The causes of thrombocytopenia after transcatheter aortic valve implantation

      Highlights

      • The mechanism of TP following TAVI is complex and mediated by some platelet as well as blood coagulation activation factors.
      • Platelet reduction shortly after TAVI procedure might be related to the amount of contrast.
      • Enhanced platelet activation following TAVI might justify the use of the second antiplatelet agent after the procedure.

      Abstract

      Introduction

      Even though thrombocytopenia following transcatheter aortic valve implantation (TAVI) has been described, further investigation of this phenomenon is needed.

      Aims

      To determine which factors may explain the fall in platelet count that occurs after implantation of a TAVI device, including markers of platelet and blood coagulation activation.

      Material and methods

      32 patients without previous indications for dual antiplatelet therapy (mean age 78.5 ± 7.9 years, 62% females) with severe aortic valve stenosis (mean gradient 54.6 ± 16.9 mm Hg) who qualified for TAVI procedure (Edwards Sapien XT) were prospectively analyzed. Platelet counts were analyzed before the surgery, on the day of the procedure and for the three following postoperative days (POD 1 to 3). To assess platelet activation P-selectin (PS, serum) and platelet factor 4 (PF-4, CTAD plasma) were measured, whereas for the evaluation of coagulation activation prothrombin fragments 1 + 2 (F1 + 2, plasma) were assessed before the procedure, on POD-1 and POD-3 (ELISA).

      Results

      During the postoperative period a significant platelet count drop, the most evident on POD-2, was observed followed by a platelet count raise. The platelet count drop correlated directly with the amount of iodinated contrast agent (r = 0.42, p = 0.016) and inversely with baseline mean platelet volume (r = −0.37, p = 0.046). Neither clinical nor perioperative parameters, except contrast medium, influenced platelet count decrease. No significant differences regarding the concentration of the evaluated markers in patients with and without thrombocytopenia were found. PF-4 and F1 + 2 significantly changed during the study (p < 0.05). Greater acute PF-4 decrease correlated with greater acute platelet count drop (r = 0.48, p = 0.043), and during the study slower PF-4 increase correlated with higher platelet count increase on POD-3 (r = −0.505, p = 0.032). Lower baseline PS correlated with lower baseline platelet count and higher platelet count increase on POD-3 (r = 0.45, p = 0.04 and =−0.55, p = 0.02, respectively). No significant correlations between F1 + 2 concentrations and platelet count changes have been found.

      Conclusions

      Platelet reduction shortly after TAVI procedure is related to the amount of contrast agent applied during the procedure. Platelet activation and blood coagulation along with impaired baseline platelet renewal might be the mechanisms of thrombocytopenia following TAVI procedure.

      Abbreviations:

      F1+2 (prothrombin fragments 1+2), MPV (mean platelet volume), PF-4 (platelet factor 4), POD (postoperative day), PS (P-selectin), TAVI (transcatheter aortic valve implantation)

