Perioperative platelet reactivity and the effects of clonidine

• Published in: Anesthesiology (Philadelphia) Vol. 79; no. 2; pp. 255 - 261
• Main Authors: ROSENFELD, B. A, FARADAY, N, CAMPBELL, D, DORMAN, T, CLARKSON, K, SIEDLER, A, BRESLOW, M. J, BELL, W
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01-08-1993
• Subjects: Abdomen - surgery; Adenosine Triphosphate - metabolism; Biological and medical sciences; Blood Platelets - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Clonidine - blood; Clonidine - therapeutic use; Female; Fibrinogen - drug effects; Humans; Intraoperative Period; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Postoperative Period; Aggregation; Human; α2-Adrenergic receptor; Chemotherapy; Platelet; Treatment; Surgery; Platelet function; Intraoperative; α-Adrenergic receptor agonist; Abdomen
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-199308000-00010

Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. alpha 2 Agonists, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared perioperative changes in platelet reactivity in 21 patients receiving either clonidine or placebo.
Patients undergoing major abdominal surgery were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative management, including preoperative sedation, general anesthesia without neuraxial opioids, or local anesthetics and postoperative patient-controlled intravenous morphine. Blood was obtained for measurement of clonidine level, fibrinogen concentration, platelet count, and platelet reactivity (impedance aggregometry and dense granule release) before induction and 24, 48, and 72 h postoperatively.
Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonidine and 8 of 10 received placebo (NS). Clonidine levels were therapeutic (1-2 ng/ml) throughout the study period. Clonidine administration had no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), compared to preoperative values, fibrinogen levels rose maximally (36%) at 72 h postoperatively and platelet counts decreased 22% at 48 h. Platelet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, and 72 h postoperatively. Thrombin-induced (supramaximal stimulus) dense granule release did not change from preoperative values.
These data indicate that major abdominal surgery causes increased platelet reactivity postoperatively but does not effect maximal degranulation. This increased platelet reactivity occurs within 48 h of surgery, coinciding with the peak incidence of postoperative arterial thrombotic complications. Clonidine administration has no effect on surgically induced changes in platelet reactivity. In this surgical patient population, the use of clonidine should not increase the risk of platelet-induced perioperative arterial thrombosis.