Thrombotic thrombocytopenic purpura is a disorder of microvascular thrombosis characterized by a sudden onset of hemolytic anemia, thrombocytopenia, and neurologic abnormalities that may be life-threatening without immediate treatment. Impaired regulation of von Willebrand factor (vWF) activity due to deficiency of ADAMTS13, a circulating metalloprotease, is the underlying cause.
Thrombotic thrombocytopenic purpura (TTP) is most frequently seen in previously healthy women in their third and fourth decades of life, with a significant predilection toward black women . However, two main types are described in literature - hereditary, in which symptoms appear soon after birth; and autoimmune, a far more common entity affecting adolescents and adults demarcated by the presence of anti-ADAMTS13 IgG antibodies . The trigger of TTP and its symptoms is still unknown, but microvascular thrombosis and microangiopathic hemolysis, two main pathological features of TTP, lead to a sudden onset of life-threatening hemolytic anemia, thrombocytopenia (due to excessive consumption of platelets), and neurological symptoms  . Headaches, confusion, syncope, ataxia, visual symptoms due to retinal hemorrhage, focal deficits (hemiparesis, slurred speech, paresthesias, aphasia), seizures or even coma have all been reported in TTP, and they may even precede initial hematologic changes  . Renal damage can manifest as hematuria and proteinuria, while the pulmonary or hepatic injury is rarely reported . Although the course may range from rapid deterioration within a few days to a slowly progressive onset for weeks or months , a prodromal period consisting of nonspecific symptoms - abdominal and chest pain, arrhythmia, fever, and malaise can often mislead the physician and delay the diagnosis . Furthermore, 30-60% of patients develop relapses, most frequently during the first month after the initial episode, but the period between symptom reoccurrence may range from days to even years . Infection, diarrhea, pregnancy, and surgery have been proposed as triggering events, but their association is yet to be established .
Initial workup should include a complete blood count (CBC) and a peripheral blood smear, as thrombocytopenia and the presence of schistocytes are considered to be the hallmarks of TTP, respectively   . In fact, a very high schistocyte count has been proposed as one of the most specific signs of TTP, having in mind that they appear in various other conditions (disseminated intravascular coagulation, sepsis, etc.) but in much lower numbers . Additional findings include anemia, elevated reticulocyte count, and negative Coombs test. Liver and kidney function (aspartate and alanine aminotransferases, blood urea nitrogen and creatinine), as well as assessment of inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, fibrinogen, and D-dimer) and lactate dehydrogenase (LDH) should be performed, while 10-50% of patients have high titers of antinuclear (ANA) antibodies . Genetic tests to confirm ADAMTS13 levels in circulation are not widely available, but its activity should be evaluated if possible . In virtually all cases, a very low functional activity (<10% of normal) is observed. TTP can also be confirmed by detection of anti-ADAMTS13 IgG antibodies in plasma and by looking at the size of vWF multimers through vWF collagen binding (vWF:CB) assays  . Ultra large vWF multimers, depending on the stage of TTP, can be present in remission, or can be completely absent during active disease   .