eMedicine Specialties > Emergency Medicine > Hematology & Oncology

Thrombotic Thrombocytopenic Purpura: Differential Diagnoses & Workup

Author: Deborrah Symonette, MD, MPH, Healthcare Consultant, DSKSD, Inc
Coauthor(s): Deepak Sharma, Touro College of Osteopathic Medicine, New York; Priya S Abraham, Touro College of Osteopathic Medicine, New York; Vanessa Yoo, Touro College of Osteopathic Medicine, New York; Wafa Qamar, Touro College of Osteopathic Medicine, New York
Contributor Information and Disclosures

Updated: Sep 16, 2009

Differential Diagnoses

Disseminated Intravascular Coagulation
Hemolytic Uremic Syndrome
Idiopathic Thrombocytopenic Purpura
Pregnancy, Eclampsia
Stroke, Hemorrhagic
Stroke, Ischemic

Other Problems to Be Considered

Autoimmune disorders
Cancer-associated TTP
Drug-induced TTP
HIV-related TTP
Infectious process and sepsis
Splenic sequestration
Transplant-associated TTP
Vasculitis

Workup

Laboratory Studies

Thrombotic thrombocytopenic purpura (TTP) is a clinical diagnosis with no pathognomonic laboratory test findings.

  • Lactate dehydrogenase level is extremely elevated due, in part, to ischemic or necrotic tissue cells rather than to hemolysis.
  • Platelets less than 20,000/m L
  • Plasma haptoglobin – Decreased
  • Complete blood count (CBC) 
    • Hemoglobin less than 10 g/dL 
    • Thrombocytopenia - Evidence of thrombocytopenia may precede the appearance of fragmented RBCs and LDH elevation by several days.
  • Peripheral blood smear - Fragmented RBCs (ie, schistocytes) are consistent with hemolysis. Schistocytes on a blood smear is the morphologic hallmark of the disease, but no guidelines exist as to the number of schistocytes required to differentiate TTP from other thrombotic microangiopathies.
  • LDH level - Indirect bilirubin level - Elevated
  • Direct bilirubin – Normal
  • Reticulocyte count - Elevated
  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT) - Normal
  • DIC panel (eg, fibrinogen, D-dimer) - The results are usually normal. Increasing D-dimer levels are the most specific DIC parameter and reflect fibrinolysis of cross-linked fibrin.
  • Pregnancy test - This helps to identify the 10-25% of patients with TTP who are pregnant or postpartum. 
  • Creatinine level - Mildly elevated (46%)
  • HIV testing - This test helps to identify patients with HIV in whom TTP is the presenting symptom.
  • Urinalysis - Proteinuria and microscopic hematuria
  • ADAMTS-13 activity assay is used to measure the activity level of the ADAMTS-13 protease. Measuring ADAMTS-13 activity or ADAMTS antigen levels via ELISA assay as a single test to distinguish TTP from HUS is not practical at this time. The absence of in vitro tests capable of detecting abnormalities in all the molecular interactions required for the cleavage of ULVWF multimers by ADAMTS-13 in vivo is a limitation.

Imaging Studies

CT scan of the head may be indicated to assess for intracranial bleeding and infarcts.

Other Tests

Bone marrow or gingival biopsy samples yield diagnostic lesions (hyaline thrombi) in 30-50% of cases. This is not a necessary test for diagnosis of TTP.

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
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References

  1. Amorosi El, Ultmann JE. Thrombocytopenic Purpura: report of 16 cases and review of the literature. Medicine. 1966;45:139-59.

  2. Jaffey PB, Feldman HA. The Clinical Spectrum of Thrombotic Thrombocytopenic Purpura. Emergency Medicine. 2005;36-44.

  3. Crowther MA, George JN. Thrombotic thrombocytopenic purpura: 2008 update. Cleve Clin J Med. May 2008;75(5):369-75. [Medline].

