Medical Mystery: What was destroying man’s red blood cells?

A man in his late 50s was referred by a physician to the emergency room for chronic iron deficiency anemia, a condition in which blood lacks adequate healthy red blood cells. The patient reported some common symptoms of the condition, including fatigue, chest pain, shortness of breath, and frequent headaches.

Initial lab results showed smaller and lighter-colored red blood cells than normal, which can signal low levels of hemoglobin — a protein that carries oxygen throughout the body. Other tests confirmed hemolysis, which is the destruction of red blood cells, and evidence of blood clots in the kidneys and brain.

The patient’s blood tests were compatible with iron deficiency anemia, but without evidence of bleeding — the most common sign of iron deficiency anemia — the diagnosis was puzzling.

At this point, we had identified iron deficiency anemia, hemolysis and thrombosis, or systemic clotting.

We also identified evidence of pancytopenia, a condition in which people have low counts of red and white blood cells, and platelets. What condition could account for the patient’s combination of iron deficiency anemia, hemolysis, thrombosis and pancytopenia?

Tests of the patient’s bone marrow revealed a predominance of immature red blood cells and an absence of iron consistent with paroxysmal nocturnal hemoglobinuria (PNH). Based on our multiple findings, we confirmed a diagnosis of PNH by identifying a deficiency of two regulatory protective proteins that prevent cells from being destroyed.

PNH is a rare bone marrow failure disorder; the United States sees only a few hundred cases each year. PNH is the result of a genetic defect in regulatory proteins in bone marrow stem cells, allowing blood cells to be destroyed more quickly. As a result, hemoglobin levels drop.

PNH leads to an increased risk of blood clotting, which is the leading cause of death among those with the condition, and various bone marrow complications.

While in the hospital, the patient experienced blood clots resulting in multiple, life-threatening strokes.

We started treatment with blood thinners to prevent blood clotting as a result of anemia.

We also prescribed vitamins and iron to help the patient reach and maintain healthy blood cell levels. After being treated for bacterial infection, we placed him on definitive maintenance antibody therapy — an infusion drug that inhibits the breakdown of regulatory proteins in bone marrow and prevents the destruction of red blood cells.

Bone marrow transplants also may be effective treatment options for patients whose condition is life-threatening. Transplants are the only cure for PNH, but they involve potential complications, including infection and transplant rejection.

More than three years after we treated the patient, he is doing well on maintenance antibody therapy with no residual health effects of his blood clots.

PNH can easily be missed because most forms of iron deficiency anemia are caused by obvious bleeding. Our patient had seen multiple physicians without the proper diagnosis before being referred to us. Doctors must also consider the intravascular breakdown of red blood cells when there is no evidence of bleeding.

Lewis Rose is the medical director of oncology at Nazareth Hospital.