guanosine-triphosphate and Thrombosis

Platelets play a vital role in regulating hemostasis and thrombosis. Rho GTPases are well known as molecular switches that control various cellular functions via a balanced GTP-binding/GTP-hydrolysis cycle and signaling cascade through downstream effectors. In platelets, Rho GTPases function as critical regulators by mediating signal transduction that drives platelet activation and aggregation. Mostly by gene targeting and pharmacological inhibition approaches, Rho GTPase family members RhoA, Rac1, and Cdc42 have been shown to be indispensable in regulating the actin cytoskeleton dynamics in platelets, affecting platelet shape change, spreading, secretion, and aggregation, leading to thrombus formation. Additionally, studies of Rho GTPase function using platelets as a non-transformed model due to their anucleated nature have revealed valuable information on cell signaling principles. This review provides an updated summary of recent advances in Rho GTPase signaling in platelet regulation. We also highlight pharmacological approaches that effectively inhibited platelet activation to explore their possible development into future antiplatelet therapies.

Topics: Blood Platelets; cdc42 GTP-Binding Protein; Guanosine Triphosphate; Humans; Platelet Activation; rac1 GTP-Binding Protein; rho GTP-Binding Proteins; Signal Transduction; Thrombosis

Tetrahydrocannabinol (THC) can alter the coagulation cascade resulting in hypercoagulability. The aim of our study is to evaluate the impact of THC use on thromboembolic complications (TEC) in geriatric trauma patients (GTP).. This is a 2017 analysis of the TQIP database including all GTP (age ≥65 years). Patients were stratified based on THC use. Propensity score matching (1:2 ratio) was performed.. A total of 2,835 patients were matched (THC+: 945 and THC-: 1,890). Mean age was 70 ± 6 years, 94% sustained blunt injuries, and median ISS was 22[12-27]. Sixty-two percent of patients received thromboprophylaxis, with median time to initiation of 27 h from admission. Overall, the rate of TEC was 2.1% and mortality was 6.0%. THC + patients had significantly higher rates of TEC compared to THC- patients (3.0% vs. 1.7%; p = 0.01). Rates of DVT (2.2% vs 0.6%, p < 0.01) and PE (1.4% vs 0.4%, p < 0.01) were higher in the THC + group.. THC exposure increases the risk of TEC in GTP. Incorporation of THC use into risk assessment protocols merits serious consideration in GTP.

Topics: Aged; Anticoagulants; Cannabinoids; Cannabis; Dronabinol; Guanosine Triphosphate; Humans; Middle Aged; Retrospective Studies; Thrombosis; Venous Thromboembolism

This study was designed to clarify the mechanism of a reversal of the ischemia-induced decrease in adenosine triphosphate (ATP) in relation to the changes in liver blood flow. All vessels to the left and median lobes were occluded for 15 or 30 min and then reperfused for 15 or 30 min, respectively. Ischemia led to a significant decrease in the ATP level. ATP levels recovered fully after 30 min of reperfusion following 15 min of occlusion. However, a significantly low ATP level was observed even after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 (5 mg/kg, i.v.), a thromboxane A2 (TXA2) synthetase inhibitor, significantly improved the recovery of ATP levels after 30 min of reperfusion following 30 min of occlusion. Liver blood flow was restored fully immediately after reperfusion following 15 min of occlusion. In contrast a significantly low liver blood flow was observed after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 accelerated the recovery of liver blood flow after reperfusion. Morphological studies revealed that microthrombi were formed during ischemia, and CV-4151 mitigated the formation of microthrombi. These results indicate that the formation of microthrombi, which might be associated with TXA2 synthesis during ischemia, inhibited the restoration of liver blood flow, which might be responsible for the obstruction of the recovery of ATP.

Topics: Adenosine Triphosphate; Animals; Fatty Acids, Monounsaturated; Guanosine Triphosphate; Liver; Male; Pyridines; Rats; Rats, Inbred Strains; Reperfusion Injury; Thrombosis; Thromboxane-A Synthase