Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation. To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation. The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels. The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation. The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.

Background/Objectives: Cardiac troponin I (cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥2R. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients after exclusion of ambiguous measurements and episodes without a preceding confirmed cTnI value. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log₂-transformed cTnI, whereas M2 additionally included the time-normalized change in log₂-transformed cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation; 95% confidence intervals were obtained from 2000 patient-level cluster bootstrap resamples. Results: In the overall cohort, M1 showed modest discrimination (AUC 0.641, 95% CI 0.592–0.689), whereas M2 provided no improvement (AUC 0.635, 95% CI 0.584–0.685; ΔAUC −0.007, 95% CI −0.021 to 0.007). Within 90 days after transplantation, neither model was informative (M1 AUC 0.503; M2 AUC 0.494). Beyond 90 days, M1 showed moderate discrimination (AUC 0.758, 95% CI 0.664–0.838), but M2 again provided no improvement (AUC 0.746, 95% CI 0.654–0.828; ΔAUC −0.012, 95% CI −0.037 to 0.008). Conclusions: Concurrent cTnI showed no discrimination within 90 days and moderate discrimination thereafter in exploratory stratified analyses. The kinetic term provided no incremental value. cTnI cannot replace endomyocardial biopsy but may warrant further evaluation as an adjunctive late-period marker.

DOI: 10.20452/pamw.16600, Published online: November 06, 2023, Authors: Justyna M. Sokolska, Magdalena Pszczołowska, Katarzyna Logoń, Magdalena Cielecka, Mateusz Sokolski, Michał Zakliczyński

BACKGROUND Coronary vasculopathy is one of the most serious late complications after heart transplantation (Htx). The aim of this study was to assess the utility and safety of the invasive assessment of coronary physiology and investigate the occurrence of coronary microvascular dysfunction (CMD) and its association with clinical characteristics of recipients and donors. MATERIAL AND METHODS Coronary microcirculation was assessed during routine coronary angiography, performed prospectively between December 1, 2020, and July 24, 2023, by using index of microcirculatory resistance (IMR) and coronary flow reserve (CFR). Values of IMR ³25 or CFR <2.0 confirmed CMD. RESULTS Thirty-three patients aged 49±14 years were included; 21 (64%) were men. CMD was found in 8 (24%) patients. There were no complications, and examination was performed in all patients. The median values for IMR and CFR were 13 [IQR: 10-20] and 3.6 [IQR: 2.2-4.9], respectively. CMD was more common in younger patients: 40±16 vs 51±13 years (P=0.045), and those with lower BMI: 22±4 vs 26±4 kg/m² (P=0.016). Patients with CMD were more likely to require pacemaker implantation, with 3 (38%) vs 1 (4%) in the post-transplant period (P=0.012). The median time since Htx was 2 [IQR: 2-10] years and was higher in the CMD group: 9.5 [IQR: 6-16] vs 2 [IQR: 1-8] years, (P=0.042). There were no significant differences in other recipient and donor characteristics. CONCLUSIONS Invasive assessment of coronary physiology was safe and effective and diagnosed CMD in nearly one-fourth of heart transplant recipients. CMD is related to age, time since transplantation, and chronotropic graft dysfunction.

Introduction: Takayasu arteritis (TA) is a rare large-vessel vasculitis that in selected patients can lead to severe cardiovascular complications, including advanced heart failure (HF), requiring heart transplantation (HTx). Marked pre-transplant high levels of anti-HLA antibodies and notable sensitization substantially complicate donor selection and may prolong time spent on transplant waitlists. In highly sensitized recipients, HTx may therefore require individualized perioperative desensitization strategies to reduce the risk of antibody-mediated graft injury. Case Summary: We present the case of a 46-year-old woman with TA and advanced HF who underwent HTx after individualized perioperative desensitization in the setting of significant pre-transplant sensitization (PRA > 60%). Her postoperative course required intensive clinical and immunological monitoring and treatment. The early PT course was complicated by severe clinical deterioration, including a life-threatening episode of asystole that occurred in temporal association with peak anti-HLA class I and II antibody levels. Discussion: The case highlights the complexity of alloimmune management in a patient with TA and marked pre-transplant sensitization. Also, the temporal relationship between peak antibody levels and clinical instability suggests the need for close immune surveillance, tailored desensitization and individualized immunosuppressive treatment strategies in this high-risk group. Conclusions: This case describes the clinical course of a highly sensitized patient with TA who underwent HTx following an individualized perioperative desensitization strategy based on a modified Hannover protocol. Although transplantation was followed by substantial postoperative complications, the patient remained clinically stable during follow-up. The efficacy of the modified desensitization strategy cannot be established from a single case.

Background/Objectives: High-sensitivity cardiac troponin I (hs-cTnI) has shown inconsistent diagnostic performance for acute cellular rejection (ACR) after heart transplantation. We evaluated whether time-normalized hs-cTnI kinetics provide incremental diagnostic value beyond the concurrent concentration for detecting ACR grade ≥ 2R and whether this association varies with time after transplantation. Methods: This retrospective single-center study included 1237 biopsy episodes from 139 heart transplant recipients. Two generalized linear mixed-effects logistic regression models with patient-specific random intercepts were compared. M1 included concurrent log₂-transformed hs-cTnI, whereas M2 additionally included the time-normalized change in log₂-transformed hs-cTnI per 7 days. Discrimination was assessed using leave-one-patient-out cross-validation with patient-level cluster bootstrap confidence intervals. Exploratory analyses examined early (≤90 days), late (>90 days), and continuous post-transplant time. Results: In the overall cohort, M1 showed modest discrimination (AUC 0.641, 95% CI 0.592–0.689), whereas M2 provided no improvement (AUC 0.635; ΔAUC −0.007). Within 90 days, neither model was informative (M1 AUC 0.503; M2 AUC 0.494). Beyond 90 days, M1 showed moderate discrimination (AUC 0.758, 95% CI 0.664–0.838), but M2 again provided no improvement (AUC 0.746; ΔAUC −0.012). Continuous-time modeling showed that the association between concurrent hs-cTnI and ACR strengthened with increasing time after transplantation, whereas the kinetic term remained non-informative. Conclusions: Time-normalized hs-cTnI kinetics did not provide incremental diagnostic value beyond concurrent hs-cTnI. Concurrent hs-cTnI may warrant further evaluation as an adjunctive late-period marker, but the 90-day threshold remains exploratory and requires external validation. Neither hs-cTnI concentration nor its kinetics should replace endomyocardial biopsy.