The real world experience of the biodegradable polymer-coated sirolimus-eluting coronary stent system: Results From an "All-Comers" Clinical Experience.

OBJECTIVES: This INDOLIMUS Registry sought to evaluate the safety and efficacy of the biodegradable polymer coated Indolimus(®) sirolimus-eluting coronary stent for the treatment of coronary artery disease across a wide range of patients treated in routine clinical practice, including those with high-risk characteristics and complex lesions. BACKGROUND: First-generation drug-eluting stents utilize nonbiodegradable polymeric coatings, whose persistent presence in the arterial wall may negatively affect long-term outcomes. It has been hypothesized that persistent presence of polymer may compromise the safety of drug-eluting stents, and that therefore biodegradable polymer coatings might reduce late adverse events in an unselected patient population. METHODS: All 530 consecutive unselected patients (415 males and 115 females) included who underwent percutaneous coronary intervention at the Sri Venkateswara Institute of Medical Sciences, Tirupati, India between August 2012 and March 2013, with an in-hospital, at 30-days and at 6-months follow-up. Retrospective analysis of those data had been done. RESULTS: A total of 617 lesions were treated in 530 enrolled patients (mean age 54.9 ± 10.8 years) with average stent length of 18.8 ± 6.0 mm. An average of 1.18 stents was implanted per patient. The patients' characteristics are noted as having 169 (31.9%) patients of diabetics and 215 (40.6%) hypertension. Smoking, alcoholism and tobacco chewing were found in 273 (51.5%), 130 (24.5%) and 17 (3.2%), respectively. The indications for intervention were unstable angina in 77 (14.5%) and previous myocardial infarction in 56 (10.6%) of the patients. Lesions were of type B2 in 264 (42.7%) and type C in 127 (20.6%). Stent delivery was successful in all cases and in-hospital, 30-days and 6-months follow-up of all 530 patients was obtained. The incidence of any major adverse cardiac events at in-hospital, at 30-days and at 6-months were 5 (0.94%), 8 (1.52%), and 18 (3.40%), respectively. Long term follow-up of this registry is ongoing to confirm safety and efficacy profiles. CONCLUSIONS: The relatively low event rate that was observed in INDOLIMUS Registry indicates that the biodegradable polymer coated Indolimus(®) sirolimus-eluting coronary stent can achieve excellent clinical performances in a large group of patients. © 2013 Wiley Periodicals, Inc.

Hydrothermal fabrication of selectively doped organic assisted advanced ZnO nanomaterial for solar driven photocatalysis.

Hydrothermal fabrication of selectively doped (Ag(+)+Pd(3+)) advanced ZnO nanomaterial has been carried out under mild pressure temperature conditions (autogeneous; 150°C). Gluconic acid has been used as a surface modifier to effectively control the particle size and morphology of these ZnO nanoparticles. The experimental parameters were tuned to achieve optimum conditions for the synthesis of selectively doped ZnO nanomaterials with an experimental duration of 4 hr. These selectively doped ZnO nanoparticles were characterized using powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV-Vis spectroscopy and scanning electron microscopy (SEM). The solar driven photocatalytic studies have been carried out for organic dyes, i.e., Procion MX-5B dye, Cibacron Brilliant Yellow dye, Indigo Carmine dye, separately and all three mixed, by using gluconic acid modified selectively doped advanced ZnO nanomaterial. The influence of catalyst, its concentration and initial dye concentration resulted in the photocatalytic efficiency of 89% under daylight.

Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker.

BACKGROUND & OBJECTIVES: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. METHODS: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. RESULTS: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; p0 = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), p0 =0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75 th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; p0 <0.001) and (62.5 vs 25%; P<0.001) respectively]. INTERPRETATION & CONCLUSIONS: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.

Technetium-99m Methoxyisobutyl Isonitrile Stress MPI in Suspected Coronary Artery Disease Patients: A Prospective Study to Evaluate Clinical Significance of Adenosine-induced ECG Changes.

