Platelet Storage Pool Diseases
Thrombotic
Thrombocytopenic
Purpura
Feature
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Roger S. Riley, M.D., Ph.D.
April, 2005
Disease Facts
Synonyms
TTP, Moschowitz syndrome.
Epidemiology
The incidence is approximately 4 out of 100,000 people. Adults from 20 to 50 are most
commonly affected, with a slight female predominance.
Etiology &
Pathogenesis
Many aspects of the pathogenesis of TTP are unclear at the present time. However,
research within the recent past has disclosed that patients have an inherited or acquired deficiency of a circulating plasma protease (ADAMTS13) responsible for the
breakdown of large multimers of von Willebrand factor (vWF). The presence of abnormally large vWF multimers is associated with endothelial injury, leading to multiple
platelet thrombi in the peripheral blood, central nervous system, and other organs.
The presence of thrombi in the vasculature causes leads to red blood cell destruction
and platelet consumption (microangiopathic hemolytic anemia).
Pattern of
Inheritance
Usually an acquired disease.
Clinical
Presentation
The classic pentad of TTP are microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal disease. However,
the disease varies in severity, and not all symptoms may be present. Neurologic manifestations include mental status alterations, seizures, hemiplegia,
paresthesias, visual disturbance, and aphasia. Petechiae are common, and hemoglobinuria may occur, but severe bleeding is uncommon. A related disorder,
hemolytic-uremic syndrome (HUS), is clinically similar to TTP but is more common in children, who have more severe renal disease and less severe neurologic symptoms.
Laboratory
Features
Severe thrombocytopenia (20-50/µL), moderate anemia, and mild neutrophilia
are present. Peripheral smear examination in advanced disease reveals frequent schistocytosis, but these may not be abundant during early disease
stages. D-dimers and fibrinogen degradation products (FDPs) are elevated from
the formation and breakdown of thrombi. The prothrombin time and aPTT are
usually within normal limits, while fibrinogen is increased. The BUN and creatinine are elevated proportional to the severity of the renal injury. The hemolytic
anemia results in elevations of serum lactic dehydrogenase (LDH) and moderate hyperbilirubinemia (2.5-4 mg/dL). A Coomb’s test should be obtained to
exclude an autoimmune hemolytic anemia, and serologic evaluation for HIV infection should be obtained because of the association of TTP/HUS with HIV. Assays for measurement of vWF-cleaving protease activity are not routinely available at this time.
Platelet Storage Pool Diseases
Feature
Disease Facts
Treatment
The mortality of untreated TTP from multiple organ damage is as high as 90%,
so aggressive therapy is usually undertaken to avoid death and ischemic consequences such as stroke, myocardial infarction, transient ischemic attacks
(TIAs), bleeding, and other problems. Daily high-volume plasma exchange for
about a week with fresh frozen plasma is the treatment of choice, usually with
corticosteroid thearpy. The mortality rate is reduced to about 10% with appropriate treatment, although disease relapse is seen in about 15% of patients.
References
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