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Semin Thromb Hemost 2023; 49(04): 319-329
DOI: 10.1055/s-0042-1760332
Review Article

Hemostasis in the Pregnant Woman, the Placenta, the Fetus, and the Newborn Infant

Beth Boulden Warren
1   University of Colorado Hemophilia and Thrombosis Center, Aurora, Colorado
2   Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado
,
Genevieve C. Moyer
1   University of Colorado Hemophilia and Thrombosis Center, Aurora, Colorado
2   Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado
,
Marilyn J. Manco-Johnson
1   University of Colorado Hemophilia and Thrombosis Center, Aurora, Colorado
2   Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado
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Abstract

The hemostasis system is composed of procoagulant, anticoagulant, and fibrinolytic proteins that interact with endothelial and blood cells and with each other in a complex system of checks and balances to maintain blood flow while preventing both hemorrhage and thrombosis. Pregnancy is a unique physiological state in which biological alterations predispose both mother and fetus to both bleeding and clotting. The placenta is a vascular interface for maternal and fetal blood exchange which predisposes the mother to hemorrhage. Maternal hemostasis presents a compensatory hypercoagulability including elevated factor VIII, von Willebrand factor, fibrinogen and thrombin generation, decreased thrombin regulation with resistance to activated protein C and decreased free protein S, and decreased fibrinolysis with increased plasminogen activator inhibitors. The placental vascular surface is of fetal trophoblastic origin that derives many characteristics of endothelium but differs in that tissue factor is constitutively expressed. Ontogeny of fetal hemostasis is characteristic. Platelets, von Willebrand factor, factor VIII, and fibrinogen are expressed and mature early in gestation, while vitamin K–dependent and contact factors exhibit delayed development. The fetal hemostatic system has a decreased capacity to generate or regulate thrombin, resulting in a fragile balance with little capacity to compensate under stress conditions, particularly in the infant born prematurely. Dysfunction of the maternal/placental/fetal unit gives rise to gestational disorders including preeclampsia, fetal growth restriction, placental abruption, and premature delivery. Knowledge of normal hemostasis levels and function are critical to evaluate bleeding or clotting syndromes in the pregnant woman and her fetus or newborn infant.

Keywords

hemostasis - pregnancy - placenta - fetus - newborn Infant - hemorrhage - thrombosis


Publication History

Article published online:
07 February 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Ataullakhanov FI, Koltsova EM, Balandina AN, Serebriyskiy II, Vuimo TA, Panteleev MA. Classic and global hemostasis testing during pregnancy and during pregnancy complications. Semin Thromb Hemost 2016; 42 (07) 696-716
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Practice Bulletin No. 183: Postpartum hemorrhage. Accessed November 9, 2022 at: https://journals.lww.com/greenjournal/Fulltext/2017/10000/Practice_Bulletin_No_183_Postpartum_Hemorrhage.56.aspx
    PubMed
  • 3 How does CDC identify severe maternal morbidity? Accessed November 9, 2022 at: https://www.cdc.gov/reproductivehealth/maternalinfanthealth/smm/severe-morbidity-ICD.htm
