van der Bruggen Myrthe M, Kremers Bram, van Oerle Rene, van Oostenbrugge Robert J, Ten Cate Hugo
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.
Thromb J. 2021 Nov 4;19(1):81. doi: 10.1186/s12959-021-00335-1.
Cerebral venous sinus thrombosis (CVST) is a relatively rare, but potentially lethal condition. In approximately 15% of the patients, the cause of CVST remains unclear. Conventional clotting tests such as prothrombin time and activated partial thromboplastin time are not sensitive enough to detect prothrombotic conditions nor mild haemostatic abnormalities. The calibrated automated thrombogram (CAT) is a physiological function test that might be able to detect minor aberrations in haemostasis. Therefore, we aimed to detect the presence of a prothrombotic state in patients who endured idiopathic CVST with the CAT assay.
Five adult patients with an idiopathic, radiologically proven CVST that had been admitted during the past 3 years were included in this study. The control group consisted of five age/gender matched healthy volunteers. Exclusion criteria were known haematological disorders, malignancy (current/past) or hormonal and anticoagulant therapy recipients. We obtained venous blood samples from all participants following cessation of anticoagulation. Using the CAT assay, we determined lag time, normalized endogenous thrombin potential (ETP), ETP reduction and normalized peak height. In addition, prothrombin concentrations were determined.
We found no significant differences in lag time (4.7 min [4.5-4.9] vs 5.3 min [3.7-5.7], p = 0.691), normalized ETP (142% [124-148] vs 124% [88-138], p = 0.222), ETP reduction (29% [26-35] vs 28% [24-58], p > 0.999), and normalized peak height (155% [153-175] vs 137 [94-154], p = 0.056) between patients and their age/gender matched controls. In addition, prothrombin concentrations did not significantly differ between patients and controls (120% [105-132] vs 127% [87-139], p > 0.999).
Reasons for absent overt hypercoagulability within this study population may be the small patient sample, long time since the event (e.g. 3 years) and avoidance of acquired risk factors like oral contraception. Given the fact that CVST is a serious condition with a more than negligible risk of venous thrombosis event recurrence, exclusion of clinically relevant hypercoagulability remains a challenging topic to further study at the acute and later time points, particularly in patients with idiopathic CVST.
脑静脉窦血栓形成（CVST）是一种相对罕见但可能致命的疾病。在大约15%的患者中，CVST的病因仍不明确。传统的凝血试验，如凝血酶原时间和活化部分凝血活酶时间，对于检测血栓前状态或轻度止血异常不够敏感。校准自动血栓图（CAT）是一种生理功能测试，可能能够检测到止血方面的微小异常。因此，我们旨在通过CAT检测来发现特发性CVST患者中血栓前状态的存在。
本研究纳入了5例在过去3年中因特发性、经影像学证实的CVST而入院的成年患者。对照组由5名年龄/性别匹配的健康志愿者组成。排除标准为已知的血液系统疾病、恶性肿瘤（现患/既往）或接受激素和抗凝治疗者。在停止抗凝后，我们从所有参与者中采集静脉血样本。使用CAT检测，我们测定了滞后时间、标准化内源性凝血酶潜力（ETP）、ETP降低率和标准化峰值高度。此外，还测定了凝血酶原浓度。
我们发现患者与其年龄/性别匹配的对照组在滞后时间（4.7分钟[4.5 - 4.9]对5.3分钟[3.7 - 5.7]，p = 0.691）、标准化ETP（142%[124 - 148]对124%[88 - 138]，p = 0.222）、ETP降低率（29%[26 - 35]对28%[24 - 58]，p > 0.999）和标准化峰值高度（155%[153 - 175]对137[94 - 154]，p = 0.056）方面没有显著差异。此外，患者和对照组之间的凝血酶原浓度也没有显著差异（120%[105 - 132]对127%[87 - 139]，p > 0.999）。
本研究人群中未出现明显高凝状态的原因可能是患者样本量小、事件发生时间长（如3年）以及避免了口服避孕药等获得性风险因素。鉴于CVST是一种严重疾病，静脉血栓事件复发风险不可忽视，排除临床相关的高凝状态在急性和后续时间点仍是一个具有挑战性的课题，需要进一步研究，尤其是在特发性CVST患者中。
