Download PDF
Semin Thromb Hemost 2003; 29(4): 405-414
DOI: 10.1055/s-2003-42590
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Arterial Ischemic Stroke in Neonates, Infants, and Children: An Overview of Underlying Conditions, Imaging Methods, and Treatment Modalities

Ulrike Nowak-Göttl1,2,3 , Gudrun Günther3 , Karin Kurnik4 , Ronald Sträter2 , Fenella Kirkham5
  • 1Professor, University of Münster Münster
  • 2Department of Paediatric Haematology/Oncology University of Münster Münster
  • 3Department of Paediatrics University Children's Hospital Magdeburg
  • 4Department of Paediatrics University Children's Hospital Munich, Germany
  • 5Neurosciences Unit, Institute of Child Health, University College, London and Southampton General Hospital NHS Trust, United Kingdom
Further Information

Publication History

Publication Date:
30 September 2003 (online)

    Permissions and Reprints

ABSTRACT

Conditions associated with arterial ischemic stroke (AIS) in children include congenital heart malformations, sickle cell disease, and meningitis, although around half of all cases are cryptogenic. Up to 80% of children with ischemic stroke have cerebrovascular disease, and case control studies demonstrate an association of arterial ischemic stroke in children with hereditary prothrombotic risk factors and infections such as VARICELLA. Conventional risk factors, such as hypertension and dyslipidemia, may also play a role and most children have several potential triggers rather than a single cause. Treatment recommendations are based on small case series or have been adapted from adult stroke studies; there are no evidence-based data on efficacy in children. Low-dose aspirin appears to be relatively safe. Anticoagulation with heparins, for example, low-molecular-weight heparin or warfarin, may be indicated in children with cardioembolic stroke, arterial dissection, or persistent hypercoagulable states, and blood transfusion has a role in patients with sickle cell disease. Tissue plasminogen activator has been used in a few patients within 3 hours of the onset of symptoms. At present, the benefit of treatment has to be weighed against the risk for each patient, but randomized controlled trials for primary prevention, acute treatment, and secondary prevention of pediatric ischemic stroke are urgently needed.

KEYWORDS

Arterial ischemic stroke - children - etiology - magnetic resonance - prothrombotic risk factors - therapy

REFERENCES

  • 1 Williams A N. Childhood stroke-beyond re-inventing the wheel.  Eur J Paediatr Neurol . 2000;  4 103-107
    CrossrefPubMedSearch in Google Scholar
  • 2 Schoenberg B, Mellinger J, Schoenberg D. Cerebrovascular disease in infants and children: a study of incidence, clinical features, and survival.  Neurology . 1978;  28 763-768
    PubMedSearch in Google Scholar
  • 3 Earley C J, Kittner S J, Feeser B R. et al . Stroke in children and sickle-cell disease.  Neurology . 1998;  51 169-176
    CrossrefPubMedSearch in Google Scholar
  • 4 Giroud M, Lemesle M, Gouyon J B, Nivelon J L, Milan C, Dumas R. Cerebrovascular disease in children under 16 years of age in the city of Dijon, France: a study of incidence and clinical features from 1985 to 1993.  J Clin Epidemiol . 1995;  48 1343-1348
    CrossrefPubMedSearch in Google Scholar
  • 5 Nicolaides P, Appelton R E. Stroke in children.  Dev Med Child Neurol . 1996;  38 172-180
    PubMedSearch in Google Scholar