    PubMed
  • 4 Taking on a leading cause of maternal death: improving postpartum hemorrhage care. Accessed November 9, 2022 at: https://www.nichq.org/insight/taking-leading-cause-maternal-death-improving-postpartum-hemorrhage-care
    PubMedGoogle Scholar
  • 5 Sood R, Kalloway S, Mast AE, Hillard CJ, Weiler H. Fetomaternal cross talk in the placental vascular bed: control of coagulation by trophoblast cells. Blood 2006; 107 (08) 3173-3180
    CrossrefPubMedGoogle Scholar
  • 6 Clark P, Greer IA, Walker ID. Interaction of the protein C/protein S anticoagulant system, the endothelium and pregnancy. Blood Rev 1999; 13 (03) 127-146
    CrossrefPubMedGoogle Scholar
  • 7 Reese JA, Peck JD, Deschamps DR. et al. Platelet counts during pregnancy. N Engl J Med 2018; 379 (01) 32-43
    CrossrefPubMedGoogle Scholar
  • 8 Valéra M-C, Parant O, Cenac C. et al. Platelet adhesion and thrombus formation in whole blood at arterial shear rate at the end of pregnancy. Am J Reprod Immunol 2015; 74 (06) 533-541
    CrossrefPubMedGoogle Scholar
  • 9 Bremme K, Ostlund E, Almqvist I, Heinonen K, Blombäck M. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynecol 1992; 80 (01) 132-137
    PubMedGoogle Scholar
  • 10 Stirling Y, Woolf L, North WRS, Seghatchian MJ, Meade TW. Haemostasis in normal pregnancy. Thromb Haemost 1984; 52 (02) 176-182
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost 2010; 103 (04) 718-727
    Google Scholar
  • 12 Hellgren M, Blombäck M. Studies on blood coagulation and fibrinolysis in pregnancy, during delivery and in the puerperium. I. Normal condition. Gynecol Obstet Invest 1981; 12 (03) 141-154
    CrossrefPubMedGoogle Scholar
  • 13 Sharief LT, Lawrie AS, Mackie IJ, Smith C, Peyvandi F, Kadir RA. Changes in factor XIII level during pregnancy. Haemophilia 2014; 20 (02) e144-e148
    CrossrefPubMedGoogle Scholar
  • 14 Alving BM, Niebyl JR, Proud D, Mason BL, Pisano JJ. Human plasma prekallikrein and high molecular weight kininogen decrease during parturition. Thromb Res 1984; 34 (06) 473-477
    CrossrefPubMedGoogle Scholar
  • 15 Sandset PM, Hellgren M, Uvebrandt M, Bergström H. Extrinsic coagulation pathway inhibitor and heparin cofactor II during normal and hypertensive pregnancy. Thromb Res 1989; 55 (05) 665-670
    CrossrefPubMedGoogle Scholar
  • 16 Petersen CM. α 2-macroglobulin and pregnancy zone protein. Serum levels, α 2-macroglobulin receptors, cellular synthesis and aspects of function in relation to immunology. Dan Med Bull 1993; 40 (04) 409-446
    PubMedGoogle Scholar
  • 17 Stimson WH, Farquharson DM, Lang GD. Pregnancy-associated alpha 2-macroglobulin - a new serum protein elevated in normal human pregnancy. J Reprod Immunol 1983; 5 (06) 321-327
    CrossrefPubMedGoogle Scholar
  • 18 Reverdiau-Moalic P, Gruel Y, Delahousse B. et al. Comparative study of the fibrinolytic system in human fetuses and in pregnant women. Thromb Res 1991; 61 (5-6): 489-499
    CrossrefPubMedGoogle Scholar
  • 19 Smith AA, Jacobson LJ, Miller BI, Hathaway WE, Manco-Johnson MJ. A new euglobulin clot lysis assay for global fibrinolysis. Thromb Res 2003; 112 (5-6): 329-337
    CrossrefPubMedGoogle Scholar
  • 20 Majumder R, Nguyen T. Protein S: function, regulation, and clinical perspectives. Curr Opin Hematol 2021; 28 (05) 339-344
    CrossrefPubMedGoogle Scholar
