Pathogenesis Of Deep Vein Thrombosis Research Articles

Metabolic and Inflammatory Proteins Differentially Expressed in Platelets from Unprovoked Deep Vein Thrombosis Patients

Deep vein thrombosis (DVT) is multi-causal disease associated to high morbidity and mortality due to complications, especially from pulmonary embolism. New factors of relevance on the DVT pathophysiology enhance our understanding of disease mechanisms and can be translated into improved management of patients, prevention of recurrence and development of new therapies. In this context, the precise role of platelets in the pathogenesis of DVT is not completely understood. Our objectives were to acquire and to analyze the whole platelet protein profile of samples from 3 DVT patients and to compare them to results obtained from 1 sibling and 1 neighbor from each patient (in order to minimize genetic and environmental interferences). These patients presented unprovoked and recurrent episodes of proximal DVT as well as a family history of DVT. Platelets were washed, lysed, and the proteins were hydrolyzed by trypsin. Peptides were first separated by HPLC and peptide fractions were further detected by LC-MS/MS. Five proteins was present on patients and absent in all the controls: Apolipoprotein A1 Binding-Protein, Coatomer (zeta1 sub-unit), 17β-hydroxysteroid dehydrogenase type XI, Leukotriene A-4 Hydrolase and Sorbitol Dehydrogenase. The analysis identified proteins that currently are not related to the pathophysiology of DVT, and the persistence of these inflammatory and lipid transportation-related proteins emphasize the relevance of these phenomena on DVT.

Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches

Interaction between vascular wall abnormalities, inflammatory leukocytes, platelets, coagulation factors and hemorheology in the pathogenesis of deep vein thrombosis (DVT) is incompletely understood, requiring well defined animal models of human disease. We subjected male C57BL/6 mice to ligation of the inferior vena cava (IVC) as a flow reduction model to induce DVT. Thrombus size and weight were analyzed macroscopically and sonographically by B-mode, pulse wave (pw) Doppler and power Doppler imaging (PDI) using high frequency ultrasound. Thrombus size varied substantially between individual procedures and mice, irrespective of the flow reduction achieved by the ligature. Interestingly, PDI accurately predicted thrombus size in a very robust fashion (r2 = 0.9734, p < 0.0001). Distance of the insertion of side branches from the ligature significantly determines thrombus weight (r2 = 0.5597, p < 0.0001) and length (r2 = 0.5441, p < 0.0001) in the IVC, regardless of the flow measured by pw-Doppler with distances <1.5 mm drastically impairing thrombus formation. Occlusion of side branches prior to ligation of IVC did not increase thrombus size, probably due to patent side branches inaccessible to surgery. Venous side branches influence thrombus size in experimental DVT and might therefore prevent thrombus formation. This renders vessel anatomy and hemorheology important determinants in mouse models of DVT, which should be controlled for.

The P2Y receptors and thrombosis

Blood platelets play a key role in arterial thrombosis which is one of the leading causes of mortality in western countries. They may also be involved in the pathogenesis of deep vein thrombosis. Adenosine 5′‐diphosphate (ADP) is one of the most important mediators of platelet activation. Two G protein‐coupled ADP receptors, P2Y1 and P2Y12, selectively contribute to platelet aggregation and formation of a thrombus. Playing a central role in platelet activation and in growth and stabilization of a thrombus, the P2Y12 receptor is an established target of antithrombotic drugs like the thienopyridines clopidogrel or prasugrel, or direct reversible antagonists such as ticagrelor or cangrelor. Each of these drugs has proven efficacy in large clinical trials. At a preclinical stage, studies in P2Y1 deficient mice and using selective P2Y1 antagonists in experimental models of thrombosis and inflammation have shown that this receptor is also an attractive target for new antithrombotic compounds. WIREs Membr Transp Signal 2013. doi: 10.1002/wmts.97Conflict of interest: The authors have declared no conflicts of interest for this article.For further resources related to this article, please visit the WIREs website.