  • 6 Roach E S. Etiology of stroke in children.  Semin Pediatr Neurol . 2000;  7 244-260
    PubMedSearch in Google Scholar
  • 7 deVeber G, Roach E S, Riela A R, Wiznitzer M. Stroke in children: recognition, treatment, and future directions.  Semin Pediatr Neurol . 2000;  7 309-317
    PubMedSearch in Google Scholar
  • 8 Abram H S, Knepper L E, Warty V S, Painter M J. Natural history, prognosis, and lipid abnormalities of idiopathic ischemic childhood stroke.  J Child Neurol . 1996;  11 2762-2782
    PubMedSearch in Google Scholar
  • 9 Lynch J K, Hirtz D G, deVeber G, Nelson K B. Report on the National Institute of Neurological Disorders and Stroke Workshop on Perinatal and Childhood Stroke.  Pediatrics . 2002;  109 116-123
    CrossrefPubMedSearch in Google Scholar
  • 10 Kirkham F J. Stroke in childhood.  Arch Dis Child . 1999;  81 85-89
    CrossrefPubMedSearch in Google Scholar
  • 11 Kirkham F J, Prengler M, Hewes K M, Ganesan V. Risk factors for arterial ischemic stroke in children.  J Child Neurol . 2000;  15 299-307
    PubMedSearch in Google Scholar
  • 12 Prengler M, Pavlakis S G, Prohovnik I, Adams R J. Sickle cell disease: the neurological complications.  Ann Neurol . 2002;  51 543-552
    CrossrefPubMedSearch in Google Scholar
  • 13 Sebire G, Meyer L, Chabrier S. Varicella as a risk factor for cerebral infarction in childhood: a case-control study.  Ann Neurol . 1999;  45 679-680
    CrossrefPubMedSearch in Google Scholar
  • 14 Roach E S, deVeber G, Kirkham F. Knowledge of consensus: understanding stroke in children.  J Child Neurol . 2000;  15 277-278
    PubMedSearch in Google Scholar
  • 15 Williams L S, Garg B P, Cohen M, Fleck J D, Biller J. Subtypes of ischaemic stroke in children and young adults.  Neurology . 1997;  49 1541-1545
    PubMedSearch in Google Scholar
  • 16 Fullerton H J, Johnston S C, Smith W S. Arterial dissection and stroke in children.  Neurology . 2001;  57 1155-1160
    CrossrefPubMedSearch in Google Scholar
  • 17 Shields W D, Ziter F A, Oeborn A G, Allen J. Fibromuscular dysplasia as a cause of stroke in infancy and childhood.  Pediatrics . 1977;  59 899-901
    PubMedSearch in Google Scholar
  • 18 Chabrier S, Rodesch G, Lasjaunias P. et al . Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke.  J Child Neurol . 1998;  13 27-32
    PubMedSearch in Google Scholar
  • 19 Ganesan V, Savvy L, Chong W K, Kirkham F J. Conventional cerebral angiography in the investigation of children with ischaemic stroke.  Pediatr Neurol . 1999;  20 38-42
    CrossrefPubMedSearch in Google Scholar
  • 20 Ganesan V, Prengler M, McShane M A, Wade A M, Kirkham F J. Investigation of risk factors in children with arterial ischemic stroke.  Ann Neurol . 2003;  53 167-173
    CrossrefPubMedSearch in Google Scholar
  • 21 Shirane R, Sato S, Yoshimoto T. Angiographic findings of ischaemic stroke in children.  Childs Nerv Syst . 1992;  8 432-436
    CrossrefPubMedSearch in Google Scholar
  • 22 Velkey I, Lombay B, Panczel G. Obstruction of the cerebral arteries in childhood stroke.  Pediatr Radiol . 1992;  22 386-387
    PubMedSearch in Google Scholar
  • 23 Kirkham F J, Prengler M. Genetics of paediatric stroke (in press). In: Markus HGenetics of Stroke. Oxford, England: Oxford University Press 2002
    Search in Google Scholar
  • 24 Akar N, Akar E, Özel D, Deda G, Sipahi T. Common mutations at the homocysteine metabolism pathway and pediatric stroke.  Thromb Res . 2001;  102 115-120
    CrossrefPubMedSearch in Google Scholar
