Neonatal Coagulation Research Articles

The impact of maternal smoking during pregnancy on hemostatic profile of neonates using thromboelastometry (ROTEM). A pilot observational study

IntroductionIn adults, the negative effect of smoking on hemostasis has been well established. Contrarily, data regarding the hemostatic status of neonates exposed to tobacco during pregnancy are limited. This study aimed to investigate the influence of antenatal tobacco exposure on the hemostatic profile of neonates using Thromboelastometry (ROTEM). MethodsThis observational study included 92 healthy full-term neonates born in the maternity department of our hospital over a 5-year period. The neonates were categorized in 2 groups: neonates born to mothers who reported smoking during the entire pregnancy and neonates born to non-smoking mothers. Neonates were matched 1:1 with regards to gestational age, delivery mode, and gender. ROTEM EXTEM assay was performed on the 2nd-3rd day of life and clotting time (CT); clot formation time (CFT); clot amplitude recorded at 10 and 30 min (A10, A30); a angle (ao); maximum clot firmness (MCF, mm); lysis index at 30 and 60 min (LI30, LI60, %); maximum clot elasticity (MCE), were measured. ResultsNeonates with antenatal exposure to tobacco had shorter CT (p < 0.001) and CFT (p = 0.035), higher A10 (p = 0.043), A30 (p = 0.028) and MCE (p = 0.028) compared to those not exposed to tobacco during pregnancy. The multivariable regression analysis adjusted for gestational age, gender, birth weight and delivery mode showed that maternal tobacco use during pregnancy is associated with an accelerated activation of coagulation in neonates expressed by shorter EXTEM CT values (coefficient: −8.68, 95%,CI: −13.51–-3.85, p = 0.001) while no association was found with the remaining ROTEM parameters. DiscussionSmoking during pregnancy results in a hypercoagulable profile of neonates, expressed by shorter ROTEM CT. Antenatal exposure to tobacco appears to be an aggravating factor for the hemostatic status of neonates.

Coagulation parameters and Apgar score are associated with severity in preterm infants.

Coagulation parameters are used to diagnose hematological diseases. The correlation between the coagulation parameters and Apgar score at 5 min is yet to be elucidated. The present study aimed at describing the neonatal coagulation parameters in preterm infants with a low Apgar score at 5 min. In this case-control study, 32 serious preterm infants were compared with 20 preterm infants, according to the Apgar score at 5 min. The prothrombin time (PT), thrombin time (TT), fibrinogen (Fbg), activated partial thromboplastin time (APTT), calculated international normalized ratio (INR), D-dimer (D2), fructose diphosphate sodium (FDP), and procalcitonin (PCT) values were recorded. The linear correlation between coagulation parameters and Apgar score at 5 min was analyzed by linear regression. The two groups were compared using GraphPad Prism 8 (LaJolla, CA, USA). In the study, the mean coagulation parameters were significantly higher in the serious preterm infants with low the Apgar score at 5 min compared to the preterm infants with normal Agar scores at 5 min (p<0.05). The correlation between coagulation parameters and Apgar score at 5 min was recorded (PT: R=0.3984; APTT: R=0.3165; INR: R=0.4139). The coagulation parameters were significantly higher in serious preterm infants with a low Apgar score at 5 min. Also, the coagulation parameters and Apgar score at 5 min are associated with severity in preterm infants.

Neonatal haemostatic parameters in correlation to gestational age and birth weight.

The aim of our study was to establish reference ranges for neonatal coagulation and fibrinolysis parameters and to investigate their relationship with gestational age (GA) and birth weight (BW). A single-centre prospective study was conducted in all healthy neonates born in our hospital during the study period, excluding those with maternal or neonatal disorders and diseases that affect haemostasis. The following parameters were measured: fibrinogen, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) as well as factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (vWF), protein C, free protein S, antithrombin (AT), activated protein C resistance (APCr), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1). Study population consisted of 327 neonates. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII were positively correlated, while PT, aPPT, INR, APCr and tPA were negatively correlated with GA and BW. Proteins C and S, factors II, VIII, IX, XI and vWF, as well AT III and PAI-1 had a significant positive linear correlation with GA, while aPTT had a significant negative one. Fibrinogen, and factors V, VII and XII had a significant positive linear correlation with BW, while factor VIII, tPA, as well PT and INR had a significant negative one. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII increase with GA and BW.

