Тромботическая тромбоцитопеническая пурпура: причины, симптомы и механизмы

About 1 per 100,000 people are affected. Neurological symptoms are very common and vary greatly in severity. Frequently reported symptoms include feeling very tired, confusion, and headaches. or dots on the skin known as petechiae. High blood pressure has also been observed as a symptom. As TTP progresses, blood clots form within small blood vessels (microvasculature), and platelets (clotting cells) are consumed. As a result, bruising, and rarely bleeding can occur. The bruising often takes the form of purpura, while the most common site of bleeding, if it occurs, is from the nose or gums. Larger bruises (ecchymoses) may also develop. The classic presentation of TTP, which occurs in less than 10% of people, includes five medical signs. These are: The two best understood causes of TTP are due to autoimmunity (acquired TTP), caused by autoantibodies targeting ADAMTS13, or congenital TTP: an inherited deficiency of ADAMTS13 (known as the Upshaw–Schulman syndrome). ADAMTS13 is a metalloproteinase responsible for the breakdown of von Willebrand factor (vWF), a protein that links platelets, blood clots, and the blood vessel wall in the process of blood coagulation. Very large vWF multimers are more prone to lead to coagulation. Hence, without proper cleavage of vWF by ADAMTS13, coagulation occurs at a higher rate, especially in the microvasculature, part of the blood vessel system where vWF is most active due to high shear stress.]] TTP may also be congenital. Such cases may be caused by mutations in the ADAMTS13 gene. This hereditary form of TTP is called the Upshaw–Schulman syndrome (also spelled Upshaw–Schülman). People with this inherited ADAMTS13 deficiency have a surprisingly mild phenotype, but develop TTP in clinical situations with increased von Willebrand factor levels, e. g. infection. Reportedly, less than 5% of all TTP cases are due to Upshaw–Schulman syndrome. People with this syndrome generally have 5–10% of normal ADAMTS 13 activity.

The underlying mechanism typically involves autoantibody mediated inhibition of the enzyme ADAMTS13, a metalloprotease responsible for cleaving large multimers of von Willebrand factor (vWF) into smaller units. The increase in circulating multimers of vWF increases platelet adhesion to areas of endothelial injury, particularly where arterioles and capillaries meet, which in turn results in the formation of small platelet clots called thrombi. As platelets are used up in the formation of thrombi, this then leads to a decrease in the number of overall circulating platelets, which may then cause life threatening bleeds. Red blood cells passing the microscopic clots are subjected to shear stress, which damages their membranes, leading to rupture of red blood cells within blood vessels,

TTP is a form of thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to microangiopathic hemolytic anemia and thrombocytopenia. Consequently, differential diagnosis of these TMA diseases is essential. Both TTP and HUS are characterized by fever, anemia, thrombocytopenia, renal failure, and neurological symptoms. Generally, TTP has higher rates of neurological symptoms (≤80%) and lower rates of renal symptoms (9%) than HUS (10–20% and 90%, respectively). Unlike HUS and aHUS, TTP is known to be caused by a defect in the ADAMTS13 protein, so a lab test showing ≤5% of normal ADAMTS13 levels is indicative of TTP. whereas absence of shiga toxin/EHEC can confirm a diagnosis of aHUS. This is an exchange transfusion involving removal of the person's blood plasma through apheresis and replacement with donor plasma (fresh frozen plasma or cryosupernatant); the procedure must be repeated daily to eliminate the inhibitor and abate the symptoms. If apheresis is not available, fresh frozen plasma can be infused, but the volume that can be given safely is limited due to the danger of fluid overload. Plasma infusion alone is not as beneficial as plasma exchange. However, the use of caplacizumab was associated with increase bleeding tendencies in some studied subjects. People with refractory or relapsing TTP may receive additional immunosuppressive therapy, e. g. vincristine, cyclophosphamide, cyclosporine A, or splenectomy. Measurements of blood levels of lactate dehydrogenase, platelets, and schistocytes are used to monitor disease progression or remission. ADAMTS13 activity and inhibitor levels may be measured during follow up, but in those without symptoms the use of rituximab is not recommended.

The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for people with idiopathic TTP diagnosed and treated early with plasmapheresis.

The incidence of TTP is about 4–5 cases per million people per year. Idiopathic TTP occurs more often in women as well as people of African descent, and TTP secondary to autoimmune disorders such as systemic lupus erythematosus occurs more frequently in people of African descent, although other secondary forms do not show this distribution. Although Black people are at an increased risk for TTP, its presentation in Black people does not have any distinguishable features compared to those of other races. Pregnant women and women in the post partum period accounted for a notable portion (12–31%) of the cases in some studies; TTP affects about one in 25,000 pregnancies.

TTP was initially described by Eli Moschcowitz at the Beth Israel Hospital in New York City in 1924. Moschcowitz ascribed the disease (incorrectly, as now known) to a toxic cause. Moschcowitz noted his patient, a 16 year old girl, had anemia, small and large bruises, microscopic hematuria, and, at autopsy, disseminated microvascular thrombi. In 1966, a review of 16 new cases and 255 previously reported cases led to the formulation of the classical pentad of symptoms and findings (i. e., thrombocytopenia, microangiopathic hemolytic anemia, neurological symptoms, kidney failure, fever); in this series, mortality rates were found to be very high (90%). While a response to blood transfusion had been noted before, a 1978 report and subsequent studies showed blood plasma was highly effective in improving the disease process. In 1982, the disease had been linked with abnormally large von Willebrand factor multimers. The identification of a deficient protease in people with TTP was made in 1998. The location of ADAMTS13 within the human genome was identified in 2001.