  • 25 Becker S, Heller C, Gropp F, Scharrer I, Kreuz W. Thrombophilic disorders in children with cerebral infarction.  Lancet . 1998;  352 1756-1758
    PubMedSearch in Google Scholar
  • 26 Bonduel M, Sciuccati G, Hepner M, Tores A F, Pieroni G, Frontroth J. Prethrombotic disorder in children with arterial ischemic stroke and sinovenous thrombosis.  Arch Neurol . 1999;  56 967-971
    CrossrefPubMedSearch in Google Scholar
  • 27 Bonduel M, Hepner M, Sciuccati G, Torres A F, Tenembaum S. Prothrombotic disorders in children with moyamoya syndrome.  Stroke . 2001;  32 1786-1792
    PubMedSearch in Google Scholar
  • 28 Cardo E, Monros E, Colome C. et al . Children with stroke: polymorphism of the MTHFR gene, mild hyperhomocysteinemia, and vitamin status.  J Child Neurol . 2000;  15 295-298
    PubMedSearch in Google Scholar
  • 29 Debus O, Koch H G, Kurlemann G. et al . Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly.  Arch Dis Child Fetal Neonatal Ed . 1998;  78 F121-F124
    PubMedSearch in Google Scholar
  • 30 Devilat M, Toso M, Morales M. Childhood stroke associated with protein C or S deficiency and primary antiphospholipid syndrome.  Pediatr Neurol . 1993;  9 67-70
    CrossrefPubMedSearch in Google Scholar
  • 31 Ganesan V, Kelsey H, Cookson J, Osborn A, Kirkham F J. Activated protein C resistance in childhood stroke.  Lancet . 1996;  347 260
    PubMedSearch in Google Scholar
  • 32 Ganesan V, McShane M A, Liesner R, Cookson J, Hann I, Kirkham F J. Inherited prothrombotic states and ischaemic stroke in childhood.  J Neurol Neurosurg Psychiatry . 1998;  65 508-511
    PubMedSearch in Google Scholar
  • 33 Kenet G, Sadetzki S, Murad H. et al . Factor V Leiden and antiphospholipid antibodies are significant risk factors for ischaemic stroke in children.  Stroke . 2000;  31 1283-1288
    CrossrefPubMedSearch in Google Scholar
  • 34 Günther G, Junker R, Sträter R. et al . Symptomatic ischaemic stroke in full-term neonates: role of acquired and genetic prothrombotic risk factors.  Stroke . 2000;  31 2437-2441
    PubMedSearch in Google Scholar
  • 35 Heller C, Becker S, Scharrer I, Kreuz W. Prothrombotic risk factors in childhood stroke and venous thrombosis.  Eur J Pediatr . 1999;  158(Suppl) S117-S121
    PubMedSearch in Google Scholar
  • 36 Lanthier S, Carmant L, David M, Larbrisseau A, deVeber G. Stroke in children. The coexistence of multiple risk factors predicts poor outcome.  Neurology . 2000;  54 371-378
    CrossrefPubMedSearch in Google Scholar
  • 37 Manco-Johnson M J, Nuss R, Key N. et al . Lupus anticoagulant and protein S deficiency in children with postvaricella purpura fulminans or thrombosis.  J Pediatr . 1996;  128 319-323
    CrossrefPubMedSearch in Google Scholar
  • 38 McColl M D, Chalmers E A, Thomas A. et al . Factor V Leiden, prothrombin 20210GA and the MTHFR C677T mutations in childhood stroke.  Thromb Haemost . 1999;  81 690-694
    PubMedSearch in Google Scholar
  • 39 Zenz W, Bodo Z, Plotho J. et al . Factor V Leiden and prothrombin gene G20210A variant in children with stroke.  Thromb Haemost . 1998;  80 763-766
    PubMedSearch in Google Scholar
  • 40 Miller V. Neonatal cerebral infarction.  Semin Pediatr Neurol . 2000;  7 278-288
    CrossrefPubMedSearch in Google Scholar
  • 41 Nguyen P, Reynaud J, Pouzol P, Munzer M, Richard O, Francois P. Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children.  Eur J Pediatr . 1994;  153 646-649