Intracranial Bleeding as a Major Problem Among Neonates With Disseminated Intravascular Coagulation After the Introduction of Recombinant Thrombomodulin.

A standard treatment for disseminated intravascular coagulation in neonates has not yet been established. We analyzed the outcomes of 23 neonates who developed disseminated intravascular coagulation due to infection or asphyxia between 2004 and 2017. The overall survival rate was 95.7% on day 28 after anticoagulant therapy. In contrast, the bleeding-free survival rate was 69.6% (95% confidence interval, 53.1%-91.2%). Of the 6 neonates with intracranial bleeding, 2 developed neurological sequelae. The current study showed that intracranial bleeding remained a major problem in the early 2000s, despite the introduction of a new anticoagulant drug, recombinant thrombomodulin, at our institution since 2009.

TEG® and ROTEM® Traces: Clinical Applications of Viscoelastic Coagulation Monitoring in Neonatal Intensive Care Unit.

The concentration of the majority of hemostatic proteins differs considerably in early life, especially in neonates compared to adulthood. Knowledge of the concept of developmental hemostasis is an essential prerequisite for the proper interpretation of conventional coagulation tests (CCT) and is critical to ensure the optimal diagnosis and treatment of hemorrhagic and thrombotic diseases in neonatal age. Viscoelastic tests (VETs) provide a point-of-care, real-time, global, and dynamic assessment of the mechanical properties of the coagulation system with the examination of both cellular and plasma protein contributions to the initiation, formation, and lysis of clots. In this work, we provide a narrative review of the basic principles of VETs and summarize current evidence regarding the two most studied point-of-care VETs, thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®), in the field of neonatal care. A literature analysis shows that viscoelastic hemostatic monitoring appears to be a useful additive technique to CCT, allowing targeted therapy to be delivered quickly. These tools may allow researchers to determine the neonatal coagulation profile and detect neonatal patients at risk for postoperative bleeding, coagulation abnormalities in neonatal sepsis, and other bleeding events in a timely manner, guiding transfusion therapies using the goal-oriented transfusion algorithm. However, diagnosis and treatment algorithms incorporating VETs for neonatal patients in a variety of clinical situations should be developed and applied to improve clinical outcomes. Further studies should be performed to make routinary diagnostic and therapeutic application possible for the neonatal population.

Thrombosis and hemostasis parameters in early life – the copenhagen baby heart and compare studies

Background and Aims: The neonatal coagulation system is not fully developed at birth. Reliable reference values in newborns and during early childhood are not well described, complicating clinical decision making within thrombosis and hemostasis. The aim of this study is to evaluate values of coagulation parameters at birth and two months after birth, and to test whether cord blood measurements can be used as proxy for neonatal venous blood measurements.

Risk factors and treatments for disseminated intravascular coagulation in neonates

BackgroundAlthough disseminated intravascular coagulation (DIC) is a critical disease, there is few gold standard interventions in neonatal medicine. The aim of this study is to reveal factors affecting neonatal DIC at birth and to assess the effectiveness of rTM and FFP for DIC in neonates at birth.MethodsWe retrospectively evaluated DIC score on the first day of life in neonates with underlying conditions associated with DIC. DIC in neonates was diagnosed according to Japan Society of Obstetrical, Gynecological & Neonatal Hematology 2016 neonatal DIC criteria.ResultsComparing neonates with DIC scores of ≥3 (n = 103) to those < 3 (n = 263), SGA, birth asphyxia, low Apgar score, hemangioma, hydrops, PIH, and PA were statistically increased. Among 55 neonates underwent DIC treatment, 53 had birth asphyxia and 12 had intraventricular hemorrhage. Forty-one neonates received FFP or a combination of FFP and antithrombin (FFP group), while 14 neonates received rTM or a combination of rTM, FFP, and antithrombin (rTM group). DIC score before treatment in the rTM group was significantly higher than in the FFP group (4.7 vs 3.6, P < 0.05). After treatment, DIC scores in both groups were significantly reduced on Day 1 and Day 2 (P < 0.05).ConclusionsAmong various factors associated with DIC in neonates at birth, birth asphyxia is particularly significant. Furthermore, rTM in combination with FFP therapy was effective for neonatal DIC at birth.

