**5.1 Acute metabolic acidosis**

Unlike in type 2 DM, acute metabolic diabetes keto-acidosis (DKA) characterized by lactic acidosis and ketonemia occurs in T1DM with a rate between 20 and 70% depending on the intensity of glucose control [53]. Subjects in DKA have increased blood levels of β-Thromboglobulin (β-TG), platelet factor-4 (PF-4), but their platelets are paradoxically less sensitive to aggregation agonists such as ADP and prostacyclin. The agonist sensitivity improves with glycemic control [54]. The initial depressed platelet function that improves with treatment is similar to previous findings by Janka [55] and Ileri et al [56].

Although ketones contribute to acidosis in DKA, only effects of lactic acid on platelets are well studied. Lactic acid dose dependently reduces platelet secondary wave aggregation *in vitro* [57–60]. The effect of pH changes is on impairing intracellular Ca++ store release [61, 62], thus interfering with cytoskeletal changes [63], facilitating platelet reactions [64]. In addition, the changes affect membrane surface expression of GP1b and P-selectin under anaerobic conditions [65] indicating metabolic effects. However, addition of lactic acid together with known platelet inhibitors such as aspirin is not additive but instead attenuates the effects [66, 67]. The paradoxical behavior can probably be accounted for by lactate being metabolized to produce ATP for platelet activation processes leaving protons to be buffered by other means.
