***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: Patients with CKD on hemodialysis exhibit increased cardiovascular risk .  Fibrin clot structure and clot lysis are crucially involved in development of cardiovascular events , but little is known about the influence of clot density on outcome in patients on hemodialysis . We determined fibrin clot structure parameters and effect on mortality in a prospect i ve cohort of 171 patients on chronic hemodialysis ( mean±SD age = 59±11 years old ; 54 % men ) using a vali date d turbidimetric assay . Kaplan-Meier analysis revealed that patients on hemodialysis with a denser clot structure had increased all-cause and cardiovascular mortality risks ( log rank P=0.004 and P=0.003 , respectively ) . Multivariate Cox regression models ( adjusted for age , diabetes , sex , and duration of dialysis or fibrinogen , C-reactive protein , and complement C3 ) confirmed that denser clots are independently related to mortality risk . We also purified fibrinogen from healthy controls and patients on hemodialysis  using the calcium-dependent IF-1 mAb against fibrinogen for additional investigation using mass spectrometric analysis and electron microscopy . Whereas purified fibrinogen from healthy controls displayed no post-translational modifications , fibrinogen from patients on hemodialysis was glycosylated and guanidinylated . Clots made of purified fibrinogen from patients on hemodialysis exhibited significantly thinner fibers compared with clots from fibrinogen of control individuals ( mean±SD = 63±2 and 77±2 nm , respectively ; P<0.001 ) . In vitro guanidinylation of fibrinogen from healthy subjects increased the formation of thinner fibers , suggesting that difference in fiber thickness might be at least partially due to post-translational modifications . Thus , in patients on hemodialysis , a denser clot structure may be a potent independent risk factor for mortality The effect of acetylsalicylic acid in preventing cardiovascular complications is ascribed to acetylation of the enzyme cyclo-oxygenase thereby inhibiting prostagl and in synthesis . Acetylsalicylic acid , however , also acetylates fibrinogen . In the present pilot study , we investigated the permeability , i.e. porosity , of the fibrin gel in male patients with stable angina pectoris treated with this drug before and at 1 and 2 weeks after withdrawal . Ten patients were treated with 75 mg and eight with 160 mg . The results were compared to those in seven untreated healthy controls .  Bleeding times were longer during treatment and were reduced after withdrawal indicating patient compliance . Fibrin gels were more porous during treatment although there were large inter-individual variations in porosity . One week after withdrawal , the porosity was reduced by 30 41 % , i.e. the network became tighter ( 75 mg group P = 0.001 ; 160 mg group P = 0.002 ) . The tightness was more pronounced after withdrawal than in the untreated controls . In conclusion , the protective effect of acetylsalicylic acid may be ascribed to its effect not only on platelets but also on fibrinogen . The withdrawal of acetylsalicylic acid may clause a markedly reduced fibrin gel porosity that we assume is disadvantageous in patients with cardiovascular disease Despite multiple interventions to reduce the risk of cardiovascular disease , the majority of people with diabetes develop macrovascular complications , and mortality following myocardial infa rct ion remains unacceptably high [ 1 ] . Antiplatelet agents are used for both the primary and secondary prevention of cardiovascular disease , although current guidelines are not consistent in their recommendation for the use of aspirin in diabetes [ 2 ] . In fact , there is little direct evidence supporting its efficacy in this group of patients . Instead , there is convincing data in the literature to suggest inadequate cardiovascular protection by aspirin in diabetes . In a meta- analysis of 287 r and omised trials , antiplatelet treatment ( aspirin in most studies ) reduced the risk of ischaemic events by 22 % , but the risk reduction in the subgroup with diabetes was only 7 % , which was not statistically significant [ 3 ] . This outcome was mirrored in the Primary Prevention Project trial , which reported that cardiovascular risk reduction with aspirin was marginal and non-significant in the presence of diabetes [ 4 ] . Despite this , there are no published studies specifically design ed to evaluate the clinical efficacy of aspirin in individuals with diabetes , a surprising omission in the era of ‘ evidence based ’ medicine . These findings from clinical trials raise the question as to why there should be a reduction in the clinical efficacy of  aspirin  in patients with diabetes compared with a nondiabetic population . Diabetes is intrinsically associated with