Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?

Abstract

INTRODUCTION: Although antifibrinolytic agents are used to prevent and treat hemorrhage, there are concerns about a potential increased risk for peripartum venous thromboembolism. We sought to determine the impact of tranexamic acid and ɛ-aminocaproic acid on in vitro clotting properties in pregnancy. METHODS: Blood samples was obtained from healthy pregnant, obese, and preeclamptic pregnant women (n = 10 in each group) prior to delivery as well as from healthy non-pregnant controls (n = 10). Maximum clot firmness (MCF) and clotting time (CT) were measured using rotation thromboelastometry in the presence of tranexamic acid (3, 30, or 300 μg/mL) or ɛ-aminocaproic acid (30, 300, or 3000 μg/mL). ANOVA and regression analyses were performed. RESULTS: Mean whole blood MCF was significantly higher in healthy pregnant vs. non-pregnant women (66.5 vs. 57.5 mm, p < 0.001). Among healthy pregnant women, there was no significant difference between mean MCF (whole blood alone, and with increasing tranexamic acid doses = 66.5, 66.1, 66.4, 66.3 mm, respectively; p = 0.25) or mean CT (409, 412, 420, 424 sec; p = 0.30) after addition of tranexamic acid. Similar results were found using ɛ-aminocaproic acid. Preeclamptic women had a higher mean MCF after the addition of ɛ-aminocaproic acid and tranexamic acid (p = 0.05 and p = 0.04, respectively) compared to whole blood alone. CONCLUSIONS: Pregnancy is a hypercoagulable state, as reflected by an increased MCF compared to non-pregnant women. Addition of antifibrinolytic therapy in vitro does not appear to increase MCF or CT for non-pregnant, pregnant, and obese women. Whether antifibrinolytics are safe in preeclampsia may require further study.

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Published Version (Please cite this version)

10.3233/NPM-16139

Publication Info

Ahmadzia, HK, EL Lockhart, SM Thomas, IJ Welsby, MR Hoffman, AH James, AP Murtha, GK Swamy, et al. (2017). Using antifibrinolytics in the peripartum period - concern for a hypercoagulable effect?. J Neonatal Perinatal Med. 10.3233/NPM-16139 Retrieved from https://hdl.handle.net/10161/13911.

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Scholars@Duke

Thomas

Samantha Thomas

Biostatistician, Principal

Samantha is the manager of the Duke Cancer Institute (DCI) Biostatistics Shared Resource. Collaboratively, she primarily works with physicians in DCI, specifically in research of Endocrine Neoplasia and Breast Cancer. She is also the director of the Biostatistics, Epidemiology, Research, and Design Methods (BERD) Core Training and Internship Program (BCTIP). Her professional experience involves study design, analysis, and reporting of clinical trials and observational studies. Her specific areas of interest include training of collaborative biostatisticians, modeling of non-linear associations, and application of partitioning analyses to identify homogeneous patient groups.

Welsby

Ian James Welsby

Professor of Anesthesiology

As a practicing cardiothoracic anesthesiologist, I have contributed to the better understanding of the management and of perioperative thrombosis (particularly HIT). This has been as a Duke site PI for the Rare Thrombotic Diseases Consortium led by Dr T.L Ortel and a clinical collaborator with the basic and translational science approach to HIT led by Dr G Arepally. I have also championed novel approaches to dealing with perioperative HIT such as plasmaperesis.

Similarly, I have been a local leader in establishing management of transfusion approaches to major cardiac surgery including the novel introduction of autologous plateletpheresis to limit exposure to allogeneic platelet transfusions in this highly transfused population, identifying the transfusion requirements during thoracic aortic reconstruction and promoting use of a lower dose of rFVIIa use in this population, changing established clinical practice.

My research interests focus on perioperative transfusion and hematology concerns. Recently, Dr Kor (Mayo Clinic) and I received a multiple PI R-01 award to evaluate point-of-care/bedside washing of packed red blood cells to reduce perioperative lung injury. This novel repurposing of commonly available “cell-saver” technology is, for most surgical cases, the only practical means of delivering a washed product, and promises to be a critical advancement in perioperative transfusion medicine. I also have a longstanding interest in the rejuvenation of RBCs to normalize oxygen delivery capacity of transfused RBCs. Such a development will be of tremendous importance to transfusion practice, particularly for highly transfused populations and with current threats to blood banking inventory. 

