A 70-year-old woman developed severe hemolysis and fulminant liver failure following a hip fracture due to a mechanical fall, and detailed examination suggested a diagnosis of cold agglutinin disease (CAD). The case was reported by Nanduri et al in Chest and was presented at the Chest 2021 Annual Meeting.

The patient remained in critical condition after being transferred to a liver transplant center, and eventually died from cardiac arrest.

The woman had a previous history of unexplained anemia requiring blood transfusions, hypertension, and hypothyroidism. At the time of clinical admission due to a hip fracture, her hemoglobin levels were 9.0 g/dL. The next day, the patient experienced right upper abdominal pain. Her hemoglobin levels decreased to 8.2 g/dL and total bilirubin was increased.

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The patient’s hemoglobin levels dropped continuously, even after blood transfusion, while her indirect bilirubinemia and synthetic liver function worsened. Clinicians did not find any obvious source of bleeding.

Biochemical analyses revealed relevant alterations in lactate dehydrogenase, indirect bilirubinemia, and D-dimer levels, with prominent agglutination on peripheral smear. At this time, the patient was transferred to an intensive care unit with hypotension, encephalopathy, and anemia requiring repeated blood transfusions.

She was transferred to a liver transplant center where she tested positive for cold agglutinins and direct Coomb’s test detected immunoglobulin G (IgG) and C3 antibodies. Additional findings suggested severe fibrosis.

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“Patients with CAD have low C3 and C4 levels due to chronic continuous consumption. However, in the setting of an acute trauma, C3 and C4 levels increase along with other pro-inflammatory cytokines causing exacerbation of hemolysis,” Nanduri et al explained.

Altogether, autoimmune analyses pointed to primary biliary cirrhosis as the cause of liver fibrosis, which was further exacerbated by erythrocyte hemolysis.

The authors stated, “A better understanding of the disease progression and associations of [CAD] with autoimmune phenomenon can lead to early interventions along with optimal treatment options.”


Nanduri A, Gulati U, Juneja P, Zheng L. Traumatic exacerbation IgG predominant cold-agglutinin disease causing fulminant liver failure. Chest. 2021;160(4):A912. doi:10.1016/j.chest.2021.07.850