Clinical Study Of Unfractionated Heparin In Prevention Of Coagulation Disorders In Infants With Placental Abruption

Placental Abruption (PA), defined as the premature separation of the placenta prior to the delivery of the fetus, occurs in approximately1%of pregnancies. The classical hallmarks of PA include vaginal bleeding accompanied by painful titanic contractions and uterine tenderness. PA is a primary cause of perinatal mortality, especially of premature neonates. Several studies have reported that placental abruption is associated with low birth weight, preterm birth, and intrauterine growth restriction. PA is associated with higher mortality and subsequent need for intensive care, in addition to affecting the child adversely for many years.The morbidity of the PA was reported0.06%-2.1%by Yangjianbo in China. The mortality which is20%-35%in these newborns whose mother has the PA is15times than that of the health. The etiology of abruption remains speculative, but epidemiologic studies have observed advanced maternal age, multiparity, smoking, cocaine, folate deficiency, hypertensive disorders, prolonged rupture of membranes and previous cesarean delivery, and those with intra-aminiotic infections are at increased risk. In these newborns whose mother has PA, the proportion of the coagulation disorder and Pre-DIC is pretty high,. However, in the severe PA, the hypercoagulable state can result in the placental thrombus and disseminated intravascular coagulation, affect the coagulation function and life-safe of the fetus, also is the latent and dangerous pathological change to the newborns.In our research, we first studied the changes of blood coagulation in newborns with different gestational age. Secondly; we concluded the clinical characteristics and coagulation parameters of the infants with placental abruption. And applied the clinical studies of Unfractionated Heparin in prevention of placental-abruption infants’ Coagulation Disorders. We proposed to observe the changes of haemoststic system and search more sensitive and effective haemostatic parameters for the monitoring of condition of PA. We found the dose of0.1mg· kg-1(12.5U·kg-1) is the most suitable for placental-abruption newborns to prevent the coagulation abnormalities progressing. VWF and ADAMTS13are a special anticoagulant factor. The VWF gene is located on the short arm of chromosome12and comprises52exons, and it is involved in primary hemostasis and in coagulation process, in which it acts as a carrier of factor Ⅷ. VWF is important for platelet adhesion at sites of vascular damage, where it mediates the initial progression of thrombus formation at the site of endothelial injury through specific interactions with the subendothelial collagen and platelet receptors. ADAMTS13, a disintegrin and metalloproteinase with thrombospondin type1domain. The ADAMTS13gene is located on the long arm of chromosome9, has29exons. It cleaves UL-VWF and removes them from circulation.The imbalance between ADAMTS13activity and VWF plasma level resulting in pro-thrombotic or hypercoagulability state. However, the physiological functions of VWF and ADAMTS13in PA are still poorly understood. The VWF and ADAMTS13plasma levels were detected in both placental abruption infants and the controls with ELISA method. In order to explore the pathogenesis of PA.Section1A clinical study for the changes of blood coagulation in newborns with different gestational ageObjective To compare components of the coagulation and fibrinolytic system in newborn of gestational age ranging from extreme prematurity to full term at birth.Method We studied293full-term infants(37～42weeks),118late preterm neonates (34～36+6weeks), and115early preterm infants (26～33+6weeks). The activated partial thromboplastin time(APTT)、prothrombin time(PT)、fibrinogen(FIB) and fibrin degradation product(FDP), as well as D-dimer(D-D) in neonates were measured within6hours after birth. There were no statistical differences among the groups for the postnatal age、gender、 number of previous pregnancies and deliveries、mode of delivery、motherhood pregnancy complications、Apgar score、amniotic fluid contamination and premature rupture of membrane (P>0.05)Results APTT, PT, FDP and D-D were higher in early pretem infants than in late preterm infants and full-term infants(P<0.01, respectively), while the FIB was lower in the early pretem infants compared with the late preterm infants and full-term infants(P<0.01, respectively), those differences were significant. No significant differences in the coagulation system components were seen(P>0.05, respectively), except that the D-D in late