Risk Of Thrombosis In Patients Research Articles

Inhibition of platelet activation could decrease thrombotic events in hemodialysis PF4/H antibody-positive patients

Background: Platelet factor 4/heparin (PF4/H) antibody detection is widely used to evaluate the risk of thrombosis in patients undergoing hemodialysis (HD). Most patients who are PF4/H-antibody-positive can survive thrombosis, but the reason has not been clarified. In addition, no valid preventive methods for thrombosis in patients undergoing HD have been confirmed. Methods: A single-center, semi-randomized controlled study was designed. In total, 157 patients fulfilled the inclusion criteria and participated. Patients were first divided according to PF4/H antibody detection and then subdivided randomly according to different anti-platelet agent descriptions. Results: (1) PF4/H antibody-positive patients suffered a significantly higher incidence of thrombosis than those who were antibody-negative; (2) PF4/H antibody-positive patients who survived a thrombosis manifested a significantly longer bleeding time and decreased maximum percentage of platelet aggregation inhibition; (3) aspirin and clopidogrel decreased the incidence of thrombosis in PF4/H antibody-positive patients by inhibiting platelet activation. Conclusion: The PF4/H antibody was effective for prediction of the risk of thrombosis, except in patients with dysfunctional platelets; aspirin manifested effects similar to clopidogrel in terms of prevention of thromboses in PF4/H antibody-positive patients, but costs much less and is therefore recommended.

A New Chemiluminescent Enzyme Immunoassay for Plasma Tissue Factor Detection

High concentrations of tissue factor (TF) in the plasma may have a major role in the elevated risk of thrombosis in patients with malignant diseases. The quantification of plasma TF concentrations in cancer patients may enable accurate assessments of the risk of thrombosis during the process of cancer progression. Whether the plasma TF concentration is associated with the tumor volume in pancreatic cancer in the field of cancer biology remains uncertain. Rat anti-human TF monoclonal antibodies were prepared in our laboratory and were used in a chemiluminescent enzyme immunoassay (CLEIA) for TF detection. In an in vitro experiment, the antibodies for human TF did not crossreact with mouse TF. Therefore, tumor-derived TF was specifically detected using a novel sensitive human TF detection system developed for this study. The plasma concentration of tumor-derived TF was positively correlated with the tumor volume in mice bearing the human pancreatic cancer cell line BxPC-3. Thus, the plasma TF concentration may be a useful tumor marker. These data warrant further preclinical and clinical investigations of our CLEIA system.

