Episode Of Deep Venous Thrombosis Research Articles

Recurrent DVT Associated with Heterozygous MS-Type alpha(1)-Antitrypsin Deficiency

Heterozygous forms of alpha(1)-antitrypsin (α1AT) deficiency are common, occurring in up to ten percent of the United States population. However, the clinical significance of these heterozygous states is unclear. Presented is a case of heterozygous protease inhibitor MS (PiMS) α1AT deficiency associated with recurrent deep venous thrombosis (DVT). A 29 year-old Latino male presenting to the Gastroenterology clinic was incidentally noted to have elevated transaminases. His evaluation revealed mildly decreased α1AT levels. Subsequent liver biopsy demonstrated periodic acid-Schiff (PAS) positive, diastase resistant granules within the hepatocytes, consistent with α1AT deficiency. Phenotyping revealed the α1AT phenotype PiMS. The patient's past medical history was notable for two episodes of DVT. Previous evaluation for underlying causes of hypercoaguability was unrevealing. α1AT is one of several serine proteinase inhibitors that regulate physiologic pathways responsible for processes such as fibrinolysis, coagulation, and complement activation. α1AT deficiency is classically associated with emphysema and cirrhosis of the liver, although recent evidence suggests that dysfunctional forms of these proteinase inhibitors can pathologically alter a number of other physiologic pathways. While our review of the literature showed no other causes of recurrent deep venous thromboses associated with PiMS phenotypes, there were rare reports of other thrombotic diseases associated with PiMZ. As further research identifies more pathologic states associated with this common mutation, screening of asymptomatic individuals may one day be warranted.

Lupus anticoagulants and the risk of a first episode of deep venous thrombosis

We have determined lupus anticoagulants, anti-beta2 glycoprotein I (beta2GPI) and antiprothrombin antibodies in the Leiden Thrombophilia Study, a population-based case-control study designed to determine risk factors for deep venous thrombosis (DVT). Lupus anticoagulant (LAC) was measured in 473 patients and 472 control subjects. Four control subjects (0.9%) and 14 patients (3.1%) had a positive LAC, resulting in a 3.6-fold increased risk [odds ratio (OR) 3.6, 95% CI: 1.2-10.9]. Of the total population, 49 were positive for anti-beta2GPI antibodies: 15 controls (3.4%) and 34 patients (7.5%), implying a 2.4-fold increased risk (95% CI: 1.3-4.2). Antiprothrombin antibodies were present in 114 subjects: 48 controls (11.0%) and 66 cases (14.6%) with an OR of 1.4 (95% CI: 1.0-2.1). When LAC was considered in the co-presence of antiprothrombin or anti-beta2GPI antibodies the OR increased to 10.1 (95% CI: 1.3-79.8). A LAC without a positive anti-beta2GPI or antiprothrombin test was not associated with a risk for DVT (OR 1.3, 95% CI: 0.3-6.0). This study demonstrates that the presence of LAC, anti-beta2GPI antibodies and antiprothrombin antibodies are risk factors for DVT in a general population. The strongest association holds for the combination LAC and the presence of anti-beta2GPI or antiprothrombin antibodies.

Pulmonary Embolism Due to Protein S Deficiency in Pregnancy

Inherited thrombophilia is an uncommon disease that may cause recurrent thrombosis and may complicate pregnancy. A patient with protein S deficiency suffered antepartum deep venous thrombosis (DVT) and antepartum pulmonary embolism (PE) in the following pregnancy. She had both successful pregnancies managed by anticoagulant and close fetal surveillance. A 28-year-old woman with protein S deficiency experienced an episode of DVT of the left lower extremity in her first pregnancy and an episode of PE in her second pregnancy. In both pregnancies, the venous thromboembolism (VTE) was treated successfully with low-molecular-weight heparin (LMWH). Prophylactic anticoagulant therapy should be administered throughout the antepartum and postpartum periods for pregnant women with inherited thrombophilia and a previously documented VTE. LMWH is the first-line drug of choice for both prophylaxis and treatment of VTE since it does not cross the placenta and is not teratogenic.