Genetic Polymorphism of NOS3 with Susceptibility to Deep Vein Thrombosis after Orthopedic Surgery: A Case-Control Study in Chinese Han Population

Deep vein thrombosis is one of the common complications of orthopedic surgery. Studies indicated that genetic factors played a considerable role in the pathogenesis of deep vein thrombosis. Endothelial nitric oxide synthase which encoded by nitric oxide synthase 3 (NOS3), can generate nitric oxide in endothelial cells. As a predominant regulator for vascular homeostasis, nitric oxide might be involved in the pathogenesis of thrombosis. It had been proved that the NOS3 polymorphism (rs1799983) was associated with the development of cardiovascular diseases. Our objective was to evaluate the association between the NOS3 polymorphism (rs1799983) and deep vein thrombosis after orthopedic surgery in Chinese Han population. The polymorphism was genotyped in 224 subjects with deep vein thrombosis after orthopedic surgery and 580 controls. Allele and genotype frequencies were compared between subjects with deep vein thrombosis and control subjects. The allele and genotype frequencies of the NOS3 polymorphism (rs1799983) were significantly different between subjects with deep vein thrombosis and control subjects. There were also significant differences when the subjects were stratified by gender, surgery type and hypertension status. These findings suggested that the NOS3 polymorphism (rs1799983) was associated with susceptibility to the deep vein thrombosis after orthopedic surgery in Chinese Han population, and NOS3 might play a role in the development of deep vein thrombosis after orthopedic surgery.

Abstract 54: Peptidylarginine Deiminase 4-dependent Generation of Neutrophil Extracellular Traps is Crucial for Deep Vein Thrombosis in Mice

Introduction Histone hypercitrullination by the enzyme peptidylarginine deiminase 4 (PAD4) leads to nuclear chromatin decondensation that is needed for neutrophil extracellular trap (NET) formation. NETs consist of chromatin and granule proteins that are released into the extracellular environment. NETs were shown to be involved in thrombosis by promoting coagulation and platelet adhesion and were identified in the thrombus scaffold in animal models of deep vein thrombosis (DVT). Objective Whether NETs are involved in the pathogenesis of DVT or whether they are merely a consequence of neutrophil recruitment to the thrombus is unknown. We hypothesized that NET formation would be impaired in PAD4-deficient mice during deep vein thrombosis and that this may affect thrombus formation and/or stability. Methods PAD4-deficient mice are incapable of citrullinating histones and therefore fail to decondense chromatin during NETosis. We performed the inferior vena cava stenosis model of DVT in wild-type or PAD4-/- mice. Intravital microscopy was done to assess leukocyte vessel wall interaction in PAD4 deficiency. Results We induced NET formation in isolated peripheral blood mouse neutrophils with ionomycin and found that PAD4-/- neutrophils had a complete inability to produce NETs (WT, 20.65±2.61% NETs; PAD4-/-, not detected. n=4). Leukocyte-endothelial interactions in PAD4-/- mice were not impaired upon induction of systemic Weibel-Palade body release (WT, 55.2±11.8; PAD4-/-, 62.0±17.5 cells/min, n=5-6). In the DVT model, while a majority (9/10) of wild-type mice formed a thrombus 48 hours after stenosis, only 1 of 11 PAD4-/- mice formed a thrombus. Thrombus formation could be rescued by infusions of isolated WT bone marrow neutrophils into PAD4-/- mice, and extracellular H3Cit+ areas were seen within these thrombi. This data suggests that neutrophil PAD4 was essential for thrombus formation in deep veins. Conclusion NETs comprise a crucial part of the pathologic thrombus scaffold, and here we report that the lack of NETs inhibits pathological thrombosis. Chromatin decondensation initiated by PAD4 in neutrophils is a key player in the formation of deep vein thrombi and targeting neutrophil histone modification could be a new way to prevent DVT.

Hyperhomocystéinémie, maladie veineuse thromboembolique et schizophrénie

ObjectivesThe aim of this study was to determine the prevalence of hyperhomocysteinemia in patients with schizophrenia (SKZ) with deep vein thrombosis (DVT) and to investigate if hyperhomocysteinaemia is a contributive risk factor for the pathogenesis of DVT. Patients and methodsThis is a retrospective study with 22 patients (14 men and eight women) suffering from various psychiatric disorders, having been supported DVT. Among them there are six patients with SKZ (five men and one woman). Hyperhomocysteinemia was found in five patients with SKZ (five male) and one patient followed for unclassifiable psychotic disorders. Hyperhomocysteinemia appears to be more common in men. The rate of hyperhomocysteinemia in our patients is consistent with what has been reported in the literature (4.7 to 6.2mg/L). For the rest of thrombophilia, protein S deficiency is predominates (seven cases), followed by hyperhomocysteinemia (six cases). ConclusionThe prevalence of SKZ from the group of subjects with hyperhomocysteinemia is consistent with the results of the literature. That hyperhomocysteinemia is likely due to the combination of genetic, enzymatic and certainly also to nutritional and vitamin deficiencies.

