eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Thrombotic Thrombocytopenic Purpura: Differential Diagnoses & Workup

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
Coauthor(s): 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
Contributor Information and Disclosures

Updated: Aug 27, 2009

Differential Diagnoses

Disseminated Intravascular Coagulation
Hypertension
Hypertension, Malignant
Immune Thrombocytopenic Purpura

Workup

Laboratory Studies

  • Complete blood count with platelets and differential
    • CBC usually reveals a normal or slightly elevated total white blood cell count.
    • Hemoglobin is moderately depressed at 8-9 g/dL.
    • Platelet count generally ranges from 20,000-50,000 per microliter.
  • Review of peripheral smears (see Image 2)
    • Review reveals 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: The coagulation studies typically are normal in patients with HUS and TTP, although some series report patients with slight elevations of both.
  • D-dimers and fibrinogen
    • 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.
  • BUN and creatinine
    • Evaluation of renal function with a 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.
  • Lactic dehydrogenase and bilirubin, direct and total
    • Lactic dehydrogenase (LDH) and bilirubin are indirect measures of the degree of hemolysis.
    • LDH level being 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.
  • 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, serologic evaluation for HIV infection should be obtained in all newly presenting patients.
  • von Willebrand factor-cleaving protease activity
    • Although not routinely available, measurement of vWF-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. However, to date, 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 clinical utility of the assays has yet to be demonstrated.

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.

Peripheral smear from a patient with thrombotic t...

Peripheral smear from a patient with thrombotic thrombocytopenic purpura: Red blood cells are fragmented and appear as schistocytes. Certain schistocytes have the appearance of helmet cells (H). Spheroidal cells often are present (S). Occasional nucleated erythroid precursors may be present.

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Peripheral smear from a patient with thrombotic t...

Peripheral smear from a patient with thrombotic thrombocytopenic purpura: Red blood cells are fragmented and appear as schistocytes. Certain schistocytes have the appearance of helmet cells (H). Spheroidal cells often are present (S). Occasional nucleated erythroid precursors may be present.

More on Thrombotic Thrombocytopenic Purpura

Overview: Thrombotic Thrombocytopenic Purpura
Differential Diagnoses & Workup: Thrombotic Thrombocytopenic Purpura
Treatment & Medication: Thrombotic Thrombocytopenic Purpura
Follow-up: Thrombotic Thrombocytopenic Purpura
Multimedia: Thrombotic Thrombocytopenic Purpura
References
Further Reading
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References

  1. Sauna ZE, Okunji C, Hunt RC, et al. Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease. PLoS One. Aug 5 2009;4(8):e6506. [Medline]. [Full Text].

  2. Bouw MC, Dors N, van Ommen H, Ramakers-van Woerden NL. Thrombotic thrombocytopenic purpura in childhood. Pediatr Blood Cancer. Jun 18 2009;53(4):537-542. [Medline].

  3. Ferrari S, Mudde GC, Rieger M, Veyradier A, Kremer Hovinga JA, Scheiflinger F. IgG-subclass distribution of anti-ADAMTS13 antibodies in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost. Aug 11 2009;[Medline].

  4. Marn Pernat A, Buturovic-Ponikvar J, Kovac J, et al. Membrane plasma exchange for the treatment of thrombotic thrombocytopenic purpura. Ther Apher Dial. Aug 2009;13(4):318-21. [Medline].

  5. Jhaveri KD, Scheuer A, Cohen J, Gordon B. Treatment of refractory thrombotic thrombocytopenic purpura using multimodality therapy including splenectomy and cyclosporine. Transfus Apher Sci. Aug 2009;41(1):19-22. [Medline].

  6. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med. Aug 8 1991;325(6):398-403. [Medline].

  7. Fakhouri F, Vernant JP, Veyradier A, et al. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood. Sep 15 2005;106(6):1932-7. [Medline].

  8. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. Nov 26 1998;339(22):1578-84. [Medline].

  9. Lara PN, Coe TL, Zhou H, et al. Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med. Dec 1999;107(6):573-9. [Medline].

  10. Lau DH, Wun T. Early manifestation of thrombotic thrombocytopenic purpura. Am J Med. Nov 1993;95(5):544-5. [Medline].

  11. Moake JL. Haemolytic-uraemic syndrome: basic science. Lancet. Feb 12 1994;343(8894):393-7. [Medline].

  12. Neild GH. Haemolytic-uraemic syndrome in practice. [published erratum appears in Lancet 1994 Feb 26;343(8896):552]. Lancet. Feb 12 1994;343(8894):398-401. [Medline].

  13. Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. Aug 8 1991;325(6):393-7. [Medline].

  14. Shumak KH, Rock GA, Nair RC. Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group. Ann Intern Med. Apr 15 1995;122(8):569-72. [Medline].

  15. Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. Nov 26 1998;339(22):1585-94. [Medline].

  16. Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. Jul 1 2003;102(1):60-8. [Medline].

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Further Reading

Related eMedicine Topics

Clinical Trials
 National Guideline Clearinghouse

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Keywords

thrombotic thrombocytopenic purpura,  TTP, thrombocytopenia, thrombosis, thrombophilia, hemolytic-uremic syndrome, HUS, microangiopathic hemolytic anemia, von Willebrand factor, vWF, platelet count, bland thrombi, Moschowitz syndrome, petechiae, paralysis, coma, ADAMST13

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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 College of Physicians, American Federation for Medical Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Coauthor(s)

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.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
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, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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