Risk Of Thrombosis In Individuals Research Articles

Percutaneous left atrial appendage closure with SeaLA device in non-valvular atrial fibrillation.

The clinical efficacy and safety of a novel left atrial appendage (LAA) occluder of the SeaLA closure system in patients with nonvalvular atrial fibrillation (NVAF) were reported. Patients with NVAF are at a higher risk of stroke compared to healthy individuals. Left atrial appendage closure (LAAC) has emerged as a prominent strategy for reducing the risk of thrombosis in individuals with NVAF. A prospective, multicenter study was conducted in NVAF patients with a high risk of stroke. The LAAC was successfully performed in 163 patients. The mean age was 66.93 ± 7.92 years, with a mean preoperative CHA2DS2-VASc score of 4.17 ± 1.48. One patient with residual flow >3 mm was observed at the 6-month follow-up, confirmed by TEE. During the follow-up, 2 severe pericardiac effusions were noted, and 2 ischemic strokes were observed. Four device-related thromboses were resolved after anticoagulation treatment. There was no device embolism. The LAAC with the SeaLA device demonstrates encouraging feasibility, safety, and efficacy outcomes.

Arterial and venous thrombosis by high platelet count and high hematocrit: 108 521 individuals from the Copenhagen General Population Study

BackgroundIt is unclear whether high platelet count or high hematocrit predict risk of thrombosis in individuals from the general population. ObjectivesWe tested the hypothesis that individuals from the general population with high platelet count or high hematocrit have high risk of arterial and venous thrombosis. MethodsWe prospectively followed 108 521 individuals from The Copenhagen General Population Study for a median of 8 years. Platelet count and blood hematocrit were measured at study entry. Results and ConclusionMultivariable adjusted hazard ratios for individuals with platelet counts in the top 5 percentiles (>398 × 109/L) vs in the 25th‐75th percentiles (231‐316 × 109/L) were 1.77 (95% confidence interval [CI], 1.38‐2.24) for arterial thrombosis in the brain (38 and 26 events/10 000 person‐years) and 0.82 (95%, 0.61‐1.11) for arterial thrombosis in the heart (23 and 28 events/10 000 person‐years). For individuals with hematocrit values in the top 5 percentiles (women/men: >45/>48%) vs the 25th‐75th percentiles (women/men: 38.1‐42/41.1‐45%), hazard ratios were 1.27 (95% CI, 0.91‐1.75) for arterial thrombosis in the brain (40 and 26 events/10 000 person‐years) and 1.46 (95% CI, 1.06‐2.00) for arterial thrombosis in the heart (43 and 25 events/10 000 person‐years). Neither high platelet count nor high hematocrit was associated with risk of venous thromboembolism. When excluding individuals with myeloproliferative neoplasia from the main analyses, results on risk of thrombosis were similar. In this prospective study, high platelet counts were associated with 1.8‐fold risk of arterial thrombosis in the brain, whereas high hematocrit was associated with 1.5‐fold risk of arterial thrombosis in the heart.

Thrombophilic risk of individuals with rare compound factor V Leiden and prothrombin G20210A polymorphisms: an international case series of 100 individuals.

The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE.

Plasma fatty acid levels may regulate the Zn 2+-dependent activities of histidine-rich glycoprotein

Histidine-rich glycoprotein (HRG) is a plasma adaptor protein involved in the formation of protein complexes that regulate a number of biological processes in the blood, most notably coagulation and the immune system. Elevated levels of HRG are clinically linked to thrombotic disorders such as blood vessel occlusion. A large body of evidence suggests that Zn 2+ ions stimulate HRG-complex formation; however, under normal conditions the vast majority of Zn 2+ in the blood is bound to human serum albumin (HSA). We have previously demonstrated that high levels of fatty acid act as an allosteric switch which disrupts the major Zn 2+-binding site on HSA. Transient or sustained elevation of plasma fatty acid levels may therefore increase the proportion of plasma Zn 2+ associated with HRG. We speculate that this mechanism may potentiate an increased risk of thrombosis in individuals with elevated fatty acid levels such as those associated with cancer, obesity and diabetes.

Travel-related venous thrombosis: results from a large population-based case control study (MEGA study).

BackgroundRecent studies have indicated an increased risk of venous thrombosis after air travel. Nevertheless, questions on the magnitude of risk, the underlying mechanism, and modifying factors remain unanswered.Methods and FindingsWe studied the effect of various modes and duration of travel on the risk of venous thrombosis in a large ongoing case-control study on risk factors for venous thrombosis in an unselected population (MEGA study). We also assessed the combined effect of travel and prothrombotic mutations, body mass index, height, and oral contraceptive use.Since March 1999, consecutive patients younger than 70 y with a first venous thrombosis have been invited to participate in the study, with their partners serving as matched control individuals. Information has been collected on acquired and genetic risk factors for venous thrombosis. Of 1,906 patients, 233 had traveled for more than 4 h in the 8 wk preceding the event. Traveling in general was found to increase the risk of venous thrombosis 2-fold (odds ratio [OR] 2.1; 95% confidence interval [CI] 1.5–3.0). The risk of flying was similar to the risks of traveling by car, bus, or train. The risk was highest in the first week after traveling. Travel by car, bus, or train led to a high relative risk of thrombosis in individuals with factor V Leiden (OR 8.1; 95% CI 2.7–24.7), in those who had a body mass index of more than 30 kg/m2 (OR 9.9; 95% CI 3.6–27.6), in those who were more than 1.90 m tall (OR 4.7; 95% CI 1.4–15.4), and in those who used oral contraceptives (estimated OR > 20). For air travel these synergistic findings were more apparent, while people shorter than 1.60 m had an increased risk of thrombosis after air travel (OR 4.9; 95% CI 0.9–25.6) as well.ConclusionsThe risk of venous thrombosis after travel is moderately increased for all modes of travel. Subgroups exist in which the risk is highly increased.

