fibrin and Venous-Thromboembolism

Plasma D-dimer, a special cross-linked fibrin derivative, is produced when fibrin is degraded by plasminase. During pregnancy, D-dimer increases along with the increase of gestational age, and the reference value of plasma D-dimer (≤0.5 mg/L) traditionally used for the screening of venous thrombosis in the normal population is not applicable to the pregnant population. Due to the lack of uniform D-dimer detection methods or measurement units, there is currently no unified D-dimer reference values for pregnancy or puerperium. Each region or laboratory should establish its own pregnancy D-dimer reference value for different gestational weeks through blood coagulation function testing of large numbers of samples of different gestational periods. More and more studies have been conducted to investigate the association between D-dimer and venous thromboembolism (VTE) during pregnancy, gestational hypertensive disorders (GHD) and pregnancy outcome. We reviewed, herein, the generation and measurement of D-dimer, the reference values of D-dimer during normal pregnancy, and the association between D-dimer and some pathological pregnancies, intending to help clinicians develop a more thorough understanding of D-dimer during pregnancy.

Topics: Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Pregnancy; Reference Values; Venous Thromboembolism

As the third most common vascular disease, venous thromboembolism is associated with significant mortality and morbidity. Pathogenesis underlying venous thrombosis is still not fully understood. Accumulating data suggest fibrin network structure and factor XIII-mediated crosslinking are major determinants of venous thrombus mass, composition, and stability. Understanding the cellular and molecular mechanisms mediating fibrin(ogen) and factor XIII production and function and their ability to influence venous thrombosis and resolution may inspire new anticoagulant strategies that target these proteins to reduce or prevent venous thrombosis in certain at-risk patients. This article summarizes fibrinogen and factor XIII biology and current knowledge of their function during venous thromboembolism.

Topics: Blood Coagulation; Factor XIII; Fibrin; Fibrinogen; Hemostatics; Humans; Thrombosis; Venous Thromboembolism; Venous Thrombosis

Coagulation factor XIII (FXIII) is converted by thrombin into its active form, FXIIIa, which crosslinks fibrin fibers, rendering clots more stable and resistant to degradation. FXIII affects fibrin clot structure and function leading to a more prothrombotic phenotype with denser networks, characterizing patients at risk of venous thromboembolism (VTE). Mechanisms regulating FXIII activation and its impact on fibrin structure in patients with acute VTE encompassing pulmonary embolism (PE) or deep vein thrombosis (DVT) are poorly elucidated. Reduced circulating FXIII levels in acute PE were reported over 20 years ago. Similar observations indicating decreased FXIII plasma activity and antigen levels have been made in acute PE and DVT with their subsequent increase after several weeks since the index event. Plasma fibrin clot proteome analysis confirms that clot-bound FXIII amounts associated with plasma FXIII activity are decreased in acute VTE. Reduced FXIII activity has been associated with impaired clot permeability and hypofibrinolysis in acute PE. The current review presents available studies on the role of FXIII in the modulation of fibrin clot properties during acute PE or DVT and following these events. Better understanding of FXIII's involvement in the pathophysiology of acute VTE might help to improve current therapeutic strategies in patients with acute VTE.

Topics: Acute Disease; Anticoagulants; Blood Coagulation; Factor XIII; Fibrin; Fibrinolysis; Genetic Variation; Humans; Models, Cardiovascular; Venous Thromboembolism

The number of people infected with human immunodeficiency virus (HIV) is rapidly increasing and the majority of those infected are living in sub-Saharan Africa. Some hallmarks of HIV are inflammation and upregulation of inflammatory markers. A pathological coagulation system may accompany these inflammatory changes and potentially result in venous thromboembolism such as a deep vein thrombosis (DVT). In this review, the authors describe the inflammatory profile in HIV, the treatment regimens currently in place in South Africa, and in particular how HIV affects the hematological system, with specific focus on platelets, red blood cells (RBCs; erythrocytes), and fibrin(ogen). They also discuss the presence of DVT in HIV, focus on screening tests, and suggest a more proactive approach to track the inflammatory profile of HIV patients, by specifically using parameters that might point to pathological coagulation; these should involve platelet, RBC, and fibrin(ogen) analysis. They conclude by suggesting that including coagulation function tests to study the effect of treatment interventions would improve outcomes in these individuals, as it could help in the diagnosis of thromboembolic disease. Furthermore, this approach could streamline treatment strategies due to improved monitoring. A better understanding of hypercoagulability of HIV-infected patients is therefore urgently needed. In conclusion, the authors suggest a panel of pathology tests that should be considered as standard procedures when HIV is present.

Topics: Africa, Southern; Anti-HIV Agents; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; HIV Infections; Humans; Venous Thromboembolism; Venous Thrombosis

Topics: Fibrin; Fibrinolysis; Fibrinolytic Agents; Histone Acetyltransferases; Humans; Hypertension, Pulmonary; Risk Factors; TATA-Binding Protein Associated Factors; Transcription Factor TFIID; Venous Thromboembolism

Coagulation factor XII (FXII), formerly known as Hageman factor, is a plasma glycoprotein which exerts a kaleidoscope of biological functions, including the initiation of the intrinsic pathway of blood coagulation, the activation of the kallikrein-kinin system, and the generation of bradykinin and angiotensin. The large body of evidence accumulated over the past decades and the revised cell-based model of hemostasis suggest that FXII may be somehow "redundant" for physiological hemostasis, drawing a potential interpretation of this protein as a possible "innocent" bystander of in vivo hemostasis. Although the contribution of FXII remains unproven in the pathogenesis of venous thromboembolism, perhaps reinforcing this perception of "redundancy," recent work identifies FXII as critical for initiation of thrombosis on artificial surfaces (e.g., polyurethanes or polytetrafluoroethylene catheters), or in patients with strong prothrombotic conditions such as vulnerable atherosclerotic plaques or severe bacterial infections. Important evidence has also emerged from recent investigations using innovative FXII inhibitors in ex vivo animal models, wherein targeted FXII-mediated inhibition of thrombin and fibrin generation may open new avenues for prevention or treatment of certain types of thrombosis. Thus, interest in FXII, waned in the recent past, is again re-emerging, and pointing to important but under-recognized contribution to in vivo hemostasis and thrombosis.

Topics: Animals; Atherosclerosis; Blood Coagulation; Disease Models, Animal; Factor XII; Fibrin; Humans; Thrombin; Thrombosis; Venous Thromboembolism

Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atherosclerotic diseases). Thrombus formed in arteries consists mainly of platelets coated with fibrin (i.e., white thrombus), while venous thrombus formed at relatively lower shear stress consists of all blood components including erythrocytes as well as leukocytes infiltrated with fibrin (red thrombus). Clinical evidence indicates beneficial roles of neuraxial anesthesia/analgesia in the prevention of VTE for patients undergoing high risk surgical procedures. To date, mechanisms of action of drugs used for neuraxial anesthesia/analgesia to prevent venous thrombosis are uncertain. However, accumulation of clinical as well as experimental findings points to the involvement of immune cells (especially monocytes) in red thrombus generation and to the interaction of anesthetics with these cells. We also suggest that adhesion molecules associated with the formation of monocyte platelet aggregates as well as substance P: neurokinin-1 receptor (SP/NK1R) pathway that involves neurogenic inflammation are crucial. Local anesthetics and NK1R antagonists are candidate drugs that may possess the capability to prevent venous thrombotic disorders in perioperative settings.

Topics: Anesthetics, Local; Animals; Blood Platelets; Fibrin; Humans; Monocytes; Neurogenic Inflammation; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Risk Factors; Venous Thromboembolism; Venous Thrombosis

Accumulating evidence indicates that accelerated formation of fibrin clots composed of compact, highly-branched networks with thin fibres which are relatively resistant to plasmin-mediated lysis can be commonly observed in patients with venous or arterial thrombosis. This review discusses characteristics of fibrin clot structure and function in patients with various thromboembolic manifestations, in particular myocardial infarction, ischaemic stroke and venous thromboembolism, based on the publications till December 2013. Moreover, factors will be presented that in vivo unfavourably determine altered fibrin clot properties in thrombotic disorders and modalities that can improve clot phenotype.

Topics: Animals; Blood Coagulation; Fibrin; Humans; Myocardial Infarction; Stroke; Thrombolytic Therapy; Venous Thromboembolism

It is well established that aspirin, an irreversible inhibitor of platelet cyclooxygenase activity, is effective in secondary prevention of arterial thromboembolic events. The pooled results of the recent randomized, multicenter WARFASA and ASPIRE aspirin trials showed a 32% reduction in the rate of recurrence of venous thromboembolism (VTE) in patients receiving aspirin following VTE. These clinical data support evidence that platelets contribute to the initiation and progression of venous thrombosis and aspirin inhibits thrombin formation and thrombin-mediated coagulant reactions. In addition to the known acetylation of serine 529 residue in platelet cyclooxygenase-1, the postulated mechanisms of aspirin-induced antithrombotic actions also involve the acetylation of other proteins in blood coagulation, including fibrinogen, resulting in more efficient fibrinolysis. This review summarizes current knowledge on the aspirin-induced antithrombotic effects that potentially explain clinical studies showing reduced rates of VTE events in aspirin-treated subjects.

