IV Fluids at Room Temperature Trigger Hemolytic Anemia in Diabetic

Progressive hemolytic anemia — the rupture and gradual depletion of red blood cells — caused by cold agglutinin disease (CAD) was triggered in a man with diabetes being treated at a hospital with intravenous fluids, according to a case report.

The man was admitted to the hospital due to diabetic ketoacidosis, a potentially life-threatening complication in which the body starts to break down fat too quickly.

His case highlights that CAD “should be considered in the differential diagnosis of progressive hemolytic anemia during fluid resuscitation, even if the solution is at room temperature,” the scientists wrote.

The case study, “Cold agglutinin-induced hemolytic anemia during room temperature fluid resuscitation: a case report,” was published in the Journal of Medical Case Reports.

CAD is caused by the presence of self-reactive antibodies called cold agglutinins that bind and destroy red blood cells at low temperatures, leading to hemolytic anemia.  Warming intravenous fluids to room temperature when treating hospitalized patients is recommended to avoid cold-induced hemolytic anemia.

In this report, however, a 71-year-old man in Japan experienced hemolytic anemia caused by CAD, despite being treated with intravenous fluids at room temperature.

The man had type 2 diabetes but was not taking any medication for that disease, and was admitted to a hospital in Niigata with low blood pressure, livedo reticularis (reddish-bluish skin discoloration), an elevated heart rate, and low body temperature of 91.4 F (33 C).

Lab tests found signs of anemia, including enlarged red blood cells, low hemoglobin levels, high white blood cell counts, and elevated levels of the inflammatory marker C-reactive protein. 

He also had high blood sugar levels, ketones in the urine, and his blood pH was too acidic. Of note, ketones are metabolic byproducts that form in the liver after the body breaks down fat to use it as a source of fuel; when ketones are produced at a fast rate, they can build in the blood, causing it to become acidic.

All these signs indicated diabetic ketoacidosis, a potentially life-threatening complication of diabetes due to the body breaking down fat for energy because it lacks insulin to use glucose. The ketones released by the burning of fat cause fatigue, and risk a loss of consciousness and a diabetic coma.

In the emergency room, the man was given intravenous fluids to replenish the body, along with insulin infusions to control his blood sugar levels, and was kept warm with blankets. 

He was then transferred to the intensive care unit (ICU), and his low blood pressure persisted, despite fluid treatment. He was then treated with norepinephrine and vasopressin to raise his blood pressure. His blood sugar levels had dropped significantly within 12 hours of ICU admission, although they remained high.

A low red blood cell count and elevated bilirubin — a byproduct of red blood cell destruction — indicated his anemia was progressing, and a non-warmed blood transfusion was given. The patient improved the following day, leading physicians to discontinue both norepinephrine and vasopressin, and reduce fluid infusions.

Five days after being admitted to the ICU, physicians noticed his red blood cells were clumping, a typical sign of CAD. A Coombs antibody test and cold agglutinins titer test confirmed a CAD diagnosis. 

The patient was discharged from the ICU after six days, and from the hospital about a month after his admission, and advised to avoid cold temperatures. No further anemic episodes were reported.

“In emergency care, fluid resuscitation is often administered. In patients with hemolytic anemia, peripheral blood smear, Coombs test, and [cold agglutinins] test should be performed, and infusion or transfusion should be changed to a warmed one,” the scientists wrote.