Clinical trial NCT00237328: Risk of Developing Antibodies to Heparin-PF4 After Heart Surgery
Official title: The Incidence of Thromboembolic Events in Patients With Antibodies to Heparin-PF4 After Cardiac Bypass
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Thrombosis
Keywords: Heparin resistance
Blood clotting
Heart surgery
Cardiopulmonary bypass
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2005-10-12
Enrollment: 1015
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals undergoing cardiac bypass surgery with heparin as the intra-operative anticoagulant at Duke University Hospital.

Brief summary: Heparin is a drug that is widely used to prevent and treat blood clotting. Individuals undergoing cardiopulmonary bypass surgery are administered high doses of heparin, and some of them develop antibodies to the drug. This immune response can lead to the formation of blood clots, setting the stage for a potential heart attack or stroke. The purpose of this study is to evaluate how often an immune response to heparin leads to the formation of blood clots in individuals who have had heart surgery.

Detailed description: Heparin is a drug that is widely used to prevent and treat blood clotting. However, heparin can also cause serious adverse events. Individuals undergoing cardiopulmonary bypass surgery are administered and therefore exposed to high doses of heparin. Studies have shown that up to 61% of cardiac bypass patients develop elevated levels of antibodies to heparin-PF4 after surgery. This immune response may activate blood platelets, possibly resulting in a blood clot. These clots most often develop in the legs and lungs, and may lead to a heart attack or stroke. The frequency of such a reaction has yet to be determined definitively. This study will evaluate the incidence of an immune response to heparin-PF4 that leads to the formation of blood clots in individuals who have had heart surgery.

Participants in this study will be recruited prior to a scheduled cardiac bypass surgery. They will first complete a structured pre-operative interview to collect baseline measures on demographics, comorbidities, history of heparin exposures, and prior thromboembolic events. Immediately prior to surgery, a blood sample will be taken to assess the individual's platelet count and level of antibodies to heparin-PF4. Following the operation, participants will be followed daily to assess heparin exposure, platelet counts, and any blood clotting. Subsequent blood samples will be taken 5 days and 1 month following the surgery to again evaluate the individual's platelet count and level of heparin-PF4 antibodies. Additionally, participants will undergo a structured interview at 1 and 3 months post-surgery to evaluate the incidence of outcomes related to heparin-PF4 antibodies.

Eligibility criteria: Inclusion Criteria:

* Scheduled for cardiac bypass surgery at Duke University Hospital

Exclusion Criteria:

* Plans to receive warfarin during the post-operative inpatient stay
* Plans to receive a full anticoagulant dose of low-molecular weight heparin during the post-operative inpatient stay
* Plans to receive a full anticoagulant dose of unfractionated heparin during the post-operative inpatient stay
* Use of any drug other than unfractionated heparin for anticoagulation during cardiopulmonary bypass
* Warfarin, heparin, or low-molecular weight heparin administered during a readmission to the hospital for a reason other than one of this study's outcomes does not constitute criteria for exclusion

Primary outcomes:
measure: Thrombotic events compatible with HIT
timeFrame: one year
Secondary outcomes:
measure: antibody positibe status post operative day 5 and day 30
timeFrame: one year
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Duke University
name: Thomas Ortel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S. doi: 10.1378/chest.126.3_suppl.311S.
citation: Alsoufi B, Boshkov LK, Kirby A, Ibsen L, Dower N, Shen I, Ungerleider R. Heparin-induced thrombocytopenia (HIT) in pediatric cardiac surgery: an emerging cause of morbidity and mortality. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2004;7:155-71. doi: 10.1053/j.pcsu.2004.02.024.
citation: Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y. Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia. Circulation. 1999 May 18;99(19):2530-6. doi: 10.1161/01.cir.99.19.2530.
citation: Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003 Dec;76(6):2121-31. doi: 10.1016/j.athoracsur.2003.09.034.
citation: Williams RT, Damaraju LV, Mascelli MA, Barnathan ES, Califf RM, Simoons ML, Deliargyris EN, Sane DC. Anti-platelet factor 4/heparin antibodies: an independent predictor of 30-day myocardial infarction after acute coronary ischemic syndromes. Circulation. 2003 May 13;107(18):2307-12. doi: 10.1161/01.CIR.0000066696.57519.AF. Epub 2003 Apr 21.