|Year : 2018 | Volume
| Issue : 4 | Page : 259-264
Mean platelet volumes and platelet counts in infants with pulmonary hemorrhage or transient tachypnea of the newborn
Yuko Sakurai, Mitsuhiro Haga, Chika Kanno, Masayuki Kanno, Ken Kawabata, Masami Kanno, Masaki Shimizu
Saitama Children's Medical Center, Division of Neonatology, Saitama, Japan
|Date of Web Publication||15-Oct-2018|
Prof. Yuko Sakurai
Saitama Children's Medical Center, Division of Neonatology, 1-2 Shintoshin, Chuo-Ku, Saitama-Shi, Saitama-Ken 330-8777
Source of Support: None, Conflict of Interest: None
Background: To compare mean platelet volume (MPV) values between full-term infants with pulmonary hemorrhage and those with transient tachypnea of the newborn to determine whether MPV is a potential predictive factor for disease. Materials and Methods: The infants were divided into 3 groups and examined: those in whom pulmonary hemorrhage was observed (P group), those with transient tachypnea of the newborn managed by ventilator (T group), and those with transient tachypnea of the newborn not managed by ventilator (t group). Results: MPV values on admission in the 3 groups were high, and there were no significant differences between the P group and T group; however, MPV values in the P group were significantly higher than those in the t group. There was a tendency for the platelet count to increase between admission and 5 days after birth in all groups. Meanwhile, between admission and 5 days after birth, MPV values tended to remain high in the P group, were significantly increased in the T group, and were elevated in the t group. Conclusion: This investigation could not predict whether infants requiring ventilator management would develop pulmonary hemorrhage based solely on the admission MPV value. However, we suggest that if further detailed conditions were added, a potential predictive factor for pulmonary hemorrhage could be found.
Keywords: Full-term infants, pulmonary hemorrhage, transient tachypnea of the newborn, ventilator management
|How to cite this article:|
Sakurai Y, Haga M, Kanno C, Kanno M, Kawabata K, Kanno M, Shimizu M. Mean platelet volumes and platelet counts in infants with pulmonary hemorrhage or transient tachypnea of the newborn. J Clin Neonatol 2018;7:259-64
|How to cite this URL:|
Sakurai Y, Haga M, Kanno C, Kanno M, Kawabata K, Kanno M, Shimizu M. Mean platelet volumes and platelet counts in infants with pulmonary hemorrhage or transient tachypnea of the newborn. J Clin Neonatol [serial online] 2018 [cited 2022 Jan 16];7:259-64. Available from: https://www.jcnonweb.com/text.asp?2018/7/4/259/243328
| Introduction|| |
Mean platelet volume (MPV), which indicates platelet size, reflects the production and stimulation of platelets because platelets are large immediately after they are produced and gradually become smaller over time. In addition, MPV is said to reflect platelet function and activity. It has also recently been reported that MPV is an important predictive factor for many diseases.
In adults, the MPV value increases in patients who have factors that raise such cardiovascular risks as diabetes, hypertension, hyperlipidemia, smoking, and obesity.,,,, Furthermore, in neonates report that the MPV value is associated with some diseases are often found. For example, it has been reported that the MPV value is useful as a predictive marker for the occurrence of necrotizing enterocolitis, bronchopulmonary dysplasia, and intracranial hemorrhage in very-low-birth-weight infants., However, there is also a report that no relationship between MPV values and diseases has been recognized in either adults or neonates., Thus, although the MPV value is used for the evaluation of platelet production and its association with various diseases has been pointed out, many unclear points currently remain.
Purpose of the study
Pulmonary hemorrhage is thought to be one of the causes of death in the early neonatal period, but there are a few cases in which pulmonary hemorrhage occurs just after birth. Yet, it is difficult to predict pulmonary hemorrhage when treating respiratory insufficiency.