preterm infants (P<0.01).Conclusions Coagulation parameters and D-D are sensitive to gestational age-related changes in haemostatic proteins, especially in the cases of early preterm infants. The D-dimer assay is considered the maker of choice for neonates with a suspicion of coagulation disorders, timely and appropriate intervention should be taken for infants especially for preterm infants when D-D increase or PT and APTT prolonged.Section2Section2.1The clinical characteristics and coagulation parameters of the infants with Placental AbruptionObjective To conclude the clinical characteristics and coagulation parameters of the infants with placental abruption.Method Analysis is made on clinical and laboratory indexes of the hospitalized children of the NICU of Bayi Children’s Hospital Affiliated to General Hospital of Beijing Military Command of PLA enrolled from August2012to January2013, including60infants with placental abruption and60infants without placental abruption as the control group.Results From clinical manifestations and lab date, significant differences were detected in premature rupture of membrane, birth weight, intrauterine growth retardation, motherhood gestational hypertension, mother gestational diabetes mellitus, asphyxia, APTT, D-dimer on admission between the observation group and control group(P<0.05).Conclusion Placental abruption is the result of placental insufficiency, which may cause coagulation disorder and thus show the pathological state of high condensation in infants. Section2.2Clinical Studies of Unfractionated Heparin in Prevention of Placental-Abruption Infants’ Coagulation DisordersObject To evaluate what’s the most suitable dose of unfractionated heparin for the placental-abruption infants.Method60preterm placental-abruption newborns were included and divided randomly into3groups receiving different doses:group A0.1mg·kg-1, group B0.2mg kg-1, and group C0.3mg·kg-1, and they were all administered as following:the first24h is q6h, the second24h is q8h, the third24h is ql2h, and transition to the withdrawal by qd or withdrawal at the fourth24h and later. At the same time every transitioning administration coagulation function markers and platelet count were detected. The clinical signs were recorded during the course.Results There is no statistical significance on neonatal demographic characteristics, blood coagulation and platelet count of newborns on admission before administering unfractionated heparin among groups (P>0.05) which means with the same conditions. Such complications as intracranial hemorrhage, gastrointestinal bleeding, pulmonary hemorrhage, necrotizing enterocolitis, neonatal jaundice, hypoxic ischemia encephalopathy, heparin-induced thrombocytopenia(HIT), the cure rate were not statistically different (P>0.05). The cure rate of group A was higher than the other two groups. The APTT and D-dimer reduced the most distinctly in the group A.Conclusion Among these three safe and effective choices, the dose of0.1mg·kg-1(12.5U·kg-1) is the most suitable for placental-abruption newborns to prevent the coagulation abnormalities progressing.Section3The content of von willebrand factor and its catenase in placental-abruption preterm infants cord blood and maternal blood Object To study the content of von willebrand factor (VWF) and its catenase(a disintegrin and metalloproteinase with a thrombospondin type1motif, member13, ADAMTS13) of the neonatal venous blood when placental abruption happening and to explore the pathophysiological mechanisms of the coagulation abnormalities of placental abruption.Method The placental abruption groups were included from the inpatients of the NICU of Bayi Children’s Hospital Affiliated to General Hospital of Beijing Military Command of PLA from August2012to January2013. Each group of neonatal venous blood was collected and VWF/ADAMTS13were measured by the means of ELISA.Results40cases were included to the placental abrupton group (group A) and40cases included to the non-placental abruption group (group B). All articles of concentration of VWF of the detected objects in the placental abruption group (945.78±282.29UL-1) are multiplier higher than the non-placental abruption group(213.93±104.39UL-1)(P<0.05) while ADAMTS13concentration of the placental abruption group (163.08±47.87UL-1) is higher than of the control group (308.37±101.21UL-1)(P<0.05)Conclusion The concentration of VWF of placental abruption neanatal body increased highly and the concentration of ADAMTS13correspongdingly decreased significantly. VWF is one of the factors of hyper-coagulable states and ADAMTS13can be protective effect.