    CrossrefPubMedSearch in Google Scholar
  • 42 Nowak-Göttl U, Sträter R, Heinecke A. et al . Lipoprotein(a) and genetic polymorphisms of clotting factor V, prothrombin and methylenetetrahydrofolate reductase are risk factors of ischaemic stroke in childhood.  Blood . 1999;  94 3678-3682
    CrossrefPubMedSearch in Google Scholar
  • 43 Prengler M, Sturt N, Krywawych S, Surtees R, Liesner R, Kirkham F. Homozygous thermolabile variant of the methylenetetrahydrofolate reductase gene: a potential risk factor for hyperhomocysteinaemia, CVD, and stroke in childhood.  Dev Med Child Neurol . 2001;  43 220-225
    CrossrefPubMedSearch in Google Scholar
  • 44 Dusser A, Goutieres F, Aicardi J. Ischemic strokes in children.  J Child Neurol . 1986;  1 131-136
    PubMedSearch in Google Scholar
  • 45 Lanska M J, Lanska D J, Horwitz S J, Aram D M. Presentation, clinical course, and outcome of childhood stroke.  Pediatr Neurol . 1991;  7 3337-3341
    PubMedSearch in Google Scholar
  • 46 Delsing B JP, Catsman-Berrevoets C E, Appel I M. Early prognostic indicators of outcome in ischaemic childhood stroke.  Pediatric Neurol . 2001;  24 283-289
    PubMedSearch in Google Scholar
  • 47 Ganesan V, Hogan A, Jones A, Shack N, Kirkham F J. Parent-reported outcome in ischaemic stroke.  Dev Med Child Neurol . 2000;  42 455-461
    CrossrefPubMedSearch in Google Scholar
  • 48 Kieslich M, Fiedler A, Heller C, Kreuz W, Jacobi G. Minor head injury as cause and co-factor in the aetiology of stroke in childhood. A report of eight cases.  J Neurol Neurosurg Psychiatry . 2002;  73 13-16
    CrossrefPubMedSearch in Google Scholar
  • 49 Shaffer L, Rich P M, Pohl K R, Ganesan V. Can mild head injury cause ischaemic stroke?.  Arch Dis Child . 2003;  88 267-269
    CrossrefPubMedSearch in Google Scholar
  • 50 Hoggard N, Wilkinson I D, Griffiths P D. The imaging of ischaemic stroke.  Clin Radiol . 2001;  56 171-183
    CrossrefPubMedSearch in Google Scholar
  • 51 Ganesan V, Kirkham F J. Recurrence after ischaemic stroke in childhood.  Dev Med Child Neurol . 1998;  40(Suppl 79) 7
    PubMedSearch in Google Scholar
  • 52 Husson B, Rodesch G, Lasjaunias P, Tardieu M, Sebire G. Magnetic resonance angiography in childhood arterial brain infarcts: a comparative study with contrast angiography.  Stroke . 2002;  33 1280-1285
    CrossrefPubMedSearch in Google Scholar
  • 53 Askalan R, Laughlin S, Mayank S. et al . Chickenpox and stroke in childhood. A study of frequency and causation.  Stroke . 2001;  32 1257-1262
    CrossrefPubMedSearch in Google Scholar
  • 54 Bydder G M, Rutherford M A. Diffusion-weighted imaging of the brain in neonates and infants.  Magn Reson Imaging Clin N Am . 2001;  9 83-98
    PubMedSearch in Google Scholar
  • 55 Kirkham F J, Hewes D KM, Prengler M, Wade A, Lane R, Evans J PM. Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease.  Lancet . 2001;  357 1656-1659
    CrossrefPubMedSearch in Google Scholar
  • 56 Hargrave D R, Wade A, Evans J P, Hewes D K, Kirkham F J. Nocturnal oxygen saturation and painful sickle cell crises in children.  Blood . 2003;  101 846-848
    CrossrefPubMedSearch in Google Scholar
  • 57 Van Beynum M I, Smeitink J A, den Heijer M, te Poele Pothoff T M, Blom H J. Hyperhomocysteinemia: a risk for ischemic stroke in children.  Circulation . 1999;  99 2070-2072
    PubMedSearch in Google Scholar
  • 58 Sträter R, Becker S, von Eckardstein A. et al . Prospective evaluation of risk factors for recurrent stroke during childhood-results of a 5-year-follow-up.  Lancet . 2002;  360 1540-1545
