Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.
BACKGROUND
Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented.


METHODS
Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests.


RESULTS
In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease.


CONCLUSIONS
This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting.


BACKGROUND
ISRCTN09968140.
Pole d'Anesthésie-Réanimation, CHU Lille, France.
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Ducloy-Bouthors
Pole de Santé Publique, CHU Lille, Lille, France EA2694, Université of Lille Nord de France, France.
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Duhamel
Pole d'Anesthésie-Réanimation, CHU Lille, France.
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Kipnis
Hématologie Transfusion, Pôle de Biologie Pathologie Génétique, CHU Lille, France Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
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Tournoys
Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France Pole d'hématologie, Maternité Monaco, Centre hospitalier, Valenciennes, France.
A
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Prado-Dupont
Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
A
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Elkalioubie
Hématologie Transfusion, Pôle de Biologie Pathologie Génétique, CHU Lille, France Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
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Jeanpierre
Pole d'hématologie, Hôpital de la Croix Rousse, Hôpitaux civils Lyon, Lyon, France.
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Debize
APHP, Hôpital Louis Mourier, Service d'Hématologie Biologique, F-92701 Colombes, France.
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Peynaud-Debayle
APHP, Hôpital Louis Mourier, Service d'Hématologie Biologique, F-92701 Colombes, France University Paris Diderot, Sorbonne Paris Cité, F-75018 Paris, France.
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DeProst
Pole d'obstétrique, Hôpital de la Croix Rousse, Hôpitaux Civils Lyon, Lyon, France.
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Huissoud
Hématologie Transfusion, Pôle de Biologie Pathologie Génétique, CHU Lille, France Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France.
A
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Rauch
Hématologie Transfusion, Pôle de Biologie Pathologie Génétique, CHU Lille, France Inserm U1011, Laboratoire de Recherche J&K, Institut Pasteur de Lille, Faculté de Médecine - Pôle recherche, University of Lille Nord de France, EGID, Lille, France sophie.susen@inserm.fr.
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Susen
D000933:Antifibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000378:metabolism; D001800:Blood Specimen Collection / Q000379:methods; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D006473:Postpartum Hemorrhage / Q000097:blood / Q000517:prevention & control*; D011247:Pregnancy; D016037:Single-Blind Method; D014148:Tranexamic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D000933:Antifibrinolytic Agents; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014148:Tranexamic Acid
fibrinogen; fibrinolysis; postpartum haemorrhage; tranexamic acid