  • 21 Hathaway WE, Bonnar J. Coagulation in pregnancy. In: Oliver Jr. TK. Perinatal Coagulation, Monographs in Neonatology. New York: Grune & Stratton; 1978: 30
    Google Scholar
  • 22 Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol 2003; 16 (02) 153-168
    CrossrefPubMedGoogle Scholar
  • 23 Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost 2003; 29 (02) 125-130
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Sattar N, Greer IA, Rumley A. et al. A longitudinal study of the relationships between haemostatic, lipid, and oestradiol changes during normal human pregnancy. Thromb Haemost 1999; 81 (01) 71-75
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Tchaikovski SN, Rosing J. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res 2010; 126 (01) 5-11
    CrossrefPubMedGoogle Scholar
  • 26 Goldenberg NA, Hathaway WE, Jacobson L, Manco-Johnson MJ. A new global assay of coagulation and fibrinolysis. Thromb Res 2005; 116 (04) 345-356
    CrossrefPubMedGoogle Scholar
  • 27 Menache D, O'Malley JP, Schorr JB. et al; Cooperative Study Group. Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Blood 1990; 75 (01) 33-39
    CrossrefPubMedGoogle Scholar
  • 28 Manco-Johnson M, Nuss R. Protein C concentrate prevents peripartum thrombosis. Am J Hematol 1992; 40 (01) 69-70
    CrossrefPubMedGoogle Scholar
  • 29 Antiphospholipid Syndrome. Obstetrics and Gynecology 2012;120:1514–21. The American College of Obstetrics and Gynecology, Practice Bulletin, #132, December, 2012
    PubMedGoogle Scholar
  • 30 Sammaritano LR, Bermas BL, Chakravarty EE. et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol 2020; 72 (04) 529-556
    CrossrefPubMedGoogle Scholar
  • 31 Preston FE, Rosendaal FR, Walker ID. et al. Increased fetal loss in women with heritable thrombophilia. Lancet 1996; 348 (9032): 913-916
    CrossrefPubMedGoogle Scholar
  • 32 Bornikova L, Peyvandi F, Allen G, Bernstein J, Manco-Johnson MJ. Fibrinogen replacement therapy for congenital fibrinogen deficiency. J Thromb Haemost 2011; 9 (09) 1687-1704
    CrossrefPubMedGoogle Scholar
  • 33 Pelcovits A, Schiffman F, Niroula R. Factor XIII deficiency: a review of clinical presentation and management. Hematol Oncol Clin North Am 2021; 35 (06) 1171-1180
    CrossrefPubMedGoogle Scholar
  • 34 Owens III AP, Byrnes JR, Mackman N. Hyperlipidemia, tissue factor, coagulation, and simvastatin. Trends Cardiovasc Med 2014; 24 (03) 95-98
    CrossrefPubMedGoogle Scholar
  • 35 Cantin C, Fuenzalida B, Leiva A. Maternal hypercholesterolemia during pregnancy: potential modulation of cholesterol transport through the human placenta and lipoprotein profile in maternal and neonatal circulation. Placenta 2020; 94: 26-33
    CrossrefPubMedGoogle Scholar
  • 36 Maltepe E, Fisher SJ. Placenta: the forgotten organ. Annu Rev Cell Dev Biol 2015; 31: 523-552
    CrossrefPubMedGoogle Scholar
  • 37 Benirschke K, Kaufmann P. Pathology of the Human Placenta. New York: Springer-Verlag; 1995
    CrossrefGoogle Scholar
  • 38 Cha J, Sun X, Dey SK. Mechanisms of implantation: strategies for successful pregnancy. Nat Med 2012; 18 (12) 1754-1767
    CrossrefPubMedGoogle Scholar
  • 39 Abbott BD, Buckalew AR. Placental defects in ARNT-knockout conceptus correlate with localized decreases in VEGF-R2, Ang-1, and Tie-2. Dev Dyn 2000; 219 (04) 526-538
    CrossrefPubMedGoogle Scholar