Procoagulant Status In Patients With Immune Thrombocytopenia

IntroductionImmune thrombocytopaenia (ITP) is an acquired immune-mediated disorder characterized by mild to severe thrombocytopaenia caused by autoantibodies against platelet proteins. Bleeding risk in patients with ITP is increased with platelet counts less than 20 or 30 x 109/L. However, patients with ITP often have few bleeding symptoms despite very low platelet counts suggesting the existence of compensatory mechanisms. Moreover, an increased risk for thrombosis in patients with ITP has been described (Nørgaard M, 2012). It has been recently reported that increased production of platelet- and red cells-derived microparticles (MP) might be one of the causes of increased thrombotic risk in ITP patients (Sewify, 2013). ObjectiveThe aim of this study was to evaluate the microparticle-associated and plasma procoagulant activities in ITP patients with thrombocytopaenia. MethodsSixty-eight patients with chronic ITP and platelet count less than 50 x 109/L and twenty-two healthy controls were included. Platelet counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Citrated blood was centrifuged at 1,500 g for 15 min at 23°C. Platelet-poor plasma obtained was additionally centrifuged twice at 23°C (15 min at 1,500 g, and 2 min at 13,000 g) and aliquots were stored at -70ºC until analysis.Phosphatidylserine-MP (Ph-MP) and tissue factor-MP (TF-MP) dependent procoagulant activities were determined with the ZYMUPHEN kits (Hyphen BioMed, Neuville sur Oise, France) following the manufacturer's instructions.Plasma thrombin generation was measured using the Calibrated Automated Thrombogram (CAT) test as described by Hemker et al (2000) at a final concentration of 1 pM tissue factor and 4 μM phospholipids (PPP-Reagent LOW, Thrombinoscope BV, Maastricht, The Netherlands). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak.To test resistance to protein C, CAT experiments were performed without and with the addition of thrombomodulin (TM) (PPP and PPP with thrombomodulin reagents, Thrombinoscope BV, Maastricht, The Netherlands). Results were expressed as the ratio [(ETP with TM)/(ETP without ETP)]x100.Results were expressed as mean±SD. Comparisons of quantitative variables were made with Mann-Whitney test and correlations with Spearman test. Values of p≤0.05 were considered statistically significant. ResultsPh-MP associated procoagulant capacity in ITP patients was higher than in controls (p<0.05) whereas MP-TF associated procoagulant activity was practically negligible in both groups. Plasma procoagulant activity was higher in ITP patients than in controls (ETP: 1604±616 nM x min in ITP patients and 1302±416, p=0.012 in controls; Peak: 328±123 nM in ITP patients and 203±74 nM in controls, p<0.001). We tested whether the higher procoagulant activity of plasma from ITP patients was due to a resistance to protein C. We observed that the mean Ratio value in ITP patients was slightly higher than the mean Ratio of controls (60±18 and 50±13 respectively, p=0.034). Despite this significant difference in the Ratio, no correlation was found between this value and the CAT parameters. ConclusionITP patients with thrombocytopaenia had a higher Ph-MP associated and plasma procoagulant activity than controls. The fact that the increased MP-procoagulant activity was not accompanied by a higher TF-MP associated procoagulant activity brings further support to the previous observation that MPs in ITP patients are from platelets and red cells, as both cells express very low levels of TF (Sewify, 2013). Regarding the increased plasma procoagulant capacity observed in ITP patients, our results suggest that resistance to protein C does not seem to be the main mechanism involved.References• Nørgaard M. Thromb Res. 2012;130 Suppl 1:S74-75.• Sewify EM, et al. Thromb Res. 2013;131:e59-63.Hemker HC, et al. Thromb Haemost 2000;83:589-9. Disclosures:No relevant conflicts of interest to declare.

Identification Of Markers Of Thrombotic Risk and Response To Cytoreductive Intervention In Philadelphia-Chromosome Negative Myeloproliferative Neoplams

