Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden

In 29 patients (17 females) homozygous Arg 506 Gln mutation (FV Leiden) was identified. 25 had been investigated because of venous thromboembolism (VTE); four asymptomatic patients were found during family studies. The first VTE had occurred significantly earlier in females (median age [m] 26 years, range 17-49) than in males (m=38 years, range 21-82) (P=0.01). 12 females (80%) had taken oral contraceptives (OC, estrogen content 0.02-0.1 mg) for 6-150 months prior to thrombosis. Further triggering conditions in females were hormone replacement (n=1) and pregnancy (n=2). In 8/10 males the first VTE had occurred spontaneously--in two after surgery. The sites of VTE were deep vein thrombosis, pulmonary embolism, caval vein thrombosis and superficial thrombophlebitis. From our data we conclude that OC medication is the most important precipitating factor for VTE in females with homozygous FV Leiden.     

Complications of superficial thrombophlebitis

Phlebitis and varicophlebitis are regarded as harmless diseases easily treated by compression and local measures such as incisions and applications. However, recent experience has revealed that they are often complicated by growth of the superficial thrombus into the deep veins, by noncontiguous calf thrombosis, and by usually asymptomatic pulmonary embolism. We prospectively examined 25 consecutive patients using duplex scanning (21x) and/or ascending venography (15x). The phlebitic process involved a varicose greater saphenous vein or a branch thereof (19x), the lesser saphenous vein (3x) or a nonvaricose superficial vein (3x). In 11 cases (44%) we found direct extension to involve the deep vein system and/or noncontiguous isolated calf or popliteal vein thrombosis. The presence of risk factors for deep vein thrombosis and a painful calf muscle were good clinical indicators of such complications. Patients with complications were anticoagulated on an outpatient basis. The course was uneventful in most cases. Our study confirms the notion that superficial thrombophlebitis is often part of a more extended thromboembolic process. This implies diagnostic and therapeutic consequences, although the prognostic significance of such complications is not clear at the moment.     

Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.     

High levels of histidine-rich glycoprotein and thrombotic diathesis. Report of two unrelated families

Two new families with history of thrombosis and high levels of histidine-rich glycoprotein (HRG) are described. The propositus of family 1 died of massive pulmonary embolism at age 34. Among his relatives, the mother and the maternal grandmother had suffered from deep and superficial vein thrombosis in their youth. A maternal aunt had several episodes of superficial vein thrombosis (SVT). High levels of HRG were found in the mother, three siblings and two nephews. In the second family, the proposita suffered from spontaneous deep vein thrombosis (DVT) at age 24. The paternal grandmother and a paternal aunt had several episodes of SVT and DVT. Also in this family, high levels of HRG cosegregated with thrombotic symptoms. These new families confirm that genetically transmitted high levels of HRG could be associated to familial and juvenile thrombophilia.     

Palmoplantar keratoderma associated with hypothyroidism

Superficial venous thrombotic (SVT) events are a feature of thrombophilic abnormalities, particularly those involving the protein C pathway. We have determined the incidence of SVT associated with pregnancy and the early postpartum period in a retrospective study involving 72000 deliveries. Fourty-nine cases occurring in 47 individuals were recorded, with an overall incidence of 0.68/1000 deliveries (95% CI 0.48-0.88). None had a previous history of deep vein thrombosis or pulmonary embolism. Most events occurred in the early postpartum period (0.54/1000 deliveries). Twenty-four/fourty-seven were screened for established thrombophilic abnormalities, with only 1 abnormality detected (FV(Leiden) heterozygote). Thrombophilia may play a minor role in the aetiology of SVT associated with pregnancy, although a larger study is required to confirm this.     

The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism

This paper describes the role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Inability to compress the common femoral or popliteal vein is usually diagnostic of a first episode of deep venous thrombosis in symptomatic patients (positive predictive value of about 97%). Full compressibility of both of these sites excludes proximal deep venous thrombosis in symptomatic patients (negative predictive value of about 98%). In patients with suspected deep venous thrombosis or in those who present with suspected pulmonary embolism but have a nondiagnostic lung scan, the subsequent risk for symptomatic venous thromboembolism is very low (<2% during 6 months of follow-up) provided that ultrasonography of the proximal veins remains normal in the course of 1 week (suspected deep venous thrombosis) or 2 weeks (suspected pulmonary embolism). Anticoagulation and further diagnostic testing can usually be safely withheld in these situations. Venous ultrasonography is much less reliable for the diagnosis of asymptomatic, isolated distal, and recurrent deep venous thrombosis than for the diagnosis of a first episode of proximal deep venous thrombosis in symptomatic patients. Clinical evaluation of the probability of deep venous thrombosis or pulmonary embolism, preferably by using a validated clinical model, complements venous ultrasonographic findings and helps to identify patients who would benefit from additional (often invasive) diagnostic testing. Thus, venous ultrasonography is thought to be a very valuable test for the diagnosis and management of patients with suspected deep venous thrombosis or pulmonary embolism.     

Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.     

The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism

BACKGROUND: Several small studies have indicated an association between deep venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but the subject is controversial. METHODS: We conducted a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism that was drawn from the Danish National Registry of Patients for the years 1977 through 1992. The occurrence of cancer in the cohort was determined by linkage to the Danish Cancer Registry. The expected number of cancer cases was estimated on the basis of national age-, sex-, and site-specific incidence rates. RESULTS: A total of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary embolism were identified. We observed 1737 cases of cancer in the cohort with deep venous thrombosis, as compared with 1372 expected cases (standardized incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the patients with pulmonary embolism, the standardized incidence ratio was 1.3, with a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially elevated only during the first six months of follow-up and declined rapidly thereafter to a constant level slightly above 1.0 one year after the thrombotic event. Forty percent of the patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis of cancer. There were strong associations with several cancers, most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer), and brain. CONCLUSIONS: An aggressive search for a hidden cancer in a patient with a primary deep venous thrombosis or pulmonary embolism is not warranted.     

HLA-B44 allele frequencies and haplotypic associations in three European populations

Thrombosis during pregnancy poses special problems. This review focuses on risk factors for the development of venous thromboembolism during pregnancy, diagnosis of deep vein thrombosis and pulmonary embolism during pregnancy, therapeutic recommendations for the treatment of acute thromboembolism during pregnancy, and thromboprophylaxis in the pregnant woman. Management of pregnant women with antiphospholipid antibodies is also reviewed.     

Venous thromboembolic disease and pregnancy

Venous thrombo-embolic disease is the most common cause of maternal death during pregnancy. Haemodynamic, anatomical and biological changes support the notion that normal pregnancy in a prethrombotic state. But thrombotic events remain unusual episodes. A pre-thrombotic disease has to be investigated in such cases. Accurate diagnosis of deep vein thrombosis or pulmonary embolism is imperative, using non-invasive approaches. Heparin is the anticoagulant of choice to treat objective thrombosis. Thrombo-embolism prophylaxis using compression stockings and heparin has to be discussed in hypercoagulable disorders.     

Peptide vaccination with an anchor-replaced CTL epitope protects against human papillomavirus type 16-induced tumors expressing the wild-type epitope

PURPOSE: Upper-extremity thrombosis appears to be more frequent today, comprising about 2% of all deep venous limb thrombosis. Its severity depends on the type of possible complications, i.e., pulmonary embolism and post-thrombotic sequelae. In this retrospective series, we investigated both the predisposing factors and the evolution of upper-extremity deep venous thrombosis. METHODS: Forty-nine consecutive patients (24 men and 25 women, mean age 50.2 years) with upper extremity deep venous thrombosis documented by color Doppler ultrasonography (n = 47) or phlebography (n = 2) were included in the study. RESULTS: Clinical manifestations were mainly pain (81.6%) and edema (93.9%). Mean time between the onset of clinical signs and diagnosis was 7.2 days. Thrombosis involved humeral (26.5%), axillary (46.9%), subclavian (73.5%) and jugular (24.5%) veins. Causative factors were malignancies (32.7%), venous catheters (22.4%), deep venous thrombosis related to effort or thoracic outlet syndrome (22.5%) and thrombophilic states (8.2%). During the 6-month follow-up, six patients developed symptomatic pulmonary embolism (12.2%); one recurrence (2.2%) and 19 post-thrombotic sequelae such as residual edema (36.7%) were also observed. Initial therapy included heparin administration, principally subcutaneous low molecular weight heparins (n = 36/49). CONCLUSION: This series highlights the fact that upper-extremity deep venous thrombosis is mainly secondary to either malignancies or catheterization. Moreover, it confirms that color Doppler ultrasonography may be useful in the diagnosis of the disease and also underlines the high frequency of severe complications, i.e., pulmonary embolism and post-thrombotic sequelae. Finally, this study also demonstrates that low molecular weight heparins should be considered as the initial treatment of choice.     

