Upper-extremity deep venous thrombosis: a review

Upper-extremity deep venous thrombosis is less common than lower-extremity deep venous thrombosis. However, upper-extremity deep venous thrombosis is associated with similar adverse consequences and is becoming more common in patients with complex medical conditions requiring central venous catheters or wires. Although guidelines suggest that this disorder be managed using approaches similar to those for lower-extremity deep venous thrombosis, studies are refining the prognosis and management of upper-extremity deep venous thrombosis. Physicians should be familiar with the diagnostic and treatment considerations for this disease. This review will differentiate between primary and secondary upper-extremity deep venous thromboses; assess the risk factors and clinical sequelae associated with upper-extremity deep venous thrombosis, comparing these with lower-extremity deep venous thrombosis; and describe an approach to treatment and prevention of secondary upper-extremity deep venous thrombosis based on clinical evidence.     

Heterozygous prothrombin gene mutation G20210A and associated diseases

PURPOSE: Prothrombin gene mutation G20210A (factor II) is, in frequency, the second genetic polymorphism involved in venous thrombosis. We report a retrospective studies on 38 patients issued from our medical department, all heterozygous for the factor II mutation and a literature review. METHODS: We have studied 38 patients, all heterozygous for the factor II mutation, selected through a population of 516 tested patients issued from our medical department from 1997 to 2002. The research was performed face with history of thrombotic or obstetrical events, angiopathy or familial screening. RESULTS: Twenty out of thirty-eight patients have at least one episode of venous thrombosis: superficial thromboses, deep thromboses and/or pulmonary embolism. One case of cerebral thrombophlebitis is observed. Venous thrombotic risk factors are associated in 12 cases (60%). Four out of thirty-eight patients have one episode of arterial thrombosis: cardiovascular, peripheral or cerebral. Arterial thrombotic risk factors are associated in all cases. Median age of the first venous thrombosis is earlier than the one of arterial thrombosis (39.11 versus 49.25 years). CONCLUSION: Our studies confirms the interest to search the prothrombin gene mutation when faced with a venous thrombotic event (deep vein thrombosis and/or pulmonary embolism) with or without acquired risk factors. Its involvement in thrombotic arterial disease is still a matter of debate. Data concerning its involvement in systemic diseases and angiopathies (thromboangeitis obliterans, Raynaud's phenomenon and migraine) are still needed. Mechanisms of thromboses could be an increase of prothrombin plasma level with high thrombin synthesis.     

Thrombosis and acute lymphoblastic leukaemia

Venous thrombosis is more frequent in patients treated for acute lymphoblastic leukaemia (ALL) than other malignancies and has distinctive causes, clinical features and remedies. The reported incidence varies from 1% to 36%, depending on the chemotherapy protocol and whether the reported cases are symptomatic or detected on screening radiography. The risk is thought to arise from increased thrombin generation at diagnosis combined with reduced thrombin inhibitory capacity due to depletion of circulating anti-thrombin (AT) by asparaginase. A number of patient and treatment variables have been reported to influence the risk of thrombosis including hereditary thrombophilia, early insertion of central venous catheters and exposure to a combination of steroids and asparaginase during induction. Erwinia asparaginase is associated with a lower risk of thrombosis compared with Escherichia coli asparaginase. The majority of symptomatic thromboses are related to central venous catheters and involve the upper venous system. Central nervous system thrombosis involving the cerebral venous sinuses is a unique feature of asparaginase-related thrombosis and is reported to occur in 1-3% of patients. Conclusive evidence to support the use of anti-coagulant treatment or AT concentrates for primary prevention is lacking, as is evidence for the efficacy of AT concentrates in the management of established thrombosis. Preventative strategies are hampered by conflicting data on factors that would enable identification of those at highest risk of thrombosis.     

