What are other Names for this Condition? (Also known as/Synonyms)

• Donath-Landsteiner Hemolytic Anemia
• Donath-Landsteiner Syndrome
• PCH (Paroxysmal Cold Hemoglobinuria)

What is Paroxysmal Cold Hemoglobinuria? (Definition/Background Information)

• Paroxysmal Cold Hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) disease in which the body’s immune system makes antibodies against one’s own red blood cells. It is also known as Donath-Landsteiner Syndrome
• The condition is more common among children and those that live in cold environments. Individuals, especially children, are more likely to contract Paroxysmal Cold Hemoglobinuria if they have a bacterial or viral infection and travel from a cold to warm climate
• Paroxysmal Cold Hemoglobinuria can show symptoms 1-2 weeks following an initial bacterial or viral infection; the common signs and symptoms noted include brownish urine, fatigue, and jaundice. PCH is diagnosed by a healthcare professional following a careful medical examination and via specialized assessments and blood tests
• Individuals with Paroxysmal Cold Hemoglobinuria usually recover spontaneously once the infection associated with PCH is taken care of. During this time, one must avoid cold temperatures. Once the damaged red blood cells are replaced naturally by the body, the signs and symptoms subside
• For most individuals with Paroxysmal Cold Hemoglobinuria, the prognosis is good, as long as cold environments are avoided and proper treatment is received. The condition is known to resolve spontaneously in many cases

Who gets Paroxysmal Cold Hemoglobinuria? (Age and Sex Distribution)

• Paroxysmal Cold Hemoglobinuria (PCH) is a rare disorder; 1-3 per 100,000 individuals are known to be affected worldwide
• It is more common among children than adults, and both male and female genders are affected
• There are known factors that make PCH more likely to affect a specific race or genetic background
• Since PCH is associated with areas having colder climates, these geographical locations are more likely to see a greater number of cases

What are the Risk Factors for Paroxysmal Cold Hemoglobinuria? (Predisposing Factors)

The risk factors for Paroxysmal Cold hemoglobinuria (PCH) may include:

• Living in cold climates
• Recent bacterial or viral infection; individuals, particularly children, have a higher risk for developing PCH
• Children with an upper respiratory tract infection are more at risk for developing PCH in the following weeks
• Historically, Paroxysmal Cold Hemoglobinuria has been associated with individuals with late-stage congenital syphilis who have complications such as jaundice and hemoglobinuria. These symptoms, aggravated by exposure to cold temperatures, places them at a higher risk for developing PCH. Nevertheless, this is a low risk factor presently due to the ability to cure syphilis with antibiotics before it reaches a late stage

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Paroxysmal Cold Hemoglobinuria? (Etiology)

In most cases, particularly in children, the cause of Paroxysmal Cold Hemoglobinuria (PCH) is due to an infection that is followed by acute hemolytic anemia.

• Hemolytic anemia generally manifests after the infection, which may be amplified by cold weather
• It is caused by a malfunctioning of the immune system, producing antibodies against the red blood cells (RBCs); antibodies bind to the RBCs and destroy them
• Hereditary factors, such as membrane defects or hemoglobin abnormalities, can also cause PCH in some children

Paroxysmal Cold Hemoglobinuria usually involves the hands and feet when in cold environments.

What are the Signs and Symptoms of Paroxysmal Cold Hemoglobinuria?

The signs and symptoms of Paroxysmal Cold Hemoglobinuria (PCH) are usually observed after an individual has begun to recover from a (previous) cold or flu-like illness. The onset of PCH begin with chills and what may seem like a recurrence of fever from (recent) past illness. Other signs and symptoms noted may include:

• Brown urine, due to pigment from breakdown of hemoglobin within the red blood cells
• Fatigue and muscle pain due to anemia
• Jaundice (yellowing of skin and whites of eyes)
• Pallor (unhealthy pale appearance)
• Headache
• Abdominal pain
• Back or leg pain
• Headache, vomiting, and diarrhea are less common 

How is Paroxysmal Cold Hemoglobinuria Diagnosed?

Paroxysmal Cold Hemoglobinuria (PCH) is diagnosed following a physical examination and a careful examination of the patient’s medical history followed by a variety of specialized tests including:

• Direct antiglobulin test (Coombs test): It is used to detect antibodies against red blood cells
• Donath-Landsteiner test: It is used to distinguish PCH from other forms of anemia
• Complete blood count (CBC) test that may be indicative of anemia
• Levels of hemoglobin in blood is higher during attacks
• Serum lactate dehydrogenase (LDH) level test; LDH levels may be high
• Reticulocyte count blood test
• Urine hemoglobin test to detect the presence of hemoglobin in urine
• Serum bilirubin level test
• Serum haptoglobin level test
• Examination of peripheral blood smear under the microscope by a pathologist

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Paroxysmal Cold Hemoglobinuria?

Complications of Paroxysmal Cold Hemoglobinuria are usually minimal because symptoms typically subside following resolution of the infection. However, in some cases, the following may be noted:

• Recurrent attacks, which are very rare
• Kidney failure
• Severe prolonged anemia
• Excessive fatigue that may make it difficult for an individual to carry out his/her day-to-day activities

How is Paroxysmal Cold Hemoglobinuria Treated?

In many cases, a treatment may not be required for Paroxysmal Cold Hemoglobinuria (PCH) because the condition typically goes away spontaneously or with the resolution of the underlying infection (if any).

• Supportive therapy may be needed until the symptoms subside
• Cold temperatures should be avoided in all cases
• In children, supportive treatment is only necessary when significant symptoms of PCH are observed, as the child may already be in the recovery period of the underlying viral infection (associated with PCH)
• In some cases, corticosteroid therapy may be considered
• Use of immunosuppressive medications, if needed
• In severe anemia, blood transfusions may be necessary, and the use of a blood warmer is usually recommended during the process

How can Paroxysmal Cold Hemoglobinuria be Prevented?

The preventative measures of Paroxysmal Cold Hemoglobinuria (PCH) are very similar for both adults and children.

• Individuals, especially children with a bacterial or viral infection, should avoid exposure to cold environments
• Individuals who had had PCH should avoid being out in the cold to prevent future attacks
• Early diagnosis and treatment of anemia can help prevent complications

What is the Prognosis of Paroxysmal Cold Hemoglobinuria? (Outcomes/Resolutions)

• The prognosis of Paroxysmal Cold Hemoglobinuria is generally good as the symptoms are known to subside and resolve quickly and spontaneously
• In most cases, the attacks end after the abnormal immune response subsides
• The prognosis also depends on the severity of the signs and symptoms. Severe untreated anemia may lead to severe complications

Additional and Relevant Useful Information for Paroxysmal Cold Hemoglobinuria:

• Paroxysmal Cold Hemoglobinuria (PCH) has become more common in children and is one of the most common causes of acute autoimmune hemolytic anemia in children. This is likely due to an increase in awareness and an increased use of specialized testing for PCH 

Usually, red blood cells have a lifespan of about 120 days, but in individuals with Paroxysmal Cold Hemoglobinuria, these (RBCs) are destroyed much earlier