Understanding hemolysis

Symptoms can be a sign of ongoing hemolysis

There are 2 types of hemolysis, intravascular (IVH) and extravascular (EVH), both of which may be responsible for ongoing PNH symptoms. The science behind the complement systemcomplement systemThe complement system, also referred to as the complement cascade, is an army of more than 50 different proteins that work together to get rid of dangerous cells and fight infection. may explain why these ongoing PNH symptoms can occur even with treatment

Two key proteins in the complement system are known as C3c3A protein located in the blood that acts as a central point of the complement system, regulating its activation. and C5c5A protein located in the blood that plays an important role in inflammation and intravascular hemolysis caused by the complement system.

C3 and C5 proteins are activated in a specific order as your immune system detects viruses, bacteria, or damaged cells. Like dominoes falling, each activation triggers another activation in a series of steps known as a “cascade”

There are 2 types of hemolysis, intravascular (IVH) and extravascular (EVH), both of which may be responsible for ongoing PNH symptoms. The science behind the complement systemcomplement systemThe complement system, also referred to as the complement cascade, is an army of more than 50 different proteins that work together to get rid of dangerous cells and fight infection. and ongoing hemolysishemolysisThe “breaking apart” of red blood cells. It can occur when the immune system attacks these cells as though they were dangerous viruses or bacteria. When red blood cells break open, hemoglobin is released. Hemolysis causes many of the symptoms of PNH. may explain why these ongoing PNH symptoms can occur even with treatment

Two key proteins in the complement system are known as C3c3A protein located in the blood that acts as a central point of the complement system, regulating its activation. and C5c5A protein located in the blood that plays an important role in inflammation and intravascular hemolysis caused by the complement system.

C3 is activated, then "kicks off" the rest of the cascade by splitting into C3a and C3b

C3b activates C5

Extravascular hemolysis occurs when red blood cells are destroyed in the liver and spleen

C5 splits into C5a and C5b

C5b is one of the proteins that forms the membrane attack complex (MAC)membrane attack complex (MAC)A structure that is formed within the chain of complement system activation. It also attaches to cells which the body believes are threatening and helps destroy them.. The MAC helps destroy dangerous cells, like viruses and bacteria, in the body.

Intravascular hemolysis attack occurs when red blood cells are destroyed inside the blood vessels by the MAC.

Both IVH and EVH can occur in your body at the same time and cause the PNH symptoms you experience

IVH is an attack that occurs when PNH red blood cells are destroyed inside the blood vessels

C3 proteins bind to PNH red blood cells, which "tag" them for destruction

This tagging sets off a chain of events within the complement system

C3 splits into 2 other proteins, C3a and C3b

C3b triggers the C5 protein

The C5 protein splits into 2 other proteins, C5a and C5b

C5b helps form the MAC. The MAC creates holes in the PNH red blood cells, causing them to burst

An EVH attack occurs when PNH red blood cells are destroyed in the liver and spleen

PNH red blood cells that are not destroyed from IVH continue to be covered in C3 proteins. This is known as C3-loading

The C3-loaded PNH red blood cells are destroyed in the liver and spleen by special cells called macrophages

There are 2 types of hemolysis, intravascular (IVH) and extravascular (EVH), both of which may be responsible for ongoing PNH symptoms. The science behind the complement systemcomplement systemThe complement system, also referred to as the complement cascade, is an army of more than 50 different proteins that work together to get rid of dangerous cells and fight infection. may explain why these ongoing PNH symptoms can occur even with treatment.

Two key proteins in the complement system are known as C3c3A protein located in the blood that acts as a central point of the complement system, regulating its activation. and C5c5A protein located in the blood that plays an important role in inflammation and intravascular hemolysis caused by the complement system.

C3 and C5 proteins are activated in a specific order as your immune system detects viruses, bacteria, or damaged cells. Like dominoes falling, each activation triggers another activation in a series of steps known as a “cascade”

Both IVH and EVH can occur in your body at the same time and cause the PNH symptoms you experience

Intravascular hemolysis attack occurs when red blood cells are destroyed inside the blood vessels by the MAC.

