OSELTAMIVIR IN THE TREATMENT OF PRIMARY IMMUNE THROMBOCYTOPENIA
(Abstract release date: 05/19/16)
EHA Library. H. 06/09/16; 134970; PB2070
Dr. Heidy
Contributions
Contributions
Abstract
Abstract: PB2070
Type: Publication Only
Background
Primary immune thrombocytopenia (ITP) is an immune bleeding disorder with an increased destruction of autologous platelets. Autoantibody specificity is usually against GPIIb/IIIa in 70-80% of patients or GPIb in 20% of them. Firts–line treatment includes immunosuppressive and immunomodulatory agents, that is corticosteroids (CS) or intravenous immunoglobulin (IVIG). Splenectomy is considered for patients with persistent lack of response. However, about 20% patients are inexplicably refractory to both therapies. Recent studies in refractory ITP patients suggest an association between anti-GPIb autoantibody and a poor response to conventional therapies, as well as platelet desialylation. This leads to platelet elimination by hepatocyte Ashwell-Morell receptors, especially in the absence of macrophages. Therefore, it may be a role for sialidase inhibitors in ITP treatment. Oseltamivir phosphate conventionally serves as anti-influenza agent. It inhibits viral neuraminidase as well as glycolipids sialylation on human T cells surface.We report a case of an adult ITP patient who was resistant to multiple therapeutic approaches but was successfully treated with Oseltamivir phosphate.
Methods
CASE REPORT: A 64-year-old female was diagnosed with ITP. She was initially treated with high dose CS and IVIG, with a complete response (CR) that lasted for 15 years. She relapsed with severe thrombocytopenia and minor bleeding. Her platelet counts remained low despite using CS and IGIV, so she initiated recombinant human thrombopoietin (TPO) agonist reaching maximum dose without response, so we added danazol and rituximab, either with non response. During this period, she presented with lower gastrointestinal bleeding so she underwent a splenectomy. She continued with TPO agonist and Danazol to maximum doses. Three months after splenectomy she reached secure but fluctuating platelet counts, presenting a massive portal and mesenteric thrombosis. She started therapeutical LMWH with close monitoring of platelets count, and suspended TPO agonist as well as danazol. Two months later, she lost platelet response and had to iniciate different immunosuppressive drugs: Vincristine, Azathioprine, Mycophenolate Mofetil and Cyclosporin, without response. Patient´s platelet was then assessed by flow cytometry and revealed a loss of terminal sialic acids in platelets surface as well as neuraminidase activity in plasma, data compatible with a platelet destruction mechanism independent of immune receptors that could justify refractoriness to prior treatments.An alternative therapeutic regimen with Oseltamivir phosphate, as a last resort for the management of this patient, was initiated. She was informed and consented. It was given orally 75mg twice daily for 5 days. Then, a new platelet assessment was done, demonstrating normalization of sialic acids expression. But thrombocytopenia persisted, so Azathioprine was added looking for a synergic effect. Nowadays, she continues treatment with Azathioprine twice a day and remains in CR for seven months
Conclusion
CONCLUSION: In this case, treatment with oseltamivir could restore platelet membrane, avoiding its destruction by the hepatic rethiculoendothelial system and allowing immunosuppressive drugs (Azathioprine) to control the immune destruction mechanism. At the present time Oseltamivir is not still approved for ITP. However, this case highlights the need for prospective studies to verify the effectiveness of this new approach and the possibility of new indications for this drug.
Session topic: E-poster
Type: Publication Only
Background
Primary immune thrombocytopenia (ITP) is an immune bleeding disorder with an increased destruction of autologous platelets. Autoantibody specificity is usually against GPIIb/IIIa in 70-80% of patients or GPIb in 20% of them. Firts–line treatment includes immunosuppressive and immunomodulatory agents, that is corticosteroids (CS) or intravenous immunoglobulin (IVIG). Splenectomy is considered for patients with persistent lack of response. However, about 20% patients are inexplicably refractory to both therapies. Recent studies in refractory ITP patients suggest an association between anti-GPIb autoantibody and a poor response to conventional therapies, as well as platelet desialylation. This leads to platelet elimination by hepatocyte Ashwell-Morell receptors, especially in the absence of macrophages. Therefore, it may be a role for sialidase inhibitors in ITP treatment. Oseltamivir phosphate conventionally serves as anti-influenza agent. It inhibits viral neuraminidase as well as glycolipids sialylation on human T cells surface.We report a case of an adult ITP patient who was resistant to multiple therapeutic approaches but was successfully treated with Oseltamivir phosphate.