Topics: Animals; Aspirin; Blood Coagulation; Blood Platelets; Fibrin; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Recurrence; Thrombin; Treatment Outcome; Venous Thromboembolism

Activation of the immune system has been increasingly recognised to be associated with procoagulatory status in patients with inflammatory rheumatic disease. Changes in endothelial cell and platelet activation, blood flow, expression and activity of different coagulation factors, and impaired fibrinolysis serve as pathophysiological basis for enhanced risk of venous thromboembolism in inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Recent studies identifying mechanisms for a functional role of coagulation factors beyond haemostasis have provided examples of interesting links between the coagulation system and innate immune activation. Furthermore, citrullinated fibrinogen is an important and early autoantigen in patients with RA carrying the HLA-DRβ1 shared epitope allele, which demonstrates an adaptive immune response to a coagulation factor in an inflammatory rheumatic disease. Additional studies have provided strong evidence that a multitude of different components of the haemostatic system (such as thrombin, fibrinogen, coagulation factor XIII and factors of the fibrinolytic system) are relevant mediators of inflammatory processes as well as of inflammatory control. Understanding the interactions between coagulation and the immune system in inflammatory rheumatic diseases will not only improve our knowledge of disease mechanisms, but could also permit the development of innovative therapeutic interventions.

Topics: Blood Coagulation; Endothelium, Vascular; Female; Fibrin; Hemostasis; Humans; Immunity, Innate; Male; Platelet Activation; Rheumatic Diseases; Venous Thromboembolism

Plasma factor XIII (FXIII) is a tetrameric zymogen consisting of two potentially active A subunits (FXIII-A) and two carrier/inhibitory B subunits (FXIII-B). In the final phase of the coagulation cascade, FXIII is converted into an active transglutaminase (FXIIIa) by thrombin and Ca (2 + ). FXIIIa strengthens fibrin clot mechanically by cross-linking fibrin chains. In addition, FXIIIa is a key regulator of fibrinolysis, protecting newly formed fibrin from the fibrinolytic machinery by binding α (2)-plasmin inhibitor to the fibrin meshwork. FXIII is essential for maintaining hemostasis; its severe deficiency causes a life-threatening bleeding diathesis. The involvement of FXIII in thrombotic diseases and its association with the risk of these disorders is less clear. The role of FXIII in atherothrombotic diseases has been recently reviewed. This article offers a general overview of the relationship between FXIII and venous thromboembolism (VTE), to collect individual publications on this topic, present conclusions, and examine limitations of published studies. Special attention is given to the association of FXIII-A polymorphism with the risk of VTE, which has provoked considerable interest over the last decade.

Topics: Factor XIII; Factor XIIIa; Fibrin; Humans; Polymorphism, Genetic; Venous Thromboembolism

Pulmonary embolism remains a common and potentially preventable cause of death.. This article reviews the epidemiology, clinical features, diagnostic process, and treatment of pulmonary embolism.. Well recognised risk factors include recent hospitalisation, other causes of immobilisation, cancer, and oestrogen exposure. Diagnostic algorithms for pulmonary embolism that incorporate assessment of pretest probability and D-dimer testing have been developed to limit the need for diagnostic imaging. Anticoagulation should be administered promptly to all patients with pulmonary embolism with low molecular weight heparin being the initial anticoagulant of choice, although thrombolysis is indicated for patients presenting with haemodynamic compromise. Following initial anticoagulation warfarin therapy should be continued for a minimum of 3 months. Long term anticoagulation with warfarin should be considered in patients with unprovoked pulmonary embolism, due to an increased risk of recurrence after ceasing anticoagulation. The availability of new anticoagulants is likely to significantly impact on the treatment of patients with pulmonary embolism, although the exact role of these drugs is still to be defined.

Topics: Algorithms; Anticoagulants; Antifibrinolytic Agents; Australia; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Risk Assessment; Risk Factors; Venous Thromboembolism

The D-dimer antigen is a unique marker of fibrin degradation that is formed by the sequential action of 3 enzymes: thrombin, factor XIIIa, and plasmin. First, thrombin cleaves fibrinogen producing fibrin monomers, which polymerize and serve as a template for factor XIIIa and plasmin formation. Second, thrombin activates plasma factor XIII bound to fibrin polymers to produce the active transglutaminase, factor XIIIa. Factor XIIIa catalyzes the formation of covalent bonds between D-domains in the polymerized fibrin. Finally, plasmin degrades the crosslinked fibrin to release fibrin degradation products and expose the D-dimer antigen. D-dimer antigen can exist on fibrin degradation products derived from soluble fibrin before its incorporation into a fibrin gel, or after the fibrin clot has been degraded by plasmin. The clinical utility of D-dimer measurement has been established in some scenarios, most notably for the exclusion of VTE. This article consists of 2 sections: in the first, the dynamics of D-dimer antigen formation is discussed and an overview of commercially available D-dimer assays is provided. The second section reviews available evidence for the clinical utilization of D-dimer antigen measurement in VTE, as well as emerging areas of D-dimer utilization as a marker of coagulation activation in other clinical settings.

Topics: Algorithms; Antibodies, Monoclonal; Clinical Laboratory Techniques; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Immunoassay; Models, Biological; Protein Structure, Tertiary; Pulmonary Embolism; Venous Thromboembolism; Venous Thrombosis

Procoagulant and anticoagulant reactions play an important role in the regulation of thrombin formation during secondary hemostasis. Three phases can be recognized in the kinetics of thrombin formation: an initiation phase, a propagation phase and a termination phase. Dysregulation of thrombin formation during each of these phases by (hereditary) changes in the plasma concentration of pro- and anticoagulants contributes to the development of venous thrombosis. Most important seems the defective down-regulation of the prothrombinase activity during the termination phase. Procoagulant and anticoagulant proteins have important roles in the regulation of fibrin formation during secondary hemostasis. Under normal physiological conditions there is a delicate balance between the procoagulant and anticoagulant reactions. After damage to the vessel wall sufficient fibrin is formed to arrest bleeding and allow repair of the lesion without obstructing blood circulation. Venous thrombosis can be considered as a hemostatic process getting out of control, where massive fibrin formation has resulted in the formation of an obstructive thrombus. Such thrombus formation is believed to be facilitated by changes in the vessel wall, blood flow and the composition of the blood. During the past 50 years substantial progress has been made in our understanding of the enzymatic reactions involved in the hemostatic process. At the same time information has been obtained on particular changes in the composition of the blood which contribute to the development of venous thrombosis. Most of these changes concern the procoagulant and anticoagulant systems. In this paper I will briefly discuss how fibrin formation is regulated by procoagulant and anticoagulant reactions and how certain changes in these pathways contribute to the development of venous thrombosis.

Topics: Animals; Blood Coagulation; Blood Coagulation Factor Inhibitors; Blood Coagulation Factors; Fibrin; Humans; Kinetics; Risk Factors; Thrombin; Thromboplastin; Venous Thromboembolism

Unfavorable fibrin clot features have been observed in patients with venous thromboembolism (VTE). We investigated whether rivaroxaban, a direct factor Xa inhibitor, and vitamin K antagonists (VKAs) can improve plasma clot viscoelastic properties. We studied four age- and sex-matched groups: 25 healthy controls, 15 VTE patients taking rivaroxaban 20 mg/day (blood concentration, 145 (67 - 217) ng/ml), 15 VTE patients taking VKA (INR: 2 - 3), and 15 VTE patients who stopped oral anticoagulant therapy (OAT). Using a hybrid rheometier the storage (G') and loss (G") moduli were evaluated in citrated plasma after addition of 5 pmol/l tissue factor. Fiber thickness within clots was assessed using scanning electron microscopy. Higher G' but not G" was observed for VTE patients taking rivaroxaban (+34%; post hoc, P = 0.029) compared to controls. As reflected by lower G' and G", patients taking rivaroxaban (-19% and -30%; post hoc, P = 0.0013 and P < 0.0001, respectively) formed less stiff and viscous clots compared to VTE patients after OAT withdrawal, also after adjustment for fibrinogen. VTE patients treated with rivaroxaban and VKA had similar clot viscoelastic properties (post hoc, P = 0.85 for G' and P = 0.29 for G"). G' and G" correlated with plasma rivaroxaban concentrations (r = -0.67, P = 0.005 and r = -0.59, P = 0.021, respectively), and the time from the last dose of rivaroxaban intake (r = 0.59, P = 0.02 and r = 0.58, P = 0.022, respectively). G' and G" showed no association with INR in patients on VKAs. G' or G" were not associated with fibrin diameter on scanning electron microscopy images in either group. Our preliminary study shows that both rivaroxaban and VKA improve clot viscoelastic properties in VTE patients, which might contribute to their antithrombotic effects. G' and G" may reflect specific clot physical features, beyond key plasma clot characteristics, which highlights benefits from comprehensive plasma clot analysis in patients with thrombotic diseases.