An EVH attack occurs when PNH red blood cells are destroyed in the liver and spleen

C3 proteins bind to PNH red blood cells, which "tag" them for destruction

This tagging sets off a chain of events within the complement system

An EVH attack occurs when PNH red blood cells are destroyed in the liver and spleen
An EVH attack occurs when PNH red blood cells are destroyed in the liver and spleen

The C3-loaded PNH red blood cells are destroyed in the liver and spleen by special cells called macrophages

Both IVH and EVH can occur in the body at the same time and cause the PNH symptoms you experience

An EVH attack occurs when PNH red blood cells are destroyed in the liver and spleen

PNH red blood cells that are not destroyed from IVH continue to be covered in C3 proteins. This is known as C3-loading

The C3-loaded PNH red blood cells are destroyed in the liver and spleen by special cells called macrophages

Despite improvements while taking C5 inhibitor treatment, many people still experience PNH symptoms. In retrospective studiesretrospective studyA type of study that takes data from previous studies and analyzes it. It is different from other studies that are designed and run to collect new data. In general, studies designed to collect new data are considered scientifically stronger than retrospective studies. and a surveysurvey studyA collection of information from individuals through responses to questions. Depending on how the survey is set up, participants may be chosen as a member of a sample group who fit certain criteria (like when you are asked to participate in a survey because you purchased something), or may self-select (you see a link for a survey and take it). of people who were treated for PNH:

  • still had
    anemia*

  • still had
    fatigue†

  • still needed a
    transfusion*

*These data are from a retrospective study of 141 people who had been treated with eculizumab in the Leeds Center of the UK PNH National Service. A retrospective study is a type of study that takes data from previous studies and analyzes it. It is different from other studies that are designed and run to collect new data.

†These data are from a survey (a collection of information from individuals through response to questions) of 58 people ≥18 years of age who were treated with eculizumab or ravulizumab in the US. They self-reported a PNH diagnosis and were recruited through a patient advocacy group in July 2020.

In general, prospective studies designed to collect new data are considered scientifically stronger than retrospective or survey studies.

To address ongoing PNH symptoms, it may be important to control both IVH and EVH, since both can occur in the body at the same time and are the cause of these symptoms.

Both IVH and EVH can occur in your body at the same time and cause the PNH symptoms you experience

IVH is an attack that occurs when PNH red blood cells are destroyed inside the blood vessels by the MAC.

test
C3 and C5 proteins are activated in a specific order as your immune system detects viruses, bacteria, or damaged cells. Like dominoes falling, each activation triggers another activation in a series of steps known as a “cascade”

Both IVH and EVH can occur in your body at the same time and cause the PNH symptoms you experience

Two key proteins in the complement system are known as C3c3A protein located in the blood that acts as a central point of the complement system, regulating its activation. and C5c5A protein located in the blood that plays an important role in inflammation and intravascular hemolysis caused by the complement system.

test

C3 and C5 proteins are activated in a specific order as your immune system detects viruses, bacteria, or damaged cells. Like dominoes falling, each activation triggers another activation in a series of steps known as a “cascade”

Taking the first steps toward greater wellness often involves considering what’s most important to you, and then choosing the areas you’d like to change. This wellness tool can help you understand the impact PNH has on your overall wellness and take steps towards the life you want.

Your doctor will look at a variety of lab results to help determine if you have ongoing hemolysis.

  • Below normal levels of HEMOGLOBIN (Hb)
  • Elevated lactate dehydrogenase (LDH)
  • elevated reticulocyte count
  • elevated levels of bilirubin

Taking the first steps toward greater wellness often involves considering what’s most important to you, and then choosing the areas you’d like to change. This wellness tool can help you understand the impact PNH has on your overall wellness and take steps towards the life you want.

PNH signs and
symptoms

Take steps toward
the life you want

Explanation of
lab tests