Coagulation System In Children Research Articles

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Свертывающая система крови у детей с воспалительными заболеваниями кишечника: нарушения и подходы к коррекции

Свертывающая система крови у детей с воспалительными заболеваниями кишечника: нарушения и подходы к коррекции

Activation of coagulation system and d-dimer levels in children with acute leukemia

Background D-dimer is a molecule as result of breaking downof excessive fibrin formation from the activation of coagulationsystem. There is evidence of increased activation of coagulation inpatients with acute leukemia which was showed by the incrementof d-dimer levels.Objective To evaluate the incidence of activation of coagulationsys tem in children with acute leukemia before receivingchemotherapy.Method This cross-sectional study was performed at Dr. CiptoMangunkusumo Hospital. All newly-diagnosed children with acuteleukemia were included in this study, prior to their receiving anychemotherapy treatment. Blast count, prothrombin time (PTI),activated partial thromboplastin time (APTf), and D-dimer levelswere examined after the diagnosis was confirmed by morphology andimmunophenotyping studies on bone marrow specimens.Results Out of 22 subjects, 13 subjects had increased D-dimervalues. The median D-dimer level of this elevated group was 1,000(range 500-14, 700) n gfmL. In the acute myeloblastic leukemia(AML) patients, activation of coagulation was found in 7 out of 8subjects. The median D-dimer levels was 950 (range 100-14, 700)ng/mL. In the acute lymphocytic leukemia (ALL) patients, 6 outof 14 subjects had increased activation of coagulation with medianD-dimer level of 300 (range 100-3,800) ngfmL. Nine out of 10subjects with blast cells on peripheral blood smear had a medianD-dimer level of 1,000 (range 500-3,800) ng/mL. Both PT andAPTT were found normal in all subjects.Conclusion Activation of coagulation sys tem occurs at thetime of diagnosis as shown by increased D-dimer levels. Thecharacteristics of activation of coagulation system are differentbetween ALL and AML subjects, as well as between subj ects withpositive and negative blast counts on peripheral blood smears.Despite the increased activation of coagulation, PT and APTfremain normal.

Coagulation Activation in Children with Sickle Cell Disease Is Associated with Cerebral Small Vessel Vasculopathy

BackgroundThrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state.MethodsMarkers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications.ResultsSS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec.ConclusionsSS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts.

Antifibrinolytika und Blutgerinnung in der Kinderchirurgie - Was ist anders als beim erwachsenen Patienten?

More than 30 years ago the pioneering work of Andrew and co-workers showed that the coagulation system of children is different than from adult. They have introduced the term of "developmental hemostasis" to describe this phenomenon. They were able to show that the concentration of coagulation factors and inhibitors are age-dependent and therefore reference limits from adult practice cannot be transferred to children one to one. Numerous studies showed that the perioperative loss of blood, and thus the use of homologous blood could be limited by administering antifibrinolytic substances such as aprotinin. Other antifibrinolytics acting substances like Epsilon-aminocaproic acid (EACA) or tranexamic acid (TXA) tended to be misfits in routine clinical practice. In 2006, the publication of a retrospective study carried out by Mangano et al, in which considerable safety concerns were expressed with regard to aprotinin led to a significant rethinking of its clinical use. Two years later the results of the BART (Blood Conservation using antifibrinolytics in a Randomized Trial) study confirmed that there was an increased postoperative mortality associated with the use of aprotinin compared to TXA and EACA. In a few adult studies so far tranexamic acid was found to be comparably as effective as aprotinin. Although TXA is a long known drug available on the market for more than 50 years, the studies connecting factors of indication, dosage regimen and safety are limited especially in children and infants. This article highlights the differences in the coagulation system in children compared to adult as well as indication, dosage regimens and possible side effects of antifibrinolytic agents in children.

Analysis of variation in coagulation function of 36 children with Mycoplasma pneumoniae

Objective To study the effect of Mycoplasma pneumoniae infection on the coagulation system in children and to clarify its mechanism in order to guide the therapeutic strategy for Mycoplasma pneumoniae infection in clinical practice.Methods A prospective and case control study was carried out in 36 children with Mycoplasma pneumoniae infection in Weifang People ' s Hospital from January through December in 2011.The 36 patients were divided into two groups according to the MP-IgM plasma titers,namely low-titer group with MP-IgM 1 ∶ 80-1 ∶ 160 (n =17) and high-titer group with MP-IgM 1 ∶ 320-1 ∶1280 (n =19).The subjects of control group (n =20) were recruited from healthy children as they took routine physical examination during the same period.Six indexes related to the coagulation function as well as D-dimer in plasma were determined.All data were analyzed by using SPSS 15.0 software.Results The levels of fibrinogen (FIB) and D-dimer in the low-titer group and high-titer group were significantly higher than those in the control group (P ＜ 0.05).The prothrombin (PT) and activated partial thromboplastin time (APTT) in the high-titer group were significantly shorter than those in the control group respectively (P ＜ 0.05).Conclusions Mycoplasma pneumoniae infection in children gives rise to the potential for activating the extrinsic and intrinsic coagulation system,promoting thrombosis and in turn inducing ischemic stroke in serious cases. Key words: Mycoplasma pneumoniae infection ; Coagulation function ; Children ; Case control

