Cost and Expected Visual Effect of Interventions to Improve Follow-up After Cataract Surgery: Prospective Review of Early Cataract Outcomes and Grading (PRECOG) Study.

IMPORTANCE: Some experts recommend increasing low rates of follow-up after cataract surgery in low- and middle-income countries using various interventions. However, little is known about the cost and effect of such interventions. OBJECTIVE: To examine whether promoting follow-up after cataract surgery creates economic value. DESIGN, SETTING, AND PARTICIPANTS: The Prospective Review of Early Cataract Outcomes and Grading (PRECOG) is a cohort study with data from patients undergoing cataract surgery from January 19, 2010, to April 18, 2012. Final follow-up was completed on August 10, 2012. Data were collected before surgery, at discharge, and at follow-up at least 40 days after surgery from 27 centers in 8 countries in Asia, Africa, and Latin America. Each center enrolled 40 to 120 consecutive patients undergoing cataract surgery. If patients did not return to the hospital for the follow-up visit, hospitals could use telephone calls or transportation subsidies to increase follow-up rate. Data were analyzed from December 2013 to January 2016. MAIN OUTCOMES AND MEASURES: Cost of interventions (telephone calls and transportation subsidies) to increase follow-up at least 40 days after surgery, visual acuity (VA) in the eye undergoing cataract surgery, presence of complications, patient and facility costs per visit, and willingness to pay for treatment or glasses if needed. The maximum incremental cost of improving VA in 1 patient (incremental cost-effect ratio [ICER]) was calculated for spontaneous follow-up (compared with no follow-up) and follow-up with the telephone and transportation interventions. Expected ICERs were estimated including only those patients willing to pay. RESULTS: Among 2487 patients (1068 men [42.9%]; 1405 women [56.5%]; 14 missing [0.6%]; mean [SD] age, 68.4 [11.3] years), 2316 (93.1%) received follow-up, of whom 369 (16.0%) were seen in an outside facility or home and were in the cost-effectiveness analysis as unable to follow up. A grand mean (a mean of means of the different countries) of 56.3% of patients needed glasses, of whom 56.9% were willing to pay, and 1.6% had treatable complications, of whom 39.4% were willing to pay. Maximum proportions with improved VA (and corresponding ICERs) were 0.08 for no follow-up, 0.45 ($151.56) for spontaneous follow-up, 0.53 ($164.46) for a telephone intervention, and 0.53 ($133.07) for a transportation intervention. These results were most sensitive to the cost of follow-up. Expected proportions (ICERs) were 0.08, 0.27 ($232.69), 0.30 ($456.22), and 0.30 ($206.47), respectively. CONCLUSIONS AND RELEVANCE: Most patients benefiting from follow-up after cataract surgery returned spontaneously when requested at discharge. Use of telephone calls or transportation subsidies to increase follow-up in low- and middle-income countries may not be cost-effective.

Safety of Spectacles for Children's Vision: A Cluster-Randomized Controlled Trial.

PURPOSE: To study safety of children's glasses in rural China, where fear that glasses harm vision is an important barrier for families and policy makers. DESIGN: Exploratory analysis from a cluster-randomized, investigator-masked, controlled trial. METHODS: Among primary schools (n = 252) in western China, children were randomized by school to 1 of 3 interventions: free glasses provided in class, vouchers for free glasses at a local facility, or glasses prescriptions only (Control group). The main outcome of this analysis is uncorrected visual acuity after 8 months, adjusted for baseline acuity. RESULTS: Among 19 934 children randomly selected for screening, 5852 myopic (spherical equivalent refractive error ≤-0.5 diopters) eyes of 3001 children (14.7%, mean age 10.5 years) had VA ≤6/12 without glasses correctable to >6/12 with glasses, and were eligible. Among these, 1903 (32.5%), 1798 (30.7%), and 2151 (36.8%) were randomized to Control, Voucher, and Free Glasses, respectively. Intention-to-treat analyses were performed on all 1831 (96.2%), 1699 (94.5%), and 2007 (93.3%) eyes of children with follow-up in Control, Voucher, and Free Glasses groups. Final visual acuity for eyes of children in the treatment groups (Free Glasses and Voucher) was significantly better than for Control children, adjusting only for baseline visual acuity (difference of 0.023 logMAR units [0.23 vision chart lines, 95% CI: 0.03, 0.43]) or for other baseline factors as well (0.025 logMAR units [0.25 lines, 95% CI 0.04, 0.45]). CONCLUSION: We found no evidence that spectacles promote decline in uncorrected vision with aging among children.