Management of deep vein thrombosis of the lower extremity in pregnancy: a challenging dilemma

This study reviews our experience in the management of deep vein thrombosis (DVT) of the lower extremity during pregnancy and analyzes the outcome of various treatment alternatives, including conventional full-dose heparin therapy and Greenfield filter insertion. Twenty-four patients treated over an 8-year period were reviewed. Fifteen patients were treated with conventional full-dose intravenous heparin therapy for 5 to 10 days, followed by subcutaneous low-dose heparin until labor, and continued for 6 weeks postpartum (Group A); Eleven patients had Greenfield filters inserted, followed by the same low-dose subcutaneous heparin regimen (Group B). There were 18 femoral or iliofemoral, 5 femoropopliteal, and 1 popliteal and below-knee DVT. The indications for Greenfield filter insertion included two patients in Group A (one with pulmonary embolism, despite adequate heparin therapy, and one with significant bleeding). Nine other patients had prophylactic indications: two for free-floating iliofemoral DVT, three with iliofemoral DVT (occurring just 1-2 weeks before labor), and four with femoropopliteal DVT. There were three immediate major complications (pulmonary embolism, bleeding, or death) in Group A; two with pulmonary embolism, one of which was fatal, and one with significant bleeding (3 of 15 patients; 20%). No major complications occurred in Group B. On long-term follow-up (mean, 61 months), 4 of 12 patients (33%) in Group A had significant leg swelling, with partial resolution of DVT in 2 patients and venous occlusion in 2 patients by duplex ultrasound. This is in contrast to 3 of 11 patients (27%) in Group B with significant leg swelling. There was no fetal morbidity or mortality in either group. Conventional full-dose heparin therapy for DVT of the lower extremity in pregnancy can carry significant morbidity and mortality. Greenfield filters may be used safely in some of these patients.     

PHLECO: a multicenter study of the fate of 1647 hospital patients treated conservatively without fibrinolysis and surgery

The PHLECO Study (phlebothrombosis conservative therapy) is a multicenter investigation of patients with deep vein thrombosis receiving conservative nonfibrinolytic hospital treatment. A second study (part II: PHLEFI, phlebothrombosis fibrinolytic treatment) to be published later deals with the outcome of fibrinolytic therapy. In both studies the incidence of life-threatening sequelae, such as pulmonary embolism, is of major interest. The 49 medical departments participating in the study mailed the relevant data to the Duisburg Coordination Center for further data analysis and the following information was gained: (a) In descending order of frequency, the clinical conditions of thrombosis were: immobility, postoperative status, malignancy, hormone treatment, posttraumatic conditions, and pregnancy. (b) In descending order of frequency, the sites of thrombosis were: femoral vein, calf vein, iliac vein, popliteal vein, and subclavian vein. Left-sided thrombosis predominated in the iliac and subclavian vein groups. (c) In descending order of frequency, the treatment regimens employed were: intravenous heparin+oral anticoagulants, intravenous heparin+subcutaneous heparin, intravenous heparin alone, subcutaneous heparin alone, intravenous heparin+subcutaneous heparin+oral anticoagulants, subcutaneous heparin+oral anticoagulants, intravenous heparin+platelet aggregation inhibitors. (d) The average hospital stay was 23.7 +/- 15.6 days. No correlation existed between duration of hospital stay and particular types of therapy. (e) The incidence of nonfatal pulmonary embolism was 16.1% while that of fatal pulmonary embolism was 2.33%. (f) Women outnumbered men in the group with fatal pulmonary embolism, and the death rate among older patients was higher than that among younger patients. (g) Patients with fatal pulmonary embolism had a shorter history of thrombosis than patients in the unselected cohort (patients with and without pulmonary embolism).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary embolism in patients with intermediate probability lung scans: diagnosis with Doppler venous US and D-dimer measurement

