Thrombin-antithrombin III complex (TAT) is a good marker of intravascular thrombin generation. Oral anticoagulant therapy can be expected to be effective when intravascular thrombin generation is suppressed to an adequate range. TAT levels in the blood plasma from 61 patients receiving warfarin therapy and 12 patients prior to the initiation of warfarin therapy were determined. The degree of anticoagulation was monitored by the one-stage prothrombin time method (PT). Although PT levels were higher than the control range (more than 35%) in 14 of the patients receiving warfarin therapy, there was no significant difference in mean plasma TAT levels between these 14 patients and the 46 patients whose PT levels were within the control range. The mean TAT level in all patients receiving warfarin therapy (1.76±0.46ng/ml) was significantly lower than that in the patients before anticoagulation (5.19±1.97ng/ml) and was nearly the same as the normal control (2.00±0.58ng/ml). No significant relationship was observed between the levels of TAT and PT (%, INR). In several patients receiving warfarin therapy, serial changes in plasma levels of TAT and PT were followed. It was noted that plasma TAT levels always remained within the normal range even if PT (%) deviated from control range, while both PT (%) and TAT levels shifted in a similar direction. These results suggest that conventional PT may not always be an appropriate index to monitor oral anticoagulant therapy, and that the optimal range of anticoagulation for hypercoagulable states should be set according to the plasma levels of TAT.

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To clarify an effect of ascitic fluid on the levels of plasma coagulation-fibrinolysis parameters in patients with liver cirrhosis, the levels of thrombin antithrombin III complex (TAT), α2plasmin inhibitor-plasmin complex (PIC), D-dimer, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) were compared with ascitic fluid and plasma.
In ascitic fluid, the levels of TAT, PIC and D-dimer were significantly higher than those levels in plasma. Moreover, plasma levels of both D-dimer and TAT were significantly decreased when the ascitic fluid was disappeared by treatment. On the other hand, plasma levels of PIC, were relatively not related whether the ascites was present or not. These results may indicate that the consumption of coagulation and fibrinolysis factors in plasma was induced by activated coagulation system in ascitic fluid.
According to the levels of t-PA, there was no significant difference between in plasma and in ascitic fluid. However, PAT-1 could hardly be detected in ascitic fluid. Those findings indicated that marked comsumption of PAT-1 had been occurred in ascitic fluid due to the formation of t-PA and PAT-1 complex as an inhibitory mechanism for hyperfibrinolysis.
In conclusion, on the assessment of plasma coagulation and fibrinolytic parameters in decompensated liver cirrhosis, an effect of the ascites could not be ignored. Moreover, an evaluation of disseminated intravascular coagulation complicated in the patients with ascites, it thought to be necessary to refer to not only the levels of plasma D-dimer and TAT but also the levels of PIC.

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Antithrombotic effect of recombinant calphobindin I (rCPB-I), which has indistinguishable biochemical and pharmacological properties from native CPB-I in vitro, was studied in vivo.
The lumen of the carotid artery was damaged by rubbing 20 strokes with 2F balloon catheter, and the injured region was stenosed by constrictor to induce the thrombus formation. rCPB-I iv infused 0.5 and 1.0mg/kg/hr showed dose-dependent suppression of the thrombus formation affecting neither APTT nor whole blood clotting time (r+k value of thromboelastogram). Heparin iv infused 100U/kg/hr also showed an antithrombotic effect as same as that caused by rCPB-I 1.0mg/kg/hr, however it revealed marked prolongation of both coagulating parameters.
To investigate the mechanism of the action of rCPB-I, the binding property of ¹²⁵I labeled rCPB-I to the damaged vessel was examined in a rabbit carotid artery perfusion system, resulting that 6-fold much radioactivity was detected in the injured region than in the normal region under the condition of physiological Ca⁺⁺ concentration.
These results suggest that rCPB-I could bind to some components in injured lumen of the carotid artery and suppress the initiation of solid phase blood coagulation.

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It is thought that anti-thrombotic properties of blood vessels are partially regulated by anticoagulantly active heparin-like compounds on the luminal surface of vascular endothelial cells. Heparan sulfate proteoglycans (HSPG_s) are also known to be located along the abluminal side of the endothelium, that is, basement membrane or extracellular matrix (ECM) of endothelial cells. Does ECM contain HSPG which interact with antithrombin III (ATIII)? If so, how abundant are they, as compared with those on the luminal surface? To answer this question, we have studied the interaction of ¹²⁵I-labeled ATIII with cultured porcine aortic endothelial cells to localize the cellular site of anticoagulantly active HSPG_s. ECM, prepared from endothelial cells cultured on plastic dishes, by removing the cells with nonenzymatic methods, specifically bound ¹²⁵I-ATIII. The amount of ATIII bound to ECM was approximately 40% of that bound to the intact cell. The binding was efficiently displaced by heparan sulfate, and almost completely abolished by pretreatment of ECM with Flavobacterium heparitinase. ECM-associated HSPG_s apparently represented approximately 40% of HSPG_s associated with intact cell, in parallel with the binding experiments. Approximately 15-20% of ECM-associated ³⁵S-glycosaminoglycans was bound to ATIII affinity column with high affinity. ECM accelerated inactivation of thrombin by ATIII. Based upon the above data, we conclude that approximately at least a half of anticoagulantly active HSPG is located in the ECM, that is, abluminal side of cultured aortic endothelial cells. The physiological significance of this finding remains to be determined.

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Cyclic AMP (cAMP) and cyclic GMP contents were measured in 63 leukemic cell lysate from patients with and without disseminated intravascular coagulation (DIC) and compared with tissue factor (TF) activity, plasminogen activator (PA) and PA inhibitor (PAI). The cAMP level was increased in acute promyelocytic leukemia and was sighificantly higher in the leukemic cell lysate from patients with DIC than in from those without DIC. The cAMP level was well correlated with TF activity in the leukemic cell lysate. There was no difference in the phosphodiesterase level between the leukemic cell lysate from patients with DIC and from those without DIC, but calmodulin and s-100 levels were significantly higher in the former. The calmodulin level was also negatively correlated with the cAMP level and TF activity in leukemic cell lysates.
It is speculated that cAMP may not be important in TF synthesis of leukemic cells and that calcium might regulate such synthesis.

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A rare case of natural killer cell (NK cell) type granular lymphocyte proliferative disorders with deficiency of multiple coagulation factors is reported. On admission, both APTT and PT were prolonged with 39% of F. II, 40% of F. V, 41% of F. VII, 161% of F. VIII, 26% of F. IX, 40% of F. X and 36% of F. X II. A good correlation between coagulation abnormalities and liver dysfunction due to leukemic infiltration was seen during the course of illness. No evidence of DIC was demonstrated. It is suggested that synthesis of multiple coagulation factors was impaired due to direct infiltration to liver of NK cell type leukemic cells.

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A 74 year-old male with rheumatoid arthritis and double cancer (laryngeal cancer and early stomach cancer) showed prolongation of prothrombin time and activated partial thromboplastin time by preoperative coagulation screening tests and was subsequently found to be suffering from an inhibitor against factor V. With specific antiserum and neutralization tests, the inhibitor was characterized as an IgG (κ) antibody. Factor V inhibitor disappeared following radiotherapy, and no inhibitor has been detected for 2 years. This inhibitor was able to inactivate Factor V of some animals such as horse, sheep, goat, rabbit and dog. Although the inhibitor inactivated Factor V either in human plasma or in animal plasmas, no clinical bleeding tendency was observed.

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