Purpose: The purpose of this study is to evaluate the adenosine pharmacological stress-induced electrocardiogram (ECG) changes and their association with stress-induced ischemic defects on myocardial perfusion scintigraphy (MPS) in the evaluation of coronary artery disease (CAD) and to evaluate event-free survival among patients with positive and negative ECG/MPS image findings. Methods: A total of 100 patients were examined using stress MPS from March 2020 to August 2021. Stress-induced ECG changes during adenosine infusion were evaluated. The summed stress score (SSS) was evaluated to identify ischemic defects in myocardium. Association of stress ECG changes and scintigraphic results was evaluated. Results: Out of 100 patients, stress ECG changes during adenosine infusion were seen among 34 patients, whereas 66 patients had normal ECG findings. Positive stress MPS findings with SSS >3 were seen in 22 patients, whereas 78 patients had SSS ≤3. There was no agreement between stress ECG changes and MPS findings with Cohen's kappa coefficient (κ) = -0.023, whereas there was mild agreement between stress ECG changes and SSS >7 with κ = 0.105. Median follow-up of 11 months showed more events among patients with positive ECG changes than negative ECG changes. Conclusion: Adenosine, pharmacological stress is safe to use, but few patients might experience some minor and transient symptoms. Adenosine may induce ECG changes in patients with or without positive MPS findings. Patients with concordant positive findings need aggressive cardiac care, whereas patients with small or no defects on MPS need close monitoring.

Assessment of mitral valve commissural morphology by transoesophageal echocardiography predicts outcome after balloon mitral valvotomy.

BACKGROUND: Balloon mitral valvotomy (BMV) is a safe and an effective treatment in patients with symptomatic rheumatic mitral stenosis. This study was conducted to validate the importance of assessing the morphology of mitral valve commissures by transoesophageal echocardiography and thereby predicting the outcome after balloon mitral valvotomy [BMV]. MATERIALS AND METHODS: Study consisted of 100 patients with symptomatic mitral stenosis undergoing BMV. The Commissural Morphology and Wilkins score were assessed by transoesophageal echocardiography. Both the commissures (anterolateral and posteromedial) were scored individually according to whether non-calcified fusion was absent (0), partial (1), or extensive (2) and calcification (score 0) and combined giving an overall commissural score of 0-4. Outcome of BMV was correlated with commissural score and Wilkins score. RESULTS: The commissural score and outcome after BMV correlated significantly. 66 of 70 patients (94%) with a commissural score of 3-4 obtained a good outcome compared with only six (20%) patients of 30 with a commissural score of 0-2 (positive and negative predictive accuracy 94% and 80%, respectively, p < 0.001). Increase in 2DMVA post BMV was more in patients with higher commissural score (score of 3-4). Wilkins score <8 usually predicts a good outcome but even in patients with Wilkins score >8 a commissural score >2 predicts a 50% chance of a good result. CONCLUSIONS: A higher commissural score predicts a good outcome after BMV hence it can be concluded that along with Wilkins score, commissural morphology and score should be assessed with TOE in patients undergoing BMV.

Effect of percutaneous mitral balloon valvuloplasty on left atrial appendage function: transesophageal echo study.

BACKGROUND: To compare left atrial appendage (LAA) function by Doppler and Doppler tissue imaging (DTI) before and after percutaneous balloon mitral valvuloplasty (PBMV). MATERIALS AND METHODS: Fifty-nine patients with symptomatic rheumatic mitral stenosis who underwent PBMV were included in this study. LAA function was measured before and after PBMV. To study LAA function, LAA late emptying (LAALE) velocity, LAA late filling (LAALF) velocity, and LAA area change percentage (LAAAC %) were measured. In the DTI study, tissue Doppler velocities of the LAA, including peak early diastolic (E(LAA)), peak late diastolic (A(LAA)), and peak systolic (S(LAA)), were measured. RESULTS: There was significant increase in LAALE velocity, LAALF velocity, E(LAA), A(LAA), S(LAA) waves measured by Doppler and DTI after PBMV compared with baseline (p < 0.001) but there was no significant change in LAAAC% (p = not significant). Spontaneous echo contrast was present in 10 of the 59 patients before the procedure. It completely disappeared (6 patients) or decreased (4 patients) after PBMV. CONCLUSIONS: Our results suggest that PBMV improves LAA function and, thereby, may have a favorable influence on future thromboembolic complications.

