CC Cardiol Croat Cardiologia Croatica Cardiol. Croat. 1848-543X 1848-5448 Croatian Cardiac Society CC 2019 14_9-10_224-5 10.15836/ccar2019.224 Extended Abstract Lower platelet count early after the heart transplantation is associated with lower rates of cellular-mediated rejection within 24 months after heart transplantation https://orcid.org/0000-0001-5979-2346SkorićBoško1 https://orcid.org/0000-0003-2633-3439FabijanovićDora1* https://orcid.org/0000-0002-3197-2190PašalićMarijan1 https://orcid.org/0000-0002-6723-6822Reschner PlanincAna2 https://orcid.org/0000-0001-8314-1770BotonjićHata3 https://orcid.org/0000-0001-7171-2206Ljubas MačekJana1 https://orcid.org/0000-0002-4772-5549ČikešMaja1 https://orcid.org/0000-0003-0561-6704PlanincIvo1 https://orcid.org/0000-0002-9346-6402SamardžićJure1 https://orcid.org/0000-0002-2599-553XJurinHrvoje1 https://orcid.org/0000-0002-5052-6559LovrićDaniel1 https://orcid.org/0000-0002-2492-3702GašparovićHrvoje1 https://orcid.org/0000-0002-7282-9753IvančanVišnja1 https://orcid.org/0000-0001-9101-1570MiličićDavor1 University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia Izola General Hospital, Izola, Slovenia University of Zagreb School of Medicine, Zagreb, Croatia ADDRESS FOR CORRESPONDENCE: Dora Fabijanović, Klinički bolnički centar Zagreb, Kišpatićeva 12, HR-10000 Zagreb, Croatia. / Phone: +385-98-9387-273 / E-mail: dora.fabijanovic@gmail.com 102019 14 9-10 224 225 08092019 16092019 2019 Croatian Cardiac Society KEYWORDS: heart transplantationplatelet countcellular-mediated rejection

Background: Decrease in platelet count following the induction with polyclonal anti-thymocyte globulin (ATG) is deemed as an adverse event, while decrease in lymphocyte count represents a therapeutic goal (1). Still, the effect on platelets may represent an important part of ATG anti-rejection mechanisms.

Patients and Methods: This was a retrospective single-center study of consecutive HTx (heart transplantation) patients (pts) from February 2010 to February 2018 in University Hospital Centre Zagreb. All pts received rATG (Thymoglobulin®) 1.5 mg/kg daily during the first 5 days. Complete blood count with differential was assessed on days 0, 7 and 14 after HTx. The incidence of cellular-mediated rejection (ACR) was monitored for two years after HTx. ACR was classified according to ISHLT classification from 1990 and expressed as ACR of grade 1B or higher (≥1B).

Results: A total of 159 pts were transplanted. Median age was 55 years (IQR, 47-62 years), 76% were male. A total of 27 pts (17%) experienced ACR ≥1B during 24 months. Pts with ACR of grade ≥1B had higher platelet count on day 7 (145 vs 104 x 103/µL, p<0.001). They also had higher the absolute lymphocyte count (ALC) on the same day, but this did not reach statistical significance (162 vs 130 x 103/µL, p=0.19) and there was no correlation between ALC and platelet counts on day 7 (Pearson’s correlation coefficient was 0.064, p=0.459). Conversely, more rejection was observed in pts with higher ALC on day 14 (326 vs 190 x 103/µL, p=0.035), with a trend towards statistical significance in the relationship with higher platelet count (210 vs 199 x 103/µL, P=0.076). In the univariate analysis, higher platelet count on day 7, younger recipient age and negative pre-transplant Cytomegalovirus (CMV) IgG serology were found as predictors of the ACR ≥1B in the first 2 years after HTx (Table 1). In multivariable model, platelet count on day 7 and pre-transplant CMV serostatus were independent predictors of rejection. ROC analysis of the aforementioned model showed a satisfying AUC of 0.75.

Univariate Analysis of Acute Cellular Rejection (ACR of grade ≥1B) in the first 2 years after heart transplantation.
Variable HR 95% CI p value
Recipient age, years 0.961 0.939-0.984 0.001
Recipient genderMale 0.625 0.281-1.392 0.25
Positive pre-transplant recipient CMV IgG 0.319 0.133-0.766 0.011
Donor/recipient CMV mismatch 2.646 0.778-8.994 0.119
Donor age, years 0.971 0.943-1.001 0.059
Donor genderMale 1.594 0.643-3.949 0.314
Pre-transplant mechanical circulatory support 1.677 0.573-4.908 0.345
Ischemia time, min 1.001 0.995-1.007 0.678
Absolute lymphocyte count on day 7, x 103/µL 1.000 0.999-1.002 0.446
Absolute lymphocyte count on day 14, x 103/µL 1.001 1.000-1.001 0.074
Platelet count on day 7, x 103/µL 1.007 1.002-1.013 0.006
Platelet count on day 14, x 103/µL 1.004 1.000-1.008 0.074
Positive post-transplant CMV PCR 0.501 0.118-2.127 0.349
Calcineurin inhibitor, No. (%)Tacrolimus vs Cyclosporine 0.840 0.393-1.796 0.653
CMV = Cytomegalovirus; PCR = polymerase chain reaction.

Conclusion: Decrease in platelet count following the induction with rATG is strongly related to less graft rejection that is independent from the lymphodepleting effect. This indicates the importance of platelet involvement in anti-rejection mechanisms of ATG induction, and consequently a possible rationale for targeting platelets in future immunosuppressive regimens.

LITERATURE SchnetzlerBLegerPVölpADorentRPavieAGandjbakhchI. A prospective randomized controlled study on the efficacy and tolerance of two antilymphocytic globulins in the prevention of rejection in first-heart transplant recipients. Transpl Int. 2002 Jun;15(6):317–25. 10.1111/j.1432-2277.2002.tb00171.x12072903