Paroxysmal cold hemoglobinuria (2023)

diseases and illnesses

Approved by

Krish Tangella MD, MBA, FCAP Pathology Jan. 10. 2022
Paroxysmal cold hemoglobinuria (2)

Paroxysmal cold hemoglobinuria (PCH) is a rare autoimmune hemolytic anemia in which the body's immune system makes antibodies against its own red blood cells.

(Video) Autoimmune Hemolytic Anemia | Warm, Cold & Paroxysmal Cold Hemoglobinuria | Symptoms, Treatment

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:

(Video) What is paroxysmal cold hemoglobinuria?

  • 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

What useful resources are there for additional information?

Information Center for Genetic and Rare Diseases (GARD).
PO Box 8126 Gaithersburg, MD 20898-8126
Toll Free: (888) 205-2311
TTY: (888) 205-3223
International phone number: (301) 251-4925
Fax: (301) 251-4911
Internet site:

American Association of Autoimmune Diseases (AARDA)
22100 Gratiot Ave., East Detroit, MI 48021
Phone: (586) 776-3900
Toll Free: (800) 598-4668
Fax: (586) 776-3903
Internet site:

National Heart, Lung, and Blood Institute (NHLBI)
6701 Rockledge Drive P.O. Postfach 30105 Bethesda, MD 20824-0105
Phone: (301) 592-8573
Fax: (301) 592-8563
Internet site:

References and sources of information used for the article: (accessed 9/1/22) (accessed 9/1/22) (accessed 1/9/22) (accessed 9/1/22)

(Video) Paroxysmal Nocturnal Hemoglobinuria (PNH) | Hemolytic Anemia | Complement Alternative Pathway

Useful peer-reviewed medical articles:

Shanbhag, S. & Spivak, J. (2015). Paroxysmale Kältehämoglobinurie.Hematology/Oncology Clinics in North America,29(3), 473-478.

(Video) Paroxysmal Nocturnal Hemoglobinuria (PNH) | Causes & Pathogenesis, Symptoms, Diagnosis & Treatment

Koppel A, Lim S, Osby M, Garratty G & Goldfinger D (2007). Rituximab as successful therapy in a patient with refractory paroxysmal cold hemoglobinuria.Transfusion,47(10), 1902-1904.

Taylor, C.J.C., Neilson, J.R., Chandra, D., and Ibrahim, Z. (2003). Recurrent paroxysmal cold hemoglobinuria in a 3-year-old child: case report.transfusion medicine,13(5), 319-321.

Ogose T, Wakata Y, Kaneko M, Shinahara K, Takechi T and Kotani H (2007). A case of recurrent cold paroxysmal hemoglobinuria with different temperature limits of Donath-Landsteiner antibodies.Journal of Pediatric Hematology/Oncology,29(10), 716-719.

Kypson AP, Warner JJ, Telen MJ. and Milano, C.A. (2003). Paroxysmal cold hemoglobinuria and cardiopulmonary bypass.Annals of Thoracic Surgery,75(2), 579-581.

Papalia, M.A. & Schwarer, A.P. (2000). Paroxysmal cold hemoglobinuria in an adult with chickenpox.British Journal of Hematology,109(2), 328-329.

Hothi DK, Bass P, Morgan M, Acharya J, Humphries SE. & Gilbert, R.D. (2007). Acute renal failure in a patient with paroxysmal cold hemoglobinuria.Pediatric Nephrology,22(4), 593-596.

Breccia, M., D'Elia, G.M., Girelli, G., Vaglio, S., Gentilini, F., Chiara, S. & Alimena, G. (2004). Paroxística Kältehämoglobinurie als Spätkomplikation der idiopathischen Myelofibrose.European Journal of Hematology,73(4), 304-306.

Approved by:Krish Tangella MD, MBA, FCAP

(Video) Paroxysmal Nocturnal Hemoglobinuria (PNH) Mnemonic!

First upload: January 10, 2022

Last updated: January 10, 2022


Paroxysmal cold hemoglobinuria? ›

Paroxysmal cold hemoglobinuria (PCH) is a rare blood disorder in which the body's immune system produces antibodies that destroy red blood cells. It occurs when the person is exposed to cold temperatures. Blood is comprised of red blood cells, platelets, and various white blood cells.

How do you diagnose paroxysmal cold hemoglobinuria? ›

The test consists of incubating a sample of the patient's serum with normal red blood cells (RBCs) in the cold for 30 minutes and then warming the mixture to body temperature (37C). Hemolysis of the RBCs in this "bi-phasic" test indicates a diagnosis of PCH.

What is the most common presentation of paroxysmal cold hemoglobinuria? ›

Patients who present with paroxysmal cold hemoglobinuria are in acute distress, with obvious pain and elevation of body temperature. Symptoms associated with respiratory infection are the most common initial presentation.

What is the treatment for paroxysmal cold hemoglobinuria? ›

The mainstay of treatment for paroxysmal cold hemoglobinuria is supportive care and the avoidance of cold exposure. Patients require hospitalization to monitor and treat complications associated with severe anemia secondary to massive hemolysis.

Is paroxysmal cold hemoglobinuria IgM or IgG? ›

PCH is caused by a biphasic autoantibody, the Donath-Landsteiner (DL) antibody, which is classified as an IgG.

What causes paroxysmal cold hemoglobinuria? ›

PCH has been linked to secondary syphilis, tertiary syphilis, and other viral or bacterial infections. Sometimes the cause is unknown. The disorder is rare.