Methods
CASE REPORT: A 64-year-old female was diagnosed with ITP. She was initially treated with high dose CS and IVIG, with a complete response (CR) that lasted for 15 years. She relapsed with severe thrombocytopenia and minor bleeding. Her platelet counts remained low despite using CS and IGIV, so she initiated recombinant human thrombopoietin (TPO) agonist reaching maximum dose without response, so we added danazol and rituximab, either with non response. During this period, she presented with lower gastrointestinal bleeding so she underwent a splenectomy. She continued with TPO agonist and Danazol to maximum doses. Three months after splenectomy she reached secure but fluctuating platelet counts, presenting a massive portal and mesenteric thrombosis. She started therapeutical LMWH with close monitoring of platelets count, and suspended TPO agonist as well as danazol. Two months later, she lost platelet response and had to iniciate different immunosuppressive drugs: Vincristine, Azathioprine, Mycophenolate Mofetil and Cyclosporin, without response. Patient´s platelet was then assessed by flow cytometry and revealed a loss of terminal sialic acids in platelets surface as well as neuraminidase activity in plasma, data compatible with a platelet destruction mechanism independent of immune receptors that could justify refractoriness to prior treatments.An alternative therapeutic regimen with Oseltamivir phosphate, as a last resort for the management of this patient, was initiated. She was informed and consented. It was given orally 75mg twice daily for 5 days. Then, a new platelet assessment was done, demonstrating normalization of sialic acids expression. But thrombocytopenia persisted, so Azathioprine was added looking for a synergic effect. Nowadays, she continues treatment with Azathioprine twice a day and remains in CR for seven months
Conclusion
CONCLUSION: In this case, treatment with oseltamivir could restore platelet membrane, avoiding its destruction by the hepatic rethiculoendothelial system and allowing immunosuppressive drugs (Azathioprine) to control the immune destruction mechanism. At the present time Oseltamivir is not still approved for ITP. However, this case highlights the need for prospective studies to verify the effectiveness of this new approach and the possibility of new indications for this drug.
Session topic: E-poster
Abstract: PB2070
Type: Publication Only
Background
Primary immune thrombocytopenia (ITP) is an immune bleeding disorder with an increased destruction of autologous platelets. Autoantibody specificity is usually against GPIIb/IIIa in 70-80% of patients or GPIb in 20% of them. Firts–line treatment includes immunosuppressive and immunomodulatory agents, that is corticosteroids (CS) or intravenous immunoglobulin (IVIG). Splenectomy is considered for patients with persistent lack of response. However, about 20% patients are inexplicably refractory to both therapies. Recent studies in refractory ITP patients suggest an association between anti-GPIb autoantibody and a poor response to conventional therapies, as well as platelet desialylation. This leads to platelet elimination by hepatocyte Ashwell-Morell receptors, especially in the absence of macrophages. Therefore, it may be a role for sialidase inhibitors in ITP treatment. Oseltamivir phosphate conventionally serves as anti-influenza agent. It inhibits viral neuraminidase as well as glycolipids sialylation on human T cells surface.We report a case of an adult ITP patient who was resistant to multiple therapeutic approaches but was successfully treated with Oseltamivir phosphate.
