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
Further Information

Publication History

Publication Date:
30 September 2003 (online)

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.

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
  • 2 Uvebrant P. Hemiplegic cerebral palsy. Aetiology and outcome. Acta Paediatr Suppl 1988 345: 1-100
  • 2a Friel J P. Dorland's Illustrated Medical Dictionary; 26th ed. Philadelphia: WB Saunders 1981
  • 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
  • 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
  • 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
  • 6 deVeber G. Stroke and the child's brain: an overview of epidemiology, syndromes and risk factors.  Curr Opin Neurol . 2002;  15 133-138
  • 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
  • 8 deVeber G, Group CPISS. Canadian Paediatric Ischemic Stroke Registry: analysis of children with arterial ischemic stroke [abstract].  Ann Neurol . 2000;  48 526
  • 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
  • 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
  • 12 Golomb M, MacGregor D, Domi T. et al . Presumed pre- and perinatal stroke: risk factors and outcomes.  Ann Neurol . 2001;  50 163-168
  • 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
  • 14 Sadler T. Langman's Medical Embryology.  Baltimore, MD: Williams & Wilkins 1990: 411
  • 15 Andrew M, Monagle P, Brooker L. Thromboembolic Complications during Infancy and Childhood. Hamilton, Ontario: BC Decker 2000
  • 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
  • 17 Burke C J, Tannenberg A E. Prenatal brain damage and placental infarction-an autopsy study.  Dev Med Child Neurol . 1995;  37 555-562
  • 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
  • 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
  • 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
  • 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
  • 22 Grafe M R. The correlation of prenatal brain damage with placental pathology.  J Neuropathol Exp Neurol . 1994;  53 407-415
  • 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
  • 24 Aune B, Gjesdal K, Oian P. Late onset postpartum thrombocytosis in pre-eclampsia.  Acta Obstet Gynecol Scand . 1999;  78 866-870
  • 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
  • 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
  • 27 Jaigobin C, Silver F L. Stroke and pregnancy.  Stroke . 2000;  31 2948-2951
  • 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
  • 29 Lanska D J, Kryscio R J. Risk factors for peripartum and postpartum stroke and intracranial venous thrombosis.  Stroke . 2000;  31 1274-1282
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 39 Ballem P. Acquired thrombophilia in pregnancy.  Semin Thromb Hemost . 1998;  24(Suppl 1) 41-47
  • 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
  • 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
  • 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
  • 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
  • 44 Khong T Y, Hague W M. The placenta in maternal hyperhomocysteinaemia.  Br J Obstet Gynaecol . 1999;  106 273-278
  • 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
  • 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
  • 47 Becroft D M, Thompson J M, Mitchell E A. The epidemiology of placental infarction at term.  Placenta . 2002;  23 343-351
  • 48 Naeye R L. Placental infarction leading to fetal or neonatal death. A prospective study.  Obstet Gynecol . 1977;  50 583-588
  • 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
  • 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
  • 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
  • 52 Naeye R L. The outcome of diabetic pregnancies: a prospective study.  Ciba Found Symp . 1978;  227-241
  • 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
  • 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
  • 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
  • 56 Slutsker L. Risks associated with cocaine use during pregnancy.  Obstet Gynecol . 1992;  79 778-789
  • 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
  • 58 Amit M, Camfield P R. Neonatal polycythemia causing multiple cerebral infarcts.  Arch Neurol . 1980;  37 109-110
  • 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
  • 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
  • 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
  • 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
  • 63 Andrew M. Developmental hemostasis: relevance to hemostatic problems during childhood.  Semin Thromb Hemost . 1995;  21 341-356
  • 64 deVeber G, Monagle P, Chan A. et al . Prothrombotic disorders in infants and children with cerebral thromboembolism.  Arch Neurol . 1998;  55 1539-1543
  • 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
  • 66 Golomb M R. Sinovenous thrombosis in neonates.  Semin Cerebrovasc Dis Stroke . 2001;  1 216-224
  • 67 Riela A R, Roach E S. Etiology of stroke in children.  J Child Neurol . 1993;  8 201-220
  • 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
  • 69 Lynch J K, Nelson K B. Epidemiology of perinatal stroke.  Curr Opin Pediatr . 2001;  13 499-505
  • 70 Kuharik M A, Edwards M K. Cerebral venous distention associated with cardiac failure in infants.  AJNR Am J Neuroradiol . 1987;  8 657-659
  • 71 Wu Y W, Miller S P, Chin K. et al . Multiple risk factors in neonatal sinovenous thrombosis.  Neurology . 2002;  59 438-440
  • 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
  • 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
  • 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
  • 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
  • 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
  • 77 Jarjour I T, Ahdab-Barmada M. Cerebrovascular lesions in infants and children dying after extracorporeal membrane oxygenation.  Pediatr Neurol . 1994;  10 13-19
  • 78 Muntean W. Coagulation and anticoagulation in extracorporeal membrane oxygenation.  Artif Organs . 1999;  23 979-983
  • 79 Andrew M. The relevance of developmental hemostasis to hemorrhagic disorders of newborns.  Semin Perinatol . 1997;  21 70-85
  • 80 Barmada M A, Moossy J, Shuman R M. Cerebral infarcts with arterial occlusion in neonates.  Ann Neurol . 1979;  6 495-502
  • 81 Roach E S. Stroke in children.  Curr Treat Options Neurol . 2000;  2 295-304
  • 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
  • 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
  • 84 Fritsch G. Acute infantile hemiplegia caused by cerebral ischemic infarction. Etiology, clinical features and investigations.  Pädiatrie Pädologie . 1984;  19 287-301
  • 85 Gebara B M, Everett K O. Dural sinus thrombosis complicating hypernatremic dehydration in a breastfed neonate.  Clin Pediatr . 2001;  40 45-48
  • 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
  • 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
  • 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
  • 89 Ruff R L, Shaw C M, Beckwith J B, Iozzo R V. Cerebral infarction complicating umbilical vein catheterization.  Ann Neurol . 1979;  6 85
  • 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
  • 91 Newton T H, Gooding C A. Compression of superior sagittal sinus by neonatal calvarial molding.  Radiology . 1975;  115 635-640
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 104 Farquharson R G, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment.  Obstet Gynecol . 2002;  100 408-413
  • 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
  • 106 Sherer Y, Levy Y, Shoenfeld Y. Intravenous immunoglobulin therapy of antiphospholipid syndrome.  Rheumatology (Oxford) . 2000;  39 421-426
  • 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
  • 108 Walker I D. Thrombophilia in pregnancy.  J Clin Pathol . 2000;  53 573-580
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 115 Hossmann V, Heiss W D, Bewermeyer H. Antithrombin III deficiency in ischaemic stroke.  Klin Wochenschr . 1983;  61 617-620
  • 116 Ueyama H, Hashimoto Y, Uchino M. et al . Progressing ischemic stroke in a homozygote with variant antithrombin III.  Stroke . 1989;  20 815-818
  • 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
  • 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
  • 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
    >