  4. Zheng XL, Sadler JE. Pathogenesis of thrombotic microangiopathies. Annu Rev Pathol. 2008;3:249-77. [Medline].

  5. Lammle B, George JN. Thrombotic thrombocytopenic purpura: advances in pathophysiology, diagnosis, and treatment--introduction. Semin Hematol. Jan 2004;41(1):1-3. [Medline].

  6. Zheng XL, Sadler JE. Pathogenesis of thrombotic microangiopathies. Annu Rev Pathol. 2008;3:249-77. [Medline].

  7. Fontana S, Hovinga JAK, Lammle, Teleghani M. Treatment of thrombotic thrombocytopenic purpura. Vox Sanguinis. 2008;90:245-254.

  8. 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].

  9. Martinelli I. von Willebrand factor and factor VIII as risk factors for arterial and venous thrombosis. Semin Hematol. Jan 2005;42(1):49-55. [Medline].

  10. Moake JL. Studies on the pathophysiology of thrombotic thrombocytopenic purpura. Semin Hematol. Apr 1997;34(2):83-9. [Medline].

  11. Moake JL. von Willebrand factor, ADAMTS-13, and thrombotic thrombocytopenic purpura. Semin Hematol. Jan 2004;41(1):4-14. [Medline].

  12. Manea M, Karpman D. Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura. Pediatr Nephrol. Mar 2009;24(3):447-58. [Medline].

  13. 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].

  14. 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].

  15. Sadler JE, Moake JL, Miyata T, George JN. Recent advances in thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2004;407-23. [Medline].

  16. Plaimauer B, Scheiflinger F. Expression and characterization of recombinant human ADAMTS-13. Semin Hematol. Jan 2004;41(1):24-33. [Medline].

  17. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med. May 4 2006;354(18):1927-35. [Medline].

  18. Tsai HM. Thrombotic thrombocytopenic purpura: a thrombotic disorder caused by ADAMTS13 deficiency. Hematol Oncol Clin North Am. Aug 2007;21(4):609-32, v. [Medline].

  19. Esplin MS, Branch DW. Diagnosis and management of thrombotic microangiopathies during pregnancy. Clin Obstet Gynecol. Jun 1999;42(2):360-7. [Medline].

  20. Sadler JE. Thrombotic thrombocytopenic purpura: a moving target. Hematology Am Soc Hematol Educ Program. 2006;415-20. [Medline].

  21. Zakarija A, Bandarenko N, Pandey DK, et al. Clopidogrel-associated TTP: an update of pharmacovigilance efforts conducted by independent researchers, pharmaceutical suppliers, and the Food and Drug Administration. Stroke. Feb 2004;35(2):533-7. [Medline].

  22. Rutherford CJ, Frenkel EP. Thrombocytopenia. Issues in diagnosis and therapy. Med Clin North Am. May 1994;78(3):555-75. [Medline].

  23. Gordon LI, Kwaan HC. Cancer- and drug-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol. Apr 1997;34(2):140-7. [Medline].

  24. Zhou W, Dong L, Ginsburg D, Bouhassira EE, Tsai HM. Enzymatically active ADAMTS13 variants are not inhibited by anti-ADAMTS13 autoantibodies: a novel therapeutic strategy?. J Biol Chem. Dec 2 2005;280(48):39934-41. [Medline].

  25. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. Aug 9 2007;357(6):580-7. [Medline].

  26. Bain BJ. Diagnosis from the blood smear. N Engl J Med. Aug 4 2005;353(5):498-507. [Medline].

  27. Bell WR. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome relapse: frequency, pathogenesis, and meaning. Semin Hematol. Apr 1997;34(2):134-9. [Medline].

  28. 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].

  29. Bridgman J, Witting M. Thrombotic thrombocytopenic purpura presenting as a sudden headache with focal neurologic findings. Ann Emerg Med. Jan 1996;27(1):95-7. [Medline].

  30. Dierickx D, Rycke AD, Vanderschueren S, Delannoy A. New treatment options for immune-mediated hematological disorders. European Journal of Internal Medicine. Aug 2007;19:579-586.