Breaking Up the Clot

Crosstalk between platelets and immune cells is essential for the pathogenesis of deep vein thrombosis.

Neutrophil extracellular traps promote deep vein thrombosis in mice

Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be prothrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). To explore the source and role of extracellular chromatin in DVT. We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared with sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs' structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development.

Evaluation of ADAMTS13 Activity and Inflammatory Markers in Deep Venous Thrombosis Patients

Abstract 5246 BACKGROUND:The role of inflammation on the pathophysiology of arterial thrombosis has been extensively studied. However, the relationship between inflammation and deep vein thrombosis (DVT) is not completely understood. Conflicting reports have been published about the levels of proteins involved in the inflammatory response in the context of DVT. Changes in ADAMTS13 levels have been reported in other inflammatory conditions such as sepsis, and this protease could be involved in the interplay between hemostasis and inflammation. OBJECTIVE:To evaluate ADAMTS13 activity in DVT patients and its association with inflammatory markers (IL-6, IL-8, CRP, TNF-α), D-dimer and von Willebrand Factor (VWF) levels. METHODOLOGY:Thirty-eight DVT patients, from 6 months to five years after the diagnosis of DVT, followed at the outpatient unit of thrombotic diseases from University of Campinas and 38 healthy volunteers selected as controls were included in the study. ADAMTS13 activity was determined by the residual binding of VWF to collagen. VWF, IL-6, IL-8 and TNF-alpha levels were determined by ELISA, and D-dimer levels was determined by a turbidimetric method. RESULTS:In this study population DVT was triggered by transient risk factors, particularly the use of oral contraceptives. No patient presented renal, hepatic or malignant disease. Median ADAMTS13 activity was not statistically different between patients (median: 98.2%; range: 70–146) and controls (median: 96.1%; range: 66–117; p=0.35). IL-6 and TNF-alfa levels were also higher in patients (median: 1.0pg/mL and 2.3pg/mL) compared to controls (median: 0.64pg/mL and 1.7pg/mL, p=0,01 and p=0,009). In addition, VWF and D-dimer levels were also significantly higher in patients (all P<0.01). No significant difference could be demonstrated between IL-8 and CRP levels from patients and controls. No significant correlation between ADAMTS13 levels and other inflammatory markers could be demonstrated. VWF levels correlated significantly with IL-8 (r=-0.4635, p< 0.0001). CONCLUSIONS:This study reinforces the role of inflammation in the pathogenesis of DVT. The correlation of VWF and IL-8 supports the notion that IL-8 stimulates the secretion of VWF. The role of ADAMTS13 in the context of DVT is yet to be determined. Disclosures:No relevant conflicts of interest to declare.

A complicated case of deep vein thrombosis

We report a case of a patient with deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) associated to portal vein thrombosis (PVT), complicated by hospital-acquired pneumonia (HAP). The pathogenesis of DVT is multifactorial; among risk factors we can list: transitory situations (surgical interventions, infectious diseases with fever, traumas), acquired conditions (neoplasms, antiphospholipid syndrome) or genetically determined situations (thrombophilia). PVT of the sovrahepatic veins is responsible for 5-10% of portal hypertension cases in adults and can be associated to local or systemic infections. PVT is present in 10% of patients with cirrhosis and often associated to cancers. It can also complicate a surgery abdominal intervention. HAP is defined as pneumonia that appears for the first time within 48 h of hospital admission. In Internal Medicine Departments the incidence is 7-10 cases/1.000 of hospital admissions, with an important impact in terms of both mortality and morbility. An early diagnosis, together with a correct identification of microbiologic agents in cause, allows a suitable antibiotic therapy with consequent improvement of clinical prognosis and a meaningful reduction of mortality. Main risk factors are: age, hospital and department. An important variable to be considered is the onset of pneumonia. The later is the onset of HAP (5 or more days from the admission to hospital), the more often is associated to multidrug resistant (MRD) microorganisms, poorly responsive to antibiotic.

