Decreased anticoagulant response to tissue factor pathway inhibitor in patients with venous thromboembolism and otherwise no evidence of hereditary or acquired thrombophilia

2004 ◽  
Vol 91 (01) ◽  
pp. 80-86 ◽  
Author(s):  
Brigitte Piccapietra ◽  
Johanna Boersma ◽  
Joerg Fehr ◽  
Thomas Bombeli
Keyword(s):  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Mean Value ◽  
Healthy Controls ◽  
Crude Odds Ratio ◽  
Sensitivity Ratio ◽  
Increased Risk ◽  
History Of ◽  
Anticoagulant Response ◽  
Acquired Thrombophilia

SummaryNo relevant deficiency of TFPI or genetic polymorphisms could thus far consistently be associated with venous thromboembolism. We hypothesized that the substrates of the TFPI protein, including FVII or FX (rather than the protein itself) could induce a hypercoagulable state. We created a novel TF-based clotting assay that evaluated the anticoagulant response to exogenously added recombinant TFPI. The response to TFPI was expressed as the ratio of the clotting time with and without TFPI. By using 118 healthy controls, we established a reference range between 1.31 and 1.93 (mean value ± 2 standard deviations (SD), 1.62 ± 0.31). We then evaluated samples from 120 patients with a history of venous thromboembolism but no evidence of hereditary and acquired thrombophilia. The range of the patients’ ratios was significantly (P < 0.001) lower, falling between 1.2 and 1.78 (mean value ± 2 SD, 1.49 ± 0.29). Of the 120 patients, 39 (32.5%) had a TFPI sensitivity ratio below the 10th percentile of the controls, compared with 11 (9.3%) of the healthy controls. The crude odds ratio for venous thrombosis for subjects with a TFPI sensitivity ratio below the 10th percentile was 13 (95% CI; range, 3.1 to 54.9) compared with those with a ratio above 1.8 (90th percentile). Patients with idiopathic thromboembolism did not have a decreased TFPI sensitivity ratio more often than patients with thrombosis with a circumstantial risk factor. Based on these results, a reduced response to TFPI may lead to an increased risk of venous thrombosis.

New Approach for Evaluation of Quantitative Risk Factors of Venous Thromboembolism Using Individualized Reference Values.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4022-4022
Author(s):  
Rainer B. Zotz ◽  
Andrea Gerhardt ◽  
Rudiger E. Scharf
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Reference Values ◽  
Protein S ◽  
Healthy Controls ◽  
New Approach ◽  
Increased Risk ◽  
Risk Determinants ◽  
Protein S Activity

Abstract The evaluation of quantitative risk factors of venous thromboembolism is characterized by several unsolved problems. The majority of quantitative components of hemostasis are dependent on age, sex, and hormone intake. The cut-off values determined in case-control studies depend on the specific patient/control group and can not be generalized on individuals with other characteristics. Furthermore, the approach does not give reference values dependent on age, sex, and hormone intake which are necessary for risk estimations in clinical practice. To overcome these disadvantages, we used a multiple regression analysis to create a system of reference values which change continuously depending on age, sex, and hormone intake according to the parameter distribution in healthy controls and calculated the relative risk of hemostatic components (729 patients with first VTE and 675 healthy controls). A significantly increased risk for venous thrombosis was associated with deficiency of protein S activity (odds ratio (OR) 2.8 to 6.1, p=0.0007), free protein S concentration (OR 2.7 to 20.4, p=0.0001), protein C activity (OR 3.2 to 9.4, p=0.0001), antithrombin activity (OR up to 75, p=0.0001), and increased levels of fibrinogen (OR 3.8, p=0.0001), factor VIII:C (OR 3.3, p=0.0001), factor IX (OR 2.3, p=0.0001), factor XI (OR 2.9, p=0.0001), vWF activity (OR 2.4, p=0.0001), and vWF antigen (OR 3.5, p=0.0001). In contrast to previously published studies, this new approach gives clinically important cut-off values dependent on age, sex, and hormone intake and allows to identify patients at increased risk for venous thrombosis on an individualized basis. Particularly parameters which are highly dependent on age and sex, like protein S activity, can be characterized more precisely using the described procedure. This comprehensive analysis demonstrates that, apart from well-known risk determinants, deficiency of protein S and increased values of FI, FVIII:C, FIX, FXI, vWF, and vWF-Ag are risk determinants predicting venous thrombosis.

