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Semin Thromb Hemost 2003; 29(4): 415-424
DOI: 10.1055/s-2003-42591
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Contribution of Prothrombotic Disorders to Peri- and Neonatal Ischemic Stroke

Meredith R. Golomb
  • Assistant Professor Division of Pediatric Neurology Department of Neurology Riley Hospital for Children Indiana University School of Medicine Indianapolis, Indiana
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Publication History

Publication Date:
30 September 2003 (online)

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ABSTRACT

Prothrombotic disorders are believed to be important contributors to the etiology of peri- and neonatal arterial ischemic stroke and sinovenous thrombosis, which may lead to life-long disability. This article reviews hematological issues unique to the perinatal period, including: the significance of the placenta as the interface between maternal and fetal circulations; normal changes in the coagulation system of mothers during and just after gestation; and the significance of prothrombotic disorders in the mother and/or fetus. Other possible maternal and neonatal contributors to peri- and neonatal stroke are discussed, including: infection, pre-eclampsia, diabetes, and drug use in the mother; and infection, dehydration, complex congenital heart disease, extracorporeal membrane oxygenation, and catheter placement in the neonate. Possible approaches to preventing and treating perinatal and neonatal stroke are presented.

KEYWORDS

Arterial ischemic stroke - sinovenous thrombosis - cerebrovascular accident - neonatal stroke - perinatal stroke - pregnancy - puerperium - placenta - prothrombotic disorder - coagulation

REFERENCES

  • 1 Humphreys P, Whiting S, Pham B. Hemiparetic cerebral palsy: clinical pattern and imaging in prediction of outcome.  Can J Neurol Sci . 2000;  27 210-219
    PubMedSearch in Google Scholar
  • 2 Uvebrant P. Hemiplegic cerebral palsy. Aetiology and outcome. Acta Paediatr Suppl 1988 345: 1-100
    Search in Google Scholar
  • 2a Friel J P. Dorland's Illustrated Medical Dictionary; 26th ed. Philadelphia: WB Saunders 1981
    Search in Google Scholar
  • 3 Schoenberg B S, Mellinger J F, Schoenberg D G. Cerebrovascular disease in infants and children: a study of incidence, clinical features, and survival.  Neurology . 1978;  28 763-768
    PubMedSearch in Google Scholar
  • 4 Broderick J, Talbot G T, Prenger E, Leach A, Brott T. Stroke in children within a major metropolitan area: the surprising importance of intracerebral hemorrhage.  J Child Neurol . 1993;  8 250-255
    CrossrefPubMedSearch in Google Scholar
  • 5 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
  • 6 deVeber G. Stroke and the child's brain: an overview of epidemiology, syndromes and risk factors.  Curr Opin Neurol . 2002;  15 133-138
    CrossrefPubMedSearch in Google Scholar
  • 7 Gunther G, Junker R, Strater R. et al . Symptomatic ischemic stroke in full-term neonates: role of acquired and genetic prothrombotic risk factors [erratum appears in Stroke 2001;32:279].  Stroke . 2000;  31 2437-4241
    PubMedSearch in Google Scholar
  • 8 deVeber G, Group CPISS. Canadian Paediatric Ischemic Stroke Registry: analysis of children with arterial ischemic stroke [abstract].  Ann Neurol . 2000;  48 526
    PubMedSearch in Google Scholar
  • 9 Monagle P, deVeber G, Chan K C, Andrew M. Thromboembolic disease and antithrombotic therapy in newborns. Blood; 43rd annual meeting of the American Society of Hematology (syllabus), December 7-11, 2001, Orlando, Florida
  • 10 Estan J, Hope P. Unilateral neonatal infarction in full term neonates.  Arch Dis Child . 1997;  76 F88-93