New insights into neonatal coagulation: normal clot formation despite lower intra-clot thrombin levels

Healthy neonates exhibit no bleeding tendencies, but exhibit longer partial thromboplastin times than adults. Lower clotting factor levels may be balanced by lower inhibitor levels, which is not reflected in routine coagulation assays, but could result in normal clot formation in vivo. The novel thrombodynamics assay simulates a damaged vessel with tissue factor immobilized to a surface. We hypothesized that intra-clot thrombin levels and spatial fibrin clot formation with this assay are comparable in neonates and adults. Coagulation was tested in plasma from venous neonatal blood (N = 12), cord blood (N = 30), and adult blood (N = 20) using thrombodynamics and calibrated automated thrombography. Neonates exhibited a higher initial rate of clot formation than adults (adult: 60.7 ± 3.9 µm/min; neonatal: 66.8 ± 3.9 µm/min; cord: 68.1 ± 3.3 µm/min; P < 0.001) and a comparable stationary rate of clot formation (adult: 35.8 ± 8.5 µm/min; neonatal: 37.0 ± 4.6 µm/min; cord: 36.0 ± 5.2 µm/min; P = 0.834). Intra-clot thrombin levels were lower in neonates (adult: 41.9 ± 11.2 AU/l; neonatal: 22.6 ± 10.2 AU/l; cord: 23.6 ± 9.7 AU/l; P < 0.001), but the longitudinal rate of thrombin propagation was comparable (adult: 27.2 ± 4.2 µm/min neonatal; 27.9 ± 2.9 µm/min; cord: 27.6 ± 3.4 µm/min; P = 0.862). Despite lower intra-clot thrombin levels, neonates exhibit normal spatial fibrin clot growth, which concurs with clinically well-functioning hemostasis in healthy neonates.

Progress of anticoagulant system and thrombotic diseases in neonates

Newborns are prone to coagulation dysfunction in stress after birth, which is related to their imperfect coagulation and anticoagulation systems.The neonatal anticoagulation system is in a process of continuous development and maturation, and its physiological changes are very complicated.In recent years, research on neonatal coagulation and anticoagulation systems has got a lot of achievement, but there is still a lack of large-scale randomized studies for a reference range of neonatal anticoagulant factors.Neonatal thrombotic diseases are more and more common.The treatment includes anticoagulative and thrombolytic therapy. Key words: Neonate; Thrombus; Anticoagulant system

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels.

