Paroxysmal cold haemoglobinuria (PCH) is a type of cold autoimmune haemolytic anaemia (cAIHA) that mainly affects children.^1-3 In PCH, the body produces antibodies that cause the immune system to mistakenly attack and destroy its own red blood cells.^1-3 These particular antibodies are called Donath-Landsteiner autoantibodies. These antibodies stick to red blood cells best at cooler body temperatures (such as in the hands and feet), but the disease can still occur at warm temperatures.

Red blood cells usually have a life span of 120 days, but in autoimmune haemolytic anaemias, the red blood cells are destroyed as fast as they are produced, leaving very few in the bloodstream. This causes symptoms of severe anaemia, which can be life threatening.

PCH usually occurs as a single severe episode of symptoms (acute PCH) that resolves by itself with rest and symptomatic treatment (self-limiting disease). PCH usually occurs after an infection, but sometimes there is no known underlying cause. There are also less common cases where PCH is recurring (chronic PCH).^{1, 2}

There is another type of cold autoimmune haemolytic anaemia, called cold agglutinin disease, where a different type of antibody causes red blood cell destruction at cold temperatures (under 30˚C).⁴ There is also a different condition (warm autoimmune haemolytic anaemia, wAIHA) where the red blood cell destruction occurs at warm temperatures (37-40˚C).⁵ 

Synonyms: cold antibody autoimmune haemolytic anaemia, cAIHA, autoimmune hemolytic anemia, primary/idiopathic autoimmune haemolytic anaemia, Donath-Landsteiner haemolytic anaemia, Donath-Landsteiner syndrome.^1,3,6,7

This condition is called Paroxysmal cold haemoglobinuria because it is named after the symptoms of chronic (recurring) PCH, and not acute (single episode) PCH. In the past, adults who had a syphilis infection that was untreated for many years sometimes developed chronic (recuring) PCH. As there are now antibiotics that treat syphilis, it is now uncommon. In chronic syphilis-associated PCH, cold temperatures triggered a sudden (paroxysmal) worsening of the disease, however this is not the case for PCH seen in children today (acute PCH). It is now recognised that the triggers and symptoms of acute PCH are different from what the name suggests.¹

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:90035, Paroxysmal cold hemoglobinuria 

ICD-11: 3A20.3 Paroxysmal cold haemoglobinuria 

PCH is usually a serious and short-term condition (acute and transient).^1-3 PCH symptoms usually occur after a period of known illness, such as a respiratory tract infection, viral infection, or other illness. The prior illness may cause flu-like symptoms such as headaches, mild fever, and aches and pains that can last for one or two weeks. The PCH symptoms will then appear as well, and often include recurring high fevers as well as signs of severe anaemia, such as weakness, dizziness, fatigue, shortness of breath (dyspnoea), back and/or leg pain, abdominal pain, pale skin colour (pallor), yellowing of skin and eyes (jaundice), and dark red-brown coloured urine. Severe anaemia can lead to multiple organ shutdown and can be life threatening.

Please speak to your medical team to learn more about the symptoms of PCH.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

Acute PCH is an autoimmune condition usually caused by an infection (in most cases a virus). This infection causes the body to make a type of antibody called Donath-Landsteiner autoantibodies.^1-3 These antibodies stick to red blood cells which causes the red blood cells to be recognised as abnormal and destroyed by the immune system.

There is no single type of infection that causes PCH; any infections may cause the body to make Donath-Landsteiner autoantibodies. It’s not clear why some people develop these antibodies after an infection. Usually, the condition resolves by itself in a few days to weeks after the initial infection is cleared.

In some adults, PCH can be chronic, which means it is a long-lasting condition that keeps coming back (recurring).^1-3 Like acute PCH, chronic PCH can be caused by an infection of any type. Sometimes the cause is unknown (idiopathic). There have also been cases where chronic PCH has been linked to blood cancers (haematological malignancies).⁸

Haemolytic anaemia may be suspected in individuals with PCH symptoms described above, and a blood test showing that they have misshapen red blood cells, and a high proportion of young compared to old red blood cells.^1,9 More specific blood or urine tests may then be performed to look for other signs of red blood cell destruction (haemolysis) and clumping of red blood cells (agglutination). These tests may include complete blood count (CBC), a bilirubin test, haptoglobin test, and a lactate dehydrogenase (LD) test.