    PubMedSearch in Google Scholar
  • 11 Lynch J, Nelson K B. Neonatal stroke in the United States: results of the national hospital discharge survey, 1980-1998 (Abst).  Neurology . 2001;  56 A10
    PubMedSearch in Google Scholar
  • 12 Golomb M, MacGregor D, Domi T. et al . Presumed pre- and perinatal stroke: risk factors and outcomes.  Ann Neurol . 2001;  50 163-168
    CrossrefPubMedSearch in Google Scholar
  • 13 deVeber G, Andrew M, Group CPSS. The epidemiology and outcome of sinovenous thrombosis in pediatric patients.  N Engl J Med . 2001;  345 417-423
    CrossrefPubMedSearch in Google Scholar
  • 14 Sadler T. Langman's Medical Embryology.  Baltimore, MD: Williams & Wilkins 1990: 411
    Search in Google Scholar
  • 15 Andrew M, Monagle P, Brooker L. Thromboembolic Complications during Infancy and Childhood. Hamilton, Ontario: BC Decker 2000
    Search in Google Scholar
  • 16 Redline R W, Wilson-Costello D, Borawski E, Fanaroff A A, Hack M. Placental lesions associated with neurologic impairment and cerebral palsy in very-low-birth-weight infants.  Arch Pathol Lab Med . 1998;  122 1091-1098
    PubMedSearch in Google Scholar
  • 17 Burke C J, Tannenberg A E. Prenatal brain damage and placental infarction-an autopsy study.  Dev Med Child Neurol . 1995;  37 555-562
    PubMedSearch in Google Scholar
  • 18 Kraus F T, Acheen V I. Fetal thrombotic vasculopathy in the placenta: cerebral thrombi and infarcts, coagulopathies, and cerebral palsy.  Hum Pathol . 1999;  30 759-769
    CrossrefPubMedSearch in Google Scholar
  • 19 Amato M, Huppi P, Herschkowitz N, Huber P. Prenatal stroke suggested by intrauterine ultrasound and confirmed by magnetic resonance imaging.  Neuropediatrics . 1991;  22 100-102
    PubMedSearch in Google Scholar
  • 20 Adams-Chapman I, Vaucher Y E, Bejar R F, Benirschke K, Baergen R N, Moore T R. Maternal floor infarction of the placenta: association with central nervous system injury and adverse neurodevelopmental outcome.  J Perinatol . 2002;  22 236-241
    CrossrefPubMedSearch in Google Scholar
  • 21 Viscardi R M, Sun C C. Placental lesion multiplicity: risk factor for IUGR and neonatal cranial ultrasound abnormalities.  Early Hum Dev . 2001;  62 1-10
    CrossrefPubMedSearch in Google Scholar
  • 22 Grafe M R. The correlation of prenatal brain damage with placental pathology.  J Neuropathol Exp Neurol . 1994;  53 407-415
    CrossrefPubMedSearch in Google Scholar
  • 23 Clark P, Greer I A, Walker I D. Interaction of the protein C/protein S anticoagulant system, the endothelium and pregnancy.  Blood Rev . 1999;  13 127-146
    CrossrefPubMedSearch in Google Scholar
  • 24 Aune B, Gjesdal K, Oian P. Late onset postpartum thrombocytosis in pre-eclampsia.  Acta Obstet Gynecol Scand . 1999;  78 866-870
    CrossrefPubMedSearch in Google Scholar
  • 25 Atalla R K, Thompson J R, Oppenheimer C A, Bell S C, Taylor D J. Reactive thrombocytosis after caesarean section and vaginal delivery: implications for maternal thromboembolism and its prevention.  Br J Obstet Gynaecol . 2000;  107 411-414
    PubMedSearch in Google Scholar
  • 26 Kittner S J, Stern B J, Feeser B R. et al . Pregnancy and the risk of stroke.  N Engl J Med . 1996;  335 768-774
    CrossrefPubMedSearch in Google Scholar
  • 27 Jaigobin C, Silver F L. Stroke and pregnancy.  Stroke . 2000;  31 2948-2951
    CrossrefPubMedSearch in Google Scholar
  • 28 Skidmore F M, Williams L S, Fradkin K D, Alonso R J, Biller J. Presentation, etiology, and outcome of stroke in pregnancy and puerperium.  J Stroke Cerebrovasc Dis . 2001;  10 1-10
    PubMedSearch in Google Scholar
  • 29 Lanska D J, Kryscio R J. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis.  Stroke . 2000;  31 1274-1282
