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Protein Disorders Causing Blood Vessel Disorders

By David J. Kuter, MD, DPhil, Professor of Medicine, Harvard Medical School; Chief of Hematology, Massachusetts General Hospital

Conditions that cause an abnormal protein or an abnormal amount of certain normal proteins in the blood can cause blood vessels to become fragile. When these fragile blood vessels break, people develop red or purple blemishes or bruises (purpura) on the skin. Conditions that may cause purpura include

  • Amyloidosis

  • Cryoglobulinemia

  • Hypergammaglobulinemic purpura

  • Hyperviscosity syndrome


Amyloidosis causes the protein amyloid to be deposited within blood vessels in the skin and subcutaneous tissues, which may increase the fragility of the blood vessels, causing purpura. When a person develops bruising around the eyes or bruising after only light stoking, doctors may suspect amyloidosis. Doctors may do an examination of tissue (biopsy) taken from the fat of the abdominal wall to confirm amyloidosis. Treatment depends on how severe amyloidosis is and what other tissues are affected.


Cryoglobulinemia occurs when abnormal immunoglobulin proteins in the blood clump together when blood cools (for example, when it flows through the arms and legs). These abnormal proteins are called cryoglobulins. When cryoglobulins clump together in blood vessels, the vessels may leak, leading to bruises and reddish sores on the skin. Cryoglobulins can be detected by laboratory testing. Treatment of the underlying disorder may reduce these symptoms.

Hypergammaglobulinemic purpura

In hypergammaglobulinemic purpura, blood vessels are damaged by inflammation related to high levels of immunoglobulins in the blood. This disorder primarily affects women. Recurrent crops of small, raised reddish purple discolorations develop on the lower legs. These crops leave small residual brown spots. Many people have manifestations of an underlying immune disorder, such as Sjögren syndrome or systemic lupus erythematosus (lupus).

Doctors usually do blood tests. Often tests show that one type of immunoglobulin (called IgG) is increased. Doctors treat the underlying disorder.

Hyperviscosity syndrome

Hyperviscosity syndrome occurs when people have too large a quantity of certain blood proteins (immunoglobulins), most commonly due to blood cancers like macroglobulinemia. The excess immunoglobulins increase the thickness (viscosity) of the blood and cause it to move slowly through the blood vessels. Hyperviscosity syndrome limits blood flow to the skin, fingers, toes, nose, and brain. The blood vessels become overfilled with blood and may leak, causing discoloration of the skin.

Recurrent nosebleeds and bleeding from the gums are the most common symptoms, but heart failure or stroke sometimes occurs when blood becomes very thick. Doctors may do blood tests, including one to measure the viscosity of the blood. People with symptoms due to hyperviscosity are treated with plasma exchange. Chemotherapy also may be required to treat an underlying blood cancer.