Thrombotic Thrombocytopenic Purpura: aetiology, pathophysiology and treatment

Murrin, Richard; Murray, Jaclyn Kuspiel

doi:10.1016/j.blre.2005.02.001

Cited by 50 publications

(27 citation statements)

References 89 publications

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“…49 However, autoantibodies against the enzyme are present in up to 5% of healthy individuals, 50,51 and might become problematic under VEGF inhibition. In addition, certain patient groups such as those suffering from immunomediated diseases like SLE and the antiphospholipid antibody syndrome can be far more susceptible to the development of inhibitory autoantibodies.…”

Section: /2mentioning

confidence: 99%

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

Erpenbeck

Demers

Zsengellér

et al. 2016

Journal of the American Society of Nephrology

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Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13 2/2 mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13 2/2 mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.

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Section: /2mentioning

confidence: 99%

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

Erpenbeck

Demers

Zsengellér

et al. 2016

Journal of the American Society of Nephrology

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“…Indeed, thrombocytopenic disorders complicating endocarditis that clinically resemble TTP have been reported previously [4,5,20]. As TTP is life-threatening and can be treated effectively by plasma exchange [21], we started daily plasmapheresis with cryosupernatant plasma exchange over a 2-week period. However, the platelet count did not improve with this therapy.…”

Section: Discussionmentioning

confidence: 99%

Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with Staphylococcus epidermidis: Role of monocyte procoagulant activity induced by bacterial supernatant

Selleng¹,

Warkentin²,

Greinacher³

et al. 2006

American J Hematol

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The pathogenesis of very severe thrombocytopenia in bacterial endocarditis is uncertain. We report a 50‐year‐old male with platelet counts < 10 × 109/l and fragmentation hemolysis complicating Staphyloccoccus epidermidis pacemaker endocarditis with a giant vegetation. Antibiotics, corticosteroids, high‐dose intravenous gammaglobulin, and plasmapheresis (for initially‐suspected thrombotic thrombocytopenic purpura) failed to produce significant platelet count increase. However, therapeutic‐dose heparin anticoagulation was associated with a platelet count increase from <10 to ∼40 × 109/l, with parallel reduction in thrombin‐antithrombin complexes (from 8.9 to 3.5 μg/l), facilitating surgical intervention. The thrombocytopenia promptly resolved following surgical removal of the vegetation. Culture supernatant from S. epidermidis isolated from the patient's blood induced monocytes to express procoagulant activity (assessed by factor Xa generation) equivalent to lipopolysaccharide (1 μg/ml), with half‐maximal activation seen with culture supernatant diluted to 1:12,800. These data are consistent with previous animal models of endocarditis demonstrating staphylococci‐induced procoagulant changes in monocytes. This case demonstrates that heparin anticoagulation can be therapeutic in infective endocarditis‐associated severe thrombocytopenia in a non‐bleeding patient, and that such therapy may ameliorate the platelet count enough to permit surgical intervention. Am. J. Hematol 2007. © 2006 Wiley‐Liss, Inc.

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“…La grossesse ne semble pas associée à un taux de mortalité supérieur [18]. Le risque hémorragique est limité malgré la présence d'une thrombopénie volontiers profonde [41]. La mortalité est le plus souvent due aux complications microangiopathiques.…”

Section: Associés Au Purpura Thrombotique Thrombocytopénique Et Au Syunclassified

Thrombopénie et grossesse : du diagnostic étiologique à la prise en charge thérapeutique

et al. 2008

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Thrombotic Thrombocytopenic Purpura: aetiology, pathophysiology and treatment

Cited by 50 publications

References 89 publications

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

Very severe thrombocytopenia and fragmentation hemolysis mimicking thrombotic thrombocytopenic purpura associated with a giant intracardiac vegetation infected with Staphylococcus epidermidis: Role of monocyte procoagulant activity induced by bacterial supernatant

Thrombopénie et grossesse : du diagnostic étiologique à la prise en charge thérapeutique

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