    CrossrefPubMedSearch in Google Scholar
  • 30 Sharshar T, Lamy C, Mas J L. Incidence and causes of strokes associated with pregnancy and puerperium. A study in public hospitals of Ile de France. Stroke in Pregnancy Study Group.  Stroke . 1995;  26 930-936
    CrossrefPubMedSearch in Google Scholar
  • 31 Hallak M, Senderowicz J, Cassel A. et al . Activated protein C resistance (factor V Leiden) associated with thrombosis in pregnancy.  Am J Obstet Gynecol . 1997;  176 889-893
    PubMedSearch in Google Scholar
  • 32 Tollin S R, Seely E W. Case report: postpartum hypopituitarism in a patient with sickle cell trait.  Am J Med Sci . 1994;  308 35-37
    PubMedSearch in Google Scholar
  • 33 van Pampus G M, Dekker G A, Wolf H. et al . High prevalence of hemostatic abnormalities in women with a history of severe pre-eclampsia.  Am J Obstet Gynecol . 1999;  180 1146-1150
    CrossrefPubMedSearch in Google Scholar
  • 34 van Pampus G M, van den Ende A, Wolf H. Elevated levels of lipoprotein(a) in women with pre-eclampsia.  Am J Obstet Gynecol . 1998;  179 1103-1104
    PubMedSearch in Google Scholar
  • 35 Dzialo A F, Black-Schaffer R M. Cerebral venous thrombosis in young adults: 2 Case reports.  Arch Phys Med Rehabil . 2001;  82 683-688
    CrossrefPubMedSearch in Google Scholar
  • 36 Gokcil Z, Odabasi Z, Vural O, Yardim M. Cerebral venous thrombosis in pregnancy: the role of protein S deficiency.  Acta Neurol Belg . 1998;  98 36-38
    PubMedSearch in Google Scholar
  • 37 Ozsener S, Terek M C, Saydam G, Celebisoy N, Oztekin K, Ozkinay E. Intracranial venous thrombosis associated with severe antithrombin-III deficiency in pregnancy.  J Obstet Gynaecol Res . 2001;  27 81-84
    PubMedSearch in Google Scholar
  • 38 Bansal B C, Gupta R R, Prakash C. Stroke during pregnancy and puerperium in young females below the age of 40 years as a result of cerebral venous/venous sinus thrombosis.  Jpn Heart J . 1980;  21 171-183
    PubMedSearch in Google Scholar
  • 39 Ballem P. Acquired thrombophilia in pregnancy.  Semin Thromb Hemost . 1998;  24(Suppl 1) 41-47
    PubMedSearch in Google Scholar
  • 40 Ogasawara M, Sasa H, Kajiura S, Aoki K, Yagami Y. Successful management of congenital protein C deficiency with recurrent pregnancy loss.  Int J Gynaecol Obstet . 1995;  50 185-187
    CrossrefPubMedSearch in Google Scholar
  • 41 Alonso A, Soto I, Urgelles M F, Corte J R, Rodriguez M J, Pinto C R. Acquired and inherited thrombophilia in women with unexplained fetal losses.  Am J Obstet Gynecol . 2002;  187 1337-1342
    CrossrefPubMedSearch in Google Scholar
  • 42 Katz V L, DiTomasso J, Farmer R, Carpenter M. Activated protein C resistance associated with maternal floor infarction treated with low-molecular-weight heparin.  Am J Perinatol . 2002;  19 273-277
    Thieme ConnectPubMedSearch in Google Scholar
  • 43 Thorarensen O, Ryan S, Hunter J, Younkin D P. Factor V Leiden mutation: an unrecognized cause of hemiplegic cerebral palsy, neonatal stroke, and placental thrombosis [comments].  Ann Neurol . 1997;  42 372-375
    CrossrefPubMedSearch in Google Scholar
  • 44 Khong T Y, Hague W M. The placenta in maternal hyperhomocysteinaemia.  Br J Obstet Gynaecol . 1999;  106 273-278
    PubMedSearch in Google Scholar
  • 45 Magid M S, Kaplan C, Sammaritano L R, Peterson M, Druzin M L, Lockshin M D. Placental pathology in systemic lupus erythematosus: a prospective study.  Am J Obstet Gynecol . 1998;  179 226-234
    PubMedSearch in Google Scholar
  • 46 Anyaegbunam A, Mikhail M, Axioitis C, Morel M I, Merkatz I R. Placental histology and placental/fetal weight ratios in pregnant women with sickle cell disease: relationship to pregnancy outcome.  J Assoc Acad Minor Phys . 1994;  5 123-125