BackgroundThrombosis is a major cause of morbidity and mortality in the Philadelphia-chromosome negative myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in patients with MPN is poorly understood. MPNs are associated with elevated levels of inflammatory cytokines and abnormal platelet activation including elevated platelet factor 4 (PF4), B-thromboglobulin (B-TG) and p-selectin levels. However the relationship between these inflammatory markers and the onset of thrombosis is unclear. Current treatment guidelines recommend the use of cytoreductive agents to decrease thrombosis risk based on history of prior thrombosis and age. The effect of cytoreduction on inflammatory markers has only been partially characterized. Furthermore, current clinical guidelines fail to predict thrombotic events in all patients. Thus, more accurate risk stratification is necessary. AimTo determine if levels of p-selectin and PF4 correlate with thrombotic events and if levels of p-selectin and PF4 are affected by cytoreductive therapy. MethodsBiobanked samples from 16 patients with a confirmed diagnosis of chronic phase MPN (per WHO 2008 criteria) were included in this study. Seven patients had primary myelofibrosis, five had polycythemia vera, and four had essential thrombocythemia. Median age of patients was 65.5 (range 44-81). Fourteen patients had a JAK2 V617F mutation. Four patients with samples collected before and after thrombotic episodes, four patients with post-thrombotic samples, four without a history of thrombosis, and four patients with samples obtained before and after cytoreduction were analyzed. Patient characteristics are summarized in Table 1. Plasma samples were analyzed for levels of PF4 and p-selectin using commercially-available ELISA assays under standard conditions. [Display omitted] ResultsMeasurement of p-selectin levels in MPN patients with a history of a thrombotic event versus disease matched control MPN patients with no history of thrombosis demonstrated an increase in the level of p-selectin in patients with thrombosis. Elevated levels of PF4 were noted in only one patient who had a history of thrombosis, and who was maintained on Aspirin. This suggests that elevated levels of p-selectin may be an indicator of thrombosis risk in patients with MPN.Levels of PF4 and p-selectin were next assessed in patients who had suffered a thrombotic event, both before and after the event had occurred. No changes in p-selectin or PF4 levels pre and post thrombosis were noted.The effect of cytoreduction was measured using samples from patients pre- and post-cytoreduction. No differences in the level of PF4 were noted with cytoreduction. In contrast, reductions in p-selectin were noted in two patients in whom cytoreduction was achieved with Ruxolitinib, but not in two patients in whom cytoreduced with hydroxyurea or pomalidomide. This suggesting that Ruxolitinib may have role in thrombosis risk reduction.Platelet levels were recorded for all 16 patients. There was no difference in platelet levels in each group of patients. In contrast to the changes observed with p-selectin, there was no difference in platelet levels in patients with out a thrombotic event compared to those with a history of thrombosis. This suggests that platelet activation, as measured by p-selectin, may be a stronger indicator of thrombotic risk than platelet levels. ConclusionsImprovements in risk stratification of thrombotic risk for patients with MPN are needed. Platelet activation in MPNs is abnormal and may serve as an additional marker of thrombotic risk. Our results suggest that levels of p-selectin, but not PF4, may be associated with increased thrombotic risk. Furthermore, treatment with the JAK1/2 inhibitor Ruxolitinib resulted in reduction in levels of p-selectin, suggesting that the role of Ruxolitinib in preventing thrombotic event should be further investigated. Additional studies with larger numbers are in progress to validate these results. [Display omitted] Disclosures:Rampal:Foundation Medicine: Consultancy.

Evaluation of the prevalence of severe hyperhomocysteinemia in adult patients with thrombosis who underwent screening for thrombophilia

Treatment with B-vitamins and betaine reduces the high risk of thrombosis in patients with homocystinuria, a metabolic syndrome that is characterized by severe hyperhomocysteinemia (HHcy). In contrast, there is no clear demonstration that B-vitamins reduce the risk of thrombosis in patients with mild HHcy: for this reason, many question the clinical utility of measuring total Hcy (tHcy) in patients with thrombosis. However, thrombosis may be the first clinical manifestation of homocystinuria in patients reaching adulthood without signs and symptoms of the syndrome. 1) to measure the prevalence of severe, previously undiagnosed, HHcy among patients with thrombosis 2) to profile these patients on the basis of their characteristics. Six Italian Thrombosis Centers completed a first questionnaire, reporting tHcy levels in patients with thrombosis who underwent thrombophilia screening, and a second questionnaire, reporting the characteristics of patients with severe HHcy (tHcy>100μmol/L). Of 19,678 cross-sectionally collected patients with thrombosis who underwent thrombophilia screening in the last 12.5years (median value, range 6-17), 38 had severe HHcy (0.2%). Their median age at diagnosis was 47years (range 19-83) and the median level of tHcy was 130μmol/L (range 101-262). Venous thromboembolism (71%) was more frequent than arterial thromboembolism (26%); recurrent thrombosis occurred in 42% of cases. Measurement of tHcy in adult patients with thrombosis may reveal the presence of severe HHcy. Since treatment of patients with severe HHcy decreases the risk of thrombosis, measurement of tHcy in patients with thrombosis may prove clinically useful.

Intermittent pneumatic compression reduced deep venous thrombosis after stroke

Source Citation CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients wh...

AB0011 The association between p-selectin polymorphisms and thrombosis in antiphospholipid syndrome: a pilot study

BackgroundAntiphospholipid syndrome (APS) is an autoimmune disease characterised by recurrent arterial or venous thrombosis, pregnancy morbidity and the persistence of positive antiphospholipid antibodies (aPLA). The selectins are cell adhesion molecules...

