Department of Clinical Pharmacology, Aalborg University Hospital, Aalborg, Denmark.
Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
J Thromb Haemost. 2022 Dec;20(12):2921-2929. doi: 10.1111/jth.15883. Epub 2022 Oct 7.
Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy.
To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis.
PATIENTS/METHODS: The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event.
Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score ≥3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score ≥2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events.
The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.
癌症患者中血栓形成较为常见。Khorana 评分指导的一级预防已被指南认可,但推荐主要依赖于接受化疗的患者的数据。
探究 Khorana 评分是否可以根据静脉和动脉血栓形成风险对接受免疫检查点抑制剂治疗的癌症患者进行风险分层。
患者/方法:利用丹麦行政健康登记数据定义研究人群和 Khorana 评分。主要结局是接受免疫检查点抑制剂治疗后 6 个月静脉血栓栓塞的风险。次要结局是动脉血栓形成和任何血栓栓塞事件。死亡被视为竞争风险事件。
在 3946 例无其他抗凝指征的癌症患者中,开始接受免疫检查点抑制剂治疗后,静脉血栓栓塞的总体 6 个月发生率为 2.6%(95%置信区间[CI]:2.1-3.1)。低危(评分 0)、中危(评分 1-2)和高危(评分≥3)Khorana 分类的风险分别为 2.1%(95% CI:1.5-3.0)、2.6%(95% CI:2.0-3.4)和 3.7%(95% CI:2.1-5.9)。根据指南(Khorana 评分≥2),适合一级预防的患者静脉血栓栓塞风险为 4.1%(95% CI:3.1-5.4)。Khorana 风险类别较高也与 6 个月动脉血栓形成和任何血栓栓塞事件的风险较高相关。
Khorana 评分能够根据 6 个月内血栓栓塞事件的风险对接受免疫检查点抑制剂治疗的癌症患者进行风险分层。静脉血栓栓塞的风险低于随机预防试验,因此质疑在接受免疫检查点抑制剂治疗的未选择人群中常规一级预防的绝对获益。