eMedicine Specialties > Neurology > Pediatric Neurology

Thrombotic Thrombocytopenic Purpura: Differential Diagnoses & Workup

Author: Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Contributor Information and Disclosures

Updated: Jan 27, 2010

Differential Diagnoses

Acute Disseminated Encephalomyelitis
Dizziness, Vertigo, and Imbalance
Anterior Circulation Stroke
Meningococcal Meningitis
Aphasia
Migraine Headache
Aseptic Meningitis
Migraine Variants
Brucellosis
Partial Epilepsies
Cardioembolic Stroke
Posterior Cerebral Artery Stroke
Cerebral Venous Thrombosis
Sudden Visual Loss
Childhood Migraine Variants
Uremic Encephalopathy
Complex Partial Seizures
Viral Encephalitis
Confusional States and Acute Memory Disorders
Viral Meningitis
Dissection Syndromes

Other Problems to Be Considered

Sepsis
Rocky Mountain spotted fever
Disseminated fungal infection
Lymphoma
Endocarditis
Malignant hypertension
Factor H Deficiency
Drug effects
Toxins

Workup

Laboratory Studies

  • TTP is a TMA hemolytic anemia from which various associated abnormalities develop. HUS is fundamentally a microangiopathic nonimmune hemolytic anemia with which a variety of ensuing complications may develop.
  • Although the effects of ADAMTS-13 deficiency on clotting homeostasis provide an important conceptual framework for understanding and managing TTP, the microangiopathy of TTP is less well understood. This uncertainty is reflected in the fact that TMA with a TTP phenotype occurs in individuals who do not have abnormalities in the ADAMTS-13 pathway. Other factors, such as heterozygosity for factor V Leiden may contribute to vulnerability to a TTP-like illness.
  • Laboratory findings of TMA in TTP include anemia, and thrombocytopenia, as in HUS and other TMAs.
    • Anemia is an invariable finding
    • Thrombocytopenia is partly the result of platelet consumption in clot formation in the microcirculation.
    • Platelet survival time is shortened.
    • Platelet counts are typically <60 X 109/L (<60,000/mm3) and tend to be lower than those seen in HUS.
    • An increasing platelet count is a sensitive indicator of the response to therapies such as plasma exchange, increasing within about 5 days of the onset of effective therapy.
    • The peripheral blood smear reveals microangiopathic changes, including fragmented RBCs (eg, schistocytes, spherocytes, segmented RBCs, burr cells, helmet cells). In a case of childhood B-12 deficiency with ADAMTS-13 deficient TTP, macrocytosis was found in addition to microcytosis and characteristic microangiopathic changes. Mean corpuscular volume was elevated.
    • Reticulocytosis (proportional to hemolysis) and circulating free hemoglobin may be found, though not when the bone marrow response to anemia is impaired.
    • Moderate neutrophilia is usually found, though some individuals with TTP are neutropenic.
    • Because hemolytic anemia is nonimmune, results of Coombs testing are negative.
    • Unlike many cases of HUS, case of TTP do not commonly manifest changes consistent with disseminated intravascular coagulopathy (elevated levels of fibrin split products, prolonged activated partial thromboplastin time, and low antithrombin III levels). Fibrinogen values may be normal or increased.
    • Prolongation of the prothrombin time (PT) and elevated levels of fibrin degradation products are especially likely to be detected in adult TTP after enterohemorrhagic E coli O157:H7 infection.
    • Because of intravascular hemolysis, the direct bilirubin level is elevated, whereas the haptoglobin value is usually low.
    • Another important indicator of intravascular hemolysis is elevation of serum lactate dehydrogenase (LDH) levels. Because tissue ischemia further elevates value, it may be extremely high.
    • LDH is the most sensitive indicator of ongoing hemolysis. Therefore, it is often used as a sensitive indicator of the response to therapeutic interventions, such as plasma exchange. The value often decreased within about 3 days of the start of plasma exchange.
    • Although no universally accepted criterion standard test is available for the diagnosis of TTP, the identification of possible abnormalities in the ADAMTS-13–vWF axis is of great importance.
    • Identification of unusually large circulating plasma vWF multimers strongly indicates deficiency of ADAMTS-13 activity on an heritable or acquired basis.
    • Several assays have been developed to measure plasma ADAMTS-13 activity. The nature and reliability of these various assays was reviewed.54
    • Severe deficiency of ADAMTS-13 activity (levels <5% of normal activity) may be specific for the diagnosis of TTP in an appropriate clinical setting.
    • Activity levels even slightly higher than 5% are thought to protect against TTP on the basis of ADAMTS-13 activity deficiency.
    • Approximately one half of all patients with thrombocytopenia, microangiopathic hemolytic anemia, and severely diminished ADAMTS-13 activity (<5% of normal) retain normal renal function, and approximately 25% have no clinical neurologic abnormalities.
    • Testing of asymptomatic parents of an individual thought to have heritable ADAMTS-13 deficiency should be considered for diagnostic and counseling purposes. Testing of relatives who have clinical episodes suggestive of TTP should also be considered.
    • Care should be taken in interpreting low values of ADAMTS-13 activity or specific inhibitory antibodies because the assays are not easy to perform and may not be adequately standardized in some laboratories.28 Although some new assays are simpler to perform, older, more complex, and more time-consuming assays may be more reliable and sensitive.
  • Until well-standardized, reliable, and sensitive assays for ADAMTS-13 activity become widely available, diagnostic confusion will continue to occur.
    • Because as many as 80% of individuals with TTP have renal failure at some time during their illness, testing may reflect this dysfunction.
    • Proteinuria, microscopic hematuria, urinary leukocytosis, urine hyaline casts, increased specific gravity of urine, and various degrees of elevation of blood urea nitrogen (BUN) and creatinine levels are found in patients with acute renal failure. Creatinine elevation may be seen in as many as 44% of patients with TTP.55
    • In mild cases, urinary findings may be limited to abnormalities of the urine sediment or mild azotemia on a prerenal basis that improve with correction of the patient's hydration status.
    • Blood may be detected in urine or stool
    • Stool specimens may be melenic, frankly bloody, or merely heme positive.
    • Pancreatitis may occur in TTP, elevating amylase and lipase levels.
    • CSF chemistry, cell counts, and pressure are usually normal, even in some patients with neurologic abnormalities.
    • Additional laboratory testing may entail evaluation for the various provocative illnesses described in association with TTP.
  • CSF chemistry, cell counts, and pressures are usually normal.

