Clinical trial NCT03835598: Post-Operative Thrombocytopenia After Bio-prosthesis Implantation
Official title: Post-Operative Thrombocytopenia After Bio-prosthesis Implantation (PORTRAIT Study): a Retrospective International Multicenter Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Thrombocytopenia
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2019-02-08
Enrollment: 1233
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The population is composed by adult patients submitted to isolated aortic valve replacement, percutaneous trans-catheter aortic valve implantation, and mitral valve replacement with a bio-prosthesis.

Brief summary: The objective of the study is to obtain the clinical data from patients who received a biological prosthesis in aortic or mitral position, in order to evaluate the occurrence of peri-operative thrombocytopenia.

The aim of the study is to analyze the eventual clinical impact of the phenomenon (re-operation for bleeding, blood transfusion) and the mortality rate.

This is a multicentre retrospective, observentional clinical study. This study will enroll up to 5000 patients since 2000 to date.

Detailed description: Cardiac surgery is commonly associated with a transient post-operative decrease in the platelet count. Thrombocytopenia after cardiopulmonary bypass can be explained by hemodilution, exposure to artificial surfaces with platelet activation and adhesion, hypothermia, blood loss and mechanical sequestration. It usually occurs between the second and third postoperative days, resulting in a reduction of platelet counts by 40-50% from baseline values. Moreover, when a foreign body as a valve prosthesis is literally placed into the blood flow, blood cells are constantly exposed to its surface and eventually inflammatory and, perhaps, autoimmune reactions could start. The interactions biomaterial-blood induce changes in platelet shape, metabolism as well as receptor-mediated dysfunction and lysis. Then, any significant decline in the circulating platelet count raises concerns about coagulation disorders and bleeding.

Despite the advanced hemodynamic performance, recently thrombocytopenia (defined as nadir platelet count \< 150.000 x 1000/uL) has been associated to new aortic biological prostheses, either rapid deployment or trans-catheter valves. Although several studies have been carried on, the drop in the platelet count after aortic valve replacement with certain tissue valves remains unexplained yet. The decrease after the valve implantation, however, is not exclusively limited to the surgical prostheses. Trans-catheter aortic valves, in fact, were found to be associated to post-procedure thrombocytopenia. Thrombocytopenia following transcatheter aortic valve implantation (TAVI) procedures is related to the increased adverse events rate such as death, stroke, acute kidney injury, bleeding and vascular complications. Furthermore, thrombocytopenia seems to occur most likely associated after balloon-expandable valves implantation.The literature, however, is confounding.

Despite several studies, little is known about the mechanism involved. Variations in biocompatibility of valve tissue as like a strong immune/inflammatory response could be some explanations. However, there is still uncertainty about the mechanism conditioning post-operative platelet drop. To address this uncertain the underlying process should be evaluated in a large multicentre trial.

The aims of the study are the following:

* to analyze the occurrence of thrombocytopenia after isolated aortic valve replacement/implantation and after isolated mitral valve replacement;
* to evaluate the clinical impact of thrombocytopenia (length of stay, bleeding, re-operation for bleeding, blood transfusion, mortality).

The study is multicentre, retrospective, observational and will enroll up to 5000 since 2000 to date.

Eligibility criteria: Inclusion Criteria:

* Patients undergoing isolated aortic valve replacement/implantation or isolated mitral valve replacement with a biological prosthesis.

Exclusion Criteria:

* Pre-existent thrombocytopenia;
* Oncologic diseases;
* Pre-existent infections/inflammations;
* Use of drugs inducing thrombocytopenia (\<3months);
* Combined cardiac surgery operations;
* Recent percutaneous cardiac intervention (\<1month).

Primary outcomes:
measure: Platelet count
timeFrame: During the index hospital stay, an average of 5 days
measure: Platelet count
timeFrame: 1-3months follow-up
measure: packed Red Cells transfusion, fresh frozen plasma transfusion, Platelet transfusion
timeFrame: During the index hospital stay, an average of 5 days
measure: Major bleeding (requiring more than 2 Red blood cells transfusions)
timeFrame: From the index procedure up to 3 months
measure: Re-exploration for bleeding
timeFrame: From the index procedure up to 3 months
Secondary outcomes:
measure: In-hospital mortality
timeFrame: Participants are followed during the duration of hospital stay (expected: up to 7 days post-op)
measure: In-hospital length of stay
timeFrame: From the index procedure through discharge from the hospital (expected: up to 7 days post-op)
measure: ICU length of stay
timeFrame: From the index procedure through discharge from the Intensive Care Unit (expected: up to 2 days post op)
measure: Gastro-intestinal bleeding
timeFrame: From the index procedure within 3 months
measure: Intracranial Bleeding
timeFrame: From the index procedure within 3 months
measure: Thrombosis
timeFrame: From the index procedure within 3 months
measure: 30-day mortality
timeFrame: within 30 days
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Federica Jiritano
Study officials:
References:
citation: Yerebakan C, Kaminski A, Westphal B, Kundt G, Ugurlucan M, Steinhoff G, Liebold A. Thrombocytopenia after aortic valve replacement with the Freedom Solo stentless bioprosthesis. Interact Cardiovasc Thorac Surg. 2008 Aug;7(4):616-20. doi: 10.1510/icvts.2007.169326. Epub 2008 May 27.
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citation: Repossini A, Tononi L, Martinil G, Di Bacco L, Girolettiz L, Rosati F, Muneretto C. Platelet activation after sorin freedom solo valve implantation: a comparative study with Carpentier-Edwards Perimount Magna. J Heart Valve Dis. 2014 Nov;23(6):777-82.
citation: Albacker TB. Thrombocytopenia associated with Perceval sutureless aortic valve replacement in elderly patients: a word of caution. Heart Surg Forum. 2015 Jun 26;18(3):E093-7. doi: 10.1532/hsf.1324.
citation: Stanger O, Grabherr M, Gahl B, Longnus S, Meinitzer A, Fiedler M, Tevaearai H, Carrel T. Thrombocytopaenia after aortic valve replacement with stented, stentless and sutureless bioprostheses. Eur J Cardiothorac Surg. 2017 Feb 1;51(2):340-346. doi: 10.1093/ejcts/ezw295. No abstract available.
citation: Gallet R, Seemann A, Yamamoto M, Hayat D, Mouillet G, Monin JL, Gueret P, Couetil JP, Dubois-Rande JL, Teiger E, Lim P. Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences. Am J Cardiol. 2013 Jun 1;111(11):1619-24. doi: 10.1016/j.amjcard.2013.01.332. Epub 2013 Mar 20.
citation: Jilaihawi H, Doctor N, Chakravarty T, Kashif M, Mirocha J, Cheng W, Lill M, Nakamura M, Gheorghiu M, Makkar RR. Major thrombocytopenia after balloon-expandable transcatheter aortic valve replacement: prognostic implications and comparison to surgical aortic valve replacement. Catheter Cardiovasc Interv. 2015 Jan 1;85(1):130-7. doi: 10.1002/ccd.25430. Epub 2014 Feb 27.