We have used purified proteolytic fragments of von Willebrand factor (vWF) to characterize the functional sites of the molecule interacting with platelet membrane glycoprotein (GP) Ib. A dispase-digestive 39/34kDa fragment extending residues 480/481 to 718, a trypsin-digestive 52/48 kDa fragment extending residues 449 to 728 and staphylococcus aureus V-8 and trypsin-digestive III-T2 (heavy chain; 273-511, light chain: 674-728) were evaluated. All these three fragments had similar inhibitory activity on ristocetin induced vWF binding to GPIb, suggesting that these three fragments of vWF include the entire binding domain to GPIb. 52K-2, a monoclonal antibody to vWF which inhibits vWF binding to GPIb, recognized all three fragments of vWF. However, another antibody, RG-46, recognized 52/48kDa fragment and III-T2, but failed to react with 39/34kDa fragment.

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It has been known that bovine tissue thromboplastin reacts more with activated human factor VII than with non-activated factor VII, whereas human tissue thromboplastin interacts equally with both activated and non-activated human factor VII. Thus the ratio of factor VII activity measured with bovine tissue thromboplastin to that measured with human tissue thromboplastin (b/h) reflects the relative amount of activated factor VII. In this report, we provide evidence that the b/h ratio is a very sensitive and specific indicator of the stages of accelerated coagulation. Upon activation of the extrinsic coagulation pathway by addition of a smal amount of tissue thromboplastin to blood in a plastic tube, the b/h ratio was increased from 1.0 to 1.6. The ratio was increased up to 1, 000-fold by cold induced activation of factor VII in plasma from pregnant women. In vitro activation of the intrinsic pathway by incubation of plasma in a glass tube at 37°C or by addition of kaolin raised the b/h ratio up to 98-fold and 8-fold, respectively. Patients in hypercoagulable state were divided into three groups; group A (non-DIC), group B (pre-DIC), and group C (DIC). The b/h ratios in group A (1.393±0.782) and in group C (1.260±0.455) were not significantly different from that of normal controls (1.086±0.154). However, in group B, the b/h ratio (2.868±1.993) was significantly higher than that in normal controls (p<0.05). Several lines of evidence indicated that the increased b/h ratio in group B plasmas was the result of accelerated activation of factor VII due to hypercoagulability. Thus, the b/h ratio would be a useful clinical marker to detect hypercoagulable state such as pre-DIC.

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The D-dimer, plasmin-α₂ plasmin inhibitor complex (PIC), plasminogen activator inhibitor-1 antigen (PAI-1 Ag) and thrombin-antithrombin III complex (TAT) in plasma were studied by enzyme immunoassay in 96 patients with ischemic heart disease (IHD), 114 young normal volunteers (mean age 30) and 72 aged normal controls (mean age 70).
All patients underwent coronary artery angiography for evaluation of coronary arterial disease.
D-dimer, PIC and TAT concentrations were higher in the aged controls than in young normal volunteers. PAI-1 Ag in the two groups was the same. D-dimer (161.64±116.40ng/ml), PAI-1 Ag (77.93±45.82ng/l) and TAT (4.19±4.53ng/l) concentrations were higher in patients with IHD (p<0.05, 0.005 and 0.01 respectively) than in the aged controls. PIC in the patients and aged normal controls was the same.
D-dimer concentrations were remarkably higher in 61 patients (174.76±122.85ng/ml) with angiographically positive findings (luminal diameter reduction greater than 75%) than in 18 patients (109.35±62.24ng/ml) with negative findings (p<0.01). A marketly higher proportion of patients (28/29) with higher D-dimer concentration than patients (33/50) with lower D-dimer concentration had positive coronary angiography (X²=7.115, p<0.01).
No remarkable differences in TAT, PIC and PAI-1 Ag could be found in patients with angiographically positive and negative findings.
Increase in D-dimer, TAT and PAI-1 Ag concentrations would thus appear to be associated with increased risk of coronary thrombosis, and particularly increase in the D-dimer with the severity of coronary atherosclerosis.

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A female patient with acute promyelocytic leukemia and severe bleeding tendency with acquired afibrinogenemia is described. On admission, her plasma fibrinogen was markedly decreased beyond the range of measurement (<10mg/dl). Although disseminated intravascular coagulation existed undoubtedly, the low circulating plasminogen and α 2-plasmin inhibitor, and the presence of plasmin-α 2 plasmin inhibitor complex suggested that the excessive fibrinolysis probably resulted from the liberation of plasminogen activator from the leukemic promyelocytes. To prevent lethal hemorrhage undergoing induction chemotherapy, we administered fibrinogen (5g/day) added to heparin, FUT-175, FFP and platelet transfusion. With these treatments, hypercoagulopathy and increased fibrinolytic state were well controlled to the extent that she did not have overt bleeding tendencies. Although the fibrinogen preparations always carry the risk of causing viral hepatitis, we believe the value of intensive supportive therapy including fibrinogen preparations to prevent the early death for same pathogenesis of severe hypofibrinogenemia.

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