    CrossrefPubMedSearch in Google Scholar
  • 59 deVeber G, Monagle P, Chan A. et al . Prothrombotic disorders in infants and children with cerebral thromboembolism.  Arch Neurol . 1998;  55 1539-1543
    CrossrefPubMedSearch in Google Scholar
  • 60 Lanthier S, Lindsay S, Mitchell L. et al . Anticardiolipin antibodies are associated with cardioembolic stroke but does not predict recurrent cerebral ischemia in children.  Neurology . 2001;  56(Suppl 3) A11
    PubMedSearch in Google Scholar
  • 61 Chabrier S, Husson B, Lasjaunias P, Landrieu P, Tardieu M. Stroke in childhood: outcome and recurrence risk by mechanism in 59 patients.  J Child Neurol . 2000;  15 290-294
    CrossrefPubMedSearch in Google Scholar
  • 62 Sreenan C, Bhargava R, Robertson C MT. Cerebral infarction in the term newborn: clinical presentation and long-term outcome.  J Pediatr . 2000;  137 351-355
    CrossrefPubMedSearch in Google Scholar
  • 63 Ganesan V, Chong W K, Cox T C, Chawda S J, Prengler M, Kirkham F J. Posterior circulation stroke in childhood: risk factors and recurrence.  Neurology . 2002;  26(59) 1552-1556
    PubMedSearch in Google Scholar
  • 64 Gordon A L, Ganesan V, Towell A, Kirkham F J. Functional outcome following stroke in children.  J Child Neurol . 2002;  17 429-434
    CrossrefPubMedSearch in Google Scholar
  • 65 Mancini J, Girard N, Chabrol B. et al . Ischemic cerebrovascular disease in children: retrospective study of 35 patients.  J Child Neurol . 1997;  12 193-199
    PubMedSearch in Google Scholar
  • 66 Adams R J. Lessons from the stroke prevention trial in sickle cell anemia (STOP) study.  J Child Neurol . 2000;  15 344-349
    PubMedSearch in Google Scholar
  • 67 Russel M O, Goldberg H I, Hodson A. et al . Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease.  Blood . 1984;  63 162-169
    PubMedSearch in Google Scholar
  • 68 Ware R E, Zimmerman S A, Schultz W H. Hydroxyurea as an alternative to blood transfusions for the prevention of recurrent stroke in children with sickle cell disease.  Blood . 1999;  94 3022-3026
    PubMedSearch in Google Scholar
  • 69 Manceau E, Giroud M, Dumas R. Moyamoya disease in children. A review of the clinical and radiological features and current treatment.  Childs Nerv Syst . 1997;  13 595-600
    CrossrefPubMedSearch in Google Scholar
  • 70 Albers G W, Easton J D, Sacco R L, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke.  Chest . 1998;  114 S683-S698
    PubMedSearch in Google Scholar
  • 71 Catto A, Zarter A, Irland H. et al . Factor V Leiden gene mutation and thrombin generation in relation to the development of acute stroke.  Arterioscler Thromb Vasc Biol . 1995;  15 783-785
    PubMedSearch in Google Scholar
  • 72 Press R D, Liu X Y, Beamer N, Coull M. Ischemic stroke in the elderly.  Stroke . 1996;  27 44-48
    PubMedSearch in Google Scholar
  • 73 Martinelli I, Franchi F, Akwan S, Bettini P, Merati G, Mannucci P M. The transition G to A at position 20210 in the 3'-untranslated region of the prothrombin gene is not associated with cerebral ischemia.  Blood . 1997;  90 3806
    PubMedSearch in Google Scholar
  • 74 Longstreth W T, Rosendaal F R, Siscovick D S. et al . Risk of stroke in young women and two prothrombotic mutations: factor V Leiden and prothrombin gene variant (G20210A).  Stroke . 1998;  29 577-580
    PubMedSearch in Google Scholar
