Paroxysmal cold hemoglobinuria (PCH) (also known as Donath-Landsteiner syndrome) is a disease of humans that is characterized by the sudden presence of hemoglobin

Hemoglobin

Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

 in the urine (called hemoglobinuria

Hemoglobinuria

In medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...

), typically after exposure to cold temperatures.

Presentation

In people with PCH, a polyclonal IgG anti-P autoantibody

Autoantibody

An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...

 binds to red blood cell

Red blood cell

Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

 surface antigens in the cold. This can occur in a susceptible individual as blood passes through cold extremities in cold weather. When the blood returns to the warmer central circulation, the red blood cells are lysed with complement

Complement system

The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

, causing intravascular hemolysis

Hemolysis

Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...

. Hemoglobinuria and anemia

Anemia

Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

 can then occur. The anemia may be mild or severe.

Causes

PCH is a rare autoimmune haemolytic anaemia that can occur following an infection, when a microorganism triggers the formation of antibodies that cross-react with the P antigen on the red blood cell membrane. Viral infections that can cause PCH include measles

Measles

Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...

, mumps

Mumps

Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...

, influenza

Influenza

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

, adenovirus

Adenoviridae

Adenoviruses are medium-sized , nonenveloped icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome...

, chickenpox

Chickenpox

Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...

, cytomegalovirus

Cytomegalovirus

Cytomegalovirus is a viral genus of the viral group known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV: The species that infects humans is commonly known as human CMV or human herpesvirus-5 , and is the most studied of all cytomegaloviruses...

, and Epstein-Barr virus

Epstein-Barr virus

The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...

. Bacterial infections that can cause PCH include syphilis

Syphilis

Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

, Haemophilus influenzae

Haemophilus influenzae

Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...

and Mycoplasma pneumoniae

Mycoplasma pneumoniae

Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...

. PCH can also be a side effect of some vaccinations. Chronic idiopathic

Idiopathic

Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...

 (of unknown cause) PCH also occurs, but it is rare.

Treatment and prognosis

Acute PCH tends to be transient and self-limited, particularly in children. Chronic PCH associated with syphilis resolves after the syphilis is treated with appropriate antibiotics. Chronic idiopathic PCH is usually mild.

Risk factors

People with PCH are sometimes advised to avoid exposure to cold temperatures. If anemia is severe, blood transfusion

Blood transfusion

Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...

 may be needed. Careful compatibility testing by the blood bank is necessary because autoantibodies may interfere with blood typing. Prednisone

Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

 may be used in individuals with PCH and severe anemia.

See also

• Hemolytic anemia
  Hemolytic anemia
  Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
  
  
• Cold agglutinin disease
• List of hematologic conditions