Therefore, a comparison of MPV values between pulmonary hemorrhage and transient tachypnea of the newborn, which contribute to respiratory insufficiency in full-term infants, was conducted to determine whether MPV is a potential predictive factor for disease.
| Methods|| |
Among full-term infants hospitalized in our neonatal intensive care unit for respiratory insufficiency between April 2014 and January 2016, those in whom pulmonary hemorrhage was observed and those who were diagnosed as having transient tachypnea of the newborn comprised 101 infants, and they were examined. In this study, infants with a birth defect (n = 1), death within 5 days after birth (n = 1), hospitalization from 2 days after birth (n = 11), and those admitted out-of-hours in whom measurement devices differed (n = 20) were excluded from the study. Participants were divided into three groups as follows: infants in whom pulmonary hemorrhage was observed (P Group), those with transient tachypnea of the newborn who were managed by ventilator (T Group), and those with transient tachypnea of the newborn who were not managed by ventilator (t Group). In each group, gestational age, birth weight, standard deviations score, Apgar score, mode of delivery, primipara or multipara, platelet counts, and MPV values on admission (within 24 h after birth) and at 5 days after birth, time from birth to pulmonary hemorrhage, duration of pulmonary hemorrhage, duration of ventilator management, and duration of oxygenation were retrospectively investigated from the hospital medical records. An XN-1000 Automated Multiple Hematology Analyzer (Sysmex) was used for MPV measurements.
For statistical analysis, the Mann–Whitney U-test, Fisher's exact probability test, and the Spearman's rank correlation coefficient were used. The statistical significance level was set at P < 0.05. Data were analyzed using statistical analysis software (IBM SPSS Statistics 20, New York). Conditions of pulmonary hemorrhage were determined with reference to Brown et al. as follows: (i) sudden-onset overt hemorrhage from the lung (hemorrhage followed by voluntary medical intervention and hemorrhagic amniotic fluid were excluded), (ii) ventilator management due to serious respiratory symptoms, and (iii) diffuse unilateral or bilateral pulmonary infiltrative shadows found by chest X-ray.
| Results|| |
ThePGroup comprised 20 infants, the T Group comprised 19, and the t Group comprised 29. Characteristics of the participants are shown in [Table 1]. There were significant differences in gestational age, primipara or multipara, and cord blood pH between the P and T Groups. There was also a significant difference in the Apgar score at 5 min after birth between the P and t groups. There were no clear differences in the other items.
The correlation between the platelet count and MPV on admission is shown in [Figure 1]. No correlations were found between the P, T, and t groups (P Group: P = 0.35, r = 0.16; T Group: P = 0.10, r = −0.24; and t Group: P = 0.44, r = −0.47). Platelet counts on admission were maintained, and the mean platelet counts of the P, T, and t Groups were 24.4 ± 6.3 × 104/μL, 27.3 ± 6.7 × 104/μL, and 25.6 ± 7.4 × 104/μL, respectively. The results of each examination between the P and T Groups and between the P and t groups are shown in [Figure 2]a. There were no significant differences between the P and T Groups (P = 0.19) and between the P and t Groups (P = 0.51). In contrast, MPV values on admission were high [Figure 2]b. Mean MPV values of the P, T, and t Groups were 10.3 ± 0.8 fL, 9.8 ± 0.7 fL, and 9.7 ± 0.5 fL, respectively. There was no significant difference between the P and T Groups (P = 0.14); however, the mean MPV value of the P Group was significantly higher than that of the t Group (P = 0.01).
|Figure 1: Correlation between platelet count and mean platelet volume value on admission. No correlations were found between the P, T, and t Groups (P Group: P = 0.35, r = 0.16; T Group: P = 0.10, r = -0.24; and t Group: P = 0.44, r = -0.47)|
Click here to view
|Figure 2: Platelet count and mean platelet volume value on admission. (a) There were no significant differences in platelet count between the P Group and T Group (P = 0.19) and between the P Group and t Group (P = 0.51). (b) There were no significant differences in mean platelet volume between the P Group and T Group (P = 0.14); however, the mean platelet volume value of the P Group was significantly higher than that of the t Group (P = 0.01)|
Click here to view
Changes in platelet counts from admission to 5 days after birth are shown in [Figure 3]a. Platelet counts from admission to 5 days after birth tended to increase in all groups (P Group: P = 0.02, T Group: P = 0.03, and t Group: P < 0.01). However, as shown in [Figure 3]b, changes in MPV values from admission to 5 days after birth differed among the three groups. In the P Group, the MPV value tended to remain high (P = 0.20). In the T Group, the MPV value increased significantly (P = 0.03), and in the t Group, although no obvious rise (P = 0.05) was observed, it tended to be elevated.