Factor V Leiden mutation is not a predisposing factor for acute coronary syndromes.

BACKGROUND: The prevalence of Coronary artery disease (CAD) in India has increased considerably over the past few years and could become the number one killer disease if interventions are not done. Factor V Leiden (FVL) mutation and FII G20210A polymorphism are two recently described genetic factors with a propensity towards venous thrombosis. This warrants the investigations for thrombophilia in myocardial infarction patients in India. METHODS: The study cohort consisted of 51 patients aged below 50 years presenting with acute coronary syndromes. In both patient group and normal individuals the major risk factors Protein C deficiency, Protein S deficiency, anticardiolipin antibodies, Fibrinogen and Lipoprotein [a] were studied. Factor V Leiden (FVL) G1691A mutation in both control and patient group was looked by using Polymerase chain reaction (PCR) followed by sequencing of the PCR products. RESULTS: Our results indicated significantly higher levels of anticardiolipin antibodies and fibrinogen in the patients and absence of FVL (G1691A) mutation in our study cohort. One of the patients (H5) showed insertion of an extra A nucleotide in exon 10 of the Factor V gene resulting in frame shift mutation in this patient. CONCLUSION: The results of present study showed absence of FVL mutation in our population. However, there is a need to confirm the above findings on patients from different populations from different parts of the country. The insertion of an extra A in exon 10 in the patient needs to be ascertained to confirm that it is one of its kinds or is prevalent in the population.

Rapid high-performance liquid chromatography-tandem mass spectrometry method for simultaneous measurement of venlafaxine and O-desmethylvenlafaxine in human plasma and its application in comparative bioavailability study.

A rapid high-performance liquid chromatography-tandem mass spectrometry method has been developed and validated for simultaneous measurement of venlafaxine and O-desmethylvenlafaxine in human plasma using fluoxetine as an internal standard. In the liquid-liquid extraction method, compounds and internal standard were extracted from plasma using methyl tertiary butyl ether as an extraction solvent. The HPLC separation of the analytes was performed on a Zorbax SB-C(18), 50 x 4.6 mm, 5 microm column, using a isocratic elution program using a mobile phase consisting of HPLC-grade methanol: 5 mm ammonium acetate (80:20 v/v) at a flow-rate of 1.0 mL/min with a total runtime of 3.0 min. The proposed method has been validated with a linear range of 4-400 ng/mL for venlafaxine and 5-500 ng/mL for O-desmethyl venlafaxine. The method was applied for a bio-equivalence study of 75 mg tablets formulation in 32 Indian male healthy subjects under fasting conditions.

Study of contrast-induced oxidative stress in nondiabetic patients undergoing coronary angiography.

Administration of iodinated contrast media is associated with serious complications such as acute kidney injury (AKI). Oxidative stress is implicated as a major mechanism underlying the production of contrast-induced AKI (CI-AKI). There are very few human studies on oxidative stress occurring after contrast administration. Twenty-seven patients scheduled for coronary angiography were recruited. An average of 22.2 mL low-osmolal nonionic contrast was administered. Plasma conjugated dienes (CD), lipid hydroperoxides (LOOH), malondialdehyde (MDA), protein carbonyl (PC), protein thiols (PTs), ferric reducing ability of plasma (FRAP), erythrocyte super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase were estimated before, 30 min, 2 and 4 h after contrast administration. CD, LOOH, MDA, and PC increased (P <0.001), whereas PTs, FRAP, SOD, CAT (P <0.001), and GPx (P = 0.013) decreased in the first 4 h. Estimated glomerular filtration rate (eGFR) showed inverse association with MDA and positive association with GPx. The study provides evidence for oxidative stress following contrast administration even in the absence of predisposing factors. Association of eGFR with MDA and GPx indicate kidney as the source of oxidative stress. Hence, antioxidant therapy before contrast administration helps to prevent the development of oxidative stress, thereby reducing the risk of CI-AKI.

