Establishing a normal range for d‐dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis

Morse, Michael A.

doi:10.1111/j.1538-7836.2004.00776.x

Cited by 87 publications

(45 citation statements)

References 7 publications

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“…[200][201][202][203] This reduces the test's specifi city, and by the third trimester, only a minority of healthy pregnant women will have a negative D-dimer result when highly sensitive assays and the same cut point as in the nonpregnant population are used. [203][204][205][206] A prospective cohort study of a moderately sensitive but more specifi c D-dimer assay for DVT during pregnancy reported a sensitivity of 100% (95% CI, 77%-100%) and a specifi city of 60% (95% CI, 62%-68%). 186 False-positive results were docu mented in only 51% of third-trimester patients, suggesting that this test warrants further investigation.…”

Section: Pretest Probabilitymentioning

confidence: 99%

Diagnosis of DVT

Bates

Jaeschke

Stevens

et al. 2012

Chest

576

192

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Section: Pretest Probabilitymentioning

confidence: 99%

Diagnosis of DVT

Bates

Jaeschke

Stevens

et al. 2012

Chest

576

192

View full text Add to dashboard Cite

“…[51][52][53][54] This reduces the test's specificity for VTE and by the third trimester, only a minority of healthy pregnant women will have a negative Ddimer results when highly sensitive assays and the same cutoff point as in the nonpregnant population are used. [54][55][56][57] An accuracy study of the whole-blood D-dimer assay in pregnant women with suspected DVT reported a sensitivity of 100% (95% CI, 77 to 100%) and a specificity of 60% (95% CI, 62 to 68%). 58 False-positive results were documented in only 51% of third-trimester patients, suggesting that this test warrants further investigation.…”

Section: D-dimer Testing For Suspected Venous Thromboembolism During mentioning

confidence: 99%

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

Bates

2012

Semin Thromb Hemost

103

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).D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. This specific cross-linked fibrin degradation product is formed through the sequential action thrombin, activated factor XIII (FXIIIa), and plasmin (►Fig. 1). 1-3 First, thrombin, generated when coagulation is activated, converts fibrinogen to fibrin and activates FXIII. Second, FXIIIa covalently crosslinks D-domains in adjacent fibrin monomers. Third, plasmin (formed on the fibrin surface by plasminogen activation) cleaves substrate fibrin at specific sites, and when it cleaves fibrin cross-linked by FXIIIa, it generates D-dimer. D-dimer is cleared through the kidneys and the reticuloendothelial system and has a plasma half-life of approximately 8 hours. 4 Low levels of D-dimer can be found circulating under normal physiologic conditions, while pathologically elevated levels can be found in any condition associated with enhanced fibrin formation and fibrinolysis (►Table 1). 1-3 The utility of D-dimer measurement has been evaluated in several clinical situations; however, the D-dimer assays have been best validated for the exclusion of venous thromboembolism (VTE) and the diagnosis and monitoring of disseminated intravascular coagulation (DIC). This article will review the available evidence for the utilization of D-dimer antigen measurement in the management of thrombotic and bleeding disorders. Measurement of D-DimerThe presence of D-dimer in plasma can be detected using monoclonal antibodies that recognize an epitope present in FXIIIa-cross-linked fragment D-domain of fibrin but not in fibrinogen degradation products or noncross-linked fibrin degradation products. Many different D-dimer assays have been developed and marketed. All of these tests rely on the use of monoclonal antibodies to detect D-dimer molecules. In general, three techniques are available to assay D-dimer (►Fig. 2). 1-3 These are (1) enzyme-linked immunosorbent assays (ELISAs) that rely on antibody capture and labeling of D-dimer; (2) a whole-blood agglutination assay (SimpliRED, Siemens Healthcare Diagnostics, Newcastle, DE), that uses a bispecific antibody conjugate with binding sites for both D-dimer and a red cell antigen and is performed on whole blood; (3) latex agglutination assays that also use bispecific antibodies with specificity for the latex particle and D-dimer antigen. Earlier latex agglutination assays for D-dimer were qualitative or semiquantitative; however, newer automated, quantitative D-dimer assays (which are immunoturbidometric assays) are performed on routine, automated coagulation instruments. It is important to recognize that results are not comparable between different assays, even between those of similar formats. Potential reasons for the lack of comparable results are listed in ►Table 2. Numeric results of D-dimerAbstract D-dimer is a global indicator of coagulation activation and fibrinolysis and, therefore, an indirect marker of thrombotic activity. The utility of D-dimer measur...