    PubMedSearch in Google Scholar
  • 47 Becroft D M, Thompson J M, Mitchell E A. The epidemiology of placental infarction at term.  Placenta . 2002;  23 343-351
    CrossrefPubMedSearch in Google Scholar
  • 48 Naeye R L. Placental infarction leading to fetal or neonatal death. A prospective study.  Obstet Gynecol . 1977;  50 583-588
    PubMedSearch in Google Scholar
  • 49 Schjetlein R, Abdelnoor M, Haugen G, Husby H, Sandset P M, Wisloff F. Hemostatic variables as independent predictors for fetal growth retardation in pre-eclampsia.  Acta Obstet Gynecol Scand . 1999;  78 191-197
    CrossrefPubMedSearch in Google Scholar
  • 50 Weenink G H, Treffers P E, Vijn P, Smorenberg-Schoorl M E, ten Cate W J. Antithrombin III levels in pre-eclampsia correlate with maternal and fetal morbidity.  Am J Obstet Gynecol . 1984;  148 1092-1097
    PubMedSearch in Google Scholar
  • 51 Bendon R W, Bornstein S, Faye-Petersen O M. Two fetal deaths associated with maternal sepsis and with thrombosis of the intervillous space of the placenta.  Placenta . 1998;  19 385-389
    CrossrefPubMedSearch in Google Scholar
  • 52 Naeye R L. The outcome of diabetic pregnancies: a prospective study.  Ciba Found Symp . 1978;  227-241
    PubMedSearch in Google Scholar
  • 53 Grether J K, Nelson K B. Maternal infection and cerebral palsy in infants of normal birth weight [comments] [erratum published in JAMA 1998;279:118].  JAMA . 1997;  278 207-211
    CrossrefPubMedSearch in Google Scholar
  • 54 Grether J K, Nelson K B, Emery 3rd S E, Cummins S K. Prenatal and perinatal factors and cerebral palsy in very-low-birth-weight infants [comments].  J Pediatr . 1996;  128 407-414
    PubMedSearch in Google Scholar
  • 55 Beebe L A, Cowan L D, Altshuler G. The epidemiology of placental features: associations with gestational age and neonatal outcome.  Obstet Gynecol . 1996;  87 771-778
    CrossrefPubMedSearch in Google Scholar
  • 56 Slutsker L. Risks associated with cocaine use during pregnancy.  Obstet Gynecol . 1992;  79 778-789
    PubMedSearch in Google Scholar
  • 57 Burstein Y, Giardina P J, Rausen A R, Kandall S R, Siljestrom K, Peterson C M. Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users.  J Pediatr . 1979;  94 895-899
    PubMedSearch in Google Scholar
  • 58 Amit M, Camfield P R. Neonatal polycythemia causing multiple cerebral infarcts.  Arch Neurol . 1980;  37 109-110
    PubMedSearch in Google Scholar
  • 59 Clancy R, Malin S, Laraque D, Baumgart S, Younkin D. Focal motor seizures heralding stroke in full-term neonates.  Am J Dis Child . 1985;  139 601-606
    PubMedSearch in Google Scholar
  • 60 Govaert P, Achten E, Vanhaesebrouck P, De Praeter C, Van Damme J. Deep cerebral venous thrombosis in thalamo-ventricular hemorrhage of the term newborn.  Pediatr Radiol . 1992;  22 123-127
    PubMedSearch in Google Scholar
  • 61 Konishi Y, Kuriyama M, Sudo M, Konishi K, Hayakawa K, Ishii Y. Superior sagittal sinus thrombosis in neonates.  Pediatr Neurol . 1987;  3 222-225
    CrossrefPubMedSearch in Google Scholar
  • 62 Andrew M, Paes B, Milner R. et al . Development of the human coagulation system in the full-term infant.  Blood . 1987;  70 165-172
    PubMedSearch in Google Scholar
  • 63 Andrew M. Developmental hemostasis: relevance to hemostatic problems during childhood.  Semin Thromb Hemost . 1995;  21 341-356
    PubMedSearch in Google Scholar
  • 64 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
  • 65 Powars D R, Weiss J N, Chan L S, Schroeder W A. Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia?.  Blood . 1984;  63 921-926
    PubMedSearch in Google Scholar
  • 66 Golomb M R. Sinovenous thrombosis in neonates.  Semin Cerebrovasc Dis Stroke . 2001;  1 216-224
