Lippi Giuseppe, Franchini Massimo
Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università di Verona, Verona, Italy.
Semin Thromb Hemost. 2008 Nov;34(8):747-61. doi: 10.1055/s-0029-1145257. Epub 2009 Feb 12.
A comprehensive understanding of the pathogenesis of venous thrombosis is essential for identifying patients at increased risk and who may therefore benefit from more aggressive preventive and therapeutic measures. As for other pathologies, the pathogenesis of venous thromboembolism is multifactorial. All risk factors, either congenital or acquired, are relatively "innocent" when considered alone. However, when an individual is unlucky enough to inherit one or more abnormality, compounded in many cases by environmental hazards, that person may be propelled over a threshold that precipitates the development of thrombosis. An appropriate analogy is that where "the last drop makes the cup run over." A reinterpretation of the traditional Virchow's triad (abnormal vessel wall, abnormal blood flow, and abnormal blood constituents) was provided by Eberhard Mammen throughout his research, and this has contributed greatly to the understanding of the pathogenesis of this serious disorder. Mammen postulated immobility as the leading event, because it reduced blood flow as a result of decreased muscle contraction. The subsequent "stasis of flow" led to accumulation of blood within the intramuscular sinuses, especially of the calf, triggering hypercoagulability due to local accumulation of activated clotting factors and coagulation activation products and the simultaneous consumption of blood coagulation inhibitors. On Mammen's "hit list" nearly 20 years ago were included (among inherited abnormalities) decreased protein C, protein S, antithrombin III, plasminogen, and tissue plasminogen activator, and increased plasminogen activator inhibitor-1, whereas (among acquired predisposing conditions) surgery, trauma, previous thromboembolism, prolonged immobility and paralysis, malignancy, congestive heart failure, obesity, advanced age, pregnancy and puerperium, varicose veins, and oral contraceptives were also identified. Some two decades later, the situation has perhaps not changed so much, although studies continue to expand our knowledge of this topic, clarifying the relative contribution of each single risk factor in the pathogenesis of venous thrombosis.
全面了解静脉血栓形成的发病机制对于识别风险增加的患者至关重要，这些患者可能因此受益于更积极的预防和治疗措施。与其他病理情况一样，静脉血栓栓塞的发病机制是多因素的。所有风险因素，无论是先天性的还是后天获得的，单独考虑时都相对“无害”。然而，当一个人不幸遗传了一种或多种异常，并且在许多情况下又受到环境危害的影响时，这个人可能会超过一个阈值，从而引发血栓形成。一个恰当的比喻是“最后一滴水使杯子满溢”。埃伯哈德·马门在其整个研究过程中对传统的维勒霍夫三联征（血管壁异常、血流异常和血液成分异常）进行了重新诠释，这对理解这种严重疾病的发病机制有很大帮助。马门假定不动是主要事件，因为它会因肌肉收缩减少而导致血流减少。随后的“血流淤滞”导致肌肉内窦，尤其是小腿内的血液积聚，由于活化凝血因子和凝血激活产物的局部积聚以及同时消耗血液凝固抑制剂而引发高凝状态。近20年前，马门的“风险清单”中包括（在遗传性异常中）蛋白C、蛋白S、抗凝血酶III、纤溶酶原和组织纤溶酶原激活物减少，以及（在后天易患因素中）手术、创伤、既往血栓栓塞、长期不动和瘫痪、恶性肿瘤、充血性心力衰竭、肥胖、高龄、妊娠和产褥期、静脉曲张和口服避孕药。大约二十年后，情况可能变化不大，尽管研究不断扩展我们对这个主题的认识，阐明每个单一风险因素在静脉血栓形成发病机制中的相对作用。
