Studies of the Primate Inflammatory Hemostatic Axis and Its Response to Inflammatory Mediators
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Figure 1A shows the four functional domains of the hemostatic system. The anticoagulant and coagulant domains acting through the vascular endothelium and platelets, respectively, compete to control clot formation. The fibrinolytic and antifibrinolytic domains compete in the same manner to control clot removal. All four domains respond to thrombin through its action on the vascular endothelium, platelets, and fibrinogen (2). The key to understanding this integrated system is that there is a hierarchy of responses to thrombin. The vascular endothelium and its associated anticoagulant/fibrinolytic domains are the most responsive, platelets are next, and fibrinogen is the last and least responsive. Under normal circumstances the small amounts of thrombin that are generated “spontaneously” in the microvasculature bind to receptors on the vascular endothelium such as thrombomodulin (TM) (3,4). These interactions lead to the generation of activated protein C (APC) (3) and the release of tissue plasminogen activator (t-PA) (5,6). The activated protein C inhibits further production of thrombin by inactivating factors Va and Villa in a negative feedback (3,4). The tissue plasminogen activator lyses any fibrin (fdp) that might have formed by activating plasminogen to plasmin (7).
Von Willebrand Disease
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
There is an increased risk of both primary (within 24 hours of delivery) and secondary (>24 hours after delivery) postpartum hemorrhage. vWF and factor VIII levels return to baseline 1–3 weeks following delivery, thus close monitoring and additional doses of DDAVP or vWF/factor VIII concentrates may be warranted [15]. Oral antifibrinolytic therapy can also be used to prevent delayed postpartum bleeding [11]. Patients with type 2B VWD also have an increased risk of morbidity related to primary and secondary postpartum hemorrhage as well as severe thrombocytopenia [16]. Products that inhibit platelet adhesion, such as nonsteroidal anti-inflammatory drugs, should be avoided [8]. As the neonate has up to a 50% chance of having VWD, circumcision should be delayed until VWD status is determined [8].
Obstetric Hemorrhage II: Postpartum Hemorrhage
Lauren A. Plante in Expecting Trouble, 2018
There are acquired coagulopathic conditions such as disseminated intravascular coagulopathy (DIC), which is not only most commonly due to hemorrhage, but can also develop after a large placental abruption, sepsis, severe preeclampsia, and amniotic fluid embolism. Importantly, DIC is initially a clinical diagnosis based on various observations of diffuse bleeding from previously hemostatic sites, from venipuncture sites and from other surfaces. Laboratory studies can help confirm the diagnosis, but waiting for results should not delay interventions (Table 14.6). A rapid bedside assessment of a coagulation abnormality can be performed using an extra red top tube of blood that is set aside. Nonclotting of the blood in 8–10 minutes suggests delayed clot formation suggesting a coagulation abnormality. When DIC is suspected, blood and coagulation product replacement should begin immediately and aggressively with the activation of a massive transfusion protocol (Table 14.4). The use of tranexamic acid as an antifibrinolytic therapy may reduce maternal mortality from obstetric hemorrhage when used early if initial medical interventions have failed (21,22).
The clinical management of factor XI deficiency in pregnant women
Published in Expert Review of Hematology, 2020
Allison P. Wheeler, Celeste Hemingway, David Gailani
Antifibrinolytic therapy is frequently used in persons with and without bleeding disorders to enhance hemostasis. The lysine-mimetics tranexamic acid and ε-amino caproic acid interfere with plasminogen binding to fibrin and formation of plasmin, the enzyme primarily responsible for enzymatic degradation of clots. Dosing varies based on the clinical circumstance and administration route. Tranexamic acid is a Category B medication (animal studies fail to demonstrate fetal risk), and is effective for routine treatment of postpartum hemorrhage in patients without bleeding disorders. In the WOMAN trial, an international randomized controlled study, the risks of hemorrhage-related death and laparotomy were reduced when tranexamic acid was given shortly (<3 hours) after postpartum hemorrhage [45]. There was no increase in thrombotic events. A 2015 meta-analysis concluded that tranexamic acid given prophylactically with vaginal or cesarean delivery reduces the risk of postpartum hemorrhage and blood transfusion [46]. Obstetric [47], trauma [48], and orthopedic [49] studies have demonstrated a low risk of thrombosis with tranexamic acid use.
Safety and efficacy of tranexamic acid in spinal canal tumors: a retrospective cohort study
Published in British Journal of Neurosurgery, 2020
Heng Zhu Zhang, Lun Dong, Huan Ming Wang, Fei Hu, Qiang Shao, Xu Chen, Lang Chen
Currently, the main antifibrinolytic drugs used are aprotinin, acidum tranexamicum (TXA), 6-aminocaproic acid, and para-aminomethylbenzoic acid. Because of complications associated with peptides, there are few clinical applications except TXA. In addition, acidum tranexamicum competitively combines with profibrinolysin, thereby not allowing profibrinolysin to combine with the fibrin, which contains multiple lysine residues. Thus, profibrinolysin cannot be converted to plasmin to achieve hemostasis.10 There are three options for the use of TXA: before, during, and after surgery. One study11 showed that preoperative intravenous injection of TXA is more suitable because fibrinolytic activation is an enzymatic cascade process that is easily inhibited during the early stages. The appropriate TXA dosage is not clear. The reported preoperative dosage range is 10–150 mg/kg, and that used for maintenance during the operation is 1–100 mg/kg per hour.2,12 In this study, lower doses of TXA were given both preoperatively and intraoperatively, taking into account the patient’s safety.
Disseminated intravascular coagulation in children with cancer: A systematic review
Published in Pediatric Hematology and Oncology, 2020
Christine Kongstad, Torben Stamm Mikkelsen, Anne-Mette Hvas
Supportive treatment regimens of DIC were reported in ten articles.25,27–31,36–39 Unfractionated heparin27,29,30,36,37,39 and recombinant thrombomodulin were used as anticoagulant treatment.38 Substitution therapy included transfusion of platelet concentrate,25,27,28,30,38 fresh frozen plasma28,30,38 and cryoprecipitate.28 Antifibrinolytic treatment with tranexamic acid was only administrated in one cohort study by Rovelli et al.30