Haemostasis in critically ill patients with advanced chronic liver disease

血液凝固和肝脏疾病之间的联系是什么？肝病很常见，现在是30至59岁成年人的最大死因。肝病的两个严重并发症是出血和血凝块（血栓形成）。出血每年影响多达1/10的肝病成人，每年多达1/20的肝病成人发生血栓。大多数出血是由于腹部血管的压力变化导致食管周围静脉肿胀（称为静脉曲张）。 什么是已知的血液凝固在肝脏疾病？肝脏产生许多与血液凝固有关的物质，肝病患者通常有明显的血液凝固异常，这些异常是通过常规检查测量的。这是因为常规可用的测试仅测量增加血液凝固的蛋白质（促凝剂）的作用。在肝脏疾病中，减少血液凝固的蛋白质（抗凝剂）也减少，总体而言，凝血被认为是“重新平衡”。专业测试（凝血酶生成和血栓弹性描记术）能够测量身体的抗凝剂或血细胞的影响，表明大多数肝病患者的凝血实际上是正常的或增加的。 为什么血液检查在肝病中测量凝血很重要？目前的常规检查在预测肝病患者的出血和凝血并发症方面很差。由于肝病患者的凝血试验看起来异常，因此可以给予血浆（凝血蛋白），血小板（对凝血很重要的小细胞）或纤维蛋白原（血凝块形成所需的最终蛋白质）等治疗，以尝试改善血液检查结果，即使这可能不会降低出血的风险。在出血患者中，治疗方法基于不同患者组的研究，例如创伤，血浆输注已显示可改善结局。在肝脏疾病中，研究表明血浆治疗会增加静脉压力，从而使静脉曲张出血恶化。肝病患者也有血栓形成的风险增加;大多数住院患者都服用药物来降低血栓形成的风险（“血液稀释剂”或抗凝剂），但由于常规实验室检查的变化，医生有时担心这些药物可能会增加出血的风险。平衡出血和血栓形成的风险，并决定应该处理哪些血液检查结果可能非常困难。这对重症患者尤其重要，因为他们出血和血栓形成的风险更高，并且通常需要多次手术。 我该怎么办？我将在重症监护的肝病患者中观察专业血液检查（凝血酶生成，血栓弹力图，中性粒细胞胞外陷阱），以了解这些检查是否可以常规用于指导输血需求并预测出血或血栓形成的风险。我还将研究这些测试是否随着时间的推移保持不变，以及输血如何改变结果。 为什么这项研究很重要？由于目前的测试是没有帮助的，许多患者得到输血时，他们可能不需要。这是浪费的，昂贵的，并使患者面临副作用的风险。这对于患有肝病和出血（4000/年）的患者以及那些接受手术/手术的患者都很重要。更好的测试将使医生在不需要输血时放心，并将改善出血并发症的管理和预防医院血栓形成。

What is the link between blood clotting and liver disease? Liver disease is common and is now the largest cause of death in adults aged 30 to 59 years of age. Two serious complications of liver disease are bleeding and blood clots (thrombosis). Bleeding affects up to 1 in 10 adults with liver disease per year and blood clots up to 1 in 20 adults with liver disease per year. Most bleeding is due to pressure changes in the blood vessels in the abdomen leading to swelling of veins around the oesophagus (called varices). What is known about blood clotting in liver disease? The liver produces many of the substances involved in blood clotting, and patients with liver disease often have marked abnormalities in blood clotting measured with routinely available tests. This is because routinely available tests only measure the effect of proteins which increase blood clotting (pro-coagulants). In liver disease, the proteins which reduce blood clotting (anti-coagulants) are also reduced and overall, clotting is thought to be 'rebalanced'. Specialist tests (thrombin generation and thromboelastography) which are able to measure either the effect of the body's anti-coagulants or blood cells demonstrate that clotting is actually normal or increased in most patients with liver disease. Why are blood tests to measure blood clotting in liver disease important? Current routine tests are poor at predicting bleeding and clotting complications in patients with liver disease. Because the blood clotting tests in patients with liver disease look abnormal, treatments like transfusion of plasma (blood clotting proteins), platelets (small cells important for blood clotting) or fibrinogen (the final protein needed for blood clot formation) may be given to try and improve the blood test results, even though this might not reduce the risk of bleeding. In patients who are bleeding, the treatment approach is based on studies in different patient groups such as trauma where plasma transfusion has been shown to improve outcomes. In liver disease, studies show treatment with plasma can worsen bleeding from varices by increasing the pressure in the veins. Patients with liver disease are also at increased risk of thrombosis; most patients in hospital are given medications to reduce the risk of thrombosis ('blood thinners' or anticoagulants) but due to the changes seen on routine laboratory tests, doctors sometimes worry these medications might increase the risk of bleeding. Balancing the risks of bleeding and thrombosis and deciding which blood test results should be treated can be very difficult. This is particularly important in seriously ill patients as they are at higher risk of bleeding and thrombosis, and often need multiple procedures. What will I do? I will look at specialist blood tests (thrombin generation, thromboelastography, neutrophil extracellular traps) in patients with liver disease admitted to intensive care to see whether these tests could be used routinely to guide the need for transfusion and predict the risk of bleeding or thrombosis. I will also look at whether these tests remain the same over time and how transfusion changes the results. Why is this research important? As current tests are not helpful, many patients get transfusions when they probably don't need to. This is wasteful, costly and puts patients at risk of side effects. This is important both for patients with liver disease and bleeding (4000/year) and those having procedures/operations. Better tests will reassure doctors when transfusion is not needed and will improve management of bleeding complications and prevention of thrombosis in hospital.