Effect of providing free glasses on children's educational outcomes in China: cluster randomized controlled trial.

OBJECTIVE: To assess the effect of provision of free glasses on academic performance in rural Chinese children with myopia. DESIGN: Cluster randomized, investigator masked, controlled trial. SETTING: 252 primary schools in two prefectures in western China, 2012-13. PARTICIPANTS: 3177 of 19,934 children in fourth and fifth grades (mean age 10.5 years) with visual acuity <6/12 in either eye without glasses correctable to >6/12 with glasses. 3052 (96.0%) completed the study. INTERVENTIONS: Children were randomized by school (84 schools per arm) to one of three interventions at the beginning of the school year: prescription for glasses only (control group), vouchers for free glasses at a local facility, or free glasses provided in class. MAIN OUTCOME MEASURES: Spectacle wear at endline examination and end of year score on a specially designed mathematics test, adjusted for baseline score and expressed in standard deviations. RESULTS: Among 3177 eligible children, 1036 (32.6%) were randomized to control, 988 (31.1%) to vouchers, and 1153 (36.3%) to free glasses in class. All eligible children would benefit from glasses, but only 15% wore them at baseline. At closeout glasses wear was 41% (observed) and 68% (self reported) in the free glasses group, and 26% (observed) and 37% (self reported) in the controls. Effect on test score was 0.11 SD (95% confidence interval 0.01 to 0.21) when the free glasses group was compared with the control group. The adjusted effect of providing free glasses (0.10, 0.002 to 0.19) was greater than parental education (0.03, -0.04 to 0.09) or family wealth (0.01, -0.06 to 0.08). This difference between groups was significant, but was smaller than the prespecified 0.20 SD difference that the study was powered to detect. CONCLUSIONS: The provision of free glasses to Chinese children with myopia improves children's performance on mathematics testing to a statistically significant degree, despite imperfect compliance, although the observed difference between groups was smaller than the study was originally designed to detect. Myopia is common and rarely corrected in this setting.Trial Registration Current Controlled Trials ISRCTN03252665.

Two-year changes in refractive error and related biometric factors in an adult Chinese population.

IMPORTANCE: This article provides, to our knowledge, the first longitudinal population-based data on refractive error (RE) in Chinese persons. OBJECTIVE: To study cohort effects and changes associated with aging in REs among Chinese adults. DESIGN, SETTING, AND PARTICIPANTS: A 2-year, longitudinal population-based cohort study was conducted in southern China. Participants, identified using cluster random sampling, included residents of Yuexiu District, Guangzhou, China, aged 35 years or older who had undergone no previous eye surgery. METHODS: Participants underwent noncycloplegic automated refraction and keratometry in December 2008 and December 2010; in a random 50% sample of the participants, anterior segment ocular coherence tomography measurement of lens thickness, as well as measurement of axial length and anterior chamber depth by partial coherence laser interferometry, were performed. MAIN OUTCOMES AND MEASURES: Two-year change in spherical equivalent refraction (RE), lens thickness, axial length, and anterior chamber depth in the right eye. RESULTS: A total of 745 individuals underwent biometric testing in both 2008 and 2010 (2008 mean [SD] age, 52.2 [11.5] years; 53.7% women). Mean RE showed a 2-year hyperopic shift from -0.44 (2.21) to -0.31 (2.26) diopters (D) (difference, +0.13; 95% CI, 0.11 to 0.16). A consistent 2-year hyperopic shift of 0.09 to 0.22 D was observed among participants aged 35 to 64 years when stratifying by decade, suggesting that a substantial change in RE with aging may occur during this 30-year period. Cross-sectionally, RE increased only in the cohort younger than 50 years (0.11 D/y; 95% CI, 0.06 to 0.16). In the cross-sectional data, axial length decreased at -0.06 mm/y (95% CI, -0.09 to -0.04), although the 2-year change in axial length was positive and thus could not explain the cross-sectional difference. These latter results suggest a cohort effect, with greater myopia developing among younger persons. CONCLUSIONS AND RELEVANCE: This first Chinese population-based longitudinal study of RE provides evidence for both important longitudinal aging changes and cohort effects, most notably greater myopia prevalence among younger persons.