Outpatient Management of Venous Thromboembolic Disease with Subcutaneous Lepirudin: A Case Report

Outpatient treatment of deep venous thrombosis has gained widespread acceptance and is facilitated by the use of subcutaneous low molecular weight heparins (LMWH). We report two patients in whom subcutaneous lepirudin was used for long term anticoagulation after heart transplant or surgical pulmonary embolectomy because treatment with LMWH or warfarin was contraindicated, unsuccessful, or impractical. Neither bleeding complications nor recurrent thromboses developed. Subcutaneous lepirudin may be safely and effectively employed for the outpatient treatment of venous thrombosis in selected cases including patients with heparin-induced thrombocytopenia and in those who fail LMWH.     

Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from the General Population?

Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis with or without pregnancy morbidity in the presence of autoantibodies targeting proteins that associate with membrane phospholipids, termed “antiphospholipid antibodies” (aPL). Management of arterial and venous thromboses shares some similarities with management of arterial and venous thromboses in the general population; however, there are key differences. The majority of studies addressing management of thrombotic APS focus on secondary prevention. Vitamin K antagonists (VKA) are typically used for secondary prevention of venous thromboembolism in APS. Optimal management of isolated arterial thrombosis, in particular ischemic stroke, in patients with APS is controversial, and proposed therapeutic options have included antiplatelet agents and VKA. Primary prophylaxis in aPL-positive patients should be an individualized decision taking into account patient-specific risks. There may be a role for adjuvant therapies such as hydroxychloroquine, vitamin D, statins, or novel therapeutics in specific patient populations.     

Vascular complications of homocystinuria: a retrospective multicenter study

PURPOSE: Arterial or venous thromboses are frequent in patients with homocystinuria. Because severe homocystinuria is rare, prevalence of thrombosis, especially in France, is still unknown. METHODS: Review of the clinical outcome of 37 patients with homocystinuria due to cystathionine-cystathionine beta-synthase deficiency (34) and 5,10-methylenetetrahydrofolate reductase (three) lead us to describe vascular complications occurring in 12 (32%) of them. RESULTS: Venous thromboembolism is the earlier and the most frequent one and is mainly found in untreated late-diagnosed cases. Under specific treatment of homocystinuria, thromboses are rare and always a complication of surgery associated with high thromboembolic risk. Association with factor V Leiden increased the risk of venous thrombosis.     

Symptomatic thrombosis in central venous catheter in oncology: a predictive score?

BACKGROUND: Central venous catheters are essential to management of cancer patients. Thrombotic complications are potentially severe, but it is difficult to prescribe systematically a prophylactic treatment. So it is necessary to identify the higher risk patients who need a prophylaxis. AIM: To identify factors associated with the development of clinically significant venous thrombosis in cancer patients with long-term catheters. METHODS: Monocentric prospective study about 5447 long-term central venous catheters inserted into patients receiving treatment for solid tumours (50% of breast cancers). Clinically significant catheter-related thromboses are confirmed by ultrasonography, phlebography or scanner. RESULTS: The median duration of catheter use is 147 days. There are 135 clinically significant catheter-related thromboses. The risk for thrombosis is 0.1149 events per 1000 device days. The incidence of symptomatic thrombosis is 0.9% at 30 days, 1.36% at 60 days, 1.83% at 90 days and 2.25% at 120 days. The multivariate analysis shows that female sex, duration of insertion procedure (more than 25 minutes) and place of insertion (femoral place) are factors associated with clinically significant venous thrombosis. The right subclavian insertion causes less risk. The catheters with their tip too "high" in the superior vena cava are systematically changed, so that the position of the catheter tip does not appear as a risk factor in our study. The disease stage and the type of treatments are not well examined. CONCLUSIONS: A predictive score can be made with the three risk factors that have been identified. Thanks to this score it is possible to determine the patients with higher risk for clinically significant catheter-related venous thrombosis. These patients must be more frequently watched over and must receive a prophylactic treatment. The best prophylaxis has to be determined.     