particular biochemical abnormalities that may have the capacity to diminish the effects of aspirin on platelet function and cardiovascular risk — a possibility that has led to the hotly debated concept of aspirin resistance [ 5 , 6 ] . Unfortunately , aspirin resistance suffers from a lack of a st and ardised definition , although now generally thought of as either ( 1 ) reflecting clinical aspirin resistance ( or perhaps , more accurately , treatment failure ) , characterised by the occurrence of a thrombotic episode despite treatment with aspirin ; or ( 2 ) biochemical aspirin resistance where platelet responses persist despite platelet exposure to aspirin . Controversy remains as to the cause of biochemical aspirin resistance , its relevance to clinical outcomes , and the place of aspirin treatment in the management of cardiovascular risk in diabetes patients . All of this highlights the urgent need to underst and the mechanisms that underpin the interactions between diabetes and aspirin , to establish the role of aspirin in particular , and antiplatelet therapy in general , in the amelioration of cardiovascular events in individuals with diabetes . Diabetologia ( 2008 ) 51:385–390 DOI 10.1007/s00125 - 007 - 0898 - Diabetic subjects have been shown to have altered fibrin network structures . One possible cause may be fibrinogen glycation result ing in altered structure/function properties . We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes . Blood sample s were taken from twenty uncontrolled diabetic subjects at baseline to determine the levels of fibrinogen glycation and fibrin network structures . The subjects were then treated with insulin until blood glucose control was achieved before end blood sample s were taken . Twenty age- and BMI -matched non-diabetic subjects were included as a reference group . The diabetic subjects had significantly higher mean fibrinogen glycation at baseline than the non-diabetic subjects ( 7.84 vs. 3.89 mol glucose / mol fibrinogen ; p < 0.001 ) . This was significantly reduced during the intervention ( 7.84 to 5.24 mol glucose / mol fibrinogen ; p < 0.0002 ) in the diabetic group . Both groups had high mean fibrinogen concentrations ( 4.25 and 4.02 g/l , diabetic and non-diabetic subjects respectively ) . There was no difference in fibrinogen concentration , porosity , compaction and kinetics of clot formation between the diabetic subjects and non-diabetic subjects at baseline , nor were there any changes during the intervention despite the reduced fibrinogen glycation . Fibrin network characteristics correlated well with fibrinogen but not with any markers of glycaemic control . Improved glycaemic control result ed in decreased fibrinogen glycation but not fibrinogen concentration . It seems as though porosity , compaction and kinetics of clot formation are more related to fibrinogen concentration than fibrinogen glycation in this model St and ard coagulation assays were performed with control and oxidized fibrinogen ( Fg ) , using prothrombin time ( PT ; 12.5 ± 0.4 vs 25 ± 0.8 seconds , P < .001 ) and activated partial thromboplastin time ( aPTT ; 33 ± 2.5 vs 63 ± 4.7 seconds , P < .001 ) . Fibrin clot ( MA ) , clot formation initiation ( r ) , and rate of clot lysis ( LY30 ) were measured , a reflection exposure of Fg to Fe3+/ ascorbate oxidative system by thrombelastograph ( TEG ) analysis ( 0 , 6 , 12 , 24 , and 48 hours , 6.2 ± 1.3 vs 5.5 ± 1.2 , 4.3 ± 1.0 [ P < .01 ] , 3.9 ± 1.6 , 3.2 ± 0.8 , [ P < .001 ] ) . Maximum amplitude level was found to be lower than control ( 69.1 ± 7.2 vs 67.9 ± 12.4 , 64.0 ± 11.4 , 60.2 ± 21.2 , 42.2 ± 15.2 , P < .001 ) . The lysis rate was changed according to oxidation time between Fg exposed to Fe3+/ascorbate and control exposed to Fe 3+/ascorbate for the same treatment time ( 1.9 ± 0.71 vs 7 ± 0.5 , 1.6 ± 0.1 , 1.2 ± 0.5 , 0.9 ± 1.3 , P < .001 ) . We revealed dysregulation of hemostatic system with contribution of oxidized Fg , which was in direct proportion to the intensity of Fg oxidation 
    Output:
    
For the best known and studied modifications , conclusions could be drawn about their effect on clot formation and structure .
Oxidation , high levels of nitration , and glycosylation inhibit the rate of polymerization , result ing in dense clots with thinner fibers , while low levels of nitration increase the rate of polymerization .
Glycation showed different results for polymerization , but fibrinolysis was found to be decreased , as a consequence of increased density and decreased permeability of clots .
Acetylation also decreases the rate of polymerization but results in increased fiber diameters and susceptibility to fibrinolysis .
Other modifications were studied less or contrasting results were found .
Conclusions : Overall , post-translational modifications do affect clot formation and characteristics .