Pitfalls in recurrent varicose vein surgery

A 62-year-old lady previously had a left sapheno-femoral ligation with stripping of the long saphenous vein and multiple avulsions 10 years ago. The pre-operative duplex scan, performed by an experienced vascular technologist, showed a patent and competent deep venous system with no evidence of previous deep vein thrombosis. The sapheno-femoral junction (SFJ) was shown to have been surgically ligated but a small tortuous recurrence was noted to fill the groin varices. It was evident that the proximal long saphenous vein had been stripped. The residual mid-thigh long saphenous vein was significantly incompetent and filled by the sapheno-femoral junction recurrence and by a large atypical incompetent branch that coursed medially and proximally to the sapheno-femoral junction. The duplex report was reviewed by the surgeons and operative religation of the SFJ with avulsion of the new varicose veins was considered the best management. The patient had no clinical episode of deep venous thrombosis before surgery, but the large medial thigh varicose vein appeared to be unusual. Chase Farm Hospital have a policy of performing on-table varicogram for all atypical veins because a significant proportion could be a result of ovarian vein incompetence (Giannoukas et al, 2000) and the source may not be detected by duplex imaging (Urigo et al, 1993). Peri-operatively, a tributary of the atypical large medial thigh varicose vein was cannulated and an on-table varicogram was performed (Figures 1–3). It showed the absence of the ipsilateral left femoral vein with the contrast draining across the pubis into the contralateral femoral vein. The left groin was explored surgically to verify the varicogram findings and the surgeons were expecting to find an SFJ recurrence. The left femoral vein was found to be a thin solid cord structure with no doppler signal audible. This was presumed to have become fibrotic either from previous sapheno-femoral ligation or from previously unknown deep venous thrombosis prior to surgery. It was therefore decided that the SFJ recurrence should be left alone as the only venous outflow for the left leg was via these upper medial thigh recurrent varicose veins and the superficial collaterals that had developed across the pubis. The latter was recognized as being exactly the superficial venous reconstruction described by Palma (1976) for iliac venous obstruction. This phenomenon occurred naturally in our patient as a consequence of an unrecognized deep venous thrombosis in the left common femoral and external iliac veins (auto-Palma phenomenon) (Figure 4 (iv)).

Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome

About 30% of patients with an episode of adequately treated deep venous thrombosis (DVT) develop the postthrombotic syndrome (PTS) within 2 years. During treatment with vitamin K antagonists (VKA) patients spend only 60% of time between an International Normalized Ratio (INR) of 2.0 and 3.0. We hypothesized that patients who spend a large amount of their time beneath this range will have an increased risk of the PTS. To investigate the relation between the quality of anticoagulant therapy with VKA and the risk of the development of the PTS. The time spent beneath the therapeutic range was calculated for patients with a first episode of DVT, who were treated with VKA for at least 3 months. At follow-up assessments for a maximum of 5 years, presence and severity of signs and symptoms of PTS were recorded. A total of 244 patients, with a median duration of follow-up of 4.9 years were included for analysis. Of these, 81 patients (33%) developed the PTS. The multivariate model showed that patients who spend more than 50% of their time beneath an INR level of 2.0 are at higher risk for PTS [odds ratio (OR): 2.71, 95% CI: 1.44-5.10]. Low quality treatment with VKA, which is a common condition, is related to the occurrence of the PTS in patients with DVT. Strategies aimed at improving the quality of long-term anticoagulation might have the potential to reduce the incidence of this complication.

AngioTAC como método de diagnóstico y decisión quirúrgica en el tromboembolismo pulmonar crónico: Discusión a propósito de un caso

Pulmonary hypertension due to chronic pulmonary thromboembolism is frequently underdiagnosed and has a very poor prognosis if untreated. When the presence of central pulmonary artery thrombus is confirmed, thromboendarterectomy is the treatment of choice, with very good results. We report a 28 years old male with two previous episodes of deep venous thrombosis (DVT) who was admitted due to 8 months of progressive shortness of breath and a syncope. He underwent a CT pulmonary angiogram and an echocardiogram. Severe pulmonary hypertension was confirmed, secondary to a chronic pulmonary thromboembolism with an overlapped acute component. He received systemic thrombolysis with partial thrombus disappearance. Therefore a pulmonary thromboendarterectomy was performed and an inferior vena cava filter was placed. The patient was discharged with marked improvement in his functional capacity.