Imaging Studies

  • A wide variety of abnormalities on imaging studies may be found in TTP.
  • Of surprise, MRIs of the brain are often normal, especially in individuals with adult-onset TTP.
  • Severe hereditary ADAMTS-13 deficiency with infantile-onset (Schulman-Upshaw syndrome) may produce severe ischemic brain lesions readily identifiable on brain MRI. These changes are most commonly encountered after several recurrent episodes of TTP. Delayed diagnosis and treatment due to failure to recognize this rare TTP variant may be responsible for the development of such lesions.
  • Patients with TTP may have small, multifocal cortical lesions, including small areas of hemorrhagic change.
  • Infarctions in the vascular territory may be seen and range from small- to large-arterial territories and with or without hemorrhage; however, these findings are uncommon.
  • The territories of the middle or posterior cerebral artery or the cerebellar artery are among the most likely loculations where large-vessel infarctions occur. For obvious reasons, such abnormalities foretell a worsened outcome.56
  • Some patients have brain edema without focal or widespread cortical or subcortical lesions. As might be expected, the prognosis is better for these patients than for those who have strokes or hemorrhages.56
  • Changes consistent with reversible posterior leukoencephalopathy (RPLE) may be seen in patients with elevated blood pressure.56
  • Single-photon emission CT (SPECT) scans may show diminished cerebral blood flow.