    PubMedSearch in Google Scholar
  • 67 Riela A R, Roach E S. Etiology of stroke in children.  J Child Neurol . 1993;  8 201-220
    CrossrefPubMedSearch in Google Scholar
  • 68 Terplan K L. Brain changes in newborns, infants and children with congenital heart disease in association with cardiac surgery. Additional observations.  J Neurol . 1976;  212 225-236
    PubMedSearch in Google Scholar
  • 69 Lynch J K, Nelson K B. Epidemiology of perinatal stroke.  Curr Opin Pediatr . 2001;  13 499-505
    CrossrefPubMedSearch in Google Scholar
  • 70 Kuharik M A, Edwards M K. Cerebral venous distention associated with cardiac failure in infants.  AJNR Am J Neuroradiol . 1987;  8 657-659
    PubMedSearch in Google Scholar
  • 71 Wu Y W, Miller S P, Chin K. et al . Multiple risk factors in neonatal sinovenous thrombosis.  Neurology . 2002;  59 438-440
    PubMedSearch in Google Scholar
  • 72 Strater R, Vielhaber H, Kassenbohmer R, von Kries R, Göbel U, Nowak-Göttl U. Genetic risk factors of thrombophilia in ischaemic childhood stroke of cardiac origin. A prospective ESPED survey.  Eur J Pediatr . 1999;  158(Suppl 3) S122-125
    PubMedSearch in Google Scholar
  • 73 Petäjä J, Peltola K, Sairanen H. et al . Fibrinolysis, antithrombin III, and protein C in neonates during cardiac operations.  J Thorac Cardiovasc Surg . 1996;  112 665-671
    PubMedSearch in Google Scholar
  • 74 Zwischenberger J B, Nguyen T T, Upp Jr R J. et al . Complications of neonatal extracorporeal membrane oxygenation. Collective experience from the Extracorporeal Life Support Organization.  J Thorac Cardiovasc Surg . 1994;  107 838-849
    PubMedSearch in Google Scholar
  • 75 Bernbaum J, Schwartz I P, Gerdes M, D'Agostino J A, Coburn C E, Polin R A. Survivors of extracorporeal membrane oxygenation at 1 year of age: the relationship of primary diagnosis with health and neurodevelopmental sequelae.  Pediatrics . 1995;  96 907-913
    PubMedSearch in Google Scholar
  • 76 Taylor G A, Fitz C R, Kapur S, Short B L. Cerebrovascular accidents in neonates treated with extracorporeal membrane oxygenation: sonographic-pathologic correlation.  AJR Am J Roentgenol . 1989;  153 355-361
    PubMedSearch in Google Scholar
  • 77 Jarjour I T, Ahdab-Barmada M. Cerebrovascular lesions in infants and children dying after extracorporeal membrane oxygenation.  Pediatr Neurol . 1994;  10 13-19
    CrossrefPubMedSearch in Google Scholar
  • 78 Muntean W. Coagulation and anticoagulation in extracorporeal membrane oxygenation.  Artif Organs . 1999;  23 979-983
    CrossrefPubMedSearch in Google Scholar
  • 79 Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns.  Semin Perinatol . 1997;  21 70-85
    CrossrefPubMedSearch in Google Scholar
  • 80 Barmada M A, Moossy J, Shuman R M. Cerebral infarcts with arterial occlusion in neonates.  Ann Neurol . 1979;  6 495-502
    CrossrefPubMedSearch in Google Scholar
  • 81 Roach E S. Stroke in children.  Curr Treat Options Neurol . 2000;  2 295-304
    PubMedSearch in Google Scholar
  • 82 Ment L R, Ehrenkranz R A, Duncan C C. Bacterial meningitis as an etiology of perinatal cerebral infarction.  Pediatr Neurol . 1986;  2 276-279
    CrossrefPubMedSearch in Google Scholar
  • 83 Nowak-Göttl U, von Kries R, Göbel U. Neonatal symptomatic thromboembolism in Germany: two year survey [comments].  Arch Dis Child Fetal Neonatal Ed . 1997;  76 F163-167
    CrossrefPubMedSearch in Google Scholar
  • 84 Fritsch G. Acute infantile hemiplegia caused by cerebral ischemic infarction. Etiology, clinical features and investigations.  Pädiatrie Pädologie . 1984;  19 287-301
    PubMedSearch in Google Scholar
  • 85 Gebara B M, Everett K O. Dural sinus thrombosis complicating hypernatremic dehydration in a breastfed neonate.  Clin Pediatr . 2001;  40 45-48
