Hull University Teaching Hospital NHS Trust, Hull York Medical School, University of Hull, Hull, UK.
Thromb Res. 2020 Jul;191 Suppl 1:S91-S98. doi: 10.1016/S0049-3848(20)30404-7.
Venous thromboembolism (VTE) is often cited as a major cause of death and morbidity in cancer patients. Even a non-lethal VTE causes distress and is commonly perceived by patients as a set-back in the cancer journey and a threat to the cancer treatment. It is also known that the risk of VTE varies between cancers (cancer-related risk factors), between patients (patient-related risk factors), and also within the cancer journey of a single patient. Risk can increase during treatments like surgery and chemotherapy and decline during remission. Neither the low molecular weight heparins nor the vitamin K analogues have gained an established role in thromboprevention guidance other than in 'the high risk' patient, who remains a rather ambiguous entity. The recently published randomised studies of rivaroxaban and apixaban in moderate- to high-risk thrombosis patients, assigned by the Khorana Risk Score, has seen the inclusion of direct oral anticoagulants (DOACs) in recent guidelines (e.g. the American Society of Clinical Oncology 2019 guidelines) for this indication. The ease of administration and the demonstrated greater patient adherence to oral agents has heightened the expectation that a practice-changing thromboprevention study in cancer patients should be realizable. However, key unmet needs that pose familiar challenges remain and as yet do not have satisfactory solutions. Anticoagulants carry risks of bleeding that are higher in the cancer population. There is therefore the challenge of sufficient risk reduction of VTE from the intervention balanced against the number of patients that may be harmed from bleeding. There is also the challenge of penetrating the risk threshold beyond which oncologists would deem thromboprevention a clinically meaningful praxis. Thus, identifying the high-risk groups of patients or targeting the length or timing of the thromboprevention to when the risks are highest are major questions that remain the subject of ongoing research. Notably all this is taking place against a backdrop of changing therapeutics for many cancers (e.g. targeted agents, checkpoint inhibitors and combinations) and their assorted impact on VTE incidence. In this review, past data for the ambulatory cancer patient are summarised, the latest evidence for the direct oral anticoagulants apixaban and rivaroxaban are analysed and the challenges of identifying the high-risk patients that have the greater chance of benefiting from thromboprophylaxis are discussed.
静脉血栓栓塞症（VTE）常被认为是癌症患者死亡和发病的主要原因。即使是非致命性的 VTE 也会引起不适，并且通常被患者视为癌症治疗过程中的挫折和对癌症治疗的威胁。此外，VTE 的风险在不同癌症（癌症相关危险因素）、不同患者（患者相关危险因素）以及同一患者的癌症治疗过程中也有所不同。风险可能会在手术和化疗等治疗期间增加，在缓解期下降。无论是低分子肝素还是维生素 K 类似物，除了“高危”患者（这仍然是一个相当模糊的实体）之外，在血栓预防指南中都没有确立作用。最近发表的关于利伐沙班和阿哌沙班在 Khorana 风险评分中分配的中高危血栓形成患者的随机研究，使直接口服抗凝剂（DOACs）纳入了这一适应证的最新指南（例如，美国临床肿瘤学会 2019 年指南）。由于口服药物的给药方便性和患者更高的依从性，人们对癌症患者的这种具有改变实践的血栓预防研究充满期待。然而，仍存在一些关键的未满足需求和尚未解决的问题。抗凝剂在癌症人群中的出血风险更高。因此，需要平衡干预措施带来的 VTE 风险降低与因出血而可能受到伤害的患者数量，以达到足够的风险降低。此外，还需要确定高于何种风险水平，肿瘤学家会认为血栓预防具有临床意义。因此，确定高危患者群体或针对血栓预防的长度或时间，使其在风险最高时进行，是仍在进行的研究的主要问题。值得注意的是，所有这些都发生在许多癌症治疗方法（例如靶向药物、检查点抑制剂和联合治疗）发生变化以及它们对 VTE 发生率的各种影响的背景下。在这篇综述中，总结了门诊癌症患者的过去数据，分析了直接口服抗凝剂阿哌沙班和利伐沙班的最新证据，并讨论了确定具有更大获益机会的高危患者的挑战。
