Impairment of fibrynolytic capacity in experimentally induced ketoacidosis in continuous subcutaneous insulin infusion patients

Abstract number: P0957

Iorio A., Ferolla P., Orsini Federici M., Celleno R., Stabile A., Ackwe J., Canonico V., Massi Benedetti M.

Department of Internal Medicine, University of Perugia, Italy

Background  

Several reports in the literature have shown that during ketoacidosis the complex alterations of the fibrinolytic and coagulation systems already present in the diabetic patient became even worst, and patients often suffer or die of thrombotic complications. All these studies were performed in uncontrolled diabetic patients during spontaneous ketoacidosis and were not suitable to separately analyze the effects of elevated blood glucose and ketones.

Objective  

To evaluate the coagulation and fibrinolytic system in the early phase of the ketoacidosis state provoked in continuous infusion subcutaneous insulin patients.

Materials and methods  

The study was designed as open clinical trial on type I diabetic patients, and was approved by the competent Ethical Review Board. Eight patients were enrolled after informed consent, and had their insulin infusion pump stopped for four hours. Blood glucose, insulin, C-peptide, and ketones were serially measured to verify the metabolic response. Sampling times for coagulation studies were baseline, 4 h (peak), and 8 h (recovery). Blood for coagulation studies was drawn in trisodium citrate 0.32 mmol L^-1 9/1 v/v from a clean venipuncture using a 19 gauge butterfly needle and avoiding venostasis. A venocclusive test was performed applying a sphygmomanometer inflated at the mean AP for 15 min. Blood samples for tPA and PAI activities were acidified immediately after drawing. All samples were stored at -80 °C until testing. Factor VII and VIII were determined with a one-stage PTT method (Actin FS and Factor Deficient Plasmas); vWF, tPA, and PAI1 antigens were determined by ELISA method; tPA and PAI activity by chromogenic methods (all kits were from IL, Milan).

Results  

Main results after 4 h were: mean blood glucose 149.875 ± 54.393 at baseline and 224.875 ± 56.184 at 4 h (P < 0.001), mean,-hydroxybutirate 0.1 ± 0.106 at baseline and 0.95 ± 0.560 at 4 h (P < 0.001). No change from was found for factor VII, VIII, vWF, and PAI antigen. The significant increase (P < 0.001) of venostasis induced tPA release observed basally was significantly (P < 0.001) suppressed at 4 h.

Conclusions  

Impaired fibrinolytic capacity in the early phase of diabetic ketoacidosis could trigger a prothrombotic state and contribute to the explanation of the increased number of clinically relevant thrombotic episodes observed in acutely ill patients. Early detection of the ketonemia or pharmacologic prophylaxis of the prothrombotic state could constitute a step forward in diabetes care.