Thrombotic events in metastatic colorectal cancer patients treated with FOLFIRI plus bevacizumab.

e14630 Background: To determine the incidence and risk factors for thrombotic events (TEs) (arterial and venous) in patients with metastatic colorectal cancer (mCRC) who received Bevacizumab and FOLFIRI (Leucovorin, Fluorouracil and Irinotican ) compared to FOLFIRI alone. Methods: Single institution retrospective study of 450 mCRC patients who received either Bevacizumab plus FOLFIRI or FOLFIRI alone between October 2006 and September 2012. Demographics , TE risk factors and treatment data were abstracted from patients records. Multivariate analysis was used to determine factors that contributed to increased TE incidence. Results: 261 mCRC patients received Bevacizumab plus FOLFIRI ( 64.8 % males , mean Body Mass Index (BMI) 26.1 ) compared to 189 control patients who received FOLFIRI alone ( 61.1 % males ,BMI 27). The incidence of TEs was 15 % (arterial 1.8% + venous 13.2%) in the Bevacizumab plus FOLFIRI group compared to 15.8% (arterial 2.1% + venous 13.7%) in the control groups. Multivariate analysis controlled for age, BMI, gender, malignancy, metastatic sites , line of treatment, and risk factors did not suggest a significant increase in risk of TE associated with Bevacizumab (OR=0.83 95% CI: 0.40 - 1.70; p=0.602). No difference in locations of TEs was observed between both groups . The only statistically significant factor for thrombosis in Bevacizumab group was increased BMI (OR=1.05; 95% CI: 1.01- 1.10; p=0.016). Conclusions: Our data suggest that bevacizumab did not significantly increase the rate of thrombosis in patients with mCRC when added to FOLFIRI. To our knowledge this is the first study reporting the rate of TEs (arterial and venous) in this population.Our data suggest that BMI may be a risk factor for increase risk of thrombosis in patients treated with bevacizumab . Clinician should consider risk factors assessment prior to initiating bevacizumab .

Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention.

OC-14 Pregnancy related thrombosis risk in patients with protein C deficiency

Background: Venous thrombosis (VT) continues to be one of the leading causes of maternal morbidity and mortality in countries with good perinatal care. The incidence of pregnancy related VT is approximately 1 per 1000 pregnancies. Major complications from VT are post-thrombotic syndrome and death from pulmonary embolism. Limited data exist on thrombophilia and the risk of VT during pregnancy and postpartum, and further, whether biomarkers associated with VT are associated with different risk for deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods: The present study is a substudy of the Venous Thromboembolism in Pregnancy (VIP) study. 313 cases with objectively verified first time VT and 353 controls were selected from a source population of 377155 women with 613232 pregnancies. When we analyzed phenotypic hemostatic parameters, women with conditions known to influence coagulation parameters were excluded. Furthermore, women diagnosed with VT at unusual sites were excluded when we analyzed the risk for DVT and PE. Percentiles were defined in controls. Results: The odds ratios (ORs) for pregnancy related VTwas increased for women with factor VIII and factor IX above the 90th percentile, ORs 1.9; 95% CI 1.2-3.1 and 2.1; 95% CI 1.3-3.4, respectively. ORs for VT for endogenous thrombin potential and D-dimer values above the 90th percentile were 2.1; 95% CI 1.3-3.3 and 2.3; 95% CI 1.4-3.7, respectively. Women with low levels of protein S had increased risk for PE, ORs 2.1; 95% CI 1.1-4.3. Low levels of protein S were not associated with DVT. Similarly, high levels of fibrinogen were associated with PE, OR 2.5; 95% CI 1.3-4.9, whereas the risk for DVT as compared with controls was not increased. Women carrying factor V Leiden polymorphism (F5 rs6025) had increased risk for DVT, OR 7.7; 95% CI 4.7-12.7, whereas the risk for PEwas not increased. Analyzing only non-carriers of F5 rs6025, reduced sensitivity to activated protein C (aPC) was associated with increased risk for DVT, OR 3.5; 95% CI 2.2-5.4, whereas the risk for pulmonary embolism was not increased. Comment: Women with a history of pregnancy related VT showed activation of coagulation and had elevated factor VIII and IX. Furthermore, reduced sensitivity to aPC in absence of F5 rs6025, or carrying F5 rs6025 were risk factors for DVT, but not for PE, whereas high levels offibrinogen and low levels of free protein Swere associated with increased risk for PE, but not for DVT.

