In this study, we explored the role of platelets in preterm infants with hsPDA and found that the smaller gestational age and the lower birth weight, PLT, plateletocrit were associated with the greater likelihood of PDA. The ROC curve and single factor correlation analysis showed that PLT and plateletocrit were the predictive factors of hsPDA. The logistic regression analysis confirmed that plateletocrit within 24h after birth was the independent risk factor for preterm infants with hsPDA. Therefore, our findings demonstrated that the decrease in plateletocrit of the preterm infants was the independent risk factor for hsPDA.
After the preterm infants are born, the strong contraction of arterial duct smooth muscle cannot often start, and the formed neointimal pad is sufficient to fill and block the residual cavity, making it difficult for the arterial duct to reshape and permanently close anatomically [1, 9]. The aggregation and adhesion of the blood platelets inside the arterial duct have been suggested to be the influencing factors of arterial duct anatomical closures . For example, in the transgenic mice with glycoprotein IIb (blood platelet-specific integral protein) defect or platelet biosynthetic defect, the arterial duct remained open after 12 h of birth (the time for the mice arterial duct being spontaneously closed was 1-3 h after birth), as demonstrated by the angiography. Therefore, the poor blood platelet adhesion or aggregation function and reduced PLT will significantly affect the arterial duct closure [3, 10]. Besides, a small single-center retrospective study of 123 preterm infants with the gestational age from 24 to 30 weeks in Germany demonstrated that the risk of PDA in the PLT ≤ 150×109/L group was increased by 13 times (OR, 13.1; 95% CI, 3.5-49.6) in comparison with the PLT >150×109/L group, therefore, the thrombocytopenia was proposed to be an independent predicting factor for the arterial duct closure failure of the preterm infants . It has also been shown that PLT < 100 × 109/L when birth was an independent risk factor for the occurrence of PDA on the preterm infants (OR, 4.50; 95% CI, 1.39-14.61) . Consistent with previous reports, our study also showed that compared with the preterm infants with PLT ≥ 241.5 × 109/L, ≥ 150 × 109/L, and ≥ 100 × 109/L, for the preterm infants with PLT < 241.5 × 109/L, < 150 × 109/L, and < 100 × 109/L within 24 h after birth, the risk of hsPDA was increased by 1.876, 2.169, and 6.216 times. Further, a recent meta-analysis including 11 cohort studies and 3479 preterm infants with gestational age < 32 weeks examined the relationship between the PLT and occurrence of PDA on the first day after birth and found that PDA was significantly correlated with PLT < 150 × 109/L (6 studies, RR 1.215, 95% CI 1.027-1.436) and PLT < 100 × 109/L (5 studies, RR 1.255, 95% CI 1.034-1.525). The hsPDA was significantly correlated with PLT < 100 × 109/L (5 studies, RR 1.254, 95% CI 1.021-1.540), but the hsPDA was not significantly correlated with PLT < 150 × 109/L (6 studies, RR 1.289, 95% CI 0.925-1.795) .
There was also another point of view about PLT. PLT is lower than 150 × 109/L in hypoxia, preterm birth, and other pathological conditions, and these conditions can also lead to a higher incidence of PDA of the infants. Therefore, it has been speculated that the platelets in the circulation cannot help PDA closure and PLT also has no exact logic relationship with PDA closure, which is just a statistical correlation . Recently, a large two-center retrospective cohort analysis was carried out on 1350 infants with very low birth weight in Germany, and the statistics showed that PLT within 24 h after birth had no relationship with the presence of PDA by the echocardiography examination within 4-5 days after birth . The impaired platelet function rather than the reduction in PLT may have a certain relationship with the PDA. It has also been shown that there was no correlation between the closure of the arterial duct of the preterm infants and PLT . The incidence of PDA in the PLT < 50 × 109/L group was similar to that in the PLT > 50 × 109/L group, and PDA incidence would be reduced only when the PLT was over 230 ×109/L . Thus, with regard to the relationship between the thrombocytopenia and the incidence of PDA, there was still a large dispute. The reasons for the great difference among these research findings were still unclear, which could not be explained by the possible existence of difference in the neonatal intensive care unit (NICU) management . It was recommended that a prospective study should be carried out to solve these disputes .
Alyamac et al.  retrospectively analyzed that the preterm infants with the median gestational age of 28 weeks and the median birth weight of 1060 g within 3 days after birth. Their results showed that, in the hsPDA group (n = 154), PLT was significantly lower than that in the nPDA group (n = 207); PLT < 150×109/L (OR=2.13, 95% CI: 1.26-3.61) and PDW > 17% (OR = 2.68, 95% CI: 1.41-5.09) were the risk factor for the occurrence of hsPDA; the MPV was not related to hsPDA. However, the mean PDW values in the nPDA group, nhsPDA group, and hsPDA group of the present study were 11.23%, 11.10%, and 11.26%, respectively, and PDW was not correlated with hsPDA.
The single factor correlation analysis in our study showed that plateletocrit was also closely related to the closure of the arterial duct: for the preterm infants with plateletocrit < 0.245% and 0.09% within 24 h after birth, the risks of hsPDA were 1.749 and 5.407 times of preterm infants with plateletocrit ≥ 0.245% and ≥ 0.09%, respectively. By the comparison of the areas under the ROC curves for predicting hsPDA of the preterm infants, it was prompted that the predictive value of plateletocrit was slightly better than PLT. Further, the multi-factor logistic regression analysis showed that plateletocrit instead of PLT within 24 h after birth was the independent risk factor of the hsPDA of the preterm infants. Plateletocrit is the product of PLT and MPV. The PLT can only reflect the platelet counts, while the MPV may reflect the platelet function to some extent as the "young" platelet volume is relatively larger and contains more platelet factor Ⅲ, with the better adhesion and aggregation functions than the "elderly" platelets . Therefore, the plateletocrit not only reflects the platelet counts but also the platelet function, rendering itself as an independent risk factor more directly related to the hsPDA of the preterm infants.
It is noteworthy that the area under the ROC curve for predicting the hsPDA of preterm infants by the plateletocrit within 24h after birth was 0.748, and the predictive value was merely moderate. The best prediction critical value was 0.245%, and its sensitivity (68.2%) and specificity (74.2%) were not high due to the actions of multiple factors on the hsPDA in the preterm infants. In addition to the arterial duct maturity and genetic background, other factors affecting the arterial duct include the factors promoting the arterial duct smooth muscle contraction (oxygen, endothelin, calcium ion channel, catecholamines, Rho-kinase) and the factors inhibiting the arterial duct smooth muscle contraction (intraluminal pressure, prostaglandin, nitric oxide, carbon monoxide, potassium channel, cAMP, cGMP) [1, 2]. Among them, the vasodilator prostaglandins (especially prostaglandin E2) were the most important factors [1, 2] recognized currently in inhibiting arterial contraction in the late pregnancy. Therefore, although the low plateletocrit is the independent risk factor for the hsPDA of the preterm infants, further studies are required to elucidate other relevant risk factors. Similar to PLT, it also cannot be excluded that the plateletocrit level has merely a statistical correlation with PDA closure.
In summary, our study showed that the decrease in plateletocrit of the preterm infants within 24 h after birth was an independent risk factor of hsPDA on the 4th-7th day after birth. Combined with previous reports, it was speculated that the poor platelet function rather than simple reduction of the count may affect the closure of the arterial duct on the preterm infants, providing a theoretical basis for driving the arterial duct closure by the infusion of platelet-rich plasma .