This is a common disease afflicting many patients in a variety of clinical situations and involving all ages.
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CHARACTERIZATION |
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PREVALENCE |
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A study of hospital discharges for venous thromboembolism in the south of Spain. An analysis of 19,170 cases from a regional database from 1998 to 2001.
Guijarro R, San Roman CM, Perello JI, Nuno E; Efficiency Group of the Internal Medicine Services of Andalusia. Strategic Plan of the SADEMI (Andalusia Society of Internal Medicine).
Internal Medicine Service of the Carlos Haya Regional University Hospital, Malaga, Spain.
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| Eur J Intern Med. 2005 Aug;16(4):279-86. Abstract quote |
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BACKGROUND: Our objective was to learn about the incidence of hospitalization for venous thromboembolism (VTE) in the public health care system in Andalusia and to define the profile of the patients, with special reference to the Department of Internal Medicine.
METHODS: We analyzed the discharged data set of 32 hospitals in the Andalusian Health Care Service between 1998 and 2001, identifying the cases in whom the diagnosis was VTE. The age, sex, length of stay, outcome, number of diagnoses, diagnosis-related group (DRG), and coded procedures were studied.
RESULTS: During the period studied, there were 2,228,894 discharges, 19,170 of which involved VTE. In 8494 of these, VTE was the cause of the admission. Some 3961 patients (46.6%) were admitted for pulmonary embolism (PE); 45% were discharged from internal medicine, 41% from pneumology, and 14% from other departments. The average patient age was 65, the length of stay 13.8 days, and the global in-hospital mortality rate 13%. Some 4533 cases (53.4%) were admitted due to deep vein thrombosis (DVT): 38.5% to internal medicine, 21.30% to general surgery, 12.35% to angiology, and the remainder to other departments. The length of stay was 10.6 days with an in-hospital mortality rate of 2.20%. In 7721 cases, VTE was the secondary diagnosis (after excluding 2955 cases of superficial thrombophlebitis of the upper limbs); 74% was associated with a medical DRG.
CONCLUSIONS: VTE is a frequent pathology in our hospitals. It shows a great variability in clinical practice although there are differences between patients treated by different specialists. VTE as secondary diagnosis was more frequent in medical inpatients.
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| DISEASE ASSOCIATIONS |
CHARACTERIZATION |
| ANTI-PHOSPHOLIPID ANTIBODY SYNDROME |
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Anticoagulation therapy in the antiphospholipid syndrome: recent advances.
Ng HJ, Crowther MA.
aDepartment of Medicine, Singapore General Hospital, Singapore, and bDepartment of Medicine, McMaster University and St Joseph's Hospital, Hamilton, Ontario, Canada.
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| Curr Opin Pulm Med. 2005 Sep;11(5):368-372. Abstract quote |
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PURPOSE OF REVIEW: The antiphospholipid syndrome is currently best treated with anticoagulation. This review discusses the recent literature addressing the duration, intensity, and appropriateness of anticoagulation or antiplatelet therapy in various clinical subcategories of this syndrome.
RECENT FINDINGS: Several recent articles reaffirm the benefits of long-term anticoagulation in patients with venous thromboembolism or undergoing renal transplantation and support recommendations for usual International Normalized Ratio targets. Aspirin seems to confer benefits similar to those of anticoagulation in arterial stroke. Appropriate anticoagulation strategies for pregnancy are controversial.
SUMMARY: Anticoagulation will remain the mainstay of treatment for most patients with antiphospholipid syndrome. The optimal therapy for specific subgroups of patients will, however, require further good-quality studies.
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| CANCER |
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Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528 693 adults.
White RH, Chew HK, Zhou H, Parikh-Patel A, Harris D, Harvey D, Wun T.
Departments of Internal Medicine, Medicine, Medicine and Statistics, and Public Health Sciences, University of California, Davis.
