Aspirin Resistance in Single-Ventricle Physiology: Aspirin Prophylaxis Is Not Adequate to Inhibit Platelets in the Immediate Postoperative Period.
BACKGROUND
Incidence of thrombosis after initial stage 1 single-ventricle palliation is high. Most centers use aspirin as an antiplatelet agent to prevent thrombosis in surgically placed shunts. We hypothesize there is a significant incidence of aspirin resistance in infants after stage 1 palliation and this resistance can be overcome by an increased aspirin dose.


METHODS
This is a prospective observational study of 20 patients with single-ventricle physiology who required single-ventricle palliation with a controlled source of pulmonary blood flow (Norwood/Sano, Norwood/Blalock-Taussig [BT] shunt or BT shunt alone). Aspirin resistance was determined using thromboelastography with platelet mapping (TEG) and urine thromboxane (UTX). The UTX level of less than 1,500 pg/mL and TEG value of more than 50% were used to define as adequate platelet inhibition. The UTX was measured prior to starting aspirin (20 mg/day) and TEG and UTX were obtained after 5 days of aspirin therapy A repeat UTX was measured for patients who were determined to be aspirin resistant by TEG (<50% arachidonic acid inhibition) after doubling the dose (40 mg/day). Clinical variables including patient diagnosis, age of surgery, and cardiopulmonary bypass requirement, weight, hemoglobin, and platelet count were assessed to determine their association with aspirin resistance.


RESULTS
Eighty percent of patients were aspirin resistant using TEG (95% CI, 56% to 94%) and none of the patients achieved a UTX level of less than 1,500 pg/mL. Aspirin resistant patients did not respond to an increased dose of aspirin between the fifth and tenth days of therapy (p = 0.820). Patients did, however, respond to aspirin treatment when comparing the baseline UTX measurement with those recorded on the fifth day (p = 0.008) and the tenth day (p = 0.0361) of aspirin therapy. The UTX levels did not differ between those who were and those who were not aspirin resistant by TEG at any of the measurement times. The clinical variables were not associated with aspirin resistance status.


CONCLUSIONS
There is a high incidence of aspirin resistance in the immediate postoperative period after single-ventricle shunt palliation. Aspirin might not be an adequate agent for shunt prophylaxis in this patient population. Further studies are needed to identify at-risk patients who might benefit from additional testing and specific anticoagulation.
Department of Pediatrics, Section of Pediatric Cardiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address: arshid-mir@ouhsc.edu.
Arshid
A
Mir
Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
Summer
S
Frank
Department of Pediatrics, Children Medical Center Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.
Janna
J
Journeycake
Department of Pediatrics, Children Medical Center Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.
Joshua
J
Wolovitis
Department of Surgery, Children Medical Center Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.
Kristine
K
Guleserian
Department of Pediatrics, Children Medical Center Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.
Lisa
L
Heistein
Department of Pediatrics, Children Medical Center Dallas, University of Texas Southwestern Medical Center, Dallas, Texas.
Matthew
M
Lemler
D001241:Aspirin / Q000008:administration & dosage*; D058366:Blalock-Taussig Procedure / Q000009:adverse effects / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000378:metabolism / Q000601:surgery*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011446:Prospective Studies; D013781:Texas / Q000453:epidemiology; D013916:Thrombelastography; D013927:Thrombosis / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D013931:Thromboxanes / Q000652:urine
D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D001241:Aspirin