Letters
pared with the ARMOUR study (DVT prevalence, 25%; SVT prevalence, 13%). This could possibly reflect a significant proportion of outpatients with peripheral vein infusion SVT (21%). However, clinical suspicion of upper-extremity SVT is somewhat different from that of upper-extremity DVT, as upperextremity SVT is generally based on the presence of a palpable cord with very localized pain and erythema in any part of the upper limb, which are not incorporated in the Constans score.3 The D-dimer role in suspected SVT of the upper limbs may be less reliable because a high rate of false-negative results has been reported for the low thrombotic burden of SVT.6 As far as we know, our management study1 is the largest known cohort of subjects with suspected upper extremity DVT and may have a clinical effect in centers other than tertiary care hospitals, such as outpatient clinics, where D-dimer testing may not be easily obtained and where repeated ultrasonography may be burdensome to patients. Further studies are needed to refine the most efficient approach for the diagnosis of suspected DVT and SVT of the upper limbs. Michelangelo Sartori, MD, PhD Benilde Cosmi, MD, PhD Author Affiliations: Department of Angiology and Blood Coagulation, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy. Corresponding Author: Michelangelo Sartori, MD, PhD, Department of Angiology and Blood Coagulation, S.Orsola Malpighi University Hospital, Via Albertoni, 15, Bologna ([email protected]). Conflict of Interest Disclosures: None reported. 1. Sartori M, Migliaccio L, Favaretto E, et al. Whole-arm ultrasound to rule out suspected upper-extremity deep venous thrombosis in outpatients. JAMA Intern Med. 2015;175(7):1226-1227. 2. Kleinjan A, Di Nisio M, Beyer-Westendorf J, et al. Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study. Ann Intern Med. 2014;160(7):451-457. 3. Constans J, Salmi LR, Sevestre-Pietri MA, et al. A clinical prediction score for upper extremity deep venous thrombosis. Thromb Haemost. 2008;99(1):202-207. 4. Bernardi E, Camporese G, Büller HR, et al; Erasmus Study Group. Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008;300(14):1653-1659. 5. Sevestre MA, Labarère J, Casez P, et al. Accuracy of complete compression ultrasound in ruling out suspected deep venous thrombosis in the ambulatory setting: a prospective cohort study. Thromb Haemost. 2009;102(1):166-172. 6. Sartori M, Migliaccio L, Favaretto E, et al. D-dimer for the diagnosis of upper extremity deep and superficial venous thrombosis. Thromb Res. 2015;135(4): 673-678.
Subclinical Hypothyroidism Overdiagnosis in Pregnant Women To the Editor In a recent issue of JAMA Internal Medicine, Maraka and colleagues1 describe a clinical case of a healthy pregnant woman complaining of fatigue during early gestation (8 weeks). Thyroid function tests showed a thyroid-stimulating hormone (TSH) level of 2.8 mIU/L, leading to the diagnosis of subclinical hypothyroidism, according to the recommendations of international guidelines.1-3 These guidelines state that in the absence of population-based reference ranges, the recommended fixed upper cutoff for TSH levels is 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second trimester.2,3 1872
In the case described by Maraka and colleagues, treatment with 50-μg levothyroxine resulted in hyperthyroid symptoms which led the patient to seek emergency care. Overtreatment may occur more often than we think. During pregnancy, human chorionic gonadotropin (hCG) stimulates the maternal thyroid, but in contrast to TSH, hCG production is not regulated via negative feedback from free thyroxine (FT4). Therefore, levothyroxine treatment during pregnancy may lead to high FT4 levels, particularly when treatment starts before the hCG peak (at around 10 weeks). Indeed, in a large clinical trial,4 10% of women treated for mild gestational thyroid dysfunction needed dose reduction. Most studies focus on low thyroid function, yet high thyroid function is associated with preeclampsia and decreased birth weights,5 indicating that more data are needed on the effects of high thyroid hormone levels and levothyroxine treatment. As the authors1 point out, the proportion of women diagnosed with subclinical hypothyroidism is likely too high. We fully agree on this point but feel that a crucial factor that could aid physicians in decision making remains underaddressed in their report. Since the publication of the guidelines,2,3 14 sufficiently sized studies on reference ranges have been published. Although reference ranges differ according to population characteristics (eg, iodine status, ethnicity, and body mass index), 12 of these studies reported an upper trimester–specific TSH limit that was higher than 2.5 or 3.0 mIU/L.5 In addition, sensitivity analyses show that identification of women at risk for adverse pregnancy outcomes associated with high TSH is better when using a population-based cutoff as compared with the fixed TSH cutoff levels.5 These data strongly suggest that a large proportion of women worldwide will be overdiagnosed with subclinical hypothyroidism when fixed upper limits of TSH of 2.5 or 3.0 mIU/L are used instead of population-based reference ranges. We believe that doctors without access to population-based reference ranges are more likely to correctly diagnose subclinical hypothyroidism by adapting population-based reference ranges from populations with similar demographic characteristics.
