CAD Played Role in Acute Liver Failure of Elder Woman

Steve Bryson PhD avatar

by Steve Bryson PhD |

Share this article:

Share article via email
acute liver failure | Cold Agglutinin Disease | primary biliary cirrhosis | illustration of doctor with charts

Cold agglutinin disease (CAD) in an elder woman worsened an underlying autoimmune condition that subsequently led to acute liver failure, a case study reports.

This case highlights a need for informed understanding of CAD and its associations with other autoimmune processes, and how it can lead to early interventions and better treatment options, the researchers noted.

The study, “Traumatic Exacerbation IgG Predominant Cold-Aggulitinin Disease Causing Fulminant Liver Failure,” was published in the journal CHEST and presented at the CHEST 2021 Annual Meeting, held online Oct. 17–20.

In CAD, self-reactive antibodies called cold agglutinins mistakenly attack red blood cells at low temperatures. The binding of these antibodies can activate the complement cascade — part of the immune system that normally helps protect the body against invading microbes — resulting in red blood cell destruction (hemolysis).

Red blood cell damage and destruction cause anemia, a condition characterized by the lack of healthy cells to carry oxygen throughout the body. If damaged cells accumulate in the liver, scarring (fibrosis) and acute liver failure can occur.

Recommended Reading
Rare Disease Cures Accelerator-Data and Analytics Platform | Cold Agglutinin Disease News | Illustration of single person outline highlighted among many

New Data-sharing Program Aims to Speed Innovation in Rare Diseases

In this study, researchers described the case of a 70-year-old woman with CAD that further worsened acute liver disease thought to be caused by another autoimmune condition.

The woman arrived at the hospital in New Jersey with a hip fracture after falling. She had a history of high blood pressure (hypertension), low levels of thyroid hormones (hypothyroidism), and unexplained anemia requiring blood transfusions.

Initial blood tests showed she had anemia, as indicated by her low hemoglobin levels (9.0 grams per deciliter, or g/dL). Hemoglobin is the protein in red blood cells that carries oxygen. In women, its levels in the blood usually range from 12.1 to 15.1 g/dL.

The next day, she developed abdominal pain on her upper right side, with lab tests showing her hemoglobin levels had plummeted to 8.2 g/dL, while her total bilirubin levels were excessively high — a sign of red blood cell destruction.

Her hemoglobin levels continued to drop, while her bilirubin levels increased and liver function worsened. As a result, surgery to correct her hip fracture was delayed.

After eight days, and despite 48 hours of transfusions with four units of packed red blood cells, her hemoglobin levels dropped to 5.9 g/dL with no apparent signs of bleeding.

Blood work continued to show her bilirubin levels were excessively high, as were her lactate dehydrogenase and d-dimer levels. Lactate dehydrogenase is a marker of tissue damage, while d-dimer often is used as a blood-clotting indicator. A blood smear analysis revealed signs of red blood cell clumping (agglutination), consistent with CAD.

She was transferred to the intensive care unit with low blood pressure (hypotension), encephalopathy (brain disease or damage), and anemia that required repeated blood transfusions.

Eventually, she was sent to a liver transplant center due to acute liver failure, where further blood tests revealed the presence of cold agglutinins in her bloodstream.

Further analysis revealed the presence of antinuclear antibodies suggestive of a misguided immune attack against healthy tissue (autoimmunity), as well as elevated IgG antibodies, and other antibodies that target energy-production mitochondria. She also had a high liver fibrosis score, suggestive of severe liver damage.

Based on these test results, physicians suspected the underlying cause of her liver fibrosis to be primary biliary cirrhosis (PBC) — an autoimmune disease of the liver leading to the progressive destruction of small bile ducts, causing bile and other toxic substances to build up in the liver.

She remained in critical condition and died from a cardiac arrest. Authors noted that liver damage due to PBC most likely was further exacerbated by red blood cell destruction caused by CAD.

“A better understanding of the disease progression and associations of cold-agglutin disease with autoimmune phenomenon can lead to early interventions along with optimal treatment options,” the authors wrote.