Thrombotic thrombocytopenic purpura associated with polyarteritis nodosa

Fujisaki, Kazuhiro; Masutani, Kosuke; Yoshimitsu, Takahiro; Nakanishi, Keita; Matsumoto, Michio; Yagi, Haruna; Ishizashi, H.; Fujimura, Yoshihiro; Takeda, Kazuhito; Hirakata, Hideki; Iida, Mitsuo

doi:10.5414/cnp64305

Cited by 14 publications

(8 citation statements)

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“…Decreased ADAMTS13 activity (<5%) is specific for TTP and this impaired ability to cleave large von-Willebrand-factor multimers eventually traps platelets leading to thrombotic occlusion of the capillaries [1]. While severe deficiency of ADAMTS13 activity in familial TTP may occur from ADAMTS13 gene mutations [7], numerous case studies have reported the association of TTP with autoimmune diseases including SLE [2] and polyarteritis nodosa [8]. Possible mechanisms for the association of autoimmune diseases with TTP include antibody-mediated reduced ADAMTS13 activity or endothelial injury.…”

Section: Discussionmentioning

confidence: 99%

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

Agrawal

Vaidya

et al. 2011

Pediatr Nephrol

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Thrombotic thrombocytopenic purpura (TTP) rarely occurs with systemic vasculitis. A 17-year-old girl presented with non-bloody diarrhea, menorrhagia, and syncope. She had severe anemia (hemoglobin = 3.8 g/dl), thrombocytopenia (platelet = 7,000/mm(3)), and acute kidney injury (serum creatinine, Cr = 2.3 mg%). Peripheral smear examination confirmed the presence of microangiopathic hemolytic anemia. Additionally, she had a positive anti-nuclear antibody (1:1600) and normal complement levels. We considered the diagnosis of TTP, possibly associated with systemic lupus erythematosus, and promptly initiated pulse methylprednisolone and daily 3-4 l of plasma exchange therapy. Following resolution of her thrombocytopenia in 48 h, we performed a kidney biopsy that revealed diffuse proliferative, focal crescentic, and necrotizing glomerulonephritis with mild IgG immunofluorescence staining. Concomitantly, autoimmune work-up was significant for positive perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA = 1:640) and decreased von Willebrand factor cleaving protease activity (<5%). A final diagnosis of TTP with microscopic polyangiitis (p-ANCA-mediated) was made and treatment with daily oral cyclophosphamide and prednisone resolved her renal injury over 2 months (follow-up Cr = 1.0 mg%). Our case highlights the importance of identifying systemic disorders such as ANCA-associated vasculitis with TTP.

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Section: Discussionmentioning

confidence: 99%

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

Agrawal

Vaidya

et al. 2011

Pediatr Nephrol

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“…[20][21][22] Conversely, patients with idiopathic TTP and severe ADAMTS13 deficiency (< 5%) often have manifestations of systemic lupus erythematosus or other autoimmune diseases, such as antinuclear antibodies, polyarthritis, malar rash, extramembranous glomerulonephritis, discoid lupus, or autoimmune thyroiditis. 23 Many autoimmune diseases can cause hemolytic anemia, thrombocytopenia and organ dysfunction by several mechanisms, and ADAMTS13 testing may facilitate the recognition of idiopathic TTP in these complex cases.…”