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| Arch Intern Med. 2005 Aug 8;165(15):1782-7. Abstract quote |
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BACKGROUND: It is unclear how frequently unprovoked venous thromboembolism (VTE) reflects the presence of an occult cancer.
METHODS: The California Cancer Registry was used to identify diagnosed cases of 19 common malignancies during a 6-year period. Cases were linked to a hospital discharge database to identify incident VTE events in the year before the cancer diagnosis date. The standardized incidence ratio (SIR) of unprovoked VTE was determined by using the age-, race-, and sex-specific incidence rates in California.
RESULTS: Among 528 693 cancer cases, 596 (0.11%) were associated with a diagnosis of unprovoked VTE within 1 year of the cancer diagnosis, compared with 443.0 expected cases (SIR, 1.3; 95% confidence interval, 1.2-1.5; P<.001). Among cases with metastatic-stage cancer, the SIR was 2.3 (95% confidence interval, 2.0-2.6; P<.001), whereas for all other stages, the SIR was 1.07 (95% confidence interval, 0.97-1.18; P = .09). The incidence of preceding VTE was increased over that expected only during the 4-month period immediately preceding the cancer diagnosis date (P<.001). Only 7 cancer types were associated with a significantly elevated SIR: acute myelogenous leukemia; non-Hodgkin lymphoma; and renal cell, ovarian, pancreatic, stomach, and lung cancer (SIR range, 1.8-4.2).
CONCLUSIONS: In the year preceding the diagnosis of cancer, the number of cases with unprovoked VTE was modestly higher than expected, and almost all of the unexpected VTE cases were associated with a diagnosis of metastatic-stage cancer within 4 months. Given the timing and advanced stage of the unexpected cases, it is unlikely that earlier diagnosis of these cancers would have significantly improved long-term survival.
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Hormone replacement therapy and risk for venous thromboembolism: what's new and how do these findings influence clinical practice?
Douketis J.
Department of Medicine, McMaster University and St. Joseph's Hospital, Hamilton, Ontario, Canada.
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| : Curr Opin Hematol. 2005 Sep;12(5):395-400. Abstract quote |
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PURPOSE OF REVIEW: Although an association between hormone replacement therapy and venous thromboembolism has been established, several unanswered questions remain. This review will address additional questions relating to hormone replacement therapy and venous thromboembolism. Does the risk for venous thromboembolism differ according to the type of hormone replacement therapy? Does the presence of thrombophilia influence the risk for venous thromboembolism in hormone replacement therapy users? Should hormone replacement therapy be temporarily interrupted around the time of surgery?
RECENT FINDINGS: The risk for venous thromboembolism seems to be less in users of estrogen-only hormone replacement therapy (odds ratio = 1.2; 95% confidence interval: 0.6-2.6) than in users of estrogen-progestin hormone replacement therapy (odds ratio = 2.7; 95% confidence interval: 1.4-5.1), and there may be no increased risk for venous thromboembolism with transdermal hormone replacement therapy (odds ratio = 1.0; 95% confidence interval: 0.3-3.3). The presence of a prothrombotic blood abnormality, such as the factor V Leiden mutation, seems to further increase the risk for venous thromboembolism in hormone replacement therapy users (odds ratio = 17.1; 95% confidence interval: 3.7-78). Continued use of hormone replacement therapy in the perioperative period does not seem to have an impact on the overall risk for postoperative venous thromboembolism (odds ratio = 0.66; 95% confidence interval: 0.35-1.18).
SUMMARY: Recent studies have extended our understanding regarding the association between hormone replacement therapy and venous thromboembolism. The implications of these findings on clinical practice are discussed.
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Thromboembolism during hormone therapy in Japanese women.
Adachi T, Sakamoto S.
Head of Obstetrics and Gynecology, Aiiku Maternal and Child Health Center A Hospital, Tokyo, Japan.
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| Semin Thromb Hemost. 2005 Jun;31(3):272-80. Abstract quote |
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Japanese women are unaccustomed to taking hormone therapies such as oral contraceptives (OCs) and hormone replacement therapy (HRT); therefore, there are few studies associated with hormone treatment in Japan.
