Procedure-dependence and Tissue Factor-independence of Hypercoagulability during Orthopaedic Surgery

1999 ◽  
Vol 81 (06) ◽  
pp. 874-878 ◽  
Author(s):  
A. M. Gori ◽  
M. Falciani ◽  
A. P. Cellai ◽  
P. Aglietti ◽  
A. Baldini ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Plasma Levels ◽  
Orthopaedic Surgery ◽  
Blood Clotting ◽  
Endothelial Activation ◽  
Extrinsic Pathway ◽  
Vein Thrombosis ◽  
Pathway Activation ◽  
Increased Risk ◽  
Von Willebrand

SummaryThe increased risk for deep vein thrombosis (DVT) after orthopaedic surgery has been well documented as well as hypercoagulable state during both total hip arthroplasty (THA) and total knee replacement (TKR). To investigate the influence of the surgical procedure [postero-lateral (PL) or lateral (L) approach for THA, use of tourniquet (TQ) or not use of TQ for TKR] on the hypercoagulability and the role of extrinsic pathway activation and endothelial stimulation during orthopaedic surgery we have examined 40 patients (20 patients undergoing primary THA – 10 with PL approach and 10 with L approach – and 20 patients undergoing TKR – 10 with TQ application and 10 without TQ). Thrombin-antithrombin complexes (TAT), tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM) and von Willebrand factor antigen (vWF:Ag) were analyzed before and during the orthopaedic surgery. During THA, TAT plasma levels increased more markedly in patients assigned to the L than PL approach (p <0.05); during TKR an elevation of TAT of higher degree (p <0.05) was observed when TQ was not applicated. Blood clotting activation was significantly (p <0.001) more relevant during THA than TKR. No changes in TF and vWF:Ag plasma levels were observed in all patients undergoing THA and TKR. TFPI plasma levels significantly (p <0.05) decreased 1 h after the end of the THA in group PL and group L, whereas they remained unaffected in the two groups of patients undergoing TKR. Similarly TM plasma levels significantly decreased during THA, but not during TKR. In conclusion, these results show that: 1) the site of surgical procedures and the type of approach affect the degree of hypercoagulability, 2) the blood clotting activation takes place in the early phases of orthopaedic surgery, without signs of extrinsic pathway and endothelial activation.

Strong Correlation of High Endogenous Plasma Levels of Tissue Factor Pathway Inhibitor (TFPI) with Poor Blood Clotting and Corrective Action of BAX 513 Under FVIII-Inhibited Conditions

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1201-1201
Author(s):  
Michael Dockal ◽  
Monika Gorczyca ◽  
Sabine Knappe ◽  
Michael Palige ◽  
Hartmut J. Ehrlich ◽  
...  
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Blood Clotting ◽  
Sulfated Polysaccharides ◽  
Plasma Samples ◽  
Extrinsic Pathway ◽  
Human Factor Viii ◽  
Thrombin Formation

Abstract Abstract 1201 TFPI is the major physiological inhibitor of the extrinsic pathway of blood coagulation. Thus, blocking TFPI activity is a possible approach to treat bleeding disorders such as hemophilia A and B. BAX 513, a fucoidan derived from the brown seaweed L. japonica, and other non-anticoagulant sulfated polysaccharides (NASPs) improve coagulation in hemophilic blood and plasma (Liu et al. Thromb Haemost 2006;95:68). This procoagulant activity of NASPs can at least partially be attributed to the inhibition of TFPI. For this study, we predicted that endogenous TFPI levels are associated with decreased hemostatic capacity under hemophilic conditions. We correlated clotting parameters measured by global hemostatic assays with the total and full-length (FL) TFPI levels in human plasma samples in the absence or presence of BAX 513. Tissue factor-triggered coagulation of normal and FVIII-inhibited plasma or blood from 30 healthy subjects was monitored by calibrated automated thrombograph (CAT) assay and rotation thromboelastometry (ROTEM). The experiments were performed with or without factor VIII blockade with a goat anti-human Factor VIII antibody to simulate acquired hemophilia. The total and FL-TFPI plasma levels were quantified by ELISA. We observed longer clotting and clot formation times by ROTEM and decreased thrombin generation in the presence of high TFPI levels in normal plasma (p<0.05). These correlations became substantially stronger when FVIII was inhibited (reaching up to r2= 0.64; p<0.001). In the presence of BAX 513 (0.1–1.2 μg/mL), most plasma samples showed a pro-coagulant response with an at least 50% increase in thrombin peak and a decrease in time to peak. The BAX 513-mediated increase in thrombin generation correlated strongly with the individual FL-TFPI plasma level. The effect was even more apparent when FVIII was inhibited, where the extrinsic pathway is the only driver of thrombin formation. These data indicate that high endogenous TFPI levels critically compromise hemostasis in acquired factor VIII deficiency and that TFPI is a threshold factor for the intrinsic amplification of thrombin formation. As low TFPI levels are associated with increased blood clotting, TFPI inhibition is a rationale treatment approach in patients with hemophilia. Importantly, our findings validate the inhibition of TFPI activity as a mode of action for BAX 513 and related pro-coagulant compounds. Disclosures: Dockal: Baxter Innovations GmbH: Employment. Gorczyca:Medical University of Vienna: Employment. Knappe:Baxter Innovations GmbH: Employment. Palige:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment.