  • 40 Achen MG, Gad JM, Stacker SA, Wilks AF. Placenta growth factor and vascular endothelial growth factor are co-expressed during early embryonic development. Growth Factors 1997; 15 (01) 69-80
    CrossrefPubMedGoogle Scholar
  • 41 Lanir N, Aharon A, Brenner B. Procoagulant and anticoagulant mechanisms in human placenta. Semin Thromb Hemost 2003; 29 (02) 175-184
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Wang X, Campos B, Kaetzel MA, Dedman JR. Annexin V is critical in the maintenance of murine placental integrity. Am J Obstet Gynecol 1999; 180 (04) 1008-1016
    CrossrefPubMedGoogle Scholar
  • 43 Red-Horse K, Zhou Y, Genbacev O. et al. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest 2004; 114 (06) 744-754
    CrossrefPubMedGoogle Scholar
  • 44 Pijnenborg R, Bland JM, Robertson WB, Dixon G, Brosens I. The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy. Placenta 1981; 2 (04) 303-316
    CrossrefPubMedGoogle Scholar
  • 45 Dilworth MR, Kusinski LC, Cowley E. et al. Placental-specific Igf2 knockout mice exhibit hypocalcemia and adaptive changes in placental calcium transport. Proc Natl Acad Sci U S A 2010; 107 (08) 3894-3899
    CrossrefPubMedGoogle Scholar
  • 46 Battaglia FC. Placental transport: a function of permeability and perfusion. Am J Clin Nutr 2007; 85 (02) 591S-597S
    CrossrefPubMedGoogle Scholar
  • 47 Saji F, Samejima Y, Kamiura S, Koyama M. Dynamics of immunoglobulins at the feto-maternal interface. Rev Reprod 1999; 4 (02) 81-89
    CrossrefPubMedGoogle Scholar
  • 48 Schneider H, Miller RK. Receptor-mediated uptake and transport of macromolecules in the human placenta. Int J Dev Biol 2010; 54 (2-3): 367-375
    CrossrefPubMedGoogle Scholar
  • 49 Ananth CV. Ischemic placental disease: a unifying concept for preeclampsia, intrauterine growth restriction, and placental abruption. Semin Perinatol 2014; 38 (03) 131-132
    CrossrefPubMedGoogle Scholar
  • 50 Villar J, Carroli G, Wojdyla D. et al; World Health Organization Antenatal Care Trial Research Group. Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions?. Am J Obstet Gynecol 2006; 194 (04) 921-931
    CrossrefPubMedGoogle Scholar
  • 51 Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science 2014; 345 (6198): 760-765
    CrossrefPubMedGoogle Scholar
  • 52 Roberts JM. Pathophysiology of ischemic placental disease. Semin Perinatol 2014; 38 (03) 139-145
    CrossrefPubMedGoogle Scholar
  • 53 Savasan ZA, Goncalves LF, Bahado-Singh RO. Second- and third-trimester biochemical and ultrasound markers predictive of ischemic placental disease. Semin Perinatol 2014; 38 (03) 167-176
    CrossrefPubMedGoogle Scholar
  • 54 Newstead J, von Dadelszen P, Magee LA. Preeclampsia and future cardiovascular risk. Expert Rev Cardiovasc Ther 2007; 5 (02) 283-294
    CrossrefPubMedGoogle Scholar
  • 55 Osmond C, Barker DJ. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect 2000; 108 (Suppl 3(03): 545-553
    PubMedGoogle Scholar
  • 56 Barker DJ, Thornburg KL. Placental programming of chronic diseases, cancer and lifespan: a review. Placenta 2013; 34 (10) 841-845
    CrossrefPubMedGoogle Scholar
  • 57 Rho (D) immune globulin. StatPearls Publishing LLC/, National Center for Biotechnology Information (NCBI), US national Library of Medicine. Accessed November 9, 2022 at: https://www.ncbi.nlm.nih.gov/books/NBK557884/
    PubMed
