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British Journal of Anaesthesia Dec 2015The process of haemostasis is complex and is further complicated in the parturient because of the physiological changes of pregnancy. Understanding these changes and the... (Review)
Review
The process of haemostasis is complex and is further complicated in the parturient because of the physiological changes of pregnancy. Understanding these changes and the impact that they have on the safety profile of the anaesthetic options for labour and delivery is crucial to any anaesthetist caring for the parturient. This article analyses current theories on coagulation and reviews the physiological changes to coagulation that occur during pregnancy and the best methods with which to evaluate coagulation. Finally, we examine some of the more common disorders of coagulation that occur during pregnancy, including von Willebrand disease, common factor deficiencies, platelet disorders, the parturient on anticoagulants, and the more rare acute fatty liver of pregnancy, with a focus on their implications for neuraxial anaesthesia.
Topics: Anesthesia, Obstetrical; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Disorders, Inherited; Blood Coagulation Tests; Female; Hemostasis; Humans; Pregnancy; Pregnancy Complications, Hematologic
PubMed: 26658204
DOI: 10.1093/bja/aev374 -
International Journal of Molecular... Mar 2022Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases... (Review)
Review
Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.
Topics: Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; COVID-19; COVID-19 Vaccines; Combined Modality Therapy; Disease Management; Disease Susceptibility; Fibrinolysis; Humans; Prognosis; SARS-CoV-2; Treatment Outcome
PubMed: 35328761
DOI: 10.3390/ijms23063338 -
International Journal of Molecular... Nov 2022Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is...
Bleeding tendency, a prominent feature of patients with Gaucher disease (GD), is associated with abnormal platelet function. Brain-derived neurotrophic factor (BDNF) is a protein with neuroprotective potential stored in alpha granules of circulating platelets. Here we studied BDNF levels in 50 patients with type I GD (GD1) and their correlation with platelet activity and bleeding tendency. Flow cytometry was used to test unstimulated and stimulated measurement of platelet surface-activated expression of αIIbβ3 integrin, P-selectin and lysosomal-associated membrane protein (LAMP3/CD63). Serum and plasma BDNF levels were quantified using ELISA. The bleeding history was recorded by a bleeding questionnaire. Serum BDNF levels were positively correlated with platelet count and moderately correlated with unstimulated and stimulated platelet P-selectin expression. Patients with more than one bleeding manifestation were shown to have lower serum BDNF levels, albeit similar platelet count. Plasma BDNF levels were significantly elevated in splenectomized patients and showed a moderate positive correlation with stimulated platelet CD63 expression. These observations demonstrate the first association between BDNF levels in the peripheral blood with platelet dysfunction and increased bleeding manifestation. The role of measuring serum BDNF for assessing platelet alpha degranulation defects and bleeding risk in patients with GD and the general population needs further study.
Topics: Humans; Blood Platelets; Brain-Derived Neurotrophic Factor; P-Selectin; Gaucher Disease; Blood Coagulation Disorders; Hemorrhage
PubMed: 36430458
DOI: 10.3390/ijms232213982 -
Current Opinion in Anaesthesiology Apr 2015Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the... (Review)
Review
PURPOSE OF REVIEW
Sepsis, defined by the presence of infection and host inflammation, is a lethal clinical syndrome with an increasing mortality rate worldwide. In severe disease, the coagulation system becomes diffusely activated, with consumption of multiple clotting factors resulting in disseminated intravascular coagulation (DIC). When present, DIC portends a higher mortality rate. Understanding the mechanisms that tie inflammation and diffuse thrombosis will allow therapeutic interventions to be developed. The coagulopathy of acute sepsis is a dynamic process that is time and disease burden specific. Whole-blood testing of coagulation may provide more clinically useful information than the classical tests. Natural anticoagulants that regulate thrombosis are downregulated in sepsis. Patients may benefit from the modulation of the coagulation system when systemic inflammation and hypercoagulopathy exist. Proper timing of anticoagulant therapy may ultimately lead to decreased incidence of multisystem organ dysfunction.
RECENT FINDINGS
The pathogenesis of coagulopathy in sepsis is driven by an upregulation of procoagulant mechanisms and simultaneous downregulation of natural anticoagulants. Inflammation caused by the invading organism is a natural host defense that cannot be eliminated during treatment. Successful strategies to prevent multisystem organ dysfunction center on stratifying patients at high risk for DIC and restoring the balance of inflammation and coagulation.
SUMMARY
The prevention of DIC in septic patients is a key therapeutic target in preventing death from multisystem organ failure. Stratifying patients for therapy using thromboelastometry, specific markers for DIC, and composite scoring systems is an area of growing research.
Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Humans; Multiple Organ Failure; Sepsis; Thrombosis
PubMed: 25590467
DOI: 10.1097/ACO.0000000000000163 -
European Journal of Trauma and... Jun 2016Paediatric trauma is the leading cause of mortality in children. Paediatric trauma resuscitation is the first and foremost step towards a successful treatment and... (Review)
Review
PURPOSE
Paediatric trauma is the leading cause of mortality in children. Paediatric trauma resuscitation is the first and foremost step towards a successful treatment and subsequent recovery. Significant advances have taken place in the last years in relation to this field of trauma care.
METHODS
In this narrative review, we attempt to summarise the recent development in the concepts of fluid resuscitation, massive transfusion, permissive resuscitation, management of coagulopathy and use of tranexamic acid, literature pertaining to implementation of transfusion protocols in the paediatric population and education related to the paediatric trauma resuscitation.
RESULTS/CONCLUSIONS
The current evidence although emerging is still sparse and high-quality studies are needed to shed more light on most of the above domains of resuscitation.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Transfusion; Child; Clinical Protocols; Evidence-Based Medicine; Fluid Therapy; Humans; Injury Severity Score; Resuscitation; Tranexamic Acid; Wounds and Injuries
PubMed: 26696087
DOI: 10.1007/s00068-015-0614-9 -
Haemophilia : the Official Journal of... Sep 2021There is a growing interest in natural anticoagulants as a cause of mild to moderate bleeding disorders (MBDs), particularly in patients with bleeding of unknown cause... (Review)
Review
INTRODUCTION
There is a growing interest in natural anticoagulants as a cause of mild to moderate bleeding disorders (MBDs), particularly in patients with bleeding of unknown cause (BUC), which is defined as having a mild to moderate bleeding phenotype without a definite diagnosis despite exhaustive and repeated laboratory investigations. Recently, abnormalities in two natural anticoagulant pathways, thrombomodulin (TM), and tissue factor pathway inhibitor (TFPI), were identified in single patients or families as the underlying cause for a bleeding tendency.
AIM
The objective of this review is to discuss the current understanding of the role of natural anticoagulants in MBDs using available clinical and translational data.
METHODS
A Cochrane Library and PubMed (MEDLINE) search focusing on selected natural anticoagulants and their role in MBDs was conducted.
RESULTS
Data on the influence of natural anticoagulants including protein C, protein S, antithrombin, TM, and TFPI or factors with anticoagulant properties like fibrinogen gamma prime (γ') on MBDs are scarce. Observations from sepsis treatment and from translational research highlight their importance as regulators of the haemostatic balance, especially via the activated protein C-related pathway, and suggest a role in some MBDs.
CONCLUSION
Similar to the distinct genetic variants of natural anticoagulants linked to thrombosis, we hypothesize that novel variants may be associated with a bleeding tendency and could be identified using next generation sequencing.
Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Tests; Hemorrhage; Humans; Thrombosis
PubMed: 34110661
DOI: 10.1111/hae.14356 -
Journal of Thrombosis and Haemostasis :... Jul 2011Patients affected by bleeding disorders present a wide spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency to significant episodes. Women... (Review)
Review
Patients affected by bleeding disorders present a wide spectrum of clinical symptoms that vary from a mild or moderate bleeding tendency to significant episodes. Women with inherited bleeding disorders are particularly disadvantaged since, in addition to suffering from general bleeding symptoms, they are also at risk of bleeding complications from regular haemostatic challenges during menstruation, pregnancy and childbirth. Moreover, such disorders pose important problems for affected women due to their reduced quality of life caused by limitations in activities and work, and alteration of their reproductive life. These latter problems include excessive menstrual bleeding or menorrhagia, miscarriage, bleeding complications during pregnancy and after delivery and their related complications such as acute or chronic anaemia. The management of these women is difficult because of considerable inter-individual variation. Moreover, reliable information on clinical management is scarce, only a few available long term prospective studies of large cohorts provide evidence-based guideline about diagnosis and treatment.