Topics: Acenocoumarol; Adult; Anticoagulants; Elasticity; Factor Xa Inhibitors; Female; Fibrin; Humans; Male; Middle Aged; Rivaroxaban; Thrombosis; Venous Thromboembolism; Viscosity; Vitamin K; Warfarin

The fibrin-related markers (FRMs), including soluble fibrin (SF), D-dimer and fibrin and fibrinogen degradation products (FDP) are considered to be useful for the diagnosis of thrombosis; however, evidence for the diagnosis of thrombosis by SF is still not well established. The present study was designed to evaluate the usefulness of SF in the diagnosis of venous thromboembolism (VTE). The plasma concentrations of FRMs were measured in 551 in-patients suspected to have a VTE. The plasma levels of SF, D-dimer and FDP were significantly higher in patients with VTE than patients without VTE and those were significantly higher in patients without VTE than in healthy volunteers. In a receiver operating characteristic analysis for the diagnosis of VTE, the area under the curve was 0.950 for SF, 0.933 for FDP and 0.805 for D-dimer. The appropriate cut-off values for the diagnosis were as follows SF 5.9 microg/ml, FDP 2.1 microg/ml and D-dimer 4.8 microg/ml. To obtain a 100% negative predictive value for the diagnosis of VTE, the SF was less than 5.2 microg/ml, FDP was less than 1.3 microg/ml, and D-dimer was less than 0.5 microg/ml. Our findings suggest that the SF assay is useful for the diagnosis and exclusion of VTE.

Topics: Aged; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Predictive Value of Tests; Venous Thromboembolism

The coagulation inhibitor potential (CIP) assay may detect major thrombophilia at a sensitivity of 100% and a specificity of 70-80%. Subnormal CIP might be associated with increased risk of thrombosis. This study compared the effect on CIP in plasma samples from postmenopausal women treated with four different regimens. Fibrin aggregation in plasma was monitored after activation with tissue factor. The effect of potentiated inhibition of coagulation was measured. Plasma samples from 202 healthy women randomly assigned to receive treatment for 12 weeks with conventional-dose or low-dose hormone therapy, raloxifene or tibolone were examined. Major thrombophilias were excluded. Compared with baseline, the median level in CIP was reduced by 64% in the conventional-dose group, by 38% in the low-dose group and by 31% in the raloxifene group, whereas for those treated with tibolone the median CIP increased by 9%. The median changes in CIP were significant for both hormone therapy groups (P < 0.0001) and for the raloxifene group (P = 0.003), but not for the tibolone group (P = 0.653). The 12 women with heterozygous factor V Leiden mutation had a significantly reduced median CIP level (P < 0.0001) at baseline. Hormone therapy and raloxifene, associated with venous thromboembolism, reduce the CIP. Tibolone does not reduce the CIP.

Topics: Aged; Blood Coagulation; Estrogen Antagonists; Estrogen Replacement Therapy; Factor V; Female; Fibrin; Heterozygote; Humans; Middle Aged; Mutation; Norpregnenes; Postmenopause; Raloxifene Hydrochloride; Risk Factors; Thrombophilia; Venous Thromboembolism

Oral contraceptive (OC) use increases venous thromboembolism risk 2-5-fold. Procoagulant changes can be detected in plasma from OC users even without thrombosis, but cellular mechanisms that provoke thrombosis have not been identified. Endothelial cell (EC) dysfunction is thought to initiate venous thromboembolism. It is unknown whether OC hormones provoke aberrant procoagulant activity in ECs.. Characterize the effect of high-risk OC hormones (ethinyl estradiol [EE] and drospirenone) on EC procoagulant activity and the potential interplay with nuclear estrogen receptors ERα and ERβ and inflammatory processes.. Human umbilical vein and dermal microvascular ECs (HUVEC and HDMVEC, respectively) were treated with EE and/or drospirenone. Genes encoding the estrogen receptors ERα and ERβ (ESR1 and ESR2, respectively) were overexpressed in HUVEC and HDMVEC via lentiviral vectors. EC gene expression was assessed by RT-qPCR. The ability of ECs to support thrombin generation and fibrin formation was measured by calibrated automated thrombography and spectrophotometry, respectively.. Neither EE nor drospirenone, alone or together, changed expression of genes encoding anti- or procoagulant proteins (TFPI, THBD, F3), integrins (ITGAV, ITGB3), or fibrinolytic mediators (SERPINE1, PLAT). EE and/or drospirenone did not increase EC-supported thrombin generation or fibrin formation, either. Our analyses indicated a subset of individuals express ESR1 and ESR2 transcripts in human aortic ECs. However, overexpression of ESR1 and/or ESR2 in HUVEC and HDMVEC did not facilitate the ability of OC-treated ECs to support procoagulant activity, even in the presence of a pro-inflammatory stimulus.. The OC hormones EE and drospirenone do not directly enhance thrombin generation potential of primary ECs in vitro.

Topics: Contraceptives, Oral; Estrogen Receptor alpha; Estrogen Receptor beta; Ethinyl Estradiol; Female; Fibrin; Humans; Receptors, Estrogen; Thrombin; Thrombosis; Venous Thromboembolism

Aminothiols, including cysteine (Cys) and glutathione (GSH) in relation to fibrin clot phenotype were not investigated in patients with venous thromboembolism (VTE) and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene variants. We aimed to explore the associations between MTHFR variants and plasma oxidative stress indicators including aminothiols as well as fibrin clot properties with plasma oxidative status and fibrin clot properties in this group of patients.. In 387 VTE patients the MTHFR c.665C > T and c.1286A > C variants were genotyped, together with chromatographic separation of plasma thiols. We also determined nitrotyrosine levels and fibrin clot properties, including clot permeability (K. There were 193 patients with MTHFR c.665C > T (49.9%) and 214 (55.3%) with c.1286A > C variants. Both allele carriers with total homocysteine (tHcy) levels >15 μM (n = 71, 18.3%), compared to patients with tHcy ≤15 μM had 11.5% and 12.5% higher Cys levels, 20.6% and 34.3% higher GSH levels as well as 28.1% and 57.4% increased nitrotyrosine levels, respectively (all P < 0.05). The MTHFR c.665C > T carriers with tHcy levels >15 μM compared to tHcy ≤15 μM had 39.4% reduced K. Our study indicates that patients with MTHFR variants and tHcy >15 μM are characterized by elevated Cys and nitrotyrosine levels associated with prothrombotic fibrin clot properties.

Topics: Fibrin; Homocysteine; Humans; Methylenetetrahydrofolate Reductase (NADPH2); Poland; Sulfhydryl Compounds; Thrombosis; Venous Thromboembolism

Topics: Aftercare; Fibrin; Fibrin Clot Lysis Time; Humans; Patient Discharge; Thrombosis; Venous Thromboembolism

The development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients.. To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients.. The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs). NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals.. GC-induced NETs strongly increased the risk of VTE development both

Topics: Animals; Constriction, Pathologic; Endothelial Cells; Extracellular Traps; Fibrin; Mice; Neutrophils; Stomach Neoplasms; Thrombophilia; Thrombosis; Venous Thromboembolism

The outcome of surgical treatment of renal cancer depends not only on cancer-specific survival, but also on the degree of loss of renal function, which often develops after surgery, especially radical nephrectomy.. To study the features of functional changes in a solitary kidney as a compensation mechanism after radical nephrectomy for renal cancer.. The functional state of a solitary kidney in 36 patients with renal cancer who undergone to radical nephrectomy was evaluated. There were 20 and 16 women. The mean age was 59.0+/-10.8 years (from 39 to 76 years). The size of the tumor was in the range of 7.0-12.0 cm. All patients with a solitary kidney underwent a follow-up examination 3 months after surgery, including measurement of peripheral blood pressure with calculation of mean dynamic pressure, renal ultrasound, calculation of glomerular filtration rate (GFR), renal doppler ultrasound, determination of serum fibrinogen and fibrin monomers, and microscopy of the bulbar conjunctiva. Patients who had pathological abnormalities during the examination were prescribed reno-cardioprotective drugs, including perindopril in a titrated dose, apixaban 5 mg a day as thromboprophylaxis and for improvement of the flow properties of blood for a period of 3 months with re-evaluation of the above parameters.. In 61.1% of patients after radical nephrectomy, on 2-4 postoperative days, there was a tendency to increase blood pressure compared to baseline values (p<0.05). By the seventh day after the procedure, the volume of the contralateral kidney increased on average by 16% (from 110.4+/-11.2 cm3 to 132.4+/-4.8 cm3, p<0.05). After radical nephrectomy, a decrease in GFR was detected in 33 cases (91.7%; p<0.05). Renal doppler ultrasound showed a moderate increase in linear blood flow, the resistance index in the main renal artery, and a decrease in the pulse index in the segmental and arcuate arteries. The microscopy of the bulbar conjunctiva in 83.3% of patients revealed changes in the microcirculatory bed, including narrowing of arterioles, dilation of venules, a decrease in venular and capillary blood flow. After 3 months of reno-cardioprotective therapy, it was revealed that the target values of blood pressure (<130/85 mm Hg) were achieved with an average dynamic blood pressure of 93.4+/-2.6 mm Hg. In addition, a decrease in creatinine to an average of 106.2+/-6.4, fibrinogen and fibrin monomers to subnormal values of 3.2+/-0.2 g/l and up to 8.1+/-0.5x10-2 g/l, respectively were seen. Renal hypertrophy according to ultrasound examination was preserved with a mean kidney volume 119.7+/-3.6 cm3. Disturbances in peripheral microcirculation according to the microscopy of the bulbar conjunctiva was assessed as moderate.. The development of CKD in patients with a solitary kidney is accompanied by a structural reorganization of the organ with an increase in blood pressure, an increase in its volume, a decrease in function, microcirculatory disorders and hypertensive nephropathy. Considering the prognostic significance of changes in the solitary kidney, it is important not only to control the functional parameters, but also to include reno- cardioprotective therapy as a standard, since it contributes to the preservation of the renal function and prevents the rapid progression of CKD. Thus, medical and social rehabilitation of patients with a solitary kidney is required. However, it is currently cannot be considered comprehensive.