Thrombin formation and effect of unfractionated heparin during pediatric cardiac catheterization

To assess the strength of thrombin formation and determine the effects of unfractionated heparin (UFH) in children during cardiac catheterization. UFH reduces the thrombotic risk related to catheterization but the effects of UFH on the coagulation system in children, and proper monitoring of UFH remain unclear. We studied 42 patients aged 3-12 years undergoing catheterization. Twenty-seven received UFH (group A) and 15 patients did not (group B). Anticoagulation was assessed by measurements of plasma prothrombin fragment F1 + 2, thrombin-antithrombin (TAT) complexes, D-dimer, activated partial thromboplastin time (APTT), anti-FXa, and prothrombinase-induced clotting time (PiCT). Markers of thrombin generation remained low during catheterization in group A. In group B, both F1 + 2 and TAT had increased significantly (P < 0.05) by the end of the procedure versus baseline and versus respective levels in group A. In group A, 15 min after heparinization, APTT was over 180 sec (in all patients), anti-FXa 1.4 U/ml (1.1-2.4 U/ml) and PiCT 1.5 U/ml (1.3-2.4 U/ml). Anti-FXa and PiCT were correlated (R = 0.84, P < 0.0001). Thrombin generation was enhanced in patients who did not receive UFH, which may increase the risk of thrombotic complications. In group A, routine heparinization seemed excessive by all monitoring methods. UFH prevented an increase in prothrombin to thrombin conversion, resulting in unaltered fibrin formation. The current UFH protocol seemed to have no effect on postprocedural activation of coagulation. Further studies are needed to clarify adequate heparin dosing for children during cardiac catheterization to prevent thrombotic complications without predisposing the patient to bleeding complications.

Extensive Coagulation Profile in Children with Sickle Cell Disease and Its Role in Cerebral Micro-Vasculopathy

AbstractAbstract 3247Activation of the coagulation system is present in adults with Sickle Cell Disease (SCD) who display higher levels of thrombin-antithrombin complex (TAT), prothrombin fragment F1+2, D-dimer, tissue factor and platelet activity. Whether the activation of the coagulation system is a bystander phenomenon or a main determinant of clinical complications is under investigation. Although thrombotic complications in SCD arise since infancy, the coagulation system in children has been poorly explored. We performed a comprehensive and systematic evaluation of the coagulation system in children with SCD and investigated its possible role in the development of the main clinical manifestations of SCD in childhood.The following markers of hemostatic and endothelial function were evaluated during steady state: factor VIII activity (FVIII), von Willebrand factor antigen (vWF:Ag) and collagen binding activity (vWF:CBA), PAI-1 antigen (PAI-1:Ag), t-PA antigen (t-PA:Ag), D-dimer, P-selectin, Nitric Oxide (NO), F1+2, TAT, ADAMTS-13 antigen (ADAMTS-13:Ag) and activity (ADAMTS-13:act). Markers of hemolysis (hemoglobin, reticulocytes, aptoglobin, bilirubin, LDH), inflammation (white blood cells, neutrophils, C reactive protein) were measured. Children were not in chronic transfusion.Magnetic Resonance (MRI), Angio Magnetic Resonance (MRA), Transcranial Doppler (TCD), Tricuspid Regurgitant Velocity (TRV) data and frequency of clinical complications were correlated with coagulation parameters. Continuous variables were compared using two-sided Student's t-test and Mann-Whitney non-parametric test, categorical variables using Chi-square and Fisher's exact test. Correlations between variables were evaluated by the Pearson or Spearman coefficient.Thirty-five HbS/HbS- 3 HbS/betathalassemia° (20 M and 18 F, mean age 6.49 years), and 6 HbS/HbC patients (3 M and 3 F, mean age 11.2 years) were evaluated. 60% of HbS/HbS and HbS/betathalassemia° children presented higher level of FVIII, D-dimer, F1+2 and lower level of NO, revealing coagulation activation since early age in HbS/HbS and HbS/betathalassemia° but not in HbS/HbC (Table 1). Coagulation variables correlated positively with markers of inflammation, hemolysis, endothelial activation demonstrating a broad involvement of the coagulation system in these processes, while correlated negatively with HbF (Table 2). No correlation was seen between coagulation variables and cerebral large vessel vasculopathy investigated by TCD and MRA nor TRV (p >0.05). Patients with Silent Infarcts on MRI (n.9) showed significant decrease in t-PA (4.53 vs 7.67, p 0.03) and ADAMTS-13 Ag (1.15 vs 1.50, p 0.05) -suggesting the presence of endothelial dysfunction- and a tendency toward higher D-dimer (2879.01 vs 1569.51), F1+2 (319 vs 231), TAT (17.17 vs 10.46) -suggesting a trend towards enhanced clotting activation compared to patients without Silent infarcts (n.21). Increase in D-dimer was associated with a Relative risk of 6 (p <0.05) to develop Silent Infarcts. No correlation was found between coagulation activation and Acute Chest Syndrome or Vaso-occlusive crisis.Table 1Coagulation profile in HbS/HbS-HbS/Betathalassemia° and HbS/HbC patientsHbS/HbS+HbS/Betathalassemia°HbS/HbCpVariableMeanFVIII:C %184.96119.220.003VWF:Ag %150.05100.630.013VWF:CBA %135.38107.360.124PAI:Ag ng/ml8.736.850.833t-PA ng/ml6.914.520.062D-dimer ng/ml1906.39366.480.000NO μmol/L7.188.70.336P-selectin ng/ml47.7629.700.010F1+2 pmol/l254.26118.500.037TAT ng/ml12.345.140.359ADAMTS-13:Ag μg/ml1.371.460.653ADAMTS-13:act %79.4278.940.801ADAMTS-13:act/VWF:Ag0.520.780.003Table 2Correlations between hematologic and coagulation parameters in HbS/HbS- HbS/Betathalassemia° (first value is Pearson or Spearman coefficient, second is p-value)White Blood CellsNeutrophilsPlateletsFetal HemoglobinReticulocytesLDHFVIII:C−0.3740.021VWF:Ag−0.3220.049VWF:CBA0.3680.023PAI:Ag0.4490.3690.3330.3520.0050.0250.0440.033t-PA0.3440.034D-dimer0.5590.438−0.3930.3890.4210.0010.0110.0210.0230.013P-selectin0.4610.4000.520−0.4130.3810.0040.0160.0010.0110.020F1+20.4000.5120.3370.0160.0010.044TAT0.3970.3810.3760.0170.0220.024ADAMTS-13 Ag0.4710.004 Disclosures:No relevant conflicts of interest to declare.