Topics: Blood Coagulation Disorders; Delivery, Obstetric; Diagnosis, Differential; Female; Genetic Counseling; Humans; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Diagnosis; Uterine Hemorrhage
PubMed: 21781260
DOI: 10.1111/j.1538-7836.2011.04372.x -
Shock (Augusta, Ga.) Jun 2014Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric... (Review)
Review
Trauma remains the leading cause of morbidity and mortality in the United States among children aged 1 to 21 years. The most common cause of lethality in pediatric trauma is traumatic brain injury. Early coagulopathy has been commonly observed after severe trauma and is usually associated with severe hemorrhage and/or traumatic brain injury. In contrast to adult patients, massive bleeding is less common after pediatric trauma. The classical drivers of trauma-induced coagulopathy include hypothermia, acidosis, hemodilution, and consumption of coagulation factors secondary to local activation of the coagulation system after severe traumatic injury. Furthermore, there is also recent evidence for a distinct mechanism of trauma-induced coagulopathy that involves the activation of the anticoagulant protein C pathway. Whether this new mechanism of posttraumatic coagulopathy plays a role in children is still unknown. The goal of this review is to summarize the current knowledge on the incidence and potential mechanisms of coagulopathy after pediatric trauma and the role of rapid diagnostic tests for early identification of coagulopathy. Finally, we discuss different options for treating coagulopathy after severe pediatric trauma.
Topics: Adolescent; Adult; Blood Coagulation; Blood Coagulation Disorders; Child; Child, Preschool; Hemorrhage; Humans; Infant; Injury Severity Score; Pediatrics; Wounds and Injuries; Young Adult
PubMed: 24569507
DOI: 10.1097/SHK.0000000000000151 -
Journal of Thrombosis and Haemostasis :... Aug 2012Understanding the mechanism of action of normal hemostasis and how the bypassing agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived activated... (Review)
Review
Understanding the mechanism of action of normal hemostasis and how the bypassing agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived activated prothrombin complex concentrate (Factor Eight Inhibitor Bypassing Agent [FEIBA]) control abnormal bleeding is imperative for healthcare professionals who treat patients with hemophilia and other bleeding disorders. A cell-based model has improved our understanding of in vivo mechanisms of hemostasis and the basis of the bleeding tendency in hemophilia. Bypassing agents do not restore the normal pathways of hemostasis in hemophilia, but rather boost thrombin generation in spite of a lack of platelet surface FVIIIa-FIXa ('tenase') activity. Thus, the common clinical laboratory coagulation assays do not reflect the clinically relevant hemostatic activity of bypassing agents, and no validated assay is available with which to measure the in vivo efficacy of these agents or predict individual patient responses to treatment. Global hemostasis assays measuring overall coagulation capacity have potential for assessment of the effects of bypassing agents. This review will focus on the mechanisms of clotting and their relationship to understanding the mechanisms of action of the bypassing agents in vivo and the methodologies that are emerging to monitor the clinical efficacy of bypassing agent therapy.
Topics: Animals; Blood Coagulation Factors; Blood Coagulation Tests; Drug Monitoring; Factor VIIa; Hemophilia A; Hemostasis; Hemostatics; Humans; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome
PubMed: 22632160
DOI: 10.1111/j.1538-7836.2012.04793.x -
Haemophilia : the Official Journal of... Nov 2021A massive increase of soluble thrombomodulin (sTM) due to variants in the thrombomodulin gene (THBD) has recently been identified as a novel bleeding disorder.
INTRODUCTION
A massive increase of soluble thrombomodulin (sTM) due to variants in the thrombomodulin gene (THBD) has recently been identified as a novel bleeding disorder.
AIM
To investigate sTM levels and underlying genetic variants as a cause for haemostatic impairment and bleeding in a large number of patients with a mild to moderate bleeding disorder (MBD), including patients with bleeding of unknown cause (BUC).
PATIENTS AND METHODS
In 507 MBD patients, sTM levels, thrombin generation and plasma clot formation were measured and compared to 90 age- and sex-matched healthy controls. In patients, genetic analysis of the THBD gene was performed.
RESULTS
No difference in sTM levels between patients and controls was found overall (median ([IQR] 5.0 [3.8-6.3] vs. 5.1 [3.7-6.4] ng/ml, p = .762), and according to specific diagnoses of MBD or BUC, and high sTM levels (≥95th percentile of healthy controls) were not overrepresented in patients. Soluble TM levels had no impact on bleeding severity or global tests of haemostasis, including thrombin generation or plasma clot formation. In the THBD gene, no known pathogenic or novel disease-causing variants affecting sTM plasma levels were identified in our patient cohort.
CONCLUSION
TM-associated coagulopathy appears to be rare, as it was not identified in our large cohort of patients with MBD. Soluble TM did not arise as a risk factor for bleeding or altered haemostasis in these patients.
Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Hemorrhagic Disorders; Humans; Thrombin; Thrombomodulin
PubMed: 34628704
DOI: 10.1111/hae.14433