Thrombotic Thrombocytopenic Purpura (TTP) Clinical Presentation

Updated: Nov 15, 2023
  • Author: Theodore Wun, MD, FACP; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Patients with thrombotic thrombocytopenic purpura (TTP) typically report an acute or subacute onset of the following symptoms related to central nervous system (CNS) dysfunction, anemia, or thrombocytopenia:

  • Neurologic manifestations include alteration in mental status, seizures, hemiplegia, paresthesias, visual disturbance, and aphasia

  • Fatigue may accompany the anemia

  • Severe bleeding from thrombocytopenia is unusual, although petechiae are common

Clinical manifestations may also include the following:

  • Fever occurs in approximately 50% of patients

  • Patients may notice dark urine from hemoglobinuria.

Clinical differentiation of hemolytic-uremic syndrome (HUS) and TTP can be problematic. Differentiation is often based on the presence of CNS involvement in TTP and the more severe renal involvement in HUS. In HUS, an antecedent history of diarrheal illness is more often present. In fact, some investigators suggest a clinical classification of HUS based on the presence or absence of diarrhea.

In children, the distinction between HUS and TTP may be of more importance, as general supportive measures (with dialysis as needed) are the standard therapy for HUS, versus plasma exchange for TTP. However, albeit somewhat controversial, plasma exchange is performed in adults with HUS so the differentiation has less therapeutic implications at present.



Patients with TTP or HUS have no characteristic physical findings. Findings upon examination depend on the severity of involvement of the target organ systems.

Hemolytic anemia and thrombocytopenia cause pallor, jaundice, and petechiae. Abnormal findings on neurologic examination consist of mental status changes and/or focal neurologic deficits. These defects can be evanescent and, thus, present as transient ischemic attacks. Organomegaly is not typical.



The exact etiology of HUS and TTP is not clear, although much recent data are available on the role of bacterial Shiga toxin in HUS and of a deficiency in a protease designated ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in TTP. HUS, and to some extent TTP, commonly occur following a diarrheal illness with enterohemorrhagic Escherichia coli O157:H7 and Shigella dysenteriae serotype I. These bacteria, besides causing bloody diarrhea, are able to secrete an exotoxin called Shiga toxin (in the case of Shigella) or Shigalike toxin (in the case of E coli).

These toxins can bind to certain cell membrane globotriaosylceramide receptors, which, depending on the cell in question, can lead to chemokine or cytokine secretion (colonic and renal epithelial cells), cellular activation (monocytes and platelets), or secretion of unusually large von Willebrand multimers (glomerular endothelial cells). Evidence for activation of the coagulation cascade in HUS also exists. The relative specificity of the toxin for renal endothelial cells versus other types of endothelial cells is unknown.

Drugs such as mitomycin, cyclosporine, cisplatin, bleomycin, quinine, and ticlopidine have been associated with HUS and TTP. Whether the drugs and/or their metabolites have a direct effect on the vascular endothelium or whether alteration of the endothelial cells results in a neoantigen that leads to autoantibody formation remains unknown.

Formation of endothelial cell autoantibodies may underlie the association of thrombotic microangiopathies and pregnancy.

Most sporadic cases of TTP appear to be associated with severe deficiency of ADAMTS13 activity due to autoantibodies against this protease. [5] Normally, ADAMTS13 cleaves the large multimers of von Willebrand factor when they are secreted from endothelial cells. In most patients with active TTP, unusually large von Willebrand multimers are found in plasma. These multimers can bind to platelets in the absence of physiologic stimulus, and this mechanism might underlie the white clot seen in pathologic specimens from patients with TTP.

Congenital TTP results from mutations in the gene for ADAMTS13. Why individuals with such mutations do not always have clinically apparent TTP remains unknown.

Pregnancy can precipitate TTP. Onset of TTP during pregnancy may represent acute acquired TTP or the first episode of congenital TTP. In a prospective study of pregnancy-associated TTP from the United Kingdom, TTP presented primarily in the third trimester or postpartum. [18]