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 any associated inflammation, extravascular hemolysis, and, ultimately, intravascular hemolysis. and
C5c5 Part of the complement system, a protein in the blood that can lead to inflammation and, ultimately, intravascular hemolysis.
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 any associated inflammation, extravascular hemolysis, and, ultimately, intravascular hemolysis. and
C5c5 Part of the complement system, a protein in the blood that can lead to inflammation and, ultimately, intravascular hemolysis.
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 any associated inflammation, extravascular hemolysis, and, ultimately, intravascular hemolysis. and
C5c5 Part of the complement system, a protein in the blood that can lead to inflammation and, ultimately, intravascular hemolysis.
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”
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 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
Intravascular hemolysis attack occurs when red blood cells are destroyed inside the blood vessels by the MAC.
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
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
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
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:
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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.
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 any associated inflammation, extravascular hemolysis, and, ultimately, intravascular hemolysis. and
C5c5 Part of the complement system, a protein in the blood that can lead to inflammation and, ultimately, intravascular hemolysis.
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”
Your doctor will look at a variety of lab results to help determine if you have ongoing hemolysis.
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Below normal levels of HEMOGLOBIN (Hb)
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Elevated lactate dehydrogenase (LDH)
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elevated reticulocyte count
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elevated levels of bilirubin
Sometimes it might feel like your PNH symptoms are more in control than you are. The first step to reclaiming your power is having an honest conversation with your doctor about what you want. Check out our wellness tool, which can help you get started.
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“Some days are worse than others, but I tend to keep going despite the fatigue.”
– Leslie, living with PNH