Determinants of total ischemic time in primary percutaneous coronary interventions: A prospective analysis.

OBJECTIVE: To assess the factors contributing to longer total ischemic times in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: Three hundred forty-six patients who underwent PPCI from July 2016 to June 2017 were studied. From time for the patient to recognize the symptoms, time was divided into 11 stages, any reason for delay was observed. RESULTS: Mean window period was 6.7 ±â€¯9.8 hours. Mean time to recognize the symptoms, reach first medical contact and prehospital management were 150.2 ±â€¯140.5 min, 58.5 ±â€¯57.0 min and 36.3 ±â€¯38.0 min, respectively. Mean time for the patients brought in ambulance was 82.4 ±â€¯59.8 min whereas for those transported in other vehicles was 130.4 ±â€¯59.7 min (p = < 0.0001). Mean door to electrocardiogram (ECG) time, decision for PPCI, consent time and STEMI team activation time were 6.2 ±â€¯3.1 min, 8.3 ±â€¯4.5 min, 12.6 ±â€¯16.2 min and 10.7 ±â€¯8.2 min, respectively. Mean time for financial process and mean sheath to balloon time were 9.1 ±â€¯6.9 min and 21.8 ±â€¯11.7 min, respectively. Door to balloon time (DTB) was <90 min in 81% of the patients, mean DTB was 72.0 ±â€¯33.0 min. Mean DTB for cases performed during night was 72.6 ±â€¯32.9 min, whereas for those performed during day was 60.3 ±â€¯30.2 min (p < 0.05). Total 30 day mortality was 2.9%. Mortality among DTB <90 min was 1.4%, mortality among DTB > 90 min was 9% (p < 0.05). CONCLUSIONS: The main contributor for longer total ischemic time was the time taken for the patient to recognize the symptoms. DTB of <90 min can be achieved with effective hospital strategies.

Comparison of PESI, echocardiogram, CTPA, and NT-proBNP as risk stratification tools in patients with acute pulmonary embolism.

OBJECTIVE: The aim of this study is to prospectively assess the diagnostic accuracy of pulmonary embolism severity index, echocardiogram, computed tomography pulmonary angiogram (CTPA), and N-terminal pro b-type natriuretic peptide (NT-proBNP) for predicting adverse events in acute pulmonary embolism patients. METHODS: Thirty consecutive acute pulmonary embolism patients were included in this study. Combined adverse events consisted of in-hospital death or use of escalation of care including cardiopulmonary resuscitation, mechanical ventilation, vasopressor therapy, or secondary thrombolysis during hospital stay. RESULTS: The outcomes were met in 30% of patients. Qanadli index (a measure of clot burden on CTPA) and NT-proBNP were significantly higher in patients with adverse events than those without (p=0.005 and p=0.009, respectively). PESI had moderate positive correlation with right ventricular dysfunction (RVD) (r=0.449, p=0.013) but there was no significant difference in PESI between patients with and without adverse events (p=0.7). Receiver operating characteristic analysis indicated that Qanadli index was the best predictor of adverse events with area under the curve (AUC) of 0.807 (95% CI: 0.651-0.963) with a negative predictive value (NPV) of 100% and positive predictive value (PPV) of 47.4% at cut-off value of 19. Right ventricle to left ventricle ratio on CTPA was found to predict RVD with AUC of 0.94 (95% CI: 0.842-1.000), NPV (77.8%), and PPV (95.2%) at cut-off value at 1.15. CONCLUSION: Qanadli index is more accurate predictor of adverse events than pulmonary embolism severity index, NT-proBNP, and RVD on echocardiogram and CTPA.