  31. Elkins SL, Wilson PP Jr, Files JC, Morrison FS. Thrombotic thrombocytopenic purpura: evolution across 15 years. J Clin Apher. 1996;11(4):173-5. [Medline].

  32. Fontana S, Hovinga JA, Studt JD, Alberio L, Lammle B, Taleghani BM. Plasma therapy in thrombotic thrombocytopenic purpura: review of the literature and the Bern experience in a subgroup of patients with severe acquired ADAMTS-13 deficiency. Semin Hematol. Jan 2004;41(1):48-59. [Medline].

  33. Franchini M, Mannucci PM. Advantages and limits of ADAMTS13 testing in thrombotic thrombocytopenic purpura. Blood Transfus. Jul 2008;6(3):127-35. [Medline].

  34. George JN. Evaluation and management of patients with thrombotic thrombocytopenic purpura. J Intensive Care Med. Mar-Apr 2007;22(2):82-91. [Medline].

  35. George JN, Vesely SK, Terrell DR. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry: a community perspective of patients with clinically diagnosed TTP-HUS. Semin Hematol. Jan 2004;41(1):60-7. [Medline].

  36. Hymes KB, Karpatkin S. Human immunodeficiency virus infection and thrombotic microangiopathy. Semin Hematol. Apr 1997;34(2):117-25. [Medline].

  37. Kaplan RN, Bussel JB. Differential diagnosis and management of thrombocytopenia in childhood. Pediatr Clin North Am. Aug 2004;51(4):1109-40, xi. [Medline].

  38. Keusch GT, Acheson DW. Thrombotic thrombocytopenic purpura associated with Shiga toxins. Semin Hematol. Apr 1997;34(2):106-16. [Medline].

  39. Kwaan HC, Ganguly P. Introduction: Thrombolytic thrombocytopenia purpura and the hemolytic uremic syndrome. Semin Hematol. 1997;81-82.

  40. Kwaan HC, Soff GA. Management of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol. Apr 1997;34(2):159-66. [Medline].

  41. Laurence J, Mitra D. Apoptosis of microvascular endothelial cells in the pathophysiology of thrombotic thrombocytopenic purpura/sporadic hemolytic uremic syndrome. Semin Hematol. Apr 1997;34(2):98-105. [Medline].

  42. Lee GR, Paraskevas F, Lukens J, et al. Wintrobe's Clinical Hematology. 10th ed. Lippincott Williams & Wilkins; 1999.

  43. Levandovsky M, Harvey D, Lara P, Wun T. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients. J Hematol Oncol. Dec 1 2008;1:23. [Medline].

  44. Lopez JA, Dong JF. Cleavage of von Willebrand factor by ADAMTS-13 on endothelial cells. Semin Hematol. Jan 2004;41(1):15-23. [Medline].

  45. Mannucci PM. von Willebrand factor: a prima ballerina on two different stages. Semin Hematol. Jan 2005;42(1):1-4. [Medline].

  46. Matsumoto M, Yagi H, Ishizashi H, Wada H, Fujimura Y. The Japanese experience with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Semin Hematol. Jan 2004;41(1):68-74. [Medline].

  47. Matzdorf AC, George JN. Thrombotic Thrombocytopenia Purpura. New England Journal of Medicine. 2006;355(6):630.

  48. McCrae KR, Cines DB. Thrombotic microangiopathy during pregnancy. Semin Hematol. Apr 1997;34(2):148-58. [Medline].

  49. Mendolicchio GL, Ruggeri ZM. New perspectives on von Willebrand factor functions in hemostasis and thrombosis. Semin Hematol. Jan 2005;42(1):5-14. [Medline].

  50. [Best Evidence] Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kidney Dis. Feb 2009;53(2):259-72. [Medline].

  51. Moake JL, Rudy CK, Troll JH, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med. Dec 2 1982;307(23):1432-5. [Medline].

