Department of Medicine, Division of Hematology, Washington University in St. Louis, St. Louis, Missouri, USA.
Department of Medicine, Division of General Medical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA.
J Thromb Haemost. 2022 Jul;20(7):1610-1617. doi: 10.1111/jth.15743. Epub 2022 May 26.
Patients with chronic liver disease (CLD) often present with an elevated international normalized ratio (INR). Although elevated INR reflects a higher risk of hemorrhage among warfarin users, its clinical significance in CLD patients is less clear.
We used Veterans Health Administration data to quantify the association between INR and (non-variceal) hemorrhage in patients with CLD compared to warfarin users.
We performed a multivariate competing risk analysis to study the association between INR and hemorrhage in the two cohorts. We used an interaction term between INR and cohort (CLD/warfarin users) to test if INR had different effects on hemorrhage in the two cohorts.
Data from 80 134 patients (14, 412 with CLD and 65, 722 taking warfarin) were analyzed. The effect of INR on the risk of hemorrhage differed between CLD patients and warfarin users (interaction P < .001). As INR increased above 1.5, the adjusted hazard ratio (aHR) for hemorrhage in CLD patients increased to 2.25 but remained fairly constant with further elevation of INR values. In contrast, the risk of hemorrhage in patients taking warfarin remained low with INR in the subtherapeutic (INR <2.0) and therapeutic ranges (INR 2.0-3.0), and increased exponentially with INR in the supratherapeutic range (aHR 1.64 with INR >3.0-3.5, and 4.70 with INR >3.5).
The relationship between INR and risk of hemorrhage in CLD patients is different from that in warfarin users. Caution should be exercised extrapolating data from warfarin users to make clinical decisions in CLD patients.
患有慢性肝脏疾病（CLD）的患者通常国际标准化比值（INR）升高。虽然 INR 升高反映了华法林使用者出血风险较高，但在 CLD 患者中的临床意义尚不清楚。
我们使用退伍军人健康管理局的数据，定量比较 INR 与 CLD 患者（与华法林使用者相比）非静脉曲张性出血之间的关系。
我们进行了多变量竞争风险分析，以研究两组患者 INR 与出血之间的关系。我们使用 INR 与队列（CLD/华法林使用者）之间的交互项来检验 INR 是否对两组患者的出血有不同的影响。
共分析了 80134 例患者（CLD 患者 14412 例，服用华法林者 65722 例）的数据。INR 对华法林使用者和 CLD 患者出血风险的影响不同（交互 P<0.001）。当 INR 升高超过 1.5 时，CLD 患者出血的调整后危险比（aHR）增加至 2.25，但随着 INR 值的进一步升高，aHR 保持相对稳定。相比之下，服用华法林的患者出血风险在 INR 处于亚治疗范围（INR<2.0）和治疗范围（INR 2.0-3.0）时仍然较低，并且在 INR 处于超治疗范围时呈指数增加（INR>3.0-3.5 时的 aHR 为 1.64，INR>3.5 时的 aHR 为 4.70）。
INR 与 CLD 患者出血风险之间的关系与华法林使用者不同。在 CLD 患者中做出临床决策时，应谨慎外推华法林使用者的数据。