Biomarker response to contrast administration in diabetic and nondiabetic patients following coronary angiography.

Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C represent early renal injury markers for contrast-induced nephropathy (CIN). Baseline parameters such as type and quantity of contrast, patient preparation, renal function status, and diabetes mellitus (DM) are known to affect the response of the kidney to contrast-induced injury. This study was taken up to know the biomarker response to contrast administration in 58 diabetic and 59 nondiabetic male patients with same baseline parameters and baseline serum creatinine <1.2 mg/dl undergoing coronary angiography and their role in predicting the development of CIN. Serum creatinine, serum cystatin C, and urinary-NGAL (u-NGAL) were analyzed at baseline (0 h), 4 h, and 24 h after the administration of contrast medium. CIN was defined as a 25% increase in serum creatinine concentration from the baseline value or an absolute increase of at least 0.5 mg/dl within 48 h after the administration of contrast media. Serum creatinine rose 24 h after contrast administration in the diabetic group compared to 48 h in the nondiabetic group. Serum cystatin C levels rose 24 h after contrast administration in both the groups. The earliest marker to rise in both the groups was u-NGAL at 4 h. Diabetic patients had significantly higher u-NGAL (P = 0.005), and serum creatinine levels (P = 0.008) 4 h, and 24 h after contrast administration, respectively. Serum creatinine and u-NGAL/creatinine at 4 h were found to be the best predictors of CIN in the DM and non-DM patients, respectively. Biomarker response to contrast administration is different in diabetic and nondiabetic patients following contrast administration. Diabetic patients exhibit early and greater degree of renal impairment compared to the nondiabetic patients irrespective of the outcome. We propose the use of serum creatinine in patients with DM and u-NGAL/creatinine in non-DM patients to identify CIN as early as 4 h after contrast administration.

N-terminal-pro-brain natriuretic peptide, a surrogate biomarker of combined clinical and hemodynamic outcomes following percutaneous transvenous mitral commissurotomy.

AIM: To examine the relationship between plasma levels of N-terminal-proB type natriuretic peptide (NT-proBNP) and various echocardiographic and hemodynamic parameters in patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). MATERIALS AND METHODS: The study population consisted of 100 patients with rheumatic mitral stenosis who underwent PTMC. NT-proBNP levels in these patients were measured before PTMC and 48 hours after PTMC. These levels were then correlated with various echocardiographic and hemodynamic parameters measured before and after PTMC. RESULTS: Eighty-one percent of the study population were women, and the most common presenting symptom was dyspnea which was present in 94% of the patients. Dyspnea New York Heart Association class correlated significantly with baseline NT-proBNP levels (r = 0.63; p < 0.01). The plasma NT-proBNP levels in these patients increased as echocardiogram signs of left atrial enlargement and right ventricular hypertrophy developed (r = 0.59, p < 0.01). Patients in atrial fibrillation had significantly higher NT-proBNP levels than patients in sinus rhythm. Baseline NT-proBNP levels correlated significantly with left atrial volume (r = 0.38; p < 0.01), left atrial volume index (r = 0.45; p < 0.01), systolic pulmonary artery pressures (r = 0.42; p < 0.01), and mean pulmonary artery pressures (r = 0.41; p < 0.01). All patients who underwent successful PTMC showed a significant decrease in NT-proBNP (decreased from a mean 763.8 pg/mL to 348.6 pg/mL) along with a significant improvement in all echocardiographic and hemodynamic parameters (p < 0.01). The percent change in NT-proBNP correlated significantly with the percent improvement noted with left atrial volume (r = 0.39; p < 0.01), left atrial volume index (r = 0.41; p < 0.01), systolic (r = 0.32, p < 0.01), and mean pulmonary artery pressures (r = 0.31, p < 0.01). CONCLUSIONS: The decrease in NT-proBNP levels following PTMC reflects an improvement in clinical and hemodynamic status; hence, it is reasonable to suggest that NT-proBNP is helpful in evaluating the response to PTMC.