Enhanced thrombin generation and depressed anticoagulant function in children with pneumonia

To clarify the status of the coagulation system in children with community-acquired pneumonia. Coagulation activation markers (prothrombin fragment F1 + 2, thrombin-antithrombin complexes, D-dimer), the natural anticoagulants (antithrombin, protein C and S) and tissue factor were measured in 28 consecutive children with pneumonia on admission to the hospital. Patients were divided into those with either bacterial-type pneumonia (at least two of the following three criteria: plasma C-reactive protein (CRP) >80 mg/L, white blood cell count >15 × 10(9) /L and alveolar infiltrates on the chest radiograph) or viral-type pneumonia. The majority of the patients (79%) showed elevation of at least one of the three coagulation activation markers. Plasma CRP concentration correlated with F1 + 2 (R = 0.44, p < 0.05) and D-dimer (R = 0.71, p < 0.0001). Patients with bacterial-type pneumonia (n = 17) had higher D-dimer levels (p < 0.05) and lower levels of antithrombin (p = 0.005) and protein C (p = 0.08) than the patients with viral-type pneumonia. Children with community-acquired bacterial-type pneumonia show distinctive changes in their coagulation system. The finding of coagulation system activation and depressed function of natural anticoagulants in uncomplicated pneumonia helps to understand the rapid and unpredictable changes observed in the coagulation status in patients with more severe forms of disease.

The Coagulation System in Children: Developmental and Pathophysiological Considerations

The coagulation system in children is complex and ever changing, a fact encapsulated in the term developmental hemostasis. Studies confirm that there are quantitative and almost certainly qualitative differences in the coagulation system with age, and the control of these changes comes from something external to the liver. What remains uncertain is the magnitude of the qualitative changes and the implications of the changes for the growing child. At the very least, developmental hemostasis probably provides a protective mechanism for neonates and children and hence contributes to the decreased risk of thromboembolic and/or hemorrhagic events in these age groups. In addition, developmental hemostasis could also reflect the role that hemostatic proteins play in physiological development and hence the demand of other processes, such as angiogenesis. Finally, without doubt, developmental hemostasis affects the interactions of anticoagulant drugs with the coagulation system. This article will initially discuss the most recent evidence with respect to qualitative age-related changes in the coagulation system. Subsequently the article will discuss the coagulation system during childhood in light of the three aforementioned areas of clinical impact and suggest possible strategies to further understand this complex and exciting field of study.