Topics: Aged; Anticoagulants; Carcinoma, Renal Cell; Female; Fibrin; Fibrinogen; Glomerular Filtration Rate; Humans; Kidney; Kidney Neoplasms; Microcirculation; Middle Aged; Nephrectomy; Renal Insufficiency, Chronic; Retrospective Studies; Solitary Kidney; Venous Thromboembolism

Fibrinolysis is of paramount importance in maintaining or regaining the patency of veins and pulmonary arteries obstructed by thrombi. Growing experimental and clinical evidence indicates that impaired fibrinolysis mediated by multiple complex mechanisms is involved in venous thromboembolism (VTE). Global plasma fibrin clot lysis markers, especially clot lysis time, have been reported to predict recurrent deep-vein thrombosis and pulmonary embolism. The current overview summarizes available data linking fibrinolysis to VTE and its long-term sequelae.

Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Humans; Venous Thromboembolism; Venous Thrombosis

Alpha2-plasmin inhibitor (α2-PI) has a heterogeneous composition in the plasma. Both N- and C-terminal cleavages occur that modify the function of the molecule. C-terminal cleavage converts the plasminogen-binding form (PB-α2-PI) to a non-plasminogen-binding form (NPB-α2-PI). N-terminal cleavage by soluble fibroblast activation protein (sFAP) results in a form shortened by 12 amino acids, which is more quickly cross-linked to fibrin. The p.Arg6Trp polymorphism of α2-PI affects N-terminal cleavage. In this work, we aimed to investigate the association between α2-PI heterogeneity and the risk of venous thromboembolism.. Two hundred and eighteen patients with venous thromboembolism (VTE) and the same number of age and sex-matched healthy controls were enrolled. Total-α2-PI, PB-α2-PI and NPB-α2-PI antigen levels, α2-PI activity, sFAP antigen levels and p.Arg6Trp polymorphism were investigated.. Total-α2-PI and NPB-α2-PI levels were significantly elevated in VTE patients, while PB-α2-PI levels did not change. Elevated NPB-α2-PI levels independently associated with VTE risk (adjusted OR: 9.868; CI: 4.095-23.783). Soluble FAP levels were significantly elevated in the VTE group, however, elevated sFAP levels did not show a significant association with VTE risk. The α2-PI p.Arg6Trp polymorphism did not influence VTE risk, however, in the case of elevated sFAP levels the carriage of Trp6 allele associated with lower VTE risk.. Our results showed that the elevation of total-α2-PI levels in VTE is caused by the elevation of NPB-α2-PI levels. Elevated sFAP level or p.Arg6Trp polymorphism alone did not influence VTE risk. However, an interaction can be detected between the polymorphism and high sFAP levels.

Topics: alpha-2-Antiplasmin; Antifibrinolytic Agents; Fibrin; Humans; Plasminogen; Polymorphism, Genetic; Risk Factors; Venous Thromboembolism

Venous thromboembolism is associated with formation of denser fibrin clots resistant to lysis. We investigated whether prothrombotic plasma clot properties are associated with the severity of acute pulmonary embolism (PE). We enrolled 126 normotensive acute PE patients (aged 58 ± 14 years) and 25 age- and sex-matched healthy controls. Plasma fibrin clot permeability (K

Topics: Adult; Aged; Biomarkers; Blood Coagulation Tests; Case-Control Studies; Extracellular Traps; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Follow-Up Studies; Histones; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Prognosis; Pulmonary Embolism; Risk; Sensitivity and Specificity; Thrombin; Thrombosis; Venous Thromboembolism

Combined oral contraceptives (COCs) are commonly prescribed and increase the risk of venous thromboembolism (VTE). We have previously found that two COCs, both containing drospirenone (DRSP) and ethinyl estradiol (EE), cause spontaneous fibrin formation in whole blood. The aim of this study was, therefore, to use platelet-poor plasma (PPP) from the same cohort of DRSP/EE users to determine the impact of these COCs on the fibrin component, specifically the fibrin clot viscoelasticity, turbidimetry, and biophysical traits. PPP from 25 females per test group and a control group (n = 25) were analyzed using thromboelastography (TEG), turbidimetry, and scanning electron microscopy. The results highlight abnormal fibrin clot formation, lysis, and architecture; DRSP/20EE showed the greatest effect. DRSP/EE use increased the fibrin fiber diameter and showed dense matted clots. Only when the influence of COCs on the structural properties and behavior of fibrin fibers during thrombus formation and lysis is better understood are we able to predict and prevent coagulopathies associated with these synthetic hormones. Clinical practitioners should take this into consideration for female patients that either have comorbidities, which could burden the coagulation system, or may be exposed to external factors that could increase their risk for VTE.

Topics: Adolescent; Adult; Androstenes; Blood Coagulation; Blood Coagulation Tests; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Fibrin; Humans; Male; Microscopy, Electron, Scanning; Thrombelastography; Thrombosis; Venous Thromboembolism; Viscosity; Young Adult

Reduced clot permeability and lysability have been reported in patients who experienced venous thromboembolism (VTE) following lower limb injury despite pharmacological thromboprophylaxis. We hypothesized that similarly altered fibrin clot properties characterize patients with post-discharge VTE despite thromboprophylaxis during prior hospitalization due to acute medical illnesses.. In a case-control study, we assessed 48 patients who developed VTE within 4 weeks post-discharge despite pharmacological thromboprophylaxis during hospitalization (the thromboprophylaxis group) and three age- and sex-matched control groups (n = 48 each): (1) patients who developed VTE following hospitalization without pharmacological thromboprophylaxis (the no-thromboprophylaxis group), (2) patients with unprovoked VTE and (3) individuals without history of VTE (the no-VTE group). Blood samples were obtained following ≥3 months of anticoagulation in VTE patients. Fibrin clot properties, thrombin generation and fibrinolysis activators and inhibitors were assessed.. Compared with the no-VTE group, the thromboprophylaxis group formed denser fibrin networks reflected by lower clot permeability (K. Unfavorably altered plasma clot properties and increased thrombin generation characterize medical patients with post-discharge VTE despite receiving pharmacological thromboprophylaxis during hospitalization for acute conditions.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Case-Control Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Hospitalization; Humans; Male; Middle Aged; Patient Discharge; Thrombin; Venous Thromboembolism

The use of hormonal contraception is associated with an increased risk of venous thromboembolism (VTE). Unfavorably altered fibrin clot phenotype has been reported in patients following unprovoked VTE who are at risk of recurrences. It remains unknown whether fibrin clot characteristics in women with contraception-related VTE differ from those in unprovoked VTE. We studied three age-matched groups of women: (1) after contraception-related VTE, (

Topics: Adult; Case-Control Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Follow-Up Studies; Hormonal Contraception; Humans; Phenotype; Recurrence; Venous Thromboembolism

Essentials Venous thromboembolism (VTE) recurrence leads to decreased clot elastic modulus in plasma. Recurrent VTE is not linked to changes in clot structure, fiber radius, or factor XIII activity. Other plasma components may play a role in VTE recurrence. Prospective studies should resolve if clot stiffness can be used as predictor for recurrent VTE. SUMMARY: Background Venous thromboembolism (VTE) is associated with a high risk of recurrent events after withdrawal of anticoagulation. Objectives To determine the difference in plasma clot mechanical properties between patients with recurrent VTE (rVTE) and those with non-recurrent VTE (nrVTE). Methods We previously developed a system for determining clot mechanical properties by use of an in-house magnetic tweezers system. This system was used to determine the mechanical properties of clots made from plasma of 11 patients with rVTE and 33 with nrVTE. Plasma was mixed with micrometer-sized beads, and thrombin and calcium were added to induce clotting; the mixture was then placed in small capillary tubes, and clotting was allowed to proceed overnight. Bead displacements upon manipulation with magnetic forces were analyzed to determine clot elastic and viscous moduli. Fibrin clot structure was analyzed with turbidimetry and confocal microscopy. Factor XIII was measured by pentylamine incorporation into fibrin. Results Clots from rVTE patients showed nearly two-fold less elastic and less viscous moduli than clots from nrVTE patients, regardless of male sex, unprovoked events, family history of VTE, fibrinogen concentration, or body mass index. No differences were observed in clot structure, fibrinolysis rates, or FXIII levels. Conclusion Using magnetic tweezers for the first time in patient samples, we found that plasma clots from rVTE patients showed a reduced elastic modulus and a reduced viscous modulus as compared with clots from nrVTE patients. These data indicate a possible role for fibrin clot viscoelastic properties in determining VTE recurrence.