Other Tests

  • Renal biopsy may help clarify the diagnosis of TTP.
    • Patients with hereditary or acquired deficiencies of ADAMTS-13 activity may have platelet-rich, fibrin-poor thrombi in the microvasculature and other sites prone to high fluid shear stress, with ensuing shear-stress related to additional changes in circulating RBCs.
    • Microvascular fibrin and/or platelet thrombi may be found in glomerular hilar arterioles, peripheral ancillary loops, and in extraglomerular vessels of the kidney.
    • Unlike the clots of HUS, the microcirculatory clots that develop in TTP are platelet rich and fibrin-poor. This distinction can be made on the basis of renal biopsy.
  • ECGs may be abnormal.
    • ECGs may indicate pathologic changes such as cardiac hypoxia or ischemia; focal myocarditis; myocardial infarction; epicardial petechiae or microinfarction; and cardiac microvascular (eg, arteriolar) occlusion or petechial hemorrhage involving the sinus node, the atrioventricular node, or the bundle of His.
    • Conduction abnormalities ranging in severity up to complete conduction block (atrioventricular dissociation).
    • Sinus tachycardia may be present and out of proportion to fever, state of hydration, or anemia.
    • Atrial tachycardia may be found.
    • Evidence of myocardial infarction may be found.

Procedures

  • Dialysis must be undertaken in individuals who develop acute renal failure that cannot be reversed with approaches such as hydration or pressor support.

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
References
[ CLOSE WINDOW ]

References

  1. Moschowitz E. Hyaline thrombosis of the terminal arterioles and capillaries: A hitherto undescribed disease. Proc N Y Pathol Soc. 1924;24:21-4.

  2. Moake JL. Thrombotic thrombocytopenic purpura: survival by "giving a dam". Trans Am Clin Climatol Assoc. 2004;115:201-19. [Medline].

  3. Baehr G, Klemperer P, Schifrin A. Trans Ass Amer Phys. 1936;51.

  4. Adams RD, Cammermeyer J, Fitzgerald PJ. Neuropathological aspects of thrombotic acroagiothrombosis; clinico-anatomical study of generalized platelet thrombosis. J Neurol Neurosurg Psychiatry. 1948;11:27-43.

  5. Bukowski MJ, Koblenzer PJ. Thrombotic thrombocytopenic purpura. Report of a case with the unusual features of hypofibrinogenemia and leukopenia. J Pediatr. Jan 1962;60:84-90. [Medline].

  6. Bukowski RM. Thrombotic thrombocytopenic purpura: a review. Prog Hemost Thromb. 1982;6:287-337. [Medline].

  7. Symmers WS. Thrombotic microangiopathic haemolytic anaemia (thrombotic microangiopathy). Br Med J. Oct 25 1952;2(4790):897-903. [Medline].

  8. Silverstein A. Thrombotic thrombocytopenic purpura. The initial neurologic manifestations. Arch Neurol. Apr 1968;18(4):358-62. [Medline].

  9. Ruggenenti P, Remuzzi G. Thrombotic microangiopathies. Crit Rev Oncol Hematol. Dec 1991;11(4):243-65. [Medline].

  10. McLeod BC. Thrombotic microangiopathies in bone marrow and organ transplant patients. J Clin Apher. 2002;17(3):118-23. [Medline].

  11. George JN, Sadler JE, Lammle B. Platelets: thrombotic thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program). 2002;315-34. [Medline].

  12. Dimond A, George JN, Hastings C. Severe vitamin B-12 deficiency in a child mimicking thrombotic thrombocytopenic purpura. Pediatr Blood Cancer. 2009;52:420-2.

  13. Hosler GA, Cusumano AM, Hutchins GM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases. Arch Pathol Lab Med. Jul 2003;127(7):834-9. [Medline].

  14. Tsai HM. Molecular mechanisms in thrombotic thrombocytopenic purpura. Semin Thromb Hemost. Oct 2004;30(5):549-57. [Medline].

  15. Berkowitz LR, Dalldorf FG, Blatt PM. Thrombotic thrombocytopenic purpura: a pathology review. JAMA. Apr 20 1979;241(16):1709-10. [Medline].

  16. 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].

  17. Chow TW, Turner NA, Chintagumpala M, et al. Increased von Willebrand factor binding to platelets in single episode and recurrent types of thrombotic thrombocytopenic purpura. Am J Hematol. Apr 1998;57(4):293-302. [Medline].

  18. Moake JL, McPherson PD. von Willebrand factor in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Transfus Med Rev. Apr 1990;4(2):163-8. [Medline].

  19. Siedlecki CA, Lestini BJ, Kottke-Marchant KK, Eppell SJ, Wilson DL, Marchant RE. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor. Blood. Oct 15 1996;88(8):2939-50. [Medline].

