Biomedical subjects

Sabine Eichinger

Publications and source records attributed to Sabine Eichinger.

14 recordsLinked to original sources

PubMed2005

Treatment of venous thromboembolism.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two manifestations of the same disorder, venous thromboembolism, and low-molecular weight heparin is the treatment of choice for both DVT and PE. Alternatively, intravenous adjusted-dose unfractionated heparin can be used in hemodynamically unstable patients with massive PE. Secondary thromboprophylaxis with vitamin K-antagonists (VKA) should be started as soon as the diagnosis is confirmed. The dose of VKA should be adjusted to a target international normalized ratio (INR) of 2.5. For most patients with PE, thrombolysis is not recommended. Vena cava filters should be restricted to patients with active bleeding or risk of serious bleeding, and to those in whom PE has recurred despite adequate anticoagulation. Several new antithrombotics with potential advantages over heparin and VKA have been evaluated in phase II and III trials, but are currently not licensed for the treatment of venous thromboembolic events.

Acute Disease↗

PubMed2004

The risk of recurrent venous thromboembolism in men and women.

BACKGROUND: Whether a patient's sex is associated with the risk of recurrent venous thromboembolism is unknown. METHODS: We studied 826 patients for an average of 36 months after a first episode of spontaneous venous thromboembolism and the withdrawal of oral anticoagulants. We excluded pregnant patients and patients with a deficiency of antithrombin, protein C, or protein S; the lupus anticoagulant; cancer; or a requirement for potentially long-term antithrombotic treatment. The end point was objective evidence of a recurrence of symptomatic venous thromboembolism. RESULTS: Venous thromboembolism recurred in 74 of the 373 men, as compared with 28 of the 453 women (20 percent vs. 6 percent; relative risk of recurrence, 3.6; 95 percent confidence interval, 2.3 to 5.5; P<0.001). The risk remained unchanged after adjustment for age, the duration of anticoagulation, and the presence or absence of a first symptomatic pulmonary embolism, factor V Leiden, factor II G20210A, or an elevated level of factor VIII or IX. At five years, the likelihood of recurrence was 30.7 percent among men, as compared with 8.5 percent among women (P<0.001). The relative risk of recurrence was similar among women who had had their first thrombosis during oral-contraceptive use or hormone-replacement therapy and women in the same age group in whom the first event was idiopathic. CONCLUSIONS: The risk of recurrent venous thromboembolism is higher among men than women.

Adult↗

PubMed2004

Prevention of deep vein thrombosis in orthopedic surgery.

In the absence of thromboprophylaxis, venous thromboembolism (VTE) affects about 50 to 80% of the patients after total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery. Since stratification of patients in those who will become symptomatic and those who will not, is not possible, primary high risk thromboprophylaxis should be provided to all patients undergoing major orthopedic surgery of the lower extremity. Various non-pharmacologic and pharmacologic thromboprophylactic measures have been evaluated. With regard to pharmacologic thromboprophylaxis unfractionated heparin has now almost completely been replaced by low molecular weight heparin (LMWH) for VTE prophylaxis. The use of acetylsalicylic acid for thromboprophylaxis in patients undergoing major orthopedic surgery of the lower extremities is not recommended. The optimal beginning of LMWH thromboprophylaxis is either 2 hours preoperatively or 6 to 8 hours postoperatively. Extended thromboprophylaxis (beyond 7 to 10 days after surgery) is recommended for high-risk patients. New antithrombotics, such as fondaparinux or (xi)melagatran, significantly reduce the risk of asymptomatic but not of symptomatic VTE compared to LMWH. In the light of other potential side effects (e.g., an increased bleeding risk) and high costs the role of these new drugs in the prophylaxis of VTE in patients undergoing major orthopedic surgery of the lower extremities remains to be established.

Anticoagulants↗

PubMed2004

Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism.