Accuracy of rural refractionists in western China.

PURPOSE: We assessed the prevalence and predictors of inaccurate refractive error among rural refractionists in western China. METHODS: A subset of primary school children with visual acuity (VA) ≤6/12 in ≥1 eye, undergoing subjective refinement by local refractionists after cycloplegic autorefraction in an ongoing population-based study, received repeat refraction by university optometrists for quality control. RESULTS: Among 502 children (mean age 10.5 years, 53.2% girls), independent predictors of poor (inaccurate by ≥1.0 diopter [D]) refraction by 21 rural practitioners (66.7% with high school or lower education) included hyperopia (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.4-7.3, P < 0.001), astigmatism (OR = 3.8; 95% CI, 2.5-5.6; P < 0.001) and VA uncorrectable to >6/12 by the rural refractionist (OR = 4.7; 95% CI, 3.1-7.3; P = < 0.001). Among 201 children whose vision was uncorrectable in ≥1 eye by the rural refractionists, vision could be improved to >6/12 by the university optometrist in 110 (54.7%). We estimate vision could be so improved in 9.1% of all children refracted by these rural refractionists. A reason for inaccuracy in this setting is the erroneous tendency of rural refractionists to adjust instrument values for accommodation, even under cycloplegia. CONCLUSIONS: Rural refractionists in western China have little formal training and frequently fail to optimize VA among children, even when autorefractors are used. Training is needed emphasizing better use of automated refraction, particularly in children with astigmatism and hyperopia.

Assessment of cataract surgical outcomes in settings where follow-up is poor: PRECOG, a multicentre observational study.

BACKGROUND: Poor follow-up after cataract surgery in developing countries makes assessment of operative quality uncertain. We aimed to assess two strategies to measure visual outcome: recording the visual acuity of all patients 3 or fewer days postoperatively (early postoperative assessment), and recording that of only those patients who returned for the final follow-up examination after 40 or more days without additional prompting. METHODS: Each of 40 centres in ten countries in Asia, Africa, and Latin America recruited 40-120 consecutive surgical cataract patients. Operative-eye best-corrected visual acuity and uncorrected visual acuity were recorded before surgery, 3 or fewer days postoperatively, and 40 or more days postoperatively. Clinics logged whether each patient had returned for the final follow-up examination without additional prompting, had to be actively encouraged to return, or had to be examined at home. Visual outcome for each centre was defined as the proportion of patients with uncorrected visual acuity of 6/18 or better minus the proportion with uncorrected visual acuity of 6/60 or worse, and was calculated for each participating hospital with results from the early assessment of all patients and the late assessment of only those returning unprompted, with results from the final follow-up assessment for all patients used as the standard. FINDINGS: Of 3708 participants, 3441 (93%) had final follow-up vision data recorded 40 or more days after surgery, 1831 of whom (51% of the 3581 total participants for whom mode of follow-up was recorded) had returned to the clinic without additional prompting. Visual outcome by hospital from early postoperative and final follow-up assessment for all patients were highly correlated (Spearman's rs=0·74, p<0·0001). Visual outcome from final follow-up assessment for all patients and for only those who returned without additional prompting were also highly correlated (rs=0·86, p<0·0001), even for the 17 hospitals with unprompted return rates of less than 50% (rs=0·71, p=0·002). When we divided hospitals into top 25%, middle 50%, and bottom 25% by visual outcome, classification based on final follow-up assessment for all patients was the same as that based on early postoperative assessment for 27 (68%) of 40 centres, and the same as that based on data from patients who returned without additional prompting in 31 (84%) of 37 centres. Use of glasses to optimise vision at the time of the early and late examinations did not further improve the correlations. INTERPRETATION: Early vision assessment for all patients and follow-up assessment only for patients who return to the clinic without prompting are valid measures of operative quality in settings where follow-up is poor. FUNDING: ORBIS International, Fred Hollows Foundation, Helen Keller International, International Association for the Prevention of Blindness Latin American Office, Aravind Eye Care System.

