Evaluation of low PAI‐1 activity as a risk factor for hemorrhagic diathesis

Abstract

Summary.Background: Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking. Objective: To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population. Methods: In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA-PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age-and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls. Results: The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL )1 , was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11-3.77 and 2.75; 1.39-5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22-8.56, P ¼ 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA-PAI-1 was not associated with the increased bleeding tendency. Conclusion: Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations.

Increased Incorporation of Antiplasmin Into the Fibrin Network in Patients With Type 1 Diabetes

“…Notably, low PAI-1 has been associated with increased bleeding tendency (15,36). As there are differences in PAI-1 activity between patients with type 1 and type 2 diabetes, we suggest that attention should be paid to the type of diabetes when performing and analyzing large clinical studies on antithrombotic drugs, especially in the era of new antithrombotic drugs where intensified prophylactic antithrombotic treatment is increasingly common.…”

“…For improvement of the precision at lower PAI-1 levels, extra measuring points were added at the lower end of the calibration curve. In addition, a point-to-point approach was used instead of linear regression as described earlier (15), with the intraassay coefficient of variation (CV) 11.5% for the low control (PAI-1 0.9 units/mL) and 5.7% for the high control (PAI-1 19.4 units/ mL) and an interassay CV 4.5% and 3.6%, respectively.…”

Low PAI‐1 activity in relation to inflammatory parameters, insulin profile and body mass index

“…Finally, this study was confined to patients referred for bleeding tendency. However, in healthy controls described in a previous study [11], the BMI was also significantly lower amongst 10 individuals with PAI‐1 <1 U mL −1 than amongst the 90 individuals with PAI‐1 of 1 U mL −1 or higher (21.5 vs. 23.7; P = 0.04 in two‐tailed Mann–Whitney test). We did not have samples available to test the mediators of inflammation and components of the metabolic system.…”

“…The characteristics of the patients are described in Table 1. The concentration of tPA‐PAI‐1 antigen ranged between 0.02 and 16.9 ng mL −1 and none of them had a null mutation [11]. In the univariable analysis, patients with low PAI‐1 activity were significantly younger and had a lower BMI, and a higher proportion of the females used oral oestrogens.…”

Plasminogen Activator Inhibitor-1 Activity in Type 2 Diabetes

“…25 However, the prevalence of the genetic polymorphisms associated with PAI-1 have been shown to be similar for individuals with low PAI-1 activity and a bleeding tendency and healthy controls with significantly higher PAI-1 activity. 33 Nevertheless, our lack of polymorphism data are an acknowledged limitation of this study that future studies should address. Because it has been demonstrated that the ratio of PAI-1 activity to antigen concentrations can differ in people with type 2 diabetes compared with nondiabetic individuals, 34 future studies of the relationship between PAI-1 and diabetes complications should measure both PAI-1 activity and antigen concentrations.…”