The impact of fibrinolysis for predicting the risk for recurrent venous thromboembolism (VTE) is low. We prospectively followed up 600 patients with a first VTE and evaluated the thrombin-activatable fibrinolysis inhibitor (TAFI) as a risk factor for recurrence. A high TAFI level (75th or higher percentile in thrombosis patients) was associated with a 2-fold higher risk for recurrence compared with lower levels. The probability of recurrence 2 years after anticoagulation was 14.5% (95% confidence interval [CI], 8.6-20.4) among patients with high TAFI levels and 6.8% (95% CI, 4.3-9.3) among patients with lower levels (P =.006). Our data also support the concept of a linkage between fibrinolysis and the coagulation system. Patients with high TAFI levels had significantly higher levels of factors XI, VIII, and IX, and a high risk of recurrence was seen among patients with high TAFI levels and high levels of one of these factors. The relative risk (RR) for recurrence was highest among patients with high TAFI and high factor XI (RR, 2.9; 95% CI, 1.3-6.9), high factor VIII (RR, 6.5; 95% CI, 2.9-14.8), or high factor IX (RR, 2.0; 95% CI, 1.0-3.9) levels compared with patients with low levels of TAFI and one of these factors.

Anticoagulants↗

PubMed2004

Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism.

BACKGROUND: In patients with a first symptomatic pulmonary embolism (PE), the risk of recurrence is unknown. We therefore investigated the risk of recurrence among patients with spontaneous symptomatic PE and among those with deep vein thrombosis (DVT) without symptoms of PE. METHODS: After discontinuation of secondary thromboprophylaxis for a first venous thromboembolism (VTE), we prospectively observed 436 patients for an average of 30 months. Patients with secondary VTE, natural inhibitor deficiencies, lupus anticoagulant, cancer, long-term antithrombotic therapy, vena cava filters, or pregnancy were excluded. The study outcome was objectively documented recurrent symptomatic VTE. RESULTS: Recurrent VTE was seen among 28 (17.3%) of 162 patients with symptomatic PE and among 26 (9.5%) of 274 patients with DVT without symptoms of PE. Compared with patients with DVT, the relative risk of recurrent VTE among patients with symptomatic PE was 2.2 (95% confidence interval, 1.3-3.7; P =.005). The relative risk was not affected by age, sex, presence of factor V Leiden or prothrombin G20210A, hyperhomocysteinemia, or high factor VIII levels. Compared with patients with DVT without symptoms of PE, patients with symptomatic PE had an adjusted relative risk of PE at recurrence of 4.0 (95% confidence interval, 1.3-12.3; P =.03). CONCLUSION: Patients with a first symptomatic PE not only have a higher risk of recurrent VTE than those with DVT without symptoms of PE, but are also at high risk of symptomatic PE at recurrence.

Austria↗

PubMed2004

Prospective evaluation of coagulation activation in pregnant women receiving low-molecular weight heparin.

Pregnancy is a major risk factor for venous thromboembolism (VTE), and low-molecular weight heparin (LMWH) seems to be safe and effective in pregnant women. Normal pregnancy is accompanied by a state of hypercoagulability, indicated by an increase in markers of coagulation activation. In a prospective cohort study, we followed 61 women who received LMWH thromboprophylaxis throughout pregnancy because of a history of VTE, hereditary thrombophilia and/or previous pregnancy-related complications. The control group consisted of 113 healthy pregnant women without antithrombotics. D-Dimer, prothrombin fragment F1+2 (F1+2) and the resistance to activated protein C (APC-ratio) were measured in all women during the first, second and third trimester. Patients and controls did not significantly differ with regard to baseline characteristics and pregnancy outcome. A (recurrent) VTE was seen in one patient despite LMWH. D-Dimer levels significantly increased among patients and controls during pregnancy (p < 0.0001), and were significantly higher among patients compared with the controls (p <0.0001) [395 ng/ml (95% CI 340-458) and 249 ng/ml (95%CI 234-266); 710 ng/ml (95% CI 602-838) and 475 ng/ml (95% CI 431-523); 1089 ng/ml (95% CI 931-1273) and 822 ng/ml (95% CI 741-911); respectively]. Levels of F1+2 significantly increased while the APC-ratio significantly decreased during pregnancy among patients and controls. Despite LMWH, pregnancy is accompanied by a substantial activation of the coagulation system.

