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1998, British Journal of Ophthalmology
Diagnosis of activated protein C resistance in retinal vein occlusion EDITOR,-I read with interest the article published in the BJO by Hunt. 1 In this paper the author reports that the prevalence of APC resistance is more common than any other known thrombophilic state and was present in over one third of patients younger than 45 years with central retinal vein occlusion (CRVO). Therefore, many would argue that a full thrombophilia screening should be performed in a young patient (<50 years old) after CRVO. This screening should be made using an easy to perform technique and providing good discrimination between normal and APC resistant subjects. In this regard, Hunt comments that the biological technique proposed by Dhälback et al 2 yields sensitivity and specificity ranging from 85% to 90%, but that it is not reliable if the patient has abnormal clotting such as a lupus anticoagulant or is receiving anticoagulants. For these reasons this technique is not suitable for the screening of patients with venous thrombotic disorders, including CRVO. With regard to this point, it is worth taking into account that our group has proposed a technique, 3 which modifies the initial technique proposed by Dhälback et al, 2 diluting the sample of the patient's plasma with plasma lacking factor V. With this modification, both the specificity and sensitivity of the technique is 100% 4 and, moreover, it may be used in patients receiving anticoagulant therapy and in those who have lupus anticoagulant. Thus, in opinion of Dhälback, 5 this technique may be suitable for the screening of patients with venous thrombotic disorders since it is very sensitive and specific as well as inexpensive and easy to perform.
British Journal of Ophthalmology, 1998
Diagnosis of activated protein C resistance in retinal vein occlusion EDITOR,-I read with interest the article published in the BJO by Hunt. 1 In this paper the author reports that the prevalence of APC resistance is more common than any other known thrombophilic state and was present in over one third of patients younger than 45 years with central retinal vein occlusion (CRVO). Therefore, many would argue that a full thrombophilia screening should be performed in a young patient (<50 years old) after CRVO. This screening should be made using an easy to perform technique and providing good discrimination between normal and APC resistant subjects. In this regard, Hunt comments that the biological technique proposed by Dhälback et al 2 yields sensitivity and specificity ranging from 85% to 90%, but that it is not reliable if the patient has abnormal clotting such as a lupus anticoagulant or is receiving anticoagulants. For these reasons this technique is not suitable for the screening of patients with venous thrombotic disorders, including CRVO. With regard to this point, it is worth taking into account that our group has proposed a technique, 3 which modifies the initial technique proposed by Dhälback et al, 2 diluting the sample of the patient's plasma with plasma lacking factor V. With this modification, both the specificity and sensitivity of the technique is 100% 4 and, moreover, it may be used in patients receiving anticoagulant therapy and in those who have lupus anticoagulant. Thus, in opinion of Dhälback, 5 this technique may be suitable for the screening of patients with venous thrombotic disorders since it is very sensitive and specific as well as inexpensive and easy to perform.
Clinical Ophthalmology, 2008
Background: Retinal artery occlusion (RAO) is an ischemic vascular damage of the retina, which frequently leads to sudden, mostly irreversible loss of vision. In this study, blood thrombophilic factors as well as cardiovascular risk factors were investigated for their relevance to this pathology. Thrombophilic risk factors so far not evaluated were included in the study. Patients and methods: 28 RAO patients and 81 matched control subjects were examined. From blood samples, protein C, protein S, antithrombinopathy, and factor V (Leiden) mutation (FV), factor II gene polymorphism, factor VIII C level, plasminogen activity, lipoprotein(a) and fi brinogen levels, hyperhomocysteinemia and presence of anticardiolipin-antiphospholipid antibodies were investigated. Possibly relevant pathologies such as diabetes mellitus, hypertension, and ischemic heart disease were also registered. Statistical analysis by logistic regression was performed with 95% confi dence intervals. Results: In the group of patients with RAO only the incidence of hypertension (OR: 3.33, 95% CI: 1.30-9.70, p = 0.014) as an average risk factor showed signifi cant difference, but thrombophilic factors such as hyperfi brinogenemia (OR: 2.9, 95% CI: 1.29-6.57, p = 0.010) and the presence of FV (Leiden mutation) (OR: 3.9, 95% CI: 1.43-10.96, p = 0.008) increased the chances of developing this disease. Conclusions: Our results support the assumption that thrombophilia may contribute to the development of RAO besides vascular damage due to the presence of cardiovascular risk factors. Further studies are needed, however, to justify the possible use of secondary prophylaxis in form of anticoagulant/antiplatelet therapy.
Annals of internal medicine, 2003
Numerous tests are available to assess patient risk for bleeding or thrombosis. Appropriate use of these tests must involve consideration of the clinical setting, disease prevalence, performance characteristics of the tests, cost, and consequences of false-positive and false-negative results. To summarize information about coagulation testing in three common clinical settings: nonsurgical hospitalized patients, surgical patients, and patients having a first venous thromboembolic event. All English-language studies identified in searches of MEDLINE (1966 to April 2002) and reference lists of key articles. All published studies of blood coagulation testing as routine diagnostic tests or in the preoperative care of patients reporting postoperative bleeding complications, and all published studies of patients with the factor V Leiden mutation reporting venous thromboembolic outcomes. 5 observational studies of routine coagulation testing in nonsurgical hospitalized patients and 12 obser...
Thrombosis and Haemostasis, 2008
Several small case-control studies have investigated whether factor V Leiden (FVL) is a risk factor for retinal vein occlusion (RVO) and generated conflicting data. To clarify this question we performed a large two-centre case-control study and a meta-analysis of published studies. Two hundred seven consecutive patients with RVO and a control group of 150 subjects were screened between 1996 and 2006. A systematic meta-analysis was done combining our study with further 17 published European case-control studies. APC resistance was detected in 16 out of 207 (7.7%) patients and eight out of 150 (5.3%) controls. The odds ratio (OR) estimated was 1.49 with a (non-significant) 95% confidence interval (CI) of 0.62-3.57. The meta-analysis including 18 studies with a total of 1,748 patients and 2,716 controls showed a significantly higher prevalence of FVL in patients with RVO compared to healthy controls (combined OR 1.66; 95% CI 1.19-2.32). All single studies combined in the meta-analysis were too small to reliably detect the effect individually. This explains the seemingly contradictory data in the literature. In conclusion, the prevalence of APC resistance (and FVL) is increased in patients with RVO compared to controls, but the effect is only moderate. Therefore, there is no indication for general screening of factor V mutation in all patients with RVO. We recommend this test to be performed in patients older than 50 years with an additional history of thromboembolic event and in younger patients without general risk factors like hypertension.
International Journal of Molecular Sciences, 2020
Venous thrombosis is a common and potentially fatal disease, because of its high morbidity and mortality, especially in hospitalized patients. To establish the diagnosis of venous thrombosis, in the last years, a multi-modality approach that involves not only imaging modalities but also serology has been evolving. Multiple studies have demonstrated the use of some biomarkers, such as D-dimer, selectins, microparticles or inflammatory cytokines, for the diagnosis and treatment of venous thrombosis, but there is no single biomarker available to exclusively confirm the diagnosis of venous thrombosis. Considering the fact that there are some issues surrounding the management of patients with venous thrombosis and the duration of treatment, recent studies support the idea that these biomarkers may help guide the length of appropriate anticoagulation treatment, by identifying patients at high risk of recurrence. At the same time, biomarkers may help predict thrombus evolution, potentially...
Seminars in Thrombosis and Hemostasis
Annals of Internal Medicine, 1998
To review noninvasive methods for the diagnosis of first and recurrent deep venous thrombosis (DVT) and to provide evidence-based recommendations for the diagnosis of DVT in symptomatic, asymptomatic and pregnant patients. Searching MEDLINE was searched up to January 1997; the search terms were provided. Additional literature was identified by searching the authors' personal files and the bibliographies of reviews and original studies. Study selection Study designs of evaluations included in the review The review included prospective cohort studies for diagnostic accuracy and randomised controlled trials (RCTs) for management, if they satisfied the predefined methodological criteria. Specific interventions included in the review Noninvasive diagnostic tests for DVT were eligible for inclusion. Impedance plethysmography and venous ultrasonography (Duplex, B-mode or Colour Doppler) were the main focus of the review. Clinical assessment, fibrinogen leg scanning and D-dimer blood tests were considered as adjuncts. Reference standard test against which the new test was compared Diagnostic accuracy studies were required to use venography as the reference standard in all patients. For management studies, long-term follow-up served as the 'reference standard'. Participants included in the review Studies of symptomatic (in-and outpatient), asymptomatic (post-operative orthopaedic patients) and pregnant patients with first suspected or recurrent DVT were eligible for inclusion. Outcomes assessed in the review No inclusion criteria relating to outcomes were specified. For diagnostic accuracy studies, the outcomes assessed were: sensitivity for proximal DVT, isolated distal DVT, and all DVT; specificity for all DVT; positive predictive value for proximal DVT and all DVT; negative predictive value for proximal DVT, isolated DVT and all DVT. For management studies, the outcome assessed was the safety of withholding anticoagulation on the basis of negative test results, as defined by the incidence of venous thromboembolism during 6 months' follow-up. This was often supplemented by venographic determination of the positive predictive value of an abnormal test result at presentation.
American Journal of Clinical Pathology, 2003
Clinical Chemistry, 2010
BACKGROUND: Point-of-care D-dimer tests have recently been introduced to enable rapid exclusion of deep venous thrombosis (DVT) without the need to refer a patient for conventional laboratory-based D-dimer testing. Before implementation in practice, however, the diagnostic accuracy of each test should be validated.
Clinical use of coagulation tests, 2020
Sources of interference -Inaccurate results may occur if the following are present:
American Journal of Hematology, 2003
European Journal of Vascular and Endovascular Surgery, 2005
Background. Routine thrombophilia testing is controversial because of the low yield of positive tests, costs involved, and debate about the clinical usefulness of the data obtained from testing. Laboratory investigations are rarely done for those with superficial venous thrombosis (SVT) or isolated calf vein thrombosis (CVT) which are often not treated with anticoagulants. Objective. To identify the incidence of markers of thrombophilia in patients with deep vein thrombosis (DVT), SVT, isolated CVT or a history of thrombosis in a referral practice. Methods. One hundred and sixty-six patients were referred to our thrombosis unit for consultation, including patients with SVT, DVT, and preoperative patients with a previous history of SVT or DVT. Patients underwent thrombophilia screening and patients with a diagnosis of SVT or DVT were confirmed by bilateral duplex ultrasonography of all lower limb veins. Thrombophilia testing included factor V Leiden (FVL), prothrombin 20210A mutation (P2), methylene tetrahydrofolate reductase deficiency (MTHFR), fasting serum homocysteine (HC), lupus anticoagulant (LA), anticardiolipin antibodies (ACA), antithrombin deficiency (AT), protein S deficiency (PS), and protein C deficiency (PC). Results. The incidence of any significant abnormality in patients with DVT was 27/44 (61%; 95% Confidence interval [CI], 47-76%) and 10 of these patients were positive for FVL (23%; 95% CI, 10-35%). Twelve patients with isolated CVT were seen and five had at least one abnormality (42%; 95% CI, 14-70%) including one with FVL (8%; 95% CI, 0-24%). Thirtynine patients with isolated SVT were seen including 14 with at least one abnormality (36%; 95% CI, 21-51%) and five of these patients with SVT had FVL (13%; 95% CI, 2-23%). Nine patients with recurrent DVT were seen and five of these had at least one abnormal test (56%; 95% CI, 23-88%). Finally, 18 of the 166 patients had more than one abnormality (11%; 95% CI, 6-16%). Conclusion. The presence of one or more markers of thrombophilia was significantly higher in this patient population compared to reports from other centres. This study identified 18/166 (10.8%; 95% CI, 6-16%) with more than one defect where lifelong anticoagulation might be considered. The results in this subset of patients as well as the serious defects found in some patients with provoked DVT, isolated CVT or isolated SVT demonstrate the value of this screening program to both these patients and their blood relatives. On the other hand, this is a small series from a referral practice where the incidence of these defects is greater than one would expect in the general population. These studies are preliminary and it is not recommended that all VTE patients should be screened on the basis of the current report.
Journal of thrombosis and thrombolysis, 2001
Journal of Vascular Surgery: Venous and Lymphatic Disorders, 2015
Annals of Emergency Medicine, 2003
Background: Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT).
Annals of Internal Medicine, 2013
Background: D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. Objective: To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. Design: Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) Setting: 5 Canadian hospitals. Patients: Consecutive symptomatic patients with a first episode of suspected DVT. Intervention: Selective testing (n ϭ 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels Ͻ1.0 g/mL [low C-PTP] or Ͻ0.5 g/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n ϭ 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels Ͻ0.5 g/mL). Measurements: The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. Results: The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, Ϫ0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. Limitation: Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. Conclusion: A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT.
Future Science OA, 2019
Much research to identify clinically useful molecular biomarkers that reflect overall thrombotic status has been performed over the last few decades. One of the most probable molecular biomarkers appears to be D-dimer, but this lacks specificity, with poor predictive value in arterial thrombosis . It is doubtful whether any single molecular biomarker could predict a multifactorial event such as an arterial thrombotic event. Another important problem is that in vitro anticoagulation of blood sample affects the results of the test used and renders it rather unphysiological . However, some promising nonanticoagulated global hemostasis and thrombosis tests have been developed and have been used successfully in diagnosis and medical discovery and developments . These tests have been well developed and proven to be highly important for both diagnostic and therapeutic purposes. Blood is drawn directly from an antecubital vein over a prothrombotic surface consisting of either human type III collagen fibrils or human tissue factor/phospholipids, which promotes thrombus formation by activation of both platelets and coagulation. Thrombus formation is performed at vessel wall shear rates varying from 100 to 32,000 s -1 . The impact of vessel wall shear rates on the various mechanisms of thrombus formation and on anticoagulant and antiplatelet agents are very high. Platelet activation is increased by increasing arterial wall shear rate, whereas coagulation is increased by low venous wall shear rates. These physical shear rate effects have important effects on the activities of many antiplatelet and anticoagulant agents. Also, impacts of cigarette smoking and physical activities on thrombus formation have been studied with this global nonanticoagulated blood test . It should also be mentioned that the use of these human nonanticoagulated blood tests is of importance for the antithrombotic and hematologic pharma industry, since animal studies may not always predict the human reaction. Furthermore, implication of these models in the pharma industry has reduced costs of the discovery and developmental activities and the need for animal experiments.
Biomedical Papers, 2009
Journal of Internal Medicine, 1994
Hansson P-0, Eriksson H, Eriksson E, Jagenburg R, Lukes P, Risberg B (
Blood Coagulation & Fibrinolysis, 2001
The thromboelastograph (TEG), a measure of global haemostasis, is routinely used during cardiac and hepatic surgery to optimize blood product selection and usage. It has recently been suggested that it may also be a useful tool to screen patients with hypercoagulable states. Limited published data on performance characteristics has led to speculation regarding its consistency and, therefore, validity of the results. This study was designed to assess the effect of stability of blood samples prior to testing, repeated sampling, intra-and inter-assay variability using the native, celite, tissue factor (TF) and Reopro-modi®ed TEG. Analysis of native and celite samples after storage over 90 min showed a period of instability up to 30 min. Thereafter, all parameters between 30 and 90 min were stable [P not signi®cant (NS)]. When the same sample was repeatedly assayed, both native and celite TEG parameters showed a signi®cant change towards hypercoagulability (P < 0.01), whereas the TF and Reopro-modi®ed TEG showed no change. Intra-and inter-assay variability on samples tested after 30 min showed excellent reproducibility for all parameters (P NS). The data suggest that the TEG is a useful tool in haemostasis but requires a formal standard operating procedure to be adopted that takes into account the initial period of sample instability. Blood Coagul Fibrinolysis 12:555±561 # 2001 Lippincott Williams & Wilkins.
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