Thrombin generation as marker to estimate thrombosis risk in patients with abnormal test results in lupus anticoagulant routine diagnostics

BackgroundLupus anticoagulant (LA) is known to inhibit thrombin generation although patients have an increased risk to develop thrombosis. We tried to determine whether thrombin generation is altered in plasma samples of patients with abnormal test results in LA routine diagnostics and whether its measurement may improve the risk assessment of thrombosis.MethodsSamples from 63 patients (39 with abnormal test results; 24 controls) were included in the study. Measurement of diluted Russel’s viper venom time (dRVVT) was part of the initial guideline conform diagnostic procedure for detection of LA. In addition, measurement of anticardiolipin-IgM, -IgG and β2-glycoprotein-I-IgM, -IgG were performed. Thrombin generation was measured using two different phospholipid concentrations in the starting reagent.ResultsAnalyzing all samples by logistic regression, thrombin generation after induction with high phospholipid concentrations was the best predictor of thrombosis. After preselection of samples with alterations in dRVVT, specificity of selected thrombin generation derived parameters for the detection of previous thrombosis increased in this subgroup.ConclusionsIn patients with phospholipid-dependent prolongation of dRVVT, thrombin generation is variably inhibited and the degree of inhibition corresponds to the occurrence of previous thrombosis. Measuring thrombin generation in patients with phospholipid-dependent dRVVT prolongation may improve risk assessment of thrombosis.

Decanucleotide Insertion Polymorphism of F7 Influences Significantly the Risk of Thrombosis in Patients with Essential Thrombocythemia

Abstract 1730Thrombosis is one of the main complications observed in patients with myeloproliferative neoplasm (MPN). The underlying mechanisms of thrombosis are not entirely clarified. The incidence of, and risk factors for, thrombosis appear to differ in distinct and accurately diagnosed sub-entities of MPN. Similar incidences have been reported for essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (PMF) diagnosed according to the WHO 2008 criteria. However, the two sub-entities differ in terms of their risk factor profiles (Carobbio et al, Blood 2011; Buxhofer-Ausch et al, Am J Haematol 2012). A gain of function in procoagulant pathways is believed to be the reason for an inherited hypercoagulable state (Anderson et al, Crit Care Clin 2011). There is strong evidence indicating that certain thrombophilic single nucleotide polymorphisms account for increased risk of thrombotic complications (Di Castelnuovo et al, Thromb Res 2000; Shimasaki et al, J Am Coll Cardiol 1998; Elbaz et al, Stroke 2000; Mollaki et al, J Thromb Haemost 2004). Data concerning the impact of an inherited risk in patients with underlying MPN are scarce (Shetty, Thromb Res 2011). We aimed to investigate the influence of three pre-selected thrombophilic single nucleotide polymorphisms (SNPs) on the risk of thrombosis in patients diagnosed with ET or prefibrotic PMF according to the WHO 2008 criteria.In 167 patients with a valid consensus diagnosis of ET (n= 105) or prefibrotic PMF (n= 62), the thrombophilic SNPs of NOS3 (Glu 298 Asp), F7 (10 nucleotide insertion-deletion) and FCGR2A (His 131 Arg) were determined by AS-PCR or sequencing. These variables and certain disease-specific and laboratory parameters were correlated with the incidence of major arterial and venous thrombosis by using Cox-regression analysis. The latter was performed in the entire population as well as separately for ET and prefibrotic PMF.The frequency of SNPs of F7, NOS3 and FCGR2A did not differ significantly in ET and prefibrotic PMF. Notably, the homo- or heterozygous insertion variant of F7 was found to be a significant (multivariate analysis) risk factor for total thrombosis and arterial thrombosis in the entire population (HR 3.06, p= 0.0082 and HR 3.94, p= 0.0007, respectively) as well as on separate analysis of those patients with ET (HR 5.94, p= 0.001 and HR 9,47, p= 0.00024, respectively). The homozygous 298 Asp NOS variant was significantly (univariate analysis) associated with total thrombosis in the entire population (HR 3.29, p= 0.0257) as well as on separate analysis of the ET cohort (HR 4.739, p= 0.0161). These significances were lost on multivariate analysis. No significant associations were established with any of the tested thrombophilic SNPs and the risk of thrombosis in the prefibrotic PMF cohort.Our data show that the risk of thrombosis in ET diagnosed according to WHO 2008 is increased many-fold by the inherited insertion polymorphism of F7. This is very interesting because, in patients without an underlying pathological condition, this polymorphism appears to protect the organism against thrombosis by reducing FVII activity (Humphries et al, Thromb Haemost 1996). Moreover, the different impact of thrombophilic SNPs in ET compared to prefibrotic PMF might provide further evidence of the presumed difference in risk profiles between these two sub-entities of MPN. These data emphasize the importance of considering the inherited as well as acquired hypercoagulable state in patients with MPN. Larger studies are needed to confirm these findings. If proven true, we would be able to more accurately define the risk of thrombosis in an individual patient and subsequently tailor treatment and anticoagulation strategies. Disclosures:No relevant conflicts of interest to declare.