      Keywords

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      References

        • Dvir D.
        • Généreux P.
        • Barbash I.M.
        • Kodali S.
        • Ben-Dor I.
        • Williams M.
        • et al.
        Acquired thrombocytopenia after transcatheter aortic valve replacement: clinical correlates and association with outcomes.
        Eur. Heart J. 2014; 35: 2663-2671
        • Hirnle T.
        • Juszczyk G.
        • Tycinska A.
        • Stankiewicz A.
        • Zak G.
        • Lewczuk A.
        • et al.
        Thrombocytopenia and perioperative complications after stentless freedom solo valve implantation.
        Kardiol. Pol. 2013; 71: 334-340
        • Martin J.F.
        • Daniel T.D.
        • Trowbridge E.A.
        Acute and chronic changes in platelet volume and count after cardiopulmonary bypass induced thrombocytopenia in man.
        Thromb. Haemost. 1987; 57: 55-58
        • De Labriolle A.
        • Bonello L.
        • Lemesle G.
        • Roy P.
        • Steinberg D.H.
        • Xue Z.
        • et al.
        Decline in platelet count in patients treated by percutaneous coronary intervention: definition, incidence, prognostic importance, and predictive factors.
        Eur. Heart J. 2010; 31: 1079-1087
        • Flaherty M.P.
        • Mohsen A.
        • Moore 4th, J.B.
        • Bartoli C.R.
        • Schneibel E.
        • Rawasia W.
        • et al.
        Predictors and clinical impact of pre-existing and acquired thrombocytopenia following transcatheter aortic valve replacement.
        Catheter. Cardiovasc. Interv. 2015; 85: 118-129
        • Jilaihawi H.
        • Doctor N.
        • Chakravarty T.
        • Kashif M.
        • Mirocha J.
        • Cheng W.
        • et al.
        Major thrombocytopenia after balloon-expandable transcatheter aortic valve replacement: prognostic implications and comparison to surgical aortic valve replacement.
        Catheter. Cardiovasc. Interv. 2015; 85: 130-137
        • Rodés-Cabau J.
        • Palacios A.
        • Palacio C.
        • Girona J.
        • Galve E.
        • Evangelista A.
        • et al.
        Assessment of the markers of platelet and coagulation activation following transcatheter closure of atrial septal defects.
        Int. J. Cardiol. 2005; 98: 107-112
        • Sokołowska B.
        • Dmoszyńska A.
        • Kowalska A.M.
        The role of PF4 (CXCL4) in the process of clot formation.
        Acta Haematol. Pol. 2012; 43: 150-154
        • Huczek Z.
        • Kochman J.
        • Filipiak K.J.
        • Horszczaruk G.J.
        • Grabowski M.
        • Piatkowski R.
        • et al.
        Mean platelet volume on admission predicts impaired reperfusion and long-term mortality in acute myocardial infarction treated with primary percutaneous coronary intervention.
        J. Am. Coll. Cardiol. 2005; 46: 284-290
        • Chu S.G.
        • Becker R.C.
        • Berger P.B.
        • Bhatt D.L.
        • Eikelboom J.W.
        • Konkle B.
        • et al.
        Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis.
        J. Thromb. Haemost. 2010; 8: 148-156
        • McCabe J.M.
        • Huang P.H.
        • Riedl L.A.
        • Devireddy S.R.
        • Grondell J.
        • Connors A.C.
        • et al.
        Incidence and implications of idiopathic thrombocytopenia following transcatheter aortic valve replacement with the Edwards Sapien(©) valves: a single center experience.
        Catheter. Cardiovasc. Interv. 2014; 83: 633-641
        • Kappetein A.P.
        • Head S.J.
        • Généreux P.
        • Piazza N.
        • van Mieghem N.M.
        • Blackstone E.H.
        • et al.
        Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2).
        J. Thorac. Cardiovasc. Surg. 2013; 145: 6-23
        • Magri C.J.
        • Chieffo A.
        • Durante A.
        • Latib A.
        • Montorfano M.
        • Maisano F.
        • et al.
        Impact of mean platelet volume on combined safety endpoint and vascular and bleeding complications following percutaneous transfemoral transcatheter aortic valve implantation.
        Biomed. Res. Int. 2013; 645265
        • Gallet R.
        • Seemann A.
        • Yamamoto M.
        • Hayat D.
        • Mouillet G.
        • Monin J.L.
        • et al.
        Effect of transcatheter (via femoral artery) aortic valve implantation on the platelet count and its consequences.
        Am. J. Cardiol. 2013; 111: 1619-1624
        • Auffret V.
        • Boulmier D.
        • Oger E.
        • Bedossa M.
        • Donal E.
        • Laurent M.
        • et al.
        Predictors of 6-month poor clinical outcomes after transcatheter aortic valve implantation.
        Arch. Cardiovasc. Dis. 2014; 107: 10-20
        • García Bueno M.J.
        Thrombocytopenia and iodinated contrast.
        J. Investig. Allergol. Clin. Immunol. 2009; 19: 511-512
        • Bata P.
        • Tarnoki A.D.
        • Tarnoki D.L.
        • Horvath E.
        • Berczi V.
        • Szalay F.
        Acute severe thrombocytopenia following non-ionic low-osmolarity intravenous contrast medium injection.
        Korean J. Radiol. 2012; 13: 505-509
        • Sedaghat A.
        • Falkenberg N.
        • Sinning J.M.
        • Kulka H.
        • Hammerstingl C.
        • Nickenig G.
        • et al.
        TAVI induces an elevation of hemostasis-related biomarkers, which is not causative for post-TAVI thrombocytopenia.
        Int. J. Cardiol. 2016; 221: 719-725
        • Sexton T.R.
        • Wallace E.L.
        • Chen A.
        • Charnigo R.J.
        • Reda H.K.
        • Ziada K.M.
        • et al.
        Thromboinflammatory response and predictors of outcomes in patients undergoing transcatheter aortic valve replacement.
        J. Thromb. Thrombolysis. 2016; 41: 384-393
        • Nobili M.
        • Sheriff J.
        • Morbiducci U.
        • Redaelli A.
        • Bluestein D.
        Platelet activation due to hemodynamic shear stresses: damage accumulation model and comparison to in vitro measurements.
        ASAIO J. 2008; 54: 64-72
        • Páramo J.A.
        Prothrombin fragments in cardiovascular disease.
        Adv. Clin. Chem. 2010; 51: 1-23
        • Berger G.
        • Hartwell D.W.
        • Wagner D.D.
        P-selectin and platelet clearance.
        Blood. 1998; 92: 4446-4452
        • Repossini A.
        • Tononi L.
        • Martinil G.
        • Di Bacco L.
        • Girolettiz L.
        • Rosati F.
        • et al.
        Platelet activation after sorin freedom solo valve implantation: a comparative study with Carpentier-Edwards Perimount Magna.
        J. Heart Valve Dis. 2014; 23: 777-782
        • Rucinski B.
        • Niewiarowski S.
        • Strzyzewski M.
        • Holt J.C.
        • Mayo K.H.
        Human platelet factor 4 and its C-terminal peptides: heparin binding and clearance from the circulation.
        Thromb. Haemost. 1990; 63: 493-498
        • Semenov A.V.
        • Romanov Y.A.
        • Loktionova S.A.
        • Tikhomirov O.Y.
        • Khachikian M.V.
        • Vasil'ev S.A.
        • et al.
        Production of soluble P-selectin by platelets and endothelial cells.
        Biochemistry (Mosc). 1999; 64: 1326-1335
        • Blann A.D.
        • Lip G.Y.
        Hypothesis: is soluble P-selectin a new marker of platelet activation?.
        Atherosclerosis. 1997; 128: 135-138
        • Blann A.D.
        • Lip G.Y.
        • Beevers D.G.
        • McCollum C.N.
        Soluble P-selectin in atherosclerosis: a comparison with endothelial cell and platelet markers.
        Thromb. Haemost. 1997; 77: 1077-1080
        • Pernerstorfer T.
        • Eichler H.G.
        • Stohlawetz P.
        • Speiser W.
        • Jilma B.
        Effects of heparin and aspirin on circulating P-selectin, E-selectin and von Willebrand factor levels in healthy men.
        Atherosclerosis. 2001; 155: 389-393
        • Chan M.Y.
        • Andreotti F.
        • Becker R.C.
        Hypercoagulable states in cardiovascular disease.
        Circulation. 2008; 118: 2286-2297