In summary, I have dedicated my research career to improving the outcome of patients undergoing cardiothoracic surgery, understanding perioperative coagulopathy, and optimizing transfusion practice. 

Hoffman

Maureane Hoffman

Professor of Pathology

The blood coagulation system is a delicately balanced homeostatic mechanism. Inappropriate clotting is a major cause of morbidity and mortality, resulting in strokes, heart attacks, thrombophlebitis and pulmonary embolism. My research is directed toward understanding basic mechanisms in hemostasis, and the connections between inflammation/immunity and coagulation responses to injury.  We are also committed to translating our basic finding into clinical practice.

We have developed a cell-based model of tissue factor-initiated coagulation. This model is a powerful tool for understanding and studying basic mechanisms in hemostasis. It has taught us that the cellular LOCATION of activation of the clotting factors is critically important in determining their ability to initiate and support formation of a hemostatic clot. Using this model system we have been able to explain why factors VIII and IX (the factors that are deficient in hemophilia A and B) are essential for hemostasis in vivo, and also how high dose FVIIa can bypass the need for FVIII or FIX and restore hemostasis in hemophiliacs. We have also modeled the hemostatic defects in dilutional coagulopathy, liver disease and anticoagulant treatment. These models are helping us understand why the common clinical coagulation tests do not predict the risk of bleeding well in these conditions.

We have also examined the role of the coagulation process in wound healing. Clinicians have long felt that wound healing is delayed in hemophiliacs. We have now ascertained that hemophilia B mice do indeed have delayed wound healing. They have poor influx of phagocytic cells into the wound area and delayed clearance of debris and iron from hemorrhage. Surprisingly, the mice with defective hemostasis have greater angiogenesis during the healing process. This is a result of the inflammatory effects of iron in the tissues. The excess angiogenesis may be one reason why hemophiliacs often have recurrent bleeding into their joints - the healing process produces a large number of fragile vessels.

Anticoagulation also impairs wound healing.  Patients are often anti coagulated after surgery to prevent deep vein thrombosis and pulmonary embolism. However, the impact of this therapy on tissue repair is not well understood.  Our aim is to define the extent and time frame of hemostatic function that is needed for optimal healing, thereby setting the stage for scientifically based strategies for anticoagulation.

James

Andra Hohler James

Professor Emeritus of Obstetrics and Gynecology

I am an OB-GYN and a specialist in maternal-fetal medicine and high-risk obstetrics. My research and publications pertain mainly to the care of women with blood disorders (thrombosis and thrombophilia), bleeding disorders (including von Willebrand disease), platelet disorders (including ITP), and sickle cell disease.

Swamy

Geeta Krishna Swamy

Haywood Brown, MD Distinguished Professor of Women's Health

Dr. Geeta Swamy, MD, is Professor of Obstetrics and Gynecology in the Division of Maternal-Fetal Medicine, having served as the director of the Duke Perinatal Research Center and Vice Chair for Research and Faculty Development in the Department of ObGyn. She has achieved international acclaim as a clinician researcher and expert in the field of maternal immunization and perinatal infection. As a consultant to the World Health Organization, Dr. Swamy contributes her knowledge to advance international work to evaluate the immunogenicity, safety, and efficacy of vaccines in pregnant women. The American College of ObGyn has grown to be the “collective voice” for women’s health, and Dr. Swamy has been a leader within that organization for the last two decades. She currently serves as the Co-Principal Investigator for the NIH-NIAID Vaccine Treatment and Evaluation (VTEU) and CDC Clinical Immunization Safety Assessment. In addition, she has been a leader at Duke and nationally in promoting a culture of scientific integrity and transparency in research. She has been instrumental in developing and leading the School of Medicine’s research initiatives in administration, regulatory oversight, and compliance. In 2018, she became Vice Dean for Scientific Integrity in the School of Medicine and Associate Vice President for Research for Duke University. In these roles she oversees the Duke Office of Scientific Integrity (DOSI) which houses the Advancing Scientific Integrity, Services, & Training (ASIST) initiative, conflict of interest, clinical quality management, incident response in research, and research misconduct. She also oversees the Duke Office of Research Initiatives, the Duke Health IRB, Office of Research Administration (ORA), and Office of Research Contracts (ORC). 





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