Topics: Adolescent; Adult; Calcium; Elastic Modulus; Factor VIII; Female; Fibrin; Hemorheology; Hemostasis; Humans; Magnets; Male; Microscopy, Confocal; Middle Aged; Nephelometry and Turbidimetry; Recurrence; Rheology; Thrombin; Venous Thromboembolism; Viscosity; Young Adult

Compact fibrin clots relatively resistant to lysis are observed in patients at increased risk of venous thromboembolism (VTE) including malignancy. The citrullinated histone H3 (H3Cit) predicts VTE in cancer patients.. We performed a cohort study to investigate whether abnormal clot properties predict cancer diagnosis following unprovoked VTE.. In 369 consecutive patients aged <70 years without malignancy detected during routine screening, we determined plasma clot permeability (K. During follow-up (median, 37; interquartile range, 33-39 months), malignancy was diagnosed in 22 patients (6%), who were older. This group had denser fibrin networks (-13% K. Prothrombotic clot properties following unprovoked VTE might help identify patients at risk of a diagnosis of cancer within the first 3 years of follow-up.

Topics: Adult; Biomarkers; Citrullination; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Histones; Humans; Male; Middle Aged; Neoplasms; P-Selectin; Permeability; Predictive Value of Tests; Prospective Studies; Risk Assessment; Risk Factors; Thrombin; Time Factors; Venous Thromboembolism

Prothrombotic clot phenotype may characterize patients developing deep vein thrombosis (DVT) despite pharmacological thromboprophylaxis. We studied the role of fibrin clot properties and its potential determinants in individuals who experienced DVT after lower limb injury.. In a case-control study, we assessed 50 patients who developed DVT despite prophylactic use of low-molecular-weight heparins (the failed thromboprophylaxis group) after a lower limb injury, and three age- and sex-matched control groups, 50 patients each: (1) patients with trauma-related DVT without prior thromboprophylaxis; (2) individuals with unprovoked DVT; (3) patients without history of DVT (the no-DVT controls). Fibrin clot properties, along with thrombin concentration and α. Patients who experienced DVT despite thromboprophylaxis following lower limb trauma display a strongly prothrombotic fibrin clot phenotype, including increased clot density and hypofibrinolysis associated with higher plasma α

Topics: Adult; alpha-2-Antiplasmin; Anticoagulants; Blood Coagulation; Case-Control Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Genotype; Heparin, Low-Molecular-Weight; Humans; Lower Extremity; Male; Middle Aged; Odds Ratio; Permeability; Phenotype; Poland; Thrombin; Thrombosis; Ultrasonography, Doppler; Venous Thromboembolism; Venous Thrombosis; Wounds and Injuries

Introduction The HERDOO2 rule can help identify patients in whom anticoagulation can be safely discontinued. Unfavorably altered fibrin clot properties predict recurrent venous thromboembolism (VTE). Objectives We aimed to assess a possible association between fibrin clot properties and the HERDOO2 score in women after unprovoked VTE. Patients and methods Eighty women younger than 70 years after a first unprovoked VTE separately and combined with 32 women after hormone‑related VTE were followed for a median of 48.5 months (interquartile range, 37.5-67 years). Plasma fibrin clot permeability (Ks), lysability, turbidity measurements, and thrombin generation were assessed 3 months after the index event in relation to the HERDOO2 score. Results Nineteen women (23.8%) with a HERDOO2 score equal to or higher than 2 were characterized by lower Ks (-6.8%), indicating formation of more compact clots, impaired fibrinolysis as evidenced by a reduced maximum rate of D‑dimer release from clots (D‑D rate, by 6.8%), and prolonged clot lysis time (CLT, by 23.8%). No increased thrombin generation or differences in the remaining fibrin clot properties were observed. When combined with estrogen‑related VTE, the same trends were observed. D‑D rate and CLT correlated with the HERDOO2 score (r = -0.28, P = 0.01 and r = 0.35, P = 0.002, respectively) in 80 women with unprovoked VTE. Unfavorable clot phenotype, defined as Ks ≤6.55×10-9 cm2 and CLT >99.5 minutes, was associated with high risk of recurrence in the HERDOO2 rule (P = 0.02). Conclusions We showed that middle‑aged women after unprovoked VTE with high risk of recurrence based on the HERDOO2 rule are characterized by formation of denser fibrin clots and impaired fibrinolysis.

Topics: Adult; Aged; Female; Fibrin; Humans; Middle Aged; Recurrence; Risk; Thrombosis; Venous Thromboembolism

Topics: Female; Fibrin; Humans; Phenotype; Plasma; Thrombosis; Venous Thromboembolism

The prothrombotic fibrin clot phenotype has been reported in patients with thrombotic antiphospholipid syndrome (APS) and venous thromboembolism (VTE). Protein composition of plasma fibrin clots in APS has not been studied. We evaluated 23 patients with thrombotic APS, 19 with VTE alone, and 20 well-matched controls. A proteomic analysis of fibrin clots generated from citrated plasma was based on liquid chromatography-mass spectrometry. Plasma levels of thrombospondin-1 (TSP1), apolipoprotein(a), A-I, and B-100, complement components (C)3a, C5b-C9, histidine-rich glycoprotein (HRG), and prothrombin were evaluated using immunoenzymatic tests. In plasma fibrin clots of APS patients, compared with VTE subjects and controls, we identified decreased amounts of (pro)thrombin, antithrombin-III, apolipoprotein A-I, and HRG with no differences in plasma levels of antithrombin, prothrombin, along with lower plasma HRG and apolipoprotein A-I. In APS patients, plasma HRG positively correlated with amounts of clot-bound HRG, while apolipoprotein A-I was inversely associated with clot-bound levels of this protein. The most predominant proteins within the clots of APS patients were bone marrow proteoglycan, C5-C9, immunoglobulins, apolipoprotein B-100, platelet-derived proteins, and TSP1. Our study is the first to demonstrate differences in the protein composition of fibrin clots generated from plasma of thrombotic APS patients versus those with VTE alone.

Topics: Adult; Antiphospholipid Syndrome; Blood Coagulation; Blood Proteins; Case-Control Studies; Female; Fibrin; Humans; Male; Middle Aged; Proteome; Thrombosis; Venous Thromboembolism

To examine the role of soluble fibrin monomer complex (SFMC) in the prediction of hypercoagulable state after gastroenterological surgery.. We collected data on the clinical risk factors and fibrin-related makers from patients who underwent gastroenterological surgery at Hiroshima University Hospital between April 1, 2014 and March 31, 2015. We investigated the clinical significance of SFMC, which is known to reflect the early plasmatic activation of coagulation, in the view of these fibrin related markers.. The SFMC on POD 1 strongly predicted the hypercoagulable state after gastroenterological surgery than the clinical risk factors and the other fibrin related markers.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Blood Coagulation; Digestive System Surgical Procedures; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Gastroenterology; Humans; Male; Middle Aged; Multivariate Analysis; Postoperative Period; Retrospective Studies; Risk Factors; Sensitivity and Specificity; Treatment Outcome; Venous Thromboembolism

Plasminogen (Plg) is a precursor of plasmin that degrades fibrin. A race-specific A620T mutation in Plg, also known as Plg-Tochigi, originally identified in a patient with recurrent venous thromboembolism, causes dysplasminogenemia with reduced plasmin activity. The Plg-A620T mutation is present in 3-4% of individuals in East Asian populations, and as many as 50,000 Japanese are estimated to be homozygous for the mutant 620T allele. In the present study, to understand the changes of thrombotic phenotypes in individuals with the mutant 620T allele, we generated knock-in mice carrying the homozygous Plg-A622T mutation (PlgT/T), an equivalent to the A620T mutation in human Plg. PlgT/T mice grew normally but showed severely reduced plasmin activity activated by urokinase, equivalent to ~8% of that in wild-type mice. In vitro fibrin clot lysis in plasma was significantly slower in PlgT/T mice than in wild-type mice. However, all experimental models of electrolytic deep vein thrombosis, tissue factor-induced pulmonary embolism, transient focal brain ischaemic stroke, or skin-wound healing showed largely similar phenotypes between PlgT/T mice and wild-type mice. Protein S-K196E mutation (Pros1E/E) is a race-specific genetic risk factor for venous thromboembolism. Coexistence in mice of PlgT/T and Pros1E/E did not affect pulmonary embolism symptoms, compared with those in Pros1E/E mice. Hence, the present study showed that the Plg-A622T mutation, which confers ~8% plasmin activity, does not increase the risk of thrombotic diseases in mice under experimental thrombotic conditions and does not modify the thrombotic phenotype observed in Pros1E/E mice. PlgT/T mice can be used to investigate the potential pathophysiological impact of the Plg-A620T mutation.

Topics: Amino Acid Substitution; Animals; Brain Ischemia; Conjunctivitis; Disease Models, Animal; Female; Fibrin; Fibrinolysin; Gene Expression; Gene Knock-In Techniques; Humans; Male; Mice; Mice, Transgenic; Mutation; Phenotype; Plasminogen; Protein S; Pulmonary Embolism; Skin Diseases, Genetic; Stroke; Venous Thromboembolism; Venous Thrombosis; Wound Healing

Thrombosis is a leading cause of morbidity and mortality throughout the world. Thrombolytic agents are important for both the prevention and treatment of thrombosis. Fibrin clot and turbidity assays revealed that it was able to inhibit the formation of fibrin clot. Chlorogenic acid degraded blood clot and inhibited the enzymatic activity of procoagulant proteases, thrombin, activated factor X (FXa), and activated factor XIII (FXIIIa). Chlorogenic acid was found to delay activated partial thromboplastin time, prothrombin time, and thrombin time. PFA-100 assays showed that it prolonged the closure time of citrated whole human blood. It demonstrated the antithrombotic effect in collagen and epinephrine-induced acute thromboembolism mice model. These antithrombotic profiles together with its anticoagulant and platelet disaggregation properties, and lack of toxicity to NIH-3T3 and 3T3-L1 cells, make it a potential agent for thrombotic treatment and prevention.

