After a new hip, profound anemia and kidney failure

In January of 1998, I was at home sitting down to dinner when my pager went off. It was the medical resident on call, saying that she needed me to come to the hospital and look at an abnormal test result on a newly admitted patient.

He was an African American man in his late 40s, who had been born in Philadelphia and had never left, with hemoglobin SC disease, a type of sickle-cell disease. Due to this inherited abnormality of his red blood cells, he had undergone removal of his spleen. He had also had his right hip replaced in his 30s due to avascular necrosis, in which a lack of blood supply to the hip causes severe degenerative arthritis.

The artificial hip had loosened, requiring removal of the original prosthesis and placement of a new one. Because of his baseline anemia and the blood loss expected from surgery, he had been transfused with four units of red blood cells at the time of the procedure.

Two weeks after his surgery, the newly replaced hip was doing well, but the patient developed fever, chills, sweats, fatigue, and generalized achiness. Over the next 17 days, he was seen by his orthopedic surgeon and, on several occasions, by emergency room physicians.

Each time, his physical examination was unrevealing, and he was advised to take aspirin and/or acetaminophen for symptomatic relief and wait for resolution of what was thought to be a self-limited viral infection.

On the 18th day of fever, he presented again to the emergency department. This time, his temperature was 104 and his blood pressure was 80/40, dangerously low.

Blood tests revealed profound anemia (much worse than his usual level) and acute kidney failure.

An hour later, the hematology laboratory called the emergency department, suggesting that a physician come look at his blood smear.

I jumped in my car and rushed to the hospital, headed downstairs to the hematology lab, and put the patient's slide on the microscope.

The view was astounding.

Many of his red blood cells were of an abnormal shape called target cells, which are a feature of hemoglobin SC disease.

Most of them had a wrinkled membrane, which occurs in kidney failure.

Several red cells contained clots of degenerating DNA known as Howell-Jolly bodies, which are seen in patients without a functioning spleen.

But the most important and prominent abnormality was that about 20 percent of the red blood cells contained an abnormal life form - an intracellular parasite: malaria.

How did this Philadelphia native with no travel history acquire an infection in midwinter that is normally transmitted by mosquitoes in the tropics?

The key lay in the post-operative blood transfusions. The donors were investigated by the Red Cross, and it was found that one of the four units of blood came from a Nigerian man who had emigrated a year earlier.

The Red Cross keeps a sample of blood from each donor; his blood was tested and showed evidence of infection with Plasmodium falciparum, the most common and most dangerous type of malaria in West Africa.

Because of the high prevalence and intense transmission of malaria there, most of the adult population is chronically infected. They develop a condition known as semi-immunity, in which the infection causes no symptoms and the number of parasites is quite small.

If blood from one of these semi-immune persons is transfused into a non-immune recipient, however, the parasites can run amok and produce a severe or fatal infection.

Transfusion malaria is well-described, but rare. This patient was the only case in the United States in 1998.

We were worried about him. Kidney failure, severe anemia, and parasites in more than 5 percent of red blood cells are all indications that the infection is potentially fatal.

We admitted him to the intensive care unit and treated him intravenously with a drug called quinidine, a derivative of quinine, which is itself derived from the bark of the cinchona tree.

The Quechua natives of ancient Peru recognized the beneficial effects of the bark for persons with fever, some of whom undoubtedly had malaria. Curiously, while the malaria parasite has evolved resistance to a number of newer antimalarial drugs, quinine and quinidine have largely maintained their efficacy.

After a couple of days, the patient improved to the point where he could be treated orally with a combination of quinine and doxycycline.

Repeat examination of his blood revealed fewer than 1 percent of his red cells were parasitized. His kidney failure, low blood pressure, and fever all resolved.

A week after arrival at the hospital, he returned home, fully recovered.