  20. Furlan M, Robles R, Solenthaler M. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood. May 1 1997;89(9):3097-103. [Medline].

  21. Tsai HM, Sussman II, Ginsburg D, et al. Proteolytic cleavage of recombinant type 2A von Willebrand factor mutants R834W and R834Q: inhibition by doxycycline and by monoclonal antibody VP-1. Blood. Mar 15 1997;89(6):1954-62. [Medline].

  22. Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood. Sep 15 2001;98(6):1662-6. [Medline].

  23. Zheng X, Chung D, Takayama TK, et al. Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. Nov 2 2001;276(44):41059-63. [Medline].

  24. Hovinga JA, Studt JD, Alberio L, Lammle B. von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the diagnosis of thrombotic microangiopathies: the Swiss experience. Semin Hematol. Jan 2004;41(1):75-82. [Medline].

  25. Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood. Jun 1 2004;103(11):4043-9. [Medline].

  26. Veyradier A, Obert B, Houllier A, Meyer D, Girma JP. Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases. Blood. Sep 15 2001;98(6):1765-72. [Medline].

  27. George JN. Idiopathic thrombocytopenic purpura in adults: current issues for pathogenesis, diagnosis and management. Hematol J. 2004;5 Suppl 3:S12-4. [Medline].

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

  29. Porta C, Caporali R, Montecucco C. Thrombotic thrombocytopenic purpura and autoimmunity: a tale of shadows and suspects. Haematologica. Mar 1999;84(3):260-9. [Medline].

  30. Tsai HM. Shear stress and von Willebrand factor in health and disease. Semin Thromb Hemost. Oct 2003;29(5):479-88. [Medline].

  31. Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. Oct 4 2001;413(6855):488-94. [Medline].

  32. Kokame K, Matsumoto M, Soejima K, et al. Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci U S A. Sep 3 2002;99(18):11902-7. [Medline].

  33. Copelovitch L, Kaplan BS. The thrombotic microangiopathies. Pediatr Nephrol. Oct 2008;23(10):1761-7. [Medline].

  34. Hamasaki K, Mimura T, Kanda H, Kubo K, Setoguchi K, Satoh T. Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review. Clin Rheumatol. Oct 2003;22(4-5):355-8. [Medline].

  35. Starck M, Abedinpour F, Dendorfer U, Wagner-Czekalla J, Pachmann M, Mann JF. Acquired thrombotic thrombocytopenic purpura as the presenting symptom of systemic lupus erythematosus. Successful treatment with plasma exchange and immunosuppression--report of two cases. Eur J Haematol. Nov 2005;75(5):436-40. [Medline].

  36. Kapoulas S, Liakos S, Karkavelas G, Ageloudi M, Grekas D, Giannoulis E. Thrombotic thrombocytopenic purpura associated with rapidly progressive lupus nephritis: report of two cases. Clin Nephrol. Apr 2005;63(4):297-301. [Medline].

  37. Devinsky O, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, heart emboli, and thrombotic thrombocytopenic purpura. Ann Neurol. Apr 1988;23(4):380-4. [Medline].

  38. Sherer DM, Sanmugarajah J, Dalloul M, Temkin SM, Thanus J, Abulafia O. Thrombotic thrombocytopenic purpura in a patient with acquired immunodeficiency syndrome at 28 weeks gestation. Am J Perinatol. May 2005;22(4):223-5. [Medline].

  39. Alpers CE. Light at the end of the TUNEL: HIV-associated thrombotic microangiopathy. Kidney Int. Jan 2003;63(1):385-96. [Medline].

  40. Gadallah MF, el-Shahawy MA, Campese VM, Todd JR, King JW. Disparate prognosis of thrombotic microangiopathy in HIV-infected patients with and without AIDS. Am J Nephrol. 1996;16(5):446-50. [Medline].

  41. Novitzky N, Thomson J, Abrahams L, du Toit C, McDonald A. Thrombotic thrombocytopenic purpura in patients with retroviral infection is highly responsive to plasma infusion therapy. Br J Haematol. Feb 2005;128(3):373-9. [Medline].

  42. Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. Aug 2005;11(8):571-5. [Medline].

