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1.
Respir Physiol Neurobiol ; 183(3): 218-23, 2012 Sep 30.
Article in English | MEDLINE | ID: mdl-22771782

ABSTRACT

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular morbidity and mortality and hypercoagulability may be an underlying factor. We tested the hypotheses that patients with severe OSA are hypercoagulable and that two weeks of continuous positive airway pressure (CPAP) treatment reduces this hypercoagulability. In a prospective crossover study, twelve patients were randomized to either CPAP or no-CPAP for two weeks, a one week washout period, and then the other testing period for two weeks. Thromboelastography was used to assess coagulability at the start and end of each period and the apnoea-hypopnea indices (AHI) were measured at the end of each period. At baseline, ten patients had, compared to reference values, shorter clotting times, six increased rate of clot formation, twelve increased clot strength, and ten increased clotting indices. CPAP significantly reduced AHI (p=0.0003), clot strength (p=0.019) and clotting index (p=0.014). Hypercoagulability in patients with OSA can be detected by thromboelastography, and is reduced by CPAP.


Subject(s)
Continuous Positive Airway Pressure/methods , Severity of Illness Index , Sleep Apnea, Obstructive/therapy , Thrombelastography/methods , Thrombophilia/therapy , Adult , Cross-Over Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/physiopathology , Thrombophilia/diagnosis , Thrombophilia/physiopathology , Treatment Outcome
2.
Thromb Haemost ; 107(3): 438-47, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22234563

ABSTRACT

Spontaneous pregnancy loss is often associated with aberrant maternal inflammation and systemic coagulopathies. However, the role of inflammation in the development of obstetric coagulopathies is poorly understood. Further, questions remain as to whether systemic coagulopathies are linked to placental haemostatic alterations, and whether these local alterations contribute to a negative foetal outcome. Using a model of spontaneous foetal loss in which pregnant rats are given a single injection of bacterial lipopolysaccharide (LPS), we characterised the systemic maternal coagulation status following LPS administration using thromboelastography (TEG), a global haemostatic assay that measures the kinetics of clot formation. Systemic maternal coagulopathy was evident in 82% of LPS-treated rats. Specifically, we observed stage-I, -II, and -III disseminated intravascular coagulation (DIC) and hypercoagulability. Modulation of inflammation through inhibition of tumour necrosis factor α with etanercept resulted in a 62% reduction in the proportion of rats exhibiting coagulopathy. Moreover, inflammation-induced systemic coagulopathies were associated with placental haemostatic alterations, which included increased intravascular, decidual, and labyrinth fibrin deposition in cases of DIC-I and hypercoagulability, and an almost complete absence of fibrin deposition in cases of DIC-III. Furthermore, systemic and placental haemostatic alterations were associated with impaired utero-placental haemodynamics, and inhibition of these haemostatic alterations by etanercept was associated with maintenance of utero-placental haemodynamics. These findings indicate that modulation of maternal inflammation may be useful in the prevention of coagulopathies associated with complications of pregnancy.


Subject(s)
Abortion, Spontaneous/immunology , Disseminated Intravascular Coagulation/immunology , Inflammation/immunology , Placenta/metabolism , Pregnancy Complications, Hematologic/immunology , Abortion, Spontaneous/blood , Abortion, Spontaneous/chemically induced , Abortion, Spontaneous/drug therapy , Animals , Disease Models, Animal , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/chemically induced , Disseminated Intravascular Coagulation/drug therapy , Etanercept , Female , Hemostasis/drug effects , Humans , Immunoglobulin G/administration & dosage , Immunoglobulin G/adverse effects , Immunoglobulin G/pharmacology , Inflammation/blood , Inflammation/chemically induced , Inflammation/drug therapy , Lipopolysaccharides/administration & dosage , Male , Placenta/drug effects , Placenta/immunology , Placenta/pathology , Pregnancy , Pregnancy Complications, Hematologic/blood , Pregnancy Complications, Hematologic/chemically induced , Pregnancy Complications, Hematologic/drug therapy , Rats , Rats, Wistar , Receptors, Tumor Necrosis Factor/administration & dosage , Tumor Necrosis Factor-alpha/antagonists & inhibitors
3.
Semin Thromb Hemost ; 36(7): 738-46, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20978994

ABSTRACT

Pregnancy is a unique situation where significant physiological changes in all maternal organ systems take place. Most of these changes return to normal after delivery. During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability, thus decreasing bleeding complications at time of delivery. The pregnancy-associated hypercoagulability sets a foundation for hemostatic abnormalities during pregnancy and may be associated with pregnancy complications. Assessment of the hemostatic status in pregnancy and its complications can be critical to diagnosis and management not only within the obstetric ward but in trauma, anesthesia, and other situations. Conventional global tests such as prothrombin time and activated partial thromboplastin time cannot define this status appropriately, and full assessment requires measurements of several parameters. Thromboelastography (TEG) is a global hemostatic test that can analyze both coagulation and fibrinolysis. The technique has been available since the 1940s, but only recently has it shown great impact within the clinical practice arena. TEG measures the interactive dynamic coagulation process from the initial fibrin formation to platelet interaction and clot strengthening to fibrinolysis, which makes it superior to other conventional tests. In addition, TEG can guide therapy by documenting changes in coagulation in vitro before a therapy is instituted and also by helping the clinician make critical decisions. Despite the clear value as a test for monitoring hemostatic status of pregnancy-related complications, TEG is still underused for reasons such as poor awareness regarding the technique and interpretations, lack of full standardization, and the unavailability of large clinical studies. However, the fact remains that TEG is undoubtedly attractive to both researchers and clinicians, particularly in a point-of-care setting. We hope that much more investment is directed to TEG studies in both experimental and clinical fields to improve applications and promote use, especially with respect to clinical decision making in pregnancy-related complications.


Subject(s)
Hemostasis/physiology , Postpartum Period/blood , Pregnancy Complications, Hematologic/diagnosis , Pregnancy/blood , Thrombelastography/methods , Blood Coagulation Tests , Female , Humans
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