scholarly journals Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation

Blood ◽  
2010 ◽  
Vol 115 (2) ◽  
pp. 161-167 ◽  
Author(s):  
Nicholas T. Funderburg ◽  
Elizabeth Mayne ◽  
Scott F. Sieg ◽  
Robert Asaad ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Tissue Factor ◽  
Immune Activation ◽  
Interleukin 6 ◽  
Plasma Levels ◽  
Thrombus Formation ◽  
Hiv Replication ◽  
Increased Risk

Abstract HIV infection is associated with an increased risk of thrombosis; and as antiretroviral therapy has increased the lifespan of HIV-infected patients, their risk for cardiovascular events is expected to increase. A large clinical study found recently that all-cause mortality for HIV+ patients was related to plasma levels of interleukin-6 and to D-dimer products of fibrinolysis. We provide evidence that this elevated risk for coagulation may be related to increased proportions of monocytes expressing cell surface tissue factor (TF, thromboplastin) in persons with HIV infection. Monocyte TF expression could be induced in vitro by lipopolysaccharide and flagellin, but not by interleukin-6. Monocyte expression of TF was correlated with HIV levels in plasma, with indices of immune activation, and with plasma levels of soluble CD14, a marker of in vivo lipopolysaccharide exposure. TF levels also correlated with plasma levels of D-dimers, reflective of in vivo clot formation and fibrinolysis. Thus, drivers of immune activation in HIV disease, such as HIV replication, and potentially, microbial translocation, may activate clotting cascades and contribute to thrombus formation and cardiovascular morbidities in HIV infection.

Hyperhomocysteinemia in cerebral vein thrombosis

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1363-1366 ◽  
Author(s):  
Ida Martinelli ◽  
Tullia Battaglioli ◽  
Paola Pedotti ◽  
Marco Cattaneo ◽  
Pier M. Mannucci
Keyword(s):  
Plasma Levels ◽  
Odds Ratio ◽  
High Plasma ◽  
Serum Folate ◽  
First Episode ◽  
Cerebral Vein ◽  
Cerebral Vein Thrombosis ◽  
Vein Thrombosis ◽  
Control Subjects ◽  
Increased Risk

Abstract High plasma levels of total homocysteine (tHcy) are a risk factor for deep vein thrombosis. Because no information on the relationship between cerebral vein thrombosis and hyperhomocysteinemia is available, a case–control study of 121 patients with a first episode of cerebral vein thrombosis and 242 healthy control subjects was carried out. Fasting plasma levels of tHcy and their postmethionine load (PML) increments, together with other laboratory markers of thrombophilia, were measured in plasma or DNA. Hyperhomocysteinemia (high fasting tHcy and/or PML increments) was diagnosed in 33 patients (27%) and 20 control subjects (8%) (odds ratio, 4.2; 95% confidence interval [CI], 2.3-7.6). Low levels of serum folate and the 677TT methylene tetrahydrofolate reductase were associated with hyperhomocysteinemia, but in a multivariate model hyperhomocysteinemia only was associated with an increased risk of cerebral vein thrombosis. Oral contraceptive intake was associated with the disease with an odds ratio of 6.1 (95% CI, 3.3-11.0). The combined presence of the latter and hyperhomocysteinemia increased the risk of the disease with an odds ratio of 19.5 (95% CI, 5.7-67.3). In conclusion, hyperhomocysteinemia is associated with a 4-fold increased risk of cerebral vein thrombosis; whether or not its correction with vitamins reduces the risk of the disease remains to be demonstrated.

scholarly journals Effects of Melatonin and Luzindole on Plasma Levels of Tissue Factor, Tissue Factor Pathway Inhibitor and Von Willebrand Factor in Rats