Background: The neonatal hemostatic system exhibits a fragile balance featuring lower levels of clotting factors as well as inhibitors. Neonatal platelets show in-vitro hypoaggregability, but neonates exhibit well-functioning primary and secondary hemostasis despite this impairment. Recently, polyphosphate shed by activated platelets has been shown to induce a prothrombotic shift on the plasmatic coagulation system of adults. The impact of platelet derived polyphosphate might differ in neonates due to aforementioned peculiarities.Aims: We aimed to comparatively determine polyphosphate content and release from adult and neonatal platelets and to determine its impact on thrombin generation in plasma from adult and cord blood.Methods: Polyphosphate was extracted from adult and neonatal platelet lysates and releasates using silica spin-columns and quantified with a DAPI based fluorescence assay. The impact of exogenous polyphosphate in various concentrations (208–0.026 μg/ml) on thrombin generation was evaluated in plasma from adult and cord blood as well as in adult plasma with reduced tissue factor pathway inhibitor (TFPI) levels using calibrated automated thrombography.Results: Polyphosphate content was comparable in both groups, but the fraction of released polyphosphate upon stimulation with thrombin receptor activating peptide was lower in neonatal samples (adult: 84.1 ± 12.9%; cord: 58.8 ± 11.2%). Relative impact of polyphosphate on lag time of thrombin generation was higher in adult samples compared to samples from cord blood (adult: 41.0% [IQR: 35.2–71.8%] of vehicle; cord: 73.4% [IQR: 70.2–91.4%] of vehicle). However, in samples from cord blood, lower concentrations of polyphosphate were required to obtain maximal impact on thrombin generation (adult: 26 μg/ml; cord: 0.814 μg/ml). PolyP affected thrombin generation in adult plasma similarly to cord plasma, when the TFPI concentration was reduced to neonatal levels.Conclusion: Differences in the impact of polyphosphate on adult and neonatal coagulation are largely caused by differences in TFPI levels. Lower polyphosphate release from neonatal platelets, but lower optimum concentration to drive neonatal plasmatic hemostasis emphasizes the well-matched, but fragile interplay between platelets and coagulation in newborns. A potential developmental mismatch should be considered when transfusing adult platelets into neonates.

Effects of mistral-air inflatable blanket on neonatal blood coagulation function after surgery for general anesthesia

Objective To evaluate the value of mistral-air inflatable blanket in neonatal temperature , postoperative complications, and the influence of the blood coagulation function after surgery undergoing general anesthesia. Methods A total of 60 newborns with laparotomy operation undergoing general anesthesia were randomly divided into two groups, the control group and the observation group, 30 persons each group.The newborns were given mistral-air inflatable blanket in the observation group, and conventional methods in the control group, two groups were transferred to Postanesthesia Care Unit by incubator at 37℃.The introperative nasopharyngeal temprature, HR, MAP and SpO2 were recorded before induction(T0), 30 minutes during operation(T1), extubated instantly(T2), 15 minutes during PACU(T3), 30 min during PACU(T4). The extubation time and the incidence of apnoea and hyoxemia were recorded after operation.PT, APTT, TT and Fib were tested before induction and extubated instantly. Results The temperature of intraoperative and postoperative period were higher in the observation group than the control group, the difference was significant(P 0.05). The observation group extubation time were less than the control group, the difference was significant(P 0.05). The PT, APTT, TT and Fib in the observation group were better than the control group, the difference between the groups was significant(P<0.05). Conclusion Mistral-air inflatable blanket can effectively prevent the decrease of the body temperature during operation and PACU, reduce the exduction time and postoperative complications, and protect blood coagulation function. Key words: Mistral-Air inflatable blanket; Newborn; Temperature; Blood coagulation function

The evaluation and management of neonatal coagulation disorders

Background Coagulation involves a series of physiological cascades. Unlike its adult counterpart, neonatal blood coagulation system is evolving and the concentrations of some clotting-related proteins are relatively lower. Objective To review studies in neonatal blood coagulation in order to guide early diagnosis, treatment and prevention of the neonatal bleeding and clotting disorders. Content Coagulation is controlled by a balance between coagulating and anti-coagulating processes. For instance, coagulation is triggered by vascular injuries, is initiated by adjacent platelets and activated coagulating factor Ⅶ, and develops when platelets bind to von Willibrands factor and collagens. Protein C deactivates some coagulating factors, and inhibits coagulation. In neonates, these molecules are all at lower concentrations, and some of them even exist in immature format. As neonatal blood coagulation function is evaluated by routine blood tests with references for adults, it is difficult to screen neonates with potential coagulating disorders. The common causes of neonatal bleeding include primary bleeding diseases[i.e. hemophilia and von willebrand disease(vWD)] and bleeding that follows cardiovascular surgery and necrotizing enterocolitis, etc. Trend Standard references for neonatal blood tests should be specified to a particular development stage in terms of blood coagulation. More clinical trials are needed to further characterize neonatal blood coagulation system and to optimize the treatment of bleeding diseases. Key words: Neonate; Coagulation disorders; Bleeding