  43. Pettitt AR, Clark RE. Thrombotic microangiopathy following bone marrow transplantation. Bone Marrow Transplant. Oct 1994;14(4):495-504. [Medline].

  44. George JN, Li X, McMinn JR, Terrell DR, Vesely SK, Selby GB. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. Feb 2004;44(2):294-304. [Medline].

  45. Torok TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United States--analysis of national mortality data, 1968-1991. Am J Hematol. Oct 1995;50(2):84-90. [Medline].

  46. Miller DP, Kaye JA, Shea K, Ziyadeh N, Cali C, Black C, et al. Incidence of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Epidemiology. Mar 2004;15(2):208-15. [Medline].

  47. Becker S, Fusco G, Fusco J, Balu R, Gangjee S, Brennan C, et al. HIV-associated thrombotic microangiopathy in the era of highly active antiretroviral therapy: an observational study. Clin Infect Dis. Nov 1 2004;39 Suppl 5:S267-75. [Medline].

  48. Terrell DR, Williams LA, Vesely SK, Lammle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost. Jul 2005;3(7):1432-6. [Medline].

  49. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, 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].

  50. 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].

  51. Fontana S, Gerritsen HE, Kremer Hovinga J, Furlan M, Lammle B. Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor-cleaving protease. Br J Haematol. Apr 2001;113(1):100-2. [Medline].

  52. Arai S, Allan C, Streiff M, Hutchins GM, Vogelsang GB, Tsai HM. Von Willebrand factor-cleaving protease activity and proteolysis of von Willebrand factor in bone marrow transplant-associated thrombotic microangiopathy. Hematol J. 2001;2(5):292-9. [Medline].

  53. Kennedy SS, Zacharski LR, Beck JR. Thrombotic thrombocytopenic purpura: analysis of 48 unselected cases. Semin Thromb Hemost. 1980;6(4):341-9. [Medline].

  54. Furlan M, Lammle B. Assays of von Willebrand factor-cleaving protease: a test for diagnosis of familial and acquired thrombotic thrombocytopenic purpura. Semin Thromb Hemost. Apr 2002;28(2):167-72. [Medline].

  55. Conlon PJ, Howell DN, Macik G, Kovalik EC, Smith SR. The renal manifestations and outcome of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in adults. Nephrol Dial Transplant. 1995;10(7):1189-93. [Medline].

  56. Bakshi R, Shaikh ZA, Bates VE, Kinkel PR. Thrombotic thrombocytopenic purpura: brain CT and MRI findings in 12 patients. Neurology. Apr 12 1999;52(6):1285-8. [Medline].

  57. Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura. Report of 25 cases and review of the literature. Medicine (Baltimore). Nov 1981;60(6):413-28. [Medline].

  58. Byrnes JJ, Moake JL. Thrombotic thrombocytopenic purpura and the haemolytic-uraemic syndrome: evolving concepts of pathogenesis and therapy. Clin Haematol. May 1986;15(2):413-42. [Medline].

  59. Lawlor ER, Webb DW, Hill A, Wadsworth LD. Thrombotic thrombocytopenic purpura: a treatable cause of childhood encephalopathy. J Pediatr. Feb 1997;130(2):313-6. [Medline].

  60. Gerth J, Schleussner E, Kentouche K, Busch M, Seifert M, Wolf G. Pregnancy-associated thrombotic thrombocytopenic purpura. Thromb Haemost. Feb 2009;101(2):248-51. [Medline].

  61. Moake JL. The role of von Willebrand factor (vWF) in thrombotic thrombocytopenic purpura (TTP) and the hemolytic-uremic syndrome (HUS). Prog Clin Biol Res. 1990;337:135-40. [Medline].

  62. Byrnes JJ, Khurana M. Treatment of thrombotic thrombocytopenic purpura with plasma. N Engl J Med. Dec 22 1977;297(25):1386-9. [Medline].

  63. Bresin E, Gastoldi S, Daina E, Belotti D, Pogliani E, Perseghin P, et al. Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies. Thromb Haemost. Feb 2009;101(2):233-8. [Medline].