Predictors of the post‐thrombotic syndrome during long‐term treatment of proximal deep vein thrombosis

The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life. The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity. After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome. The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.

The association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 gene and deep venous thrombosis in young people

Objective: To evaluate the association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene and deep venous thrombosis (DVT) in young people. Methods: Prevalence of the 4G/5G polymorphism was investigated using DNA analysis in a population of 81 consecutive and unrelated patients with an objectively documented first episode of DVT under 40 years old and in a control group of 88 healthy subjects. Results: The frequency of genotypes among patients was 0.27 4G/4G, 0.49 4G/5G and 0.23 5G/5G, corresponding to a frequency of 0.52 for the 4G allele. In the control group the results were, respectively, 0.24, 0.44 and 0.32, corresponding to a frequency of 0.46 for the 4G allele. The odds ratio (OR) for homozygous 4G genotype was 1.5 (95% confidence interval: 0.7–3.6), which was not statistically significant ( P = 0.51). Conclusion: In this study, the 4G/5G polymorphism in the promoter of the PAI-1 gene, including the homozygous 4G genotype, was not associated with a significantly increased risk of DVT in young people.

Factor V Leiden, FII G20210A, MTHFR C677T mutations as risk factors for venous thrombosis during pregnancy and puerperium

Venous thrombosis is the most common cause of obstetric morbidity and mortality during pregnancy and puerperium. The incidence of pregnancy-associated venous thrombosis varies from 1 in 1000 to 1 in 2000 deliveries. Factor V G1691A (FV Leiden), FII G20210A and MTHFR C677T mutations are the most common genetic risk factors for thromboembolism. The aim of this study was to establish the presence of these risk factors in a group of women with an episode of deep venous thrombosis during pregnancy or puerperium. The study was carried in a group of 45 women with the first episode of deep venous thrombosis during pregnancy or puerperium. The patients with antiphospholipid antibodies, antithrombin III, protein C or protein S deficiency, and autoimmune and malignant diseases were excluded from the study. FV Leiden, FII G20210A, and MTHFR C677T mutations were detected by polymerase chain reaction, followed by digestion with specific restriction enzymes. Twenty heterozygous carriers of the FV Leiden mutation and one homozygous carrier were detected, which represents the frequencies of 44.4% and 2.2%, respectively. For the FII G20210A mutation, six heterozygous carriers were identified, giving the frequency of 13.3%. The MTHFR C677T mutation was observed in 31 patients (22 heterozygous and 9 homozygous carriers) which represents the frequencies of 48.9% and 20%, respectively. Our study suggested that the obligatory testing for FV Leiden and FII G20210A mutations was strongly recommended in women with history of venous thrombosis during pregnancy and puerperium. We found a slight effect of MTHFR 677T allele, but it should be considered in association with other risk factors.

Case 76: May-Thurner Syndrome

A 26-year-old woman presented with persistent painless swelling of the left thigh of about 6 years duration. The swelling had gradually become more severe. Physical examination revealed a swollen left thigh, which was 6 cm larger in circumference than the right thigh. The patient did not recall any episode of deep venous thrombosis. Findings were normal at bilateral lower extremity venous Doppler ultrasonography (US); abdominopelvic computed tomography (CT) and left iliac venography were performed thereafter.