Evaluation of the Coagulation System in Children with Two-Ventricle Congenital Heart Disease

Multiple coagulation factor abnormalities involving both procoagulant and anticoagulant proteins have been described in children with single-ventricle physiology. This study used age-matched controls to evaluate coagulation factors in children with two-ventricle congenital heart disease (CHD). Coagulation factors were assayed in 120 patients with CHD, divided into four age groups: group 1, 0 to 3 months; group 2, 3 to 12 months; group 3, 12 to 48 months; and group 4, older than 48 months. Healthy children without CHD were assayed as controls. Concentration of factors II, V, VII, VIII, IX, and X; protein C and S, plasminogen, and antithrombin III, were measured by standard assays. Normal ranges were determined by the empirical 95% confidence intervals. Significant reductions were found in mean levels of both procoagulant and anticoagulant factors in patients in groups 1, 2, and 3 compared with controls, but no differences were found in group 4. In group 1, all variables had significantly lower concentrations except fibrinogen and protein S; in group 2, all variables had significantly lower concentrations except for fibrinogen, factors VIII and IX, and plasminogen and protein S; and in group 3, all variables had significantly lower concentrations except fibrinogen, factors VIII and IX, and antithrombin III, plasminogen, and protein S. Neonates and infants with two-ventricle CHD have lower levels of procoagulant and anticoagulant factors compared with aged-matched controls approaching normal levels in children aged older than 4 years. These coagulation factor abnormalities are similar to those described in patients with single-ventricle physiology.

The Effect of Hydroxyurea on the Coagulation System in Sickle Cell Anemia and β-Thalassemia Intermedia Patients: A Preliminary Study

Hydroxyurea (HU) has been shown to reduce the frequency of vaso-occlusive manifestations in both adults and children with sickle cell disease (SCD), and the induction of hemoglobin F (HbF) is thought to be the underlying mechanism responsible for clinical improvement in some patients. However, there exists no good correlation between the amount of HbF increase and clinical response. Recent studies suggest that increased activity of the coagulation system may be important in the pathogenesis of vascular occlusion in sickle cell disease. To analyze the effect of HU on the coagulation system in children, the authors studied the levels of some coagulation factors and natural inhibitors. Eleven children who had been treated with HU because of SCD (5 patients), sickle- g -thalassemia (3 patients), and g -thalassemia intermedia (3 patients) were enrolled in the study. Levels of the coagulation factors II, V, VII, VIII, IX, X, XI, and XII, and of protein C and protein S, prothrombin times, activated partial thromboplastine times, thrombin times, and reptilase times were measured before the treatment and at the 5th or 6th months of HU therapy when the patients were in a steady-state condition. There was a decrease in all of the coagulation factors except for FIX and FXII and in inhibitors such as protein C and protein S. However, statistically significant decreases were observed only in factor VIII and protein C levels. The rates of decrease were 54.8 and 12.5% ( p = .015 and p = .018) in FVIII and protein C, respectively. This result shows that HU has significant effects on the coagulation and natural inhibitory systems.

Functional Maturity of the Coagulation System in Children

Functional Maturity of the Coagulation System in Children

Functional maturity of the coagulation system in children: an evaluation using thrombelastography.

There are quantitative deficiencies in the coagulation system for at least the first 6 mo of life. Clinical experience, however, does not indicate an increased risk of excessive bleeding during surgical procedures. Thrombelastography, a test providing a functional evaluation of coagulation, was used to assess the hemostatic system of pediatric patients under 2 yr of age. Thrombelastographic data were obtained from 237 healthy pediatric patients less than 2 yr of age undergoing elective noncardiac surgery. Five groups were distinguished: under 30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Thrombelastography revealed no defects in coagulation when these groups were compared to each other or to adults, indicating a functionally intact hemostatic process even in neonates. Indeed, children less than 12 mo of age were found to initiate and develop clot faster than adults, with the coagulation process slowing to adult rates after 1 yr of age. In addition to defining functional integrity, our data represents a set of pediatric control thrombelastographic values that have not been previously reported and that may become important in understanding coagulation changes that accompany disease states and surgery in pediatric patients.

Effect of corticosteroids on coagulation factors in children with nephrotic syndrome.

Prothrombin time (PT), activated partial thromboplastin time (APTT) and plasma procoagulant activities were studied in 38 children with nephrotic syndrome in the presence or absence of prednisolone therapy. PT was normal but APTT was prolonged during relapse in untreated patients. Increased factors V, VII, VIII, XI and XIII in both treated and untreated and factor IX in treated patients, as well as decreased factors X and XII in untreated patients, were observed during relapse. These coagulation factor changes were unrelated either to the dose of prednisolone or underlying renal histology and normalized with clinical remission. However, plasma levels of factors II, V, VIII, IX, X and XI were still increased in treated patients. The data suggest that corticosteroids shorten APTT, raise both intrinsic and extrinsic factors, and therefore have favorable and unfavorable effects on the coagulation system in children with nephrotic syndrome.