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 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.     

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.     

Panleukopenia

The influence of several diseases and conditions upon the prevalence of pulmonary embolism in autopsies performed during a ten year period at the University of Michigan has been analyzed. The major factors contributing to an increase in risk of development of pulmonary embolism include heart disease, certain types of cancer, obesity, acute paraplegia and accidental and operative trauma. These and several other risk factors defined in other studies should be used in a selective program designed to increase the rate of detection of deep venous thrombosis before pulmonary embolism occurs, or alternatively, patients at increased risk should receive prophylactic low dosage heparin therapy during hospitalization.     

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.     

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.     

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.     

The prevention of postoperative deep vein thrombosis and pulmonary embolism with low dose subcutaneous heparin and dextran

The standard low dose of heparin for the prevention of deep venous thrombosis in patients who are operated upon is 5,000 units administered subcutaneously two hours before operation and at eight or 12 hourly intervals for the next seven days. Heparin in low doses can at present be recommended as an effective agent in the prevention of deep venous thrombosis in patients over the age of 40 years who are undergoing a major abdominothoracic or gynecologic operation. There is reasonable evidence that heparin in low doses also offers a satisfactory protection against fatal pulmonary embolism for patients at high risk after general abdominothoracic operations. The evidence of the effectiveness of low doses of heparin in the prevention of deep venous thrombosis is less well established in other patients and particularly those at high risk, as after urologic and hip operations. This important distinction is to be made in terms of the population at risk and the efficacy of heparin in low doses. Considering the evidence so far available, it appears that the postoperative state in which dextran has been shown to reduce the incidence of phlebographically confirmed deep venous thrombosis most convincingly is after orthopedic operations. Major orthopedic operations are precisely the type in which the superiority of heparin in low doses is controversial. Unless proved otherwise, dextran 70 in an infusion of 500 to 1,000 milliliters of a 6 per cent solution started before operation and 500 milliliters the following and next three alternate days may be the agent of choice in preventing deep venous thrombosis in major orthopedic operations. Using this scheme, the prophylaxis of postoperative deep venous thrombosis appears equally effective with dextran 70 as with oral anticoagulants. Whether the protection offered by dextran 70 will also prevent fatal and nonfatal pulmonary embolism is still an open question. Low doses of heparin and dextran do not expose patients to serious risks of bleeding after operation, and with the recommended doses of the latter drug, other untoward effects are rare. At the doses recommended, neither of these two drugs requires laboratory monitoring.     

Angiographic embolization of intrahepatic arterioportal fistula

BACKGROUND: Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. METHODS: From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for genotyping. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. RESULTS: 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p < 0.05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% CI: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% CI: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. CONCLUSION: These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.     

0.9% sodium chloride injection with and without heparin for maintaining peripheral indwelling intermittent-infusion devices in infants

PURPOSE: Tachypnea in children is associated with respiratory disorders and nonrespiratory disorders such as cardiac disease, metabolic acidosis, fever, pain, and anxiety. Pulmonary embolism is seldom considered by pediatricians as a cause of tachypnea. PATIENTS AND METHODS: Three children of various ages with persistent tachypnea are described: a girl after orthopedic surgery for kyphoscoliosis, a boy with nephrotic syndrome, and a neonate with Hirschsprung disease. Other causes of tachypnea were diagnosed and treated before pulmonary embolism was considered. RESULTS: Ventilation-perfusion scanning appeared to be highly probable for pulmonary embolism in these patients. Anticoagulant therapy was started. CONCLUSION: Pulmonary embolism should be kept in mind in children with tachypnea, especially when other risk factors for venous thromboembolism are present, to avoid delay in anticoagulant treatment and a fatal outcome.     

Prophylaxis for venous thromboembolism in head and neck surgery: the practice of otolaryngologists

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are an important cause of morbidity and mortality in the surgical patient. The first guideline produced by the Scottish Intercollegiate Guidelines Network was for the prophylaxis of venous thromboembolism. Patients undergoing major head and neck cancer surgery commonly exhibit risk factors for venous thromboembolism. Currently, however, there are no data on its incidence in these patients. A questionnaire survey was performed to assess the current practice of consultant otolaryngologists regarding DVT prophylaxis in patients undergoing head and neck cancer surgery. Of those respondents who managed these patients, 57 per cent did not use routine DVT prophylaxis while 43 per cent did. A wide variety of techniques were employed among those practising DVT prophylaxis. A consensus is needed concerning the use of thromboembolism prophylaxis in head and neck surgery patients.     

Deep-vein thrombosis

Deep-vein thrombosis is an important complication of several inherited and acquired disorders, but may also occur spontaneously. Prevention of recurrent venous thrombosis and pulmonary embolism is the main reason for accurate diagnosis and adequate treatment. This seminar discusses only symptomatic deep-vein thrombosis. The diagnosis can be confirmed by objective tests in only about 30% of patients with symptoms. Venous thromboembolic complications happen in less than 1% of untreated patients in whom the presence of venous thrombosis is rejected on the basis of serial ultrasonography or ultrasonography plus either D-dimer or clinical score. Initial anticoagulant treatment (intravenous or subcutaneous heparin) should continue until oral anticoagulant treatment, started concurrently, increases the international normalised ratio above 2.0 for more than 24 h. The optimum duration of oral anticoagulant treatment is unresolved, but may be guided by the presence of temporary or persistent risk factors or presentation with recurrent venous thromboembolism.     

Popliteal venous aneurysm: report of two cases and review of the world literature

Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.     

