Polymerisation and crosslinking of fibrin monomers in diabetes mellitus

Abstract

Summary. Polymerisation and crosslinking of fibrin monomers was studied in 35 healthy volunteers and in 42 poorly controlled diabetic patients. Polymerisation did not show any difference between control subjects (n = 10) and diabetic patients (n = 11) (p > 0.1), although fibrinogen was 35% more glycated in the diabetic patients (/)<0.001). Alpha chain crosslinking in the diabetic patients, however, was impaired as is shown from an increase in intermediate alpha polymers with a concomitant decrease in alpha monomer disappearance. A significant positive correlation was found between the degree of glycation of fibrinogen and the defective alpha chain polymerisation (r = 0.86, p < 0.005). These results were consistent with the results of thrombin and reptilase experiments. The reaction rate with reptilase did not show any difference between the two groups (p > 0.1), whereas the reaction rate with thrombin was significantly slower in the diabetic group compared to the control subjects (p < 0.001). Purified fibrin clots obtained from the diabetic patients were more susceptible to plasmin than clots obtained from control subjects. It is concluded that in poorly controlled diabetic patients polymerisation of fibrin monomers is normal, but crosslinking of the alpha chains is impaired, leading to a higher susceptibility of the clots to plasmin degradation.

Coagulation Activation in Diabetes mellitus

“…Such a finding was earlier reported by Liitjens et al [28] performing in vitro tests in diabetic patients. These authors found the reaction rate with thrombin to be significantly lower in the dia betic group than in the control subjects and also lower with increasing HbAi.…”

“…An explana tion for the phenomenon mentioned might be that we used a turbidimetric method for the measurement. If the fibrin polymeriza tion after thrombin action is normal, but the cross-linking is impaired, as described by Liitjens et al [28], it is understandable that the time until a measurable turbidity change has been occurred can be prolonged.…”

Association of fibrinogen level with early neurological deterioration among acute ischemic stroke patients with diabetes

“…Prolonged glycation also induces a prothrombotic condition. Studies on fibrin clot structure under diabetic conditions have shown fibrinogen to be glycated in vivo [23], causing a change in the fibrin clot structure that reduces permeability [24], decreases fibrinolysis [25], and decreases α-chain crosslinking [26]. Thus, the effects of insulin resistance and prolonged glycation increase the risk of thrombosis, which underpins the development of vascular disease [27].…”

The molecular biology of chronic wounds and delayed healing in diabetes

“…The process of glycation involves the non‐enzymatic binding of individual sugar residues to proteins via free amino groups, with further rearrangement leading to the more complex AGEs [165]. The former leads to altered structure and function of proteins [196–198], the latter to aggregate formation, which has been linked to diabetic complications [199].…”