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The Journal of Trauma and Acute Care... Feb 2024Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury....
ABSTRACT
Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multifaceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. Trauma-induced coagulopathy may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, international normalized ratio, thrombin time, prothrombin time, and activated partial thromboplastin time; viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastography; or a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score. Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and tranexamic acid therapy. Early administration of prothrombin complex concentrate is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia.
LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Topics: Humans; Hypothermia; Blood Coagulation Disorders; Hemorrhage; Blood Coagulation Tests; Hemostasis; Thrombelastography; Wounds and Injuries
PubMed: 37828662
DOI: 10.1097/TA.0000000000004170 -
Journal of Thrombosis and Thrombolysis Jul 2023Oral factor Xa (FXa) inhibitors significantly reduce incidence of stroke and thromboembolic events in patients with atrial fibrillation or venous thromboembolism. Due to...
Real-world clinical outcomes among US Veterans with oral factor xa inhibitor-related major bleeding treated with andexanet alfa or 4-factor prothrombin complex concentrate.
Oral factor Xa (FXa) inhibitors significantly reduce incidence of stroke and thromboembolic events in patients with atrial fibrillation or venous thromboembolism. Due to various factors and the lack of a randomized controlled trial comparing andexanet alfa to usual care, non-specific replacement agents including 4 F-PCC are still used off-label for FXa inhibitor bleed management. Clinical and mortality data were extracted from the inpatient medical data and Veteran Affairs (VA) vital status files over the time of March 2014 through December 2020. Propensity score-weighted models were used for this retrospective cohort study using data from the Veterans Affairs Informatics and Computing Infrastructure (VINCI). The study included 255 patients (85-andexanet alfa and 170-4 F-PCC) exposed to an oral factor Xa inhibitor and hospitalized with an acute major, gastrointestinal (GI), intracranial (ICH) or other bleed. In-hospital mortality was significantly lower in the andexanet alfa cohort compared to the 4 F-PCC cohort (10.6% vs. 25.3%, p = 0.01). Propensity score-weighted Cox models reveal a 69% lower hazard of in-hospital mortality for those treated with andexanet alfa (HR 0.31, 95% CI 0.14-0.71) compared to those treated with 4 F-PCC. Additionally, those treated with andexanet alfa had a lower 30-day mortality rate and lower 30-day hazard of mortality in the weighted Cox model (20.0% vs. 32.4%, p = 0.039; HR 0.54, 95% CI 0.30-0.98) compared to those treated with 4 F-PCC. Among 255 US veterans with major bleeding in the presence of an oral factor Xa inhibitor, treatment with andexanet alfa was associated with lower in-hospital and 30-day mortality than treatment with 4 F-PCC.
Topics: Humans; Factor Xa; Factor Xa Inhibitors; Veterans; Retrospective Studies; Blood Coagulation Factors; Hemorrhage; Antithrombin III; Factor IX; Recombinant Proteins; Anticoagulants
PubMed: 37219827
DOI: 10.1007/s11239-023-02820-y -
Blood Coagulation & Fibrinolysis : An... Sep 2023The goal of this study was to describe hematologic and coagulation laboratory parameters and identify if these laboratory studies could predict blood loss in a cohort of... (Review)
Review
The goal of this study was to describe hematologic and coagulation laboratory parameters and identify if these laboratory studies could predict blood loss in a cohort of pediatric patients undergoing complex cranial vault reconstruction (CCVR) for repair of craniosynostosis. We reviewed records from 95 pediatric CCVR patients between 2015 and 2019. Primary outcome measures were hematologic and coagulation laboratory parameters. Secondary outcome measures were intraoperative and postoperative calculated blood loss (CBL). Preoperative laboratory values were within normal limits and did not predict outcomes. Intraoperative platelet count and fibrinogen predicted CBL but without clinically relevant thrombocytopenia or hypofibrinogenemia. Intraoperative prothrombin time (PT) and partial thromboplastin time (PTT) predicted perioperative CBL, possibly reflecting surgically induced coagulopathy. Postoperative laboratory values did not predict postoperative blood loss. We found that standard hematologic and coagulation laboratory parameters predicted intraoperative and postoperative blood loss but provided limited mechanistic information to improve our understanding of coagulopathy in craniofacial surgery.