Transcatheter device closure of multiple defects in ruptured sinus of Valsalva aneurysm.

Ruptured sinus of Valsalva aneurysm (SOVA) with multiple communications, ventricular septal defect, and aortic regurgitation are still best treated surgically. We report a case of 30-year-old male with right SOVA, with two communications with right ventricle. Both communications were successfully closed using antegrade and retrograde approaches, respectively.

Clear Cell Carcinoma of Salivary Gland with Intracranial Extension Through Jugular Foramen.

Clear cell carcinoma not otherwise specified type affecting the parotid gland is rare and extension of this tumor through the jugular foramen presenting as an intracranial space occupying lesion is extremely uncommon. We report a case of clear cell carcinoma of the parotid gland presenting as a left cerebellopontine angle tumor.

Prognostic significance of NT-proBNP, 3D LA volume and LV dyssynchrony in patients with acute STEMI undergoing primary percutaneous intervention.

OBJECTIVES: The aim of the present study was to assess the short term prognostic significance of N-terminal pro BNP (NT-proBNP), 3D left atrial volume (LAV) and left ventricular (LV) dyssynchrony in patients of acute ST-elevation myocardial infarction (STEMI) who underwent primary Percutaneous intervention (PCI). BACKGROUND: NT-proBNP, LV dyssynchrony and LAV in patients with acute coronary syndrome have been associated with PCI outcomes and predict the short and long-term prognosis. METHODS: This study consisted of 142 patients with a first STEMI who underwent primary PCI. Baseline echocardiographic data was collected at admission and at 6 months follow up. Left ventricular dyssynchrony was measured by tissue Doppler imaging and LAV by real time 3D-echocardiography, plasma NT-proBNP levels were estimated between 72 and 96 h of admission. RESULTS: During study period 3 patients expired and 4 developed congestive heart failure (CHF). Baseline NT-proBNP and LV dyssynchrony correlated with LV size and LV ejection fraction (LVEF) at baseline and during follow up. Patients with higher NT-proBNP levels and higher LV dyssynchrony showed significant increase in LV size with decrease in LVEF during follow-up. Baseline Left atrial volume index (LAVI) showed significant correlation with LV size but no association with LVEF at baseline and during follow-up. CONCLUSIONS: Higher levels of NT-proBNP and higher LV dyssynchrony can predict patients with increase in LV size, worsening of LV systolic and diastolic function during follow-up. Patients with higher NT-proBNP levels at baseline developed CHF during follow-up.

Hemorrhage from lumbar artery following percutaneous renal biopsy.

We present a 58-year-old lady who underwent ultrasound-guided renal biopsy for suspected acute glomerulonephritis. Within minutes, the radiologist noticed an echogenic band around left kidney and in the muscular planes. Computerized tomography revealed focal active contrast extravasation from arcuate or interlobular artery in lower pole of left kidney and lumbar artery at third lumbar vertebra. The bleeding vessel was occluded with gelfoam.

Platelet hyporeactivity in very low birth weight neonates.