Methods
CASE REPORT: A 64-year-old female was diagnosed with ITP. She was initially treated with high dose CS and IVIG, with a complete response (CR) that lasted for 15 years. She relapsed with severe thrombocytopenia and minor bleeding. Her platelet counts remained low despite using CS and IGIV, so she initiated recombinant human thrombopoietin (TPO) agonist reaching maximum dose without response, so we added danazol and rituximab, either with non response. During this period, she presented with lower gastrointestinal bleeding so she underwent a splenectomy. She continued with TPO agonist and Danazol to maximum doses. Three months after splenectomy she reached secure but fluctuating platelet counts, presenting a massive portal and mesenteric thrombosis. She started therapeutical LMWH with close monitoring of platelets count, and suspended TPO agonist as well as danazol. Two months later, she lost platelet response and had to iniciate different immunosuppressive drugs: Vincristine, Azathioprine, Mycophenolate Mofetil and Cyclosporin, without response. Patient´s platelet was then assessed by flow cytometry and revealed a loss of terminal sialic acids in platelets surface as well as neuraminidase activity in plasma, data compatible with a platelet destruction mechanism independent of immune receptors that could justify refractoriness to prior treatments.An alternative therapeutic regimen with Oseltamivir phosphate, as a last resort for the management of this patient, was initiated. She was informed and consented. It was given orally 75mg twice daily for 5 days. Then, a new platelet assessment was done, demonstrating normalization of sialic acids expression. But thrombocytopenia persisted, so Azathioprine was added looking for a synergic effect. Nowadays, she continues treatment with Azathioprine twice a day and remains in CR for seven months
Conclusion
CONCLUSION: In this case, treatment with oseltamivir could restore platelet membrane, avoiding its destruction by the hepatic rethiculoendothelial system and allowing immunosuppressive drugs (Azathioprine) to control the immune destruction mechanism. At the present time Oseltamivir is not still approved for ITP. However, this case highlights the need for prospective studies to verify the effectiveness of this new approach and the possibility of new indications for this drug.
Session topic: E-poster
Type: Publication Only
Background
Primary immune thrombocytopenia (ITP) is an immune bleeding disorder with an increased destruction of autologous platelets. Autoantibody specificity is usually against GPIIb/IIIa in 70-80% of patients or GPIb in 20% of them. Firts–line treatment includes immunosuppressive and immunomodulatory agents, that is corticosteroids (CS) or intravenous immunoglobulin (IVIG). Splenectomy is considered for patients with persistent lack of response. However, about 20% patients are inexplicably refractory to both therapies. Recent studies in refractory ITP patients suggest an association between anti-GPIb autoantibody and a poor response to conventional therapies, as well as platelet desialylation. This leads to platelet elimination by hepatocyte Ashwell-Morell receptors, especially in the absence of macrophages. Therefore, it may be a role for sialidase inhibitors in ITP treatment. Oseltamivir phosphate conventionally serves as anti-influenza agent. It inhibits viral neuraminidase as well as glycolipids sialylation on human T cells surface.We report a case of an adult ITP patient who was resistant to multiple therapeutic approaches but was successfully treated with Oseltamivir phosphate.
Methods
CASE REPORT: A 64-year-old female was diagnosed with ITP. She was initially treated with high dose CS and IVIG, with a complete response (CR) that lasted for 15 years. She relapsed with severe thrombocytopenia and minor bleeding. Her platelet counts remained low despite using CS and IGIV, so she initiated recombinant human thrombopoietin (TPO) agonist reaching maximum dose without response, so we added danazol and rituximab, either with non response. During this period, she presented with lower gastrointestinal bleeding so she underwent a splenectomy. She continued with TPO agonist and Danazol to maximum doses. Three months after splenectomy she reached secure but fluctuating platelet counts, presenting a massive portal and mesenteric thrombosis. She started therapeutical LMWH with close monitoring of platelets count, and suspended TPO agonist as well as danazol. Two months later, she lost platelet response and had to iniciate different immunosuppressive drugs: Vincristine, Azathioprine, Mycophenolate Mofetil and Cyclosporin, without response. Patient´s platelet was then assessed by flow cytometry and revealed a loss of terminal sialic acids in platelets surface as well as neuraminidase activity in plasma, data compatible with a platelet destruction mechanism independent of immune receptors that could justify refractoriness to prior treatments.An alternative therapeutic regimen with Oseltamivir phosphate, as a last resort for the management of this patient, was initiated. She was informed and consented. It was given orally 75mg twice daily for 5 days. Then, a new platelet assessment was done, demonstrating normalization of sialic acids expression. But thrombocytopenia persisted, so Azathioprine was added looking for a synergic effect. Nowadays, she continues treatment with Azathioprine twice a day and remains in CR for seven months
Conclusion
CONCLUSION: In this case, treatment with oseltamivir could restore platelet membrane, avoiding its destruction by the hepatic rethiculoendothelial system and allowing immunosuppressive drugs (Azathioprine) to control the immune destruction mechanism. At the present time Oseltamivir is not still approved for ITP. However, this case highlights the need for prospective studies to verify the effectiveness of this new approach and the possibility of new indications for this drug.
Session topic: E-poster
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