  • 75 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke.  N Engl J Med . 1995;  333 1581-1587
    CrossrefPubMedSearch in Google Scholar
  • 76 Kaste M, Thomassen L, Grond M. et al . Thrombolysis for acute ischaemic stroke. A consensus statement of the 3rd Karolinska Stroke Update, October 30-31, 2000.  Stroke . 2001;  32 2717-2718
    PubMedSearch in Google Scholar
  • 77 Wardlaw J M, Warlow C P, Counsell C. Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke.  Lancet . 1997;  350 607-614
    CrossrefPubMedSearch in Google Scholar
  • 78 Kitzmüller E, Gruber A, Marx M. Supraselective intra-arterial thrombolysis for acute cardioembolic stroke in a child with idiopathic dilated cardiomyopathy.  Intervent Radiol . 1999;  5 187-194
    PubMedSearch in Google Scholar
  • 79 Gruber A, Nasel C, Lang W, Kitzmüller E, Bavinzki G, Czech T. Intra-arterial thrombolysis for the treatment of perioperative childhood cardioembolic stroke.  Neurology . 2000;  54 1684-1686
    CrossrefPubMedSearch in Google Scholar
  • 80 Thirumalai S S, Shubin R A. Successful treatment for stroke in a child using recombinant tissue plasminogen activator.  J Child Neurol . 2000;  15 558
    CrossrefPubMedSearch in Google Scholar
  • 81 Noser A, Felberg R A, Alexandrov A V. Thrombolytic therapy in an adolescent ischaemic stroke.  J Child Neurol . 2001;  16 286-288
    PubMedSearch in Google Scholar
  • 82 The International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke.  Lancet . 1997;  349 1569-1581
    CrossrefPubMedSearch in Google Scholar
  • 83 CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke.  Lancet . 1997;  349 1641-1649
    CrossrefPubMedSearch in Google Scholar
  • 84 Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  Br Med J . 2002;  324 71-84
    PubMedSearch in Google Scholar
  • 85 Hankey G J, Sudlow C LM, Dunbabin D W. Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease?.  <~>A systemic review of the evidence from randomized trials. Stroke . 2000;  31 1779-1784
    PubMedSearch in Google Scholar
  • 86 Diener H C, Cunha L, Forbes C. et al . European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.  J Neurol Sci . 1996;  143 1-13
    CrossrefPubMedSearch in Google Scholar
  • 87 Wallace R C, Furlan A J, Molterno D J. et al . Basilar artery rethrombosis: successful treatment with platelet glycoprotein IIb/IIIa receptor inhibitor.  Am J Neuroradiol . 1997;  18 1257-1260
    PubMedSearch in Google Scholar
  • 88 Hathaway W E. Use of antiplatelet agents in pediatric hypercoagulable states.  Am J Dis Child . 1984;  138 301-304
    PubMedSearch in Google Scholar
  • 89 Sträter R, Kurnik K, Heller C, Schobess R, Luigs P, Nowak-Göttl U. Aspirin versus low-dose low-molecular-weight heparin: antithrombotic therapy in pediatric stroke patients. A prospective follow-up study.  Stroke . 2001;  32 2554-2558
    CrossrefPubMedSearch in Google Scholar
  • 90 LeBlanc J, Sett S, Vince D. Antiplatelet therapy in children with left-sided mechanical prostheses.  Eur J Cardiothorac Surg . 1993;  7 211-215
    CrossrefPubMedSearch in Google Scholar
  • 91 Carcao M D, Blanchette V S, Dean J A. et al . The platelet function analyser (PFA-100): a novel in-vitro system for evaluation of primary haemostasis in children.  Br J Haematol . 1998;  101 70-73
    CrossrefPubMedSearch in Google Scholar
  • 92 Israels S, Cheang T, McMillan-Ward E M, Cheang M. Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer.  J Pediatr . 2001;  138 116-119