Outcomes and cost of deep venous thrombosis among patients with cancer

Study Question: What are the outcomes of patients with cancer complicated by deep venous thrombosis (DVT)? Methods: The initial medical records and outcome of 529 consecutive cancer patients in whom DVT developed from January 1, 1994, through December 31, 1997, were tracked until December 31, 2000. The study was conducted in a major cancer center, and the cost of hospitalization was obtained from the hospital’s cost-accounting system and inflated to 2002 US dollars using the Consumer Price Index for Medical Care. Logistic regression was used to identify factors associated with a high risk of poor outcomes. Results: The mean age was 55 years, and 52% were women. Seventy-seven percent of DVT cases presented as outpatients, 15% had a previous bout of DVT, and 13% developed within 30 days of a surgical procedure. Over 70% had the diagnosis established within 24 h of symptoms onset, although 20% had symptoms for at least 2 weeks; 50% were lower extremity and 40% were a major central vein alone or with an extremity. The latter were more often associated with central venous catheters (51% with vs. 35% without, p<0.001). Ninety-three percent received anticoagulants (95% received heparin). The most common complication of DVT was bleeding, which occurred in 13% of patients. Pulmonary embolus occurred in 4%. Five patients (1%) died of complications of DVT and 5 (1%) of complications of anticoagulation. Recurrence of DVT was common (17% overall), particularly among those who had inferior vena cava filters (32%, p<0.001) or a previous episode of DVT (p=0.03). All but 4 patients were hospitalized for initial anticoagulation therapy, for a mean of 11 days. The mean cost of hospitalization was 2002 US $20,065. Conclusions: Among patients with cancer, DVT frequently is associated with serious clinical outcomes. Its treatment is resource intensive and costly. More effective agents and less costly management strategies could have a significant impact on the outcomes and cost of DVT in this population. Perspective: This study demonstrates the very high rate of recurrence of DVT in cancer patients, and as with other studies that question the efficacy of IVC filters. The latter may be selection bias, but also could infer that the presence of the filter increases the risk of distant thrombosis. Unfortunately, the data cannot be used to draw any specific therapeutic conclusions. MR

Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank.

Venous thromboembolic events (VTE) are potentially preventable causes of morbidity and mortality after injury. We hypothesized that the current clinical incidence of VTE is relatively low and that VTE risk factors could be identified. We queried the ACS National Trauma Data Bank for episodes of deep venous thrombosis (DVT) and/or pulmonary embolism (PE). We examined demographic data, VTE risk factors, outcomes, and VTE prophylaxis measures in patients admitted to the 131 contributing trauma centers. From a total of 450,375 patients, 1602 (0.36%) had a VTE (998 DVT, 522 PE, 82 both), for an incidence of 0.36%. Ninety percent of patients with VTE had 1 of the 9 risk factors commonly associated with VTE. Six risk factors found to be independently significant in multivariate logistic regression for VTE were age > or = 40 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.74 to 2.32), lower extremity fracture with AIS > or = 3 (OR 1.92; 95% CI 1.64 to 2.26), head injury with AIS > or = 3 (OR 1.24; 95% CI 1.05 to 1.46), ventilator days >3 (OR 8.08; 95% CI 6.86 to 9.52), venous injury (OR 3.56; 95% CI 2.22 to 5.72), and a major operative procedure (OR 1.53; 95% CI 1.30 to 1.80). Vena cava filters were placed in 3,883 patients, 86% as PE prophylaxis, including in 410 patients without an identifiable risk factor for VTE. Patients who need VTE prophylaxis after trauma can be identified based on risk factors. The use of prophylactic vena cava filters should be re-examined.

Outcomes and cost of deep venous thrombosis among patients with cancer.

Although deep venous thrombosis (DVT) often complicates the clinical course in patients with cancer, few studies of the outcomes of DVT in this population have been published. Furthermore, the cost of DVT is largely undescribed. We herein report the largest study of DVT in this population to date. We reviewed the medical records of 529 consecutive cancer patients in whom DVT developed from January 1, 1994, through December 31, 1997, and followed up these patients through December 31, 2000, for outcomes. The cost of hospitalization was obtained from our hospital's cost-accounting system and inflated to 2002 US dollars using the Consumer Price Index for Medical Care. Logistic regression was used to identify factors that were associated with a high risk of poor outcomes. The most common complication of DVT was bleeding, which occurred in 13% of patients. Pulmonary embolus occurred in 4%. Five patients (1%) died of complications of DVT and 5 (1%) of complications of anticoagulation. Recurrence of DVT was common (17% overall), particularly among those who had inferior vena cava filters (32%; P<.001) or a previous episode of DVT (P =.03). All but 4 patients were hospitalized for initial anticoagulation therapy, for a mean of 11 days. The mean cost of hospitalization was 2002 US $20 065. Among patients with cancer, DVT frequently is associated with serious clinical outcomes. Its treatment is resource intensive and costly. More effective agents and less costly management strategies could have a significant impact on the outcomes and cost of DVT in this population.