Evidence-based indications for thrombophilia screening

VASA ◽  
2008 ◽  
Vol 37 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Lindhoff-Last ◽  
Luxembourg
Keyword(s):  
Venous Thromboembolism ◽  
Family History ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Pregnancy Loss ◽  
Late Pregnancy ◽  
Evidence Based ◽  
Increased Risk ◽  
Thrombophilia Screening ◽  
History Of

Thrombophilic defects have been shown to be associated with an increased risk of venous thrombosis, fetal loss, and gestational complications. The knowledge about the clinical relevance of thrombophilic defects is increasing, and evidence-based indications for thrombophilia screening are therefore discussed in this review. Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism is more cost-effective than universal screening in all patient groups evaluated. In the majority of patients with acute venous thrombosis, the results of thrombophilia screening do not influence the duration of oral anticoagulation. The only patient population who clearly profits from thrombophilia screening in this situation are patients with a newly diagnosed antiphospholipid syndrome, because prolonged anticoagulation can avoid the high incidence of recurrence in this patient population. Because of the increased risk of venous thrombosis during pregnancy and the puerperium, thrombophilia screening is indicated in selected patients with a previous history of venous thrombosis or a positive family history. Significant associations with early and late pregnancy loss are observed for carriers of the heterozygous factor V Leiden mutation, the heterozygous prothrombin-mutation G20210A and anticardiolipin antibodies, while protein S deficiency is significantly associated with late pregnancy loss. Antithrombotic drugs like UFH, LMWH or low-dose aspirin may have a potential therapeutic benefit in patients with recurrent pregnancy loss and thrombophilia, but placebo-controlled, multicenter trials are urgently needed to clarify this issue. Although a supra-additive effect for the risk of venous thrombosis is observed between oral contraceptives and some thrombophilias, the absolute incidence of venous thromboembolism is low in premenopausal women and mass screening strategies are therefore unlikely to be effective. While antiphospholipid antibodies are known to be associated with arterial thrombosis, screening for heritable thrombophilias is not useful in arterial thrombosis, although subgroup analysis indicates that they may play a role particularly in young patients and children.

Hereditary Heparin Cofactor II Deficiency and the Risk of Development of Thrombosis

1987 ◽  
Vol 57 (02) ◽  
pp. 196-200 ◽  
Author(s):  
R M Bertina ◽  
I K van der Linden ◽  
L Engesser ◽  
H P Muller ◽  
E J P Brommer
Keyword(s):  
Liver Disease ◽  
Venous Thrombosis ◽  
Healthy Volunteers ◽  
Mean Value ◽  
Age Group ◽  
Normal Range ◽  
Heparin Cofactor Ii ◽  
History Of ◽  
Group 2 ◽  
Hereditary Nature

SummaryHeparin cofactor II (HC II) levels were measured by electroimmunoassay in healthy volunteers, and patients with liver disease, DIC, proteinuria or a history of venous thrombosis. Analysis of the data in 107 healthy volunteers revealed that plasma HC II increases with age (at least between 20 and 50 years). HC II was found to be decreased in most patients with liver disease (mean value: 43%) and only in some patients with DIC. Elevated levels were found in patients with proteinuria (mean value 145%). In 277 patients with a history of unexplained venous thrombosis three patients were identified with a HC II below the lower limit of the normal range (60%). Family studies demonstrated hereditary HC II deficiency in two cases. Among the 9 heterozygotes for HC II deficiency only one patient had a well documented history of unexplained thrombosis. Therefore the question was raised whether heterozygotes for HC II deficiency can also be found among healthy volunteers. When defining a group of individuals suspected of HC II deficiency as those who have a 90% probability that their plasma HC II is below the 95% tolerance limits of the normal distribution in the relevant age group, 2 suspected HC II deficiencies were identified among the healthy volunteers. In one case the hereditary nature of the defect could be established.It is concluded that hereditary HC II deficiency is as prevalent among healthy volunteers as in patients with thrombotic disease. Further it is unlikely that heterozygosity for HC II deficiency in itself is a risk factor for the development of venous thrombosis.