    CrossrefPubMedSearch in Google Scholar
  • 93 Sandercock P AG, van den Belt G M A, Lindley R I, Slattery J. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.  J Neurol Neurosurg Psychiatry . 1993;  56 17-25
    PubMedSearch in Google Scholar
  • 94 Andrew M, Marzinotto V, Blanchette V. et al . Heparin therapy in pediatric patients: a prospective cohort study.  Pediatr Res . 1994;  35 78-83
    CrossrefPubMedSearch in Google Scholar
  • 95 Schmugge M, Risch L, Huber A R, Benn A, Fischer J E. Heparin-induced thrombocytopenia-associated thrombosis in pediatric intensive care patients.  Pediatrics . 2002;  109 U69-U72
    CrossrefPubMedSearch in Google Scholar
  • 96 Zöhrer B, Zenz W, Rettenbacher A. et al . Danaparoid sodium (Orgaran;rM) in four children with heparin-induced thrombocytopenia type II.  Acta Paediatr . 2001;  90 765-771
    PubMedSearch in Google Scholar
  • 97 Hirsh J, Levine M. Low-molecular-weight heparin.  Blood . 1992;  79 1-17
    PubMedSearch in Google Scholar
  • 98 Kay R, Wong K S, Yu Y L. et al . Low-molecular-weight heparin for the treatment of acute ischaemic stroke.  N Engl J Med . 1995;  333 1588-1593
    CrossrefPubMedSearch in Google Scholar
  • 99 Samama M M, Desnoyers P C, Conard J, Busser M G. Acute ischaemic stroke and heparin treatments.  Thromb Haemost . 1997;  78 173-179
    PubMedSearch in Google Scholar
  • 100 Kalafut M A, Gandhi R, Kidwell C S, Saver J L. Safety and cost of low-molecular-weight heparin as bridging anticoagulant therapy in subacute cerebral ischaemia.  Stroke . 2000;  31 2563-2568
    PubMedSearch in Google Scholar
  • 101 Bath P MW, Iddenden R, Bath F J. Low-molecular-weight heparins and heparinoids in acute ischaemic stroke-a meta-analysis of randomized controlled trials.  Stroke . 2000;  31 1770-1778
    CrossrefPubMedSearch in Google Scholar
  • 102 Dix D, Andrew M, Marzinotto V. et al . The use of low-molecular-weight heparin in pediatric patients: a prospective cohort study.  J Pediatr . 2000;  136 439-445
    CrossrefPubMedSearch in Google Scholar
  • 103 Mary V, Wahl F, Uzan A, Stutzmann J M. Enoxaparin in experimental stroke. Neuroprotection and therapeutic window of opportunity.  Stroke . 2001;  32 993-999
    PubMedSearch in Google Scholar
  • 104 Massicotte P, Adams M, Marzinotto V. et al . Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.  J Pediatr . 1996;  128 313-318
    CrossrefPubMedSearch in Google Scholar
  • 105 Hofmann S, Knoefler R, Lorenz N. et al . Clinical experience with low-molecular-weight heparins in pediatric patients.  Thromb Res . 2001;  103 345-353
    CrossrefPubMedSearch in Google Scholar
  • 106 Mohr J P, Thompson J LP, Lazar R M. et al . A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.  N Engl J Med . 2001;  345 1444-1451
    CrossrefPubMedSearch in Google Scholar
  • 107 Andrew M, Marzinotto V, Brooker L. et al . Oral anticoagulant therapy in pediatric patients. A prospective study.  Thromb Haemost . 1994;  71 265-269
    PubMedSearch in Google Scholar
  • 108 Streif W, Andrew M, Marzinotto V. et al . Analysis of warfarin therapy in pediatric patients: a prospective cohort study of 319 patients.  Blood . 1999;  94 3007-3014
    PubMedSearch in Google Scholar
  • 109 Massicotte P, Marzinotto V, Vegh P, Adams M, Andrew M. Home monitoring of warfarin therapy in children with a whole blood prothrombin time monitor.  J Pediatr . 1995;  127 389-394
    PubMedSearch in Google Scholar