Tim. I. M. Korevaar, MD Marco Medici, MD, PhD Robin P. Peeters, MD, PhD Author Affiliations: Rotterdam Thyroid Center, Erasmus University Medical Center, the Netherlands. Corresponding Author: Tim. I. M. Korevaar, MD, Erasmus University Medical Center, Rotterdam Thyroid Center, Molewaterplein 51, 3015 GE, Rotterdam, Zuid-Holland 3051 GE, the Netherlands ([email protected]). Conflict of Interest Disclosures: None reported. 1. Maraka S, O’Keeffe DT, Montori VM. Subclinical hypothyroidism during pregnancy–should you expect this when you are expecting? a teachable moment. JAMA Intern Med. 2015;175(7):1088-1089. 2. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-2565. 3. Stagnaro-Green A, Abalovich M, Alexander E, et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and
JAMA Internal Medicine November 2015 Volume 175, Number 11 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
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Letters
management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. 4. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493-501. 5. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal? Clin Chem. 2015;61(5):704-713.
In Reply We were pleased to read the letter from the Rotterdam Thyroid Center, and we thank Dr Korevaar and colleagues for their comments in response to our recent publication.1 Currently, in the absence of a laboratory trimester-specific reference range for thyroid-stimulating hormone (TSH) levels, the guidelines recommend a fixed upper limit of 2.5 mIU/L for first trimester and 3.0 mIU/L for second and third trimesters of pregnancy.2 Implementation of a fixed cutoff rather than a population-based cutoff for TSH levels could lead to overdiagnosis of subclinical hypothyroidism in pregnancy and to subsequent overtreatment. As Korevaar et al point out, the reference range for TSH and free thyroxine vary with geography and ethnic origin.3,4 With multiple population-based studies showing an upper trimester–specific TSH limit higher than 2.5 or 3 mIU/L,4 the current fixed cutoff TSH levels seem problematic. However, while the appropriate reference range for TSH levels is important for helping the physicians establish the diagnosis of subclinical hypothyroidism, adapting the range is only 1 step in the decision-making process. Perhaps of greater value would be to identify the TSH levels above which levothyroxine use leads to better outcomes. For nonpregnant adults with subclinical hypothyroidism, recommendations for treatment are stronger when TSH levels exceed 10 mIU/L.5 Similarly, we believe that a treatment threshold should be established for subclinical hypothyroidism in pregnancy. Evidence from small observational studies with various definitions of subclinical hypothyroidism, including a different cutoff for TSH levels, imprecise results, and high risk of bias, support an association of subclinical hypothyroidism during pregnancy with multiple adverse maternal and neonatal outcomes. However, there is still uncertainty regarding the effect of levothyroxine use on improving those outcomes. It is possible that pregnant women with higher TSH levels, and therefore more severe thyroid dysfunction, would benefit from levothyroxine hormone therapy, whereas while pregnant women who have milder elevations of their TSH level may have little or no benefit at all. Randomized clinical trials are urgently needed to assess the effectiveness of levothyroxine therapy in preventing adverse maternal and neonatal events in pregnant women with subclinical hypothyroidism and to define the upper limit of TSH where treatment leads to more good than harm. Trialists should set up TSH strata within such trials to uncover a treatmentdefined upper limit of normal TSH level in pregnancy. An ongoing randomized clinical trial (NCT00388297) may offer some answers in the near future. High-risk pregnant women (eg, women with multiple gestation pregnancies and/or medical comorbidities) have been excluded from this trial unfortunately. Additional trials, including trials studying populations of high-risk pregnant women, women from iodine-deficient areas, or women with positive thyroid peroxidase antibodies, may identify other subgroups in whom levothyroxine use may jamainternalmedicine.com
be beneficial. While waiting for more reliable evidence, clinicians should engage in frank shared decision making with pregnant women diagnosed with subclinical hypothyroidism to determine together what is best for each patient. Spyridoula Maraka, MD Naykky Singh Ospina, MD Victor M. Montori, MD Author Affiliations: Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. Corresponding Author: Victor M. Montori, MD, 200 First St SW, Rochester, MN 55905 ([email protected]). Conflict of Interest Disclosures: None reported. Correction: This article was corrected on November 12, 2015, to fix the spelling of Dr Korevaar’s name. 1. Maraka S, O’Keeffe DT, Montori VM. Subclinical hypothyroidism during pregnancy—should you expect this when you are expecting? a teachable moment. JAMA Intern Med. 2015;175(7):1088-1089. 2. Stagnaro-Green A, Abalovich M, Alexander E, et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. 3. Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ. 2014;349:g4929. 4. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal? Clin Chem. 2015;61(5):704-713. 5. Garber JR, Cobin RH, Gharib H, et al; American Association Of Clinical Endocrinologists And American Thyroid Association Taskforce On Hypothyroidism In Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-1235.
Imaging Tests for Suspected Deep Vein Thrombosis To the Editor It is with great interest that we read the article by Silveira et al1 regarding the utility of the Wells score for inpatients with suspected deep vein thrombosis (DVT). Based on the presented data, we agree that the accuracy of the Wells score for risk stratification of inpatients seems to be inferior to outpatients, although it should be noted the authors have not performed a direct comparison between both groups. This conclusion should be interpreted in the perspective of the complete diagnostic algorithm of suspected DVT since the Wells score was not designed as a stand-alone diagnostic test but rather as a first-line tool for determining the optimal order of subsequent imaging and/or blood tests to rule out or establish the diagnosis.2,3 A diagnostic strategy4 starting with the Wells score and followed by a D-dimer test and/or compression ultrasonography (CU) was shown to safely rule out DVT with an associated negative predictive value of greater than 99.5% and an average of 0.8 CU examinations per patient. It is unfortunate that D-dimer blood levels were not available in a larger number of patients in the study by Silveira et al,1 which would have provided more insight into the true diagnostic service of the Wells score in the patient category under study.1 We hypothesize that, analogously to the comparable diagnostic strategy of suspected acute pulmonary embolism (PE), the specificity of both the decision rule and D-dimer blood test is considerably decreased in patients who are hospitalized compared with outpatients because of underlying and often acute (Reprinted) JAMA Internal Medicine November 2015 Volume 175, Number 11
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Pittsburgh User on 12/04/2015
1873
pared with the ARMOUR study (DVT prevalence, 25%; SVT prevalence, 13%). This could possibly reflect a significant proportion of outpatients with peripheral vein infusion SVT (21%). However, clinical suspicion of upper-extremity SVT is somewhat different from that of upper-extremity DVT, as upperextremity SVT is generally based on the presence of a palpable cord with very localized pain and erythema in any part of the upper limb, which are not incorporated in the Constans score.3 The D-dimer role in suspected SVT of the upper limbs may be less reliable because a high rate of false-negative results has been reported for the low thrombotic burden of SVT.6 As far as we know, our management study1 is the largest known cohort of subjects with suspected upper extremity DVT and may have a clinical effect in centers other than tertiary care hospitals, such as outpatient clinics, where D-dimer testing may not be easily obtained and where repeated ultrasonography may be burdensome to patients. Further studies are needed to refine the most efficient approach for the diagnosis of suspected DVT and SVT of the upper limbs. Michelangelo Sartori, MD, PhD Benilde Cosmi, MD, PhD Author Affiliations: Department of Angiology and Blood Coagulation, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy. Corresponding Author: Michelangelo Sartori, MD, PhD, Department of Angiology and Blood Coagulation, S.Orsola Malpighi University Hospital, Via Albertoni, 15, Bologna ([email protected]). Conflict of Interest Disclosures: None reported. 1. Sartori M, Migliaccio L, Favaretto E, et al. Whole-arm ultrasound to rule out suspected upper-extremity deep venous thrombosis in outpatients. JAMA Intern Med. 2015;175(7):1226-1227. 2. Kleinjan A, Di Nisio M, Beyer-Westendorf J, et al. Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study. Ann Intern Med. 2014;160(7):451-457. 3. Constans J, Salmi LR, Sevestre-Pietri MA, et al. A clinical prediction score for upper extremity deep venous thrombosis. Thromb Haemost. 2008;99(1):202-207. 4. Bernardi E, Camporese G, Büller HR, et al; Erasmus Study Group. Serial 2-point ultrasonography plus D-dimer vs whole-leg color-coded Doppler ultrasonography for diagnosing suspected symptomatic deep vein thrombosis: a randomized controlled trial. JAMA. 2008;300(14):1653-1659. 5. Sevestre MA, Labarère J, Casez P, et al. Accuracy of complete compression ultrasound in ruling out suspected deep venous thrombosis in the ambulatory setting: a prospective cohort study. Thromb Haemost. 2009;102(1):166-172. 6. Sartori M, Migliaccio L, Favaretto E, et al. D-dimer for the diagnosis of upper extremity deep and superficial venous thrombosis. Thromb Res. 2015;135(4): 673-678.
