***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Cancer patients are at high risk for  venous thromboembolism ( VTE ) . Laboratory parameters with a predictive value for VTE could help stratify patients into high- or low-risk groups . The cell adhesion molecule P-selectin was recently identified as risk factor for VTE . To investigate  soluble P-selectin ( sP-selectin )  in cancer patients as risk predictor for VTE , we performed a prospect i ve cohort study of 687 cancer patients and followed them for a median ( IQR ) of 415 ( 221 - 722 ) days . Main tumor entities were malignancies of the breast ( n = 125 ) , lung ( n = 86 ) , gastrointestinal tract ( n = 130 ) , pancreas ( n = 42 ) , kidney ( n = 19 ) , prostate ( n = 72 ) , and brain ( n = 80 ) ; 91 had hematologic malignancies ; 42 had other tumors .  VTE occurred in 44 ( 6.4 % ) patients . In multivariable analysis , elevated sP-selectin ( cutoff level , 53.1 ng/mL , 75th percentile of study population ) was a statistically significant risk factor for VTE after adjustment for age , sex , surgery , chemotherapy , and radiotherapy ( hazard ratio = 2.6 , 95 % confidence interval , 1.4 - 4.9 , P = .003 ) . The cumulative probability of VTE after 6 months was 11.9 % in patients with sP-selectin above and 3.7 % in those below the 75th percentile ( P = .002 ) . High sP-selectin plasma levels independently predict VTE  in cancer patients . Measurement of sP-selectin at diagnosis of cancer could help identify patients at increased risk for VTE Venous thromboembolism ( VTE ) is a frequent complication in cancer patients . Mean platelet volume ( MPV ) has been associated with arterial and venous thrombosis in patients without cancer . We analysed  MPV in cancer patients and investigated the association of MPV with risk of VTE and mortality . MPV was routinely determined in the Vienna Cancer and Thrombosis Study , a prospect i ve , observational cohort study of patients with newly diagnosed or progressive cancer after remission . Study endpoints were occurrence of symptomatic VTE or death during a maximum follow-up of two years . Out of 1,544 included patients , 114 ( 7.4 % ) developed VTE and 573 ( 37.1 % ) died during a median observation time of 576 days . High MPV ≥75th percentile of the study population ; ≥10.8 fL ) was associated with decreased risk of VTE compared to MPV below the 75th percentile ( HR [ 95 % CI ] : 0.59 [ 0.37 - 0.95 ] , p=0.031 ) . In multivariable analysis , including age , sex , cancer groups , newly diagnosed vs recurrent disease , platelet count and soluble P-selectin , this association remained statistically significant ( 0.65 [ 0.37 - 0.98 ] , p=0.041 ) . Mortality of patients with MPV ( ≥75th percentile was significantly decreased compared to those with lower MPV ( 0.72 [ 0.59 - 0.88 ] , p=0.001 ) . Two-year probability of VTE and overall survival was 5.5 % and 64.7 % in patients with high MPV compared to 9 % and 55.7 % in those with lower MPV . In conclusion , high MPV is associated with decreased VTE risk and improved survival  in cancer patients . This finding is contrary to results observed in patients without cancer . Further studies are needed to confirm our results and eluci date underlying mechanisms The reported incidence of thromboembolism in children with acute lymphoblastic leukemia ( ALL ) treated with L-asparaginase , vincristine , and prednisone  varies from 2.4 % to 11.5 % . The present study was design ed to prospect ively evaluate the role of the TT677 methylenetetrahydrofolate reductase ( MTHFR ) genotype , the prothrombin G20210A mutation , the factor V G1691A mutation , deficiencies of protein C , protein S , antithrombin , and increased lipoprotein ( a ) concentrations in leukemic children treated according to the ALL-Berlin-Frankfurt-Muenster ( BFM ) 90/95 study protocol s with respect to the onset of vascular events . Three hundred and one consecutive leukemic children were enrolled in this study . Fifty-five of these 301 subjects investigated had one established single prothrombotic risk factor : 20 children showed the TT677 MTHFR genotype ; 5 showed the heterozygous prothrombin G20210A variant ; 11 were carriers of the factor V G1691A mutation ( heterozygous , n = 10 ; homozygous , n = 1 ) ; 4 showed familial protein C , 4 protein S , and 2 antithrombin type I deficiency ; 9 patients were suffering from familially increased lipoprotein ( a ) [ Lp(a ) ] concentrations ( > 30 mg/dL ) . In addition , combined prothrombotic defects were found in a further 10 patients : the FV mutation was combined with the prothrombin G20210A variant ( n = 1 ) , increased Lp(a ) ( n = 3 ) , protein C deficiency ( n = 1 ) , and homozygosity for the C677 T MTHFR gene mutation ( n = 1 ) . Lp(a ) was combined with protein C deficiency ( n = 2 ) and the MTHFR TT 677 genotype ( n = 2 ) . Two hundred eighty-nine of the 301 patients were available for thrombosis-free survival analysis . In 32 ( 11 % ) of these 289 patients venous thromboembolism occurred . The overall thrombosis-free survival in patients with at least one prothrombotic defect was significantly reduced compared with patients without a prothrombotic defect within the hemostatic system ( P < .0001 ) . In addition , a clear-cut positive correlation ( P < .0001 ) was found between thrombosis and the use of central lines . However , because the prothrombotic defects diagnosed in the total childhood population studied were all found within the prevalences reported for healthy Caucasian individuals , the interaction between prothrombotic risk factors , ALL treatment , and further environmental factors is likely to cause thrombotic manifestations Although the occurrence of thrombosis in acute promyelocytic leukemia ( APL ) has been reported during retinoic acid