Thrombotic Thrombocytic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS) - Differentiation

10/03/01 (Phan)

Question: What is the difference between Thrombotic Thrombocytic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS)?

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Unique Identifier: 20370957 / PubMed Identifier: 10910429

Authors: Furlan M. Lammle B.

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Unique Identifier: 20073689 / PubMed Identifier: 10605756

Authors: Furlan M. Lammle B.

Institution: Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.

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Unique Identifier: 99274142 / PubMed Identifier: 10344345

Authors: Taylor CM. Howie AJ. Williams JM.

Institution: Department of Nephrology, The Birmingham Children's Hospital, UK.

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Unique Identifier: 99156241 / PubMed Identifier: 10048496

Authors: Ruggenenti P. Remuzzi G.

Institution: Mario Negri Institute for Pharmacological Research and Unit of Nephrology and Dialysis, Azienda Ospedaliera, Ospedali Riuniti di Bergamo, Italy.

Abstract: Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are syndromes of microangiopathic hemolytic anemia, and thrombocytopenia in which endothelial dysfunction appears to be an important factor in the sequence of events leading to microvascular thrombosis. They are termed thrombotic microangiopathies (TMA). Differentiation of the several primary forms of TMA is crucial to predict disease outcome and to establish the most appropriate therapeutic approach. Typical verotoxin-associated HUS, mostly due to E.coli 0157:H7 infection, is associated with prodromal diarrhea followed by acute renal failure, and considered a disease with a good outcome. Antibiotics are not necessary and antimotility agents are contraindicated. No specific therapies aimed at preventing or limiting the microangiopathic process have been proved to affect the course of the disease in children. Atypic HUS covers two clinical conditions: one characterized by severe gastrointestinal prodromes, acute onset anuria, and neurological involvement, and associated to high mortality rate; the second form without diarrhea prodromes but with progressive renal function deterioration and neurological involvement that resembles TTP. Supportive therapy is required in the diarrhea-associated form, while more specific therapies are needed in the latter form. Neurological symptoms usually dominate the clinical picture of acute TTP. Infusion or exchange of fresh frozen plasma have dramatically changed the outcome of a disease that in the sixties was almost invariably fatal. Relapsing episodes of TTP are being reported increasingly often because more patients recover from the initial acute episode thanks to improved treatments. Plasma infusion has been extensively used for this form of TTP, and remission of relapsing episodes documented in most cases. Plasma-resistant HUS or TTP have invariably a poor outcome if alternative treatments are not effective. Bilateral nephrectomy may be an effective rescue therapy for patients who failed to respond to plasma. Familial HUS/TTP is a form of TMA with recessive or dominant inheritance of unknown pathogenesis. The outcome is usually poor. In summary, a general consensus has been achieved that therapies (i.e. plasma exchange or infusion) aimed at stopping the microangiopathic process should always be tried in TTP and in adult and/or atypical forms of HUS to minimize the risk of death or long-term sequela. This approach is seldom effective in secondary forms whose outcome mainly depends on the prognosis of the underlying condition, and is not risk-effective in typical childhood HUS, that usually recovers spontaneously. [References: 58]

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Unique Identifier: 99151162 / PubMed Identifier: 10027100

Authors: Sutor GC. Schmidt RE. Albrecht H.

Institution: Medizinische Hochschule Hannover, Zentrum Innere Medizin, Germany.

Abstract: Haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are thrombotic microangiopathies increasingly reported in patients with HIV infection. However, characteristic features of thrombotic microangiopathies associated with HIV disease have not been defined yet. The typical courses of HUS and TTP in two patients are presented. The data as well as the analysis of cases published in the literature demonstrate the association of thrombotic microangiopathies with late-stage HIV disease. Moreover, differences between HUS and TTP can be detected. Patients with HUS present with more severe immunologic deterioration. Although clinical symptoms are fewer, HUS implicates a very poor prognosis. Life expectancy rarely exceeded 1 year after diagnosis. HUS and TTP should therefore be added to the international AIDS classification. [References: 45]

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Unique Identifier: 99092944 / PubMed Identifier: 9877117

Authors: Laurence J. Dang C.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 99032031 / PubMed Identifier: 9828246

Authors: Tsai HM. Lian EC.