Laboratory Evaluation and Clinical Characteristics of 2,132 Consecutive Unselected Patients with Venous Thromboembolism – Results of the Spanish Multicentric Study on Thrombophilia (EMET*-Study)

1997 ◽  
Vol 77 (03) ◽  
pp. 444-451 ◽  
Author(s):  
José Mateo ◽  
Artur Oliver ◽  
Montserrat Borrell ◽  
Núria Sala ◽  
Jordi Fontcuberta ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Odds Ratio ◽  
Protein C ◽  
Protein S ◽  
Laboratory Evaluation ◽  
Clinical Factors ◽  
Recurrent Thrombosis ◽  
Heparin Cofactor Ii ◽  
Crude Odds Ratio ◽  
History Of

SummaryPrevious studies on the prevalence of biological abnormalities causing venous thrombosis and the clinical characteristics of thrombotic patients are conflicting. We conducted a prospective study on 2,132 consecutive evaluable patients with venous thromboembolism to determine the prevalence of biological causes. Antithrombin, protein C, protein S, plasminogen and heparin cofactor-II deficiencies, dysfibrinoge-nemia, lupus anticoagulant and antiphospholipid antibodies were investigated. The risk of any of these alterations in patients with familial, recurrent, spontaneous or juvenile venous thrombosis was assessed. The overall prevalence of protein deficiencies was 12.85% (274/2,132) and antiphospholipid antibodies were found in 4.08% (87/2,132). Ten patients (0.47%) had antithrombin deficiency, 68 (3.19%) protein C deficiency, 155 (7.27%) protein S deficiency, 16 (0.75%) plasminogen deficiency, 8 (0.38%) heparin cofactor-II deficiency and 1 had dysfib-rinogenemia. Combined deficiencies were found in 16 cases (0.75%). A protein deficiency was found in 69 of 303 (22.8%) patients with a family history of thrombosis and in 205/1,829 (11.2%) without a history (crude odds ratio 2.34, 95% Cl 1.72-3.17); in 119/665 (17.9%) patients with thrombosis before the age of 45 and in 153/1,425 (10.7%) after the age of 45 (crude odds ratio 1.81, 95% Cl 1.40-2.35); in 103/616 (16.7%) with spontaneous thrombosis and in 171/1,516 (11.3%) with secondary thrombosis (crude odds ratio 1.58, 95% Cl 1.21-2.06); in 68/358 (19.0%) with recurrent thrombosis and in 206/1,774 (11.6%) with a single episode (crude odds ratio 1.78,95% Cl 1.32-2.41). Patients with combined clinical factors had a higher risk of carrying some deficiency. Biological causes of venous thrombosis can be identified in 16.93% of unselected patients. Family history of thrombosis, juvenile, spontaneous and recurrent thrombosis are the main clinical factors which enhance the risk of a deficiency. Laboratory evaluation of thrombotic patients is advisable, especially if some of these clinical factors are present.

Abstract 524: Influenza Vaccination Reduces The Risk Of Venous Thromboembolism

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tienan Zhu ◽  
Laure Carcaillon ◽  
Isabelle Martinez ◽  
Jean-Pierre Cambou ◽  
Xavier Kyndt ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protective Effect ◽  
Influenza Vaccination ◽  
Varicose Veins ◽  
Personal History ◽  
Protective Effects ◽  
Crude Odds Ratio ◽  
Confounding Variables ◽  
History Of