C0176 Influence of common thrombophilia polymorphisms on the thrombosis risk in patients with JAK2-V617F-positive myeloproliferative neoplasms

C0176 Influence of common thrombophilia polymorphisms on the thrombosis risk in patients with JAK2-V617F-positive myeloproliferative neoplasms

C0355 Pregnancy related thrombosis risk in patients with protein C deficiency

Venous thromboembolism (VTE) is a common adverse event during pregnancy. The risk of VTE in pregnant women with FV Leiden(FVL) or prothrombin gene mutation has been extensively studied. However, data is scarce for patients having inherited protein C(PC) deficiency. The aim of this study was to determine the risk of pregnancy related-VTE in patients with PC deficiency compared to patients with heterozygous FVL.

687 Aortic Surgery Patients With a Positive Hit Elisa Are at Increased Risk of Thrombosis

Heparin induced thrombocytopenia (HIT) and thrombosis (HITT) is an important cause of morbidity/mortality/cost after cardiac surgery (CS). Thrombotic complications include deep venous thrombosis (DVT), pulmonary emboli (PE) and arterial occlusion (AO). The rapidly available ELISA (positive if the optical density is ≥ 0.4) is sensitive but non-specific. The serotonin release assay (SRA) is specific but generally not immediately available. If HITT is clinically suspected (positive ELISA), a non-heparin based anticoagulant should be started which is associated with increased cost and risk of bleeding. If there were known pre- and intraoperative factors associated with thrombosis, this would assist in clinical decision making with regard to starting a non-heparin anticoagulant. We sought to determine pre- and intraoperative factors associated with increased risk of DVT,PE and AO post CS in patients suspected of HIT. The CS patients having a HIT ELISA between 2008 - 2010 were divided into 2 groups: the high risk thrombosis (HRT) group had a positive ELISA with a positive SRA, or positive ELISA with evidence of DVT/PE/AO (but negative SRA); the low risk thrombosis (LRT) group had a negative ELISA, a negative SRA, or a positive ELISA with negative SRA. Regression analysis was performed to determine factors associated with thrombotic risk. Of the 269 patients having ELISA assays, 47 (17.4%) were positive. Of these 47, 11 had a positive SRA, and 6 had negative SRA but evidence of thrombosis - i.e. 17 patients in HRT group. The remaining 252 were the LRT group. (See table for univariate analysis). Multivariate analysis revealed aortic surgery to be associated with HRT (OR 4.9, 95% CI 1.3 - 17.8, p=0.017). ICU LOS was longer in HRT group - 4.8 (3.8 - 8.0) vs. 3.8 (2.2 - 6.8) days in LRT group, p=0.05.Tabled 1 Our data suggest that there appears to be an increased risk of thrombosis in patients having aortic surgery and who have a positive HIT ELISA.

