Paroxysmal cold hemoglobinuria (2023)

What are other names for this condition? (aka/synonyms)

• Second Donath-Landsteiner hemolytic anemia
• Donath-Landsteiner syndrome
• PCH (cold paroxysmal hemoglobinuria)

What is Paroxysmal Cold Hemoglobinuria? (definition/basic information)

• Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia (AIHA) in which the body's immune system makes antibodies against its own red blood cells. It is also known as Donath-Landsteiner Syndrome.
• The condition is more common in children and people who live in cold environments. People, especially children, are more likely to develop paroxysmal cold hemoglobinuria when they have a bacterial or viral infection and are traveling from a cold to a warm climate.
• Paroxysmal cold hemoglobinuria may present with symptoms 1 to 2 weeks after an initial bacterial or viral infection; The most common signs and symptoms include brownish urine, tiredness and jaundice. PCH is diagnosed by healthcare professionals after a thorough medical evaluation, special tests, and blood tests.
• Individuals with paroxysmal cold hemoglobinuria usually recover spontaneously when the PCH-associated infection is treated. Cold temperatures should be avoided during this period. Once the damaged red blood cells are naturally replaced by the body, the signs and symptoms disappear.
• For most people with paroxysmal cold hemoglobinuria, the prognosis is good as long as cold environments are avoided and appropriate treatment is administered. The disease is known to resolve spontaneously in many cases.

Who has paroxysmal cold hemoglobinuria? (distribution by age and sex)

• Paroxysmal cold hemoglobinuria (PCH) is a rare condition; Known to affect 1-3 per 100,000 people worldwide
• It is more common in children than adults and affects both men and women.
• There are known factors that increase the likelihood that PCH will affect a specific breed or genetic background.
• Because PCH is associated with areas with colder climates, a greater number of cases are more likely to occur in these geographic locations.

What are the risk factors for paroxysmal cold hemoglobinuria? (predisposing factors)

Risk factors for paroxysmal cold hemoglobinuria (PCH) may include:

• Living in cold climates
• Recent bacterial or viral infection; Individuals, especially children, are at greater risk of developing PCH
• Children with an upper respiratory tract infection are at increased risk of developing HCP in the following weeks
• Historically, paroxysmal cold hemoglobinuria has been associated with individuals with late-stage congenital syphilis who present with complications such as jaundice and hemoglobinuria. These symptoms, made worse by exposure to cold, increase the risk of developing HCP. However, this is currently a small risk factor because syphilis can be cured with antibiotics before it reaches the advanced stages.

It is important to note that having a risk factor does not mean you will have the disease. Having a risk factor increases the likelihood of developing a disease compared to a person without these risk factors. Some risk factors are more important than others.

Even the absence of a risk factor does not mean that a person will not develop this disease. It is always important to discuss the impact of risk factors with your doctor.

What are the causes of paroxysmal cold hemoglobinuria? (Etiology)

In most cases, particularly in children, the cause of paroxysmal cold hemoglobinuria (PCH) is infection followed by acute hemolytic anemia.

• Hemolytic anemia usually manifests after infection, which can be exacerbated by cold weather
• It is caused by a malfunction of the immune system, which produces antibodies against red blood cells (erythrocytes); Antibodies attach to red blood cells and destroy them
• Hereditary factors, such as membrane defects or hemoglobin abnormalities, can also cause HCP in some children.

Paroxysmal cold hemoglobinuria usually affects the hands and feet in cold environments.

What are the signs and symptoms of paroxysmal cold hemoglobinuria?

The signs and symptoms of Paroxysmal Cold Hemoglobinuria (PCH) are usually noticed after a person has started to recover from a (previous) cold or flu-like illness. The onset of PCH begins with chills and what may look like a recurrence of fever from a past (recent) illness. Other observed signs and symptoms may include:

• Brown urine caused by pigmentation from the breakdown of hemoglobin in red blood cells
• Fatigue and muscle pain due to anemia
• jaundice (yellowing of the skin and whites of the eyes)
• Pallor (unhealthy pale appearance)
• Headache
• stomachache
• back or leg pain
• Headaches, vomiting, and diarrhea are less common

How is paroxysmal cold hemoglobinuria diagnosed?

The diagnosis of paroxysmal cold hemoglobinuria (PCH) is made after a physical examination and a careful review of the patient's medical history, followed by a series of specific tests, including:

• Direct antiglobulin test (Coombs test): is used to detect antibodies against red blood cells
• Donath-Landsteiner test: is used to distinguish PCH from other forms of anemia
• A complete blood count (CBC), which may indicate anemia
• During seizures, the level of hemoglobin in the blood is higher
• serum lactate dehydrogenase (LDH) level test; LDH levels can be high
• Blood test for reticulocyte count
• Urine hemoglobin test to detect the presence of hemoglobin in the urine
• Serum bilirubin level test
• Serum haptoglobin level test
• Examination of a peripheral blood smear under the microscope by a pathologist

Many clinical conditions can have similar signs and symptoms. Your doctor may perform additional tests to rule out other medical conditions and make a definitive diagnosis.

What are the possible complications of paroxysmal cold hemoglobinuria?

Complications of paroxysmal cold hemoglobinuria are usually minimal as the symptoms usually resolve after the infection resolves. In some cases, however, the following may be observed:

• Recurrent seizures, which are very rare
• kidney failure
• Persistent severe anemia
• Excessive tiredness, which can make it difficult to carry out daily activities

How is paroxysmal cold hemoglobinuria treated?

In many cases, treatment for paroxysmal cold hemoglobinuria (PCH) may not be necessary because the condition usually resolves spontaneously or with resolution of the underlying infection (if present).

• Supportive therapy may be needed until symptoms resolve
• Cold temperatures should be avoided at all costs.
• In children, supportive care is only needed if significant symptoms of PCH are observed, as the child may already be recovering from the underlying viral infection (related to PCH).
• In some cases, corticosteroid therapy may be considered.
• If necessary, take immunosuppressive drugs
• Severe anemia may require blood transfusions, and the use of a blood warmer is usually recommended during the process.

How to prevent paroxysmal cold hemoglobinuria?

Preventive measures for paroxysmal cold hemoglobinuria (PCH) are very similar in adults and children.

• People, especially children, with bacterial or viral infection should avoid contact with cold environments
• People who have 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 for paroxysmal cold hemoglobinuria? (Results/Resolutions)

• The prognosis of paroxysmal cold hemoglobinuria is generally good as the symptoms are known to resolve and disappear quickly and spontaneously.
• In most cases, attacks end after the abnormal immune response subsides.
• The prognosis also depends on the severity of signs and symptoms. Untreated severe anemia can lead to serious complications

Additional useful and relevant information about paroxysmal cold hemoglobinuria:

• Paroxysmal cold hemoglobinuria (PCH) is becoming more common in children and is one of the most common causes of acute autoimmune hemolytic anemia in children. This is likely due to increased awareness and use of dedicated PCH tests

Normally, red blood cells have a lifespan of about 120 days, but in people with paroxysmal cold hemoglobinuria, these (erythrocytes) are destroyed much sooner