2015 ◽  
Vol 47 (1) ◽  
pp. 64
Author(s):  
Negrin Negrev ◽  
Yuri Nyagolov ◽  
Antoaneta Zarkova ◽  
Irina Ilieva Pashalieva ◽  
Emiliya Stancheva ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Von Willebrand Factor ◽  
Plasma Levels ◽  
Tissue Factor Pathway Inhibitor ◽  
Tissue Factor Pathway ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Sudden Increase of Antipsychotics and Induction of Deep Vein Thrombosis

2020 ◽  
Author(s):  
Arghavan Fariborzifar ◽  
Forouzan Elyasi ◽  
Marzieh Azizi
Keyword(s):  
Internal Medicine ◽  
Deep Vein Thrombosis ◽  
Blood Clotting ◽  
Common Type ◽  
Sudden Increase ◽  
Case Presentation ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Daily Dose ◽  
Deep Vein

Introduction: Antipsychotics (APs) can induce pathological blood clotting. Deep Vein Thrombosis (DVT) is a common type of Venous Thromboembolism (VTE) and a significant cause of morbidity and mortality worldwide. First or second generation APs have been specifically correlated with an increased risk of thromboembolism. Case presentation: We report a case of a bipolar female patient who developed DVT following an increase in her daily dose of APs (olanzapine and chlorpromazine). Conclusion: Physicians in other medical fields, including internal medicine and surgery, should be trained about the complication of DVT induced by APs.

scholarly journals Von Willebrand Factor:Antigen And Adamts-13 Level, But Not Soluble P-Selectin, Are Risk Factors For The First Asymptomatic Deep Vein Thrombosis In Cancer Patients Undergoing Chemotherapy

2020 ◽  
Author(s):  
Budi Setiawan ◽  
Cecilia Oktaria Permatadewi ◽  
Baringin de Samakto ◽  
Ashar Bugis ◽  
Ridho M. Naibaho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Deep Vein Thrombosis ◽  
Cancer Patients ◽  
Plasma Levels ◽  
Blood Type ◽  
Vein Thrombosis ◽  
Soluble P ◽  
Von Willebrand ◽  
Deep Vein

Abstract BackgroundThere is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy.MethodsThis prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy.ResultsDVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15-12.48, p=0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22-23.82, p=0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance. ConclusionPrechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence.

scholarly journals Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy

2015 ◽  
Vol 6 (03) ◽  
pp. 407-409 ◽  
Author(s):  
Josef Finsterer ◽  
Ernst Sehnal
Keyword(s):  
Venous Thrombosis ◽  
Factor Viii ◽  
Plasma Levels ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Intestinal Bleeding ◽  
Recurrent Bleeding ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Recurrent Epistaxis

ABSTRACTRecent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT), low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis), insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability.

Bleeding Events and Other Complications during Pregnancy and Childbirth in Women with von Willebrand Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1015-1015
Author(s):  
Andra H. James ◽  
Margaret G. Jamison
Keyword(s):  
Deep Vein Thrombosis ◽  
Gestational Diabetes ◽  
Placental Abruption ◽  
Von Willebrand Disease ◽  
Bleeding Events ◽  
Pregnancy And Childbirth ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Von Willebrand ◽  
Deep Vein