LOW MOLECULAR WEIGHT HEPARIN INDUCED PRIAPISM

A 52-year-old male had right lower extremity swelling following a long automobile ride. Venous duplex scan revealed a right popliteal deep venous thrombosis (DVT), and outpatient treatment with daily subcutaneous injection of 5,000 units dalteparin sodium, an LMWH, was instituted. Approximately 2 hours following the injection on the third day painful priapism developed without preceding trauma or sexual activity. The patient had no history of priapism and denied ingestion of alcohol or cocaine. The priapism was successfully treated with corporeal irrigation with saline and phenylephrine. Dark blood was irrigated from the corpora, which was suggestive of low flow priapism. Oral warfarin was started the next day and maintained for 6 months as DVT therapy. The patient responded well and suffered no further episodes of DVT or priapism.

Has time come for screening for occult cancer in patients with venous thromboembolism?

The association between symptomatic venous thromboembolism (VTE) and the presence of a still asymptomatic malignancy has fascinated the medical community for almost 70 years. Over and over again the name of Armand Trousseau is quoted when reference is made to this association. However, upon careful reading of the original Trousseau lessons nothing is mentioned about occult cancer [1, 2]. In fact, he describes the other well-known association: patients with overt cancer often suffer from (recurrent) episodes of deep venous thrombosis, as well as superficial phlebitis. Two British physicians, James and Matheson, have the honour to be the first ones. They reported in 1935 the subsequent development of cancer in a patient who experienced a venous thrombosis 2 months earlier and speculated about the role of occult cancer as a possible cause of the thrombosis [3]. Subsequent retrospective and prospective studies have confirmed that the incidence of new cancers in patients with idiopathic VTE in the next 2–3 years is approximately 7.5%, while in those with secondary VTE this rate is around 1.6%[4-9]. There is also, in part from these studies, suggestive evidence that when these cancers are detected earlier they are predominantly at an early stage. The major challenge is whether we can diagnose these occult cancers and whether if detected the balance between good and harm is positive. In this issue of the Journal, Monreal and colleagues [10] present their interesting findings of a two-step approach to detect asymptomatic malignancies in a cohort of VTE patients. They included 1089 consecutive patients with a first episode of VTE (80% had deep vein thrombosis). At entry 17% had known cancer and they were excluded. The remaining 864 patients (40% with idiopathic VTE) underwent what the authors called a routine examination, including a thorough history taking, physical examination and laboratory investigation. Upon careful reading it is obvious that this ‘routine examination’ was quite extensive, with clear guidelines about subsequent investigations based on the findings. The relevance of this approach is that in less dedicated centers this examination may be less thorough and therefore less effective. Nevertheless, the authors identified 167 patients (19%) who based on this routine examination had a suspicion of an occult cancer, the majority (58%) based on careful history taking. The presence of cancer was confirmed in 34 patients, i.e. in a fifth of those suspected of having cancer, and 3.9% of all patients investigated. The remaining patients, i.e. those with a normal routine examination, as well as those with normal findings despite the initial suspicion of cancer raised during routine examination, underwent what the authors called a ‘limited diagnostic work-up’. This consisted of ultrasonography of the abdomino-pelvic region and several cancer laboratory markers. Of the 830 patients who underwent this testing, 13 (1.6%) were diagnosed as having cancer of which 60% were early stage. During the 1-year follow-up an additional 14 (1.7%) cases of cancer became apparent. Which questions are answered by this study and which are raised? The most impressive finding is the high yield of the initial, albeit quite standardized routine examination. Thirty-four of the total of 61 cancers seen in this study with a follow-up of 1 year were detected with this initial step. This is 56% of all cancers. The limited diagnostic work-up found another 21%, whereas 23% were missed. The second conclusion therefore is that the limited diagnostic work-up strategy needs to be improved. Other studies partly by the same investigators suggested that spiral computed tomography or other imaging modalities might increase the sensitivity of this step to above 90%[10]. Finally, although this study provides additional evidence that those cancers detected by screening are often early stage, we lack evidence that the overall benefit–risk ratio is positive. All investigators worldwide interested in this topic should cooperate in answering this question, only than time has come to include screening for occult cancer in patients with idiopathic VTE.

