WHAT CAUSES TTP?
TTP is caused by a deficiency of a normal blood enzyme that is named ADAMTS13 (you don’t need to know why it has this name). To cause TTP, ADAMTS13 must be absent or severely deficient. We usually describe a severe deficiency as less than 10% of the normal levels. Levels above 10% seem to be enough. ADAMTS13 acts to prevent platelet clumping in the circulation of small blood vessels. ADAMTS13 is needed to trim a very long protein of the blood, that is named von Willebrand factor, abbreviated as VWF (it’s named after a person, you don’t need to know that either). VWF is an extremely long string of a protein, and this is how it catches and clumps platelets. If there is no ADAMTS13 in the blood, these extremely long strings persist and platelet clumping can occur where it shouldn’t occur, in the normal circulation in a normal blood vessel. If ADAMTS13 is present, it trims these long strings down to their normal size. Normal size VWF can still effectively clump platelets, but only when there is a cut or trauma or damage to the blood vessel and blood clotting with platelet clumping needs to occur. The absence of ADAMTS13 doesn’t mean that platelets are going to clump and block blood vessels all the time, every day, causing constant TTP. The absence of ADAMTS13 only means that a person is vulnerable to the platelet clumping and the disorder we call TTP when some stress occurs. The stress can be any illness (like influenza), or surgery, or pregnancy. In most patients we don’t know what the stress or the “trigger event” is.
ADAMTS13 deficiency can be inherited or acquired.
- Among infants and young children, ADAMTS13 deficiency is rare; when it occurs, it is commonly inherited. Acquired TTP is very rare in children. The inheritance is described as recessive, which means that a child has to inherit an abnormal gene from both parents to have the risk for developing TTP. The parents are normal, because with only one of the two genes being abnormal, the ADAMTS13 level is 50%, and that’s plenty to keep the VWF in its normal size.
- Among adults, ADAMTS13 deficiency is almost always acquired. Some people can have inherited absent ADAMTS13 but never be sick until they are adults. One of the situations which can “trigger” an initial episode of TTP in an adult with an inherited absence of ADAMTS13 is pregnancy. If a woman has an initial episode of TTP during a pregnancy, inherited ADAMTS13 deficiency should be considered. But in over 90% of adults, ADAMTS13 deficiency is acquired, caused by inhibition of its activity by an autoantibody. Therefore acquired TTP is an autoimmune disorder. Autoimmune disorders are more common in women than men, and some autoimmune disorders are more common in specific racial groups. Acquired TTP occurs more commonly in women (among our patients, 80% are women) and occurs more common in African-Americans (among our patients, about one-third are African-American, which is about seven times what we’d expect from our Oklahoma population). Most of our patients are young adults; the average is 40. These features are similar to another autoimmune disorder, systemic lupus erythematosus (commonly called “lupus” or SLE). Lupus also occurs predominantly in young, black women.
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