Thrombotic Thrombocytopenic Purpura 

In 1924, Eli Moschowitz, MD, described a girl who presented with an abrupt onset of petechiae and pallor followed rapidly by paralysis, coma, and death. Upon pathologic examination, the small arterioles and capillaries of the patient were found to have thrombi consisting mostly of platelets. Dr. Moschowitz hypothesized a "powerful poison which had both agglutinative and hemolytic properties" as the cause of the disease. The syndrome described by Moschowitz is now known as thrombotic thrombocytopenic purpura (TTP). See image below.

In its full-blown form, the disease consists of the pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal disease. A closely related disorder, hemolytic-uremic syndrome (HUS), shares many clinical characteristics of TTP but is more common in children. Renal abnormalities tend to be more severe in HUS. Although once considered variants of a single syndrome, recent evidence suggests differing pathogenic mechanisms of TTP and HUS. The mortality of TTP is greatly reduced with the routine use of aggressive high-volume total plasma exchange (TPE). The effect of TPE on the outcome of patients with HUS is more controversial.

TTP can affect any organ system, but involvement of the peripheral blood, the central nervous system, and the kidneys causes the clinical manifestations. The classic histologic lesion is one of bland thrombi in the microvasculature of affected organs. These thrombi consist predominantly of platelets with little fibrin and red cells compared to thrombi that occur secondary to intravascular coagulation. The ultimate cause of TTP is unknown; however, recent research has uncovered some clues about the pathophysiology.

Patients with TTP have unusually large multimers of von Willebrand factor (vWF) in their plasma. Patients with TTP lack a plasma protease that is responsible for the breakdown of these ultralarge vWF multimers. In the congenital form of TTP, mutations in the gene encoding this protease have been described. In the more common sporadic form, an antibody inhibitor can be isolated in most patients. This protease has been isolated and cloned and is designated ADAMTS13 (a disintegrinlike and metalloprotease with thrombospondin type 1 motif 13). The activity of this protease is normal in most patients with classic HUS suggesting differing pathogenesis of these closely related entities.^[1]

Frequency

United States

Exact incidence figures are not available, although TTP is thought to be a rare disease. One series showed the frequency was 1 in approximately 50,000 hospital admissions. In a 25-year period in the Sacramento, California region (population at risk 1.2 million), at least 176 documented cases of TTP were reported. In another 1-year study, 20 institutions reported 115 patients with TTP.

International

International incidence figures are not available.

Mortality/Morbidity

• Untreated, TTP has a mortality rate of as high as 90%. With plasma exchange, the mortality rate is reduced to 10-20%.
• Acute morbidities include ischemic events such as stroke, transient-ischemic attacks, myocardial infarction and arrhythmia, bleeding, and azotemia.
• In general, survivors have no long-term sequelae, with the exception of residual neurologic deficits in a minority of patients. However, relapses are not uncommon, occurring in 13-36% of patients.

Race

• An ethnic predisposition to TTP is not established.

Sex

• In the larger series reported, a female predominance of approximately 2:1 was noted.

Age

• In several large studies, the median age at diagnosis is approximately 40 years. However, in the authors' series of 126 consecutive patients, the median age was 52 years.
• In general, HUS is diagnosed in children and TTP is diagnosed in adults. Ninety percent of cases of HUS occur in children.
• Bouw et al recently presented a review article of TTP in children.^[2]