It is widely accepted that influenza vaccination reduces the risk of cardiovascular events in patients with coronary artery diseases. However, no information is available concerning the role of influenza vaccination in venous thromboembolism (VTE). Methods: A case-control study was conducted in 727 cases and 727 age and sex-matched controls from 11 centers in France (the FARIVE study). Cases were patients with a first documented episode of VTE and without any personal history of cancer within the last 5 years; controls were recruited in the same hospital and had no personal history of venous or arterial thrombosis. Results: Overall, 202 (28.2%) of cases and 233 (32.1%) of controls had influenza vaccination during the previous 12 months at the time of recruitment. Information was not available for only 12 subjects out of 1454. The crude odds ratio (OR) for VTE associated with influenza vaccination was 0.76 (95% CI 0.58–0.99). After adjustment for potential confounding variables (age, sex, inclusion date, BMI, educational levels and varicose veins), the OR for VTE associated with vaccination was 0.74 (95% CI 0.57–0.97). The protective effect of vaccination toward VTE was higher in the population below 52 years (median of age), with an OR of 0.52 (95% CI 0.32–0.85). In women below the age of 51, the crude OR for VTE associated with influenza vaccination was 0.50 (95% CI 0.24–1.05) and was significant after adjustment for confounding variables including oral contraceptives, with an OR of 0.41 (95% CI 0.19–0.92). The protective effect of vaccination was similar for different types of VTE (DVT or PE). There was no statistical differences in the protective effects when we compared provoked with unprovoked VTE events. Conclusion: This is the first study that demonstrates a protective effect of influenza vaccination in VTE. In vitro influenza induces activation of coagulation and inflammation but we cannot rule out that the protective effect of influenza vaccination was due to other unknown mechanisms, as the protective effect was similar within the different seasons of the year. Influenza vaccination may reduce the risk of VTE by 26%. This relationship between influenza vaccination and VTE and its underlying mechanism still need to be analyzed and confirmed in further studies.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

What the Standard APTT Didn’t Tell You - Dynamic Plasma Clotting Parameters Reveal Hypercoagulation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2634-2634
Author(s):  
Benny Sørensen ◽  
Peter Johansen ◽  
Kirsten Christiansen ◽  
Lisbeth Norengaard ◽  
Ole H. Larsen ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Reference Group ◽  
Maximum Velocity ◽  
Reference Interval ◽  
Healthy Controls ◽  
Dynamic Parameters ◽  
Healthy Individuals ◽  
Fibrin Formation ◽  
Number Of Patients ◽  
History Of

Abstract Patients with a history of venous thrombosis have significantly shorter APTTs as compared with healthy references. The clinical feasibility of a short APTT is hindered because only a small number of patients have APTT values actually below the reference interval of healthy individuals. The APTT merely reflects the very early start of fibrin polymerization; however, clot formation is a continuous dynamic process. It may be speculated that additional prognostic information may be obtained from parameters describing the entire profile of the APTT clotting signal. Hence, we have developed algorithms to derive additional dynamic parameters from a continuous APTT plasma clotting signal, including the maximum velocity of fibrin formation (APTT-MaxVel). The aim of the present study was to characterize dynamic APTT profiles from patients with verified venous thrombosis. We hypothesized that the APTT-MaxVel was significantly accelerated in patients with a history of verified venous thrombosis as compared with healthy controls. A total of 46 patients, 19 males and 27 females, with a verified venous thrombosis were enrolled in the study. Fifty-two percentages of patients had a positive thrombophilia risk factor. Patients with antiphospholipid syndrome were not included. In total 89 healthy individuals, 43 males and 46 females, established a reference group. A standard APTT was recorded using platelet poor plasma, Platelin® as test reagent, and a BCT coagulation analyzer. The digital continuous clotting signal was exported and processed in a software program to derive dynamic coagulation parameters. Comparative statistics and un-paired t-tests were adopted to assess differences between groups and multiple linear regression was performed to predict the value of APTT-MaxVel from levels of FVIII:C and fibrinogen. P-values &lt; 0.05 were considered statistical significant. Patients had a significantly more accelerated mean APTT-MaxVel (193.5 x/sec, SD=57, 95%CI: 176.6–210.4) as compared with healthy controls (137.3 x/sec, SD=21, 95%CI: 126.7–143.8). Patients also had a significantly shorter mean APTT (27.2 sec, SD=3.2, 95%CI: 26.3–28.2) than healthy controls (28.5 sec, SD=2.8, 95%CI: 27.9–29.1). Whereas only 1 of 46 (2.2%) patients had a standard APTT below the lower reference interval, 17 of the 46 (37%) patients had an APTT-MaxVel above the upper reference limit. Regression analysis revealed a linear correlation between FVIII:C, level of fibrinogen, and APTT-MaxVel (R2=0.89, p&lt;0.05). Our data suggest that the APTT-MaxVel of fibrin formation represent a more sensitive marker for hypercoagulation in patients with verified venous thrombosis than standard APTT measures. The APTT-MaxVel may reflect the functional importance of both FVIII:C and level of fibrinogen. Additional studies are required to further assess the possible clinical and laboratory relevance of using dynamic parameters to predict risk of recurrent thrombosis.

