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1.
Thromb Haemost ; 82 Suppl 1: 112-6, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10695499

ABSTRACT

This review analyses literature reports from 1970 to 1998 assessing the use of streptokinase (SK), urokinase (UK) or recombinant tissue-type plasminogen activator (rt-PA) for thrombolytic therapy in neonates and infants. From 1970 to 1998 182 infants were reported to have received SK (n = 54; 29.5%), UK (n = 41; 22.5%) or rt-PA (n = 87; 48%). During thrombolytic therapy no concomitant heparin administration or low dose heparin therapy (5 U/kg/h) were recorded. To perform reocclusion prophylactics heparin was reinitiated at the end of thrombolytic therapy usually in the recommended dosage of 20 U/ kg/h. The overall thrombolytic patency rate in neonates varied from 39% to 86%. Besides bleeding from local puncture sites or recent catheterisation sites (10.4%), pulmonary embolism was reported in 1.1% of the 182 infants. Major bleeding complications, i.e. pulmonary bleeding (0.6%), gastrointestinal bleeding (0.6%) or intraventricular haemorrhage (IVH 2.7%) are rarely reported side effects and only 2 thrombolysis related deaths due to haemorrhage were mentioned. Bleedings reported in the central nervous system (n = 4) mainly occurred in preterm infants (n = 3). In conclusion, data of this preliminary analysis suggest that there is no big difference (p = 0.09; chi2-test) in the efficacy rate between the 3 thrombolytic agents used in the first year of life. In each case an assessment must be made with respect to the relative benefit conferred by thrombolytic therapy in preventing organ or limb damage versus the potential side effects, costs and inconvenience for the childhood patient. Controlled prospective multicentre studies on thrombolytic therapy in neonates and infants are recommended to evaluate patency rates and adverse effects for the different thrombolytic agents used.


Subject(s)
Fibrinolytic Agents/therapeutic use , Streptokinase/therapeutic use , Thrombosis/drug therapy , Tissue Plasminogen Activator/therapeutic use , Urokinase-Type Plasminogen Activator/therapeutic use , Child, Preschool , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Humans , Infant , Infant, Newborn , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Streptokinase/administration & dosage , Streptokinase/adverse effects , Thrombosis/physiopathology , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Urokinase-Type Plasminogen Activator/administration & dosage , Urokinase-Type Plasminogen Activator/adverse effects
2.
Eur J Pediatr ; 158 Suppl 3: S187-91, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10650867

ABSTRACT

UNLABELLED: Consumption coagulopathy is a serious problem in childhood. In addition to treatment of the underlying disease, consumption coagulopathy was previously treated with heparin. Nowadays it is treated by substitution of coagulation factors, especially antithrombin (AT) concentrate, alone or in combination with heparin. In this pilot study we administered AT concentrate (dosage 80 U/kgbw/d), without additional heparin treatment, to 29 children beyond infancy with acquired AT deficiency. Antithrombin, platelet count, fibrinogen, PT, and APTT were assayed before and during the course of AT substitution. These coagulation parameters returned to normal 48 hours after normalisation of the plasma AT level. AT levels normalised within 24 h of initial substitution in all children. Lethal outcome due to the underlying disease was observed in only two children. CONCLUSION: Data of this pilot study suggest that, concomitantly with the treatment of the underlying disease, consumption coagulopathy in childhood can be managed successfully with early substitution of AT concentrate.


Subject(s)
Antithrombin III Deficiency/drug therapy , Antithrombin III/therapeutic use , Disseminated Intravascular Coagulation/drug therapy , Sepsis/complications , Adolescent , Age of Onset , Antithrombin III Deficiency/etiology , Child , Child, Preschool , Disseminated Intravascular Coagulation/etiology , Humans , Infant , Pilot Projects , Statistics, Nonparametric
3.
Klin Padiatr ; 204(3): 134-40, 1992.
Article in German | MEDLINE | ID: mdl-1614177

ABSTRACT

Consumption coagulopathy in childhood is still a serious problem. Besides treatment of the underlying diseases therapy of consumption coagulopathy was performed with heparin and nowadays with substitution of coagulation factors, especially antithrombin III concentrate, alone or in combination with heparin. We performed administration of AT III concentrates only, without additional heparin treatment in children with proven septicaemia (preterm infants n = 21, children beyond the newborn period n = 18). Antithrombin III, platelet count, fibrinogen, PT, aPTT and TT were assayed. These coagulation parameters turned to be normal 48 hours after normalisation of the antithrombin III plasma level-AT III increased to normal values within 24 hours after the initial substitution in all children. Lethal outcome was not observed after sole administration of AT III as well as no other side effects have been seen. In summary, these data indicate that consumption coagulopathy in childhood can be managed successfully with early substitution of AT III concentrate.


