfusing Crossmatch-Incompatible
Ram Kakaiya, MD,
Medical Director, LifeSource Blood Center
In patients with autoimmune
hemolytic anemia (AIHA), antibodies are present, which react with both the
patientís own red blood cells and nearly all donor RBCs. Therefore,
serologically compatible blood is rarely available for transfusion. The
inability to provide crossmatch-compatible blood has led to concerns that
transfusion of these patients could precipitate acute hemolysis with potentially
severe consequences (hemoglobinemia, hemoglobinuria, acute renal failure,
disseminated intravascular coagulation and death).1
These concerns are based on
a few published reports of post-transfusion hemolysis in such cases. Because of
the limited amount of this data and anecdotal experience suggesting a lack of
severe adverse events after transfusion, the indications for and advisability of
transfusion in these patients remain controversial issues.
REPORTS OF ADVERSE EVENTS
1967: Eleven deaths were seen among 47
patients with autoimmune hemolytic anemias.2 At autopsy, one case
showed acute tubular necrosis after an acute hemolytic episode. The decedent
also had multiple pulmonary emboli and Staphylococcal sepsis. Whether
this case involved transfusion or not is not clear from the report. The authors
did not implicate blood transfusion as a cause of death in any of the eleven
1971: Case report: A six-month old
child experienced chills, fever, and worsening of her hemolgobinuria after
transfusion of 30 ml of packed red blood cells (PRBCs).3 After
testing post-transfusion samples, using the differential agglutination method
for the detection of donor RBCs, the authors concluded that the post-transfusion
hemolysis seen was not due to hemolysis of the transfused cells.
1973: Report describing 2 cases of
renal failure after blood transfusion in AIHA patients.4 One was
recovering from renal failure at the time of publication. No details were given
to implicate transfusion as the cause.
1980: Review paper: 2 deaths in
transfused AIHA patients.5 The first was a 34-year old who required
transfusion of one to two units of red blood cells daily to keep hemoglobin
level between 4.5 and 6.0 gm/dL. The patient was reported to have increasingly
severe hemoglobinemia and hemoglobinuria after the transfusions that cleared
within a few hours. The patient underwent splenectomy and two days later was
transfused and developed acute respiratory distress, cardiac arrest and died.
Autopsy showed multiple fresh small pulmonary emboli.
The second fatal case was a
patient who was admitted in a semi-stuporous condition with a hemoglobin level
of 1.6 gm/dL. After transfusion of 3 units of PRBCs, the patientís level of
consciousness improved, but she developed a fever with striking hemoglobinemia
and hemoglobinuria, which improved over 3 hours. Her hemoglobin level rose to
5.7 gm/dL, but then rapidly declined. She subsequently developed severe
respiratory distress, cardiac arrest and died. At autopsy, death was attributed
to multiple fresh small pulmonary emboli.
In these two cases, there is
a temporal relationship between the transfusions and the onset of hemolysis.
However, the cause of death in both cases was multiple pulmonary emboli. One of
the patients had a clear risk factor for pulmonary thromboembolism, namely, a
post-operative state. In the second case, details for risk factor assessment
were lacking. While post-transfusion hemolysis may have occurred, it cannot be
concluded that the deaths were due to transfusion.
1994: Case report: An AIHA patient
with HIV infection was rapidly transfused 8 units of PRBCs (<24 hours) and died
shortly thereafter of disseminated intravascular coagulation (DIC), pulmonary
thrombi, and right heart failure.6 The authors concluded that these
lethal complications were most likely related to aggressive transfusion therapy,
with associated intravascular hemolysis.
1998: Review of AIHA and HIV
infection: 4 additional cases with pulmonary thrombi suggestive of a
hypercoagulable state. One of the four had received a single unit transfusion.7
additional fatal AIHA cases have been reported in the literature. 8-13
Blood transfusion was not implicated in these deaths.
REPORTS OF SAFETY & EFFICACY
1988: 1685 AIHA patients, 7052 units
transfused, no reports of adverse reactions.14
1992: 79 AIHA patients (75 adults, 4
children), 3 to 231 PRBC units/patient, followed up to 12 years, no increased
alloimmunization or hemolysis, transfusions were well tolerated.15.
1995: Over 5000 AIHA patients, 21,500
units transfused, adverse effects reports lacking.16
2001: 14 AIHA patients, age: 8 to 81,
51 units transfused, pre-transfusion Hgb: 2.8 to 8.7 gm/dL, post: 7.1 to 11.7,
average increase 0.99 gm/dL per unit transfused, no hemolysis or adverse
effects.17 Bilirubin increased in 7, but only 0.02 to 0.45 mg/dL per
PRBC unit. LDH rose in 6 with average increase of 40 IU/dL.
2002: 20 AIHA patients, 293
phenotypically matched units (2 to 47 per patient), expected post-transfusion
Hgb increment achieved, adverse reactions absent.18
2000, 2001: 3
other articles describing effectiveness & lack of adverse events in a total of
There are several other case
reports describing chronic transfusion support for refractory AIHA patients
(references available from the author).
Concern regarding the
precipitation of acute hemolytic transfusion reactions leading to morbidity and
mortality after transfusion of red blood cells in patients with autoimmune
hemolytic anemia stems from a few early reports of fatalities in these
patients. While a temporal relationship between transfusion and hemoglobinemia/hemoglobinuria
has been seen in a handful of cases, a careful analysis of these reports does
not support a cause and effect relationship between transfusion and death. The
available safety and efficacy data for transfusion in patients with autoimmune
hemolytic anemia, while somewhat limited, suggests that blood transfusion is
well tolerated and efficacious.
Garratty & Petz, Lancet 1993;
Allgood & Chaplin, Am J
Med 1967; 43:254-273.
Zuck & Head, Lancet 1971; 2(7720):382-3.
Bell et al., Am J Clin Path 1973; 60:903-911.
Petz & Garratty. Acquired Immune Hemolytic Anemias. 1980; pp:358-391.
Bilgrami et al., Transfusion 1994; 34(3):248-52.
Saif et al., Connecticut Med 1998; 62(2):67-70.
Friedmann et al., J Pediatr Hem/Onc 1998; 20(5): 502-505.
Mainwaring et al., Br J Haematol 2000; 109(3-I):641-643.
Nowak-Wegrzyn et al., J Pediatr Hem/Oncol 2001; 23(4):250-252.
Okada et al., Jap J Clin Hem 1989; 30(10):1892-7.
Seldon et al., Am J Clin Path 1980; 73:716-717.
Shirey et al., Vox Sang 1987; 52(3): 219-22.
Sokol et al., Clin Lab Haematol 1988; 10(3):257- 64.
Salama et al., Lancet 1992; 340(8834):1515-18.
Sokol et al., J Clin Pathol 1995; 48(7):602-10.
Narvios et al., Curr Issues Trans Med 2001;9(3):1-5.
Shirey et al., Transfusion 2002; 42(11): 1435-41.
Kohan et al., Vox Sanguinis 1994; 67(2):195-8.
Mauro et al., Blood 2000; 95(9):2786-92.
Biondi C, Cotorruelo C, Borras SG, Ensinck A, Racca et al., Medicina (Buenos
©2003, Institute For Transfusion
Editor: Donald L. Kelley, M.D., MBA: