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ORIGINAL ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 2  |  Page : 94-99

The effect of short-term elevation of 17B estradiol (E2) levels on the coagulation system as measured by D-Dimer in women undergoing in vitro fertilization


1 Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and IVF, Technion, Haifa, Israel
2 Department of Haematology, Carmel Medical Centre, Rappaport Faculty of Medicine, Technion, Haifa, Israel

Date of Web Publication4-Sep-2014

Correspondence Address:
Zofnat Wiener-Megnazi
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and IVF, Technion, Haifa
Israel
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-2907.140124

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  Abstract 

Objective: The objective of this study is to evaluate the short-term effect of elevated estrogen levels on the coagulation system, as measured by D-dimer in in vitro fertilization (IVF). Design: Prospective open cohort trial. Setting: University affiliated IVF division. Patients: A total of 62 IVF patients. Interventions: Serum 17B estradiol (E2) and D-dimer levels were measured in patients undergoing long protocol IVF at down regulation (DR) (E2 ≤200 pmol/L) and on the day of oocyte retrieval (OR). Data was analyzed and correlated with clinical and laboratory parameters. Main Outcome Measures: Serum D-dimer levels at DR and oocyte pick-up days and their association with clinical and laboratory parameters. Results: From DR to OR day serum D-dimer levels increased in 31 (66%) and decreased in 16 (34%) women. Mean increased was by 21% ( P < 0.024). Among women with an increase in D-dimer levels, mean increase was 44% above levels on DR day. D-dimer levels increased among all patients with a body mass index (BMI) ≥30 kg/m 2 and among 57.6% of patients with BMI <30 kg/m 2 ( P < 0.009) and increase tended to be higher among obese patients ( P = 0.06). Prothrombin time (PT) on DR day was shorter among patients whose D-dimer levels increased ( P < 0.017). Conclusions: D-dimer serum levels increase during ovarian stimulation; however, levels rarely exceed the normal range. Therefore, short-term exposure to supraphysiological E2 levels in IVF does not seem to affect thromboembolic status as expressed by D-dimer levels. D-dimer increase was associated with a shorter PT on DR day and tended to be comprehensive and higher among overweight women. Therefore, obesity may pose a risk factor for thromboembolism.

Keywords: Body mass index, D-dimer, estradiol, in vitro fertilization, thrombosis


How to cite this article:
Sokal-Arnon T, Wiener-Megnazi Z, Auslender R, Kassel A, Quitt M, Dirnfeld M. The effect of short-term elevation of 17B estradiol (E2) levels on the coagulation system as measured by D-Dimer in women undergoing in vitro fertilization. IVF Lite 2014;1:94-9

How to cite this URL:
Sokal-Arnon T, Wiener-Megnazi Z, Auslender R, Kassel A, Quitt M, Dirnfeld M. The effect of short-term elevation of 17B estradiol (E2) levels on the coagulation system as measured by D-Dimer in women undergoing in vitro fertilization. IVF Lite [serial online] 2014 [cited 2022 May 23];1:94-9. Available from: http://www.ivflite.org/text.asp?2014/1/2/94/140124


  Introduction Top


Though thromboembolic (TE) events are relatively rare among young women, they bare serious consequences. Their incidence increases in the presence of risk factors such as thrombophilia and prolonged exposure to high levels of exogenous estrogen, such as oral contraceptive agents and estrogen replacement therapy. [1],[2],[3],[4]

TE events pose a diagnostic challenge, especially in the young population with a low prevalence of TE events. D-dimer is a fibrin degradation product, which is a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two cross-linked D fragments of the fibrinogen protein. D-dimer is considered a marker of hypercoagulable state and of endogenous fibrinolysis. Increased D-dimer is detectable in patients affected by thrombosis. [5] Normal D-dimer level is <500 ng/ml. D-dimer is usually used in clinical management due to its high negative predictive value in suspected thrombosis, particularly in a deep vein thrombosis and/or pulmonary embolism. [6] Several studies have demonstrated increased D-dimer levels also in patients affected by subclinical thrombophilia without ongoing thrombosis. [7] Other clinical conditions associated with elevated D-dimer levels are malignancy, chronic inflammation, infections, acute coronary syndromes, necrosis and eldership. [8],[9],[10],[11],[12],[13] In particular, long-standing hyperestrogenic states associated with either endogenous (pregnancy) or exogenous (use of oral contraception or hormonal replacement therapy) estrogens, have been related to alterations in some coagulation parameters favoring hypercoagulation and have been implicated as a cause of venous thromboembolism. [1],[2],[3],[4] They have also been associated with an increase in D-dimer level. [1],[14],[15],[16]

In vitro fertilization (IVF) involves the administration of exogenous gonadotropin hormones to stimulate the ovaries, induce ovulation and support implantation. As a result, endogenous E2 levels increase from minimal to supraphysiological levels during a period of several days.

Since 30 years ago, indications for assisted reproductive technologies have expanded, and the use of controlled ovarian hyperstimulation and IVF has been continuously increasing. TE complications have been reported among patients undergoing ovarian stimulation and IVF. [17] Consequently, there is an increasing need to understand the underlying risk factors and avoid TE events which may result in significant morbidity and mortality in a young female population. In contrast to conditions with long duration of exposure to estrogens such as pregnancy, the use of oral contraception pills and hormone replacement therapy, women undergoing IVF treatments and do not conceive, are exposed to transient high estrogen levels for a short period. In the "long protocol" gonadotropin releasing hormone (GnRH) agonists are used to down regulate the pituitary, resulting in minimal plasma estrogen levels (postmenopausal levels) at baseline. Subsequently, stimulation with gonadotropins causes fast and significant increases in endogenous estrogen levels (similar or even higher than maximal levels of estrogen during pregnancy), by stimulating maturation of multiple ovarian follicles. The ovarian stimulation usually continues 8-14 days and as a result, estrogen levels are high for a relative short time.

Therefore, patients undergoing IVF present an opportunity to study isolated short-term estrogen effect on the coagulation system. Data is scant regarding the assessment of D-dimer levels among women undergoing IVF treatment and its correlation with estrogen levels along the treatment cycle. The objective of this study, therefore, was to measure D-dimer levels and their association with estradiol levels among IVF patients exposed to supraphysiologic endogenous E2 levels for a short time span of 8-14 days.


  Materials and methods Top


A total of 62 healthy patients scheduled to undergo IVF procedures were included in the study. The study was approved by the Institutional Review Board and written informed consent was obtained from all participants upon entering. Exclusion criteria included age over 40 years, smoking, personal or familial history of TE event or chronic illness. During the study period, women whose maximal E2 level was <2000 pmol/L were excluded from the study. All patients underwent long protocol IVF cycle. Pituitary desensitization was achieved using 800-1000 mcg/d of GnRH agonist (Superfact, Sanofi-Aventis, Frankfurt, Germany) administered at the mid-luteal or early follicular phase, followed by administration of 150-375 IU/d recombinant follicle-stimulating hormone or human menopausal gonadotropins (Gonal F, Merck Serono, Aubonne, Switzerland; Menogon, Ferring, Saint-Prex, Switzerland) for ovarian stimulation once pituitary down regulation (DR) was achieved. Cycle monitoring included serial vaginal sonographic measurements of follicular growth and endometrial thickness and serum E2 and progesterone levels. When four or more follicles reached a diameter of ≥18 mm and serum E2 was >2000 pmol/L, administration of subcutaneous 250 mcg of choriogonadotropin alfa (Ovitrelle, Merck Serono, Aubonne, Switzerland) was carried out, followed by transvaginal-guided oocyte retrieval (OR) 34-36 h later. Serum levels of D-dimer and E2 were taken on days of maximal DR and on OR. In addition, platelet count, fibrinogen level, prothrombin time (PT, expressed as seconds, percent's and international normalized ratio [INR]) and activated partial thromboplastin time ratio serum levels were taken on DR day. D-dimer serum levels were measured by the enzyme-linked immunosorbent assay vidas method. Demographic, clinical and laboratory data was recorded and analyzed.

Statistical analysis

The planned sample size (62 women) enabled us to detect a 0.4 standard deviation (SD) (medium effect) difference with 80% power and adjusted alpha of 0.01 for multiple comparisons. The final sample size (47 women), enabled us to detect a 0.4 SD (medium effect) difference of with 80% power and alpha of 0.02 for multiple comparisons and to identify significant coefficient correlation (≥0.5) with 80% power and alpha of 0.02. Analysis was performed using the SPSS statistical package version 15 (SPSS, Chicago, IL, USA). Paired t-test has been employed to analyze the ∆D-dimer. Comparison of D-dimer level between two body mass index (BMI) groups (<30 kg/m 2 , ≥30 kg/m 2 ) was performed by Mann-Whitney test. For correlation we used Pearson correlation coefficients. P values were two-sided and significance was defined as P < 0.05.


  Results Top


From the initial 62 participants enrolled, 47 met the protocol requirements. Mean patient's age and BMI were 28.7 ± 4.4 years and 26.3 ± 5.2 kg/m 2 respectively. Baseline clinical and coagulation characteristics are summarized in [Table 1]. Mean duration of ovarian stimulation until OR was 12.1 ± 5.4 days. Mean serum E2 levels at DR and OR days were 125 pmol/L ± 36 and 6549 pmol/L ± 3803 respectively. Mean serum D-dimer on DR and OR days were 208 ± 84 (range: 45-476) mcg/L and 245 ± 129 (range: 89-661) mcg/L respectively (P < 0.024) [Table 2]. From DR to OR day, serum D-dimer levels increased in 31 (66%) and decreased in 16 (34%) women. Mean increase in D-dimer level for all study population was 21%.
Table 1: Demographic, clinical and baseline laboratory parameters

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Table 2: Cycle parameters

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Among the 31 women with an increase in D-dimer levels, mean increase was 44% and a correlation trend was found between the ∆D-dimer and ∆ E2 (r = 0.3, P < 0.09). In two women (4.2%) D-dimer levels increased to > 500 ng/ml. The mean number of aspirated oocytes was 10.4 ± 5.5. Forty women (85%) of the study patients underwent embryo transfer. 19 (47.5%) became pregnant. An inverse correlation was found between D-dimer levels on OR day and number of mature and fertilized oocytes and rate of cleaved embryos (P < 0.01, P < 0.05, P < 0.02, respectively). No association was found between D-dimer levels on OR day or ∆D-dimer and occurrence of conception. Mean BMI of the patients with a positive ∆D-dimer was higher than that of patients with a negative ∆D-dimer (27.7 ± 5 kg/m 2 vs. 22.1 ± 2.4 kg/m 2 , P < 0.0001). 12 (25.5%) patients were obese (BMI ≥30 kg/m 2 ). A trend of correlation was found between BMI and D-dimer on OR day and ∆D-dimer (r = 0.294, P < 0.053, r = 0.273, P < 0.073). When patients were divided into two groups according to the obesity criteria for BMI, D-dimer levels increased from DR to OR day among all patients with BMI ≥30 kg/m 2 , whereas among non-obese patients, it increased only among 57% (P < 0.009) [Table 3]. A trend of association was found between ∆D-dimer and obesity, whereas among patients with BMI ≥30 kg/m 2 it was higher compared with patients with BMI <30 kg/m 2 (38.5% vs. a 18.8%, P = 0.06) [Figure 1]. PT on DR day was shorter among patients with a positive ∆D-dimer levels compared with patients with a negative ∆D-dimer (14.7 ± 1.1 s vs. 13.9 ± 0.8 s, P < 0.017, 98.38 ± 12.31% vs. 90.31 ± 10.58%, P < 0.036, INR-1.01 ± 0.07 vs. 1.07 ± 0.08, P < 0.037). A trend of correlation was found between fibrinogen levels on DR day and D-dimer level on OR day (r = 0.43, P < 0.09). No difference in fibrinogen levels was found between patients with a positive versus negative ∆D-dimer. No correlation was found between BMI and these coagulation parameters. None of the study participants have developed thromboembolism during or after the treatment cycle.
Figure 1: Comparison of ĢD-dimer (%) among obese versus non-obese patients. Closed rectangles represent range; horizontal lines represent mean; vertical lines represent standard deviation (P < 0.06)

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Table 3: Correlation between BMI and the percent of differentiation in D-dimer (DR to OR day)

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  Discussion Top


In this study, we found that the increase in E2 serum levels during ovarian stimulation by gonadotropins in IVF was accompanied by a significant increase in serum D-dimer levels among 2/3 of the patients. This finding is similar to the existing data regarding the elevation in D-dimer under chronic hyperestrogenic states. Cosman et al. have found that the administration of 0.625 mg conjugated equine estrogen for 6 months resulted in an increase in D-dimer level. [1] During normal pregnancy, there is a progressive increase in D-dimer serum levels to above the conventional normal threshold of 500 ng/ml. [14],[15] At the beginning of the second trimester, more than one-half of pregnant women have a D-dimer level that exceeds 500 ng/ml and by the third trimester, more than 90% of women will exceed these levels. [15] This increase restricts the use of D-dimer as a screening tool during pregnancy due to high false positive rate when venous thromboembolism is suspected in a pregnant woman. These above-mentioned long-standing hyperestrogenic states have been also implicated as a risk factor for venous thromboembolism. Estrogen replacement therapy, another situation with long-term exposure to estrogens, has been associated with two- to three-fold increased risk in the occurrence of venous thrombosis. [1] The women's health initiative hormone trials identified a 39% increase in ischemic stroke risk under the use of estrogen. [2]

In a recent meta-analysis, estrogen therapy was associated with a relative risk of 2.14-3.75 for the occurrence of thromboembolism. [3] These finding were in accordance with the results of Pιrez Gutthann et al., who have found that hormone replacement therapy was associated with a higher risk for venous thromboembolism (hazard ratio 2.11, 95% confidence interval 1.26-3.55). [4] IVF involves the administration of exogenous gonadotropin hormones to stimulate the ovaries, induce ovulation and support implantation. In the "long protocol" GnRH analogs are used to down regulate the pituitary, resulting in minimal plasma estradiol levels (equivalent to postmenopausal levels) at baseline. Subsequently, stimulation with gonadotropins sharply increases the secretion of endogenous estrogen to supraphysiological levels (similar or even higher than maximal levels of estrogen during pregnancy), by stimulating maturation of multiple ovarian follicles. Until the administration of human chorionic gonadotropin, which induces final oocyte maturation and a steroidogenetic shift from estradiol to progesterone by granulosa cells, ovarian stimulation usually lasts 8-14 days. As a result, estrogen levels are high for a relative short time. This is in contrast to various conditions that were described above, such as pregnancy, oral contraception pills and hormone replacement therapy, in which estrogen levels increase gradually and exposure is long-standing. The trend of correlation which was found between ∆D-dimer and ∆E2 among patients which increased their D-dimer levels may be due to the small size of the study. Our findings, at least partially, are in contrast to those of Magnani et al., [18] who studied the fibrinolytic status of 32 women undergoing IVF. They have found that as opposed to a decrease in Plasminogen activator inhibitor-1 and an increase in plasmin-alpha 2-antiplasmin complexes which were observed at high estrogen levels, (suggesting an increase in fibrinolytic potential), the products of fibrinolysis, as measured by D-dimer levels, decreased at high estrogen levels. On the other hand, they are in concordance with studies assessing D-dimer levels among women with ovarian hyperstimulation syndrome (OHSS). This syndrome occurs in 0.2-1% of IVF treatment cycles and constitutes a risk factor for TE events due to extremely high endogenous E2 levels. [19] Rogolino et al. have found that D-dimer levels were higher among women with OHSS, compared to IVF patients without OHSS and that levels correlated with serum E2 levels and number of aspirated oocytes. [20] Kodama et al. have found that markers of fibrinolysis including D-dimer can even precede the onset of OHSS. [21] In this study, elevation of D-dimer levels exceeded normal ranges only in 2 women (4.2%). This may imply that although healthy women are exposed to significantly higher estradiol levels during controlled ovarian stimulation in IVF, the relatively short duration of exposure probably does not pose an additional risk for venous thromboembolism as expressed by D-dimer. An important modifiable risk factor for thrombosis is obesity. Obesity, which is defined as a BMI ≥30 kg/m 2[22] has prevalence of 20-25% [21] and has been associated with a 2-3-fold higher risk of venous thrombosis in both sexes. [22],[23],[24],[25] In the study of Abdollahi et al., the relationship of obesity to thrombosis risk was not mediated by differences in levels of fibrinogen, factor VIII, factor IX and D-dimer. [22] Obese people have a further increase in thrombosis risk when they are exposed to other thrombosis risk factors, such as exogenous contraceptive or postmenopausal hormones. [22],[24] D-dimer levels increased from DR to OR day for all patients with BMI ≥30 kg/m 2 as opposed to only 57.6% in patients with BMI under 30 kg/m 2 . Among women with BMI ≥30 kg/m 2 ΔD-dimer was more than two fold (38% vs. 18%) the levels among non-obese women. Kabrhel et al., [26] in a prospective observational study among 4346 patients evaluated for pulmonary embolus, have found no correlation between BMI and positive D-dimer levels. These women were also characterized by higher baseline endogenous levels of thrombotic markers as PT compared with women whose D-dimer levels decreased. This may imply that higher tendency for coagulation may be associated with a different fibrinolytic response to estrogen, as measured by D-dimer. These results may imply that obese women (being already in a hypecoagulable state compared to women with lower BMI) [23],[25] who undergo IVF treatments do bare an additional risk factor for TE events. Large scale prospective studies are needed in order to validate our results in this preliminary study. The association of obesity with thrombosis is especially important because obesity is increasing dramatically world-wide and obese polycystic ovary or normal cycling patients are frequently seeking fertility treatments including, IVF. Therefore, this subpopulation of obese patients should be appropriately counseled prior to treatment regarding these risks.

 
  References Top

1.Cosman F, Baz-Hecht M, Cushman M, Vardy MD, Cruz JD, Nieves JW, et al. Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: A randomized-controlled study and review of the literature. Thromb Res 2005;116:1-13.  Back to cited text no. 1
    
2.Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002;288:321-33.  Back to cited text no. 2
    
3.Miller J, Chan BK, Nelson HD. Postmenopausal estrogen replacement and risk for venous thromboembolism: A systematic review and meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 2002;136:680-90.  Back to cited text no. 3
    
4.Pérez Gutthann S, García Rodríguez LA, Castellsague J, Duque Oliart A. Hormone replacement therapy and risk of venous thromboembolism: Population based case-control study. BMJ 1997;314:796-800.  Back to cited text no. 4
    
5.Perrier A, Bounameaux H. Cost-effective diagnosis of deep vein thrombosis and pulmonary embolism. Thromb Haemost 2001;86:475-87.  Back to cited text no. 5
    
6.Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: An overview. Thromb Haemost 1994;71:1-6.  Back to cited text no. 6
    
7.Arkel YS, Paidas MJ, Ku DH. The use of coagulation activation markers (soluble fibrin polymer, TpP, prothrombin fragment 1.2, thrombin-antithrombin, and D-dimer) in the assessment of hypercoagulability in patients with inherited and acquired prothrombotic disorders. Blood Coagul Fibrinolysis 2002;13:199-205.  Back to cited text no. 7
    
8.Le Blanche AF, Siguret V, Settegrana C, Bohus S, Le Masne de Chermont E, Andreux JP, et al. Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old. Angiology 1999;50:873-82.  Back to cited text no. 8
    
9.Francalanci I, Comeglio P, Alessandrello Liotta A, Cellai AP, Fedi S, Parretti E, et al. D-dimer plasma levels during normal pregnancy measured by specific ELISA. Int J Clin Lab Res 1997;27:65-7.  Back to cited text no. 9
    
10.Kinasewitz GT, Yan SB, Basson B, Comp P, Russell JA, Cariou A, et al. Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism [ISRCTN74215569]. Crit Care 2004;8:R82-90.  Back to cited text no. 10
    