  52. Murrin RJ, Murray JA. Thrombotic thrombocytopenic purpura: aetiology, pathophysiology and treatment. Blood Rev. Jan 2006;20(1):51-60. [Medline].

  53. Nabhan C, Kwaan HC. Current concepts in the diagnosis and management of thrombotic thrombocytopenic purpura. Hematol Oncol Clin North Am. Feb 2003;17(1):177-99. [Medline].

  54. Rodeghiero F, Castaman G. Treatment of von Willebrand disease. Semin Hematol. Jan 2005;42(1):29-35. [Medline].

  55. Schneppenheim R, Budde U. Phenotypic and genotypic diagnosis of von Willebrand disease: a 2004 update. Semin Hematol. Jan 2005;42(1):15-28. [Medline].

  56. Schneppenheim R, Budde U, Hassenpflug W, Obser T. Severe ADAMTS-13 deficiency in childhood. Semin Hematol. Jan 2004;41(1):83-9. [Medline].

  57. Schriber JR, Herzig GP. Transplantation-associated thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Semin Hematol. Apr 1997;34(2):126-33. [Medline].

  58. Smith BR, Rinder HM. Interactions of platelets and endothelial cells with erythrocytes and leukocytes in thrombotic thrombocytopenic purpura. Semin Hematol. Apr 1997;34(2):90-7. [Medline].

  59. Soejima K, Nakagaki T. Interplay between ADAMTS13 and von Willebrand factor in inherited and acquired thrombotic microangiopathies. Semin Hematol. Jan 2005;42(1):56-62. [Medline].

  60. Tsai HM. Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura. J Am Soc Nephrol. Apr 2003;14(4):1072-81. [Medline].

  61. Veyradier A, Girma JP. Assays of ADAMTS-13 activity. Semin Hematol. Jan 2004;41(1):41-7. [Medline].

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Further Reading

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Keywords

thrombocytopenic purpura, Moschcowitz disease, thrombotic thrombocytopenic purpura, TTP, multisystem disorder, plasma exchange, fresh-frozen plasma, FFP, microangiopathic hemolytic anemia, hemolytic uremic syndrome, HUS, familial thrombotic thrombocytopenic purpura, familial TTP, acquired idiopathic thrombotic thrombocytopenic purpura, acquired idiopathic TTP, von Willebrand factor multimers, vWF, vWF multimers, vWF-cleaving protease, anemia, petechiae, microscopic hematuria, disseminated microvascular thrombi, thrombocytopenia, renal dysfunction, Escherichia coli, E coli O157:H7, Shigalike toxin, microangiopathic hemolysis, platelet microthrombi, ultralarge von Willebrand factor multimers, ULVWF multimers, ADAMTS-13 gene mutations, ULVWF multimer–induced platelet thrombosis, ULVWF-cleaving protease, petechial hemorrhages, seizures, CNS bleeding, heart failure, arrhythmias, gross hematuria, purpuric spots, plasmapheresis, plasma transfusion, thrombotic microangiopathic

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Contributor Information and Disclosures

Author

Deborrah Symonette, MD, MPH, Healthcare Consultant, DSKSD, Inc
Deborrah Symonette, MD, MPH is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Deepak Sharma, Touro College of Osteopathic Medicine, New York
Disclosure: Nothing to disclose.

Priya S Abraham, Touro College of Osteopathic Medicine, New York
Priya S Abraham is a member of the following medical societies: Student Osteopathic Medical Association (SOMA)
Disclosure: Nothing to disclose.

Vanessa Yoo, Touro College of Osteopathic Medicine, New York
Disclosure: Nothing to disclose.

Wafa Qamar, Touro College of Osteopathic Medicine, New York
Wafa Qamar is a member of the following medical societies: Microscopy Society of America
Disclosure: Nothing to disclose.

Medical Editor

Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT, Associate Clinical Professor; Medical and Managing Director, South Texas Poison Center, Department of Surgery/Emergency Medicine and Toxicology, University of Texas Health Science Center at San Antonio
Miguel C Fernández, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

 
 
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