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The presence of hereditary protein C deficiency has been shown to predispose patients to the development of venous thrombosis. We used radioimmunoassays for the protein C activation peptide (PCP) and the prothrombin fragment F1 + 2 to quantitate the extent of in vivo activation of protein C by thrombin-thrombomodulin and prothrombin by factor Xa, respectively, in the blood of individuals with this clinical disorder. A total of 46 protein C deficient subjects from 18 kindreds were studied. In 23 nonanticoagulated patients with an isolated deficiency of protein C, the mean level of PCP was substantially reduced while the mean concentration of F1 + 2 was significantly elevated as compared with normal controls (1.10 pmol/L v 1.78 pmol/L, P less than .0005 and 2.54 nmol/L v 1.51 nmol/L, P less than .0005, respectively). The metabolic behavior of 131I-F1 + 2 was found to be similar in protein C deficient patients and normal individuals. However, we were unable to establish a significant correlation between decreased PCP levels and increased F1 + 2 measurements in these 23 patients. This study demonstrates that heterozygous protein C deficient individuals with equivalent plasma levels of the zymogen may have markedly different biochemical profiles when assay techniques are used that quantitate the in vivo activity of the coagulation system. Six individuals from three pedigrees were identified as having combined deficiencies of protein C and either antithrombin III or protein S; the genetic basis for the combined deficiency state was determined in two of the kindreds. Finally we observed that hemostatic system activity as measured by the PCP and F1 + 2 assays is markedly suppressed in protein C deficient patients who are chronically anticoagulated with coumarin derivatives.

This is a report of a 62-year-old male patient who had a bleeding disorder due to the presence of a factor VII (proconvertin) inhibitor. After treatment with a high-dose intravenous (IV) immunoglobulin failed and a life-threatening intracranial hemorrhage occurred, plasma exchanges were performed and immunosuppressive therapy was given. The factor VII inhibitor promptly disappeared, and the patient's parameters of hemostasis became normal. Even though a relapse occurred some months later, the patient responded to immunosuppressive therapy. No underlying disorder was evidenced after 17 months of follow-up.

In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and fibrinolytic activity were measured in these samples. During venous stasis, plasminogen activator inhibitor (PAI) activity decreased in almost all patients (81 of 83), from a median value of 8.2 to 2.9 U/mL (P less than .001, Wilcoxon signed-rank test). Because PAI-1 antigen augmented from a median value of 16 to 19.2 ng/mL (P less than .001), the decline in PAI activity was attributed to an increase in t-PA antigen from a median value of 10 to 21.7 ng/mL (P less than .001). Neutralization of PAI activity thus reflects the patient's capacity to overcome basal inhibitory potential through t-PA release. Based on residual PAI activity after 10-minute stasis, patients were classified as good or bad responders (PAI activity below detection limit, ie, less than or equal to 1.0 and greater than 1.0 U/ml, respectively). Good responders had a significantly higher fibrinolytic response after stasis than bad responders (median euglobulin clot lysis time 60 v 180 minutes; dilute whole blood clot lysis time 60 v 120 minutes; fibrinolytic activity on fibrin plates 7.7 v 0 U/mL). Furthermore, good responders, as compared with bad responders, had higher t-PA release (median 16.5 v 11.5 ng/mL), lower basal PAI activity (median 4.8 v 11.2 U/mL), and lower basal PAI-1 (median 11 v 21 ng/mL) and u-PA antigen (median 7.9 v 9.0 ng/mL, P less than .02). Hypofibrinolysis, as defined by the inability of released t-PA to overcome PAI-1 basal inhibitory potential, was observed in 45 of 83 patients (54%) and resulted either from an insufficient release of t-PA or from an increased basal PAI activity.

In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.