Haemostasis in critically ill patients with advanced chronic liver disease

血液凝结和肝病之间有什么联系？肝病很常见，现在是30岁至59岁成年人的最大死因。肝脏疾病的两个严重并发症是出血和血栓(血栓)。每年每10名患有肝病的成年人中就有1人出血，每年每20名患有肝病的成年人中就有1人患有血栓。大多数出血是由于腹部血管的压力变化导致食道周围的静脉肿胀(称为静脉曲张)。关于肝病中的血液凝结，我们知道些什么？肝脏会产生许多与凝血有关的物质，而肝病患者通常会出现明显的凝血异常，这是通过常规检测得出的。这是因为常规测试只测量增加血液凝结的蛋白质(促凝血剂)的效果。在肝病中，减少血液凝结的蛋白质(抗凝剂)也会减少，总体来说，凝血被认为是重新平衡的。能够测量身体抗凝剂或血细胞效果的专业测试(凝血酶生成和血栓弹性成像)表明，在大多数肝病患者中，凝血实际上是正常的或增加的。为什么血液测试在肝病中测量血液凝结很重要？目前的常规检测在预测肝病患者的出血和凝血并发症方面做得很差。因为肝病患者的凝血测试看起来不正常，所以可能会接受输注血浆(凝血蛋白)、血小板(对凝血至关重要的小细胞)或纤维蛋白原(凝血形成所需的最终蛋白)等治疗，试图改善血液测试结果，尽管这可能无法降低出血的风险。对于正在出血的患者，治疗方法是基于对不同患者组的研究，例如在创伤患者中，血浆输注已被证明可以改善结果。在肝病中，研究表明，血浆治疗可以通过增加静脉压力来恶化静脉曲张出血。患有肝病的患者血栓形成的风险也增加了；大多数住院患者都服用了降低血栓形成风险的药物(血液稀释剂或抗凝剂)，但由于常规实验室测试中出现的变化，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，并决定应该治疗哪些血液测试结果可能是非常困难的。这对病情严重的患者尤其重要，因为他们出血和血栓形成的风险更高，而且往往需要多次手术。我该怎么办呢？我将查看住进重症监护病房的肝病患者的专业血液测试(凝血酶生成、血栓弹性成像、中性粒细胞外陷阱)，看看这些测试是否可以常规用于指导输血需求和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？由于目前的测试没有帮助，许多患者可能不需要输血，但却接受了输血。这是浪费、昂贵的，并将患者置于副作用的风险中。这对患有肝病和出血的患者(每年4000例)和那些接受手术/手术的患者都很重要。当不需要输血时，更好的测试将使医生放心，并将改善医院内出血并发症的管理和血栓的预防。

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.