Adult↗

PubMed2003

D-dimer levels and risk of recurrent venous thromboembolism.

CONTEXT: Widespread screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors has become common clinical practice. Because of the increasing number of risk factors, assessing the risk of recurrence in an individual patient is intricate; therefore, a laboratory method that measures multifactorial thrombophilia is required. OBJECTIVE: To prospectively study the relationship between the risk of recurrent VTE and D-dimer, a global marker of coagulation activation and fibrinolysis. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 610 patients older than 18 years who were treated with oral anticoagulants for at least 3 months with a first spontaneous VTE, in whom D-dimer levels were measured shortly after discontinuation of oral anticoagulation. The study was conducted at the Department of Internal Medicine I, University Hospital, Vienna, Austria. Patients entered the study at time of discontinuation of oral anticoagulants and were observed at 3-month intervals during the first year and every 6 months thereafter from July 1992 to October 2002. MAIN OUTCOME MEASURE: Objectively documented symptomatic recurrent VTE. RESULTS: A total of 79 (13%) of 610 patients had recurrent VTE with a mean observation time of 38 months. Patients with recurrence had significantly higher D-dimer levels compared with those without recurrence (553 ng/mL vs 427 ng/mL, P =.01). Compared with patients with D-dimer levels of 750 ng/mL or higher, the relative risk (RR) of recurrence was 0.6 (95% confidence interval [CI], 0.3-1.4), 0.6 (95% CI, 0.3-1.2), and 0.3 (95% CI, 0.1-0.6) in patients with D-dimer levels of 500 to 749 ng/mL, 250 to 499 ng/mL, and less than 250 ng/mL, respectively. The cumulative probability of recurrent VTE at 2 years was 3.7% (95% CI, 0.9%-6.5%) among patients with D-dimer levels of less than 250 ng/mL compared with 11.5% (95% CI, 8.0%-15.0%) among patients with higher levels (P =.001). Patients with D-dimer levels of less than 250 ng/mL had a 60% lower RR of recurrence compared with patients with higher levels (RR, 0.4; 95% CI, 0.2-0.8). CONCLUSION: Patients with a first spontaneous VTE and a D-dimer level of less than 250 ng/mL after withdrawal of oral anticoagulation have a low risk of VTE recurrence.

Adult↗

PubMed2003

The risk of recurrent venous thromboembolism: the Austrian Study on Recurrent Venous Thromboembolism.

Venous thromboembolism (VTE) is a chronic disease. After withdrawal of oral anticoagulation at least a third of patients will experience a subsequent episode of venous thrombosis. Of these patients, approximately 5% will die from pulmonary embolism. The Austrian Study on Recurrent Venous Thromboembolism (AUREC) is a prospective cohort study aiming to investigate the overall rate of recurrent VTE, the predictive value of laboratory assays, the importance of acquired or congenital risk factors for thrombosis and the impact of extended or modified secondary thromboprophylaxis on the risk of recurrence among high-risk patients. So far, the AUREC investigators have identified subgroups of patients with a particular high risk of recurrence: patients with a history of venous thrombosis, elevated levels of coagulation factors VIII, IX and XI, pulmonary embolism or superficial venous thrombosis and a history of venous thrombosis and hyperhomocysteinemia. Patients with a history of venous thrombosis and mutations in genes encoding for coagulation factors (factor V Leiden, factor II, G20210A) do not have an enhanced risk of recurrence and, thus, do not qualify for extended secondary thromboprophylaxis. At present, interventional trials are in progress in patients with high factor VIII or hyperhomocysteinemia in order to investigate if these patient groups might benefit from extended oral anticoagulation or vitamin supplementation, respectively.