PURPOSE: To test the usefulness of lower limb Doppler venous compression ultrasound (US) and serum D-dimer measurements in diagnosis of pulmonary embolism in patients in whom ventilation-perfusion (V-P) scans indicate intermediate probability of pulmonary embolism. MATERIALS AND METHODS: V-P scanning, pulmonary angiography, US, and D-dimer measurements were performed in 36 patients without known deep venous thrombosis but with intermediate probability of having a pulmonary embolism. RESULTS: Pulmonary angiography demonstrated pulmonary embolism in 15 (41%) of 36 patients. US demonstrated deep venous thrombosis in only two patients, both with pulmonary embolism. Sensitivity of US was only 13%, but specificity was 100%. Five (14%) of the 36 patients had normal (< 220 micrograms/L) D-dimer levels; none of the five had pulmonary embolism. Sensitivity and specificity of D-dimer values were 100% and 16%, respectively, with a negative predictive value of 100%. CONCLUSION: Combined D-dimer measurement and US were helpful in correctly diagnosing pulmonary embolism in only seven (20%) of 36 patients. Pulmonary angiography is still required to diagnose pulmonary embolism in the majority of patients.     

Superficial dorsal penile vein thrombosis (Mondor's disease)

Superficial venous thrombosis of the chest wall was first described by Mondor in 1939. Braun-Falco reported in 1955 superficial penile vein involvement in diffuse thrombophlebitis of the abdominal wall and in 1958 Helm and Hodge first described isolated superficial dorsal penile vein thrombosis. Since then, fewer than 50 cases have been reported. The clinical presentation is usually redness and swelling of the dorsum of the penis, accompanied by a palpable, tender thrombotic vein. This acute and painful disease frightens the patients, who is concerned about his fertility and sexual function. The main cause of this disease is frequent sexual intercourse. Diagnosis is based upon anamnesis, physical examination and penile sonography with color Doppler imaging. It is usually a benign disease which resolves quickly under appropriate medical therapy. We present a man who was admitted for this condition and was successfully treated.     

Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection

BACKGROUND: The outpatient treatment of patients with deep vein thrombosis and pulmonary embolism using low-molecular-weight heparin has the potential to reduce health care costs, but it is unclear if most patients with deep vein thrombosis and pulmonary embolism can be treated as outpatients. In the published studies, more than 50% of patients were excluded from outpatient treatment for reasons such as comorbid conditions, short life expectancy, concomitant pulmonary embolism, and previous deep vein thrombosis, and many patients were not treated entirely at home. We sought to determine if expanding patient eligibility for the outpatient treatment of deep vein thrombosis and pulmonary embolism affects the safety and effectiveness of the treatment, and to determine if patient self-injection compared with injections administered by a homecare nurse affected these outcomes. PATIENTS AND METHODS: We treated as outpatients all patients with deep vein thrombosis and pulmonary embolism, except for those with massive pulmonary embolism, high risk for major bleeding or an active bleed, phlegmasia, and patients hospitalized for reasons that prevented discharge. We compared 2 models of outpatient care to determine feasibility, safety, and efficacy. Both models involved nurse managers who provided daily patient contact and ongoing treatment; however, in one model the patients were taught to inject themselves and in the other model homecare nurses administered the injections. We expanded the population of patients eligible for outpatient treatment by including many patients not treated at home in previous studies. Most patients in our study were treated with dalteparin sodium, 200 U/kg every 24 hours, for a minimum of 5 days. Therapy with warfarin sodium was started on the day of diagnosis or the following day. Patients were followed up for 3 months to determine rates of recurrent venous thromboembolism, bleeding, and death. RESULTS: In this study, 194 (83%) of 233 consecutive patients were deemed eligible and treated as outpatients. Of the 39 patients who did not receive home therapy, 20 had concomitant medical problems responsible for their admission or were already inpatients, 6 had massive pulmonary embolism, 6 refused to pay for the dalteparin therapy, 4 had active bleeding, and 3 had phlegmasia cerulea dolens, which required treatment with intravenous narcotics for pain control. More than 184 (95%) of the 194 patients were treated entirely at home. There was no significant difference (P>.99) in the rate of recurrent venous thromboembolic events between the patients who were injected by homecare nurses (3/95 [3.2%]) and those who injected themselves (4/99 [4.0%]). Combining the 2 models, the overall recurrent event rate was 3.6% (95% confidence interval, 1.5%-7.4%). Similarly, there were no significant differences in rates of major hemorrhage (2/95 vs 2/99; P>.99), minor hemorrhage (8/95 vs 2/99; P = .06), and death (6/95 vs 8/99; P = .63). The overall rate of major hemorrhage was 2.0% (95% confidence interval, 0.6%-5.2%). CONCLUSIONS: We demonstrate that more than 80% of patients at our tertiary care hospital could be treated at home using 1 of the 2 models of care we describe. Our results demonstrate that patients can safely and effectively perform home self-injection under the supervision of a hospital-based nurse. Injections at home by a homecare nurse are similarly effective. Our overall rates of recurrent venous thromboembolism, bleeding, and death are at least as favorable as those previously reported despite using 1 dose per day of dalteparin for most patients.     