Portomesenteric venous thrombosis:An early postoperative complication after laparoscopic biliopancreatic diversion

The number of bariatric operations,as well as the incidence of perioperative complications,has risen sharply in the past ten years.Perioperative acute portal vein thrombosis is an infrequent and potentially severe postoperative complication that has not yet been reported after biliopancreatic diversion(BPD).Three cases are presented of portal vein thrombosis that occurred following BPD treatment for morbid obesity and type 2 diabetes.The thromboses were detectedby abdominal ultrasound and computed tomography with intravenous contrast.The portomesenteric venous thromboses in all three cases presented as unexpected abdominal pain several days after discharge from the hospital.The complications occurred despite adequate perioperative prophylaxis and progressed to bowel gangrene in the diabetic patients only.These cases demonstrate the occurrence of this rare type of complication,which may be observed by physicians that do not routinely treat bariatric patients.Awareness of this surgical complication will allow for early diagnosis and prompt initiation of adequate therapy.     

Thrombolytic therapy for inferior vena cava thrombosis in paroxysmal nocturnal hemoglobinuria

Two patients with paroxysmal nocturnal hemoglobinuria had increasing abdominal girth and ascites. The Budd-Chiari syndrome or inferior vena cava thrombosis was shown by angiography. After thrombolytic therapy, both patients improved, and thrombolysis was shown by radiography. Neither patient had induction of hemolysis secondary to these agents. These studies suggest that both streptokinase and urokinase are safe and effective in the treatment of intra-abdominal venous thromboses associated with paroxysmal nocturnal hemoglobinuria.     

Calf muscle venous thrombosis and pulmonary embolism]

INTRODUCTION: The clinical significance of calf muscle venous thrombosis (CMVT) still remains a matter of debate. Detected by ultrasonography, they are overlooked by venography. This prompted us to evaluate the frequency of such localizations and their association to pulmonary embolism (PE). METHODS: Retrospective review of our database over a three-year period. All patients with an isolated CMVT were included. RESULTS: Isolated CMVT were detected in 106 patients (mean age 68.6 years; 65% women), that is 12.5% of all venous thromboses diagnosed in the vascular sonography unit over the study period Sixteen associated PE were detected (15%). CONCLUSIONS: Association of CMVT and PE is not infrequent. Whether or not such thromboses have the potential to extend into deep veins and/or to migrate into pulmonary circulation requires further studies.     

Thrombosis in children with cardiac pathology: analysis of acquired and inherited risk factors

The present study was conducted to analyze the features and risk factors of childhood thrombotic events in patients with cardiac defect followed-up at our hospital. The clinical and laboratory findings of 59 patients diagnosed with cardiac defects and thromboses between 1997 and 2006 were retrospectively analyzed. Thirty-one children (52.5%) had venous system thromboses, 21 (35.6%) had arterial system thromboses, and seven (11.9%) had venous and arterial system thromboses. Presence of congenital heart disease and cardiomyopathy (CMP) were significant risk factors for developing intracardiac thrombosis. In addition, presence of congenital heart disease was the significant statistical risk factor for developing left atrium and right ventricle thromboses. Presence of congenital heart disease was a significant risk factor for developing a central nervous system thrombosis. Presence of pulmonary stenosis and aortic coarctation were significant risk factors for developing a peripheral arterial system thrombosis. Acquired risk factors including major surgery, angiography, central venous catheter, systemic infection, and hypoxia were identified in 49 of the 59 patients. Many patients had more than one of these acquired risk factors. Analysis of the relationship between thrombosis and type of major surgery demonstrated a statistically significant relationship between an intracardiac thrombosis and total correction of tetralogy of Fallot and a peripheral venous system thrombosis and a Blalock Taussig shunt. Twenty-three of the 52 patients (44.2%) had at least one thrombophilic mutation. Overall, a heterozygous factor V Leiden mutation was found in nine patients (17.3%), a methylenetetrahydrofolate reductase 677C-T mutation in 15 patients (28.8%), and a PT 20210G-A mutation in three patients (5.8%). Our data suggest that cardiac defects are common risk factors for developing a childhood thrombosis. The type of disorder determines the site of thrombosis. Acquired risk factors may contribute to the development of a thrombosis. The results of this study also indicate that to ensure early diagnosis, routine screening for thrombosis should be performed in patients with a cardiac defect and that screening for factor V Leiden and PT 20210G-A mutations and other genetic risk factors should be included when assessing all patients with cardiac defects who present with a thrombosis, whether or not a predisposing factor has been identified.     