Addressing the Issue of the Pathogenesis of Deep Vein Thrombosis In Cancer

AbstractAbstract 4220The risk of thrombotic complications during tumor development has been the focus of several clinical studies over the past decades. Thrombotic disease is a common cause of death in cancer patients and almost one in five of all symptomatic cases of Deep Vein Thrombosis (DVT) are thought to be cancer related. Tumor cells generate and profit from a local and systemic hypercoagulable state, which promotes tumor growth, angiogenesis, and metastasis. The resulting procoagulant state is responsible for the heightened risk for thrombotic complications and the etiology of the resulting DVT event. However, despite the fact that some molecules, such as tissue factor, have recently been described as potential modulators of clot formation in DVT, the true trigger of DVT in cancer patients remains unknown. To determine whether the presence of cancer cells can trigger formation of a thrombus in a deep vein in vivo, we combined a murine model of Trousseau's Syndrome with a model of DVT. First, we induced the development of a tumor by subcutaneous injection of syngeneic pancreatic tumor cells in C57BL/6 mice. It was previously demonstrated that these mice have significantly reduced tail bleeding time and time to occlusion in injured mesenteric arteries and veins compared to control vessels. After 3 hours of partial flow restriction of the inferior vena cava, we observed that all tumor-bearing mice developed an occlusive thrombus (n=8) while only 29% of the control mice (n=7) formed occlusive thrombi. Interestingly, perfusion of cancer-derived microparticles in mice also induced thrombus formation in this DVT model, reproducing the tumor-bearing mice phenotype. This new approach showed that microparticles shed by cancer cells have a key role in the pathogenesis of cancer-associated DVT, and they may become a reasonable pharmaceutical target to prevent thrombosis associated with cancer development. Disclosures:No relevant conflicts of interest to declare.

In too deep: understanding, detecting and managing DVT

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is a serious health and social care problem of the developed world, affecting 1 in 1000 adults every year, and with an annual financial overhead of approximately £640 million. The nature of DVT means that often the condition can go unrecognized until the thrombus becomes an embolus. The pathogenesis of DVT continues to be based on Virchow's triad, which attributes VTE to 'hypercoagulability', 'stasis' and 'intimal injury'. The diagnosis of DVT is often the result of a number of tests performed either sequentially or in combination before mechanical and/or chemical treatment is embarked on. Creating public awareness of DVT and PE is the best way to prevent this condition. Nurses are in an ideal position to discuss the importance of lifestyle changes and other related measures to prevent DVT.

DECREASED ACTIVITY of ADAMTS13 IN PATIENTS with DEEP Vein Thrombosis.

Abstract 3991Poster Board III-927 IntroductionSeveral risk factors, including increased levels of factor VIII (FVIII) and von Willebrand factor (VWF), have already been identified in patients with deep vein thrombosis (DVT). Recently we published a study showing that in a Brazilian population, plasma levels of FVIII over 180U/dl and VWF over 165U/dl were associated with the occurrence of venous thrombosis (odds ratio = 4.1 and 3.8 respectively) (Mello TB et al, 2009). The level of VWF in plasma and consequently FVIII is the result of genetic and acquired factors. ADAMTS13 (ADisintegrin And Metalloprotease with Thrombospondin type 1 repeats) is an enzyme responsible for cleavage of VWF, and its activity could contribute to VWF and FVIII plasmatic levels in patients with DVT. ObjectiveTo evaluate the activity of ADAMTS13 in patients with DVT associated with an increase of VWF and FVIII. Patients and methods: Fifty-six patients with FVIII > 180U/dl or FVW>165U/dl were selected from a cohort of 175 patients with DVT from the study mentioned above. Fifty-four normal subjects were selected as controls. The activity of ADAMTS 13 was performed by binding of residual VWF to collagen; VWF activity was measured by collagen binding, VWF antigen was determined by ELISA and FVIII was measured by a one-stage coagulation assay. Continuous variables were analyzed by Mann-whitney test and categorical variables by the Chi-square test. ResultsThe demographic distribution of patients and controls were similar. Among the 56 patients the median age was 37.5 years, 39 were women, 46 had blood typing “non-O”, 34 had DVT caused by transient risk factor, especially the use of oral contraceptives, 10 patients had a hereditary thrombophilia and 3 were carriers of antiphospholipid antibodies. No patient had renal, hepatic or malignant disease. The median ADAMTS 13 activity was significantly lower in patients (112.9%, 44.4 - 327.6%) when compared to controls (142.9%, 76.7 - 323.6%), P = 0.001. The VWF activity was also higher in patients (109.7%, 26.8 - 422.6%) when compared to controls, (79.1%, 45.5 - 203.8%), P=0.038. The median level of VWF antigen was significantly higher in the group of patients when compared to the control group (178.1U/dl versus 111.9 U/dl respectively, P <0.0001). There was an inverse correlation between ADAMTS13 activity and VWF activity. Conclusion: This study suggests that the increased VWF and FVIII activity in patients with DVT can be a result of decreased ADAMTS13 activity. The decreased activity of ADAMTS13 may be influenced by the action of cytokines in inflammatory processes, even after acute period. Future studies will be important to determine the correlation between activity of ADAMTS 13, VWF, and inflammatory markers in the pathogenesis of DVT. Disclosures:No relevant conflicts of interest to declare.