  64. Amorosi EL, Karpatkin S. Antiplatelet treatment of thrombotic thrombocytopenic purpura. Ann Intern Med. Jan 1977;86(1):102-6. [Medline].

  65. Birgens H, Ernst P, Hansen MS. Thrombotic thrombocytopenic purpura: treatment with a combination of antiplatelet drugs. Acta Med Scand. 1979;205(5):437-9. [Medline].

  66. Meacham GC, Orbiston JL, et al. Thrombotic thrombocytopenic purpura: A disseminated disease of arterioles. Blood. 1952;6:706.

  67. Hayward CP, Sutton DM, Carter WH Jr, Campbell ED, Scott JG, Francombe WH, et al. Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Arch Intern Med. May 9 1994;154(9):982-7. [Medline].

  68. Hollenbeck M, Kutkuhn B, Aul C, Leschke M, Willers R, Grabensee B. Haemolytic-uraemic syndrome and thrombotic-thrombocytopenic purpura in adults: clinical findings and prognostic factors for death and end-stage renal disease. Nephrol Dial Transplant. Jan 1998;13(1):76-81. [Medline].

  69. Lara PN Jr, Coe TL, Zhou H, Fernando L, Holland PV, Wun T. Improved survival with plasma exchange in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Am J Med. Dec 1999;107(6):573-9. [Medline].

  70. Lewis QF, Lanneau MS, Mathias SD, Terrell DR, Vesely SK, George JN. Long-term deficits in health-related quality of life after recovery from thrombotic thrombocytopenic purpura. Transfusion. Jan 2009;49(1):118-24. [Medline].

  71. Baker KR, Moake JL. Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Curr Opin Pediatr. Feb 2000;12(1):23-8. [Medline].

  72. Blaker F, Altrogge H, Hellwege HH, et al. Treatment of severe haemolytic-uraemic syndrome by dialysis [in German]. Dtsch Med Wochenschr. Aug 4 1978;103(31):1229-32. [Medline].

  73. Bohle A, Helmchen U, Grund KE, et al. Malignant nephrosclerosis in patients with hemolytic uremic syndrome (primary malignant nephrosclerosis). Curr Top Pathol. 1977;65:81-113. [Medline].

  74. Bukowski RM, Hewlett JS, Harris JW, et al. Exchange transfusions in the treatment of thrombotic thrombocytopenic purpura. Semin Hematol. Jul 1976;13(3):219-32. [Medline].

  75. Chin D, Chyczij H, Etches W, et al. Treatment of thrombotic thrombocytopenic purpura with intravenous gammaglobulin. Transfusion. Jan-Feb 1987;27(1):115-6. [Medline].

  76. Cimolai N, Basalyga S, Mah DG, et al. A continuing assessment of risk factors for the development of Escherichia coli 0157:H7-associated hemolytic uremic syndrome. Clin Nephrol. Aug 1994;42(2):85-9. [Medline].

  77. Drews RE, Weinberger SE. Thrombocytopenic disorders in critically ill patients. Am J Respir Crit Care Med. Aug 2000;162(2 Pt 1):347-51. [Medline].

  78. Elliott MA, Nichols WL. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Mayo Clin Proc. Nov 2001;76(11):1154-62. [Medline].

  79. Espinosa G, Bucciarelli S, Cervera R, Lozano M, Reverter JC, de la Red G. Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies. Ann Rheum Dis. Jun 2004;63(6):730-6. [Medline].

  80. Fakhouri F, Vincent F, Legendre C. Pathological and therapeutic distinctions in HUS/TTP. Lancet. Feb 5 2000;355(9202):497; discussion 497-8. [Medline].

  81. Fiorani L, Vianelli N, Gugliotta L, et al. Brain MRI and SPET in thrombotic thrombocytopenic purpura. Ital J Neurol Sci. Apr 1995;16(3):149-51. [Medline].

  82. Furlan AJ, Robles R. von Willebrand. n Engl J Med. 1998.

  83. Furlan M, Lammle B. Haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura-- new insights into underlying biochemical mechanisms. Nephrol Dial Transplant. Aug 2000;15(8):1112-4. [Medline].

  84. 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].

  85. Furlan M, Robles R, Solenthaler M, Lammle B. Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood. Apr 15 1998;91(8):2839-46. [Medline].

