Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe haemophilia A

Williams, Lance A.; Drwiega, Joseph C.; Cao, Wenjing; Pham, Huy P.; Bertoli, Luigi F.; Zheng, X. Long

doi:10.1111/hae.13091

Cited by 4 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The incidence of TTP in the general population is approximately 10 per million per year . TMA has rarely been observed in hemophilia patients undergoing factor replacement therapy . Thus, the development of this complication in 3 of 109 patients in the HAVEN 1 trial was immediately perceived as unlikely to be a chance occurrence.…”

Section: Thrombotic Microangiopathymentioning

confidence: 99%

Emicizumab and thrombosis: The story so far

Makris

Iorio

Lenting

2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

Section: Thrombotic Microangiopathymentioning

confidence: 99%

Emicizumab and thrombosis: The story so far

Makris

Iorio

Lenting

2019

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

show abstract

“…Although some mechanisms of DITMA have been proposed, such as complement activation 20 , for most cases, the underlying mechanisms are unknown. TMA has been rarely reported in PwHA 21 ; therefore, its occurrence in participants who had received emicizumab and a concomitant cumulative dose of > 100 U/kg/24 h of aPCC for at least 24 h in the HAVEN 1 14 trial is unlikely to be a chance occurrence 22 . Moreover, TMA in those individuals, in contrast to the typical clinical course, resolved rapidly following discontinuation of the bypassing agent, aPCC 22 .…”

Section: Introductionmentioning

confidence: 97%

Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab

Valls

Wagg

Paz‐Priel³

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Emicizumab is a bispecific monoclonal antibody that substitutes for the function of missing or deficient factor VIII (FVIII) in people with hemophilia A (PwHA). Long-term safety and efficacy of emicizumab have been demonstrated in several clinical trials. Nevertheless, in the first of these, three cases of thrombotic microangiopathy (TMA) occurred in PwHA treated with emicizumab receiving high doses of activated prothrombin complex concentrate (aPCC), a bypassing agent used for treating breakthrough bleeds when FVIII neutralizing antibodies (inhibitors) make FVIII replacement ineffective. The aim of the present work is to offer a method to elucidate the pathophysiological and pharmacological mechanisms involved in this treatment-induced TMA. Systems biology and machine learning-based Therapeutic Performance Mapping System is a validated in silico technology that allowed us to construct models of potential mechanisms behind induced TMA. Two drug combinations were modeled and assessed: emicizumab plus aPCC and emicizumab plus recombinant activated factor VII (another bypassing agent). Our models showed that both combinations were related to activation of the coagulation cascade. However, mechanisms involved mainly in platelet activation and possibly in complement activation were detected only for emicizumab plus aPCC, potentially explaining the occurrence of TMA only in this combination.

show abstract

Acquired haemophilia A with a recalcitrant high-titre factor VIII inhibitor in the setting of interstitial lung disease

Sun

Sykes²

2017

BMJ Case Reports

View full text Add to dashboard Cite

Acquired haemophilia A (AHA) is a bleeding disorder that results from autoantibodies against factor VIII (FVIII). A 70-year-old man with a history of interstitial lung disease presented with spontaneous bleeding into his thigh. He had undetectable FVIII levels and a high-titre FVIII inhibitor (>2000Ã¢â'¬â€°Bethesda units/mL) and was diagnosed with AHA. He had several relapses, required multiple haemostatic and immunosuppressive treatments but eventually achieved a stable remission after 2Ã¢â'¬â€°years of therapy.Our patient matches the typical elderly male demographic of AHA. His relapsing course with remarkably high and persistent inhibitor titre highlights the need for close monitoring and aggressive upfront treatment. Whereas cyclophosphamide and steroids are often used first line in AHA, rituximab has also shown efficacy in refractory patients with high inhibitor levels. The FVIII and inhibitor concentration on presentation have been associated with treatment response and may be used as prognostic factors to tailor immunosuppressive regimens.

show abstract

Acquired autoimmune thrombotic thrombocytopenic purpura in a case of severe haemophilia A

Cited by 4 publications

References 9 publications

Emicizumab and thrombosis: The story so far

Emicizumab and thrombosis: The story so far

Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab

Acquired haemophilia A with a recalcitrant high-titre factor VIII inhibitor in the setting of interstitial lung disease

Contact Info

Product

Resources

About