Risk of haemolytic anaemia after alemtuzumab

Alemtuzumab use has been associated with the development of secondary autoimmunities.

Antibodies to Red blood cells can be one of these



di Ioia M, Farina D, di Tommaso V, Travaglini D, Pietrolongo E, Onofrj M, de Luca G. Simultaneous early-onset severe autoimmune haemolytic anemia and albuminuria during alemtuzumab treatment for multiple sclerosis. Mult Scler. 2018 Jan 1:1352458517743093. doi: 10.1177/1352458517743093. [Epub ahead of print]


BACKGROUNDAlemtuzumab, approved for multiple sclerosis (MS), can cause secondary autoimmune adverse events including thyroid disorders, immune thrombocytopenia (ITP), and glomerular nephropathies. Non-ITP autoimmune cytopenias are rarely reported.

OBJECTIVE:

To report a case of autoimmune hemolytic anemia (AIHA) and nephropathy in a MS patient treated with alemtuzumab.

CASE REPORT:

A 34-year-old man with MS developed albuminuria and AIHA after the first and only alemtuzumab treatment, with positive Coombs' direct and indirect tests and IgG autoantibodies. Both AIHA and nephropathy resolved 1 month after treatment with steroids and intravenous immunoglobulins.

CONCLUSION:

Our report adds to the literature on AIHA and nephropathy after alemtuzumab treatment and suggests to add Coombs' tests to the screening panel required for alemtuzumab treatment.

Meunier B, Rico A, Seguier J, Boutiere C, Ebbo M, Harle JR, Schleinitz N, Pelletier J. Life-threatening autoimmune warm haemolytic anemia following treatment for multiple sclerosis with alemtuzumab. Mult Scler. 2018 1352458517729766. doi: 10.1177/1352458517729766. [Epub ahead of print]

BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed at CD52 approved as a disease-modifying therapy for relapsing forms of multiple sclerosis (MS).


OBJECTIVE: To describe a case of a life-threatening autoimmune anemia occurring after a first course of alemtuzumab for relapsing-remitting MS in a 28-year-old male.


METHODS: Case report.


RESULTS: A 28-year-old male developed a life-threatening autoimmune anemia occurring 11 months after first alemtuzumab course.


CONCLUSION: We report the third case of autoimmune haemolytic anemia following treatment with alemtuzumab in a young MS patient. Due to the severity of this adverse event, neurologists using this treatment should be alert.

Haemolytic anemia or haemolytic anaemia is a form of anemia due to haemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, but usually in the spleen). It has numerous possible consequences, ranging from relatively harmless to life-threatening.

Symptoms of haemolytic anaemia are similar to other forms of anaemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice.
Chronic haemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free haemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral oedema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).
Coombs test (also known as antiglobulin test or AGT) The direct Coombs test is used to test for autoimmune hemolytic anemia; i.e., a condition of a low count of red blood cells (RBCs) caused by immune system lysis or breaking of RBC membranes causing RBC destruction. In certain diseases or conditions, an individual's blood may contain IgG antibodies that can specifically bind to antigens on the RBC surface membrane, and their circulating RBCs can become coated with IgG alloantibodies and/or IgG autoantibodies. Complement proteins may subsequently bind to the bound antibodies and cause RBC destruction. The direct Coombs test is used to detect the antibodies or complement proteins that are bound to the surface of red blood cells; a blood sample is taken and the RBCs are washed (removing the patient's own plasma) and then incubated with anti-human globulin (also known as "Coombs reagent"). If this produces agglutination of RBCs, the direct Coombs test is positive, a visual indication that antibodies (and/or complement proteins) are bound to the surface of red blood cells.

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