|Figure 3: Changes in platelet counts and mean platelet volume values from admission to 5 days after birth. (a) Platelet counts from admission to 5 days after birth tended to increase in all groups (P Group: P = 0.02, T Group: P = 0.03, and t Group: P < 0.01). (b) In the P Group, the mean platelet volume value tended to remain high (P = 0.20). In the T Group, the mean platelet volume value increased significantly (P = 0.03), and in the t Group, there was no obvious rise (P = 0.05); however, a tendency for it to increase was found|
Click here to view
Then, there were no differences in MPV values between the groups with pulmonary hemorrhage and that with transient tachypnea of the newborn requiring a ventilator, we examined whether the prediction of short-term prognosis was possible in the P Group. As shown in [Table 2], as short-term predictors of prognosis, time from birth to pulmonary hemorrhage, duration of pulmonary hemorrhage, duration of oxygenation, and duration of ventilator management were examined. However, no correlation between the items examined, and the MPV value could be found.
|Table 2: Relationship between the duration of pulmonary hemorrhage or respiratory insufficiency and mean platelet volume in the P Group|
Click here to view
| Discussion|| |
This investigation could not predict whether an infant requiring ventilator management would develop pulmonary hemorrhage based solely on the MPV value on admission. However, there was a difference in MPV values between infants with transient tachypnea of the newborn requiring ventilator management and those not requiring ventilator management, which suggested that the MPV value might be helpful in clarifying neonatal respiratory insufficiency.
The mortality rate in the early neonatal period is high in neonates with pulmonary hemorrhage, which occurs suddenly in the form of the excretion of bloody discharge from the upper respiratory tract or the tracheal tube. However, it is difficult to predict whether a respiratory disorder that is recognized in a full-term infant with risk factors for pulmonary hemorrhage will actually lead to pulmonary hemorrhage. The onset is often recognized by the appearance of symptoms.
Neonatal pulmonary hemorrhage is thought to be caused by hemorrhagic edema resulting from stress failure in the pulmonary capillaries,, which include (1) circumferential tension of the capillary wall caused by intravascular pressure of the capillaries, (2) surface tension of the alveolar layers caused by the distended capillary wall, and (3) longitudinal tension to alveolar wall tissues caused by lung distention. The mortality rate of premature infants with moderate-to-severe pulmonary hemorrhage is reported to be 38%–57%.,, Although approximately 50% of infants, who develop pulmonary hemorrhage, have been salvaged, pulmonary hemorrhage is ranked as a severe symptom. Before the 1990s, neonatal pulmonary hemorrhage mainly appeared as the last symptom in infants who were small for their gestational age or in newborn infants suffering asphyxiation. However, after the administration of artificial pulmonary surfactant was introduced, pulmonary hemorrhage began to receive attention in premature infants with neonatal respiratory distress syndrome.,, Although there is a variation in frequency in the reports, it is reported that pulmonary hemorrhage occurs in 0.5%–11% of infants with very low birth weight,, and in 1–12 per 1000 births as a whole. Pulmonary hemorrhage in the full-term infant is still frequently observed.
[Figure 4] shows the causes of pulmonary hemorrhage in full-term infants and in premature infants.,,,, As only full-term infants were examined in this study, the causes are thought to be neonatal asphyxia, resuscitation by positive-pressure respiration in the delivery room, and hypotension. From these causes, the process leading to pulmonary hemorrhage progresses from hypoxia or acidosis based on the disease-related situation. Myocardial damage that accompanies these disorders, i.e., acute left ventricular failure, causes elevated pulmonary capillary pressure that leads to hemorrhagic pulmonary edema in which obvious bleeding occurs in the pulmonary interstitium, and the alveolar spaces. This is thought to be the process leading to pulmonary hemorrhage. In full-term newborn infants, it is suggested that the circulation is greatly involved in pulmonary hemorrhage.
|Figure 4: Cause of pulmonary hemorrhage. The cause of pulmonary hemorrhage is roughly divided into premature infant cases and full-term infant cases. Hypoxia or acidosis progresses from these causative situations, and myocardial damage that accompanies these disorders, i.e., acute left ventricular failure and causes elevated pulmonary capillary pressure. Such stress failure in the pulmonary capillaries leads to hemorrhagic pulmonary edema in which obvious bleeding occurs in the pulmonary interstitium and the alveolar spaces|
Click here to view
Although an infant can have a risk factor for pulmonary hemorrhage on the basis of the perinatal situation, it is difficult to predict whether pulmonary hemorrhage will occur in the subsequent disease course. In this study, the median time from birth to the occurrence of pulmonary hemorrhage was 236 min, and if some parameters can be found to be predictive factors, early therapeutic intervention may lead to an improvement in prognosis.