Subject(s)
Antithrombin III/therapeutic use , Disseminated Intravascular Coagulation/therapy , Infant, Premature, Diseases/therapy , Shock, Septic/therapy , Adolescent , Antithrombin III Deficiency , Blood Coagulation Tests , Child , Child, Preschool , Disseminated Intravascular Coagulation/blood , Female , Humans , Infant , Infant, Newborn , Infant, Premature, Diseases/blood , Male , Shock, Septic/blood
4.
Monatsschr Kinderheilkd ; 140(3): 183-7, 1992 Mar.
Article in German | MEDLINE | ID: mdl-1603102

ABSTRACT

QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1-antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1-inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.


Subject(s)
Blood Coagulation Factors/analysis , Blood Coagulation Tests , Thrombosis/genetics , Adolescent , Blood Coagulation Factors/genetics , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Platelet Aggregation/genetics , Protein C/analysis , Protein C/genetics , Risk Factors , Thrombosis/blood , alpha 1-Antichymotrypsin/analysis , alpha 1-Antichymotrypsin/genetics , alpha-2-Antiplasmin/analysis , alpha-2-Antiplasmin/genetics , von Willebrand Factor/analysis , von Willebrand Factor/genetics
5.
Klin Padiatr ; 204(1): 37-42, 1992.
Article in German | MEDLINE | ID: mdl-1531514

ABSTRACT

In order to establish an univariate nonparametric pediatric tolerance region platelet function has been investigated in 105 healthy children and adolescents. In comparison to adult normal values, the bleeding time is shortened, spontaneous platelet aggregation is enhanced as well as collagen-induced platelet aggregation. 30% of the children showed an increased disaggregation in ADP-induced aggregation. A slight delay was found in the spreading of thrombocytes. Platelet volume shifted to the left. Values of beta-thromboglobulin were raised. Compared to adult values no alterations could be found in platelet shape-change. Changes of platelet functions were more apparent in the younger children.


Subject(s)
Platelet Function Tests , Adenosine Diphosphate/pharmacology , Adolescent , Bleeding Time , Child , Child, Preschool , Collagen/pharmacology , Female , Humans , Male , Platelet Aggregation , Reference Values , beta-Thromboglobulin/chemistry
6.
Monatsschr Kinderheilkd ; 139(12): 821-5, 1991 Dec.
Article in German | MEDLINE | ID: mdl-1770958

ABSTRACT

Platelet count, spontaneous platelet aggregation, ADP- and collagen-induced platelet aggregation platelet adhesion, platelet volume, shape change, beta-thromboglobulin and von-Willebrand-factor have been investigated in 51 insulin dependent diabetic children without clinical signs of diabetic angiopathy. Compared to an age matched healthy control group diabetic children showed a significant enhancement of spontaneous platelet aggregation, elevated plasma levels of von-Willebrand-factor, increased platelet shape change and adhesion. No alterations could be found in ADP--and collagen--induced platelet aggregation and in beta-thromboglobulin levels. Significant correlations could be found between the total glycosylated haemoglobin concentrations (Hb A1) and spontaneous platelet aggregation, as well as between duration of diabetes Hb A1, and platelet volume. In this study we could demonstrate changes in platelet function in diabetic children without clinical signs of diabetic angiopathy. However these changes could be due to metabolic adjustment and may precede diabetic vasculopathy.