Inferior Vena Cava Ligation Rapidly Induces Tissue Factor Expression and Venous Thrombosis in Rats

Although stasis is important in the pathogenesis of deep vein thrombosis (DVT), how it contributes to thrombogenesis is largely unknown. To gain mechanistic insight, we used a rat model of inferior vena cava (IVC) ligation. Rats were subjected to IVC ligation for 15 to 60 minutes. Ligation resulted in rapid IVC dilatation and by 60 minutes, thrombi were detected in all rats. Small thrombi were detected in the IVC of most rats after 15 minutes of ligation. Thrombi were rich in fibrin, contained aggregated platelets as well as trapped leukocytes and red cells, and most originated at sites of localized endothelial denudation. Immunohistochemical analysis revealed tissue factor (TF)-expressing leukocytes within the thrombi and adherent to the vessel wall. Despite a largely intact vessel wall, endothelial cells also stained for TF. The expression of TF colocalized with that of protein disulfide isomerase (PDI), an enzyme implicated in TF decryption. These findings suggest that the rapid development of DVT after IVC ligation reflects a combination of stasis-induced vein wall injury and enhanced TF expression in endothelial cells and leukocytes. Because TF expression occurs so soon after ligation, new synthesis is unlikely. Instead, stasis-induced venous dilatation with or without exposure of subendothelial TF, may be responsible for vessel wall TF expression. Colocalization of TF and PDI raises the possibility that PDI-mediated TF decryption plays a role in the pathogenesis of DVT.

NF-κB Transcription Factor p50 Critically Regulates Tissue Factor in Deep Vein Thrombosis

NF-kappaB transcription factors regulate the expression of tissue factor (TF), a principal initiator of the coagulation cascade. Dominant among them is the p50/p65 heterodimer. Here we report that Andrographolide (Andro; a p50 inhibitor) and genetic deletion of p50 attenuated TF activity in stimulated endothelial cells and monocytes/macrophages. Results of the electrophoretic mobility "supershift" assay and chromatin immunoprecipitation demonstrated the direct interaction of the p50/p65 heterodimer with the NF-kappaB site of the human TF promoter. Andro-treated and p50 null mice both exhibited blunted TF expression and reduced venous thrombosis, which were recapitulated by an anti-murine TF antibody in vivo. Our findings thus indicate that regulation of TF by NF-kappaB transcription factor p50 is essential for the pathogenesis of deep vein thrombosis and suggest that specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and perhaps treating venous thrombosis.

Coexistence of left-sided inferior vena cava, deep vein thrombosis of the upper and lower extremities and prothrombotic polymorphisms in a young patient: a case report

A literature review suggests an interaction between an anomaly of the inferior vena cava and thrombophilia in the pathogenesis of deep vein thrombosis. Genetic thrombotic abnormalities have been found in some of the subjects having venous thromboembolic diseases. We report a case of a young man presenting with venous thrombosis of the upper and lower extremities, left-sided vena cava inferior and with combination of heterozygosity of the mutation of the genes Methylenetetrahydrofolate reductase 677 and Factor V 1691.