Very few studies have examined platelet function in very low birth weight (VLBW) preterm neonates, because of the relatively large volumes of blood required. In this study, platelet function in clinically stable VLBW neonates was examined by whole blood flow cytometry, which requires only 5 microliters of whole blood per assay. The following monoclonal antibodies were used: S12 (P-selectin-specific, reflecting alpha granule secretion), PAC1 (directed against the fibrinogen binding site exposed on the GPIIb-IIIa complex of activated platelets), F26 (directed against a conformational change in fibrinogen bound to the GPIIb-IIIa complex), and 6D1 (directed against the von Willebrand factor binding site on the GPIb-IX-V complex). VLBW neonates, like normal adults, did not have circulating activated platelets, as determined by the lack of binding of S12, PAC1, and F26 in the absence of an added agonist. VLBW neonatal platelets were markedly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619 (a stable thromboxane A2 analogue), as determined by the extent of increase in the platelet binding of S12, PAC1, and F26, and the extent of decrease in the platelet binding of 6D1. In summary, compared to adults, the platelets of VLBW neonates are markedly hyporeactive to thrombin, ADP/epinephrine and a thromboxane A2 analogue in the physiologic milieu of whole blood, as determined by: 1) the increase in platelet surface P-selectin; 2) the exposure of the fibrinogen binding site on the GPIIb-IIIa complex; 3) fibrinogen binding; and 4) the decrease in platelet surface GPIb. This platelet hyporeactivity may be a factor in the propensity of VLBW neonates to intraventricular hemorrhage. In addition to its previously defined use as a test of platelet hyperreactivity, the present study suggests that whole blood flow cytometry may be useful in the clinical assessment of platelet hyporeactivity.

Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.

Platelet-derived microparticles (PDMP) appear to play a major role in the generation of procoagulant activity. In this study, we describe a novel flow cytometric method that allows direct evaluation of the procoagulant activity of PDMP and platelets in the physiological milieu of whole blood. The percent PDMP generated in response to calcium ionophore A23187 and calcium was increased in preterm neonates (67.5+/-3.4%, mean +/- S.E.M., n = 8, p <0.05) and term neonates (67.2+/-2.7%, n = 7, p<0.05) compared with adults (49.5+/-3.4%, n = 13). However, in preterm neonates A23187/calcium-induced binding of factor V/Va to PDMP and platelets (22.8+/-5.6 fluorescence units) was markedly reduced (p <0.05) compared to term neonates (58.2+/-7.2) and adults (50.6+/-6.3). In preterm blood, A23187/calcium-induced binding of factor V/Va to PDMP and platelets returned to adult levels when: a) adult plasma, rather than autologous preterm neonatal plasma, was added; or b) factor V, but not factor VIII, was added to autologous preterm neonatal plasma. In summary: 1) We have developed a flow cytometric method for the direct detection of procoagulant PDMP and platelets in whole blood. 2) Compared to adults and term neonates, PDMP and platelets of preterm neonates bound markedly less factor V/Va (reflecting reduced procoagulant activity), because of a relative lack of factor V in preterm neonates. 3) This procoagulant defect in PDMP and platelets may contribute to the propensity of preterm neonates, but not term neonates, to intraventricular hemorrhage. 4) The percent PDMP does not necessarily reflect the degree of procoagulant activity of PDMP or platelets.

Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood.

Previous studies have reported that the platelets of healthy term neonates have either diminished or normal reactivity compared to the platelets of adults. To circumvent the methodologic problems of previous studies, we used a whole blood flow cytometric method to study neonatal platelet reactivity to thrombin, a combination of ADP and epinephrine, and U46619 (a stable thromboxane A2 analogue). Inclusion in the assay of the peptide GPRP (an inhibitor of fibrin polymerization) enabled us to study platelet reactivity to human alpha-thrombin in whole blood. Umbilical cord blood and day 1 peripheral blood were collected from 30 healthy term neonates and compared to peripheral blood from 20 normal adults. In whole blood samples without added agonist, there were no significant differences between neonates and adults in the platelet binding of monoclonal antibodies 6D1 (GPIb-specific) or 7E3 (GPIIb-IIIa complex-specific). As determined by S12 (a P-selectin-specific monoclonal antibody), neither neonates nor adults had circulating degranulated platelets. However, in both cord and peripheral whole blood samples, neonatal platelets were significantly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619, as determined by the extent of increase in the platelet surface expression of P-selectin and the GPIIb-IIIa complex, and the extent of decrease in the platelet surface expression of the GPIb-IX complex.(ABSTRACT TRUNCATED AT 250 WORDS)