Topics: 3T3-L1 Cells; Animals; Blood Coagulation; Chlorogenic Acid; Collagen; Disease Models, Animal; Epinephrine; Factor Xa; Factor XIIIa; Fibrin; Fibrinolytic Agents; Humans; Mice; Platelet Aggregation; Thrombosis; Venous Thromboembolism

We report the study of a familial rare disease with recurrent venous thromboembolic events that remained undiagnosed for many years using standard coagulation and hemostasis techniques.. Exome sequencing was performed in three familial cases with venous thromboembolic disease and one familial control using NimbleGen exome array. Clot lysis experiments were performed to analyze the reasons of the altered fibrinolytic activity caused by the mutation found.. We found a mutation that consists of a R458C substitution on the fibrinogen alpha chain (FGA) gene confirmed in 13 new familial subjects that causes a rare subtype of dysfibrinogenemia characterized by venous thromboembolic events. The mutation was already reported to be associated with a fibrinogen variant called fibrinogen Bordeaux. Clot-lysis experiments showed a decreased and slower fibrinolytic activity in carriers of this mutation as compared to normal subjects, thus demonstrating an impaired fibrinolysis of fibrinogen Bordeaux.. The exome sequencing and clot-lysis experiments might be powerful tools to diagnose idiopathic thrombophilias after an unsuccessful set of biochemical laboratory tests. Fibrinogen Bordeaux is associated with impaired fibrinolysis in this family with idiopathic thrombophilia.

Topics: Blood Coagulation; Blood Coagulation Tests; Exome; Family Health; Female; Fibrin; Fibrinogen; Humans; Male; Mutation; Pedigree; Sequence Analysis, DNA; Thrombin; Thrombophilia; Thrombosis; Venous Thromboembolism

Venous thromboembolism (VTE) is a common complication in patients who have undergone major orthopedic surgery, but there are few predictors of VTE after major orthopedic surgery treated with an anticoagulant. We measured levels of fibrin-related markers (FRMs), such as D-dimer, soluble fibrin (SF), and fibrinogen and fibrin degradation products (FDPs) in 66 patients with acute-phase VTE, and 367 patients undergoing major orthopedic surgery. Plasma FDP, D-dimer, and SF levels were significantly higher in patients with acute VTE, but only FDP and D-dimer levels were significantly higher in subclinical VTE. Adequate cut-off levels of D-dimer were 2.2 μg/ml for diagnosing acute VTE and 1.5 μg/ml for diagnosing subclinical VTE. D-dimer of less than 1.9 or 0.7 μg/ml ruled out acute VTE or subclinical VTE. D-dimer of more than 1.3 μg/ml preoperatively showed a moderate risk for postoperative VTE. Measurement of FRMs is useful for evaluating the risk of subclinical or postoperative VTE in patients with major orthopedic surgery. In particular, FDP is the most valuable marker for diagnosing acute VTE, whereas D-dimer is the most valuable for diagnosing subclinical VTE or predicting VTE.

Topics: Acute Disease; Aged; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Orthopedic Procedures; Venous Thromboembolism; Young Adult

We present a case of a 39-year-old, gravida 3 para 2, Chinese female with a history of inherited type 1 Antithrombin deficiency and multiple prior episodes of venous thromboembolism. She presented at 29+4 weeks' gestation with severe pre-eclampsia complicated by haemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. She subsequently underwent an emergency caesarean section for non-reassuring fetal status, which was complicated by postpartum haemorrhage secondary to uterine atony, requiring a B-Lynch suture intraoperatively.

Topics: Adult; Cesarean Section; China; Female; Fibrin; HELLP Syndrome; Humans; Pre-Eclampsia; Pregnancy; Uterine Inertia; Venous Thromboembolism

This study compared patients with venous thromboembolism (VTE) to non-VTE patients using a biomarker of clot microstructure (df ) and clot formation time (TGP ). df was the only marker that identified a significant difference (P < 0·001) between the VTE (n = 60) and non-VTE cohorts (n = 69). The 'abnormal' clot microstructures in the VTE patients suggests either inadequate response to anticoagulant therapy or the presence of a procoagulant state not detected by other markers of coagulation (i.e., International Normalized Ratio). Furthermore, elevated values of df in first time VTE patients who later develop a secondary event indicates that df may identify those at risk of recurrence.

Topics: Aged; Anticoagulants; Biomarkers; Blood Coagulation Tests; Elasticity Imaging Techniques; Female; Fibrin; Fibrinolysis; Gels; Hemorheology; Humans; Male; Middle Aged; Time Factors; Venous Thromboembolism; Viscoelastic Substances; Warfarin

Induction therapy in patients with multiple myeloma increases the risk of thromboembolism. We have recently shown that multiple myeloma patients tend to form denser fibrin clots displaying poor lysability. We investigated the effect of induction therapy on fibrin clot properties in multiple myeloma patients. Ex-vivo plasma fibrin clot permeability, turbidity, susceptibility to lysis, thrombin generation, factor VIII and fibrinolytic proteins were compared in 48 multiple myeloma patients prior to and following 3 months of induction therapy, mainly with cyclophosphamide-thalidomide-dexamethasone regimen. Patients on thromboprophylaxis with aspirin or heparins were eligible. A 3-month induction therapy resulted in improved clot properties, that is higher clot permeability, compaction, shorter lag phase and higher final turbidity, along with shorter clot lysis time and higher rate of D-dimer release from fibrin clots than the baseline values. The therapy also resulted in lower thrombin generation, antiplasmin and thrombin-activatable fibrinolysis inhibitor (TAFI), but elevated factor VIII. Progressive disease was associated with lower posttreatment clot permeability and lysability. Despite thromboprophylaxis, two patients developed ischemic stroke and 10 had venous thromboembolism. They were characterized by pretreatment lower clot permeability, prolonged clot lysis time, longer lag phase, higher peak thrombin generation, TAFI and plasminogen activator inhibitor -1. Formation of denser plasma fibrin clots with reduced lysability and increased thrombin generation at baseline could predispose to thrombotic complications during induction treatment in multiple myeloma patients. We observed improved fibrin clot properties and thrombin generation in multiple myeloma patients except those with progressive disease.

Topics: Drug Therapy; Female; Fibrin; Fibrinolysis; Humans; Male; Multiple Myeloma; Venous Thromboembolism

Venous thromboembolism (VTE) is common in cancer patients, and is the second commonest cause of death associated with the disease. Patients with chronic inflammation, such as cancer, have been shown to have pathological clot structures with modulated mechanical properties. Fractal dimension (df) is a new technique which has been shown to act as a marker of the microstructure and mechanical properties of blood clots, and can be performed more readily than current methods such as scanning electron microscopy (SEM). We measured df in 87 consecutive patients with newly diagnosed lung cancer prior to treatment and 47 matched-controls. Mean group values were compared for all patients with lung cancer vs controls and for limited disease vs extensive disease. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. Significantly higher values of df were observed in lung cancer patients compared with controls and patients with extensive disease had higher values than those with limited disease (p< 0.05), whilst conventional markers failed to distinguish between these groups. The relationship between df of the incipient clot and mature clot microstructure was confirmed by SEM and computational modelling: higher df was associated with highly dense clots formed of smaller fibrin fibres in lung cancer patients compared to controls. This study demonstrates that df is a sensitive technique which quantifies the structure and mechanical properties of blood clots in patients with lung cancer. Our data suggests that df has the potential to identify patients with an abnormal clot microstructure and greatest VTE risk.

Topics: Aged; Algorithms; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Case-Control Studies; Female; Fibrin; Fractals; Hemorheology; Humans; Lung Neoplasms; Male; Microscopy, Electron, Scanning; Middle Aged; Neoplasm Staging; Prospective Studies; Risk; Single-Blind Method; Smoking; Thrombophilia; Venous Thromboembolism

Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0·0385 and P = 0·017, respectively), and as expected, were much higher in SSversusAA (P < 0·0001 for both). Thrombin generation in platelet poor plasma was indistinguishable between AA and AS subjects, whereas a paradoxical decrease in endogenous thrombin potential was observed in SS (P ≤ 0·0001). Whole blood tissue factor was elevated in SS compared to AA (P = 0·005), but did not differ between AA and AS. Plasma microparticle tissue factor activity was non-significantly elevated in AS (P = 0·051), but was clearly elevated in SS patients (P = 0·004) when compared to AA controls. Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation.

