thromboxane-a2 and Peripheral-Arterial-Disease

The goal of this study is to establish the prevalence of high on-treatment platelet reactivity to aspirin (HPRA) and clopidogrel (HPRC) in patients with critical limb ischemia (CLI).. CLI is associated with an increased risk of death and cardiovascular events. Unlike other patient populations with atherosclerotic cardiovascular disease, previous studies failed to demonstrate a benefit of antiplatelet therapy in patients with CLI.. From June 2014 to November 2016, we performed platelet reactivity studies for P2Y12 and thromboxane A2 (TXA2) inhibition in 100 CLI patients receiving daily treatment with aspirin and clopidogrel. P2Y12 inhibition was measured by two assays: vasodilator-stimulated phosphoprotein (VASP) and VerifyNow P2Y12 assays. HPRC was defined as VerifyNow P2Y12 reactive units (PRU) >208 and VASP-platelet reactivity index (VASP-PRI) >50%. TXA2 inhibition was measured with the VerifyNow aspirin test and HPRA was defined as aspirin reaction units (ARU) >550.. Mean age was 67±11 years, 50% were male, 80% had diabetes mellitus, and 26% had chronic renal insufficiency. Thirty-three percent of patients had a PRU >208 and 46% a VASP-PRI >50%. HPRC was present in 26% of patients based on the criteria of both a PRU >208 and VASP-PRI >50%. HPRA was present in 25% of patients. The overall prevalence of HPR to ASA or clopidogrel was 35% and HPR to both drugs was present in 8% of patients. Clinical characteristics were similar between groups.. HPR to aspirin or clopidogrel is highly prevalent in patients with CLI. Nearly one in ten patients with CLI is a hyporesponder to both aspirin and clopidogrel.

Topics: Aged; Aged, 80 and over; Aspirin; Blood Platelets; Cell Adhesion Molecules; Clopidogrel; Critical Illness; Drug Therapy, Combination; Female; Humans; Ischemia; Male; Microfilament Proteins; Middle Aged; Peripheral Arterial Disease; Phosphoproteins; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Thromboxane A2; Time Factors; Treatment Outcome

The authors investigated prostacyclin (PGI2) and thromboxane (TX) productions in peripheral venous blood after lower limb revascularization by percutaneous transluminal angioplasty (PTA) versus diagnostic angiography. The purpose of this study was to investigate PGI2/TX imbalance after PTA. This imbalance is of pathophysiologic importance and it is a potential sign of platelet function alteration.. Twenty-five patients requiring PTA were compared with 20 patients undergoing angiography alone from April 2004-December 2005 from a single vascular unit. Patient age range was 42-90 years, and the majority of patients were men. Prostaglandin F2-alpha (PGF2-alpha) and thromboxane B2 (TXB2) were measured sequentially (preprocedure, at 1 hour, and 24 hours after procedure). Differences between postprocedure and preprocedure level were compared statistically between angiography and PTA.. Baseline demographics were distributed equally between the two groups except presence of critical ischemia and ankle brachial pressure index, which were two significant confounders. TXB2 was significantly higher after PTA at 1 hour and 24 hours after PTA (P = .005 and P = .014 respectively), PGF2-alpha was significantly higher 24 hours after PTA only (P = .018) (Mann-Whitney U test).. PGI2/TX balance homeostasis is of significant pathophysiologic importance. The authors found that PTA results in significant PGI2/TX imbalance and shifts more toward increased TX production. This finding is partly suggestive of significant platelet activation. This imbalance in PGI2/TX level may have implications for future failure of PTA. Future research in reducing this platelet activation is recommended.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty; Ankle Brachial Index; Biomarkers; Blood Platelets; Constriction, Pathologic; Dinoprost; England; Epoprostenol; Female; Femoral Artery; Humans; Iliac Artery; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Platelet Activation; Prostaglandins I; Radiography, Interventional; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors; Treatment Outcome