Understanding hemolysis
Despite improvements while taking 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. of people who were treated for PNH:
-
still had
anemia* -
still had
fatigue† -
still needed a
transfusion*
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. In general, studies designed to collect new data are considered scientifically stronger than retrospective studies.
*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.
†These data are from a group of people within a retrospective study. This group had 491 people with PNH who did not have aplastic anemia and had high disease activity when they enrolled in the International PNH Registry.
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 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 occurs when red blood cells are destroyed inside the blood vessels
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. 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 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
Both IVH and EVH can occur in your body at the same time and cause the PNH symptoms you experience
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
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
The C3-loaded PNH red blood cells are destroyed in the liver and spleen by special cells called macrophages
To address ongoing PNH symptoms, it may be important to control both IVH and EVH
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
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.
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 lab values and symptoms may help determine if you have ongoing hemolysis
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Below normal levels of HEMOGLOBIN (Hb)
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Normal or slightly elevated lactate dehydrogenase (LDH)
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elevated reticulocyte count and/or
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elevated levels of bilirubin
Every person’s experience with this disease can be unique. Your doctor will consider a variety of test results and all your signs and symptoms when monitoring your PNH. It’s always best to speak to your doctor about your test results and what they may mean for your health
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“Some days are worse than others, but I tend to keep going despite the fatigue.”
– Leslie, living with PNH
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