Examining the transplacental passage of apixaban using the dually perfused human placenta

Essentials Apixaban is a novel oral anticoagulant that has not been studied in pregnant patients. Our objective was to determine the rate and extent of the placental transfer of apixaban. Apixaban rapidly crosses the ex vivo term human placenta from maternal to fetal circulation. Fetal apixaban levels in vivo are estimated to be 35-90% of the corresponding maternal levels. Background Apixaban is a novel oral anticoagulant that is increasingly being prescribed to women of reproductive age. However, information regarding its placental transfer is non-existent. Objective To determine the rate and extent of placental transfer of apixaban, using the human placenta ex vivo. Methods Placentae collected after Caesarean or vaginal delivery of healthy term infants were perfused in the respective maternal and fetal circulation. At the start of the experiment, apixaban was added to the maternal circulation at a concentration of 150 ng mL(-1) , and samples from maternal and fetal reservoirs were collected over 3 h. Results There was a rapid decline of apixaban in the maternal compartment, followed by emergence in the fetal compartment with a median fetal-to-maternal drug concentration ratio of 0.77 (interquartile range [IQR], 0.76-0.81) and fetal concentration of 39.0 ng mL(-1) (IQR, 36.8-40.6) after 3 h (n = 5). The perfusion results were subsequently adjusted to account for differences in the concentration of plasma proteins in maternal and fetal blood, as apixaban remains highly bound to albumin and alpha-1 acid glycoprotein. After the adjustment, the predicted fetal-to-maternal ratio of total (bound plus unbound) apixaban concentrations in vivo ranged from 0.35 to 0.90. Conclusions We conclude that unbound apixaban rapidly crosses from the maternal to fetal circulation. We further predict that total apixaban concentrations in cord blood in vivo are 35-90% of the corresponding maternal levels, suggesting that apixaban could have a possible adverse effect on fetal and neonatal coagulation.

Optimizing Thrombin Generation with 4-Factor Prothrombin Complex Concentrates in Neonatal Plasma After Cardiopulmonary Bypass.

