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Thrombotic Thrombocytopenic Purpura (TTP) Workup

  • Author: Theodore Wun, MD, FACP; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Jun 20, 2016
 

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 who are classified as TTP in some studies have 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.[10]

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Imaging Studies

See the list below:

  • 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.
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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.

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Contributor Information and Disclosures
Author

Theodore Wun, MD, FACP Professor of Medicine, Professor of Pathology and Laboratory Medicine, University of California Davis School of Medicine; Chief of Hematology/Oncology, Program Director, Veterans Affairs Northern California Health Care System; Medical Director, University of California Davis CCRC

Theodore Wun, MD, FACP is a member of the following medical societies: American Association of Blood Banks, American Society for Blood and Marrow Transplantation, American College of Physicians, American Federation for Medical Research, American Society of Hematology, SWOG

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Acknowledgements

Wadie F Bahou, MD Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook

Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

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Differential diagnosis of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome.
 
 
 
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