Amorosi EL and Ultmann JE.

Thrombotic thrombocytopenic purpura: report of 16 cases and review of the literature.
Medicine. 1966; 45: 139–159.
Description: This is a wonderful review of the clinical manifestations of thrombotic thrombocytopenic purpura (TTP) at diagnosis in 271 previously reported cases of and provides important information about the natural history of the disease in an era when effective therapy was lacking.

Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, Seder RH, Hong SL, and Deykin D.

Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura.
N Engl J Med. 1982 Dec 2; 307(23): 1432-1435.
Description: This was the first study to implicate unusually large vWF multimers in the pathogenesis of TTP and postulate that the above phenomenon was due to the deficiency of a plasma-derived protease.
PubMed citation number: 6813740

Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, Krause M, Scharrer I, Aumann V, Mittler U, Solenthaler M, and Lammle B.

von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.
N Engl J Med. 1998 Nov 26; 339(22): 1578-1584.
PubMed citation number: 9828245

Tsai HM and Lian EC.

Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998 Nov 26; 339(22): 1585-1594.
PubMed citation number: 9828246
Description: The above two groups independently characterized the von Willebrand factor cleaving protease, currently known as ADAMTS13, and identified inhibitory antibodies to ADAMTS13 in patients with acquired TTP. Both studies also suggest that antibodies to ADAMTS13 are specific for TTP and help distinguish it from hemolytic uremic syndrome (HUS), however neither study described how patients with TTP were distinguished from those with HUS.

Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, and Tsai HM.

Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura.
Nature. 2001 Oct 4; 413(6855): 488-494.
Description: The above study identified mutations in the ADAMTS13 gene in families with congenital TTP, thereby demonstrating a role for ADAMTS13 in normal vascular homeostasis and identifying the likely gene product to which inhibitory antibodies are directed in acquired TTP.
PubMed citation number: 11586351

Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, and Spasoff RA.

Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group.
N Engl J Med. 1991 Aug 8; 325(6): 393-397.
Description: The above study demonstrated that plasma exchange: 1) is an effective therapy for TTP; 2) is better than plasma infusion alone (although the difference in volume of plasma infused between the two arms remains a point of contention) and 3) established plasma exchange as the standard of care for patients with this disease.
PubMed citation number: 2062330

Shumak KH, Rock GA and Nair RC.

Late relapses in patients successfully treated for thrombotic thrombocytopenic purpura. Canadian Apheresis Group.
Ann Intern Med. 1995 Apr 15; 122(8): 569-572.
Description: This study shows that while therapeutic plasma exchange is effective in the treatment of TTP, over one-third (36%) of patients will have one or more relapses over a follow-up of ten years.
PubMed citation number: 7887549

Vesely SK, George JN, Lammle B, Studt JD, Alberio L, El-Harake MA, and Raskob GE.

ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients.
Blood. 2003 Jul 1; 102(1): 60-8.
Description: This study showed that while severely low (<5%) von Willebrand factor-cleaving protease activity levels are specific for idiopathic TTP, they are not sensitive nor do they predict who will respond to plasma exchange, thus limiting the clinical utility of this test.
PubMed citation number: 12637323

Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, and Lior H.

The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli.
J Infect Dis. 1985 May; 151(5): 775-82.
Description: This study firmly established verotoxin-producing Escherichia coli as the inciting infectious agent in most children with diarrheal illness-related hemolytic uremic syndrome.
PubMed citation number: 3886804

Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, and Clark WF.

Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression.
JAMA. 2003 Sep 10; 290(10): 1360-70.
Description: The above meta-analysis of the clinical course of diarrhea-associated HUS better defines clinical features that portend worse long-term renal outcomes in patients with this disease.
PubMed citation number: 12966129

Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Muslumanoglu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, and Goodship TH.

Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome.
Proc Natl Acad Sci. 2003 Oct 28; 100(22): 12966-71.
PubMed citation number: 14566051

Warwicker P, Goodship TH, Donne RL, Pirson Y, Nicholls A, Ward RM, Turnpenny P, and Goodship JA.

Genetic studies into inherited and sporadic hemolytic uremic syndrome. Kidney Int. 1998 Apr; 53(4): 836-44.
PubMed citation number: 9551389
Description: The above two studies identified inactivating mutations in the membrane cofactor protein (MCP) and factor H genes, gene products that negatively regulate C3b deposition on target substrates, in patients with familial HUS. These studies: 1) provide a biologic rationale for the observation of low C3 levels in many patients with HUS; and 2) provide a framework for investigating complement deregulation in patients with the more common sporadic variant of the disease.

Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, Yarnold PR, Kwaan HC, and Green D.

Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases.
Ann Intern Med. 1998 Apr 1; 128(7): 541-4.
PubMed citation number: 9518398

Kojouri K, Vesely SK, and George JN.

Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes.
Ann Intern Med. 2001 Dec 18; 135(12): 1047-1051.
Description: This study established quinine as an important and under-recognized cause of drug-related TTP-HUS and reviews the clinical features of this entity.
PubMed citation number: 11747383

Lesesne JB, Rothschild N, Erickson B, Korec S, Sisk R, Keller J, Arbus M, Woolley PV, Chiazze L, Schein PS, et al.

Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry.
J Clin Oncol. 1989 Jun; 7(6): 781-9.
Description: This registry identified a severe, therapy-refractory, TTP-HUS syndrome associated with the use of mitomycin-C for patients with a variety of solid tumors, most notably gastrointestinal adenocarcinomas. This study also demonstrates that while the pathologic and clinical features of TTP-HUS can occur in a variety of disorders, the underlying pathophysiology of mitomycin-C-associated TTP-HUS is likely different given the poor clinical responses to therapeutic plasma exchange.
PubMed citation number: 2497229

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. 2004 Feb; 44(2): 294-304.
Description: This is a systematic review of the literature that characterizes the clinical features of TTP-HUS in the allogeneic bone marrow / stem cell transplantation setting and suggests that, in most cases, these patients have other systemic diseases mimicking the entity of TTP-HUS.
PubMed citation number: 14962323

Select review articles

McCrae KR, Cines DB.

Thrombotic microangiopathy during pregnancy.
Semin Hematol. 1997 Apr; 34(2): 148-58.
PubMed citation number: 9109217

George JN, Sadler JE, Lammle B.

Platelets: thrombotic thrombocytopenic purpura.
Hematology (Am Soc Hematol Educ Program). 2002;:315-34.
PubMed citation number: 12446430

Moake JL.

Thrombotic microangiopathies.
N Engl J Med. 2002 Aug 22; 347(8): 589-600.
PubMed citation number: 12192020

George JN.

How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
Blood. 2000 Aug 15; 96(4): 1223-9.
PubMed citation number: 10942361

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