    PubMedSearch in Google Scholar
  • 86 Barron T F, Gusnard D A, Zimmerman R A, Clancy R R. Cerebral venous thrombosis in neonates and children.  Pediatr Neurol . 1992;  8 112-116
    CrossrefPubMedSearch in Google Scholar
  • 87 Vailas G N, Brouillette R T, Scott J P, Shkolnik A, Conway J, Wiringa K. Neonatal aortic thrombosis: recent experience.  J Pediatr . 1986;  109 101-108
    CrossrefPubMedSearch in Google Scholar
  • 88 Lemke R P, Idiong N, al-Saedi S. et al . Spinal cord infarct after arterial switch associated with an umbilical artery catheter.  Ann Thorac Surg . 1996;  62 1532-1534
    CrossrefPubMedSearch in Google Scholar
  • 89 Ruff R L, Shaw C M, Beckwith J B, Iozzo R V. Cerebral infarction complicating umbilical vein catheterization.  Ann Neurol . 1979;  6 85
    CrossrefPubMedSearch in Google Scholar
  • 90 Reinecke H, Nabavi D G, Allroggen A, Droste D W, Breithardt G, Ringelstein E B. Detection of circulating cerebral microemboli by transcranial Doppler ultrasonography [in German].  Z Kardiol . 2001;  90 43-51
    CrossrefPubMedSearch in Google Scholar
  • 91 Newton T H, Gooding C A. Compression of superior sagittal sinus by neonatal calvarial molding.  Radiology . 1975;  115 635-640
    PubMedSearch in Google Scholar
  • 92 Cowan F, Thoresen M. Changes in superior sagittal sinus blood velocities due to postural alterations and pressure on the head of the newborn infant.  Pediatrics . 1985;  75 1038-1047
    PubMedSearch in Google Scholar
  • 93 Earley C J, Kittner S J, Feeser B R. et al . Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study.  Neurology . 1998;  51 169-176
    CrossrefPubMedSearch in Google Scholar
  • 94 Strater R, Becker S, von Eckardstein A. et al . Prospective assessment of risk factors for recurrent stroke during childhood-a 5-year follow-up study.  Lancet . 2002;  360 1540-1545
    CrossrefPubMedSearch in Google Scholar
  • 95 Golomb M. Walking after neonatal arterial ischemic stroke and sinovenous thrombosis: predictors of probability of walking over time and parental perception of gait [master's thesis]. Toronto: University of Toronto 2002
    Search in Google Scholar
  • 96 Lanthier S, Carmant L, David M, Larbrisseau A, de Veber G. Stroke in children: the coexistence of multiple risk factors predicts poor outcome.  Neurology . 2000;  54 371-378
    CrossrefPubMedSearch in Google Scholar
  • 97 Sun P M, Wilburn W, Raynor B D, Jamieson D. Sickle cell disease in pregnancy: twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia.  Am J Obstet Gynecol . 2001;  184 1127-1130
    CrossrefPubMedSearch in Google Scholar
  • 98 Rahimy M C, Gangbo A, Adjou R, Deguenon C, Goussanou S, Alihonou E. Effect of active prenatal management on pregnancy outcome in sickle cell disease in an African setting.  Blood . 2000;  96 1685-1689
    PubMedSearch in Google Scholar
  • 99 Kutteh W H, Ermel L D. A clinical trial for the treatment of antiphospholipid antibody-associated recurrent pregnancy loss with lower dose heparin and aspirin.  Am J Reprod Immunol . 1996;  35 402-407
    CrossrefPubMedSearch in Google Scholar
  • 100 Pattison N S, Chamley L W, Birdsall M, Zanderigo A M, Liddell H S, McDougall J. Does aspirin have a role in improving pregnancy outcome for women with the antiphospholipid syndrome?.  <~>A randomized controlled trial. Am J Obstet Gynecol . 2000;  183 1008-1012
    CrossrefPubMedSearch in Google Scholar
  • 101 Sher G, Matzner W, Feinman M. et al . The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody-positive women undergoing in vitro fertilization.  Am J Reprod Immunol . 1998;  40 74-82
    PubMedSearch in Google Scholar
