Hämostaseologie in der Pädiatrie

Karin Kurnik; Christoph Bidlingmaier; Sebastian Hütker; Martin Olivieri

doi:10.5482/HAMO-15-04-0016

Hämostaseologie, Table of Contents

Hamostaseologie 2016; 36(02): 109-125
DOI: 10.5482/HAMO-15-04-0016

Übersichtsarbeit

Schattauer GmbH

Hämostaseologie in der Pädiatrie

Haemostatic disorders in children

Authors

Karin Kurnik

¹Abteilung Pädiatrische Hämostaseologie, Dr. von Haunersches Kinderspital, LMU München
Christoph Bidlingmaier

¹Abteilung Pädiatrische Hämostaseologie, Dr. von Haunersches Kinderspital, LMU München
Sebastian Hütker

¹Abteilung Pädiatrische Hämostaseologie, Dr. von Haunersches Kinderspital, LMU München
Martin Olivieri

¹Abteilung Pädiatrische Hämostaseologie, Dr. von Haunersches Kinderspital, LMU München

Abstract

Zusammenfassung

Im Kindesalter werden wie bei Erwachsenen hämorrhagische Diathesen und thrombotische Erkrankungen beobachtet. Die Ursachen sind angeboren oder erworben. Schwerere angeborene Störungen mit Blutungsfolgen manifestieren sich meist im Kleinkindalter, während angeborene thrombophile Störungen meist in Kombination mit zusätzlichen Risikofaktoren das Entstehen von Thrombosen mit Gipfeln im Neugeborenen- und Pubertäts- bzw. Adoleszentenalter begünstigen. Zur Beurteilung von Hämostaseparametern in Verbindung mit klinischem Befund ist die Kenntnis einiger kindlicher Besonderheiten, wie die Altersabhängigkeit der Gerinnungswerte, wichtig. Nur so können adäquate Therapieentscheidungen getroffen werden.

Summary

Haemorrhagic and thrombotic events occur in both children and adults. The underlying causes are congenital or acquired disorders. In contrast to haemorrhagic disorders, inherited thrombotic disorders nearly exclusively in association with additional external risk factors lead to thrombotic events predominantly during the newborn period and adolescence. It is necessary to be aware of age-specific properties of coagulation in order to correctly interpret clinical and laboratory findings and to provide optimal care for children with haemorrhagic and thrombotic complications.

Schlüsselwörter

Hämostasestörungen bei Kindern - Blutungsneigung bei Kindern - Thrombosen bei Kindern - Therapie

Keywords

Haemostatic disorders - haemorrhagic disorders in children - thrombotic disorders in children - therapy