Subject(s)
Diabetes Mellitus, Type 1/blood , Platelet Function Tests , Adenosine Diphosphate/pharmacology , Adolescent , Child , Child, Preschool , Collagen/pharmacology , Humans , Infant , Platelet Adhesiveness , Platelet Aggregation/drug effects , Platelet Count , von Willebrand Factor/analysis
7.
Klin Padiatr ; 203(6): 424-8, 1991.
Article in German | MEDLINE | ID: mdl-1758145

ABSTRACT

The prevalence of inherited thrombotic syndrome in the general population appears to be higher than that of inherited bleeding disorders. The most important candidates for screening are patients with unexplained venous thromboembolism at ages of less than 40 years: In 18 children and adolescents suffering from "idiopathic" vein thrombosis laboratory screening has been performed: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2-antiplasmin and alpha-2-macroglobulin. Compared to an age matched healthy control group in children with idiopathic vein thrombosis we could demonstrate in vitro platelet activation with significant enhanced platelet aggregation and elevated levels of von Willebrand factor in the onset of the disease. Antithrombin III, protein C, alpha-2-antiplasmin and alpha-2-macroglobulin were significantly decreased. These changes turned to be normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, alpha-1-antichymotrypsin and c1-inactivator showed no alterations compared to the control. Platelet activation and alteration of platelet function in vivo and in vitro is established to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The decreased inhibitors of the hemostatic system antithrombin III and protein C in the onset period of thrombotic diseases are discussed to be an increased turnover, whereas the decreased levels of alpha-2-antiplasmin and alpha-2-macroglobulin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system.


Subject(s)
Blood Coagulation , Thrombosis/blood , Adolescent , Blood Coagulation Factors/analysis , Blood Coagulation Tests , Child , Female , Humans , Male , Platelet Aggregation , Platelet Count
8.
Klin Padiatr ; 203(5): 359-62, 1991.
Article in German | MEDLINE | ID: mdl-1942942

ABSTRACT

Thrombolytic therapy usually used for thrombosis in the adult has been administered as a therapeutic regiment in pediatric patients (parental consent was sought prior to the treatment with rt-PA). We report our experience with rt-PA in 17 children and adolescents suffering from arterial (n = 4) or venous thrombosis (n = 13) due to local rhabdomyosarcoma, acute lymphoblastic leukemia, chronic myeloblastosis, sickle cell anaemia, parenteral nutrition, haemolytic uremic syndrome, central arterial and venous catheters and septicemia Thrombotic diseases have been diagnosed by Doppler ultrasound, computed tomography, angiography and phlebography. Rt-PA therapy was started immediately after diagnostic procedures had been performed. Rt-PA dose varied from 0.2 mg as a single dose to 0.8 mg/kg bw/d over a three day period in children local thrombolysis was performed. In patients requiring systemic thrombolytic therapy rt-PA was administered from 0.8 mg/kg bw/d in three days to 2.0 mg/kg bw/d over a whole period of three weeks in both groups during thrombolysis low dose heparin was added. When rt-PA infusion was terminated heparin (70 IU - 400 IU/kg bw/d) was administered for 7 to 14 days in order to prevent reocclusion. Later prophylaxis with coumarin derivatives in venous thrombosis and antiplatelet agents in arterial occlusive diseases was performed. In no patient did we see a decrease of fibrinogen and plasminogen during rt-PA therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Thrombosis/drug therapy , Tissue Plasminogen Activator/therapeutic use , Adolescent , Child , Child, Preschool , Drug Therapy, Combination , Female , Heparin/administration & dosage , Humans , Infant , Infant, Newborn , Infusions, Parenteral , Male , Postphlebitic Syndrome/prevention & control , Recombinant Proteins/therapeutic use , Thrombosis/etiology , Tissue Plasminogen Activator/administration & dosage
9.
Monatsschr Kinderheilkd ; 139(7): 403-8, 1991 Jul.
Article in German | MEDLINE | ID: mdl-1922117

ABSTRACT

In order to establish age related univariate nonparametric tolerance regions in 74 healthy children and adolescents (age 2-18 years) undergoing elective surgery the following haemostatic parameters have been investigated: platelet count, von Willebrand factor, factor VIIIC, ristocetin-cofactor, antithrombin III, protein C fibrinogen, plasminogen, alpha-2-antiplasmin, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin and alpha-macroglobulin. Compared to adult normal values medians of von Willebrand factor and protein C were lowered, alpha-2-antiplasmin, C1-inactivator and alpha-2-macroglobulin were elevated, whereas the medians of alpha-1-antitrypsin and alpha-1-antichymotrypsin reached the lower adult borderline. The other investigated parameters showed no difference to those of adults.


Subject(s)
Blood Coagulation Tests , Fibrinolysis , Hemostasis , Adolescent , Blood Proteins/chemistry , Child , Child, Preschool , Female , Humans , Infant , Male , Platelet Count , Prospective Studies , Reference Values
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