This study focused on evaluating thromboembolism during hormone therapy in Japanese women. In February 2002, we mailed questionnaires regarding the monthly average number of patients who had received prescriptions for OCs and HRT, and the incidence of arterial and venous thromboemboli during hormone therapy for the last 10 years. The mailings were sent to hospitals and clinics that are registered as monitoring institutions with the Japan Association of Obstetricians and Gynecologists. Of 1083 institutes, 771 responded (71% response rate).
In July 2002, to obtain additional information on hormone therapy, patient history, and outcomes, we sent follow-up questionnaires to 39 institutions that responded as having experienced cases of thromboembolism. Thirty-nine institutions (5.1% of institutions responding to survey) experienced 53 cases of thromboembolism during hormone therapy. The 53 patients included 29 who received OCs (OC patients), 13 who received HRT (HRT patients), and 11 who received other hormone treatment.
Among the 29 OC patients, eight had been diagnosed as having arterial thromboembolism (ATE), including two patients with myocardial infarction (MI) and six with ischemic stroke, whereas 20 had venous thromboembolism (VTE), including two with pulmonary embolism (PE) The remaining patient had an unknown thromboembolic event. Of the OC patients, 75.9% had a thromboembolism within the first year, and 58.6% patients were in their 40s. In 13 HRT patients, seven had ATE, including two MI patients and three with ischemic brain stroke, whereas six had VTE, including one PE patient. The duration of HRT varied widely from less than 1 year to more than 3 years; moreover, the HRT type did not affect thromboembolism occurrence. More than 70% of ATE patients and less than one third of VTE patients had to be hospitalized for the treatment of thromboembolism, and more than 75% of VTE patients recovered completely. However, one third of the ATE patients recovered with mild sequelae, one OC patient had severe sequelae due to stroke, and another OC patient died due to an ischemic event. The estimated incidence of thromboembolism in OC patients and HRT patients was 3.6 to 14.4 and 1.7 to 3.4 per 100,000 woman-years, respectively.
The risk factors of thromboembolism, which were found consistently in this study, included obesity, smoking, lifestyle, and aging. Approximately 95% of institutions had not experienced thromboembolism in their hormone therapy patients, suggesting the incidence of thromboembolism during hormone therapy might be low. However, according to an analysis of risk factors, screening users of hormone supplements may be essential for providing safe hormone therapy. Moreover, because of the early occurrence of thromboembolism during hormone therapy, especially with OCs, it is important to monitor and instruct patients with caution from immediately after therapy initiation.
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| LEUKEMIA, ACUTE |
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The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment.
DE Stefano V, Sora F, Rossi E, Chiusolo P, Laurenti L, Fianchi L, Zini G, Pagano L, Sica S, Leone G.
Institute of Hematology, Catholic University, Rome, Italy.
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| J Thromb Haemost. 2005 Jul 8; [Epub ahead of print] Abstract quote |
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Summary. Background: Thromboembolism can occur during acute leukemia, especially acute lymphoid leukemia (ALL) treated with l-asparaginase. Yet, most reports are anecdotical and scarce data are available on the risk of thrombosis in acute myeloid leukemia (AML).
Objectives: To evaluate the risk of thrombosis in patients with acute leukemia. Patients and methods: Three-hundred and seventy-nine consecutive adult patients with newly diagnosed acute leukemia were recruited in an observational cohort study conducted from January 1994 to December 2003. Diagnosis was ALL in 69 patients, acute promyelocytic leukemia (APL; FAB subtype M3) in 31, and non-M3 AML in 279. All first or recurrent symptomatic thromboembolic events objectively diagnosed were recorded.