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“…Table V summarises the D-dimer ranges in recent studies sorted by trimester. Pregnant women with confi rmed VTE have much higher D-dimer levels than pregnant women without VTE, and pregnancy-specifi c threshold values for each trimester have been suggested on this basis [111,113,118,120,121]. Currently, several diff erent D-dimer testsstratifi ed as moderately sensitive or highly sensitive -are available, and test results vary depending on the diff erent assays in use.…”

Section: D-dimer Testingmentioning

confidence: 99%

“…Guideline recommendations about D-dimer testing during pregnancy have been controversial [27,49,74]. During an uncomplicated pregnancy, there is a steady increase in D-dimer levels with a peak on the fi rst day after delivery [38,[109][110][111]. Multiple pregnancies [112,113], pregnancy complications (e.g., pre-eclampsia, abruptio placentae, preterm labour, OHSS) [112,114,115] and FVL mutation [116] have been demonstrated to increase D-dimer levels further during pregnancy.…”

Section: D-dimer Testingmentioning

confidence: 99%

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

Linnemann¹,

Scholz

Rott

et al. 2016

Vasa

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EpidemiologyVTE is a leading cause of maternal morbidity in the developed world and, in the case of PE, of mortality as well [1]. While the relative risk of VTE is greatly increased during pregnancy compared with that in non-pregnant women, the absolute risk remains low: estimates of the incidence of pregnancy-associated VTE have varied from 1:500 to 1:1500 pregnancies [2 -7]. The risk of VTE is approximately 5-fold greater in pregnant women than in non-pregnant women.Approximately 80 % of pregnancy-associated VTEs are isolated DVTs, and approximately 20 % are PEs or both DVTs and PEs [5]. Although a systematic review reported weighted event rates for DVT of 21.9 %, 33.7 % and 47.6 % for the fi rst, second and third trimesters, respectively [6], a recent study suggested that the risk might in fact increase exponentially over the duration of the pregnancy [7], with 12.4 % of VTEs diagnosed in the fi rst trimester, 15.3 % in the second trimester and 72.3 % in the third trimester. This detailed risk assessment for each gestational week demonstrated a 21-fold increased risk for the last two weeks before delivery [7]. Summary: Pregnancy and the postpartum period are associated with an increased risk of venous thromboembolism (VTE). Over the past decade, new diagnostic algorithms have been established, combining clinical probability, laboratory testing and imaging studies for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the non-pregnant population. However, there is no such generally accepted algorithm for the diagnosis of pregnancy-associated VTE. Studies establishing clinical prediction rules have excluded pregnant women, and prediction scores currently in use have not been prospectively validated in pregnancy or during the postpartum period. D-dimers physiologically increase throughout pregnancy and peak at delivery, so a negative D-dimer test result, based on the reference values of non-pregnant subjects, becomes unlikely in the second and third trimesters. Imaging studies therefore play a major role in confi rming suspected DVT or PE in pregnant women. Major concerns have been raised against radiologic imaging because of foetal radiation exposure, and doubts about the diagnostic value of ultrasound techniques in attempting to exclude isolated iliac vein thrombosis grow stronger as pregnancy progresses. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarise evidence from the available literature and aim to establish a more uniform strategy for diagnosing pregnancy-associated VTE. Review Diagnosis of pregnancy-associated

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Establishing a normal range for d‐dimer levels through pregnancy to aid in the diagnosis of pulmonary embolism and deep vein thrombosis

Cited by 87 publications

References 7 publications

Diagnosis of DVT

Diagnosis of DVT

D-Dimer Assays in Diagnosis and Management of Thrombotic and Bleeding Disorders

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

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