  86. Galbusera M, Noris M, Rossi C, et al. Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian. Blood. Jul 15 1999;94(2):610-20. [Medline].

  87. Galbusera M, Ruggenenti P, Noris M, et al. alpha 1-Antitrypsin therapy in a case of thrombotic thrombocytopenic purpura. Lancet. Jan 28 1995;345(8944):224-5. [Medline].

  88. George JN. How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Blood. Aug 15 2000;96(4):1223-9. [Medline].

  89. George JN, Vesely SK. How can we provide the best care for our patients with immune thrombocytopenic pupura?. Mayo Clin Proc. Apr 2004;79(4):456-7. [Medline].

  90. George JN, Vesely SK, Terrell DR, George JN. 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].

  91. Habib R, Mathieu H, Royer P. Arteriole-capillary thrombotic disease of the kidney in children. [in French]. Rev Fr Etud Clin Biol. Oct 1958;3(8):891-4. [Medline].

  92. Ho VT. Blood and marrow. 2005.

  93. Jubinsky PT, Moraille R, Tsai HM. Thrombotic thrombocytopenic purpura in a newborn. J Perinatol. Jan 2003;23(1):85-7. [Medline].

  94. Kakishita E. Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Int J Hematol. Jun 2000;71(4):320-7. [Medline].

  95. Kaplan BS, Thomson PD. Hyperuricemia in the hemolytic-uremic syndrome. Am J Dis Child. Aug 1976;130(8):854-6. [Medline].

  96. Karlsberg RP, Lacher JW, Bartecchi CE. Adult hemolytic-uremic syndrome. Familial variant. Arch Intern Med. Sep 1977;137(9):1155-7. [Medline].

  97. Kojouri K, Vesely SK, Terrell DR, George JN. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term platelet count responses, prediction of response, and surgical complications. Blood. Nov 1 2004;104(9):2623-34.

  98. Kovacs MJ, Roddy J, Gregoire S, et al. Thrombotic thrombocytopenic purpura following hemorrhagic colitis due to Escherichia coli 0157:H7. Am J Med. Feb 1990;88(2):177-9. [Medline].

  99. MacWhinney JB, Packer JT, Miller G, Greendyke RM. Thrombotic thrombocytopenic purpura in childhood. Blood. 1962;18:181-99.

  100. Malbrain ML, Lambrecht GL, Brans B, et al. Acute renal failure in non-fulminant hepatitis A [letter]. Clin Nephrol. Mar 1994;41(3):180-1. [Medline].

  101. Martin DL, MacDonald KL, White KE, et al. The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota [see comments]. N Engl J Med. Oct 25 1990;323(17):1161-7. [Medline].

  102. Misiani R, Appiani AC, Edefonti A, et al. Haemolytic uraemic syndrome: therapeutic effect of plasma infusion. Br Med J (Clin Res Ed). Nov 6 1982;285(6351):1304-6. [Medline].

  103. Moake JL. Thrombotic microangiopathies. N Engl J Med. Aug 22 2002;347(8):589-600. [Medline].

  104. Moake JL. Thrombotic thrombocytopenic purpura. Thromb Haemost. Jul 1995;74(1):240-5. [Medline].

  105. Moake JL. TTP--desperation, empiricism, progress [editorial; comment]. N Engl J Med. Aug 8 1991;325(6):426-8. [Medline].

  106. Moake JL. von Willebrand factor in the pathophysiology of thrombotic thrombocytopenic purpura. Clin Lab Sci. Nov-Dec 1998;11(6):362-4. [Medline].

  107. Nair JM, Bellevue R, Bertoni M, Dosik H. Thrombotic thrombocytopenic purpura in patients with the acquired immunodeficiency syndrome (AIDS)-related complex. A report of two cases. Ann Intern Med. Aug 1 1988;109(3):209-12. [Medline].

  108. Noris M, Ruggenenti P, Perna A, et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic P. J Am Soc Nephrol. Feb 1999;10(2):281-93. [Medline].

  109. Raife TJ. Pathogenesis of thrombotic thrombocytopenic purpura. Curr Hematol Rep. Mar 2003;2(2):133-8. [Medline].

  110. Raniele DP, Opsahl JA, Kjellstrand CM. Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature. Am J Kidney Dis. Aug 1991;18(2):264-8. [Medline].