Section: Iiib Exceptional Causes Of Autoimmune Ttpmentioning

confidence: 99%

Thrombotic Thrombocytopenic Purpura: A Moving Target

Sadler

2006

Hematology

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Almost 80 years after Eli Moschcowitz published the first description of the disease, most patients with idiopathic thrombotic thrombocytopenic purpura (TTP) were found to have acquired autoantibody inhibitors of the ADAMTS13 metalloprotease. Plasma ADAMTS13 normally cleaves von Willebrand factor within nascent platelet-rich thrombi, and ADAMTS13 deficiency allows unchecked thrombus growth to cause microangiopathic hemolysis, thrombocytopenia, and tissue infarction. At present, ADAMTS13 deficiency with a high-titer inhibitor level appears to be associated with an increased risk of early death and subsequent relapse. Thus, acquired ADAMTS13 deficiency identifies a specific mechanism of TTP and is a potential biomarker of disease activity or risk. At present, two major clinical questions in the field may be summarized as follows. First, by emphasizing TTP caused by ADAMTS13 deficiency, are we in danger of neglecting other causes that should be treated with plasma exchange? Second, should we treat asymptomatic patients who have severe ADAMTS13 deficiency to prevent future disease, and if so, how?The last few years have set the stage for a new approach to the management of thrombotic thrombocytopenic purpura (TTP). The criteria for idiopathic TTP have remained approximately constant, and plasma exchange is still the standard therapy. But the discovery of the ADAMTS13 metalloprotease has revolutionized our understanding of TTP and initiated a period of experimentation with regard to diagnosis and treatment. The management of TTP has been reviewed recently, 1 and I will not discuss it comprehensively. Instead, I will try to integrate the new knowledge about ADAMTS13 into a model for the pathogenesis of TTP, relate it to our experience in caring for these patients, and suggest where we may look for further advances during the next few years.

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“…[51][52][53] Patients with autoimmune diseases such as systemic lupus erythematosis can develop thrombocytopenia and neurologic dysfunction as a result of vasculitis, but they also can have autoimmune ADAMTS13 deficiency. 37,[54][55][56] Thrombotic microangiopathy during pregnancy may be caused by preeclampsia or HELLP (hemolysis, elevated liver function, and low platelets) syndrome, which are not associated with ADAMTS13 deficiency. 57 However, pregnancy can also induce acute TTP in women with congenital or acquired ADAMTS13 deficiency, 58 and ADAMTS13 assays may be useful to identify patients who could benefit from prophylactic plasma exchange therapy during pregnancy.…”

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confidence: 99%

Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura

Sadler

2008

Blood

507

398

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Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency. Clinical features of idiopathic TTPIn January of 1924 1 and apparently for a second time in February, 2 Moschcowitz presented a case before the New York Pathological Society of "a hitherto undescribed disease (ref. 1 at 21)" that he felt was "remarkable, clinically and anatomically (ref. 2 at 89)." A healthy 16-year-old girl suddenly developed weakness in her arms, pain on moving her wrists and elbows, pallor, and fever (38°C-39°C). Her symptoms worsened and on the tenth day of illness she was admitted to the hospital with anemia, leukocytosis, a few petechiae on one arm, and occult blood in gastric contents and stool. The serum creatinine was normal. Four days later she developed mild left hemiparesis and facial paralysis. The next day she became comatose and died. A limited autopsy showed hyaline thrombi in terminal arterioles and capillaries of the heart, kidney, spleen, and liver; the lungs were spared. Moschcowitz did not obtain a platelet count and did not report schistocytes in the blood film, so we do not have a complete description from him of thrombocytopenia or microangiopathic hemolytic anemia. But based on the pathology at autopsy, we recognize this patient as the first published example of idiopathic thrombotic thrombocytopenic purpura (TTP).During the next 50 years, the clinical features of TTP became progressively better defined. Most patients were females between the ages of 10 and 39, and they usually exhibited a pentad of signs without obvious alternative causes: microangiopathic hemolytic anemia, thrombocytopenia, neurologic findings, renal damage, and fever. Unfortunately, the prognosis remained grim: mortality exceeded 90%, the average hospital stay was 14 days before death, and 80% of patients died within 3 months after the onset of symptoms. 3 Plasma therapyMoschcowitz also reported that one of his colleagues, Lederer, had seen 4 patients resembling his own case, and all recovered promptly after a single blood transfusion. 2 Lederer published his observations 4,5 but none of the patients had significant thrombocytopenia, which cast doubt on their diagnosis, a...

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Thrombotic thrombocytopenic purpura associated with polyarteritis nodosa

Cited by 14 publications

References 0 publications

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent

Thrombotic Thrombocytopenic Purpura: A Moving Target

Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura

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