Controversial Issues in the Diagnosis of Venous Thromboembolism

Although considerable progress has been made in the diagnosis of venous thromboembolism, several issues remain that are awaiting a proper solution. Among them are: the respective role of compression ultrasound of the proximal veins and ultrasonography of the entire leg vein system in the diagnostic approach of patients with the clinical suspicion of the first episode of deep venous thrombosis (DVT) of the lower extremities; the safety of managing subgroups of patients with suspected DVT without objective tests, i.e., with the use of pre-test probability scores and D-dimer assays; the role of ultrasonography in the diagnostic approach of patients with suspected ipsilateral recurrent thrombosis; and the role of spiral CT in the diagnostic approach of patients with clinically symptomatic pulmonary embolism.

Effect of graduated elastic compression stockings on leg symptoms and signs during exercise in patients with deep venous thrombosis: a randomized cross-over trial

Graduated elastic compression stockings (ECS) are often prescribed after deep venous thrombosis (DVT) to alleviate acute symptoms and to prevent and treat post-thrombotic syndrome (PTS). In patients with DVT, leg symptoms tend to worsen with exercise. The effects of ECS use during exercise have not been studied. Objectives were to determine whether ECS improve symptoms and signs and increase exercise capacity when worn during treadmill exercise by patients with prior DVT, with or without PTS. The methods employed a randomized cross-over trial. We recruited subjects who had a first episode of unilateral DVT at least 1 year earlier and categorized them as having, or not having, the PTS using a validated scale. Subjects underwent two identical treadmill exercise sessions at least 1 week apart, and were randomly assigned to wear knee-length 30 mmHg ECS on the affected leg during one of the two sessions. Venous symptoms, leg volume, leg circumference and calf muscle flexibility were measured in the affected leg before and after both exercise sessions. Subjects achieved similar percentage maximum predicted heart rates during both sessions. Comparing the ECS to no ECS session, there were no significant differences in treadmill time (21.2 vs. 21.2 min, P = 0.94), gain in leg volume (71 vs. 73 mL, P = 0.83), or change in soleus or gastrocnemius flexibility, whether or not PTS was present. Symptoms in general worsened slightly with exercise regardless of whether or not ECS were worn and did not differ according to PTS status. Per-subject analysis showed that use of ECS resulted in global improvement of symptoms in 25% of subjects, global worsening in 33% of subjects, and had no or inconsistent effects in 42% of subjects. Whether or not PTS was present, the use of ECS during exercise by patients with prior DVT did not improve symptoms and signs during exercise or increase exercise capacity.

Prevalence of factor V Leiden, FII G20210A, FXIII Val34Leu and MTHFR C677T polymorphisms in cancer patients with and without venous thrombosis

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. In addition to well-established acquired risk factors for VTE, several genetic risk factors, mainly related to the haemostatic system, are known to influence thrombotic risk. However, the contribution of gene abnormalities to thrombotic tendency in cancer patients remains poorly explored. We performed a prospective study to evaluate the prevalence and clinical significance of four gene variations (factor V Leiden [FVL], factor II G20210A, factor XIII Val34Leu and MTHFR C677T) in cancer patients, with and without VTE. Enrolled were 211 unrelated and unselected patients (M/F ratio 0.5, mean age 57 years, range 12–91 years) with a diagnosis of cancer, admitted to two University Oncology Clinics in the city of São Paulo, Southeastern Brazil. After admission, all patients were evaluated for the presence of symptoms and signs of VTE. Sixty-four patients (30.3%) had an episode of deep venous thrombosis (DVT) or pulmonary embolism (PE), which has been objectively verified; 147 patients (69.7%) had no evidence of VTE. FVL was found with a frequency of 1.5% and 2.7% in the VTE and non-VTE group, respectively (odds ratio [OR] for VTE 0.6, 95% CI: 0.06–5.3). FII G20210A was found in 1.5% and 1.3% of thrombotic and nonthrombotic patients, respectively, yielding an OR of 1.2 (95% CI: 0.1–13.1). FXIII Val34Leu was detected in 29.6% of the thrombotic patients and in 28.5% of the non-thrombotic patients (OR 1.1, 95% CI: 0.5–2). MTHFR 677T was present in 53.1% and 60.5% of patients with and without thrombosis, respectively (OR 0.8, 95% CI: 0.4–1.4). The present data do not point to an association between the four polymorphisms here investigated and the risk of VTE in cancer patients.

