Inhibitors of fibrinolysis in diabetic children, mothers, and their newborn

Abstract

Late diabetic complications are often related to vascular changes and formation of thrombi in the altered vasculature. Contributing factors to thrombosis susceptibility of diabetic patients include changes in clotting factors, platelets, and inhibition of fibrinolysis. We have measured various fibrinolytic inhibitors in the blood of diabetic children, diabetic pregnant women and their offspring, and healthy controls. Inhibitors studied included 1) fast (immediate) antiplasmin, 2) slow (progressive) antiplasmin, 3) alpha-2-macroglobulin, and 4) alpha-1-antitrypsin. It appears from our study that high fast-antiplasmin levels, and low or missing slow-antiplasmin levels are characteristic of diabetic patients and of newborn of diabetic mothers. The reason for high fast-antiplasmin levels is not clear: Levels are not connected with the age of the patient or duration of diabetes, and are not elevated in response to a fibrinolytic process (fibrin decomposition products could not be shown to be present in the serum of diabetic children). Alpha-2-macroglobulin was significantly higher and alpha-1-antitrypsin significantly lower in diabetic women than in controls. In the other groups of patients studied differences in these inhibitors from the appropriate control groups were not statistically significant.

Evaluation of Serum Fibrinogen, Plasminogen,α2-Anti-Plasmin, and Plasminogen Activator Inhibitor Levels (PAI) and Their Correlation with Presence of Retinopathy in Patients with Type 1 DM

“…To our knowledge, there are only a small number of studies evaluating α 2-anti-plasmin levels in Type 1 diabetes, although findings are consistent with our observations. In a recent study, the plasma plasmin- α 2-anti-plasmin complex (PAP) was associated with diabetic retinopathy and sight threatening diabetic retinopathy in Type 2 diabetics [10], and correlation was still significant after adjustments of the groups for age, gender, race, the study center, SBP, the use of diabetes medications, disease duration, HbA1c, and waist-to-hip ratio were made [25, 26]. A positive correlation between α 2-anti-plasmin with HbA1c suggests that fibrinolytic markers may improve with disease regulation and better glycemic control.…”

In utero arterial thrombosis treated with recombinant tissue plasminogen activator in an infant of a diabetic mother: A case report and literature review

“…Although the specific mechanism of increased thrombosis in IDM remains unclear, it is likely multifactorial with an interplay between genetic and environmental factors that lead to changes in the procoagulation, anticoagulation and thombolytic pathways. Various authors have reported increased proaggregatory platelet endoperoxide levels, decreased anti-aggregatory vascular prostacyclin levels (9), decreased plasminogen activity (6,7), protein C deficiency (10) and altered levels of fibrinolysis inhibitors, specifically increased fast antiplasmin and decreased slow antiplasmin levels (11). Compared with infants of nondiabetic mothers, thromboses in IDM were also reported to show more organization, calcification and earlier fatalities, with more than one-half of IDM expiring in utero, at birth or within the first 24 h of life (1,5).…”

A Radioimmunometric Assay for Urinary .ALPHA.2-Macroglobulin.

“…Plasma levels of a2-macroglobulin in diabetic patients are reported to be high (Almer et al 1974;Ambrus et al 1979;James et al 1980) and to increase in parallel with the rise of HbAlc (Watzke et al 1988). The increase of plasma a 2-macroglobulin may delay correction of thickening of glomerular basement membrane by inhibiting of neutral protease activity and therefore inducing diabetic nephropathy (Brownlee 1976).…”

“…It has been reported that in diabetic patients, levels of a2-macroglobulin in blood increased irrespective of types of diabetes (Almer et al 1974;Ambrus et al 1979;James et al 1980). Furthermore, there is a positive correlation between plasm a2-macroglobulin levels and HbAlc (Watzke et al 1988).…”

“…radioimmunometric assay; urinary a2-macroglobulin; diabetes mellitus a2-Macroglobulin is a major glycoprotein in blood and acts as a protease inhibitor (Harpel and Rosenberg 1976;Hall and Roberts 1978). The molecular weight and the pI of a2-macroglobulin are 770 kDa and 5.4, respectively, and it was produced by the liver (Jones et al 1972;Hall and Roberts 1978;Pochon et al 1978).It has been reported that in diabetic patients, levels of a2-macroglobulin in blood increased irrespective of types of diabetes (Almer et al 1974;Ambrus et al 1979;James et al 1980). Furthermore, there is a positive correlation between plasm a2-macroglobulin levels and HbAlc (Watzke et al 1988).…”