Topics: Humans; Child; Blood Loss, Surgical; Blood Transfusion; Blood Coagulation Disorders; Blood Coagulation Tests; Postoperative Hemorrhage
PubMed: 37395200
DOI: 10.1097/MBC.0000000000001234 -
Current Opinion in Anaesthesiology Apr 2024The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive transfusion.
RECENT FINDINGS
Severe trauma patients require massive transfusion, but consensual international definitions for traumatic hemorrhage shock and massive transfusion are missing. Current literature defines a massive transfusion as transfusion of a minimum of 3-4 packed red blood cells within 1 h. Using standard laboratory and/or viscoelastic tests, earliest diagnosis and treatment should focus on trauma-induced coagulopathy and substitution of substantiated deficiencies.
SUMMARY
To initiate therapy immediately massive transfusion protocols are helpful focusing on early hemorrhage control using hemostatic dressing and tourniquets, correction of metabolic derangements to decrease coagulopathy and substitution according to viscoelastic assays and blood gases analysis with tranexamic acid, fibrinogen concentrate, red blood cells, plasma and platelets are recommended. Alternatively, the use of whole blood is possible. If needed, further support using prothrombin complex, factor XIII or desmopressin is suggested.
Topics: Humans; Hemorrhage; Blood Coagulation Disorders; Blood Coagulation Factors; Hemostatics; Blood Transfusion; Wounds and Injuries
PubMed: 38390985
DOI: 10.1097/ACO.0000000000001347 -
Annals of Laboratory Medicine Nov 2023Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT),... (Review)
Review
Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.
Topics: Humans; Hemostatics; Thrombosis; Thrombin; Prothrombin Time; Hemostasis
PubMed: 37387486
DOI: 10.3343/alm.2023.43.6.531 -
Thrombosis and Haemostasis Jun 2024Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or...
BACKGROUND
Venous thromboembolism (VTE) is predisposed by thrombotic mutations in patients with hereditary thrombophilia. Although prothrombin deficiencies caused by homozygous or compound heterozygous mutations are associated with bleeding diathesis, rare cases have shown a correlation between heterozygous prothrombin mutations and thrombosis.
MATERIAL AND METHODS
We surveyed genetic variants involved in thrombosis and hemostasis in 347 patients with unprovoked VTE or having a positive family history of thrombosis. For patients identified with heterozygous prothrombin mutations, we conducted family investigations and performed thrombin generation test (TGT) to elucidate the thrombotic risk. Novel mutants were expressed and subjected to functional assays to clarify the underlying thrombotic mechanisms.
RESULTS
Heterozygous prothrombin mutations were identified in 3.5% of patients (12/347), including three novel mutations Phe382Ser, Phe382Leu and Asp597Tyr found in one patient each, as well as previously reported Arg541Trp mutation in four patients and Arg596Gln mutation in five patients. A total of 42 mutation carriers were identified within the 12 pedigrees, among whom 64.3% (27/42) had experienced thrombotic events. TGT results demonstrated hypercoagulability for carriers of the five mutations, with Arg596Gln showing the highest thrombin generation potential followed by Arg541Trp. The Phe382-associated mutations severely impaired thrombomodulin binding ability of thrombin, resulting in obviously reduced protein C (PC) activation. The Asp597Tyr mutation exhibited a mild reduction in both antithrombin inhibition and PC activation reactions.
CONCLUSIONS
The presence of heterozygous prothrombin mutations represents a potential genetic predisposition for VTE. All thrombosis associated mutations potentiate coagulation activity by either conferring antithrombin resistance and/or impairing PC pathway activity.
PubMed: 38914130
DOI: 10.1055/a-2350-8338 -
Arteriosclerosis, Thrombosis, and... Oct 2023Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome characterized by platelet anti-PF4 (platelet-activating antiplatelet factor 4)-related...