Circulating Microparticles and Risk of Venous Thromboembolism.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3987-3987
Author(s):  
Paolo Bucciarelli ◽  
Emanuele Previtali ◽  
Ida Martinelli ◽  
Andrea Artoni ◽  
Serena M Passamonti ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Venous Thromboembolism ◽  
Body Mass ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Control Group ◽  
Dependent Manner ◽  
Healthy Controls ◽  
Increased Risk

Abstract Abstract 3987 Poster Board III-923 Background Microparticles (MPs) are circulating, submicroscopic fragments (<1 μm of diameter) of membrane-bound cytoplasm that shed from the surface of an activated or apoptotic cell and play a role in coagulation, inflammation, cell remodelling and proliferation. There is increasing evidence that MPs are involved in thrombosis, but whether or not they are an independent risk factor for venous thromboembolism (VTE) is not established. Aim of the study To investigate the association between high plasma levels of MPs and risk of VTE Patients and Methods In a case-control study, 186 patients with a first episode of VTE (deep venous thrombosis and/or pulmonary embolism) and 418 healthy controls were included. MPs were analyzed by flow cytometry with a gate defined by a 1 μm beads and using APC-Annexin V together with FITC anti-CD41 or FITC anti-CD142 antibodies in order to identify platelet MPs (MP-Plts) and MPs exposing tissue factor (MP-TF), respectively. MPs levels were expressed as number/μL. Results Patients had significantly higher median plasma levels of both MPs-Plts and MPs-TF than controls [1942 vs 1519 (p<0.0001) and 579 vs 454 (p<0.0001)]. Higher median levels of MP-Plts and MP-TF were found in 41 patients who underwent blood sampling within 6 months from VTE than in those sampled later [2114 vs 1694 (p=0.086) and 652 vs 543 (p=0.120)]. Sex, age, body mass index and factor VIII plasma levels had no influence on MPs levels, as well as the use of oral contraceptives (this latter evaluated only in controls). In the whole study population, carriership of thrombophilia (antithrombin, protein C or protein S deficiency, factor V Leiden, prothrombin G20210A, antiphospholipid antibodies, hyperhomocysteinemia or combined abnormalities) had higher levels of MP-Plts and MP-TF than non-carriers [1907 vs 1565 (p=0.002) and 532 vs 468 (p=0.011)]. The odds ratio (OR) for VTE, adjusted for sex, age, body mass index and thrombophilia was 2.5-fold higher in individuals with MPs plasma levels >95th percentile of the control group (3633/μL for MPs-Plts and 1113/μL for MPs-TF) than in those with MPs levels ≤95th percentile [for MPs-Plts: OR=2.59 (95%CI 1.23 – 5.45); for MPs-TF: OR=2.38 (1.15 – 4.92)]. The risk increased in a dose-dependent manner for both MPs-Plts and MPs-TF, particularly above the 75th percentile of the distribution in controls. The exclusion of patients whose MPs levels were measured within 6 months from VTE (in order to avoid the possible effect of the acute phase on MPs measurements), did not change the results [adjusted OR: 2.63 (1.18 – 5.89) for MPs-Plts and 2.36 (1.10 – 5.19) for MPs-TF]. The Table shows the relative risks of VTE associated with the presence or absence of high MPs levels and thrombophilia. Individuals with MPs >95th percentile or thrombophilia alone had a 2 to 3-fold increased risk of VTE, whereas those with both MPs-Plts >95th percentile and thrombophilia had a 9-fold increased risk of VTE. This synergistic effect was confirmed also for MPs-TF and remained after the exclusion of patients whose blood sample was collected within 6 months from VTE [OR 7.72 (1.68-35.4) for MP-Plts and 8.14 (2.08-31.8) for MP-TF]. Conclusions Plasma levels of MPs are significantly higher in patients with VTE than in healthy controls. MPs levels >95th percentile are associated with a 2.5-fold increased risk of VTE. There is a synergistic interaction between high levels of MPs and thrombophilia on VTE risk. Disclosures: No relevant conflicts of interest to declare.