  • 58 Bussel JB, Vander Haar EL, Berkowitz RL. New developments in fetal and neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 2021; 225 (02) 120-127
    CrossrefPubMedGoogle Scholar
  • 59 Tong M, Viall CA, Chamley LW. Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by treatment. Hum Reprod Update 2015; 21 (01) 97-118
    CrossrefPubMedGoogle Scholar
  • 60 Quenby S, Mountfield S, Cartwright JE, Whitley GS, Chamley L, Vince G. Antiphospholipid antibodies prevent extravillous trophoblast differentiation. Fertil Steril 2005; 83 (03) 691-698
    CrossrefPubMedGoogle Scholar
  • 61 Gaiday AN, Tussupkaliyev AB, Bermagambetova SK. et al. Effect of homocysteine on pregnancy: a systematic review. Chem Biol Interact 2018; 293: 70-76
    CrossrefPubMedGoogle Scholar
  • 62 Silver RM, Branch DW. Placenta accreta spectrum. N Engl J Med 2018; 378 (16) 1529-1536
    CrossrefPubMedGoogle Scholar
  • 63 Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009; 29 (02) 130-136
    CrossrefPubMedGoogle Scholar
  • 64 Reverdiau-Moalic P, Delahousse B, Body G, Bardos P, Leroy J, Gruel Y. Evolution of blood coagulation activators and inhibitors in the healthy human fetus. Blood 1996; 88 (03) 900-906
    CrossrefPubMedGoogle Scholar
  • 65 Hathaway WE, Bonnar J. Hemostatic Disorders of the Pregnant Woman and Newborn Infant. New York, NY: Elsevier Science Publishing Company; 1987: 56-57
    Google Scholar
  • 66 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (05) 1651-1657
    CrossrefPubMedGoogle Scholar
  • 67 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
    CrossrefPubMedGoogle Scholar
  • 68 Manco-Johnson MJ. Development of hemostasis in the fetus. Thromb Res 2005; 115 (Suppl. 01) 55-63
    PubMedGoogle Scholar
  • 69 Van den Hof MC, Nicolaides KH. Platelet count in normal, small, and anemic fetuses. Am J Obstet Gynecol 1990; 162 (03) 735-739
    CrossrefPubMedGoogle Scholar
  • 70 Margraf A, Nussbaum C, Sperandio M. Ontogeny of platelet function. Blood Adv 2019; 3 (04) 692-703
    CrossrefPubMedGoogle Scholar
  • 71 Curley A, Stanworth SJ, Willoughby K. et al; PlaNeT2 MATISSE Collaborators. Randomized trial of platelet-transfusion thresholds in neonates. N Engl J Med 2019; 380 (03) 242-251
    CrossrefPubMedGoogle Scholar
  • 72 McDonald MM, Hathaway WE, Reeve EB, Leonard BD. Biochemical and functional study of antithrombin III in newborn infants. Thromb Haemost 1982; 47 (01) 56-58
    Article in Thieme ConnectPubMedGoogle Scholar
  • 73 Greffe BS, Manco-Johnson MJ, Marlar RA. Molecular forms of human protein C: comparison and distribution in human adult plasma. Thromb Haemost 1989; 62 (03) 902-905
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 McDonald MM, Johnson ML, Rumack CM. et al. Role of coagulopathy in newborn intracranial hemorrhage. Pediatrics 1984; 74 (01) 26-31
    CrossrefPubMedGoogle Scholar
  • 75 Manco-Johnson MJ, Abshire TC, Jacobson LJ, Marlar RA. Severe neonatal protein C deficiency: prevalence and thrombotic risk. J Pediatr 1991; 119 (05) 793-798
    CrossrefPubMedGoogle Scholar
  • 76 Manco-Johnson MJ, Jacobson LJ, Hacker MR, Townsend SF, Murphy J, Hay Jr W. Development of coagulation regulatory proteins in the fetal and neonatal lamb. Pediatr Res 2002; 52 (04) 580-588
    CrossrefPubMedGoogle Scholar