Hydroxychloroquine Use Is Associated with Lower Odds of Persistently Positive Antiphospholipid Antibodies and/or Lupus Anticoagulant in Systemic Lupus Erythematosus

Antiphospholipid antibodies (aPL) play an active role in the pathogenesis of the antiphospholipid syndrome (APS). Primary prevention in APS may be aimed at decreasing existing elevated aPL levels, or preventing high aPL titers and/or lupus anticoagulant (LAC) from developing in the first place. Hydroxychloroquine (HCQ) has been shown in retrospective studies to decrease aPL titers in laboratory studies, and to decrease thrombosis risk in patients with systemic lupus erythematosus (SLE). We investigated an association between HCQ use and persistent aPL and/or LAC in SLE. We identified all patients over 21 years old with SLE from an urban tertiary care center who had aPL and LAC measured on at least 2 occasions at least 12 weeks apart. We defined the presence of persistent LAC+ and/or at least 1 aPL ≥ 40 U [immunoglobulin A (IgA), IgG, or IgM] as the main outcome variable. Among 90 patients included in the study, 17 (19%) had persistent LAC+ and/or at least 1 aPL ≥ 40 U. HCQ use was associated with significantly lower odds of having persistent LAC+ and/or aPL ≥ 40 U (OR 0.21, 95% CI 0.05, 0.79, p = 0.02), adjusted for age, ethnicity, and sex. This is the first study to show that HCQ use is associated with lower odds of having persistently positive LAC and/or aPL. Data from this study provide a basis for the design of future prospective studies investigating the role of HCQ in primary and secondary prevention of APS.

Relationship between tissue factor expression by human pancreatic cancer cells and activation of coagulation and thrombosis in a mouse model.

e14505 Background: The increased risk of thrombosis in patients with cancer has been well established. However, the triggers in these patients have yet to be fully defined. Under pathological conditions, the potent procoagulant protein Tissue Factor (TF) is found in the circulation and may trigger thrombosis. Methods: We evaluated the level of TF expression in 4 different human pancreatic cancer cell lines. We also measured TF microparticle (MP) release from these tumors in vivo by flow cytometry and TF activity assay. We then used these lines in a mouse model of pancreatic cancer to evaluate the sources of TF that activate coagulation and contribute to thrombosis using a saphenous vein model. Results: We found that mice bearing orthotopic pancreatic tumors which express higher levels of TF (HPAC and HPAF) show increased activation of coagulation (measured by thrombin-antithrombin complex) as compared to mice bearing TF negative tumors (MIA-PaCa-2 and PANC-1). This activation of coagulation could be reduced by treatment with a human TF antibody. Further, mice bearing tumors derived from TF high cell line HPAC demonstrated an activation of coagulation despite a lack of circulating TF-positive MPs. Mice bearing TF expressing pancreatic tumors also demonstrated increased thrombosis by a saphenous vein model. Treatment of tumor-free mice with TF MPs did not result in an activation of coagulation or increased thrombosis unless mice were given 40-100 fold higher levels of TF bearing MPs than are found in the circulation of tumor bearing mice. Conclusions: The data suggest that TF on the tumor itself is involved in the activation of coagulation whereas circulating TF-positive MPs is likely to contribute to thrombosis. Elevated levels of TF-positive MPs may be used as a biomarker to identify cancer patients at risk for thrombosis.

Abstract 518: Antithrombotic Effects of Apelin: Implication During Metabolic Disorders

Thrombotic risk, that is partly related to a disturbed adipokine/cytokine profile, is strongly increased in obese and type 2 diabetic patients and. Apelin is an adipokine with pleiotropic function and cardiovascular fluid, and energetic homeostasis, and acts through the APJ transmembrane receptor. In this project, we show for the first time that apelin displays a potent antithrombotic effect The antithrombotic effect is APJ- mediated and requires the proteolytic maturation of apelin. Apelin strongly inhibits thrombin- or collagen- induced platelet aggregation, independently of ADP secretion. It prevents platelet activation and thrombin-activated intracellular signaling pathways. As a consequence, in mice models, intravenous apelin injection increases tail-bleeding time and delays chemically- induced vessel occlusion and thrombus stabilization. We also determined that functional APJ is strongly over-expressed in platelet from obese subjects or mice (DIO mice, db/db), but apelin preserved its antithrombotic function during these metabolic disorder conditions. In conclusion, in this original study, we enlighten a new biological function of apelin that could be considered as a new strategy to reduce the increased risk of thrombosis in patients with metabolic disorders.

