Doctors Puzzled Why Only Some Ebola Patients Bleed

One of Ebola's most notorious symptoms is bleeding from places like the nose and mouth, but such bleeding has only occurred in a minority of cases in the current outbreak.

It remains a mystery why some people experience this bleeding while others don't. The bleeding, which is properly called "hemorrhagic syndrome," happens in the late stages of the disease, about 24 to 48 hours before death.

In the current West Africa outbreak, about 18 percent of people infected with the virus are developing hemorrhagic syndrome, according to the Centers for Disease Control and Prevention (CDC). Typically, the Ebola virus leads to hemorrhagic syndrome about 30 percent to 50 percent of the time, said Angela Rasmussen, a research assistant professor of microbiology at the University of Washington. [Ebola Virus: 5 Things You Should Know]

Cases with bleeding are "usually quite severe and dramatic," Rasmussen told Live Science. "But many Ebola cases don't have that feature. And that feature only presents in the very late stages of the disease."

The current Ebola outbreak is the worst on record. In Guinea, Liberia and Sierra Leone, more than 7,400 people have become infected and more than 3,400 have died since the outbreak began in early 2014, according to the CDC. Nigeria also had a cluster of 20 cases, and Senegal, Spain and the United States have each reported one Ebola case.

In fact, the relatively low prevalence of hemorrhagic syndrome in the current outbreak may explain why the outbreak remained under the radar for a time before it was recognized.

"I have heard speculation that a lower incidence of hemorrhagic syndrome may explain why the outbreak may not have been recognized early on as [being caused by] Ebola," Rasmussen said, "since it was geographically outside of what we previously thought was the range for Zaire Ebola virus, and since without hemorrhage, it appears similar to malaria or typhoid."

Ebola's mechanisms aren't entirely known, but like other severe viral infections, it starts with a fever, which is often followed by vomiting, diarrhea, body aches and nausea. The virus targets the immune system, infecting white blood cells and replicating itself until patients have high levels of the virus circulating throughout their body.

Hemorrhagic syndromestems from the fact that as the virus grows in numbers, it can infect the liver, the organ that makes proteins that help the blood clot. Normally, clotting factors circulate throughout the body and stop bleeding where they're needed.

In people with Ebola, the virus causes severe inflammation that can cause these clotting proteins to go into overdrive, and form small blood clots that clog blood vessels. These clots can also block the flow of blood to vital organs, such as the liver, brain or kidneys, leading to organ damage.

Eventually, the body runs out of available clotting factors, and the infected liver is unable to make more, Rasmussen said.

Meanwhile, the infected immune cells are going out of control, triggering a chaotic inflammatory response, Rasmussen said. In turn, the cells that line the body's blood vessels also become inflamed, and start to leak, which leads to hemorrhagic syndrome.

It typically takes five to eight days for hemorrhagic syndrome to develop in patients with the Ebola virus, she said. After this amount of time, patients have very low levels of clotting factors, she said.

Infected mice

Rasmussen and her colleagues are learning more about the virus by studying its effects in mice. Rasmussen works in Seattle, but her collaborators work at Rocky Mountain Laboratories, a high-security lab in Montana run by the National Institutes of Health. The team is examining how the Ebola virus affects different types of mice.

About 20 to 25 percent of the infected mice develop only a mild case of Ebola. "They usually have weight loss," Rasmussen said. "They might be a little subdued behaviorally, but they usually recover their weight and survive."

Another 30 to 40 percent of the mice develop severe symptoms, but no bleeding. They have pale-colored livers, indicating severe hepatitis. "They just die before or without developing those hemorrhagic symptoms," she said.

About 40 percent of the mice develop full-blown hemorrhagic syndrome, Rasmussen said. Their blood won't clot at the time of their death, and they have low levels of serum fibrinogen, a molecule important for clotting.

"The ones that do develop the hemorrhagic syndrome usually die between days seven and 10," Rasmussen said. "And that's pretty similar to what we see in humans."

Bleeding can happen throughout the body. Infected people may have internal bleeding, or may find petechial rashes — a sign that the capillaries within the skin are bleeding.

"[Bleeding] can take on a variety of shapes and forms, with the worst cases being people vomiting blood, having bloody diarrhea, bleeding from their nose and mouth and where the sun don't shine," Rasmussen said.

Mouse genetics may help researchers learn why some people develop hemorrhagic syndrome and others don't. Rasmussen and her colleagues are examining whether any genetic factors predispose an individual to developing the bleeding, she said.

Ebola isn't the only virus that causes hemorrhagic syndrome. Dengue virus, often seen in the world's tropical areas, and Lassa fever, seen in West Africa, can lead to bleeding. Marburg, a virus carried by bats, also causes similar symptoms.

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