Results: Twenty-four patients of the overall 379 (6.3%; 95% CI 4.1%-9.2%) had a first thrombosis, venous in 80% of the cases and arterial in 20%. At diagnosis, thrombosis was a presenting manifestation in 13 cases (3.4% of the whole cohort): 1.4% in ALL, 9.6% in APL, and 3.2% in non-M3 AML patients. Follow-up was carried out on 343 patients without thrombosis at diagnosis and further 11 thrombotic events (3.2%) were recorded. At 6 months from diagnosis, the cumulative incidence of thrombosis was 10.6% in ALL, 8.4% in APL, and 1.7% in non-M3 AML patients. The patients who received l-asparaginase had a 4.9-fold increased risk of thrombosis in comparison with those who did not (95% CI 1.5-16.0). The fatality rate due to thrombosis was 0.8%.
Conclusions: In patients with acute leukemia, the risk of thrombosis is not negligible. Thombosis can be a presenting symptom at diagnosis in a significant portion of cases with APL (9.6%) and non-M3 AML (3.2%); a similar rate of thrombosis can occur during the subsequent course of the disease. The incidence of symptomatic thrombosis at diagnosis is relatively low in ALL patients (1.4%), but is significantly increased by further treatment up to 10.6%. Strategies of antithrombotic prophylaxis should be investigated in this setting.
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A Case Control Study on the Contribution of Factor V-Leiden, Prothrombin G20210A, and MTHFR C677T Mutations to the Genetic Susceptibility of Deep Venous Thrombosis.
Almawi WY, Tamim H, Kreidy R, Timson G, Rahal E, Nabulsi M, Finan RR, Irani-Hakime N.
Al-Jawhara Center for Molecular Medicine, Genetics, and Inherited Diseases, Arabian Gulf University, Manama, Bahrain.
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| J Thromb Thrombolysis. 2005 Jun;19(3):189-96. Abstract quote |
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Background: Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous thromboembolism (VTE), the aim of this study was to determine the prevalence of single and combined SNPs in 198 patients with documented deep venous thrombosis (DVT), and 697 control subjects, and to estimate the associated risks.
Methods: Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by PCR and restriction fragment length polymorphism (RFLP).
Results: The prevalence of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR 6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T, and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis showed a further increased odds for FV-Leiden in combination with PRT G20210A (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT G20210A in combination with homozygous MTHFR C677T (20.812).
Conclusions: This indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important risk factors for DVT, and that the presence of more than one prothrombotic SNPs was associated with a significant risk of DVT.
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| LABORATORY/
RADIOLOGIC/
OTHER TESTS |
CHARACTERIZATION |
| RADIOLOGIC |
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Three-Dimensional Gadolinium-Enhanced Magnetic Resonance Angiography Used as a ;;One-stop Shop'' Imaging Procedure for Venous Thromboembolism: A Pilot Study.
Obernosterer A, Aschauer M, Portugaller H, Koppel H, Lipp RW.
Divisions of Angiology and Nuclear Medicine, Department of Internal Medicine, and Magnetic Resonance Institute, Karl-Franzens University Hospital, Graz, Austria.
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| Angiology. 2005 Jul-Aug;56(4):423-30. Abstract quote |
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Pulmonary embolism and deep venous thrombosis are individual manifestations of a single entity, venous thromboembolic disease.
This study aimed to assess the feasibility of 3-dimensional gadolinium-enhanced magnetic resonance angiography used as an ;;one-stop shop'' imaging procedure visualizing both the pulmonary arteries and the deep lower venous system within a single investigation. The inclusion criterion was a proven or excluded venous thromboembolism.
Diagnosis was based on an imaging work-up for pulmonary embolism including either perfusion lung scan or contrast-enhanced spiral computed tomography, or both, and an imaging work-up for deep venous thrombosis including either venous color-coded duplex sonography or ascending phlebography, or both. A gadolinium-enhanced ;;one-stop shop'' magnetic resonance angiography was performed within 24 hours of completed diagnostic imaging work-up for pulmonary embolism and deep venous thrombosis in 20 patients. Results of pulmonary magnetic resonance angiography were concordant with perfusion lung scan and/or computed tomography in 90% of patients. Magnetic resonance angiography results of the deep lower venous system were concordant with venous duplex sonography and/or phlebography in 75% of patients and seemed to be more precise in 25% of patients.