Topics: Adult; Anemia, Sickle Cell; Antithrombin III; Black or African American; Case-Control Studies; Cell-Derived Microparticles; Cytokines; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Inflammation Mediators; Male; Middle Aged; Peptide Hydrolases; Plasma; Sickle Cell Trait; Thrombin; Thrombophilia; Thromboplastin; Venous Thromboembolism

Prevention and early detection of venous thromboembolism (VTE) is important after arthroplasty of the lower limb. The purpose of this study was to investigate the associations between VTE and hemostatic markers after minimally invasive total knee arthroplasty (MIS-TKA).. We performed a retrospective study of 50 patients (55 knees) who underwent primary unilateral MIS-TKA with periodic determination of D-dimer and soluble fibrin monomer complex (SFMC) concentrations and with ultrasonography. The development of symptomatic and asymptomatic VTE, location of deep venous thrombosis (DVT; proximal or distal), changes in SFMC and D-dimer concentrations, and correlations between hemostatic markers and VTE onset were evaluated.. Twenty-six patients (47%) had an asymptomatic distal DVT, but none had proximal DVT, pulmonary embolism, or symptomatic DVT. DVT was detected at postoperative day 1 (POD1) in 16 patients, POD3 in six, and POD5 in three (excluding detections of the same DVT in the same position on different days). DVT onset correlated significantly with SFMC concentration on POD1 and with D-dimer concentration on POD3. The D-dimer concentration did not differ significantly between patients who developed DVT (DVT+) and those who did not (DVT-) at each postoperative time. SFMC concentration differed between DVT+ and DVT- patients only on POD1. Analysis of each hemostatic marker classified as either within or outside the normal concentration range showed no significant correlations between D-dimer concentration and DVT onset at each period. There were significant correlations between SFMC concentrations and DVT onset on POD1 and POD3. There were also significant correlations between D-dimer positive (+) findings and/or SFMC+ findings and DVT onset on POD1 and POD3. D-dimer+ and/or SFMC+ findings had better specificity on POD1 and a positive predictive value on POD1 and POD3 compared with SFMC+ alone.. SFMC concentration is an effective hemostatic marker for early detection of DVT. D-dimer concentration alone has limited value as a hemostatic marker for early detection of DVT. Measurement of both D-dimer and SFMC concentrations might be a more sensitive diagnostic tool than measuring SFMC concentration alone.

Topics: Aged; Arthroplasty, Replacement, Knee; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostasis; Humans; Male; Middle Aged; Minimally Invasive Surgical Procedures; Perioperative Care; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Venous Thromboembolism

We measured fibrin monomer complex (FMC) levels in all subjects who gave birth at our hospital and evaluated the feasibility of using FMC for screening for venous thromboembolism (VTE) in patients during late pregnancy and the post-partum period.. From August 2010 to January 2012, all women who gave birth at our hospital were included. FMC and D-dimer levels were determined during the late pregnancy and post-partum periods. Compression ultrasonography of the lower extremities was performed in women with high FMC values.. Of the 673 women enrolled, measurements were performed in 595 women (88.4%) during late pregnancy and in 610 women (90.6%) during the post-partum period. The FMC levels were normal during late pregnancy in 400 women (67.2%) and during the post-partum period in 399 women (78.5%) having vaginal delivery and 83 women (81.4%) who underwent a cesarean section. The FMC levels were abnormal during late pregnancy in 50 women (8.4%) and during the post-partum period in nine women (1.8%) having vaginal delivery and in none (0%) who underwent a cesarean section. Ultrasonography detected thrombi in three (6.0%) women during late pregnancy. The FMC levels were strongly correlated with D-dimer levels (R = 0.726, P < 0.0001, in late pregnancy; and R = 0.888, P < 0.0001, in the post-partum period following vaginal delivery).. FMC levels could identify pregnancy-related abnormalities requiring compression ultrasonography examination, without changing the cut-off values for non-pregnant individuals. Thus, this marker may be used to screen for VTE.

Topics: Adult; Biomarkers; Feasibility Studies; Female; Fibrin; Humans; Japan; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Prenatal Diagnosis; Up-Regulation; Venous Thromboembolism

The purpose of this prospective study was to evaluate the utility of preferential application of pharmacoprophylaxis based on the quantitative evaluation by soluble fibrin (SF) and plasminogen activator inhibitor-1 (PAI-1) analysis on the day after total hip arthroplasty (THA).. A hundred and sixteen patients were enrolled. High-risk patients were defined as those with elevated levels of SF or PAI-1, beyond their cut-off values, on the day after THA. For high-risk patients, fondaparinux was administered for 10 days postoperatively. When both plasma levels of SF and PAI-1 were less than their cutoff levels, the patients were regarded to be at low risk. For low-risk patients, only mechanical prophylaxis was applied.. Sixty patients (52%) were considered to be at high risk. Among them, venous thromboembolism (VTE) was detected in five patients (8%) by CT angiography. In addition, there were four patients (3%) who developed bleeding complications. Fifty-six patients (48%) were considered to be at low risk, and only one patient (2%) developed VTE.. The measurement of SF and PAI-1 levels on the day after surgery may be helpful to identify the individual risk for postoperative VTE. According to this evaluation, a half of patients might not need to administer anticoagulant agents following surgery.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Female; Fibrin; Fondaparinux; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Polysaccharides; Prospective Studies; Risk Assessment; Treatment Outcome; Venous Thromboembolism

Many patients with malignant diseases are frequently complicated with some type of thrombosis, such as venous thromboembolism (VTE) or disseminated intravascular coagulation (DIC).. This retrospective study was designed to examine the frequency of thrombosis in 478 patients with malignant diseases in comparison to that observed in 121 patients without malignant diseases and to evaluate the efficacy of fibrin-related markers (FRMs), such as soluble fibrin, fibrinogen and fibrin degradation products and D-dimer, in diagnosing thrombosis.. The frequency of thrombosis, including 62 cases of VTE, 63 cases of DIC and nine cases of cerebrovascular thrombosis, was significantly higher in the patients with malignant diseases (28.0%) than in the patients without malignant diseases (12.5%). DIC was frequently detected in the patients with hepatic cell cancer and hematopoietic malignancy, while VTE was frequently observed in the patients with colon cancer, breast cancer and urinary tract cancer. The FRMs levels were significantly higher in the patients with thrombosis than in the patients without thrombosis. A receiver operating characteristic analysis showed these markers to be useful for diagnosing thrombosis.. Patients with malignant diseases have a high risk of thrombosis, and elevated FRMs levels are useful for diagnosing thrombosis in patients with malignant diseases.

Topics: Adult; Aged; Biomarkers, Tumor; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; ROC Curve; Venous Thromboembolism

We tested the hypothesis that plasma fibrin clot structure/function is unfavourably altered in patients with antiphospholipid syndrome (APS). Ex vivo plasma clot permeability, turbidity and susceptibility to lysis were determined in 126 consecutive patients with APS enrolled five months or more since thrombotic event vs 105 controls. Patients with both primary and secondary APS were characterised by 11% lower clot permeability (p<0.001), 4.8% shorter lag phase (p<0.001), 10% longer clot lysis time (p<0.001), and 4.7% higher maximum level of D-dimer released from clots (p=0.02) as compared to the controls. Scanning electron microscopy images confirmed denser fibrin networks composed of thinner fibres in APS. Clots from patients with "triple-antibody positivity" were formed after shorter lag phase (p=0.019) and were lysed at a slower rate (p=0.004) than in the remainder. Clots from APS patients who experienced stroke and/or myocardial infarction were 8% less permeable (p=0.01) and susceptible to lysis (10.4% longer clot lysis time [p=0.006] and 4.5% slower release of D-dimer from clots [p=0.01]) compared with those following venous thromboembolism alone. Multivariate analysis adjusted for potential confounders showed that in APS patients, lupus anticoagulant and "triple-positivity" were the independent predictors of clot permeability, while "triple-positivity" predicted lysis time. We conclude that APS is associated with prothrombotic plasma fibrin clot phenotype, with more pronounced abnormalities in arterial thrombosis. Molecular background for this novel prothrombotic mechanism in APS remains to be established.