Full Text

References

References
1 Abdallah C. Considerations in perioperative assessment of valproic acid coagulopathy. J Anaesthesiol Clin Pharmacol 2014; 30: 7-9.
2 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72: 1651-1657.
3 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70: 165-172.
4 Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften.. Prophylaxe der venösen Thromboembolie (VTE) – Kapitel Pädiatrie und Neonatologie. AWMF-Leitlinien-Register 2015 Nr. 003–001.
5 Attard C, Monagle P, Kubitza D, Ignjatovic V. The in vitro anticoagulant effect of rivaroxaban in children. Thromb Res 2012; 130: 804-807.
6 Attard C, van der Straaten T, Karlaftis V. et al. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Hae-most 2013; 11: 1850-1854.
7 Avila ML, Lee KJ, Bouskill V. et al. Acquired von Willebrand syndrome in paediatric patients with congenital heart disease: challenges in the diagnosis and management of this rare condition. Haemophilia 2015; 21: e89-e92.
8 AWMF.. Immunthrombozytopenie im Kindes- und Jugendalter AWMF-Leitlinien-Register. 2011 Nr. 086/001.
9 Bakchoul T, Bassler D, Heckmann M. et al. Management of infants born with severe neonatal alloimmune thrombocytopenia: the role of platelet transfusions and intravenous immunoglobulin. Transfusion 2014; 54: 640-645.
10 Bernard TJ, Rivkin MJ, Scholz K. et al. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial. Stroke 2014; 45: 2018-2023.
11 Bidlingmaier C, Eberl W, Knöfler R. et al. Haemostatic testing prior to elective surgery in children?. Not always! Hämostaseologie 2009; 29: 64-67.
12 Bidlingmaier C, Grote V, Budde U. et al. Prospective evaluation of a pediatric bleeding questionnaire and the ISTH bleeding assessment tool in children and parents in routine clinical practice. J Thromb Haemost 2012; 10: 1335-1341.
13 Bidlingmaier C, Kenet G, Kurnik K. et al. Safety and efficacy of low molecular weight heparins in children: a systematic review of the literature and meta-analysis of single-arm studies. Semin Thromb Hemost 2011; 37: 814-825.
14 Bidlingmaier C, Olivieri M, Kurnik K. Hautblutungen bei Kindern. Monatsschrift Kinderheilkunde 2012; 160: 538-544.
15 Bührer C, Genzel-Boroviczény O, Jochum F. et al. Vitamin-K-Prophylaxe bei Neugeborenen. Monatsschrift Kinderheilkunde 2013; 161: 351-353.
16 Bührer C, Genzel-Boroviczény O, Jochum F. et al. Vitamin-K-Prophylaxe bei Neugeborenen. Monatsschrift Kinderheilkunde 2014; 162: 62-63.
17 Castaman G, Goodeve A, Eikenboom J. et al. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica 2013; 98: 667-674.
18 Collins PW, Blanchette VS, Fischer K. et al. Breakthrough bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009; 7: 413-420.
19 Cooper N. A review of the management of childhood immune thrombocytopenia: how can we provide an evidence-based approach?. Br J Haematol 2014; 165: 756-767.
20 Deutsche Gesellschaft für Hals-Nasen-OhrenHeilkunde K-uH-C.. Leitlinie Adenoide Vegetation / Rachenmandelhyperplasie. AWMF-Leitlinien-Register 2011 Nr. 017/021.
21 Eberl W, Wendt I, Schroeder H-G. Präoperatives Screening auf Gerinnungsstörungen vor Adenotomie und Tonsillektomie. Klin Padiatr 2005; 217: 20-24.
22 Goldenberg NA, Branchford B, Wang M. et al. Percutaneous mechanical and pharmacomechanical thrombolysis for occlusive deep vein thrombosis of the proximal limb in adolescent subjects: findings from an institution-based prospective inception cohort study of pediatric venous thromboembolism. J Vasc Interv Radiol 2011; 22: 121-132.
23 Goldenberg NA, Donadini MP, Kahn SR. et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica 2010; 95: 1952-1959.
24 Gouw SC, van den Berg HM, Fischer K. et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study. Blood 2013; 121: 4046-4055.
25 Gouw SC, van den Berg HM, le Cessie S, van der Bom JG. Treatment characteristics and the risk of inhibitor development: a multicenter cohort study among previously untreated patients with severe hemophilia A. J Thromb Haemost 2007; 5: 1383-1390.
26 Hertfelder HJ. Thrombolytische Therapie im Kindesalter. In: Pötzsch B, Madlener K. (eds). Hämostaseologie. Berlin, Heidelberg: Springer; 2010: 689-694.
27 Higham JM, O’Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990; 97: 734-739.
28 Holzhauer S, Goldenberg NA, Junker R. et al. Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study. Blood 2012; 120: 1510-1515.
29 Iorio A, Marchesini E, Marcucci M. et al. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev. 2011 CD003429.
30 Jaeken J. Congenital disorders of glycosylation. Handb Clin Neurol 2013; 113: 1737-1743.
31 Kamphuis MM, Paridaans NP, Porcelijn L. et al. Incidence and consequences of neonatal alloimmune thrombocytopenia: a systematic review. Pediatrics 2014; 133: 715-721.
32 Kenet G, Kirkham F, Niederstadt T. et al. Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: a multicentre cohort study. Lancet Neurol 2007; 6: 595-603.
33 Kitchens CS. To bleed or not to bleed?. Is that the question for the PTT? J Thromb Haemost 2005; 3: 2607-2611.
34 Klostermeier UC, Limperger V, Kenet G. et al. Role of protein S deficiency in children with venous thromboembolism. An observational international cohort study. Thromb Haemost 2015; 113: 426-433.
35 Knöfler R, Eberl W, Schulze H. et al. Diagnosis of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.). Hämostaseologie 2014; 34: 201-212.
36 Kucine N, Chastain KM, Mahler MB, Bussel JB. Primary thrombocytosis in children. Haematologica 2014; 99: 620-628.
37 Kuhle S, Massicotte P, Dinyari M. et al. Dose-finding and pharmacokinetics of therapeutic doses of tinzaparin in pediatric patients with thromboembolic events. Thromb Haemost 2005; 94: 1164-1171.
38 Law C, Raffini L. A guide to the use of anticoagulant drugs in children. Paediatr Drugs 2015; 17: 105-114.
39 Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol 2009; 145: 24-33.
