新規血液凝固マーカー(ETP-based APC-sr)を用いた深部静脈血栓・肺塞栓症の管理(<特集>第57回シンポジウム: 肺塞栓-その予防と治療-)

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  • Management for Deep Vein Thrombosis and Pulmonary Thromboembolism Using a New Blood Coagulation Marker (ETP-based APC-sr)

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Pregnancy is known to be a major risk factor for deep vein thrombosis (DVT) and pulmonary thromboembolism (PE). The latter is a major cause of maternal death in the United States, Europe and Japan. Caesarian delivery increases the risk of venous thromboembolism (VTE). Little is known, though, about the mechanisms underlying thrombotic disorders during pregnancy and puerperium, and there is no specific coagulation marker that would allow early detection of DVT and PE. Thrombin-antithrombin-complex (TAT) and fibrin/fibrinogen-degradation product (FDP)-D-dimer are used as markers of DVT and PTE. However, mean levels of FDP-D-dimer and TAT change dramatically during puerperium, making them unsuitable as blood markers for making predictions of DVT and PTE risk during puerperium. Thrombin plays a central role in the entire clotting process. The Thrombogram System can enable the analysis of appearance of thrombin generation over time. On the other hand, protein C is a principal component in the anticoagulant pathway, and the elevated risk of DVT and PTE in patients with congenital activated protein C (APC) resistance suggests that APC plays a major role in the onset of thrombotic disorders APC-sr is defined as the ratio of endogenous thrombin potential (ETP) in the presence and absence of APC (final concentration, 5.9nM). An elevated APC-sr thus indicates reduced sensitivity to APC. We have designed special ELISA plates coated with activated protein C reagent to simplify the APC-sr assay procedure. We examined the changes in APC-sr values during pregnancy and puerperium. APC-sr levels in late pregnancy and early puerperium revealed lower sensitivity to APC than 4 weeks after delivery (p<0.01). We also examined APC-sr levels during early puerperium in 6 Japanese DVT and PE patients. Mean APC-sr in the patient group was significantly higher than in the control group (p<0.05). We detected markedly elevated APC-sr in a case that developed superior sagittal sinus thrombosis during puerperium. APC-sr levels were significantly higher in patients who had asymptomatic DVT of the lower leg detected by ultrasonography after caesarian section. We believe APC-sr to be a potentially useful blood marker for identifying elevated risk of DVT and PTE during puerperium.

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