It is reported that MPV, which indicates platelet size, not only reflects the production and stimulation of platelets but also their function and activity. Some studies have revealed that large platelets are more responsive to hemostasis than normal-sized platelets, and thus platelet size correlates with platelet function.,, In other words, larger platelets are considered to be an independent factor that can predict poor responsiveness to antiplatelet therapy.
Various functions and activities of platelets can be predicted by assessing the MPV value. With the application of this finding, the relationship between the MPV value and many diseases has received attention. In adults, it is reported that when the coronary blood flow becomes slow, the MPV will rise. As indicated in [Figure 4], in neonatal pulmonary hemorrhage, which involves the circulation, the effect on the circulation might cause the MPV value to increase. Thus, it was hypothesized that infants, who ultimately develop pulmonary hemorrhage, would have a higher MPV value than those with transient tachypnea of the newborn. However, there was, in fact, no significant difference in MPV values between the P and T Groups, and a relationship between the MPV value and the disease could not be shown.
One possible limitation of this study might be that the process used to measure the MPV value was not investigated. Some reports have studied the involvement of not only the circulation but also the processes of inflammation or oxidation in the relationship between the MPV value and disease. The MPV value can change even as a result of such therapeutic interventions as ventilator management or oxygenation. Particularly, regarding ventilator management, no significant difference was found between the P and T Groups whereas a significant difference might have been present between the P and t Groups.
Furthermore, the results of the out-of-hours examinations in which the measurement devices differed could not be included, and the small number of participants was another limitation of this study. In addition, pulmonary hemorrhage is a symptom resulting from the involvement of many factors. With regard to the contents of the treatments, the MPV value was measured in samples on admission, and more than a few samples were collected after the onset of oxygenation or endotracheal intubation. Therefore, it would be difficult to explain pulmonary hemorrhage by changes in MPV alone.
However, it is difficult to predict an accurate prognosis only by MPV; however, we suggest that if detailed conditions are added in future studies, and the number of participants is increased, the MPV value could likely play a role as a predictive parameter.
| Conclusion|| |
In this study, we could show the MPV values in the full-term infants with pulmonary hemorrhage and transient tachypnea of the newborn. However, no apparent significant difference between the two groups was found.
By accumulating detailed data on the factors involved, we believe it is possible to combine MPV values with other factors to predict prognosis in infants with pulmonary hemorrhage.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, et al.
Mean platelet volume as a predictor of cardiovascular risk: A systematic review and meta-analysis. J Thromb Haemost 2010;8:148-56.
Cekmez F, Tanju IA, Canpolat FE, Aydinoz S, Aydemir G, Karademir F, et al.
Mean platelet volume in very preterm infants: A predictor of morbidities? Eur Rev Med Pharmacol Sci 2013;17:134-7.
Papanas N, Symeonidis G, Maltezos E, Mavridis G, Karavageli E, Vosnakidis T, et al.
Mean platelet volume in patients with type 2 diabetes mellitus. Platelets 2004;15:475-8.
Nadar S, Blann AD, Lip GY. Platelet morphology and plasma indices of platelet activation in essential hypertension: Effects of amlodipine-based antihypertensive therapy. Ann Med 2004;36:552-7.
Pathansali R, Smith N, Bath P. Altered megakaryocyte-platelet haemostatic axis in hypercholesterolaemia. Platelets 2001;12:292-7.
Kario K, Matsuo T, Nakao K. Cigarette smoking increases the mean platelet volume in elderly patients with risk factors for atherosclerosis. Clin Lab Haematol 1992;14:281-7.
Coban E, Ozdogan M, Yazicioglu G, Akcit F. The mean platelet volume in patients with obesity. Int J Clin Pract 2005;59:981-2.
Bolouki Moghaddam K, Zarkesh M, Kamali A, Dalili S, Heidarzadeh A, Hassanzadeh Rad A, et al.
The association of mean platelet volume with intra ventricular hemorrhage and broncho pulmonary dysplasia in preterm infants. Iran J Ped Hematol Oncol 2015;5:227-32.
Catal F, Tayman C, Tonbul A, Akça H, Kara S, Tatli MM, et al.
Mean platelet volume (MPV) may simply predict the severity of sepsis in preterm infants. Clin Lab 2014;60:1193-200.
