Fall Uncovers Undiagnosed CAD in Elderly Woman, Case Study Reports

Researchers in the U.K. have described the case of an 81-year-old woman who was diagnosed with secondary cold agglutinin disease (CAD) only after falling and being treated at the hospital for several broken bones.

The woman’s fall reactivated a cytomegalovirus or CMV infection, which triggered hemolytic anemia — a disorder in which red blood cells are destroyed faster than they can be made — caused by an undiagnosed case of secondary CAD, a case study reported. Of note, CMV is a common virus for individuals of all ages that stays in a person’s body for life and can reactivate. 

The investigators recommended that physicians consider a CMV infection and secondary CAD as a cause of hemolytic anemia in adults with significant skeletal trauma. 

The study, “Lessons of the month 1: Polytrauma in a geriatric patient resulting in reactivation of cytomegalovirus infection and secondary cold agglutinin disease-induced haemolytic anaemia,” was published in the Clinical Medicine Journal. 

An autoimmune disease characterized by hemolytic anemia, CAD is caused by the attack and destruction of red blood cells by autoantibodies, called cold agglutinins.

CAD can present as a primary condition, in which the underlying cause is unknown, or as a secondary disease triggered by infections, other autoimmune disorders, or certain types of cancer. 

A diagnosis of CAD may be made after symptoms appear, in which case several types of tests are performed. However, in some cases, the diagnosis can occur by chance after routine blood tests or during treatment for different conditions.

In this report, researchers at Wexham Park Hospital, in Berkshire, described the case of a elderly woman who was diagnosed with secondary CAD only breaking several bones in a fall. 

The woman was found in the hallway of her home following a fall from a standing position. At the hospital, she complained of pain in her right shoulder and hip, was unable to bear weight, and had extensive bruising of the right upper and lower limbs. Her right shoulder was deformed, swollen, and painful to touch. 

She was alert and coherent; her temperature and her vital signs were all normal. 

X-rays showed she had a broken right collar bone but her pelvis was not damaged. Blood tests revealed low hemoglobin levels at 88 g/L, in which a range between 115–165 g/L is considered normal. Her bilirubin level, which comes from the breakdown of red blood cells, was also high at 68 micromolar/L; it should be below 21 micromolar/L.

C-reactive protein, a measure of inflammation, and urea, formed by the breakdown of proteins, were both above normal. All other blood and biochemistry tests were normal.

The woman vomited a large volume of blood for which she was given a blood transfusion and various medications. However, an examination of her digestive tract found no source for the bleeding. 

Over the following three days, she complained of neck pain and developed a need for oxygen supplementation. Her anemia worsened, with her hemoglobin levels dropping to 62 g/L and her bilirubin rising to 71 micromolar/L. Extended anemia screens and thyroid function tests were normal.

A CT scan of the neck discovered broken neck vertebrae and her neck was therefore immobilized with a collar. Blood and fluid in the lung also were noted. 

Further CT scans for her chest, abdomen, and pelvis confirmed blood in her lungs due to a small air leak, as well as the broken collar bone. She also had broken ribs on both sides of her body and a fracture of the pelvis that had not been detected in the x-rays. The blood in her chest was resolved after being drained over three days. 

Blood film analysis revealed the presence of enlarged red blood cells and cold agglutinin autoantibodies. Blood tests were positive for antibodies against cytomegalovirus (CMV) but were negative for other infectious microbes. 

As such, she was diagnosed with secondary CAD caused by the CMV infection. 

The hemolytic anemia continued after her initial transfusion, in which her hemoglobin levels dropped from 92 to 76 g/L within 48 hours. Despite being treated with the immunosuppressive medicine prednisolone for one week, her anemia remained.

That led the woman’s clinicians to treat her with 500 mg of the biological immunosuppressive therapy rituximab (marketed by Roche in the U.K. under the brand name MabThera; biosimilars are also available) once a week for a planned four weeks. Within two weeks, her hemoglobin levels rose from 70 to 95 g/L without further transfusions. 

At the time of this report, which was four months after hospital admission, the patient was discharged from the hospital with a stable hemoglobin level of 107 g/L and the neck collar still in place. 

The investigators concluded that the trauma from the fall caused the woman to be immunocompromised, “allowing reactivation of dormant CMV,” which led to the deterioration of the previously undiagnosed CAD, “triggering severe haemolysis in an already critically ill patient.” 

“Clinicians should consider CMV infection in the differential diagnosis of haemolytic anaemia in [immune healthy] older adults who are admitted with significant musculoskeletal trauma,” they added.