Adolescent↗

PubMed2003

Novel anticoagulants for the prevention and treatment of venous thromboembolism.

Unfractionated heparin, low molecular weight heparin and vitamin K antagonists are anticoagulants currently used for the prevention and treatment of deep vein thrombosis and pulmonary embolism. Considerable limitations of these agents, such as a narrow therapeutic window, a variable dose response or lack of oral bioavailability, created the need for new anticoagulants. Numerous new compounds with different mechanisms of action have been developed and some have been already approved for clinical use. Quite recently, fondaparinux, an indirect anti-factor Xa inhibitor, has been licensed in Europe and in the US for prevention of VTE in patients undergoing hip or knee replacement surgery. In addition, lepirudin, a recombinant hirudin derivative, and the heparinoid danaparoid, have been approved in Austria for treatment of heparin-induced thrombocytopenia. Recombinant nematode anticoagulant protein c2, the orally available thrombin inhibitor ximelagatran and ART-123, a recombinant soluble thrombomodulin, are in advanced stages of clinical development. This article reviews mechanisms and sites of action, and the current state of preclinical and clinical research of these and various other agents with respect to the prevention and treatment of venous thromboembolism).

Anticoagulants↗

PubMed2003

Superficial thrombophlebitis and risk for recurrent venous thromboembolism.

OBJECTIVE: Superficial thrombophlebitis (ST) is a frequent and potentially serious disease if complicated with venous thromboembolism (VTE). Data on risk factors and incidence rates for ST are scarce. It is also unknown whether ST is a risk factor for recurrence of VTE. METHODS: After discontinuation of secondary thromboprophylaxis for a first spontaneous VTE, we prospectively observed 615 patients on average for 30 +/- 26 months. Patients with natural coagulation inhibitor deficiency, lupus anticoagulant, or cancer, who were pregnant, or were receiving long-term antithrombotic therapy were excluded. The study outcomes were occurrence of symptomatic ST or objectively documented recurrent symptomatic VTE. RESULTS: ST developed in 45 patients (7.3%) with a first VTE. High factor VIII concentration emerged as an independent risk factor for ST (relative risk [RR], 2.0; 95% confidence interval [CI], 1.0-5.2), compared with lower levels after adjustment for age and sex; factor V Leiden and prothrombin G20210A concentration; hyperhomocysteinemia; high body mass index; and duration of oral anticoagulation therapy. VTE recurred in 12 (27%) of 45 patients with ST and in 67 (12%) of 570 patients without ST. In patients with VTE, subsequent ST emerged as an independent risk factor for recurrent VTE. Patients with ST had twofold higher RR (2.1; 95% CI, 1.0-4.2) for recurrence than did patients without ST after adjustment for putative confounding variables. CONCLUSION: Patients with a first spontaneous VTE and subsequent ST are at increased risk for recurrent VTE. High factor VIII concentration is an independent risk factor for ST.

Adult↗

PubMed2002

The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism.

BACKGROUND: Factor V (FV) Leiden is a risk factor for venous thrombosis (VT). Data on its influence on the risk of recurrent venous thromboembolism (VTE) are controversial owing to different study designs and patient cohorts. METHODS: We reevaluated the risk of recurrence among heterozygous carriers and noncarriers of FV Leiden with a first spontaneous proximal VT of the leg and/or pulmonary embolism. Patients with secondary VTE, homozygous FV Leiden, natural inhibitor deficiencies, lupus anticoagulant, cancer, or long-term anticoagulation were excluded. The study end point was objectively documented, symptomatic, recurrent VTE. RESULTS: After discontinuation of oral anticoagulant therapy for a first VTE, we prospectively observed 287 patients, 83 (29%) of whom were heterozygous for FV Leiden. Recurrent VTE was seen in 17 (20%) of 83 patients with and 44 (21.6%) of 204 without FV Leiden. The probability of recurrence among heterozygotes was 12% (95% confidence interval [CI], 8%-16%), 27% (95% CI, 21%-33%), and 27% (95% CI, 21%-33%) after 2, 4, and 6 years, respectively, and was not higher than that among patients without the mutation (16%, 23%, and 34%, respectively). The relative risk of recurrence in heterozygotes was 0.9 (95% CI, 0.5-1.6; P =.60) after adjustment for confounding variables. The risk of recurrence among patients with and without FV Leiden was not different when sex distribution or duration of anticoagulation therapy was taken into account. CONCLUSIONS: The risk of recurrence is similar among carriers and noncarriers of FV Leiden. Heterozygous patients should receive secondary thromboprophylaxis for a similar length of time as patients without FV Leiden.