  111. Remis RS, MacDonald KL, Riley LW, et al. Sporadic cases of hemorrhagic colitis associated with Escherichia coli 0157:H7. Ann Intern Med. Nov 1984;101(5):624-6. [Medline].

  112. Remuzzi G, Ruggenenti P. The hemolytic uremic syndrome. Kidney Int. Jul 1995;48(1):2-19. [Medline].

  113. Richards A, Goodship JA, Goodship TH. The genetics and pathogenesis of haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Curr Opin Nephrol Hypertens. Jul 2002;11(4):431-5. [Medline].

  114. Rizzoni G, Claris-Appiani A, Edefonti A, et al. Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial. J Pediatr. Feb 1988;112(2):284-90. [Medline].

  115. Robertson RJ, Gilcher R, Metz KF, et al. Hemoglobin concentration and aerobic work capacity in women following induced erythrocythemia. J Appl Physiol. Aug 1984;57(2):568-75. [Medline].

  116. Ruggenenti P, Remuzzi G. The pathophysiology and management of thrombotic thrombocytopenic purpura. Eur J Haematol. Apr 1996;56(4):191-207. [Medline].

  117. Ruggenenti P, Remuzzi G. Treatment of adult hemolytic-uremic syndrome. Adv Nephrol Necker Hosp. 2000;30:83-94. [Medline].

  118. Schwartz SG, McPherson AR, Mieler WF, et al. Bilateral combined occlusion of the central retinal artery and vein secondary to thrombotic thrombocytopenic purpura. Arch Ophthalmol. Sep 2000;118(9):1304-5. [Medline].

  119. Sheth KJ, Swick HM, Haworth N. Neurological involvement in hemolytic-uremic syndrome. Ann Neurol. Jan 1986;19(1):90-3. [Medline].

  120. Studt JD, Hovinga JA, Antoine G, et al. Fatal congenital thrombotic thrombocytopenic purpura with apparent ADAMTS13 inhibitor: in vitro inhibition of ADAMTS13 activity by hemoglobin. Blood. Jan 15 2005;105(2):542-4. [Medline].

  121. Studt JD, Hovinga JA, Radonic R, et al. Familial acquired thrombotic thrombocytopenic purpura: ADAMTS13 inhibitory autoantibodies in identical twins. Blood. Jun 1 2004;103(11):4195-7. [Medline].

  122. Tarr PI, Neill MA, Allen J, et al. The increasing incidence of the hemolytic-uremic syndrome in King County, Washington: lack of evidence for ascertainment bias. Am J Epidemiol. Mar 1989;129(3):582-6. [Medline].

  123. Tsai HM. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. J Mol Med. Oct 2002;80(10):639-47. [Medline].

  124. Tsai HM, Shulman K. Rituximab induces remission of cerebral ischemia caused by thrombotic thrombocytopenic purpura. Eur J Haematol. Mar 2003;70(3):183-5. [Medline].

  125. 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].

  126. Vesely SK, Perdue JJ, Rizvi MA, et al. Management of adult patients with persistent idiopathic thrombocytopenic purpura following splenectomy: a systematic review. Ann Intern Med. Jan 20 2004;140(2):112-20. [Medline].

  127. Zhou W, Inada M, Lee TP, et al. ADAMTS13 is expressed in hepatic stellate cells. Lab Invest. Jun 2005;85(6):780-8. [Medline].

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Further Reading

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Keywords

TTP, thrombocytic acroangiothrombosis, Schulman-Upshaw syndrome, Upshaw-Schulman syndrome, constitutional TTP, severe ADAMTS13 deficiency, thrombotic microangiopathy, TMA, hemolytic uremic syndrome, HUS, TTP-HUS, TTP/HUS, ADAMTS13, ADAMTS-13, Shiga toxin, Stx

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Contributor Information and Disclosures

Author

Robert Stanley Rust Jr, MD, MA, Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia; Chair-Elect, Child Neurology Section, American Academy of Neurology
Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

David A Griesemer, MD, Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina
David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Neurology, American Epilepsy Society, Child Neurology Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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