Acute Effects of Exercise in Patients With Previous Deep Venous Thrombosis : Impact of the Postthrombotic Syndrome

The postthrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) and is believed to worsen with upright posture and physical activity. However, the effects of exercise in patients with previous DVT have not been studied.To determine whether previous DVT and PTS limit the ability to exercise, and whether exercise increases the severity of venous symptoms and signs.A repeated-measures cohort study that was conducted at a university-affiliated teaching hospital, 1999-2000.Subjects with a first episode of unilateral DVT at least 1 year earlier were recruited from the Thrombosis Clinic (total, 41 subjects; with PTS, 19 subjects).Treadmill exercise session.Venous symptoms, calf muscle fatigability, flexibility, and leg volume before and after treadmill exercise were measured and compared. Exercise did not worsen venous symptoms, despite a higher gain in affected leg volume in subjects with PTS vs subjects without PTS (mean difference: affected leg, 53 mL; unaffected leg, -15 mL; p = 0.018). Calf flexibility significantly improved after exercise in subjects with PTS (gastrocnemius: affected-unaffected, PTS vs no PTS + 4.5 degrees, p = 0.0029; soleus: affected-unaffected, PTS vs no PTS + 5.7 degrees, p = 0.0011).Exercise did not acutely exacerbate symptoms and, in subjects with PTS, resulted in improved flexibility in the affected leg. Our findings suggest that treadmill or similar exercise is unlikely to make symptoms of PTS worse, and may improve flexibility. Further study is indicated to determine whether a regular exercise-training program might have a role in the management of patients with PTS, since, to date, the treatment options for this condition are limited.

A single complete ultrasound investigation of the venous network for the diagnostic management of patients with a clinically suspected first episode of deep venous thrombosis of the lower limbs

In patients clinically suspected of deep-vein thrombosis (DVT) of the lower limbs, it is safe to withhold anticoagulant therapy after a negative ultrasound (US) limited to the popliteal and the femoral veins, provided that this can either be repeated or combined with other diagnostic procedures. To assess the safety of withholding anticoagulants after a single negative complete US, we performed a multicenter, prospective, cohort study including consecutive ambulatory outpatients from institutional and private practice settings, with a clinically suspected first episode of DVT. Patients fulfilling the inclusion criteria were enrolled after careful clinical assessment. A complete US examination of the proximal and the distal veins was performed according to a standardized and detailed protocol. Anticoagulant therapy was administered in patients with proximal or isolated distal DVT and withheld in those with negative results. The main outcome measure was the occurrence of objectively documented clinical thromboembolic events during a three-month follow-up after a negative US. Out of 623 patients, 401 (64.4%) had a baseline negative US, were not anticoagulated and could be followed-up for three months. Two patients presented a calf DVT within three months. The incidence of venous thromboembolic events, including distal DVT, was 0.5% [95% confidence interval: 0.1-1.8]. No proximal DVT, or non-fatal or fatal pulmonary embolism occurred (incidence: 0.0% [95% confidence interval: 0.0-0.9]). In conclusion, it is safe to withhold anticoagulant therapy in patients with clinically suspected DVT after a single, negative, complete US. Integrating this method within diagnostic strategies for DVT could improve management and be more acceptable for patients and physicians.