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Protein Disorders Causing Bruising or Bleeding


David J. Kuter

, MD, DPhil, Harvard Medical School

Reviewed/Revised May 2023
Topic Resources

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 bruises (purpura) on the skin. Conditions that may cause purpura include

  • Amyloidosis

  • Cryoglobulinemia

  • Hypergammaglobulinemic purpura

  • Hyperviscosity syndrome


Amyloidosis Amyloidosis Amyloidosis is a rare disease in which abnormally folded proteins form into collections called amyloid fibrils that accumulate in various tissues and organs, sometimes leading to organ dysfunction... read more 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, usually on the arms. When a person develops bruising around the eyes or bruising after only light stroking, doctors may suspect amyloidosis. Doctors may do a blood test to look for the amyloid substance in the blood and also examine a sample of fat from the abdominal wall or of tissue from any affected organ to confirm amyloidosis. Treatment depends on how severe amyloidosis is and what other tissues are affected.


Cryoglobulinemia What Is Cryoglobulinemia? What Is Cryoglobulinemia? occurs when abnormal immunoglobulin (antibody Antibodies One of the body's lines of defense ( immune system) involves white blood cells (leukocytes) that travel through the bloodstream and into tissues, searching for and attacking microorganisms and... read more Antibodies ) 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

Doctors usually do blood tests. Often tests show that one type of immunoglobulin (called IgG) is increased. Doctors may also need to take a sample of skin for testing (biopsy).

Doctors treat the underlying disorder.

Immunoglobulin A–associated vasculitis

Immunoglobulin A–associated vasculitis Immunoglobulin A–Associated Vasculitis Immunoglobulin A–associated vasculitis (formerly called Henoch-Schönlein purpura) is inflammation of mainly small blood vessels that most often occurs in children. A rash of reddish purple bumps... read more Immunoglobulin A–Associated Vasculitis (Henoch-Schonlein purpura) is inflammation mainly of small blood vessels that occurs primarily in children. It involves the skin, joints, intestine, and kidneys. A rash of reddish purple bumps and spots typically develops, most often on the lower legs and buttocks.

Doctors do blood tests and a skin biopsy. Finding inflammation and deposits of IgA immunoglobulin confirms the diagnosis.

Many of the symptoms of immunoglobulin A–associated vasculitis resolve on their own. Doctors treat the joint pain caused by the blood vessel inflammation with pain medications. Corticosteroids and immunosuppressants may be needed to treat inflammation in the kidney.

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 Macroglobulinemia Macroglobulinemia is a plasma cell cancer in which a single clone of plasma cells produces excessive amounts of a certain type of large antibody (IgM) called macroglobulins. Although many people... read more or multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells in which abnormal plasma cells multiply uncontrollably in the bone marrow and occasionally in other parts of the body. People often have bone pain... read more . 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 plasmapheresis. Plasmapheresis is a process in which blood is taken from the person and put through a machine that separates the blood cells from the liquid part of the blood (plasma). The plasma, which contains the disease-causing proteins, is discarded and the blood cells are returned to the person.

Chemotherapy also may be required to treat an underlying blood cancer.

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