A matched analysis comparing the epidemiology of intraductal papillary mucinous neoplasms to standard pancreatic adenocarcinoma and healthy controls.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 173-173
Author(s):  
E. Ludwig ◽  
S. H. Olson ◽  
R. C. Kurtz ◽  
J. Simon ◽  
M. F. Brennan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pancreatic Adenocarcinoma ◽  
Prior History ◽  
Healthy Controls ◽  
Degree Relative ◽  
Intraductal Papillary Mucinous Neoplasms ◽  
Increased Risk ◽  
Mucinous Neoplasms ◽  
History Of ◽  
And Control

173 Background: The epidemiology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is poorly defined. Methods: An epidemiologic questionnaire was administered to patients (pts) with IPMN (n=79), pancreatic adenocarcinoma (PC) (n=689) and healthy controls (n=307). Results were adjusted for age, gender and BMI. IPMN was defined either by surgical pathology (n=62) or characteristic endoscopic ultrasound appearance and cyst fluid CEA>200 ng/ml (n=17). Results: In unadjusted analysis IPMN pts were more likely to be ≥ 70 years of age (OR 5.40 [2.88, 10.46]) when compared with PC pts (OR 2.82) and controls. After adjustment for age, gender and BMI, current tobacco smoking was associated with PC (OR 3.06 [1.78, 5.23]) but not IPMN. Pts with IPMN more often had diabetes mellitus for >3 years compared with controls (OR 3.25 [1.45, 7.00], while pts with PC (OR 1.52 (0.86, 2.67]) did not. IPMN pts were more likely to have a history of hypercholesterolemia compared with controls (OR 1.77 [1.05-2.98]); this was not seen for PC pts (OR 1.16 [0.87-1.55]). A first degree relative with PC was not associated with increased risk for IPMN (OR 0.84 [0.27, 2.62]) or PC (OR 1.48 [0.82, 2.67]). Compared to PC, pts with IPMN were more likely to have a history of an unrelated cancer (OR 1.84 [1.08, 3.14]). Conclusions: Risk factors for IPMN and PC may differ. Compared to PC and control pts, IPMN patients were older; more often had diabetes mellitus and hypercholesterolemia; and did not currently smoke. IPMN was more often associated with a prior history of cancer than PC. No significant financial relationships to disclose.

scholarly journals A Possible Association of Diindolylmethane with Pulmonary Embolism and Deep Venous Thrombosis

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Peter V. Bui ◽  
Maan Moualla ◽  
Dona J. Upson
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thromboembolism ◽  
Lower Extremity ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Single Case ◽  
The United States ◽  
Middle Lobe ◽  
History Of ◽  
Right Middle Lobe

Introduction.3,3′-Diindolylmethane is available as a supplement in the United States for “cancer prevention” and “augmentation of physical fitness.” A derivative of indole-3-carbinol found in plants, diindolylmethane, binds to receptors associated with the sex steroid pathways and has unclear effects on estrogen and androgen physiology. We present a patient who had been taking diindolylmethane and developed right lower extremity deep venous thrombosis and bilateral pulmonary embolism.Case Presentation.A 65-year-old man presented with swelling, erythema, and warmth of his right lower extremity for three to four weeks. He had been taking diindolylmethane one tablet daily for three to four months. Risk factors for venous thromboembolism included tobacco use, personal history of possible pulmonary embolism, body mass index, and age. Imaging studies found extensive deep venous thrombosis in his right lower extremity and bilateral pulmonary embolism with probable right middle lobe infarction. Follow-up imaging showed chronic deep venous thrombosis in his right lower extremity.Discussion.As suggested in this single case, patients who take diindolylmethane may be at greater risk for venous thromboembolism. Further reports and studies are necessary in order to elucidate this possible association. Clinicians should question patients about supplements in the setting of venous thromboembolism.

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