What is paroxysmal cold hemoglobinuria caused by? ›

Paroxysmal cold hemoglobinuria (PCH) is a very rare subtype of autoimmune hemolytic anemia (AIHA, see this term), caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria, typically after exposure to cold temperatures.

When should you suspect PNH? ›

A diagnosis of PNH may be suspected in individuals who have symptoms of intravascular hemolysis (e.g., hemoglobinuria, abnormally high serum LDH concentration) with no known cause. A diagnosis may be made based upon a thorough clinical evaluation, a detailed patient history and a variety of specialized tests.

Can PNH go away on its own? ›

In some cases, people who have or have been treated for another blood disease called aplastic anemia may develop PNH. In a small number of affected individuals, the signs and symptoms of PNH disappear on their own.

What antibody is associated with paroxysmal cold hemoglobinuria? ›

Paroxysmal cold hemoglobinuria caused by an IgM-class Donath-Landsteiner antibody.

What is the prognosis for PNH? ›

Left untreated, PNH can cause hemolytic anemia, chronic kidney disease or thrombosis (blood clots). Healthcare providers treat PNH with medication that prevents blood cell damage.

What is the triad of paroxysmal cold hemoglobinuria? ›

Paroxysmal nocturnal hemoglobinuria (PNH), first described in the 18th century, is characterized by the typical clinical triad of hemolytic anemia, bone marrow failure, and propensity to thromboembolism (Rotoli and Luzzatto 1989; Dunn et al 2000; Rotoli et al 2006; Hill et al 2007a).

What diseases are associated with PNH? ›

As mentioned above common complications of PNH include thrombosis including hepatic, cerebral, and abdominal and both venous and arterial thrombosis, acute or chronic renal disease, pulmonary hypertension, erectile dysfunction, and dysphagia.

Is PNH a form of leukemia? ›

People with PNH get a type of leukemia called acute myeloid leukemia (AML). It affects the bone marrow and blood. Acute means the cancer comes on quickly. Their bone marrow makes lots of abnormal blood cells that don't work as they should.

Is PNH life threatening? ›

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood. The disease is characterized by destruction of red blood cells, blood clots, and impaired bone marrow function.

Is PNH an autoimmune disease? ›

Paroxysmal nocturnal hemoglobinuria (PNH) is a very rare clonal autoimmune disease manifesting with hemolysis, thrombosis, or bone marrow failure. We present an atypical association of myasthenia gravis, aplastic anemia, and PNH occurring years after thymectomy.

What is the most common cause of death in PNH? ›

Thrombosis is the most common cause of death in persons with PNH, accounting for 50% of the mortality from the disease. The most frequent sites of thrombosis include the hepatic, pulmonary, cerebral, and deep and superficial veins, as well as the inferior vena cava.

What is the leading cause of death in PNH? ›

Incidence and sites of thrombosis. Thromboembolism is the most common cause of mortality in patients with PNH and accounts for approximately 40% to 67% of deaths of which the cause is known.

What is the average age diagnosis PNH? ›

Most patients with PNH are initially diagnosed in their 30s. Most patients with PNH fall between 30 and 40 years of age.

Can PNH go into remission? ›

Thus, it has been suggested that remission of PNH may occur through the emergence of a new dominant clone carrying multiple somatic mutations rather than restoration of normal hematopoiesis [5,8,9]. As a result, the highly variable clinical spectrum of PNH is also reflected in cases of remission.

Is PNH acquired or inherited? ›

Although not an inherited disease, PNH is a genetic disorder, known as an acquired genetic disorder. The affected blood cell clone passes the altered PIG-A to all its descendants—red cells, leukocytes (including lymphocytes), and platelets.

Are you born with PNH? ›

If you have it, your immune system attacks red blood cells in your body and breaks them down. They lack certain proteins that protect them. You can get paroxysmal nocturnal hemoglobinuria (PNH) at any age. You aren't born with it.

What is the gold standard test for diagnosis of PNH? ›

Diagnostic flow cytometry is regarded as the gold standard method for diagnosing PNH. It uses several monoclonal antibodies and a reagent called fluorescent aerolysin reagent (FLAER), which specifically binds to the glycan region of GPI-anchored proteins.

How is hemoglobinuria diagnosed? ›

Hemoglobinuria test is a urine test that checks for hemoglobin in the urine. A clean-catch urine sample is performed by collecting the sample of urine in midstream.

What color is PNH urine? ›

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder named for a single symptom: Red/brown/dark urine noticed during late night or early morning trips to the bathroom. “Paroxysmal” means sudden; “nocturnal” means night; and “hemoglobinuria” refers to pee stained with blood.

What kind of doctor treats PNH? ›

To ensure you're being treated properly, it's important to see a PNH specialist — or at least a hematologist — for treatment. These specialists are more likely to be familiar with this rare illness and stay on top of advances in treating and managing PNH.


1. Lesson 12-2 Paroxysmal Cold Hemoglobinuria - PCH
(د.عبدالرزاق الأغبري .Dr.Abdulrazzaq Alagbare)
2. Paroxysmal nocturnal hemoglobinuria
(Dr. Megren Alkhayatt)
3. About Paroxysmal Nocturnal Hemoglobinuria (PNH)
(Apellis Pharmaceuticals)
4. Case 19 - Paroxysmal cold hemoglobinuria – PCH
(د.عبدالرزاق الأغبري .Dr.Abdulrazzaq Alagbare)
5. Hemolytic Anemias- Part 7: Paroxysmal nocturnal hemoglobinuria (PNH)
(Trans Connect)


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