The ;;one-stop shop'' imaging procedure using gadolinium-enhanced magnetic resonance angiography was feasible and proved to offer a reliable and rapid diagnostic approach in thromboembolic disease, sparing patients' exposure to ionizing radiation and iodinated contrast media.
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| D-DIMER |
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The role of the d-dimer in the diagnosis of venous thromboembolism.
Ahearn GS, Bounameaux H.
Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
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| Semin Respir Crit Care Med. 2000;21(6):505-22. Abstract quote |
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Classic enzyme-linked immunosorbent assay (ELISA) D-dimer assays are sensitive in screening for thromboembolic disease; however, they are cumbersome and time consuming to perform, which limits their routine use. Latex agglutination assays are easier to perform, but they are not as sensitive as the ELISA assays.
New D-dimer assays incorporating novel technologies can be performed rapidly with a sensitivity approaching that of classic ELISA assays. D-dimer assays are uniformly sensitive in detecting thromboembolic disease in different patient populations; however, low specificity limits the clinical utility of D-dimer measurements in medical inpatients and postoperative patients.
Increasingly, these measurements are being incorporated into diagnostic algorithms for venous thromboembolism and are reducing the need for invasive diagnostic studies.
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| TREATMENT |
CHARACTERIZATION |
| GENERAL |
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| ANTI-COAGULATION THERAPY |
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Duration of anticoagulation following venous thromboembolism: a meta-analysis.
Ost D, Tepper J, Mihara H, Lander O, Heinzer R, Fein A.
Center for Pulmonary and Critical Care Medicine, North Shore University Hospital, Manhasset, NY 11030, USA.
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| JAMA. 2005 Aug 10;294(6):706-15. Abstract quote |
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CONTEXT: Patients with venous thromboembolism (VTE) are susceptible to recurrent events, but whether prolonging anticoagulation is warranted in patients with VTE remains controversial.
OBJECTIVE: To review the available evidence and quantify the risks and benefits of extending the duration of anticoagulation in patients with VTE.
DATA SOURCES: PubMed, EMBase Pharmacology, the Cochrane database, clinical trial Web sites, and a hand search of reference lists.
STUDY SELECTION: Included studies were randomized controlled trials with results published from 1969 through 2004 and evaluating the duration of anticoagulation in patients with VTE that measured recurrent VTE. Excluded studies were those enrolling only pure populations of high-risk patients. Two independent reviewers assessed each article for inclusion and exclusion criteria, with adjudication by a third reviewer in cases of disagreement. Fifteen of 67 studies were included in the analysis.
DATA EXTRACTION: Two independent reviewers performed data extraction using a standardized form, with adjudication by the remainder of the investigators in cases of disagreement. Data regarding recurrent VTE, major bleeding, person-time at risk, and study quality were extracted.
DATA SYNTHESIS: If patients in the long-term therapy group remained receiving anticoagulation, the risk of recurrent VTE with long- vs short-term therapy was reduced (weighted incidence rate, 0.020 vs 0.126 events/person-year; rate difference, -0.106 [95% confidence interval {CI}, -0.145 to -0.067]; P<.001; pooled incidence rate ratio [IRR], 0.21 [95% CI, 0.14 to 0.31]; P<.001). If anticoagulation in the long-term therapy group was discontinued, the risk reduction was less pronounced (weighted incidence rate, 0.052 vs 0.072 events/person-year; rate difference, -0.020 [95% CI, -0.039 to -0.001]; P = .04; pooled IRR, 0.69 [95% CI, 0.53 to 0.91]; P = .009). The risk of major bleeding with long- vs short-term therapy was similar (weighted incidence rate, 0.011 vs 0.006 events/person-year; rate difference, 0.005 [95% CI, -0.002 to 0.011]; P = .14; pooled IRR, 1.80 [95% CI, 0.72 to 4.51]; P = .21).