Surgical prophylaxis for pulmonary embolism

The trauma patient population is at special risk for fatal pulmonary embolism. We experienced 11 fatalities in one 12-month period. Specific risk factors for both deep venous thrombosis and pulmonary embolism can be identified among trauma patients. The latter usually cannot be offered prophylactic anticoagulation, and the nature of their injuries (e.g., long bone fractures) makes not only bedside surveillance difficult but also precludes use of pneumatic compression, etc. We have developed a protocol for prophylactic inferior vena caval filtration for our trauma patients deemed at particular risk for pulmonary embolism. Since 1986 we have inserted 205 Greenfield filters in 201 patients. Two hundred were inserted prophylactically. There was no mortality, and morbidity was minimal. No patient with a Greenfield filter sustained a fatal pulmonary embolism during this period. Four patients died from pulmonary embolism before vena caval filters could be inserted. We believe that the trauma patient, at risk for pulmonary embolism, should be offered a Greenfield filter prophylactically as soon after hospitalization as logistically possible.     

Risk factors for major thromboembolism and bleeding tendency after elective general surgical operations. The Fragmin Multicentre Study Group

OBJECTIVE: To elucidate those factors that contribute to the risk of major postoperative thromboembolism and perioperative bleeding tendency. DESIGN: Retrospective multiple logistic regression analysis. SETTING: 7 Scandinavian hospitals (6 Swedish and 1 Norwegian). SUBJECTS: 2070 patients undergoing elective major abdominal surgery. INTERVENTIONS: Patients were randomised to receive 2500 or 5000 XaI units of low molecular weight heparin daily. MAIN OUTCOME MEASURES: Major thromboembolism (proximal deep vein thrombosis confirmed by phlebography or necropsy, or pulmonary embolism confirmed by scintigraphy or necropsy, or both). Bleeding tendency (bleeding complications which were not explained by local haemorrhagic lesions or by coexisting disease). RESULTS: Previous thromboembolism, leg fracture or arthroplasty, present leg ulcer or malignant disease, operating time longer than 150 minutes, preoperative transfusion of 2 or more units, and preoperative hospital stay of 6 days or more (but not age, body weight, or varicose veins) were independent predictors for major postoperative thromboembolism. The risk was significantly increased with an increasing number of such risk factors. The risk of developing a diffuse bleeding complication was dependent on the dose of low molecular weight heparin, particularly in patients without risk factors. CONCLUSIONS: The use of a narrow definition of thromboembolism lead to a pattern of risk factors which was partly different from that found in previous studies, which were usually based on diagnosis with the 125I-fibrinogen uptake test.     

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.     

Early elective open surgical repair of small abdominal aortic aneurysms is not recommended: results of the UK Small Aneurysm Trial. Steering Committee

Acute pulmonary thromboembolism is a life-threatening disease and in almost all cases originates from deep venous thrombosis in the proximal deep venous system of the legs. In order to prevent further episodes of thromboembolism in 2 patients with acute pulmonary thromboembolism, we inserted an Antheor temporary vena cava filter after catheter-directed fragmentation and thrombolysis. No complications occurred during the insertion of the filters and our results suggest that this filter device may be clinically safe and effective for temporary protection against pulmonary thromboembolism.     

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.     

Venous thromboembolism in connection with physical restraint

A 29-year old man was admitted to an emergency psychiatric ward because of exacerbation of a chronic paranoid schizophrenia. He was restrained after arrival, and seven days later a deep venous thrombosis and a pulmonary embolism were diagnosed. No haematological predisposing factors (coagulation inhibitor deficiency, activated protein C resistance, or antiphospholipid antibodies) were identified, except for a questionable borderline increase of the fibrinolysis inhibitor PAI-1, and combined type II hyperlipidaemia. During the last 15-20 years, there has been a considerable reduction in the use of restraint and seclusion in Norway. The use of seclusion and restraint may be effective in preventing injury and reducing agitation, but these procedures may also have harmful physical, and in particular psychological side-effects. To our knowledge, this is the first report to demonstrate an association between venous thromboembolism and physical restraint. Immobilisation is a well-known risk factor for thrombophlebitis, and special attention should be paid to this problem on psychiatric wards. However, until more is known about thrombosis in relation to restraint, it is not advisable to recommend prophylactic treatment of thrombosis.     

Venous thrombosis causing arterial embolization to the same limb through a patent foramen ovale

We describe a patient who presented with acute ischemia affecting the left lower limb. Because a transthoracic echocardiogram was abnormal, a transesophageal study was arranged. This demonstrated an atrial septal aneurysm and right-to-left shunting of contrast, raising the possibility of paradoxical embolism. The diagnosis was confirmed by contrast venography, which showed extensive thrombosis in the deep veins of the left thigh, and a ventilation-perfusion scan which was consistent with multiple pulmonary emboli. Among the lessons from this case was the finding that in patients with arterial embolism the likely origin of the embolus should be considered and, in the absence of common risk factors (atrial fibrillation, rheumatic heart disease, left ventricular dilatation, widespread atheroma), occult venous thrombosis and a right-to-left shunt should be sought. In this select group of patients, transesophageal echocardiography is significantly more sensitive than transthoracic study and should be the investigation of choice. Second, in the patient described in this report the clinical signs of deep venous thrombosis (DVT) were masked by the more prominent features of acute arterial ischemia. Without the incidental echocardiographic abnormality, it is likely that the important diagnoses of DVT, pulmonary embolism, and paradoxical embolism would not have been made.