Risk of Developing Antibodies to Heparin-PF4 After Heart Surgery

Thrombosis Clinical Trial

— HIT  

Official title:

The Incidence of Thromboembolic Events in Patients With Antibodies to Heparin-PF4 After Cardiac Bypass

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00237328
• Other study ID #: Pro00010736
• Status: Completed
• Phase: N/A
• First received: October 11, 2005
• Last updated: February 22, 2013
• Start date: June 2006
• Est. completion date: July 2012

Study information

• Verified date: February 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1015
• Est. completion date: July 2012
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Thrombosis

Intervention

Drug:
• Heparin
Heparin will be used as the intra-operative anticoagulant

Locations

Country	Name	City	State
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Wisconsin	Madison	Wisconsin
United States	Mayo Clinic, Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View Citation

Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003 Dec;76(6):2121-31. Review. — View 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. Review. Erratum in: Chest. 2005 Jan;127(1):416. — View 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. Epub 2003 Apr 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Thrombotic events compatible with HIT		one year	No
Secondary	antibody positibe status post operative day 5 and day 30		one year	No