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Best Practice & Research Clinical Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn
Coagulation in pregnancy
Patrick Thornton, BMSc, MBBCh, FCARCSI, Clinical Research Fellow, Joanne Douglas, MD, FRCPC, Clinical Professor *
Departmentof Anesthesia, University of British Columbia, BC Women’s Hospital, Vancouver, BC, Canada
Keywords: coagulation haemostasis ﬁbrinolysis platelets thrombocytopaenia coagulation factors factor deﬁciencies pregnancy heparin thrombophilia neuraxial anaesthesia neuraxial haematoma
The coagulation system undergoes signiﬁcant change during pregnancy. The clinician caring for the parturient mustunderstand these changes, particularly when the parturient has a pre-existing haematological condition. Because many haematological conditions are rare, there often is limited information to guide the obstetric and anaesthetic management of these parturients. Ó 2009 Elsevier Ltd. All rights reserved.
To limit blood loss after trauma it is essential to seal bleeding vessels without affecting bloodﬂow permanently. Haemostasis, deﬁned as the arrest of bleeding, comes from the Greek roots, haeme meaning blood and stasis meaning causing to stop. The process of haemostasis is a dynamic and delicate equilibrium between coagulation and ﬁbrinolysis (Fig. 1). Coagulation results from an interaction among vessel walls, platelets and coagulation factors.1 Following endothelial damage, platelets adhereto the subendothelium forming a platelet plug which then becomes permanent with ﬁbrin deposition.1 Clot formation is limited by antithrombin (AT) and proteins C and S. The ﬁbrinolytic system functions to maintain the ﬂuid state through the breakdown of ﬁbrin by plasmin. Plasmin is generated from plasminogen by the action of tissue plasminogen activator (t-PA). Physiological changes to coagulationduring pregnancy Pregnancy is associated with changes in haemostasis, including an increase in the majority of clotting factors, a decrease in the quantity of natural anticoagulants and a reduction in ﬁbrinolytic
* Corresponding author. Department of Anesthesia, BC Women’s Hospital, Room 1Q72, 4500 Oak Street, V6H 3N1 Vancouver, BC, Canada. Tel.: þ1 604 875 2158; Fax: þ1 604 875 2733. E-mailaddress: firstname.lastname@example.org (J. Douglas). 1521-6934/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.bpobgyn.2009.11.010
P. Thornton, J. Douglas / Best Practice & Research Clinical Obstetrics and Gynaecology 24 (2010) 339–352
INTRINSIC Collagen Kallikrein XII XIa Prekallikrein XIIa + Kininogen XI IXa
Ca++ Va PF3
Fibrinogen (I) FIBRINOLYTIC SYSTEM Large Fragments Inhibition Fibrin degradation products Small fragments
Soluble fibrin polymer
XIIIa Double chain urokinase Insoluble polymer Kallikrein Fibrin Single chain urokinase Plasmin ProurokinasePlasminogen activator Fibrin Plasminogen
Fig. 1. Normal coagulation pathway.
activity.2–4 These changes result in a state of hypercoagulability,2,4 are likely due to hormonal changes5 and increase the risk of thromboembolism. The increase in clotting activity is greatest at the time of delivery with placental expulsion, releasing thromboplastic substances.2 These substances stimulate clot formation tostop maternal blood loss. As placental blood ﬂow is up to 700 ml minÀ1, considerable haemorrhage can occur if clotting fails. Coagulation and ﬁbrinolysis generally return to pre-pregnant levels 3–4 weeks postpartum.2,3 a. Platelets The platelet count decreases in normal pregnancy possibly due to increased destruction and haemodilution with a maximal decrease in the third trimester.6 b....