Platelet aggregation in children with end-stage kidney disease in relation to level of L-arginine as a risk factor for vascular thrombosis

objectives: The aim of the study is to evaluate the level of L‑arginine in patients of end‑stage kidney disease (ESKD) under regular hemodialysis and to determine its relation to platelet aggregation as a risk factor for vascular thrombosis which is a very important complication that affects the life span of those patients. In addition, we also tried to establish the relationship between L‑arginine, platelet aggregation, and nutritional state of patients with ESKD. s ubjects and Methods: Our study was “a case‑control study”, comparing data between 30 patients with ESKD under treatment with regular hemodialysis‑group (A); group A1 (16)‑patients with ESKD on regular hemodialysis with malnutrition, group A2 (14)‑patients with ESKD on regular hemodialysis with normal nutrition state, and group B 10 subjects as healthy control group, each patient was evaluated for serum arginine level by high‑performance liquid chromatography, and platelet aggregation, as well as other routine investigations. A thorough clinical history and examination were performed for all the patients. results: Our study shows significant higher level of platelet aggregation to ADP in group A than group B (119±11.9% and 81.1±6.5% respectively, P<0.05), a lower level of serum arginine in group A (71±45.3 μg/L) than in group B (120.5±14.6 μg/L) with P<0.05. Also our study shows a lower level of serum arginine in group A1 (60.5±12.3 μg/L) than group A2 (83±27 μg/L) and a lower level in group A2 than group B (120.5±14.6 μg//l), and we found a negative correlation between serum arginine level and platelet aggregation expressing a more risk for thrombosis in patients with ESKD specially those with malnutrition. conclusions: We concluded that patients with ESKD has a low level of L‑arginine specially in those with malnutrition and this leads to increase in platelet aggregation and may increase the possibility of thrombus formation in malnourished patients with ESKD. We suggest the use of nutritional supplementation of L‑arginine to suppress this process of atherothrombosis.

Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes.

There are limited reports of thrombosis among myelodysplastic syndrome patients exposed to erythropoiesis stimulating agents. It is not clear whether erythropoiesis stimulating agents are associated with an increased risk of thrombosis in myelodysplastic syndromes, as they are among patients with solid tumors. The association between use of erythropoiesis stimulating agent and transient thrombosis risk in patients with myelodysplastic syndromes was assessed in a case-crossover study nested within a cohort of incident myelodysplastic syndrome patients. Using the US Surveillance, Epidemiology, and End Results Medicare-linked database, cases with an incident diagnosis of deep vein thrombosis were identified. Using conditional logistical regression, the odds of exposure to erythropoiesis stimulating agents in the 12 weeks prior to the incident deep vein thrombosis (hazard period) was compared to the exposure odds in a prior 12-week comparison period. Within the cohort of eligibles with myelodysplastic syndromes (n = 5,673) there were 212 incident cases of deep vein thrombosis events. Mean age was 76.2 (standard deviation = ± 8.6) years. Use of erythropoiesis stimulating agents was not associated with deep vein thrombosis in the crude nor the adjusted models (OR = 1.21, 95% CI: 0.60, 2.43). Central venous catheter placement (OR = 6.47, 95% CI: 2.37, 17.62) and red blood cell transfusion (OR = 4.60, 95% CI: 2.29, 9.23) were associated with deep vein thrombosis. Despite the link between use of erythropoiesis stimulating agents and thrombosis among patients with solid tumors, this study provides evidence that their safety profile may be different among patients with myelodysplastic syndromes.