Bleeding is a serious complication after pediatric cardiopulmonary bypass (CPB) that is associated with an increase in perioperative morbidity and mortality. Four-factor prothrombin complex concentrates (4F-PCCs) have been used off-label to supplement transfusion protocols for bleeding after CPB in adults; however, data on their use in neonates are limited. In this study, we hypothesized that 4F-PCCs administered ex vivo to neonatal plasma after CPB will increase thrombin generation. Fifteen neonates undergoing complex cardiac repairs requiring CPB were enrolled in this prospective study. Arterial blood was obtained after anesthesia induction but before CPB (baseline), after CPB following heparin reversal, and after our standardized transfusion of a quarter of a platelet apheresis unit (approximately 20 mL·kg) and 3 units of cryoprecipitate. Kcentra (CSL Behring), a 4F-PCC with nonactivated factor VII (FVII), and factor 8 inhibitor bypassing activity (FEIBA; Baxter Healthcare Corporation), a 4F-PCC with activated FVII, were added ex vivo to plasma obtained after CPB to yield concentrations of 0.1 and 0.3 IU·mL. Calibrated automated thrombography was used to determine thrombin generation for each sample. The addition of Kcentra to plasma obtained after CPB resulted in a dose-dependent increase in the median (99% confidence interval) peak amount of thrombin generation (42.0 [28.7-50.7] nM for Kcentra 0.1 IU·mL and 113.9 [99.0-142.1] nM for Kcentra 0.3 IU·mL). The rate of thrombin generation was also increased (15.4 [6.5-24.6] nM·min for Kcentra 0.1 IU·mL and 48.6 [29.9-66.6] nM·min for Kcentra 0.3 IU·mL). The same was true for FEIBA (increase in peak: 39.8 [27.5-49.2] nM for FEIBA 0.1 IU·mL and 104.6 [92.7-124.4] nM for FEIBA 0.3 IU·mL; increase in rate: 17.4 [7.4-28.8] nM·min FEIBA 0.1 IU·mL and 50.5 [26.7- 63.1] nM·min FEIBA 0.3 IU·mL). In the posttransfusion samples, there was a significant increase with Kcentra in the median (99% confidence interval) peak amount (41.1 [21.0-59.7] nM for Kcentra 0.1 IU·mL and 126.8 [106.6- 137.9] nM for Kcentra 0.3 IU·mL) and rate (18.1 [-6.2 to 29.2] nM·min for Kcentra 0.1 IU·mL and 53.2 [28.2-83.1] nM·min for Kcentra 0.3 IU·mL) of thrombin generation. Again, the results were similar for FEIBA (increase in peak: 43.0 [36.4-56.7] nM for FEIBA 0.1 IU·mL and 109.2 [90.3-136.1] nM for FEIBA 0.3 IU·mL; increase in rate: 25.0 [9.1-32.6] nM·min for FEIBA 0.1 IU·mL and 59.7 [38.5-68.7] nM·min for FEIBA 0.3 IU·mL). However, FEIBA produced in a greater median reduction in lag time of thrombin generation versus Kcentra in samples obtained after CPB (P = 0.003 and P = 0.0002 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL, respectively) and in samples obtained after transfusion (P < 0.0001 for FEIBA versus Kcentra at 0.1 and 0.3 IU·mL). After CPB, thrombin generation in neonatal plasma was augmented by the addition of 4F-PCCs. The peak amount and rate of thrombin generation were enhanced in all conditions, whereas the lag time was shortened more with FEIBA. Our findings suggest that the use of 4F-PCCs containing activated FVII may be an effective adjunct to the initial transfusion of platelets and cryoprecipitate to augment coagulation and control bleeding in neonates after CPB.

Neonatal haemostasis and the management of neonatal thrombosis.

Two detailed reviews of the management of neonatal thrombosis were published in 2012; one was an up-dated version of guidance first issued in 2004 and the other was a comprehensive review. Both of these publications gave very similar advice regarding the practical aspects of the indications, dosage and management of antithrombotic therapy. The authors stated that the evidence supporting most of their recommendations for anti-thrombotic therapy in neonates remained weak and so the therapy for a neonate with a thrombosis has to be based on an individualized assessment of estimated risk versus potential benefit. The aim of this present review is to give the treating physician an outline of the unique physiology of neonatal coagulation and how this affects the monitoring, dosing and even the choice of therapeutic strategy for the management of thrombosis in the neonate.

Evaluation of the GEM®PCL Plus point-of-care device for neonatal coagulation assessment: An observational study on cord blood

IntroductionPoint of care devices (POCT) are used for coagulation evaluation in adults. Reduced blood volumes and the direct use of whole blood allow studies when venous puncture is difficult, such as in newborns. Elimination of sample transport is attractive for use in emergencies and intensive care. ObjectiveTo prospectively compare neonatal coagulation parameters measured by the GEM®PCL POCT versus a central laboratory. Materials and MethodsProthrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) were performed on whole cord blood (POCT) and plasma (central laboratory) collected from consecutive newborns at Geneva University Hospitals. Agreement was assessed with a Bland & Altman plot and intra-class correlation coefficient (ICC) in 213 newborns cord blood; intra-assay variability (repeatability) was assessed using ICC and coefficient of variation (CV). Results189 samples were available for the agreement analysis, 24 were excluded for technical problems. The 95% limits of agreements in the Bland & Altman plot ranged from -5.6 to 11.6 and from -39.6 to 11.6seconds for the PT and aPTT, respectively. The ICC between the two methods was 0.28 (CI 95% 0.06 to 0.47) for PT and 0.20 (CI 95% -0.06 to 0.42) for aPTT. Repeatability (ICC) on the 43 eligible samples was 0.46 (CI 95% 0.19 to 0.67) for PT and 0.52 (CI 95% 0.26 to 0.71) for aPTT. The CV was 10.6% and 12% for PT and aPTT, respectively. ConclusionsIn newborn cord blood, PT and aPTT measurements with the GEM®PCL POCT had poor agreement with the central laboratory and poor repeatability.