Determinants and two-year change in anterior chamber angle width in a Chinese population.

OBJECTIVE: To study the population distribution and longitudinal changes in anterior chamber angle width and its determinants among Chinese adults. DESIGN: Prospective cohort, population-based study. PARTICIPANTS: Persons aged 35 years or more residing in Guangzhou, China, who had not previously undergone incisional or laser eye surgery. METHODS: In December 2008 and December 2010, all subjects underwent automated keratometry, and a random 50% sample had anterior segment optical coherence tomography with measurement of angle-opening distance at 500 µm (AOD500), angle recess area (ARA), iris thickness at 750 µm (IT750), iris curvature, pupil diameter, corneal thickness, anterior chamber width (ACW), lens vault (LV), and lens thickness (LT) and measurement of axial length (AL) and anterior chamber depth (ACD) by partial coherence laser interferometry. MAIN OUTCOME MEASURES: Baseline and 2-year change in AOD500 and ARA in the right eye. RESULTS: A total of 745 subjects were present for full biometric testing in both 2008 and 2010 (mean age at baseline, 52.2 years; standard deviation [SD], 11.5 years; 53.7% were female). Test completion rates in 2010 varied from 77.3% (AOD500: 576/745) to 100% (AL). Mean AOD500 decreased from 0.25 mm (SD, 0.13 mm) in 2008 to 0.21 mm (SD, 13 mm) in 2010 (difference, -0.04; 95% confidence interval [CI], -0.05 to -0.03). The ARA decreased from 21.5 ± 3.73 10(-2) mm(2) to 21.0 ± 3.64 10(-2) mm(2) (difference, -0.46; 95% CI, -0.52 to -0.41). The decrease in both was most pronounced among younger subjects and those with baseline AOD500 in the widest quartile at baseline. The following baseline variables were significantly associated with a greater 2-year decrease in both AOD500 and ARA: deeper ACD, steeper iris curvature, smaller LV, greater ARA, and greater AOD500. By using simple regression models, we could explain 52% to 58% and 93% of variation in baseline AOD500 and ARA, respectively, but only 27% and 16% of variation in 2-year change in AOD500 and ARA, respectively. CONCLUSIONS: Younger persons and those with the least crowded anterior chambers at baseline have the largest 2-year decreases in AOD500 and ARA. The ability to predict change in angle width based on demographic and biometric factors is relatively poor, which may have implications for screening. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clot lysis time and the risk of myocardial infarction and ischaemic stroke in young women; results from the RATIO case-control study.

Reduced overall fibrinolytic capacity increases the risk of myocardial infarction (MI), as demonstrated in studies with predominantly male participants. We determined the influence of altered fibrinolysis on the risk of MI and ischaemic stroke (IS) in young women. The RATIO (Risk of Arterial Thrombosis In relation to Oral contraceptives) study is a population-based case-control study including young women with MI (n=203), IS (N=175) and 638 matched healthy controls. Fibrinolytic potential was determined with a tissue factor/tissue plasminogen activator induced clot-lysis assay. Odds ratios (OR) adjusted for cardiovascular risk factors were obtained with logistic regression. Clot-lysis time (CLT) was divided into tertiles based on the control group (T1-T3), with T2 as reference. Hypofibrinolysis (prolonged CLT) was associated with an increase in risk of MI (T3 vs. T2, OR 2·8; 95%confidence interval [CI] 1·7-4·7). Hyperfibrinolysis (decreased CLT) had no clear effect (T1 vs. T2, OR 1·6; 95% CI 0·9-2·9). Hypofibrinolysis did not affect the risk of IS (T3 vs. T2, OR 1·5; 95% CI 0·7-3·0), whereas hyperfibrinolysis increased this risk (T1 vs. T2, OR 4·1; 95% CI 2·1-8·0). Oral contraceptive use and smoking further increased these risks. Hypofibrinolysis increases the risk for MI in young women, a finding similar to previous studies. Counter-intuitively, hyperfibrinolysis increased the risk of IS four-fold, which suggests that MI and IS have different aetiologies.

Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1.

Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and alpha2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for alpha2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors.

Plasma levels of fibrinolytic proteins and the risk of myocardial infarction in men.

Hypofibrinolysis as measured with overall clot lysis assays is associated with risk of arterial thrombosis. Individual components of the fibrinolytic system, however, have not been studied extensively in relation to arterial disease, or results of studies were inconsistent. The relation between plasminogen and alpha2-antiplasmin levels and cardiovascular risk factors and the association between plasminogen, alpha2-antiplasmin, tissue-plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) and risk of myocardial infarction was investigated in the Study of Myocardial Infarctions Leiden (555 men with a first myocardial infarction and 635 controls). alpha2-antiplasmin was associated with age and lipid levels, whereas plasminogen correlated with lipids, C-reactive protein, and smoking. Increased levels of all fibrinolytic factors were associated with myocardial infarction. Age-adjusted odds ratios (ORs; 95% confidence interval) for quartile 4 compared with 1 were 1.7 (1.2-2.3) for plasminogen, 1.9 (1.3-2.6) for alpha2-antiplasmin, 1.7 (1.2-2.3) for t-PA, and 1.7 (1.2-2.4) for PAI-1. After adjusting for cardiovascular risk factors, only alpha2-antiplasmin levels remained associated with risk (OR, 1.4; [1.0-2.0]). t-PA and PAI-1 levels predominantly reflected lipid levels, whereas plasminogen reflected the inflammatory state. Concluding, elevated alpha2-antiplasmin levels are independently associated with risk of myocardial infarction. t-PA, PAI-1, and plasminogen levels appear to reflect other cardiovascular risk factors.

The impact of the fibrinolytic system on the risk of venous and arterial thrombosis.

In this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, alpha2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibrinolytic proteins, including roles in inflammation, vascular remodeling, atherosclerosis, and the metabolic syndrome. The nonfibrinolytic properties of these proteins may have opposing effects on development of arterial disease as compared with the lytic properties, which may explain opposite results in different studies with slightly different population characteristics. These properties may be more relevant in arterial than in venous thrombosis.

Low thrombin activatable fibrinolysis inhibitor activity levels are associated with an increased risk of a first myocardial infarction in men.

BACKGROUND: Studies on the relation between thrombin activatable fibrinolysis inhibitor (TAFI) and arterial thrombosis have produced conflicting results. TAFI regulates fibrinolysis, but other roles of this inhibitor, including anti-inflammatory properties, have also been demonstrated. DESIGN AND METHODS: We investigated the association between TAFI activity and the risk of myocardial infarction. Additionally, we studied the association of common single nucleotide polymorphisms in the TAFI gene with levels of the TAFI protein and risk of myocardial infarction.We included 554 men under 70 years old with a first myocardial infarction and 643 controls participating in the Study of Myocardial Infarctions Leiden (SMILE), a case-control study. RESULTS: We found odds ratios (95% confidence intervals) of a first myocardial infarction of 2.4 (1.6-3.6), 3.2 (2.1-4.7) and 3.4 (2.3-5.1) for subjects whose TAFI levels were in the third, second and first quartiles (lowest TAFI levels), respectively, compared with the fourth quartile, after adjusting for arterial disease risk factors. The rare -438A and 1040T alleles were associated with lower, and the rare 505G allele with higher TAFI levels than the common alleles. Carriers of the -438A allele had an increased risk of myocardial infarction (odds ratio 1.6 (1.0-2.5) for AA; odds ratio 1.2 (0.9-1.5) for AG compared with GG). The other single nucleotide polymorphisms were not associated with myocardial infarction. CONCLUSIONS: Low TAFI activity levels are associated with increased risk of a first myocardial infarction in men. The results on the association between TAFI single nucleotide polymorphisms and myocardial infarction were inconsistent.

Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men.

Studies on the relationship between fibrinolysis and arterial thrombosis have been conflicting. Previously, we demonstrated that hypofibrinolysis, as measured by a plasma-based assay, increased the risk of venous thrombosis. The present study investigated increased clot lysis time (CLT) measured with the same assay as a risk factor for myocardial infarction in a case-control study including 421 men with a first myocardial infarction and 642 controls below 70 years. CLT was strongly associated with body-mass index, lipid levels, blood pressure and C-reactive protein. Overall, risk of myocardial infarction was 1.4-fold (95% confidence interval (CI) 1.0-1.9) increased for CLT in the fourth quartile (longest CLT) compared with the first quartile. After adjusting for cardiovascular risk factors this risk disappeared (OR 1.0, 95%CI 0.6-1.5). In men aged <50 years the association was pronounced (OR 3.2, 95%CI 1.5-6.7). After adjustment for cardiovascular risk factors the risk was nearly twofold increased (OR 1.8, 95%CI 0.7-4.8). In men aged > or = 50 years, no clear association between CLT and risk of myocardial infarction was found. Our study suggests that hypofibrinolysis increases the risk of a first myocardial infarction in young men, although the causality of this association remains to be determined.

Synergistic effects of hypofibrinolysis and genetic and acquired risk factors on the risk of a first venous thrombosis.

BACKGROUND: Previously, we demonstrated that hypofibrinolysis, a decreased capacity to dissolve a blood clot as measured with an overall clot lysis assay, increases the risk of venous thrombosis. Here, we investigated the combined effect of hypofibrinolysis with established risk factors associated with hypercoagulability. METHODS AND FINDINGS: Fibrinolytic potential was determined with a plasma-based clot lysis assay in 2,090 patients with venous thrombosis and 2,564 control participants between 18 and 70 y of age enrolled in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based case-control study on venous thrombosis. Participants completed a standardized questionnaire on acquired risk factors. Hypofibrinolysis alone, i.e., clot lysis time (CLT) in the fourth quartile (longest CLT) (in absence of the other risk factor of interest) increased thrombosis risk about 2-fold relative to individuals with CLT in the first quartile (shortest CLT). Oral contraceptive use in women with CLT in the first quartile gave an odds ratio (OR) of 2.6 (95% confidence interval [CI] 1.6 to 4.0), while women with hypofibrinolysis who used oral contraceptives had an over 20-fold increased risk of venous thrombosis (OR 21.8, 95% CI 10.2 to 46.7). For immobilization alone the OR was 4.3 (95% CI 3.2 to 5.8) and immobilization with hypofibrinolysis increased the risk 10.3-fold (95% CI 7.7 to 13.8). Factor V Leiden alone increased the risk 3.5-fold (95% CI 2.3 to 5.5), and hypofibrinolysis in factor V Leiden carriers gave an OR of 8.1 (95% CI 5.3 to 12.3). The combination of hypofibrinolysis and the prothrombin 20210A mutation did not synergistically increase the risk. All ORs and 95% CIs presented are relative to individuals with CLT in the first quartile and without the other risk factor of interest. CONCLUSIONS: The combination of hypofibrinolysis with oral contraceptive use, immobilization, or factor V Leiden results in a risk of venous thrombosis that exceeds the sum of the individual risks.

Fibrinolysis and the risk of venous and arterial thrombosis.

PURPOSE OF REVIEW: The fibrinolytic system is often regarded as just an innocent bystander in the pathogenesis of venous and arterial thrombosis, while (hyper)coagulation as a risk factor has been studied extensively. In this review, we evaluated studies that investigated the association between fibrinolysis and thrombosis. RECENT FINDINGS: There is some evidence for an association between impaired overall fibrinolytic activity and increased risk of venous or arterial thrombosis. Plasminogen levels were found not to be related to thrombosis. Plasma levels of tissue-type plasminogen activator were related to arterial thrombosis in a number of studies but not to venous thrombosis. Thrombin activatable fibrinolysis inhibitor levels appeared to be associated with venous thrombosis. Studies on the association between thrombin activatable fibrinolysis inhibitor or plasminogen activator inhibitor-1 and arterial thrombosis had conflicting results. SUMMARY: Current evidence on an association between fibrinolysis and thrombosis is inconclusive. Although overall assays point to an association, not all individual factors have an association with thrombosis. Most importantly, plasminogen deficiency is not related to thrombosis, which suggests that the fibrinolytic system as a whole is unimportant in the occurrence of thrombosis. Certain components of the fibrinolytic system, however, appear to be involved in processes unrelated to fibrin degradation but related to other processes important in the development of thrombosis.