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Hiệu quả của antithrombin trong các ứng dụng tiền lâm sàng và lâm sàng đối với đông máu nội mạch lan tỏa liên quan đến nhiễm khuẩn huyết
Tóm tắt
Antithrombin (AT) được biết đến như một chất chống đông sinh lý quan trọng. AT làm mất hoạt tính của thrombin và nhiều yếu tố đông máu khác, do đó ức chế mạnh mẽ sự hoạt hóa quá mức của hệ thống đông máu trong trường hợp đông máu nội mạch lan tỏa (DIC). AT cũng ức chế các phản ứng gây viêm được xúc tác bởi thụ thể được kích hoạt bởi protease-1 trong nhiễm khuẩn huyết. Một trong những đặc điểm độc đáo của AT là sự thay đổi hình dạng mà nó trải qua khi liên kết với các phân tử giống heparin. Chức năng chống đông được tăng tốc mạnh mẽ sau khi AT liên kết với heparin được thu nạp từ bên ngoài vào máu lưu thông. Trong khi đó, AT cũng liên kết với syndecan-4 trên bề mặt tế bào trong các điều kiện sinh lý, từ đó góp phần vào khả năng chống tạo huyết khối tại chỗ. Sự liên kết giữa AT và syndecan-4 kích thích sản xuất prostaglandin I2, giảm sản xuất cytokine gây viêm, và ức chế sự tương tác giữa bạch cầu và tế bào nội mô. Ngoài các hoạt động này, các nghiên cứu tiền lâm sàng gần đây đã báo cáo rằng AT có thể ức chế cái chết tế bào hoại tử của bạch cầu trung tính và sự thải ra các bẫy ngoại bào của bạch cầu trung tính. Tất cả những tác động này có thể dẫn đến việc giảm mức độ viêm bằng cách làm giảm các mẫu phân tử liên quan đến tổn thương. Mặc dù một số nghiên cứu trên động vật đã chứng minh lợi ích sống sót của AT, nhưng lợi ích lâm sàng đã được tranh cãi từ lâu vì tác động của AT liều cao đã bị phủ nhận vào năm 2001 trong một thử nghiệm ngẫu nhiên có đối chứng quy mô lớn nhằm vào những bệnh nhân bị nhiễm khuẩn huyết nghiêm trọng. Tuy nhiên, những nghiên cứu lâm sàng gần đây kiểm tra hiệu ứng của liều bổ sung AT ở những bệnh nhân có DIC liên quan đến nhiễm khuẩn huyết đã tiết lộ rằng AT có thể có hiệu quả trong việc giải quyết DIC và cải thiện sự sống sót mà không làm tăng nguy cơ chảy máu. Bởi vì DIC vẫn là một mối đe dọa lớn trong nhiễm khuẩn huyết, cần phải xác định phương pháp tối ưu để nhận diện loại thuốc hứa hẹn này.
Từ khóa
#antithrombin #đông máu nội mạch lan tỏa #nhiễm khuẩn huyết #chất chống đông #phản ứng viêmTài liệu tham khảo
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