Prevention of DVT after orthopaedic surgery: the A-V Impulse System

Deep vein thrombosis (DVT) is a major health problem, which affects 1 in 1000 people in the general population each year. It may be asymptomatic or cause swelling and pain, and can lead to potentially fatal complications. Immobilisation following bone surgery significantly increases the risk of DVT, and prevention is a salient goal for nursing. This article reviews the pathogenesis of DVT, and therapeutic venous thromboembolic prophylaxis in the prevention of DVT following orthopaedic surgery. Best nursing practice is outlined from management of the Arteriovenous (A-V) Impulse System(R), the advent of which has had a positive impact on the incidence of DVT following orthopaedic surgery but requires further research to substantiate its effectiveness and determine patient acceptability.

Fetal head impaction as a cause of iliofemoral phlebothrombosis: Contribution to the pathogenesis of deep vein thrombosis during pregnancy

Fetal head impaction as a cause of iliofemoral phlebothrombosis: Contribution to the pathogenesis of deep vein thrombosis during pregnancy -

Deep vein thrombosis and heterotopic ossification in spinal cord injury: a 3 year experience at the Swiss Paraplegic Centre Nottwil.

Retrospective review of patient data. (i) To determine the incidence and time of deep vein thrombosis (DVT) under low molecular weight heparin (LMWH) prophylaxis in spinal cord injury (SCI), (ii) to determine the incidence and time of heterotopic ossification (HO) and (iii) to assess a possible aetiologic relationship in the pathogenesis of DVT and HO. Swiss Paraplegic Centre, Nottwil. We analyzed the incidence of DVT and HO in 1209 SCI patients (275 first rehabilitations) at the Swiss Paraplegic Centre Nottwil from 1998 to 2000. Clinical files and laboratory data were scrutinised for particularities preceding DVT and HO. The incidence of DVT was 6.55% for first rehabilitation compared to only 1.59% in all patients hospitalised. DVT was complicated by pulmonary embolism (PE) in 1.45% and 0.47% respectively. Incidence of HO was 8% for first rehabilitation and 1.82% for all patients hospitalised. In first rehabilitation patients the peak for DVT occurred around day 30 contrary to HO with a peak around day 120. In single patients HO was identified by MRI as a rapidly progressing process. Laboratory profiles were inflammatory in both HO and DVT. Increased physical activity preceding HO was observed in four patients. In two patients acute HO was complicated by ipsilateral DVT. Prophylaxis with LMWH and elastic stockings significantly reduces the frequency of DVT during first rehabilitation in SCI. DVT and HO are both associated with laboratory parameters of non-infectious inflammation. The later onset of HO coinciding with ongoing mobilisation, argues for a different pathogenetic mechanism. Acute HO of the hip region appears to favour ipsilateral DVT by well known thrombogenic mechanisms.

HYPERCHOLESTEROLEMIA AS A RISK FACTOR FOR DEEP-VEIN THROMBOSIS

Our retrospective study has shown that hyperlipidemia is a novel etiologic factor in deep-vein thrombosis (DVT) and that most of the idiopathic DVT patients were hyperlipidemic (Thrombosis Research 79, 147–151, 1995). The aim of our current study is to analyze the interrelationship between hyperlipidemia and DVT by means of a case-control study. A series of lipid parameters were analyzed using serum from 109 patients with deep vein thrombosis (DVT). One hundred nine age- and sex-matched subjects served as controls. Diagnosis of hyperlipidemia was made if the serum cholesterol level was above 220 mg/dL or if the triglyceride level was above 150 mg/dL. Among several types of hyperlipidemia examined, the risk factor associated with the highest estimated odds ratio was carriage of hypercholesterolemia associated with hypertriglyceridemia (odds ratio 5.1) followed in order by hypercholesterolemia without hypertriglyceridemia (odds ratio 2.6) and hypertriglyceridemia without hypercholesterolemia (odds ratio 0.9). These findings support the hypothesis that hypercholesterolemia plays an important role in the pathogenesis of DVT. © 1997 Elsevier Science Ltd