treatment , no studies carried out in large clinical cohorts have specifically addressed this issue . We analyzed 124 APL patients treated with the all-trans retinoic acid and idarubicin protocol  and compared clinico-biologic characteristics of 11 patients who developed thrombosis with those of 113 patients who had no thrombosis . In seven patients , the events were recorded during induction , whereas in four patients deep vein thrombosis occurred in the post-induction phase . Comparison of clinico-biological characteristics of patients with and without thrombosis revealed in the former group higher median white blood cell ( WBC ) count ( 17 × 109/l , range 1.2–56 , P=0.002 ) , prevalence of the bcr3 transcript type ( 72 vs 48 % , P=0.01 ) , of FLT3-ITD ( 64 vs 28 % , P=0.02 ) , CD2 ( P=0.0001 ) and CD15 ( P=0.01 ) expression . No correlation was found with sex , age , French-American-British subtype , all-trans-retinoic acid syndrome or with thrombophilic state that was investigated in 5/11 patients . Our findings suggest that , in APL patients consistent biologic features of leukemia cells may predict increased risk of developing thrombosis Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia ( ALL ) receiving Escherichia coli asparaginase ( CASP ) combined with steroids .  Moreover , hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocol s ( including  CASP combined with prednisone during induction therapy ) . To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities ( prednisone or dexamethasone ) , the present analysis was performed . Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocol s ( PRED group , n = 280 , 60 mg/m(2 ) prednisone ; DEXA group , n = 56 , 10 mg/m(2 ) dexamethasone during induction therapy ) were studied . Study end point was the onset of symptomatic vascular accidents during induction therapy . Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group ( thrombosis frequency , 10.4 % ) compared with children in the DEXA group ( thrombosis frequency , 1.8 % ; P = .028 ) . Although no significant difference was found in the overall prevalence of prothrombotic risk factors , 46.5 % of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor , whereas no carrier in the DEXA group had a thromboembolism . At the time of maximum CASP activity , fibrinogen and activities of antithrombin , plasminogen , and protein S were significantly reduced in the PRED group . No significant correlation could be found between CASP activity and levels of coagulation factors . In conclusion , the use of dexamethasone instead of prednisone , administered with CASP , significantly reduced the onset of venous thromboembolism Venous thromboembolism is a common complication in patients with cancer , but only limited data are available in acute myeloid leukemia ( AML ) . In a prospect i ve study in a cohort of 272 adult patients ( aged 18 - 65 ) and an independent validation cohort of 132 elderly adults ( aged > 60 ) with newly diagnosed AML , we assessed markers of disseminated intravascular coagulation ( DIC ) ( fibrinogen , D-dimer , α-2-antiplasmin , antitrombin , prothrombin time , and platelet count ) and the DIC score according the International Society of Thrombosis and Haemostasis and their associations with the occurrence of venous and arterial thrombosis during follow-up . The prevalence of thrombosis was 8.7 % ( 4.7 % venous , 4.0 % arterial ) in the younger adults over a median follow-up of 478 days and 10.4 % ( 4.4 % venous , 5.9 % arterial ) in elderly patients . Most thrombotic events ( 66 % ) occurred before the start of the second course of chemotherapy . The calculated DIC score significantly predicted venous and arterial thrombosis with a hazard ratio ( HR ) for a high DIC score ( ≥5 ) of 4.79 ( 1.71 - 13.45 ) . These results were confirmed in the validation cohort of elderly patients with AML ( HR 11.08 [ 3.23 - 38.06 ] ) . Among all DIC parameters , D-dimer levels are most predictive for thrombosis with an HR of 12.3 ( 3.39 - 42.64 ) in the first cohort and an HR of 7.82 ( 1.95 - 31.38 ) in validation cohort for a D-dimer > 4 mg/L vs ≤4 mg/L. It is concluded that venous and arterial thrombosis may develop in ∼10 % of AML patients treated with intensive chemotherapy , which to a large extent can be predicted by the presence of DIC at time of AML diagnosis Purpose : Cancer patients are at an increased risk of venous thromboembolism ( VTE ) . VEGF promotes the growth of highly thrombogenic tumor vessels . Here , we explored the utility of soluble plasma VEGF-A ( sVEGF ) as a biomarker for the prediction of VTE in patients with cancer . Experimental Design : Eight hundred four patients with newly diagnosed cancer or progression after remission were prospect ively followed for 2 years until the occurrence of VTE or death [ tumor sites : brain ( n = 87 ) , breast ( n = 137 ) , lung ( n = 120 ) , gastrointestinal ( n = 143 ) , pancreas ( n = 53 ) , prostate ( n = 95 ) , kidney ( n = 22 ) , myeloma and lymphoma ( n = 99 ) , and others ( n = 48 ) ] . Primary endpoint was symptomatic or fatal VTE . sVEGF  was measured by immunoassay in baseline plasma . Results : Fifty-five patients developed VTE ( 6.8 % ) and 364 patients ( 45.3 % ) died . Five-hundred and forty-two ( 68.3 % ) participants had sVEGF levels above the detection limit of 0.5 pg/mL. The median sVEGF level ( 25th–75th percentile ) was 8.1 pg/mL ( 0–1 
    Output:
    
RESULTS AND CONCLUSIONS The most studied biomarkers , d-dimer and fibrinogen , demonstrated some degree of efficacy in identifying high-risk patients at levels > 4.0 mg/L or < 1.0 g/L respectively .
Additional markers which demonstrated promise included thrombin generation , mean platelet volume , soluble VEGF , soluble P-selectin and extracellular vesicles .