A bleeding tendency is one of the most common complaints observed by hematologists. It is challenging to differentiate a clinically insignificant bleeding from a bleeding phenotype that requires hemostatic evaluation and medical intervention. A thorough review of personal and familial history, objective assessment of bleeding severity using a bleeding assessment tool, and a focused physical examination are critical to correctly identifying suspected patients with mild to moderate bleeding disorders (MBDs). A basic laboratory work‐up should be performed in all patients referred for a bleeding tendency. If a hemostatic abnormality is found such as evidence of von Willebrand disease, a platelet function disorder, or a coagulation factor deficiency, more extensive testing should be performed to further characterize the bleeding disorder. Conversely, if all results are normal the patient is considered to have bleeding disorder of unknown cause (BDUC). For patients with BDUC, further evaluation may include non‐routine testing to look for rare bleeding disorders not detected by routine hemostasis tests, such as thrombomodulin‐associated coagulopathy, tissue factor pathway inhibitor‐related bleeding disorder, hyperfibrinolytic‐bleeding disorders or impaired tissue factor production. In this review, we summarize the stepwise diagnostic procedure in MBDs and provide some insights into the biological features of BDUC.

中文翻译：

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如何调查轻度至中度出血性疾病和不明原因出血性疾病

出血倾向是血液科医生观察到的最常见的症状之一。将临床上不严重的出血与需要止血评估和医疗干预的出血表型区分开来是具有挑战性的。彻底回顾个人和家族病史、使用出血评估工具客观评估出血严重程度以及重点体检对于正确识别轻度至中度出血性疾病 (MBD) 疑似患者至关重要。所有因出血倾向而转诊的患者均应进行基本的实验室检查。如果发现止血异常，例如血管性血友病、血小板功能障碍或凝血因子缺乏的证据，则应进行更广泛的测试以进一步表征出血性疾病。相反，如果所有结果均正常，则患者被视为患有不明原因出血性疾病 (BDUC)。对于 BDUC 患者，进一步评估可能包括非常规检测，以寻找常规止血检测未检测到的罕见出血性疾病，例如血栓调节蛋白相关凝血病、组织因子途径抑制剂相关出血性疾病、纤溶亢进性出血性疾病或组织因子受损生产。在这篇综述中，我们总结了 MBD 的逐步诊断程序，并对 BDUC 的生物学特征提供了一些见解。