Abstract OBJECTIVE: Case reports and case series suggest that women with von Willebrand disease (VWD) are at an increased risk of bleeding and other complications during pregnancy, delivery and the postpartum period. The purpose of this study was to estimate the incidence of bleeding events and other complications in women with VWD during pregnancy and childbirth using a large national database. METHODS: The Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 2000–2003 was queried for all pregnancy-related discharges. Records with a diagnosis of VWD (ICD-9 code 286.4) were compared to records without a diagnosis of VWD. Logistic regression analyses using stratified sample weights were used to compute odds ratios with 95% confidence intervals. RESULTS: There were 4067 deliveries to women with VWD which was 0.024% of all women who delivered. Black women (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1, 0.3) and Hispanic women (OR 0.3, 95% CI 0.2, 0.4) were significantly less likely to be diagnosed with VWD than white women. During pregnancy, women with VWD were more likely to be diagnosed with hypertension, cardiomyopathy, anemia and thrombocytopenia, but they were no more likely to develop preeclampsia, eclampsia or placental abruption and were less likely to develop gestational diabetes. Although they were more likely to experience antepartum bleeding, they were no more likely to labor prematurely, have a growth restricted fetus or suffer an intrauterine fetal demise. Although their risk of pulmonary embolism was no different than that of other women, none of the women with VWD experienced a deep vein thrombosis. Women with VWD were more likely to experience a postpartum hemorrhage and had a 5-fold increased risk of being transfused. 5 of the 4067 women with VWD died. Their maternal morality rate of 123 per 100,000 deliveries was 10 times higher than the rate for all other women which was 12.7 per 100,000 deliveries. CONCLUSION: Although women with VWD do not appear to be at an increased risk of poor fetal outcomes, they are at an increased of bleeding events and death during pregnancy and childbirth. Odds Ratios (OR) with 95% Confidence Intervals (CI) for Co-Existing Medical Conditions, Pregnancy-Related Complications and Events during Pregnancy in Women with VWD Count OR with 95% CI p value Co-Existing Medical Conditions: Hypertension 54 2.2 (1.1, 3.8) .03 Cardiomyopathy 9 6.8 (1.7, 27.5) .01 Diabetes 34 1.0 (0.4, 2.5) NS Anemia 551 2.1 (1.7, 2.6) &lt; .01 Thrombocytopenia 63 2.5 (1.4, 4.7) &lt; .01 Obesity 21 0.6 (0.2, 1.6) NS Smoking 220 1.9 (1.4, 2.7) &lt; .01 Pregnancy-Related Complications: Gestational diabetes 112 0.6 (0.4, 0.9) .02 Preeclampsia 327 0.9 (0.7, 1.20) NS Eclampsia 13 2.7 (0.7, 10.9) NS Placental abruption 53 1.0 (0.5, 1.8) NS Antepartum bleeding 280 10.2 (7.1, 14.6) &lt; .01 Preterm labor 417 1.1 (0.8, 1.4) NS Fetal growth restriction 49 0.7 (0.3, 1.5) NS Intrauterine fetal death 24 1.6 (0.7, 3.9) NS Thromboembolism, Hemorrhage & Infection: Deep vein thrombosis 0 - - Pulmonary embolus 5 2.0 (0.3, 15.1) NS Postpartum hemorrhage 261 1.5 (1.1, 2.0) &lt; .01 Transfusion 152 4.7 (3.2, 7.0) &lt; .01 Postpartum infection 54 1.0 (0.5, 1.9) NS

Extrinsic-pathway activation in cancer with high factor Vlla and tissue factor

The Lancet ◽  
1995 ◽  
Vol 346 (8981) ◽  
pp. 1004-1005 ◽  
Author(s):  
A.K. Kakkar ◽  
N. DeRuvo ◽  
V. Chinswangwatanakul ◽  
S. Tebbutt ◽  
R.C.N. Williamson
Keyword(s):  
Tissue Factor ◽  
Extrinsic Pathway ◽  
Pathway Activation

Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis?

2003 ◽  
Vol 104 (4) ◽  
pp. 397-404 ◽  
Author(s):  
Andrew J. MAKIN ◽  
Natalia A.Y. CHUNG ◽  
Stanley H. SILVERMAN ◽  
Gregory Y.H. LIP
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Tissue Factor ◽  
Plasma Levels ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease ◽  
Endothelial Growth Factor

Increasing evidence points towards a prothrombotic state in atherosclerosis and its manifestations, such as peripheral artery disease (PAD), which is associated with thrombosis-related complications, such as acute limb ischaemia, graft thrombosis and stroke. We hypothesized that the increased risk of thrombogenesis in PAD may be related to abnormal angiogenesis and, thus, an increased risk of future vascular disease. To test this hypothesis, we measured plasma levels of tissue factor (TF) and related levels to indices of angiogenesis, that is vascular endothelial growth factor (VEGF) and its soluble receptor sFlt-1. We studied 234 patients (145 males; mean age 68.6±10 years) with proven PAD (ankle brachial pressure index <0.8) and compared them with 50 healthy controls. Levels of VEGF (P = 0.001) and TF (P = 0.043) were increased in patients compared with controls. There were significant correlations between VEGF and TF levels in both patients (Spearman r = 0.351, P<0.001) and healthy controls (Spearman r = 0.335, P = 0.017). Amongst PAD patients, levels of VEGF were related to gender, with women having higher levels than men. There was no difference in the levels of sFlt-1 between the patients and controls, or between the subgroups of patients. There were however significant correlations between the levels of sFlt-1 and TF (Spearman r = 0.268, P<0.001) and between sFlt-1 and VEGF (Spearman r = 0.499, P<0.001). In conclusion, patients suffering from proven PAD have higher plasma levels of TF and VEGF compared with controls, with a significant correlation between the two. This suggests a link between the hypercoagulable state in PAD and the process of angiogenesis.

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