Topics: Adult; Antiphospholipid Syndrome; Autoantibodies; Biomarkers; Blood Coagulation Tests; Case-Control Studies; Chi-Square Distribution; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Linear Models; Male; Microscopy, Electron, Scanning; Middle Aged; Multivariate Analysis; Myocardial Infarction; Poland; Predictive Value of Tests; Prognosis; Risk Factors; Stroke; Thrombosis; Time Factors; Venous Thromboembolism

Markers of coagulation and fibrinolysis, such as soluble fibrin (SF), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), have been developed in order to determine thrombotic tendency. We investigated whether these markers could be used to diagnose venous thromboembolism (VTE) in the early phase after primary total hip arthroplasty (THA).. This prospective study involved 2 groups: an intermittent pneumatic compression (IPC) group (67 patients who underwent IPC only as prophylaxis for VTE) and a fondaparinux (FPX) group (103 patients who received IPC and FPX postoperatively). Plasma levels of SF and PAI-1 were measured on postoperative day 1. To diagnose postoperative VTE, multi-detector row computed tomography (MDCT) and duplex ultrasonography (US) were performed on postoperative day 7.. VTE was detected postoperatively in 17 cases in the IPC group (25%) and in 8 cases in the FPX group (6%). In the IPC group, plasma levels of SF and PAI-1 were higher in patients with VTE (p < 0.01) than in those without VTE. On the other hand, in the FPX group there were no differences in the levels of SF or PAI-1 measured before administration of FPX on postoperative day 1. The diagnostic criterion of an increase in SF or PAI-1 above the cutoff level (19.8 µg/mL and 53.5 ng/mL, respectively) provided a sensitivity of 100% and a specificity of 67% in the IPC group. In addition, when this criterion was applied to FPX patients, 7 of the 8 patients with VTE met the criterion, and there was a negative agreement rate of 48/49.. Screening using the cutoff levels of SF and PAI-1 may be useful and shows high sensitivity in predicting postoperative VTE in the early phase after THA.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antithrombin III; Arthroplasty, Replacement, Hip; Biomarkers; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fondaparinux; Humans; Male; Middle Aged; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Polysaccharides; Primary Prevention; Prospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; Venous Thromboembolism

Topics: Atorvastatin; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Dyslipidemias; Fibrin; Fibrinolytic Agents; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Poland; Pyrroles; Treatment Outcome; Ultrasonography, Doppler, Color; Venous Thromboembolism

Cancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VTE at study entry and 22 healthy volunteers, markers of in vivo and MP-dependent coagulation were measured and patients were prospectively followed for six months for the development of VTE. Procoagulant activity of MPs was measured in vitro using a tissue factor (TF)-independent phospholipid dependent test, a factor Xa-generation assay with and without anti-TF, and a fibrin generation test (FGT) with and without anti-factor VII(a). Markers of in vivo coagulation activation and total number of MPs at baseline were significantly elevated in cancer patients compared to controls (F1+2 246 vs. 156 pM, thrombin-antithrombin complexes 4.1 vs. 3.0 mg/l, D-dimer 0.76 vs. 0.22 mg/l and 5.53 x 10⁶ vs. 3.37 x 10⁶ MPs/ml). Five patients (11.6%) developed VTE. Patients with VTE had comparable levels of coagulation activation markers and phospholipid-dependent MP procoagulant activity. However, median TF-mediated Xa-generation (0.82 vs. 0.21 pg/ml, p=0.016) and median VIIa-dependent FGT (13% vs. 0%, p=0.036) were higher in the VTE group compared with the non-VTE group. In this exploratory study the overall hypercoagulable state in cancer patients was not associated directly with the MP phospholipid-dependent procoagulant activity. However, in the patients who developed VTE within six months when compared to those who did not, an increased MP procoagulant activity was present already at baseline, suggesting this activity can be used to predict VTE.

Topics: Aged; Blood Coagulation Tests; Blood Platelets; Cell-Derived Microparticles; Factor VIIa; Factor Xa; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasms; Phospholipids; Platelet Activation; Prognosis; Prospective Studies; Risk; Venous Thromboembolism

Oral contraceptives (OC) in the presence of factor V Leiden mutation (FVL) markedly increase the risk of venous thromboembolism (VTE). Little is known about the OC and FVL-related alterations in fibrin clot properties.. Plasma fibrin clot permeability (K(s)) and efficiency of lysis, reflected by clot lysis time (CLT) and the rate of D-dimer release from clots (D-D(rate)) induced by recombinant tissue plasminogen activator (tPA) were determined in 25 women with a family history of VTE who were heterozygous for FVL [FVL(+/-) - twice, on third-generation OC and after their discontinuation. Female non-carriers of FVL, matched for demographics, using OC and after their discontinuation served as controls (n=25). All participants had no personal history of VTE.. OC discontinuation in FVL(+/-) women resulted in shortened CLT (-9%), and increased K(s) (+4%) and D-D(rate) (+1.4%; all p<0.01). Alterations in fibrin clot properties were associated with decreased prothrombin fragments 1+2 (F1+2) (-8%), plasminogen activator inhibitor-1 (PAI-1) antigen (-11%), and thrombin activatable fibrinolysis inhibitor (TAFI) activity (-20%; all p<0.01). During OC use FVL(+/-) carriers compared with non-carriers had higher platelet count, activity of PAI-1, TAFI, and tPA, as well as prolonged CLT and higher D-D(max), along with lower D-D(rate) and K(s). Multiple regression analysis adjusted for fibrinogen and age, showed that PAI-1 antigen and TAFI activity independently predicted CLT in FVL(+/-) women on OC.. FVL(+/-) is associated with hypofibrinolysis in apparently healthy women and third-generation OC administration unfavorably alters plasma clot characteristics in female FVL(+/-) carriers with a family history of thrombotic events.

Topics: Adult; Case-Control Studies; Contraceptives, Oral; Factor V; Female; Fibrin; Fibrin Clot Lysis Time; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Heterozygote; Humans; Venous Thromboembolism; Young Adult

Pulmonary embolism development may be prevented if asymptomatic venous thromboembolism (VTE) can be predicted and treated preoperatively or soon after total knee arthroplasty (TKA). The purpose of this study was to evaluate whether asymptomatic VTE can be predicted by blood coagulation markers preoperatively or early after TKA. This prospective single-centre study enrolled 68 patients (6 men, 62 women; mean age: 71 years) who underwent TKA between September 2004 and August 2009. Sixteen-row multidetector computed tomography was performed 4 days before and after surgery for diagnosis of asymptomatic VTE. Blood samples were taken to measure the plasma levels of soluble fibrin monomer complex (SFMC), D-dimer and cross-linked fibrin degradation products by leukocyte elastase (e-XDP) at 4 days preoperatively, and at 1 hour, 1 day and 4 days postoperatively. The preoperative SFMC, D-dimer and e-XDP levels did not differ significantly between the thrombus (n=36) and no-thrombus (n=32) groups. D-dimer and e-XDP levels showed the most significant increases at days 4 and 1, respectively, after surgery in the thrombus group. With cut-off points of 7.5 μg/ml for D-dimer and 8.2 U/ml for e-XDP, the sensitivities were 75% and 75%, and the specificities were 63% and 59%, respectively. By multiple logistic regression analysis, D-dimer at day 4 and e-XDP at day 1 postoperatively were independent markers for early diagnosis of VTE (odds ratio=1.61 and 1.19, P=0.01 and 0.04, respectively). The postoperative occurrence of new asymptomatic VTE may be predicted by D-dimer at day 4 and e-XDP at day 1 after TKA.

Topics: Aged; Arthritis, Rheumatoid; Arthroplasty, Replacement, Knee; Biomarkers; Blood Coagulation; Early Diagnosis; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Leukocyte Elastase; Male; Multidetector Computed Tomography; Osteoarthritis, Knee; Prospective Studies; Venous Thromboembolism

Topics: C-Reactive Protein; Coronary Artery Disease; Female; Fenofibrate; Fibrin; Fibrinolysis; Heptanoic Acids; Homocysteine; Humans; Hypersensitivity, Immediate; Laser Coagulation; Lipoprotein(a); Male; Pyrroles; Retinal Vein; Retinal Vein Occlusion; Simvastatin; Tetrahydroisoquinolines; Thrombosis; Venous Thromboembolism; Venous Thrombosis

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives. We conclude that altered fibrin clot features are associated with idiopathic VTE with a different profile of fibrin variables in PE. Similar features can be detected in VTE relatives. Fibrin properties might represent novel risk factors for thrombosis.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Factor XIII; Female; Fibrin; Fibrinogen; Fibrinolysis; Genotype; Humans; In Vitro Techniques; Male; Middle Aged; Nephelometry and Turbidimetry; Pulmonary Embolism; Risk Factors; Venous Thromboembolism; Young Adult

It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation.

Topics: Animals; Blood Platelets; Fibrin; Glycophorins; Humans; Immunohistochemistry; Integrin beta3; Male; Platelet Activation; Platelet Glycoprotein GPIb-IX Complex; Rabbits; Venous Thromboembolism; von Willebrand Factor

Venous thromboembolism (VTE) is a critical complication after hip replacement surgery, so both early diagnosis and prophylaxis are important. The purpose of this study was to clarify the rapid changes of the fibrin monomer complex (FMC) and soluble fibrin (SF) during the perioperative period of hip replacement surgery.. The subjects were 32 patients (7 men, 25 women) who underwent elective hip replacement surgery between November 2004 and January 2006. Their ages ranged between 34 to 82 years (mean 56.8 years). According to their thromboembolic risk, the patients received different prophylaxis: unfractionated heparin (4 patients), danaparoid sodium (14 patients), or mechanical therapy only (14 patients).. FMC and SF became rapidly elevated during the operation and just after surgery but declined to preoperational levels 3 days after surgery; they were higher in lupus anticoagulant (LA)-positive patients. In contrast, FDP and D-dimer had gradually become elevated 3 and 7 days after surgery. According to venous ultrasonography and lung perfusion scintigraphy, VTE occurred in 7 patients overall (21.9%). The incidence of VTE was 7.1% in the danaparoid group, whereas it was 35.7% in the mechanical therapy group. We also found that danaparoid sodium rapidly decreased FMC and SF within 3 days.. FMC and SF were rapidly elevated during hip replacement surgery and differentiated in LA-positive and LA-negative patients.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Arthroplasty, Replacement, Hip; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Heparitin Sulfate; Humans; Intraoperative Period; Lupus Coagulation Inhibitor; Male; Middle Aged; Postoperative Period; Venous Thromboembolism