Thrombosis of renal veins

According to whether they are acute or progressive, complete or partial, uni- or bilateral, renal venous thromboses have quite various clinical expressions and biological consequences. The diagnosis is readily suggested by acute pain in the side with an increase in the size of one or both kidneys, associated with hematuria, proteinuria, or in case of renal failure, which is characteristic of acute bilateral thrombosis. On the other hand, chronic thrombosis of a renal vein is sometimes suggested only when complications such as pulmonary embolism occur. This explain why it is often discovered on autopsy. The diagnosis is confirmed on the basis of radiology, with ultrasound combined with vascular Doppler becoming increasingly important. Renal venous thrombosis may have various causes: disorders in renal blood flow, especially in the acute forms in newborns; hypercoagulability, in particular in nephrotic syndromes and above all in extramembranous glomerulonephritis; extension of vena cava thrombosis; retroperitoneal diseases involving the renal pedicle or extension of a renal tumor. The treatment of renal vein thrombosis is mainly medical and based on anticoagulants. The role of fibrinolytic treatment is controversial. Surgery is exceptional.     

Treatment of paroxysmal nocturnal hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria is an acquired clonal disorder of the hematopoietic stem cell in which intravascular hemolysis is due to an intrinsic defect in the membrane of red cells that makes them increasingly susceptible to lysis by complement. The phenotypic hallmark of PNH cells is an absence or marked deficiency of GPI-anchored proteins such as CD 59+, CD 55+ and others which normally protect cells from the action of complement. PHN is closely associated with aplastic anemia. Some degree of bone marrow failure is always present. Management of PNH is complicated by a highly variable clinical picture and course. Some patients have severe anemia aggravated by hemolytic crises and associated thromboses. Bone marrow failure is accompanied with frequent infections and hemorrhagic manifestations due to thrombocytopenia. With the exception of marrow transplantation, no definite therapy is available. In the exceptional circumstance in which the patient has a syngeneic twin, bone marrow transplantation is the most appropriate therapy for severe PNH because of absence of graft-versus-host disease. In general syngeneic transplantation without preconditioning has been unsuccessful because abnormal hematopoiesis returns. Allogeneic bone marrow transplantation has been used, but the transplant-associated morbidity and mortality are high due mainly to the fatal graft-versus-host disease and severe posttransplant marrow failure. Use of an unrelated donor transplant has to be considered as contraindicated. PNH is associated with striking predisposition to intravascular thrombosis which often involves the portal system or the brain. Fatal thromboses account for about 40-50% of all deaths in patients with PNH. The etiology of the thrombophilia in PNH is not fully clarified. Anticoagulation or thrombolytic therapy is required for treatment of venous thrombosis, the latter vena cava. Prophylactic anticoagulation in patients without contraindications such as severe thrombocytopenia seems to be justified. However, whether such therapy may be efficacious in reducing the incidence of thromboses or affect survival is conjectural. PNH patients have varying degree of platelet activation and some authors suggest that antiplatelet therapy might be efficacious in reducing the incidence and severity of venous thrombosis in PNH. Pregnancy is hazardous. Female patients should avoid the use of oral contraceptives. Pregnant patients require combined care of an experienced hematologist and obstetrician specialized in the management of high-risk pregnancies.     

Deep venous thrombosis caused by central venous catheter]

Infections and venous thromboses are the major complications of central venous access catheters and ports. The frequency of thrombosis depends on the venous access systems used, their material, their diameters and the position of their tips. The lowest rate of thrombotic complications is seen with single or double lumen Hickman- or port catheters made of silicone with their tips in the lower half of the superior vena cava or in the right atrium. Antibiotics given preoperatively and heparin for at least 90 days after catheter placement must be recommended in oncological patients with a high risk of thrombosis. In case of thrombosis-related occlusion of the catheters low-dose urokinase and streptokinase can be helpful to restore the catheter's function. Else, therapy is identical to that of other types of thrombosis.     

