The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders

Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe; Stenner, Rachel

doi:10.1160/th06-06-0317

Cited by 51 publications

(6 citation statements)

References 68 publications

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“…Previously, the total published literature has described the effect of immunosuppression with steroids and cytotoxics in 345 patients 1 ; this study reports on 225 patients. A recent review on the role of rituximab described 65 patients, 21 and this study reports on a further 51 patients. As such, the data described here contribute substantially to the published literature.…”

Section: Discussionmentioning

confidence: 91%

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Collins

Baudo

Knöbl

et al. 2012

Blood

301

423

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Section: Discussionmentioning

confidence: 91%

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Collins

Baudo

Knöbl

et al. 2012

Blood

301

423

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“…Published small series and case reports have described approximately 100 patients with refractory or relapsing idiopathic TTP treated with rituximab, usually at doses of 375 mg/m 2 weekly for an average of 4 doses. 64,68,69 Approximately 95% of reported patients have had a complete clinical and laboratory responses within 1 to 3 weeks of starting treatment, including a normal ADAMTS13 level and disappearance of anti-ADAMTS13 antibodies. Mild acute reactions to ritixumab infusions were controlled by premedication with steroids, antihistamines, and analgesics.…”

Section: When Should We Use Immunosuppressive Therapy For Idiopathic mentioning

confidence: 99%

Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura

Sadler

2008

Blood

509

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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“…70 Although this agent was originally developed for the use in patients with B-cell non-Hodgkin lymphomas, its use has been successfully extended to many autoimmune disorders. 71 Indeed, biotherapy with rituximab has been also used to treat cohorts of patients with acquired hemophilia. 72 Wiestner et al 73 described 3 patients with high-titer FVIII autoantibodies who experienced rapid and durable responses following treatment with rituximab alone or in association immunosuppressive therapy.…”

Section: Novel Eradicating Therapies: Rituximabmentioning

confidence: 99%

“…We have recently reviewed the literature data and collected 65 patients with acquired hemophilia A treated with this agent. 71 In the majority of the cases, the dosing regimen of rituximab was 375 mg/m 2 weekly for 4 weeks, with the cycle repeated if the patient relapsed. Although a response was observed in more than 90% of cases, we advise caution in the overinterpretation of these data as they are derived from case reports or small trials.…”

Section: Novel Eradicating Therapies: Rituximabmentioning

confidence: 99%

Acquired factor VIII inhibitors

Franchini

Lippi

2008

Blood

Self Cite

248

321

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Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with hightiter inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors. (Blood. 2008;112:250-255)

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The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders

Cited by 51 publications

References 68 publications

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura

Acquired factor VIII inhibitors

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