Kaya Z, Günebakmaz Ö, Yıldız A, Sezen Y, Biçer Yeşilay A, Erkuş E, et al.
Mean platelet volume is not associated with coronary slow flow: A retrospective cohort study. Anatol J Cardiol 2015;15:18-24.
Ahmad MS, Waheed A. Platelet counts, MPV and PDW in culture proven and probable neonatal sepsis and association of platelet counts with mortality rate. J Coll Physicians Surg Pak 2014;24:340-4.
Brown CM, Redd SC, Damon SA; Centers for Disease Control and Prevention (CDC). Acute idiopathic pulmonary hemorrhage among infants. Recommendations from the working group for investigation and surveillance. MMWR Recomm Rep 2004;53:1-2.
Bendapudi P, Narasimhan R, Papworth S. Causes and management of pulmonary haemorrhage in the neonate. Paediatr Child Health (Oxford) 2012;22:528-31.
Cole VA, Normand IC, Reynolds EO, Rivers RP. Pathogenesis of hemorrhagic pulmonary edema and massive pulmonary hemorrhage in the newborn. Pediatrics 1973;51:175-87.
West JB, Mathieu-Costello O. Stress failure of pulmonary capillaries: Role in lung and heart disease. Lancet 1992;340:762-7.
West JB, Tsukimoto K, Mathieu-Costello O, Prediletto R. Stress failure in pulmonary capillaries. J Appl Physiol (1985) 1991;70:1731-42.
Pandit PB, O'Brien K, Asztalos E, Colucci E, Dunn MS. Outcome following pulmonary haemorrhage in very low birthweight neonates treated with surfactant. Arch Dis Child Fetal Neonatal Ed 1999;81:F40-4.
Finlay ER, Subhedar NV. Pulmonary haemorrhage in preterm infants. Eur J Pediatr 2000;159:870-1.
Bhandari V, Gagnon C, Rosenkrantz T, Hussain N. Pulmonary hemorrhage in neonates of early and late gestation. J Perinat Med 1999;27:369-75.
Tomaszewska M, Stork E, Minich NM, Friedman H, Berlin S, Hack M, et al.
Pulmonary hemorrhage: Clinical course and outcomes among very low-birth-weight infants. Arch Pediatr Adolesc Med 1999;153:715-21.
Clyman RI, Jobe A, Heymann M, Ikegami M, Roman C, Payne B, et al.
Increased shunt through the patent ductus arteriosus after surfactant replacement therapy. J Pediatr 1982;100:101-7.
Kluckow M, Evans N. Ductal shunting, high pulmonary blood flow, and pulmonary hemorrhage. J Pediatr 2000;137:68-72.
Zola EM, Overbach AM, Gunkel JH, Mitchell BR, Nagle BT, DeMarco NG, et al.
Treatment investigational new drug experience with Survanta (beractant). Pediatrics 1993;91:546-51.
van Houten J, Long W, Mullett M, Finer N, Derleth D, McMurray B, et al.
Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: An autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group. J Pediatr 1992;120:S40-4.
Ferreira CH, Carmona F, Martinez FE. Prevalence, risk factors and outcomes associated with pulmonary hemorrhage in newborns. J Pediatr (Rio J) 2014;90:316-22.
Berger TM, Allred EN, Van Marter LJ. Antecedents of clinically significant pulmonary hemorrhage among newborn infants. J Perinatol 2000;20:295-300.
Giles H, Smith RE, Martin JF. Platelet glycoprotein IIb-IIIa and size are increased in acute myocardial infarction. Eur J Clin Invest 1994;24:69-72.
Karpatkin S, Khan Q, Freedman M. Heterogeneity of platelet function. Correlation with platelet volume. Am J Med 1978;64:542-6.
Jakubowski JA, Adler B, Thompson CB, Valeri CR, Deykin D. Influence of platelet volume on the ability of prostacyclin to inhibit platelet aggregation and the release reaction. J Lab Clin Med 1985;105:271-6.
Guthikonda S, Alviar CL, Vaduganathan M, Arikan M, Tellez A, DeLao T, et al.
Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. J Am Coll Cardiol 2008;52:743-9.
Duygu H, Turkoglu C, Kirilmaz B, Turk U. Effect of mean platelet volume on postintervention coronary blood flow in patients with chronic stable angina pectoris. J Invasive Cardiol 2008;20:120-4.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]