Treatment of deep venous thrombosis with a very low molecular weight heparin fragment (CY 222)

Thirty patients presenting with phlebographically confirmed deep venous thrombosis were treated with a very low molecular weight heparin fragment (CY 222) in an open and prospective phase-2 trial. A uniform dosage of 750 IC anti-factor Xa units/kg/day was administered subcutaneously for 10 days or more to patients whose thromboses were categorized as postsurgical (17 cases) or medical (13 cases). The clinical symptoms of venous thrombosis diminished in 93% of the patients overall. The extent of vascular clearing was assessed by an original scoring system which compared the pre- and posttreatment phlebographies. The effect of treatment was globally rated 'very good' (more than 75% lysis) in 37% of the patients, 'good' (about 50% lysis) in 40% and 'poor' (0-25% lysis) in 17%; the phlebographic thrombosis worsened in 6.6%. Little change occurred in laboratory tests exploring thrombolysis, but a strong anti-factor Xa activity was detected.     

Follow-up after deep venous thrombosis in azygos continuation

BACKGROUND: To determine the sequelae of patients after deep venous thrombosis inpatients with azygos continuation defined as agenesis of the inferior vena cava with collateral flow. PATIENTS AND METHODS: Five patients post deep venous thrombosis in the context of azygos continuation were followed up clinically and with colour duplex ultrasonography. RESULTS: All five patients had to our knowledge after the initial deep venous thrombosis no further thromboembolic events. Three patients after isolated iliac thromboses are symptom free or nearly symptom free, two after more extended thromboses still sufferfrom venous claudication. Four patients are without anticoagulation, one patient is permanently orally anticoagulated. CONCLUSIONS: Azygos continuation may not influence the risk of recurrent venous thrombo-embolism nor the outcome of a deep venous thrombosis. Careful deep venous thrombosis prophylaxis in patients with azygos continuation may be sufficient when a risk factor is present but conclusions lack due to the small numbers of patients of enough supportive data.     

Functional disorders of the venous muscular pump seen in chronic venous insufficiency

The study of the functioning of the venous muscle pump by means of plethysmographic tests allowed us to discover a clearly marked condition in the varicose veins combined with chronic venous deficiency and in the thromboses of the deep veins. In the case of varicose veins, we found an interdependence between the gravity of the functional lesions and the existence of insufficient perforating veins. The study, which dealt with cases of thrombosis, showed that the trophic skin lesions appear only after several years of poor nervous pump functioning.     

Chylothorax following apparently spontaneous central venous thrombosis in a patient with septic shock

Within the pediatric age group, chylothorax is rare and has been reported almost exclusively in the setting of thoracic surgical procedures or central venous hypertension secondary to central venous catheter thrombosis. We report on the development of central venous thrombosis and chylothorax in the absence of the usual risk factors in a patient with septic shock, and we expand on the role that procoagulant states, such as those induced by sepsis, might play in the development of this complication. This case reminds the practitioner that central venous thromboses and their complications may occur in the absence of the usually reported risk factors and must therefore still be considered when other clinical events suggest their presence.     

Arterial thrombotic complications in Crohn's disease

In a series of 230 observations of Crohn's disease, the authors describe 4 cases of arterial thrombosis; two of them involving cerebral arteries. These complications occurred in young women without any notable risk factor for atheroma. All patients had highly active Crohn's disease when arterial thrombosis occurred: two of them had several episodes of thrombosis and three, extraintestinal manifestations. As the arterial thromboses are often severe, rarely foreseeable and the venous thromboses frequent, the point is whether to use anticoagulants. When Crohn's disease is highly active, but only if there are no hemorrhagic lesions, anticoagulants at prophylactic doses may be recommended. How to define more exactly a high risk thromboses population deserves further investigation.