High levels of factor IX increase the risk of venous thrombosis

AbstractElevated plasma levels of factor VIII (> 150 IU/dL) are an important risk factor for deep vein thrombosis (DVT). Factor VIII is the cofactor of factor IXa in the activation of factor X. The risk of thrombosis in individuals with an elevated factor IX level is unknown. This study investigated the role of elevated factor IX levels in the development of DVT. We compared 426 patients with a first objectively diagnosed episode of DVT with 473 population controls. This study was part of a large population-based case-control study on risk factors for venous thrombosis, the Leiden Thrombophilia Study (LETS). Using the 90th percentile measured in control subjects (P90 = 129 U/dL) as a cutoff point for factor IX levels, we found a 2- to 3-fold increased risk for individuals who have factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by adjustment for possible confounders (age, sex, oral contraceptive use, and high levels of factor VIII, XI, and vitamin K-dependent proteins). After exclusion of individuals with known genetic disorders, we still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of premenopausal women not using oral contraceptives (OR: 12.4, CI: 3.3-47.2). These results show that an elevated level of factor IX is a common risk factor for DVT.

High levels of factor IX increase the risk of venous thrombosis

Elevated plasma levels of factor VIII (> 150 IU/dL) are an important risk factor for deep vein thrombosis (DVT). Factor VIII is the cofactor of factor IXa in the activation of factor X. The risk of thrombosis in individuals with an elevated factor IX level is unknown. This study investigated the role of elevated factor IX levels in the development of DVT. We compared 426 patients with a first objectively diagnosed episode of DVT with 473 population controls. This study was part of a large population-based case-control study on risk factors for venous thrombosis, the Leiden Thrombophilia Study (LETS). Using the 90th percentile measured in control subjects (P90 = 129 U/dL) as a cutoff point for factor IX levels, we found a 2- to 3-fold increased risk for individuals who have factor IX levels above 129 U/dL compared with individuals having factor IX levels below this cutoff point. This risk was not affected by adjustment for possible confounders (age, sex, oral contraceptive use, and high levels of factor VIII, XI, and vitamin K-dependent proteins). After exclusion of individuals with known genetic disorders, we still found an odds ratio (OR) of 2.5 (95% confidence interval [CI]: 1.6-3.9). The risk was higher in women (OR: 2.6, CI: 1.6-4.3) than in men (OR: 1.9, CI: 1.0-3.6) and appeared highest in the group of premenopausal women not using oral contraceptives (OR: 12.4, CI: 3.3-47.2). These results show that an elevated level of factor IX is a common risk factor for DVT.

The anti-phospholipid antibody syndrome (Hughes syndrome): therapeutic aspects.

Despite the enormous amount of work focused on the pathogenesis and clinical manifestations of the Hughes or anti-phospholipid syndrome (APS), there is little published on management. Usually, the diagnosis of APS is made after the first thrombotic event, when a thrombophilia screen is performed. These patients have a high risk of recurrent thromboses and current therapy centres on the use of thromboprophylaxis with warfarin. However, a number of clinical questions keep recurring: do arterial and venous thrombosis require the same intensity of anti-coagulation? When should warfarin be stopped? Should patients who develop thrombosis when other risk factors (oral contraceptive pill, prolonged resting etc.) are present be treated like those without any risk factors but the presence of anti-phospholipid antibodies (aPL)? How to manage a patient with recurrent thrombosis despite a high intensity anti-coagulation (International normalized ratio (INR) between 3.0-4.0)? Since many of the patients with aPL are fertile women, a substantial group of patients are diagnosed after recurrent pregnancy loss. Low-dose aspirin for those patients without previous thrombosis and aspirin plus heparin for patients with a history of thrombotic events are the current therapeutic options. However, some questions remain unanswered: does the addition of heparin to low-dose aspirin in women with first trimester recurrent miscarriage but without previous thrombosis improve foetal outcome over and above aspirin alone? Which is the best therapeutic regime during pregnancy for patients with aPL-associated stroke? When should high-dose intravenous gammaglobulin be considered? Finally, very little is known about the risk of thrombosis in individuals positive for aPL but still free of thrombosis. Should these individuals receive any treatment? If so, which one? In this review we attempt to address some of these questions taking into account available data from retrospective and prospective studies and our own clinical experience.