Adult↗

PubMedDate not supplied

Deep vein thrombosis.

Deep vein thrombosis and its sequelae pulmonary embolism and post-thrombotic syndrome are some of the most common disorders. A thrombus either arises spontaneously or is caused by clinical conditions including surgery, trauma, or prolonged bed rest. In these instances, prophylaxis with low-dose anticoagulation is effective. Diagnosis of deep vein thrombosis relies on imaging techniques such as ultrasonography or venography. Only about 25% of symptomatic patients have a thrombus. Thus, clinical risk assessment and D-dimer measurement are used to rule out deep vein thrombosis. Thrombus progression and embolisation can be prevented by low-molecular-weight heparin followed by vitamin K antagonists. Use of these antagonists for 3-6 months is sufficient for many patients. Those with antithrombin deficiency, the lupus anticoagulant, homozygous or combined defects, or with previous deep vein thrombosis can benefit from indefinite anticoagulation. In cancer patients, low-molecular-weight heparin is more effective than and is at least as safe as vitamin K antagonists. Women seem to have a lower thrombosis risk than men, but pregnancy or use of oral contraceptives or hormone replacement therapy represent important risk factors.

Humans↗

PubMedDate not supplied

D-dimer testing in pregnancy.

During pregnancy, elevated markers of coagulation and fibrinolytic system activation, such as D-Dimer, indicate increased thrombin activity and increased fibrinolysis following fibrin formation. Testing for D-Dimer during pregnancy could therefore be useful for the diagnosis and prediction of a venous thromboembolic event (VTE) or pregnancy-related complications, and for monitoring antithrombotic treatment. This approach, however, is hampered by the fact that even an uncomplicated pregnancy in healthy women is accompanied by a substantial increase of D-Dimer. Thus, prior to clinical application reference values of D-Dimer according to gestational age need to be established. A substantial increase of D-Dimer during pregnancy is seen despite thromboprophylaxis with low molecular weight heparin (LMWH) indicating that further studies are needed to evaluate monitoring of LMWH during pregnancy and to investigate the optimal beginning and dose of LMWH thromboprophylaxis in pregnant women.

Female↗

PubMedDate not supplied

Homocysteine, vitamin B6 and the risk of recurrent venous thromboembolism.

Hyperhomocysteinemia (HHC) is an independent risk factor for cardiovascular disease, and even mildly to moderately elevated homocysteine levels have been associated with a heightened risk for a first and recurrent venous thromboembolism (VTE). Within the frame of a large prospective cohort study (Austrian Study on Recurrent Venous Thromboembolism), we assessed the impact of HHC on the risk of recurrence among 602 patients with a first unprovoked VTE. HHC was an independent risk factor of recurrence conferring a relative risk of 1.5 (95th% CI 1.0-2.4). HHC is caused either by genetic defects and/or by a deficiency of the vitamins (B12, B6 and folic acid) involved in the homocysteine metabolism. Low vitamin B6 levels are associated with an increased risk of a first venous thrombosis. We currently investigate whether or not low plasma levels of PLP are associated with a heightened risk for recurrent VTE.

Homocysteine↗