New fundamentals in hemostasis Versteeg, Henri H; Heemskerk, Johan W M; Levi, Marcel ...
Physiological reviews
93, Številka:
1
Journal Article
Recenzirano
Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a plethora of vascular and ...extravascular receptors that act in concert with blood components to seal off the damage inflicted to the vasculature and the surrounding tissue. The first important component that contributes to hemostasis is the coagulation system, while the second important component starts with platelet activation, which not only contributes to the hemostatic plug, but also accelerates the coagulation system. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors and proteolytic feedback loops. This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation. It further speculates on the (patho)physiological roles of intra- and extravascular receptors that operate in response to these proteases. Furthermore, this review provides a new framework for understanding how signaling and adhesive interactions between endothelial cells, leukocytes, and platelets can regulate thrombus formation and modulate the coagulation process. Now that the key molecular players of coagulation and platelet activation have become clear, and their complex interactions with the vessel wall have been mapped out, we can also better speculate on the causes of thrombosis-related angiopathies.
Disorders of coagulation in pregnancy Katz, D.; Beilin, Y.
British journal of anaesthesia : BJA,
December 2015, 20151201, 2015-Dec, 2015-12-00, Letnik:
115, Številka:
suppl_2
Journal Article
Recenzirano
Odprti dostop
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.
Background
Few observations exist with respect to the pro‐coagulant profile of patients with COVID‐19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce ...but suggestive for a clinical relevance of the problem.
Objectives
Prospective observational study aimed to characterize the coagulation profile of COVID‐19 ARDS patients with standard and viscoelastic coagulation tests and to evaluate their changes after establishment of an aggressive thromboprophylaxis.
Methods
Sixteen patients with COVID‐19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases.
Results
At baseline, the patients showed a pro‐coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35‐63), platelet contribution to CS (PCS, 43 hPa; interquartile range 24‐45), fibrinogen contribution to CS (FCS, 12 hPa; interquartile range 6‐13.5) elevated D‐dimer levels (5.5 μg/mL, interquartile range 2.5‐6.5), and hyperfibrinogenemia (794 mg/dL, interquartile range 583‐933). Fibrinogen levels were associated (R2 = .506, P = .003) with interleukin‐6 values. After increasing the thromboprophylaxis, there was a significant (P = .001) time‐related decrease of fibrinogen levels, D‐dimers (P = .017), CS (P = .013), PCS (P = .035), and FCS (P = .038).
Conclusion
The pro‐coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.
Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial ...sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.
Essentials
ClotChip is a novel microsensor for comprehensive assessment of ex vivo hemostasis.
Clinical samples show high sensitivity to detecting the entire hemostatic process.
ClotChip readout ...exhibits distinct information on coagulation factor and platelet abnormalities.
ClotChip has potential as a point‐of‐care platform for comprehensive hemostatic analysis.
Summary
Background
Rapid point‐of‐care (POC) assessment of hemostasis is clinically important in patients with a variety of coagulation factor and platelet defects who have bleeding disorders.
Objective
To evaluate a novel dielectric microsensor, termed ClotChip, which is based on the electrical technique of dielectric spectroscopy for rapid, comprehensive assessment of whole blood coagulation.
Methods
The ClotChip is a three‐dimensional, parallel‐plate, capacitive sensor integrated into a single‐use microfluidic channel with miniscule sample volume (< 10 μL). The ClotChip readout is defined as the temporal variation in the real part of dielectric permittivity of whole blood at 1 MHz.
Results
The ClotChip readout exhibits two distinct parameters, namely, the time to reach a permittivity peak (Tpeak) and the maximum change in permittivity after the peak (Δεr,max), which are, respectively, sensitive towards detecting non‐cellular (i.e. coagulation factor) and cellular (i.e. platelet) abnormalities in the hemostatic process. We evaluated the performance of ClotChip using clinical blood samples from 15 healthy volunteers and 12 patients suffering from coagulation defects. The ClotChip Tpeak parameter exhibited superior sensitivity at distinguishing coagulation disorders as compared with conventional screening coagulation tests. Moreover, the ClotChip Δεr,max parameter detected platelet function inhibition induced by aspirin and exhibited strong positive correlation with light transmission aggregometry.
Conclusions
This study demonstrates that ClotChip assesses multiple aspects of the hemostatic process in whole blood on a single disposable cartridge, highlighting its potential as a POC platform for rapid, comprehensive hemostatic analysis.
There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are common and contribute to organ ...failure and mortality. Patients with severe COVID-19 present with hemostatic abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis, with the major difference being increased risk of thrombosis rather than bleeding. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2. RNA sequencing demonstrated distinct changes in the gene-expression profile of circulating platelets of COVID-19 patients. Pathway analysis revealed differential gene-expression changes in pathways associated with protein ubiquitination, antigen presentation, and mitochondrial dysfunction. The receptor for SARS-CoV-2 binding, angiotensin-converting enzyme 2 (ACE2), was not detected by messenger RNA (mRNA) or protein in platelets. Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared with healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that SARS-CoV-2 infection is associated with platelet hyperreactivity, which may contribute to COVID-19 pathophysiology.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent pathogen responsible for the coronavirus disease 2019 (COVID-19). Since its emergence, the novel coronavirus has rapidly ...achieved pandemic proportions causing remarkably increased morbidity and mortality around the world. A hypercoagulability state has been reported as a major pathologic event in COVID-19, and thromboembolic complications listed among life-threatening complications of the disease. Platelets are chief effector cells of hemostasis and pathological thrombosis. However, the participation of platelets in the pathogenesis of COVID-19 remains elusive. This report demonstrates that increased platelet activation and platelet-monocyte aggregate formation are observed in severe COVID-19 patients, but not in patients presenting mild COVID-19 syndrome. In addition, exposure to plasma from severe COVID-19 patients increased the activation of control platelets ex vivo. In our cohort of COVID-19 patients admitted to the intensive care unit, platelet-monocyte interaction was strongly associated with tissue factor (TF) expression by the monocytes. Platelet activation and monocyte TF expression were associated with markers of coagulation exacerbation as fibrinogen and D-dimers, and were increased in patients requiring invasive mechanical ventilation or patients who evolved with in-hospital mortality. Finally, platelets from severe COVID-19 patients were able to induce TF expression ex vivo in monocytes from healthy volunteers, a phenomenon that was inhibited by platelet P-selectin neutralization or integrin αIIb/β3 blocking with the aggregation inhibitor abciximab. Altogether, these data shed light on new pathological mechanisms involving platelet activation and platelet-dependent monocyte TF expression, which were associated with COVID-19 severity and mortality.
Coagulopathy in COVID‐19 Iba, Toshiaki; Levy, Jerrold H.; Levi, Marcel ...
Journal of thrombosis and haemostasis,
September 2020, Letnik:
18, Številka:
9
Journal Article
Recenzirano
Odprti dostop
The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation ...(DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.
Traumatic brain injury (TBI)–induced coagulopathy is a common and well-recognized risk for poor clinical outcomes, but its pathogenesis remains poorly understood, and treatment options are limited ...and ineffective. We discuss the recent progress and knowledge gaps in understanding this lethal complication of TBI. We focus on (1) the disruption of the brain-blood barrier to disseminate brain injury systemically by releasing brain-derived molecules into the circulation and (2) TBI-induced hypercoagulable and hyperfibrinolytic states that result in persistent and delayed intracranial hemorrhage and systemic bleeding.
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