Once haemolytic anaemia is confirmed, a direct antiglobulin test (DAT, also known as Coomb’s test) can identify if there are autoantibodies sticking to red blood cells, and if so what type. This test can diagnose cold autoimmune haemolytic anaemia (cAIHA) and distinguish it from warm autoimmune haemolytic anaemia (wAIHA) (which involves a different type of antibody).^2,10 A Donath-Landsteiner test can then confirm a PCH diagnosis and differentiate it from other types of cAIHA.

More information about the various tests can be found at Pathology Tests Explained: Anaemia – includes information on full blood count tests. 

As part of the diagnostic process, doctors may do a differential diagnosis, where they rule out other conditions that have similar symptoms. This may include paroxysmal nocturnal hemoglobinuria, other forms of autoimmune haemolytic anaemia such as warm autoimmune haemolytic anaemia, mixed-type autoimmune haemolytic anaemia, and drug-induced autoimmune haemolytic anaemia.^1,2 Other conditions to rule out are Evans syndrome, and thrombotic microangiopathies.

Please speak to your medical team to learn more about the available diagnostic pathways for PCH.

Acute PCH typically lasts for a few weeks and ends spontaneously. Treatment usually involves only symptomatic management, as acute PCH usually resolves by itself.^1,2,9

Chronic (recurring) PCH can be treated with biological medications that suppress the immune system. These treatments might need to be taken for a long time.^3,9 In severe chronic cases, corticosteroids may also be used to suppress the immune system. Plasmapheresis may provide temporary relief in life threatening situations.^8,9 Plasmapheresis is the removal of blood plasma, a component of blood. Plasma contains antibodies and can be removed from the body whilst the red blood cells remain.

For both acute and chronic PCH, blood transfusions might be necessary in emergencies to provide healthy red blood cells quickly.^1-3,9

It has been recommended that anti-pyretics (anti-fever medications) be used to treat fevers instead of actively cooling the person (such as with a cold compress or cold bath).^1,2

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the care of individual with PCH may include general practitioners (GP), paediatricians and haematologists.¹¹ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any clinical care guidelines for PCH in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page. 

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:  

• Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting by a group of international experts, published in 2020.

• The diagnosis and management of primary autoimmune haemolytic anaemia developed by the British Society for Haematology in collaboration with UK based experts, published in 2016.

• Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia developed by the British Society for Haematology in collaboration with UK based experts, published in 2017. 

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with PCH at emergency departments/services: 

• Blood transfusions might be necessary in emergencies to provide healthy red blood cells quickly. Due to the autoimmune and temperature sensitive nature of PCH, extra precautions may need to be considered when giving blood transfusions to individuals with PCH.^2,9,12 

More details on emergency protocols for PCH, including transfusion guidelines, can be found at:  

• Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting contains emergency management recommendations. Develop by a group of international experts, published in 2020.

• Emergency Transfusion Guidelines for Autoimmune Hemolytic Anemia published in 2005 in Canada . 

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

There are currently no known organisations for PCH in Australia or internationally. If you are aware of any organisations, please let us know via the Contribute page.      

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

PCH varies between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on PCH can be found at: 

• National Organization for Rare Disorders (NORD): Paroxysmal Cold Hemoglobinuria 

• Genetic and Rare Diseases (GARD) Information Center: Paroxysmal cold hemoglobinuria 

The Royal Children’s Hospital Melbourne: Anaemia Clinical Practice Guidelines 

Online Mendelian Inheritance in Man (OMIM): #205700 Anemia, Autoimmune Hemolytic 

Orphanet: Paroxysmal cold hemoglobinuria

Human Phenotype Ontology (HPO): Autoimmune hemolytic anemia 

This page has been developed by Rare Voices Australia (RVA)‘s RARE Portal team.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.