First Case of 2 Unrelated Autoimmune Disorders Reported in Patient

Researchers have reported for the first time a case of the autoimmune disorder antiphospholipid syndrome (APLS) in a woman who also developed cold agglutinin disease. 

More studies are needed to explore the possible relationship between the two conditions, according to authors of the report.

The case was described in a study, “Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia in Association with Antiphospholipid Syndrome,” published in the journal Acta Haematologica.

APLS is an autoimmune disorder in which antibodies generated by the immune system mistakenly attack blood proteins that bind to phospholipids — fatty molecules found in all living cells, including blood cells — making blood more prone to clot. APLS can occur either as an isolated disease (primary APLS), or be associated with other autoimmune diseases, including systemic lupus erythematosus. 

Autoimmune hemolytic anemia (AIHA) comprises a group of autoimmune disorders in which antibodies bind and destroy red blood cells, resulting in anemia. There are two major subtypes of AIHA, depending on the temperature at which these harmful antibodies tend to bind to red blood cells. When this happens mainly at low  temperatures, one is said to have cold agglutinin disease (CAD). 

Although both APLS and CAD are autoimmune diseases, no clear association exists between the two conditions. 

In the study, researchers at the Hebrew University-Hadassah Medical Center, in Israel, reported the case of a woman with established APLS who developed CAD. 

“To the best of our knowledge, such an association has not been described thus far,” the team wrote. 

The 53-year-old woman was a heavy smoker who visited her primary care physician after two weeks of experiencing worsening fatigue and pain in both knees. Lab tests revealed she had severe anemia with a hemoglobin level of 6.4 grams per deciliter (g/dL) (normal range is 12.0–16.0 g/dL). 

She reported a single episode of low-grade fever and mild weight loss over the preceding months. She was hospitalized and a detailed review found no signs of external bleeding or organ damage. 

Her medical records revealed she had previously been diagnosed with APLS after having six miscarriages and a blood clotting event. Lab tests revealed the presence of antiphospholipid antibodies (aPL). She was taking the anticoagulant medication warfarin, a blood thinner, as maintenance therapy. 

In the two years before being hospitalized, the patient developed pancytopenia (low blood cell levels). Her white cell counts were low (3,700–3,800 U/L when the normal range is 4,500–11,000 U/L), as were her hemoglobin levels (9.1–10.0 g/dL; normal range 12.0–16.0 g/dL), and platelet counts (43,000–88,000 U/L; normal range: 150,000–450,000 U/L). Short-term elevated liver enzymes, a sign of liver damage and inflammation, and mildly enlarged spleen were also reported. 

Upon arrival at the hospital, she underwent lab tests again, which revealed she had pancytopenia, as well as high levels of lactate dehydrogenase (a marker of tissue damage consistent with CAD), and low haptoglobin levels (an indication that red blood cells were being destroyed faster than they were being made). 

A blood smear analysis revealed the presence of spherical red blood cells and red cell fragments, compatible with hemolysis (red blood cell destruction). The patient was also positive for C3d, another indicator of CAD. She had mild folic acid deficiency, and additional blood and urine test parameters were normal. 

A chest X-ray was normal, and a computed tomography scan of the chest, abdomen, and pelvis showed she had an enlarged spleen with no further abnormalities. Tests for infections associated with CAD, including cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae, were all negative. 

Immune-specific blood analysis revealed she had high levels of aPL and immunoglobulin M (IgM) antibodies, another sign of CAD. Further tests confirmed the presence of the antibodies, while markers of other autoimmune disorders were all negative. 

Based on these findings, she was diagnosed with IgM-mediated CAD in association with APLS. 

Although a brief treatment with corticosteroids provided no benefits, her hemoglobin levels remained stable over the course of her hospitalization. She was released from the hospital in good condition and received folate supplementation and an anticoagulant.

Over the next two months, she received two red blood cell units at monthly outpatient visits, which gradually eased her symptoms and improved her lab test results. On her third visit, three months after being discharged from the hospital, her white blood cell count was at 4,400 U/L, hemoglobin levels were at 11.3 g/dL, and platelet count was 70,000 U/L.

“With a limited follow-up period on an outpatient basis so far, the patient has remained stable, without evidence of progression and without clinical symptoms requiring intervention,” the authors wrote. “In summary, we present here a previously unreported combination of [two] immune-mediated diseases, [CAD] and APLS.” 

“Further reports are required to discern a possible [causal] association between these [two] entities and to consider therapies targeting the common underlying process,” they wrote.