Institution: Division of Hematology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY 10467, USA.

Abstract: BACKGROUND: Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, von Willebrand factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis. METHODS: We studied the activity of von Willebrand factor-cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin cofactor activity of purified von Willebrand factor in the cryosupernatant fraction of the plasma samples. RESULTS: Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of von Willebrand factor-cleaving protease. No deficiency was detected in 16 samples of plasma from patients with thrombotic thrombocytopenic purpura in remission or in 74 plasma samples from normal subjects, randomly selected hospitalized patients or outpatients, or patients with hemolysis, thrombocytopenia, or thrombosis from other causes. Inhibitory activity against the protease was detected in 26 of the 39 plasma samples (67 percent) obtained during the acute phase of the disease. The inhibitors were IgG antibodies. Shear stress increased the ristocetin cofactor activity of von Willebrand factor in the cryosupernatant of plasma samples obtained during the acute phase, but decreased the activity in cryosupernatant of plasma from normal subjects. CONCLUSIONS: Inhibitory antibodies against von Willebrand factor-cleaving protease occur in patients with acute thrombotic thrombocytopenic purpura. A deficiency of this protease is likely to have a critical role in the pathogenesis of platelet thrombosis in this disease.

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[Link Directly to Fulltext Article in OVID]

Unique Identifier: 99032030 / PubMed Identifier: 9828245

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

Institution: Central Hematology Laboratory, University Hospital, Bern, Switzerland.

Abstract: BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. METHODS: Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome. Von Willebrand factor-cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor-cleaving protease was present, we measured the protease activity in normal plasma after incubation with plasma from the patients. RESULTS: We examined 30 patients with thrombotic thrombocytopenic purpura and 23 patients with the hemolytic-uremic syndrome. Of 24 patients with nonfamilial thrombotic thrombocytopenic purpura, 20 had severe and 4 had moderate protease deficiency during an acute event. An inhibitor found in 20 of these patients was shown to be IgG in five of five tested plasma samples. Of 13 patients with nonfamilial hemolytic-uremic syndrome, 11 had normal levels of activity of von Willebrand factor-cleaving protease during the acute episode, whereas in 2 patients, the activity was slightly decreased. All 6 patients with familial thrombotic thrombocytopenic purpura lacked von Willebrand factor-cleaving protease activity but had no inhibitor, whereas all 10 patients with familial hemolytic-uremic syndrome had normal protease activity. In vitro proteolytic degradation of von Willebrand factor by the protease was studied in 5 patients with familial and 7 patients with nonfamilial hemolytic-uremic syndrome and was normal in all 12 patients. CONCLUSIONS: Nonfamilial thrombotic thrombocytopenic purpura is due to an inhibitor of von Willebrand factor-cleaving protease, whereas the familial form seems to be caused by a constitutional deficiency of the protease. Patients with the hemolyticuremic syndrome do not have a deficiency of von Willebrand factor-cleaving protease or a defect in von Willebrand factor that leads to its resistance to protease.

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Unique Identifier: 98133635 / PubMed Identifier: 9475488

Authors: Neild GH.

Institution: Institute of Urology and Nephrology, University College London Medical School, England, United Kingdom. g.neild@ucl.ac.uk

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Unique Identifier: 97263008 / PubMed Identifier: 9109216

Authors: Gordon LI. Kwaan HC.

Institution: Department of Medicine, Northwestern University Medical School, Chicago, IL, USA.

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Unique Identifier: 97220793 / PubMed Identifier: 9067955

Authors: Ruggenenti P. Lutz J. Remuzzi G.

Institution: Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Bergamo, Italy.

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Unique Identifier: 94133804 / PubMed Identifier: 7905557

Authors: Neild GH.

Institution: Division of Nephrology, Institute of Urology &#38; Nephrology, University College London Hospitals, University College London, UK.

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Unique Identifier: 94133803 / PubMed Identifier: 7905556

Authors: Moake JL.

Institution: Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030.