Subclinical Hypothyroidism Overdiagnosis in Pregnant Women To the Editor In a recent issue of JAMA Internal Medicine, Maraka and colleagues1 describe a clinical case of a healthy pregnant woman complaining of fatigue during early gestation (8 weeks). Thyroid function tests showed a thyroid-stimulating hormone (TSH) level of 2.8 mIU/L, leading to the diagnosis of subclinical hypothyroidism, according to the recommendations of international guidelines.1-3 These guidelines state that in the absence of population-based reference ranges, the recommended fixed upper cutoff for TSH levels is 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second trimester.2,3 1872
In the case described by Maraka and colleagues, treatment with 50-μg levothyroxine resulted in hyperthyroid symptoms which led the patient to seek emergency care. Overtreatment may occur more often than we think. During pregnancy, human chorionic gonadotropin (hCG) stimulates the maternal thyroid, but in contrast to TSH, hCG production is not regulated via negative feedback from free thyroxine (FT4). Therefore, levothyroxine treatment during pregnancy may lead to high FT4 levels, particularly when treatment starts before the hCG peak (at around 10 weeks). Indeed, in a large clinical trial,4 10% of women treated for mild gestational thyroid dysfunction needed dose reduction. Most studies focus on low thyroid function, yet high thyroid function is associated with preeclampsia and decreased birth weights,5 indicating that more data are needed on the effects of high thyroid hormone levels and levothyroxine treatment. As the authors1 point out, the proportion of women diagnosed with subclinical hypothyroidism is likely too high. We fully agree on this point but feel that a crucial factor that could aid physicians in decision making remains underaddressed in their report. Since the publication of the guidelines,2,3 14 sufficiently sized studies on reference ranges have been published. Although reference ranges differ according to population characteristics (eg, iodine status, ethnicity, and body mass index), 12 of these studies reported an upper trimester–specific TSH limit that was higher than 2.5 or 3.0 mIU/L.5 In addition, sensitivity analyses show that identification of women at risk for adverse pregnancy outcomes associated with high TSH is better when using a population-based cutoff as compared with the fixed TSH cutoff levels.5 These data strongly suggest that a large proportion of women worldwide will be overdiagnosed with subclinical hypothyroidism when fixed upper limits of TSH of 2.5 or 3.0 mIU/L are used instead of population-based reference ranges. We believe that doctors without access to population-based reference ranges are more likely to correctly diagnose subclinical hypothyroidism by adapting population-based reference ranges from populations with similar demographic characteristics.
Tim. I. M. Korevaar, MD Marco Medici, MD, PhD Robin P. Peeters, MD, PhD Author Affiliations: Rotterdam Thyroid Center, Erasmus University Medical Center, the Netherlands. Corresponding Author: Tim. I. M. Korevaar, MD, Erasmus University Medical Center, Rotterdam Thyroid Center, Molewaterplein 51, 3015 GE, Rotterdam, Zuid-Holland 3051 GE, the Netherlands ([email protected]). Conflict of Interest Disclosures: None reported. 1. Maraka S, O’Keeffe DT, Montori VM. Subclinical hypothyroidism during pregnancy–should you expect this when you are expecting? a teachable moment. JAMA Intern Med. 2015;175(7):1088-1089. 2. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-2565. 3. Stagnaro-Green A, Abalovich M, Alexander E, et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and
JAMA Internal Medicine November 2015 Volume 175, Number 11 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Pittsburgh User on 12/04/2015
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Letters
management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. 4. Lazarus JH, Bestwick JP, Channon S, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med. 2012;366(6):493-501. 5. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal? Clin Chem. 2015;61(5):704-713.