11.So AK, Varisco PA, Kemkes-Matthes B, Herkenne-Morard C, Chobaz-Péclat V, Gerster JC, et al. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J Thromb Haemost 2003;1:2510-5.  Back to cited text no. 11
    
12.Di Micco P, De Lucia D, De Vita F, Niglio A, Di Micco G, Martinelli E, et al. Acquired cancer-related thrombophilia testified by increased levels of prothrombin frament 1+2 and d-dimer in patients affected by solid tumors. Exp Oncol 2002;24:108-11.  Back to cited text no. 12
    
13.Derhaschnig U, Laggner AN, Röggla M, Hirschl MM, Kapiotis S, Marsik C, et al. Evaluation of coagulation markers for early diagnosis of acute coronary syndromes in the emergency room. Clin Chem 2002;48:1924-30.  Back to cited text no. 13
    
14.Nolan TE, Smith RP, Devoe LD. Maternal plasma D-dimer levels in normal and complicated pregnancies. Obstet Gynecol 1993;81:235-8.  Back to cited text no. 14
    
15.Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: New diagnostic thresholds are needed. Clin Chem 2005;51:825-9.  Back to cited text no. 15
    
16.Quehenberger P, Kapiotis S, Pärtan C, Schneider B, Wenzel R, Gaiger A, et al. Studies on oral contraceptive-induced changes in blood coagulation and fibrinolysis and the estrogen effect on endothelial cells. Ann Hematol 1993;67:33-6.  Back to cited text no. 16
    
17.Chan WS, Dixon ME. The "ART" of thromboembolism: A review of assisted reproductive technology and thromboembolic complications. Thromb Res 2008;121:713-26.  Back to cited text no. 17
    
18.Magnani B, Tsen L, Datta S, Bader A. In vitro fertilization. Do short-term changes in estrogen levels produce increased fibrinolysis? Am J Clin Pathol 1999;112:485-91.  Back to cited text no. 18
    
19.Binder H, Dittrich R, Einhaus F, Krieg J, Müller A, Strauss R, et al. Update on ovarian hyperstimulation syndrome: Part 1-Incidence and pathogenesis. Int J Fertil Womens Med 2007;52:11-26.  Back to cited text no. 19
    
20.Rogolino A, Coccia ME, Fedi S, Gori AM, Cellai AP, Scarselli GF, et al. Hypercoagulability, high tissue factor and low tissue factor pathway inhibitor levels in severe ovarian hyperstimulation syndrome: Possible association with clinical outcome. Blood Coagul Fibrinolysis 2003;14:277-82.  Back to cited text no. 20
    
21.Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. Characteristics of blood hemostatic markers in a patient with ovarian hyperstimulation syndrome who actually developed thromboembolism. Fertil Steril 1995;64:1207-9.  Back to cited text no. 21
    
22.Abdollahi M, Cushman M, Rosendaal FR. Obesity: Risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003;89:493-8.  Back to cited text no. 22
    
23.Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thromboembolism incidence: The longitudinal investigation of thromboembolism etiology. Arch Intern Med 2002;162:1182-9.  Back to cited text no. 23
    
24.Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, et al. Estrogen plus progestin and risk of venous thrombosis. JAMA 2004;292:1573-80.  Back to cited text no. 24
    
25.Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007;44:62-9.  Back to cited text no. 25
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26.Kabrhel C, Mark Courtney D, Camargo CA Jr, Plewa MC, Nordenholz KE, Moore CL, et al. Factors associated with positive D-dimer results in patients evaluated for pulmonary embolism. Acad Emerg Med 2010;17:589-97.  Back to cited text no. 26
    

 
  Authors Top


Dr. Tamar Sokal-Arnon obtained her Medical Degree from the Technion - Israel institute of Technology in 2002. She obtained a specialist degree in obstetrics and gynecology at the Carmel Medical Center, Haifa, Israel, in 2009. From 2011 to 2013 Dr. Sokal-Arnon specialized in reproductive medicine at the McGill University Reproductive Center of the Royal Victoria Hospital in Montreal, Quebec, Canada. At present she is working as a senior physician in the IVF Unit of the Galilee Medical Center, Israel.


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