Deep venous thrombosis and neoplastic pathology: our experience in emergencies

Deep vein thrombosis incidence is 1/1000 per year; it is associated with many risk factors which is considered as "thrombophilic states". Its pathogenesis is complex, caused by alterations of hemostasis system. Many studies have established the relation between cancer and subsequent venous thromboembolism, confirming the relationship of neoplastic cell interaction with coagulation system. Forty-seven patients admitted to the hospital from 1987 to 1996 with symptomatic clinically proved deep vein thrombosis were included in a retrospective study. Routine examination at the time of diagnosis of deep vein thrombosis revealed an occult cancer in 8 out of 47 patients; 9 out of 47 patients were admitted in hospital with vein thrombosis and known cancer. The aim of this study is to suggest the best, first treatment of vein thromboembolism in emergency to avoid the dangerous pulmonary embolism complication. The patients affected with deep vein thrombosis and cancer were elderly (over 70 years old, in mean); the neoplasia was of digestive system (8/17) in advanced metastatic stage there was cancer familiarity in 7 out of 47 patients. The high risk of pulmonary embolism associated to deep vein thrombosis suggests the importance of early starting the anticoagulant therapy and placing caval filter.     

Renal vein thrombosis and constitutional protein S deficiency

Venous and arterial thrombosis due to a constitutional protein S deficiency is well-known. We report the case of a 36 year-old patient admitted to hospital in 1991 for primary renal vein thrombosis due to a constitutional protein S deficiency of type I. The diagnosis was made by CT scan and angiography. Left nephrectomy, which was made because of doubt with regard to subjacent neoplasm, showed left renal vein thrombosis and multiple renal infarcts. In 1994, after 4 months of discontinuation of oral anticoagulants, the patient presented pulmonary embolism documented by pulmonary scintigraphy and CT scan, partial portal thrombosis and sural thrombophlebitis documented by echography coupled with Doppler. To our knowledge, this is the first reported case of a constitutional protein S deficiency associated with primary renal vein thrombosis.     

Treatment of venous thromboembolism

This review provides meta-analytic data of studies aiming at improved treatment of deep vein thrombosis and pulmonary embolism. The introduction of low molecular weight heparin has considerably ameliorated the initial treatment of deep vein thrombosis, and should now be regarded as the treatment of choice for most patients with deep vein thrombosis. Oral anticoagulant treatment is presently considered safe and effective for the long-term treatment of venous thromboembolism, provided that the INR is maintained at 2.0-3.0. However, the optimal duration as well as the optimal intensity of anticoagulation have still to be determined. Patients with submassive pulmonary embolism should presently be treated with adjusted dose unfractionated heparin and coumarins. Studies determining the efficacy and safety of low molecular weight heparin in this condition deserve priority. Thrombolytic therapy should be restricted to patients with massive pulmonary embolism, unless safer methods of thrombolysis have been developed. Surgical embolectomy and catheter fragmentation of emboli seem alternative options but deserve further investigations.     

Venous thromboembolism--incidence and risk factors in Oslo

Over a period of three years, 378 patients with objectively verified venous thromboembolism were treated at Aker University Hospital. Below the age of 60, men and women had about the same incidence of venous thromboembolism, but that age the incidence was significantly higher among men than among women. Incidence increased exponentially with age, from about 1:10,000 at age 20 to about 1:1,000 at age 50. The incidence found here is lower than in earlier Nordic studies. The great majority of the patients (93%) had deep venous thrombosis in the lower extremities, 11% had symptomatic and verified pulmonary embolism, and 1% had their thrombus in an inner organ vein. 23% of patients were previously treated for venous thromboembolism, and 22% had cancer. Seven women were on oral contraception, and 22 used postmenopausal hormone substitution. An obvious temporary precipitating factor was present in 42% of the patients, while 36% had a spontaneous venous thromboembolism. Hereditary thrombophilic disorder was found in 32% of patients below the age of 60.