40 Limperger V, Franke A, Kenet G. et al. Clinical and laboratory characteristics of paediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency. An observational multicentre cohort study. Thromb Haemost 2014; 112: 478-485.
41 Limperger V, Klostermeier UC, Kenet G. et al. Clinical and laboratory characteristics of children with venous thromboembolism and protein C-deficiency: an observational Israeli-German cohort study. Br J Haematol 2014; 167: 385-393.
42 Lo GK, Juhl D, Warkentin TE. et al. Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 2006; 4: 759-765.
43 McCrindle BW, Li JS, Manlhiot C. et al. Challenges and priorities for research: a report from the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on thrombosis in pediatric cardiology and congenital heart disease. Circulation 2014; 130: 1192-1203.
44 Meissner MH, Gloviczki P, Comerota AJ. et al. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg 2012; 55: 1449-1462.
45 Middeldorp S. Is thrombophilia testing useful?. Hematology Am Soc Hematol Educ Program 2011; 2011: 150-155.
46 Minford A, Behnisch W, Brons P. et al. Subcutaneous protein C concentrate in the management of severe protein C deficiency--experience from 12 centres. Br J Haematol 2014; 164: 414-421.
47 Monagle P, Barnes C, Ignjatovic V. et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95: 362-372.
48 Monagle P, Chan AK, Goldenberg NA. et al. Anti-thrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9^thed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (Suppl. 02) e737S-e801S.
49 Morley SL. Management of acquired coagulopathy in acute paediatrics. Arch Dis Child Educ Pract Ed 2011; 96: 49-60.
50 Nowak-Göttl U, Bidlingmaier C, Krumpel A. et al. Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children. Br J Pharmacol 2008; 153: 1120-1127.
51 Nowak-Göttl U, Janssen V, Manner D, Kenet G. Venous thromboembolism in neonates and children--update 2013. Thromb Res 2013; 131 (Suppl. 01) S39-S41.
52 Nowak-Göttl U, Kurnik K, Manner D, Kenet G. Thrombophilia testing in neonates and infants with thrombosis. Semin Fetal Neonatal Med 2011; 16: 345-348.
53 Olivieri M, Bidlingmaier C, Schetzeck S. et al. Arterial thrombosis in homozygous antithrombin deficiency. Hämostaseologie 2012; 32 (Suppl. 01) S79-S82.
54 Olivieri M, Kurnik K, Bidlingmaier C. Coagulation testing in the evaluation of suspected child abuse. Hämostaseologie 2009; 29: 190-192.
55 Parker RI. Coagulopathies in the PICU: DIC and liver disease. Critical Care Clinics 2013; 29: 319-333.
56 Peyvandi F, Bidlingmaier C, Garagiola I. Management of pregnancy and delivery in women with inherited bleeding disorders. Semin Fetal Neonatal Med 2011; 16: 311-317.
57 Peyvandi F, Palla R, Menegatti M. et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost 2012; 10: 615-621.
58 Pfanner G, Koscielny J, Pernerstorfer T. et al. Pre-operative evaluation of the bleeding history. Recommendations of the working group on perioperative coagulation of the Austrian Society for Anaesthesia, Resuscitation and Intensive Care. Anaesthesist 2007; 56: 604-611.
59 Provan D, Stasi R, Newland AC. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115: 168-186.
60 Psaila B, Petrovic A, Page LK. eT AL. Intracranial hemorrhage (ICH) in children with immune thrombocytopenia (ITP): study of 40 cases. Blood 2009; 114: 4777-4783.
61 Revel-Vilk S, Ergaz Z. Diagnosis and management of central-line-associated thrombosis in newborns and infants. Semin Fetal Neonatal Med 2011; 16: 340-344.
62 Rivkin MJ, deVeber G, Ichord RN. et al. Thrombolysis in pediatric stroke study. Stroke 2015; 46: 880-885.
63 Rodeghiero F, Stasi R, Gernsheimer T. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113: 2386-2393.
64 Rott H, Kruempel A, Kappert G. et al. Contraception and thrombophilia. Hämostaseologie 2009; 29: 193-196.
65 Scott LM, Tong W, Levine RL. et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356: 459-468.
66 Strauß J, Becke K, Schmidt J. Gerinnungsstörungen: Auf die Anamnese kommt es an. Dtsch Arztebl 2006; 103: B1670.
67 Streif W, Knöfler R, Eberl W. et al. Therapy of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.). Hämostaseologie 2014; 34: 269-275.
68 Thom K, Male C, Mannhalter C. et al. No impact of endogenous prothrombotic conditions on the risk of central venous line-related thrombotic events in children: results of the KIDCAT study (KIDs with Catheter Associated Thrombosis). J Thromb Hae-most 2014; 12: 1610-1615.
69 Trame MN, Mitchell L, Krumpel A. et al. Population pharmacokinetics of enoxaparin in infants, children and adolescents during secondary thromboembolic prophylaxis: a cohort study. J Thromb Haemost 2010; 8: 1950-1958.
70 Veldman A, Fischer D, Wong FY. et al. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care 2010; 14: R156.
71 Watson HG, Greaves M. Can we predict bleeding?. Semin Thromb Hemost 2008; 34: 97-103.
72 Witmer C, Presley R, Kulkarni R. et al. Associations between intracranial haemorrhage and prescribed prophylaxis in a large cohort of haemophilia patients in the United States. Br J Haematol 2011; 152: 211-216.
73 Yee DL, O’Brien SH, Young G. Pharmacokinetics and pharmacodynamics of anticoagulants in paediatric patients. Clin Pharmacokinet 2013; 52: 967-980.
74 Young G. New anticoagulants in children: a review of recent studies and a look to the future. Thromb Res 2011; 127: 70-74.
75 Young G, Albisetti M, Bonduel M. et al. Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation 2008; 118: 1373-1382.
76 Young G, Boshkov LK, Sullivan JE. et al. Argatroban therapy in pediatric patients requiring nonheparin anticoagulation: an open-label, safety, efficacy, and pharmacokinetic study. Pediatr Blood Cancer 2011; 56: 1103-1109.
77 Zwiauer K. Vitamin-K-Prophylaxe bei Neugeborenen – Update 2013. Monatsschrift Kinderheilkunde 2014; 162: 64-67.