BACKGROUND
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome characterized by platelet anti-PF4 (platelet-activating antiplatelet factor 4)-related thrombosis. Platelet-neutrophil interaction has been suggested to play a role, but the underlying mechanism has not been fully elucidated.
METHODS
The study included 10 patients with VITT after ChAdOx1 (chimpanzee adenovirus Oxford 1) nCoV-19 (Oxford-AstraZeneca) vaccine administration, 10 patients with ischemic stroke (IS), 10 patients with acute deep vein thrombosis, and 10 control subjects in whom blood levels of neutrophil extracellular traps (NETs), soluble TF (tissue factor), and thrombin generation were examined. Furthermore, we performed in vitro studies comparing the effect of serum from patients and controls on NETs formation. Finally, immunohistochemistry was performed in cerebral thrombi retrieved from a patients with VITT and 3 patients with IS.
RESULTS
Compared with patients with IS, patients with deep vein thrombosis, controls, and patients with VITT had significantly higher blood values of CitH3 (citrullinated histone H3), soluble TF, D-dimer, and prothrombin fragment 1+2 (<0.0001). Blood CitH3 significantly correlated with blood soluble TF (Spearman rank correlation coefficient=0.7295; =0.0206) and prothrombin fragment 1+2 (Spearman rank correlation coefficient=0.6809; <0.0350) in patients with VITT. Platelet-neutrophil mixture added with VITT plasma resulted in higher NETs formation, soluble TF and thrombin generation, and platelet-dependent thrombus growth under laminar flow compared with IS and deep vein thrombosis plasma; these effects were blunted by PAD4 (protein arginine deiminase 4) and cathepsin G inhibitors, anti-FcγRIIa (Fc receptor for IgG class IIa), and high doses of heparin. Immunohistochemistry analysis showed a more marked expression of PAD4 along with more diffuse neutrophil infiltration and NETs formation as well as TF and cathepsin expression in VITT thrombus compared with thrombi from patients with IS.
CONCLUSIONS
Patients with VITT display enhanced thrombogenesis by PAD4-mediated NETs formation via cathepsin G-mediated platelet/neutrophil interaction.
Topics: Humans; Neutrophils; Cathepsin G; Thrombin; Thrombosis; Vaccines; Thrombocytopenia
PubMed: 37586040
DOI: 10.1161/ATVBAHA.123.319522 -
International Journal of Laboratory... May 2024Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease characterized by thrombotic manifestations and/or obstetric complications in patients with persistently positive antiphospholipid antibodies (aPL). aPL are a heterogeneous group of autoantibodies, but only lupus anticoagulant, anticardiolipin (aCL), and antibeta2-glycoprotein I antibodies (aβ2GPI) IgG or IgM are included as laboratory classification criteria. Seronegative APS patients are usually defined as patients with the clinical symptoms of APS but who test negative for aPL. The negativity to classic aPL criteria does not exclude the presence of other aPL. Several noncriteria aPL have been identified. Some noncriteria aPL are well studied, such as IgA aCL and aβ2GPI, the antiphosphatidylserine-prothrombin (aPS/PT) antibodies, and the antibodies against the domain I of beta2-glycoprotein I (aDI), both latter groups receiving more attention for their role in thrombotic events and pregnancy complications. Other noncriteria aPL that have been studied are antibodies against annexin V, prothrombin, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, vimentin-cardiolipin complex, anti-protein S/protein C. Measurement of some of these noncriteria aPL (aPS/PT, aDI) is useful in the laboratory work-out of APS in specific situations. We have to differentiate between patients who are positive for noncriteria aPL only, and patients who have both criteria and noncriteria aPL to enable us to study their role in the diagnosis or risk stratification of APS. The research on noncriteria aPL is continually developing as the clinical relevance of these antibodies is not yet fully clarified.
Topics: Humans; Antiphospholipid Syndrome; Antibodies, Antiphospholipid; Female; Pregnancy; Thrombosis; beta 2-Glycoprotein I; Autoantibodies
PubMed: 38584293
DOI: 10.1111/ijlh.14268 -
Biomedicines Jan 2024The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and... (Review)
Review
The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.
PubMed: 38397876
DOI: 10.3390/biomedicines12020274