Increased incorporation of antiplasmin into the fibrin network in patients with type 1 diabetes.
OBJECTIVE
Diabetes is associated with various vascular complications and is suggested to induce a prothrombotic state. In the current study, we characterized antiplasmin incorporation into fibrin in relation to other fibrinolytic compounds in patients with type 1 diabetes.


METHODS
A total of 236 patients with type 1 diabetes and 78 control subjects were investigated. The incorporation of antiplasmin into the fibrin network and the plasma levels of plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator (tPA) activity, tPA/PAI-1 complex, plasmin-antiplasmin complex, antiplasmin, factor XIII, and d-dimer were measured. In addition, we used global assays to study fibrinolysis.


RESULTS
The incorporation of antiplasmin into the fibrin network was significantly higher in patients with type 1 diabetes than in control subjects without diabetes (1.65 ± 0.25 vs. 1.35 ± 0.18 mg/L, respectively; P < 0.0001). The patients also had lower PAI-1 activity (2.19 units/mL [interquartile range 0.96-5.42] vs. 4.25 units/mL [1.95-9.0]; P = 0.0012) and antiplasmin level in plasma (78.5 ± 13.3 vs. 83.2 ± 15.4 mg/L; P < 0.05), resulting in a higher fibrinolytic capacity (shorter clot lysis time; P = 0.0090). We did not find any important sex differences regarding fibrinolysis in the patients or in the control subjects.


CONCLUSIONS
Patients with type 1 diabetes incorporate more antiplasmin into the fibrin network than control subjects without diabetes do and have a reduced PAI-1 activity and a shorter clot lysis time. These results suggest that patients with type 1 diabetes produce a fibrin clot that is more resistant to fibrinolysis, which, however, may be counteracted by an increased fibrinolytic potential in plasma.
Coagulation Unit, Division of Haematology, Department of Medicine, Karolinska University Hospital, Stockholm, SwedenDepartment of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden anna.agren@karolinska.se.
Anna
A
Agren
Division of Internal Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Gun
G
Jörneskog
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Graciela
G
Elgue
Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Peter
P
Henriksson
Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Håkan
H
Wallen
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
Björn
B
Wiman
D000328:Adult; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C036309:fibrin fragment D; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin