The association of factor V Leiden with various clinical patterns of venous thromboembolism-the factor V Leiden paradox.

BACKGROUND: Factor V Leiden (FVL) supposedly carries relatively higher risk of deep vein thrombosis (DVT), compared to the risk of pulmonary embolism (PE). AIM: To prove this paradox in a group of patients with various clinical presentation of venous thromboembolism (VTE). MATERIALS AND METHODS: We retrospectively evaluated clinical pattern of VTE in patients who had been referred to vascular clinic shortly after an acute VTE event. In FVL positive and FVL negative groups we compared the prevalence of isolated symptomatic DVT (proximal or distal) and symptomatic PE with/without DVT, and, moreover, asymptomatic DVT or PE. RESULTS: Of 575 patients (mean age 57 years, 50.1% women), 120 were FVL positive and those had significantly higher prevalence of isolated symptomatic DVT, compared to symptomatic PE with/without DVT. Proximal DVT location was significantly more frequent in FVL carriers. The prevalence of asymptomatic PE did not differ between the two groups. The rate of asymptomatic DVT tended to be higher in FVL negative group. In a multivariate analysis, we confirmed FVL to be positively associated with isolated DVT presentation (odds ratio OR 1.757; 95% confidence interval (CI) 1.148-2.690). On the contrary, increasing age and unprovoked nature of VTE event carried a higher risk of symptomatic PE. CONCLUSIONS: We confirmed FVL to be significantly associated with isolated symptomatic DVT despite higher prevalence of proximal DVT in FVL carriers. The fact of relatively lower risk of PE in FVL positive patients might have clinical implication. However, mechanisms of FVL paradox remain to be elucidated.

Deep vein thrombosis and/or pulmonary embolism concurrent with superficial vein thrombosis of the legs: cross-sectional single center study of prevalence and risk factors.

AIM: The aim of this paper was to assess the prevalence of concurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in the patients with superficial vein thrombosis (SVT) of the legs and to find factors significantly and independently associated with coincident DVT/PE. METHODS: In the setting of a tertiary referral hospital, patients with SVT, attending vascular clinic, underwent physical examination, laboratory testing and leg vein ultrasound (in the case of clinically suspected PE also perfusion/ventilation lung scan or/and helical CT pulmonary angiography). In statistical analysis, we used unpaired t-test, non-parametric Wilcoxon rank sum test, stepwise logistic regression and multivariable logistic regression model. RESULTS: We examined 138 patients (age 61.4 ± 13.9 years, 36.2% men), with ST mostly on varicose veins (89.9%). The prevalence of concurrent DVT/PE was 34.1%. Neither the clinical manifestation nor SVT localization differed significantly between the group with isolated SVT and that with coincident DVT/PE. Of all the assessed patients characteristics (age and sex, BMI, history of SVT, DVT or PE, hypercoagulable states, cardiovascular risk factors) only two factors were significantly and independently associated with the presence of concurrent DVT/PE. Log BMI was significantly higher in the patients with isolated SVT. Factor V Leiden (FVL) was proved as an independent risk factor for concomitant DVT/PE with odds ratio 2,531 (95% CI 1,064-6,016). CONCLUSION: The prevalence of concurrent DVT/PE in patients with SVT, referred to hospital vascular clinic was 34.1%. Lower BMI (log BMI, respectively) and the presence of FVL were significantly and independently associated with concurrent DVT/PE. Our results should be further investigated in a larger prospective study.

[Superficial thrombophlebitis, unjustly underestimated disease - has the time come to change our view?]. / Povrchová tromboflebitida, neprávem podcenovaná choroba - je cas zmenit názor?

Superficial thrombophlebites represent a very heterogeneous group of diseases which is caused by the difference between two basic forms of ST - varicophlebitis and thrombophlebitis of a "healthy" vein, as well as by other factors - the ratio of thrombotic and inflammatory process, the location and extent of thrombosis in superficial venous system, the distance from deep venous system, the stage of venous insufficiency and the general thrombotic risk of a patient. ST shares many common features with deep vein thrombosis (clinical risk factors, thrombophilic disorders), both diseases often coincide or follow one another. Some authors suggest considering ST as a part of venous thromboembolism in a broader sense. There are ensuing unresolved questions regarding ST management. So far, no evidence-based treatment has been clearly defined. Anticoagulation is recommended in more serious cases but no consensus about dosing and duration has been reached. The CALISTO trial confirmed a benefit of fondaparinux in prophylactic dose in the therapy of isolated ST and the results have been reflected in recent guidelines of expert groups. Further studies to improve our knowledge of ST and to earn more evidence about its management are definitely needed.

Risk factors for residual thrombotic occlusion after proximal deep vein thrombosis of the legs.

AIM: Residual thrombotic occlusion (RTO) after deep vein thrombosis (DVT) is considered as a risk factor of recurrent venous thromboembolism (VTE). We searched for risk factors associated with RTO after proximal DVT at the lower extremities. METHODS: Using compression ultrasound, we evaluated the presence of RTO at 6 months after DVT (RTO defined as a residual thrombus occupying, at maximum compressibility, >/=20% of the vein lumen before compression). RESULTS: We examined 126 Czech patients: mean age 57.5 years; 50.0% women, 68.3% femoral location of DVT (otherwise popliteal), RTO found in 45.2%. While accounting for covariates, in the whole population, RTO was significantly associated with following factors: (OR; 95% confidence limit; p value): male sex (2.01; 1.27-3.19; P=0.003), femoral location (2.76; 1.59-4.78; P=0.0003). In women, but not in men, an association was demonstrated for: concurrent pulmonary embolism (PE) (18.51; 1.85-185.7; P=0.0131), diabetes mellitus (4.62; 1.38-15.51; P=0.0133) and statin use (0.11; 0.02-0.62; P=0.0125). In contrast, in men RTO was associated with an unprovoked DVT (2.6; 1.26-5.34; P=0.0094). CONCLUSION: In the whole study population, male sex and femoral location of DVT were positively associated with RTO. In women, concurrent PE and diabetes mellitus were risk factors for RTO, while the use of statins was a protective factor. There was a positive association between RTO and unprovoked DVT in men. These findings deserve further evaluation in a larger study.

Laboratory evaluation of antiphospholipid antibodies in patients with venous thromboembolism.

The objective of our study was to evaluate the significance of extended antiphospholipid profile in patients with venous thromboembolism without any systemic autoimmune disease. In 140 patients (age 18-69 years; 47.1% men) with venous thromboembolism and 136 control participants we tested anticardiolipin antibodies, anti-beta 2 glycoprotein I (anti-beta2-GPI) and also non-criteria antiphospholipid antibodies: antiphosphatidic acid, antiphosphatidylethanolamine, antiphosphatidylglycerol, antiphosphatidylinositol, antiphosphatidylserine. Commercial and in-house enzyme-linked immunosorbent assays were used. The antibodies with significantly higher prevalence in patients (compared to controls) were: immunoglobulin (Ig) M-anticardiolipin antibodies (12.9%; P = 0.035), IgG-anti-beta2-GPI (16.4%; P = 0.0032), IgM-antiphosphatidylethanolamine (14.3%; P = 0.014). In most cases, these three antibodies did not overlap. In conclusion, of non-criteria antiphospholipid antibodies, only antiphosphatidylethanolamine were significantly more prevalent in patients with venous thromboembolism, with only minor overlapping with the criteria antiphospholipid antibodies. Our results suggest the possible utility of searching for antiphosphatidylethanolamine in the clinical suspicion of antiphospholipid syndrome and the absence of criteria antiphospholipid antibodies.

[The optimum length of anticoagulation therapy after venous thromboembolism--universal or individualised approach?]. / Optimální délka antikoagulainí lécby po zilní tromboembolické príhode: obecný ci individualizovaný prístup?

Long-term peroral anticoagulation treatment is indicated after a thromboembolic event. The length of treatment should be based on balancing the risk of recurrence against the risk of bleeding complications. The minimum period of treatment is 3 months and can be reduced in certain cases; however, for many patients, a longer period of treatment may be recommendable. The presence or absence of a provoking factor and the nature of such a factor are of primary relevance when deciding on the length of treatment. Patients after a thromboembolic event provoked by a transitory (reversible) risk factor (surgery, accident, estrogen treatment etc.) have a very low risk of recurrence and a three-month treatment period is sufficient for them. In the remaining cases, extended treatment is recommendable, spanning from 6 to 12 months minimally. The type and scope of the event and the number of possible previous events should also be considered. Patients with a malignancy have a higher risk of recurrence and benefit most from long-term therapy with low-molecular weight heparin. Male sex, some thrombophilias and, according to some studies, the presence of residual thrombus in the vein, all increase the risk of recurrence. D-dimer detection results may also be useful in determining treatment length. They should be measured both before discontinuation of treatment and, more importantly, one month after treatment termination. A negative result in the D-dimer detection test means that there is a very low recurrence risk whilst a positive result indicates high risk of recurrence, in which case renewal of anticoagulation therapy should be considered. Deciding on the length of therapy is a complex process and should involve interdisciplinary cooperation.

[The prophylaxis against venous thromboembolic complications in internal medicine--the gap between theory and practice]. / Profylaxe zilních tromboembolických komplikaci v interních oborech--rozpor mezi teorií a praxí.

Venous thromboembolism is an important cause of morbidity and mortality in internal medicine but antithrombotic prophylaxis is not being sufficiently used in comparison with surgical settings. In medical patients there are usually multiple risk factors, often with cumulative effect and the comprehensive risk assessment is complicated. The most important agents for pharmacological thromboprophylaxis are heparins - unfractionated and low-molecular-weight. The metaanalysis of randomised trials comparing unfractionated or low-molecular-weight heparin against control (placebo or aspirin) in medical patients has confirmed a significant risk reduction for deep vein thrombosis (56 %) as well as pulmonary embolism (58 %). Low-molecular-weight heparin is as effective as unfractionated heparin in reducing mortality as well as venous thromboembolism but has the advantage of significantly fewer bleeding complications. A novel synthetic pentasaccharide antithrombotic agent fondaparinux has been successfully proved in thromboprophylaxis in medical patients too. In most trials the duration of pharmacological prophylaxis was up to 2 weeks, the possible benefit of extended prophylaxis has not been clarified yet. Specific groups are intensive care patients; the elderly for their high thromboembolic as well as bleeding risk and significant comorbidity; the patients with acute ischaemic stroke who have very high thromboembolic risk but there are concerns about the risk of haemorrhagic transformation of stroke. The economic studies have shown that low-molecular-weight heparin in prophylactic doses in acutely ill medical patients is cost-effective strategy.

[Clinical importance of aspirin resistance]. / Klinický význam aspirinové rezistence.

The antiplatelet effect of aspirin is mostly explained by the irreversible cyclooxygenase-1 inhibition resulting in the suppression of thromboxane A2 synthesis. The benefit of aspirin was proved in various cardiovascular diseases. However, the inter- and intraindividual variability of its antiplatelet effect is well known. Aspirin resistance can be understood from the clinical point of view--as a failure of the protective effect of aspirin from thrombotic complication or can be defined from the laboratory aspect--as an inability to cause in vitro detectable platelet function inhibition. The cause of this phenomenon has not been completely explained yet and more mechanisms have been proposed, incomplete suppression of thromboxane A2 generation being one of them. Laboratory diagnostics of aspirin resistance is based on the demonstration of the insufficient inhibition of platelet aggregation or the incomplete suppression of thromboxane A2 synthesis (assay for its metabolite, 11-dehydrothromboxane B2 in urine). The results of some trials raise the possibility that aspirin resistance could be a new independent predictor of cardiovascular events.

[Long-term drug interaction of warfarin with amiodarone]. / Dlouhotrvající léková interakce warfarinu s amiodaronem.

Authors describe a case of drug interaction between amiodarone and warfarin in 66-year-old man with recurrent atrial fibrillation. In spite of a relatively low dose of warfarin, prothrombin time became extremely prolonged and bleeding manifestations occurred. Effects of the interaction persisted for a long time after the withdrawal of both drugs. Various approaches to oral anticoagulant reversal are discussed. Pharmacokinetics of both drugs is explained, as well as the mechanism of their interaction through cytochrome P450 inhibition in the liver. Authors emphasize the great interindividual variability and long persistence of this interaction. It is necessary to consider carefully the indication of using these drugs together and when the use is inevitable, it is recommended to lower the warfarin dose to 50-70% and to perform thorough and frequent INR monitoring.