CONCLUSIONS: Patients who receive extended anticoagulation are protected from recurrent VTE while receiving long-term therapy. The clinical benefit is maintained after anticoagulation is discontinued, but the magnitude of the benefit is less pronounced.
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| HEPARIN, LOW MOLECULAR WEIGHT |
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Low-molecular-weight heparin for the prevention of postoperative venous thromboembolism after abdominal surgery: a review.
Bergqvist D.
Department of Surgery, University Hospital, Uppsala, Sweden.
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| Curr Opin Pulm Med. 2005 Sep;11(5):392-7. Abstract quote |
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PURPOSE OF REVIEW: To analyze the effect of low-molecular-weight heparin in abdominal surgery, which carries a significant risk of thrombosis, a risk further increased by cancer.
RECENT FINDINGS: Searches in EMBASE and PubMed between 1980 and 2004 were conducted to identify studies of thromboprophylaxis in abdominal surgery patients. Sixteen comparative studies were identified. They showed that low-molecular-weight heparin is as effective as unfractionated heparin in reducing venous thromboembolism and, at appropriate doses, can reduce bleeding complications. In very-high-risk cancer patients, a higher dose of low-molecular-weight heparin may offer increased efficacy without increasing the risk of bleeding. Extending the standard 7-10-day low-molecular-weight heparin prophylaxis period may benefit certain high-risk patient groups.
SUMMARY: Patients undergoing abdominal surgery should be stratified according to thromboembolism risk and given prophylaxis accordingly. Low-molecular-weight heparin is a recommended alternative to unfractionated heparin in moderate- or high-risk patients. In patients with cancer, high doses of low-molecular-weight heparin may offer increased efficacy without increased bleeding, and an extended 4-week period of prophylaxis could be beneficial.
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| HEPARIN, SUBCUTANEOUS FRACTIONATED |
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Subcutaneous unfractionated heparin compared with low-molecular-weight heparin for the initial treatment of venous thromboembolism.
Bernardi E, Prandoni P.
aEmergency Department, Azienda Ospedaliera di Padova, and bDepartment of Internal Medicine, University of Padova, Padua, Italy.
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| Curr Opin Pulm Med. 2005 Sep;11(5):363-7. Abstract quote |
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PURPOSE OF REVIEW: Low-molecular-weight heparin is the preferred choice for the initial treatment of acute, uncomplicated venous thromboembolism. In this context, unfractionated heparin is as safe and effective as low-molecular-weight heparin but requires strict laboratory monitoring. Twice-daily subcutaneous unfractionated heparin is more effective than, and as safe as, intravenous unfractionated heparin and may simplify patient treatment in or out of the hospital, being possibly cost saving, especially if it is used in weight-based, fixed, unadjusted doses. The present review focuses on the relative values of low-molecular-weight heparin and subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism.
RECENT FINDINGS: The major advantages of low-molecular-weight heparin over unfractionated heparin seem to be ease of administration and cost savings associated with home therapy or early hospital discharge; however, many patients with venous thromboembolism are still admitted to the hospital for treatment, and unfractionated heparin is extensively used to this purpose, especially in the United States. Subcutaneous unfractionated heparin, adjusted according to activated partial thromboplastin time algorithms, is as safe and effective as low-molecular-weight heparin for the treatment of venous thromboembolism, allows for quick mobilization and early discharge of suitable patients, and represents a cost-effective strategy. Fixed-dose unfractionated heparin, like low-molecular-weight heparin, may be used for the home treatment of deep vein thrombosis.
SUMMARY: Subcutaneous unfractionated heparin, targeted on activated partial thromboplastin time results or in fixed doses, may be used in or out of the hospital for the treatment of venous thromboembolism, being possibly cost effective; however, these findings need confirmation through appropriate, large-sample, randomized clinical trials.
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