In Reply We were pleased to read the letter from the Rotterdam Thyroid Center, and we thank Dr Korevaar and colleagues for their comments in response to our recent publication.1 Currently, in the absence of a laboratory trimester-specific reference range for thyroid-stimulating hormone (TSH) levels, the guidelines recommend a fixed upper limit of 2.5 mIU/L for first trimester and 3.0 mIU/L for second and third trimesters of pregnancy.2 Implementation of a fixed cutoff rather than a population-based cutoff for TSH levels could lead to overdiagnosis of subclinical hypothyroidism in pregnancy and to subsequent overtreatment. As Korevaar et al point out, the reference range for TSH and free thyroxine vary with geography and ethnic origin.3,4 With multiple population-based studies showing an upper trimester–specific TSH limit higher than 2.5 or 3 mIU/L,4 the current fixed cutoff TSH levels seem problematic. However, while the appropriate reference range for TSH levels is important for helping the physicians establish the diagnosis of subclinical hypothyroidism, adapting the range is only 1 step in the decision-making process. Perhaps of greater value would be to identify the TSH levels above which levothyroxine use leads to better outcomes. For nonpregnant adults with subclinical hypothyroidism, recommendations for treatment are stronger when TSH levels exceed 10 mIU/L.5 Similarly, we believe that a treatment threshold should be established for subclinical hypothyroidism in pregnancy. Evidence from small observational studies with various definitions of subclinical hypothyroidism, including a different cutoff for TSH levels, imprecise results, and high risk of bias, support an association of subclinical hypothyroidism during pregnancy with multiple adverse maternal and neonatal outcomes. However, there is still uncertainty regarding the effect of levothyroxine use on improving those outcomes. It is possible that pregnant women with higher TSH levels, and therefore more severe thyroid dysfunction, would benefit from levothyroxine hormone therapy, whereas while pregnant women who have milder elevations of their TSH level may have little or no benefit at all. Randomized clinical trials are urgently needed to assess the effectiveness of levothyroxine therapy in preventing adverse maternal and neonatal events in pregnant women with subclinical hypothyroidism and to define the upper limit of TSH where treatment leads to more good than harm. Trialists should set up TSH strata within such trials to uncover a treatmentdefined upper limit of normal TSH level in pregnancy. An ongoing randomized clinical trial (NCT00388297) may offer some answers in the near future. High-risk pregnant women (eg, women with multiple gestation pregnancies and/or medical comorbidities) have been excluded from this trial unfortunately. Additional trials, including trials studying populations of high-risk pregnant women, women from iodine-deficient areas, or women with positive thyroid peroxidase antibodies, may identify other subgroups in whom levothyroxine use may jamainternalmedicine.com
be beneficial. While waiting for more reliable evidence, clinicians should engage in frank shared decision making with pregnant women diagnosed with subclinical hypothyroidism to determine together what is best for each patient. Spyridoula Maraka, MD Naykky Singh Ospina, MD Victor M. Montori, MD Author Affiliations: Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota. Corresponding Author: Victor M. Montori, MD, 200 First St SW, Rochester, MN 55905 ([email protected]). Conflict of Interest Disclosures: None reported. Correction: This article was corrected on November 12, 2015, to fix the spelling of Dr Korevaar’s name. 1. Maraka S, O’Keeffe DT, Montori VM. Subclinical hypothyroidism during pregnancy—should you expect this when you are expecting? a teachable moment. JAMA Intern Med. 2015;175(7):1088-1089. 2. Stagnaro-Green A, Abalovich M, Alexander E, et al; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081-1125. 3. Negro R, Stagnaro-Green A. Diagnosis and management of subclinical hypothyroidism in pregnancy. BMJ. 2014;349:g4929. 4. Medici M, Korevaar TI, Visser WE, Visser TJ, Peeters RP. Thyroid function in pregnancy: what is normal? Clin Chem. 2015;61(5):704-713. 5. Garber JR, Cobin RH, Gharib H, et al; American Association Of Clinical Endocrinologists And American Thyroid Association Taskforce On Hypothyroidism In Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-1235.
Imaging Tests for Suspected Deep Vein Thrombosis To the Editor It is with great interest that we read the article by Silveira et al1 regarding the utility of the Wells score for inpatients with suspected deep vein thrombosis (DVT). Based on the presented data, we agree that the accuracy of the Wells score for risk stratification of inpatients seems to be inferior to outpatients, although it should be noted the authors have not performed a direct comparison between both groups. This conclusion should be interpreted in the perspective of the complete diagnostic algorithm of suspected DVT since the Wells score was not designed as a stand-alone diagnostic test but rather as a first-line tool for determining the optimal order of subsequent imaging and/or blood tests to rule out or establish the diagnosis.2,3 A diagnostic strategy4 starting with the Wells score and followed by a D-dimer test and/or compression ultrasonography (CU) was shown to safely rule out DVT with an associated negative predictive value of greater than 99.5% and an average of 0.8 CU examinations per patient. It is unfortunate that D-dimer blood levels were not available in a larger number of patients in the study by Silveira et al,1 which would have provided more insight into the true diagnostic service of the Wells score in the patient category under study.1 We hypothesize that, analogously to the comparable diagnostic strategy of suspected acute pulmonary embolism (PE), the specificity of both the decision rule and D-dimer blood test is considerably decreased in patients who are hospitalized compared with outpatients because of underlying and often acute (Reprinted) JAMA Internal Medicine November 2015 Volume 175, Number 11
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Pittsburgh User on 12/04/2015
1873