  • 77 Manco-Johnson MJ, Carver T, Jacobson LJ, Townsend SF, Hay Jr WW. Hyperglycemia-induced hyperinsulinemia decreases maternal and fetal plasma protein C concentration during ovine gestation. Pediatr Res 1994; 36 (03) 293-299
    CrossrefPubMedGoogle Scholar
  • 78 Kisker CT, Manco-Johnson M. Effect of hyperinsulinemia on the development of blood coagulation in the lamb fetus. Pediatr Res 1995; 38 (02) 169-172
    CrossrefPubMedGoogle Scholar
  • 79 Manco-Johnson MJ, Hacker MR, Jacobson LJ, Hay Jr WW. Pharmacokinetics of protein C and antithrombin in the fetal lamb: a model to predict human neonatal replacement dosing. Neonatology 2009; 95 (04) 279-285
    CrossrefPubMedGoogle Scholar
  • 80 Kulkarni R, Soucie JM, Lusher J. et al; Haemophilia Treatment Center Network Investigators. Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from the Centers for Disease Control and Prevention's (CDC) Universal Data Collection (UDC) project. Haemophilia 2009; 15 (06) 1281-1290
    CrossrefPubMedGoogle Scholar
  • 81 Shearer MJ, Rahim S, Barkhan P, Stimmler L. Plasma vitamin K1 in mothers and their newborn babies. Lancet 1982; 2 (8296): 460-463
    CrossrefPubMedGoogle Scholar
  • 82 Shapiro AD, Jacobson LJ, Armon ME. et al. Vitamin K deficiency in the newborn infant: prevalence and perinatal risk factors. J Pediatr 1986; 109 (04) 675-680
    CrossrefPubMedGoogle Scholar
  • 83 Jullien S. Vitamin K prophylaxis in newborns. BMC Pediatr 2021; 21 (Suppl. 01) 350-356
    CrossrefPubMedGoogle Scholar
  • 84 Hartman KR, Manco-Johnson M, Rawlings JS, Bower DJ, Marlar RA. Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol Oncol 1989; 11 (04) 395-401
    PubMedGoogle Scholar
  • 85 Mahasandana C, Suvatte V, Chuansumrit A. et al. Homozygous protein S deficiency in an infant with purpura fulminans. J Pediatr 1990; 117 (05) 750-753
    CrossrefPubMedGoogle Scholar
  • 86 Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. Haemophilia 2008; 14 (06) 1214-1221
    CrossrefPubMedGoogle Scholar
  • 87 Ghassemi F, Abdi F, Esfahani M. Ophthalmic manifestations of congenital protein C deficiency: a case report and mini review. BMC Ophthalmol 2020; 20 (01) 282-287
    CrossrefPubMedGoogle Scholar
  • 88 Manco-Johnson MJ, Bomgaars L, Palascak J. et al. Efficacy and safety of protein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency. Thromb Haemost 2016; 116 (01) 58-68
    PubMedGoogle Scholar
  • 89 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 (03) 414-421
    CrossrefPubMedGoogle Scholar
  • 90 Oguma Y, Sakuragawa N, Maki M, Nakagawa M, Hasegawa H. Clinical effect of low molecular weight heparin (Fragmin) on DIC: a multicenter cooperative study in Japan. Thromb Res 1990; 59 (01) 37-49
    CrossrefPubMedGoogle Scholar
  • 91 Bassan H. Intracranial hemorrhage in the preterm infant: understanding it, preventing it. Clin Perinatol 2009; 36 (04) 737-762 , v
    CrossrefPubMedGoogle Scholar
  • 92 McDonald MM, Koops BL, Johnson ML. et al. Timing and antecedents of intracranial hemorrhage in the newborn. Pediatrics 1984; 74 (01) 32-36
    CrossrefPubMedGoogle Scholar
  • 93 Bhatt MD, Chan AKC. Venous thrombosis in neonates. Fac Rev 2021; 10: 20
    CrossrefPubMedGoogle Scholar
  • 94 Dunbar M, Kirton A. Perinatal stroke. Semin Pediatr Neurol 2019; 32: 100767
    CrossrefPubMedGoogle Scholar
  • 95 Smith N, Warren BB, Smith J. et al. Antithrombin deficiency: a pediatric disorder. Thromb Res 2021; 202: 45-51
    CrossrefPubMedGoogle Scholar