Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report
© Yoshida et al; licensee BioMed Central Ltd. 2009
Received: 2 April 2009
Accepted: 10 September 2009
Published: 10 September 2009
Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies targeting at least red blood cells and platelets. HS and Evans' syndrome have different mechanisms of pathophysiology one another. We reported the quite rare case of an infant who had these diseases concurrently. Possible explanations of the unexpected complication are discussed.
Hereditary spherocytosis (HS) is caused by a variety of molecular defects of erythrocyte membrane proteins. These proteins are necessary to maintain the normal shape of erythrocytes. As the spleen normally targets abnormal shaped red blood cells (RBCs), it also destroys spherocytes. Autoimmune hemolytic anemia (AIHA) is the most common autoimmune hemolytic diseases. The RBC attached antibodies was recognized and grabbed onto by macrophages in the spleen. These cells will pick off portions of RBC membrane, that causes spherocytic change. Spherocytes are not as flexible as normal shaped RBCs, and will be singled-out for destruction in the reticuloendothelial system, that gives rise to extravascular hemolysis . Immune thrombocytopenic purpura (ITP) is a condition of having a low platelet count caused by autoimmune with antibodies against platelets. The coating of platelets with antibodies renders them susceptible to opsonization and phagocytosis by splenic macrophages . Evans' syndrome refers to a major disorder in immunoregulation characterized by AIHA accompanied by ITP . HS and Evans' syndrome have different mechanisms of pathophysiology one another. Herein, we report the first case confirmed Evans' syndrome associated with HS.
at 2 days
at 6 months
at 2 days
A, Rh (+)
Direct anti-globulin test
Indirect anti-globuin test
5020 × 103
2840 × 103/μl
osmotic fragility in erythroresistant test
(after leaving 24 hours)
osmotic pressure starting hemolysis
>0.50% normal saline
305 × 103
57 × 103/μl
osmotic pressure finishing hemolysis
0.42% normal saline
at 6 months
anti nuclear Ab
anti-parvo B-19 IgM
239 ng/107 cells
Direct anti-globulin test (2nd times)
Indirect anti-globuin test (2nd times)
Bone marrow examination
nucleated cell count
310 × 103/μl
Methods & results
We reported a case of 6 month-old infant affected by HS, accompanied by Evans' syndrome. The diagnosis of HS was made by family history (his mother had already been diagnoed with HS), a negative DAT, high osmotic fragility in erythroresistant test and later typical spherocytic morphology.
Platelet surface GPIIb/IIIa and GPIb are the most common antigenic targets in ITP . No increasing of the number of B cells producing GPIIb/IIIa antibody in the patient peripheral blood with ELISPOT assay and the unbinding of anti-GPIb antibody to the patient's platelets with flow cytometric analysis suggested that autoantibody adhering to GPIb on the platelets was responsible for thrombocytopenia.
The hallmark of AIHA is a positive DAT by which IgG and/or complement are found on the RBC surface. However, the incidence of a negative DAT in patients with AIHA has been reported to be between 2 to 4% . Explanation for the negative DAT in some patients with AIHA is that the number of IgG molecules on RBC necessary for accelerated in vivo destruction is sometimes lower than the number of that to yield a positive DAT. Because in our patient anemia improved with a decrement of bilirubin following IVIG and an erythrocyte binding IgG elevated moderately, we diagnosed him with AIHA. To our knowledge, there have been two reports that IVIG or corticosteroid were effective to HS [10, 11]. Compared with those cases, our patient respond to IVIG and corticosteroid much better. These findings suggest that anemia in our patient is partially caused by immunological alteration as well as thrombocytopenia.
Since the complication of HS with AIHA or ITP has not been reported previously, it cannot be denied that these complications occurred coinsidentally. However, it is possible to supeculate some explanation for occurring AIHA or ITP with HS based on the some reason. First, a retrospective analysis of blood-bank records showed that out of 2618 patients who had a positive DAT or indirect anti-globulin test (IAT), 121 were identified with RBC autoantibodies; 41 of these patients had both allo- and autoantibodies to RBC antigens, whereas the remainder, 80, had only autoantibodies. At least 34 percent (12/41) of these patients developed their autoantibodies in temporal association with alloimmunization after recent blood transfusion . Another report showed presence of both an anti-protein 4.2 antibody and other undefined autoantibodies against RBC associated with heavy transfusions in protein 4.2-negative HS patient . Although it is unclear whether transfusion was related to production of autoreactive antibodies against RBC, it is suspected that activation of immune sysytem against both external and internal antigens was elicited by exposing alloprotein derived from transfused donor's RBC. Second, hypergammaglobulinemia may arise when specific helper T cells recognize B cells that have processed viral antigens irrespective of the B cell receptor specificity . This deleterious role for nonspecific B cell activation by viral infection, arguing that it could potentially turn on anti-self-responses, may contribute to autoantibodies-associated hemolytic or thrombocytopenic manifestations. Moreover, Ward et al. has been reported that RBC-autoantigen-specific, interleukin-10-secreting regulatory T cell clones from a patient with autoimmune hemolytic anemia (AIHA), which had a functional phenotype . Further careful observation is required for disclosing that this complication is not occurred incidentally.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in Chief of this journal.
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