  • 102 Buchanan N M, Khamashta M A, Morton K E, Kerslake S, Baguley E A, Hughes G R. A study of 100 high-risk lupus pregnancies.  Am J Reprod Immunol . 1992;  28 192-194
    PubMedSearch in Google Scholar
  • 103 Diejomaoh M F, Al-Azemi M M, Bandar A. et al . A favorable outcome of pregnancies in women with primary and secondary recurrent pregnancy loss associated with antiphospholipid syndrome.  Arch Gynecol Obstet . 2002;  266 61-66
    CrossrefPubMedSearch in Google Scholar
  • 104 Farquharson R G, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.  Obstet Gynecol . 2002;  100 408-413
    CrossrefPubMedSearch in Google Scholar
  • 105 Branch D W, Peaceman A M, Druzin M. et al . A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group.  Am J Obstet Gynecol . 2000;  182 122-127
    CrossrefPubMedSearch in Google Scholar
  • 106 Sherer Y, Levy Y, Shoenfeld Y. Intravenous immunoglobulin therapy of antiphospholipid syndrome.  Rheumatology (Oxford) . 2000;  39 421-426
    CrossrefPubMedSearch in Google Scholar
  • 107 Many A, Pauzner R, Carp H, Langevitz P, Martinowitz U. Treatment of patients with antiphospholipid antibodies during pregnancy.  Am J Reprod Immunol . 1992;  28 216-218
    PubMedSearch in Google Scholar
  • 108 Walker I D. Thrombophilia in pregnancy.  J Clin Pathol . 2000;  53 573-580
    CrossrefPubMedSearch in Google Scholar
  • 109 Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration.  Thromb Haemost . 1992;  68 325-330
    PubMedSearch in Google Scholar
  • 110 Massicotte P, Adams M, Marzinotto V, Brooker L A, Andrew M. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study.  J Pediatr . 1996;  128 313-318
    CrossrefPubMedSearch in Google Scholar
  • 111 deVeber G, Chan A, Monagle P. et al . Anticoagulation therapy in pediatric patients with sinovenous thrombosis: a cohort study.  Arch Neurol . 1998;  55 1533-1537
    CrossrefPubMedSearch in Google Scholar
  • 112 Ettingshausen C E, Veldmann A, Beeg T, Schneider W, Jäger G, Kreuz W. Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans.  Semin Thromb Hemost . 1999;  25 537-541
    Thieme ConnectPubMedSearch in Google Scholar
  • 113 Dreyfus M, Masterson M, David M. et al . Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency.  Semin Thromb Hemost . 1995;  21 371-381
    Thieme ConnectPubMedSearch in Google Scholar
  • 114 Kreuz W D, Schneider W, Nowak-Göttl U. Treatment of consumption coagulopathy with antithrombin concentrate in children with acquired antithrombin deficiency-a feasibility pilot study.  Eur J Pediatr . 1999;  158(Suppl 3) S187-191
    CrossrefPubMedSearch in Google Scholar
  • 115 Hossmann V, Heiss W D, Bewermeyer H. Antithrombin III deficiency in ischaemic stroke.  Klin Wochenschr . 1983;  61 617-620
    CrossrefPubMedSearch in Google Scholar
  • 116 Ueyama H, Hashimoto Y, Uchino M. et al . Progressing ischemic stroke in a homozygote with variant antithrombin III.  Stroke . 1989;  20 815-818
    PubMedSearch in Google Scholar
  • 117 de Jonge E, van der Poll T, Kesecioglu J, Levi M. Anticoagulant factor concentrates in disseminated intravascular coagulation: rationale for use and clinical experience.  Semin Thromb Hemost . 2001;  27 667-674
    Thieme ConnectPubMedSearch in Google Scholar
  • 118 Kahn M J, Scher C, Rozans M, Michaels R K, Leissinger C, Krause J. Factor V Leiden is not responsible for stroke in patients with sickling disorders and is uncommon in African Americans with sickle cell disease.  Am J Hematol . 1997;  54 12-5
    CrossrefPubMedSearch in Google Scholar
  • 119 Mader I, Schoning M, Klose U, Kuker W. Neonatal cerebral infarction diagnosed by diffusion-weighted MRI: pseudonormalization occurs early.  Stroke . 2002;  33 1142-1145
    CrossrefPubMedSearch in Google Scholar