Coagulation and the surgical neonate

Both coagulopathy and abnormal thrombosis can complicate the anesthetic and surgical management of neonatal patients; however, the patterns of bleeding and thrombosis in neonates differ from those in adults or older children. Severe coagulopathic bleeding most commonly occurs during heart surgery and almost certainly contributes to morbidity and mortality in this population. Such severe bleeding is rare during other surgery; the exception is babies presenting to the operating room with established coagulopathy secondary to severe sepsis. Alternatively, pathological thrombosis will mainly occur in association with indwelling vascular access devices or surgically created vascular shunts. There are important differences between the coagulation system in neonates and older patients. The implication of this is that therapies established in other patient groups will not be optimal for neonates without adaptation. While evidence from high-quality clinical trials is rarely available, an understanding of how coagulation in neonates differs can help to guide practice. This review will discuss important differences between the coagulation system of neonates and older patients and how these relate to newer models of coagulation. The emphasis will be on issues likely to impact on perioperative care. In particular, the management of severe bleeding, the manipulation of coagulation during heart surgery, and the management of coagulopathy in septic neonates will be discussed in detail.

The conundrum of neonatal coagulopathy.

The maturation and postnatal development of the human coagulation system was first studied and described more than 20 years ago. These older studies, supported by more recent data, confirm the significant and important differences in the physiology of coagulation and fibrinolysis in neonates and young children compared with older children and adults. Subsequently, significant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis. These differences, which mostly reflect the immaturity of the neonatal hemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults. Systemic diseases may affect hemostasis, predisposing ill neonates to increased hemorrhagic or thrombotic complications. The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage. Therapies targeting the hemostasis system can be effective for preventing and treating these events. The concept of "neonatal coagulopathy" has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates. For diagnosis of hemostasis disorders, diagnostic laboratories processing pediatric samples should use age-, analyzer-, and reagent-appropriate reference ranges. Age-specific guidelines should be followed for the management of neonates with hemostatic disorders.

The conundrum of neonatal coagulopathy

Abstract The maturation and postnatal development of the human coagulation system was first studied and described more than 20 years ago. These older studies, supported by more recent data, confirm the significant and important differences in the physiology of coagulation and fibrinolysis in neonates and young children compared with older children and adults. Subsequently, significant differences were also described in the physiology of primary hemostasis and in global in vitro tests for hemostasis. These differences, which mostly reflect the immaturity of the neonatal hemostasis system, are functionally balanced. Healthy neonates show no signs of easy bruising or other bleeding diathesis and no increased tendency to thrombosis for any given stimulus compared with adults. Systemic diseases may affect hemostasis, predisposing ill neonates to increased hemorrhagic or thrombotic complications. The immaturity of the hemostasis system in preterm and very-low-birth-weight neonates may contribute to a higher risk for intraventricular hemorrhage. Therapies targeting the hemostasis system can be effective for preventing and treating these events. The concept of “neonatal coagulopathy” has an important impact on both the diagnosis and management of hemorrhagic or thrombotic events in neonates. For diagnosis of hemostasis disorders, diagnostic laboratories processing pediatric samples should use age-, analyzer-, and reagent-appropriate reference ranges. Age-specific guidelines should be followed for the management of neonates with hemostatic disorders.

Haemostatic profile of healthy premature small for gestational age neonates

BackgroundThe pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. ObjectiveTo evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. Study designWe performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. ResultsPremature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. ConclusionsDespite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms.