Thrombotic thrombocytopenic purpura (TTP) is an ultra rare blood disorder, with between 1.2 and 11 new cases every year per million of population. 1,2 It is more common in women than men and, although it can affect people of all ages, the average age of diagnosis is 40 years. 1,2
TTP episodes are serious and life-threatening. It is considered a medical emergency and it is estimated that 10-20% of acute patients die from TTP, despite currently available treatments. 3-5 TTP is a lifelong condition, as after their initial diagnosis many patients will experience further episodes of TTP (called recurrences). 3
(TTP) is a rare blood disorder
- TTP is a serious, ultra rare and potentially life-threatening condition
- 30%-50% of patients will experience multiple episodes of TTP (called relapses) after their initial diagnosis
- It occurs when the ADAMTS13 enzyme does not function as it should, leading to small blood clots in the blood vessels, low platelet counts and destruction of red blood cells
- It is not known what causes the body to start producing antibodies against ADAMTS13 in acquired TTP
- Patients with TTP may experience a wide variety of symptoms, including fever, fatigue, headache, confusion and bruises or dots on the skin
- There are two main types of TTP – inherited TTP and acquired TTP
Introduction to TTP
The name thrombotic thrombocytopenic purpura actually describes three of the main features of the condition:
- Thrombotic refers to the formation of a blood clot inside a blood vessel.
- Thrombocytopenic refers to a condition in which the number of platelets in the blood is lower than normal.
- Purpura refers to purple bruises caused by bleeding underneath the skin.
However, these three features only tell part of the story of TTP. To fully understand how TTP affects the body, we first need to look in more detail at some of the components of blood. With TTP, we are interested in three components in particular:
- a protein called von Willebrand Factor (vWF) that is present in blood plasma
- and an enzyme called ADAMTS13 that is also found in the blood plasma
Platelets are one of the most important components of blood. Their main function is to form blood clots when bleeding occurs. They do this by sticking together, along with other materials in the blood, to seal a cut or injury and prevent further bleeding. One of the materials that helps platelets to stick together to form a clot is a protein called von Willebrand Factor (vWF). You can think of vWF as the sticky substance that platelets attach to in order to form a clot.
Normally, as soon as von Willebrand Factor is produced in the body it is cut up into smaller pieces by an enzyme called ADAMTS13. This is because large molecules of vWF attract platelets at a very high rate, forming blood clots even though there is no bleeding and reducing the number of platelets circulating in the blood. TTP occurs when this enzyme, ADAMTS13, does not work correctly.6 This condition can potentially lead to a wide variety of problems.
Without functioning ADAMTS13, the blood clotting process goes into overdrive, with small clots forming spontaneously throughout the body.6
These clots can block the flow of blood to organs such as the brain, heart or kidneys and can cause serious or potentially fatal problems such as stroke, acute myocardial infarction, or kidney failure.6 When these clots are formed, many of the platelets in the blood are used up. A low number of platelets in the blood (a condition called thrombocytopenia) can cause bleeding problems, such as bleeding inside the body or underneath the skin.6 Finally, the small blood clots in the blood vessels can damage the red blood cells travelling around the body, causing the red blood cells to break up into fragments.6 This leads to a type of anemia called hemolytic anemia.
Two types of TTP
Some people have inherited TTP (also called congenital TTP, hereditary TTP, familial TTP and Upshaw-Schulman syndrome), where the gene that produces ADAMTS13 is faulty.6 These people are born with the condition and either have too little ADAMTS13 in their bodies or the ADAMTS13 that their bodies produce doesn’t work properly.6 Inherited TTP is very rare – it is estimated that only 5% of all cases of TTP are inherited TTP.6,7
Acquired TTP (aTTP)
More commonly, people aren’t born with faulty genes but instead develop TTP at some point later in their lives.6
This is called acquired TTP (aTTP) or immune-mediated TTP. In aTTP, the body’s immune system starts producing antibodies that stop ADAMTS13 from working.6 aTTP accounts for around 95% of all cases of TTP.8
aTTP - causes and symptoms
Acquired TTP is caused by the immune system producing antibodies against ADAMTS13. However, it is not known why the body starts to produce these antibodies.6 Although patients often try to understand if there is something that they have done that may have caused it, the truth is that there is no clear reason why patients, who are often young and healthy, are affected. Although the cause is not fully understood, there are certain triggers that may be linked to TTP in some patients. These include6:
- Certain diseases or conditions including cancer, HIV, lupus, infections, or pregnancy
- Surgery or certain other medical procedures
- Certain medications, including chemotherapy, ticlopidine, clopidogrel, cyclosporine A, and hormone therapy and estrogens
Each TTP patient is different and they may experience a wide range of symptoms, because the entire body is affected by the disease. Many patients may initially experience general, non-specific symptoms such as fever or flu-like symptoms.3 However, the different processes described in the Introduction to TTP section generally lead to two main types of symptoms: symptoms caused by bleeding and symptoms caused by the formation of blood clots.
Symptoms of TTP caused by bleeding include3,6 :
- Bleeding from the gums or nose, which may be caused by thrombocytopenia
- Purple bruises on the skin, called purpura, & red or purple dots on the skin, called petechiae, which are caused by bleeding under the skin
Symptoms caused by the formation of blood clots include3,6 :
- Headaches, confusion & disturbed vision which may be caused by blood clots blocking the flow of blood to the brain
- Chest pain, which may be caused by blood clots blocking the flow of blood to the heart
- Fatigue, jaundice (a yellowing of the skin and eyes) & dark urine which may be caused by haemolytic anemia
- Kidney problems, which may be caused by blood clots blocking the flow of blood to the kidney
Inherited TTP - causes and symptoms
Inherited TTP is a genetic condition where the ADAMTS13 gene is faulty and doesn’t make normally functioning ADAMTS13 enzymes.6 People with inherited TTP have two copies of the faulty gene, one passed down through the genes from each parent.9 When a person has only one copy, they won’t show any signs and symptoms of TTP, but a person with two copies may be affected by inherited TTP.9
Like aTTP, it is not clear what triggers inherited TTP in all patients – some patients show the signs and symptoms at birth while others do not show them until adulthood.3 As with aTTP, there are certain factors, such as pregnancy or infection, that seem to play a role in triggering inherited TTP.3
Patients with inherited TTP have similar symptoms as patients with aTTP (see section above).
- Terrell DR et al. J Thromb Haemost 2005;3:1432-1436.
- Miller DP et al. Epidemiology 2004;15:208-215.
- Scully et al. Br J Haematol 2012;158:323– 35;
- Kremer Hovinga et al. Blood 2010;115:1500–11;
- Benhamou et al. Haematologica 2012;97:1181–86;
- National Institute of Health. What Is Thrombotic Thrombocytopenic Purpura? [online]. 2014. Available at: https://www. nhlbi.nih.gov/health/health-topics/topics/ ttp;
- Orphanet. Congenital thrombotic thrombocytopenic purpura [online]. 2015. Available at: http://www.orpha. net/consor/cgi-bin/OC_Exp.php?Expert=93583
- Orphanet. Acquired thrombotic throm- bocytopenic purpura [online]. 2015. Available at: http://www.orpha.net/con- sor/cgi-bin/OC_Exp.php?lng=EN&Expert=93585;
- National Institute of Health. What Caus- es Thrombotic Thrombocytopenic Pur- pura? [online]. 2014. Available at: https:// www.nhlbi.nih.gov/health/health-topics/ topics/ttp/causes;