Thromboembolic Risks of Non-Factor Replacement Therapies in Hemophilia

Tiede, Andreas

doi:10.5482/20170004

Cited by 21 publications

(26 citation statements)

References 25 publications

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“…However, a sinus vein thrombosis was observed in a noninhibitor HA patient with the combination of fitusiran and FVIII product (see fitusiran description in "Thromboembolic risk"). 31,66,67 Following this SAE, the fitusiran trials were immediately suspended. After widespread consideration of clinical risk and safety assessment, including the education strategy and protocolspecified guidelines (reduced dosing of FVIII or BPAs) to treat breakthrough bleeds in these circumstances, these trials have been reopened.…”

Section: Fitusiranmentioning

confidence: 99%

“…Thromboembolic risk Three TMAs and 2 VTEs (sinus vein thrombosis and superficial thrombophlebitis) under prophylactic emicizumab were recorded. 30,31 One patient developed TMA after 4 consecutive days of aPCC treatment for rectal bleeding, which was eventually fatal, although the TMA had resolved at the time of death. All thromboembolic events commonly occurred during adjunctive treatment with aPCC for breakthrough bleeds, and the thrombotic risk appeared to be dose related.…”

Section: Challenges To Address For Nonfactor Productsmentioning

confidence: 99%

“…A thromboembolic event was reported in a noninhibitor HA patient with a concomitant therapy of fitusiran and FVIII product. 31,66,67 Supplementary therapeutic doses of FVIII (31-46 U/kg) were given for breakthrough bleeds, but the patient complained of a severe headache. A subarachnoid hemorrhage was diagnosed by computed tomography, and FVIII replacement was continued.…”

Section: Challenges To Address For Nonfactor Productsmentioning

confidence: 99%

“…64,65 A thrombotic event occurred with FVIII replacement in a noninhibitor patient. 31 The protocol-specified reduced dosing of FVIII or BPAs has been used for the treatment of breakthrough bleeds, and no thrombotic events have occurred. BPA treatment at breakthrough bleeds has not been reported in concizumab-treated inhibitor patients.…”

Section: Breakthrough Bleedsmentioning

confidence: 99%

“…Complications of thrombotic microangiopathy (TMA) and thromboembolism in 5 emicizumab-treated patients receiving aPCC and a sinus vein thrombosis in a fitusiran-treated patient receiving FVIII products have been reported. 30,31 A current review focuses on current clinical trial data for nonfactor products that offer the potential for a paradigm shift in hemophilia treatment.…”

Section: Introductionmentioning

confidence: 99%

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New therapies using nonfactor products for patients with hemophilia and inhibitors

Nogami

Shima

2019

Blood

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Regular prophylaxis with factor VIII (FVIII) or FIX products to prevent bleeding in patients with severe hemophilia A (HA) and HB, respectively, results in marked suppression of the onset of arthropathy and contributes greatly to improvements in quality of life. Some issues remain with the use of clotting factor replacement therapy, however. The need for multiple IV infusions is associated with a substantial mental and physical burden, and the hemostatic effect of bypassing agents (BPAs) in patients with inhibitor is inconsistent. The development of subcutaneous products with prolonged hemostatic efficiency, irrespective of the presence of inhibitors, has been a longtime wish for patients. A new class of therapeutic agents that act by enhancing coagulation (emicizumab) and inhibiting anticoagulant pathways (fitusiran and concizumab) have been established, and clinical trials using these nonfactor products are ongoing. The current findings have demonstrated that prophylaxis by nonfactor products supports marked reductions of bleeding episodes in hemophilia patients with or without inhibitor. Emicizumab has already been approved for use internationally. Some concerns are evident, however. Thrombotic microangiopathy and thromboembolism have occurred in 5 emicizumab-treated patients receiving repeated infusions of activated prothrombin complex concentrates, and a sinus vein thrombosis has occurred in a fitusiran-treated patient receiving repeated infusions of FVIII product. Moreover, reliable techniques to monitor hemostatic function in patients receiving nonfactor products with concomitant BPA or FVIII/FIX therapies require further assessment. These novel therapeutic agents have promising hemostatic properties, although wider experience in hemophilia centers is warranted to establish appropriate therapeutic strategies.

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Section: Fitusiranmentioning

confidence: 99%

Section: Challenges To Address For Nonfactor Productsmentioning

confidence: 99%

Section: Challenges To Address For Nonfactor Productsmentioning

confidence: 99%

Section: Breakthrough Bleedsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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