Laboratory Studies
Complete blood count (CBC) findings in patients with thrombotic thrombocytopenic purpura (TTP) are usually as follows:
-
Total white blood cell count is normal or slightly elevated
-
Hemoglobin concentration is moderately depressed at 8-9 g/dL
-
Platelet count generally ranges from 20,000-50,000/μL
Peripheral blood smears reveal moderate-to-severe schistocytosis.
Early in the course of illness, schistocytes may not be seen, but, eventually, they will be present. Some consider schistocytosis the sine qua non for diagnosis.
Prothrombin time (International Normalized Ratio) and activated partial thromboplastin time results typically are normal in both TTP and in hemolytic-uremic syndrome (HUS), although some series report patients with slight elevations on both tests.
D-dimer and fibrinogen assay findings are as follows:
-
D-dimers are indicative of fibrinolysis and thus, thrombin activation, which usually is normal or mildly elevated in patients with TTP
-
Fibrinogen typically is in the high to high-normal range
-
These tests are useful in differentiating TTP/HUS from disseminated intravascular coagulation (DIC), in which most of these coagulation parameters are abnormal
Evaluation of renal function with a blood urea nitrogen (BUN) and creatinine level is necessary to establish the presence and severity of renal impairment. This also aids in differentiating HUS from TTP, but patients classified as TTP in some studies have had an elevated creatinine level and those with HUS have had neurologic abnormalities, again emphasizing that these are clinical diagnoses.
Lactate dehydrogenase (LDH) and bilirubin (direct and total) levels are indirect measures of the degree of hemolysis. An LDH level in the 1000 IU/L range (normal, < 200 IU/L) is not unusual. Generally, a moderate degree of hyperbilirubinemia (2.5-4 mg/dL) is present, with the indirect form predominating.
The direct Coombs test determines the presence of antibodies on red cells. Antibodies, if present, are more consistent with autoimmune hemolytic anemia.
Because of the association of TTP/HUS with HIV infection, serologic evaluation for HIV infection should be obtained in all newly presenting patients.
Although not routinely available, measurement of von Willebrand factor–cleaving protease (ADAMTS13) activity holds the promise of helping diagnose TTP with greater certainty. Ideally, patients with TTP have either an inherited or an acquired lack of this protease activity, whereas those with HUS do not have an abnormality of the enzyme.
To date, however, studies with different variations of the activity assay have not clearly distinguished between patients thought to have TTP from patients thought to have HUS. In addition, patients with other causes of thrombocytopenia—as well as liver disease, pregnancy, and sepsis—may have moderately depressed levels of ADAMTS13 activity. Thus, the diagnostic utility of the assays has yet to be demonstrated.
Wu et al reported that ADAMTS13 response to early plasma exchange therapy in patients with acquired TTP has prognostic value. In their study of 19 patients, recovery of ADAMTS13 activity to more than 10% within 7 days was significantly associated with a timely clinical response. In contrast, patients whose ADAMTS13 level failed to exceed 10% by 7 days tended to experience TTP exacerbation, treatment refractoriness, or death. [14]
Imaging Studies
Imaging studies generally are not required in the evaluation of patients for TTP or HUS. In patients where stroke is suspected, CT scan or MRI may be performed to rule out infarct and/or hemorrhage.
Histologic Findings
Biopsy is not required for the diagnosis of HUS or TTP. When biopsies have been performed, they generally have revealed thrombi that are relatively platelet-rich and fibrin-poor in the microcirculation (white clot). These lesions are most prominent in the kidneys and the CNS.
-
Differential diagnosis of immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC).
