Clin Chem Lab Med 2014; 52(11): e257–e259
Letter to the Editor Frauke Bergmann*, Nadine Pingel, Andreas Czwalinna and Matthias Koch
D-Dimer in normal pregnancy: determination of reference values for three commercially available assays Keywords: D-dimer; pregnancy; reference values. DOI 10.1515/cclm-2014-0054 Received January 20, 2014; accepted April 18, 2014; previously published online May 7, 2014
To the Editor, D-dimer (DD) determination for several indications becomes more frequent in pregnant women. Its physiological increase during pregnancy has been described [1], but many physicians are not aware of this physiological behavior, especially in an emergency room setting. Determination of DD is a well-established assay and available in most laboratories to exclude deep venous thrombosis (DVT) in outpatients. The assay is also used to determine the optimal duration of anticoagulation in patients with previous DVT [2]. In normal pregnancy the increased risk of DVT is primarily due to physiological changes that predispose women to a procoagulant state [3]. In 1999, Eichinger et al. described the significant increase in DD-values over the course of pregnancy in women with or without Factor V-Leiden-Mutation (heterozygous) and no thromboembolic complications [4]. However, DD increases in pregnancy physiologically; but insufficient standardization of reference values in pregnancy and insufficient knowledge about the behavior of DD in pregnancy can result in misinterpretation and potentially overtreatment of otherwise healthy pregnant women [5]. The specificity of DD-assay to rule out DVT in a pregnant woman is low and decreases during pregnancy [6]. Some *Corresponding author: Frauke Bergmann, Labassociation Wagnerstibbe, Amedes Group, Georgstr. 50, 30159 Hannover, Germany, E-mail: [email protected] Nadine Pingel and Matthias Koch: Labassociation Wagnerstibbe, Amedes Group, Göttingen, Germany Andreas Czwalinna: Labassociation Wagnerstibbe, Amedes Group, Hannover, Germany
data on DD behavior during pre- and post-partum period are available [7]. Cut-off values for currently available DD assays were established in a non-pregnant population only. The aim of our study was to establish gestational age-specific reference intervals for three different DD-assays frequently used. We collected 1069 heparinized blood samples of pregnant women from 5th to 36th week of gestation. We excluded 47 women with a history of DVT. Samples were collected for routine maternal checkups as recommended in Germany. Aliquots were frozen at –20 °C the same day and analyzed in batches. For comparison of DD results obtained by heparinized and citrated specimens a conversion factor of 0.84 for heparinized plasma was used [8, 9]. Three frequently used commercially available LIAassays were chosen: Hemosil D-Dimer HS 500® (Instrumentation Laboratory), using ACL Top-analyzer; Innovance D-Dimer® (Siemens Healthcare) using BCS-analyzer and Tina-quant® (Roche) using Modular analyzer. All three assays have the same cut-off value of
Letter to the Editor Frauke Bergmann*, Nadine Pingel, Andreas Czwalinna and Matthias Koch
D-Dimer in normal pregnancy: determination of reference values for three commercially available assays Keywords: D-dimer; pregnancy; reference values. DOI 10.1515/cclm-2014-0054 Received January 20, 2014; accepted April 18, 2014; previously published online May 7, 2014
To the Editor, D-dimer (DD) determination for several indications becomes more frequent in pregnant women. Its physiological increase during pregnancy has been described [1], but many physicians are not aware of this physiological behavior, especially in an emergency room setting. Determination of DD is a well-established assay and available in most laboratories to exclude deep venous thrombosis (DVT) in outpatients. The assay is also used to determine the optimal duration of anticoagulation in patients with previous DVT [2]. In normal pregnancy the increased risk of DVT is primarily due to physiological changes that predispose women to a procoagulant state [3]. In 1999, Eichinger et al. described the significant increase in DD-values over the course of pregnancy in women with or without Factor V-Leiden-Mutation (heterozygous) and no thromboembolic complications [4]. However, DD increases in pregnancy physiologically; but insufficient standardization of reference values in pregnancy and insufficient knowledge about the behavior of DD in pregnancy can result in misinterpretation and potentially overtreatment of otherwise healthy pregnant women [5]. The specificity of DD-assay to rule out DVT in a pregnant woman is low and decreases during pregnancy [6]. Some *Corresponding author: Frauke Bergmann, Labassociation Wagnerstibbe, Amedes Group, Georgstr. 50, 30159 Hannover, Germany, E-mail: [email protected] Nadine Pingel and Matthias Koch: Labassociation Wagnerstibbe, Amedes Group, Göttingen, Germany Andreas Czwalinna: Labassociation Wagnerstibbe, Amedes Group, Hannover, Germany
data on DD behavior during pre- and post-partum period are available [7]. Cut-off values for currently available DD assays were established in a non-pregnant population only. The aim of our study was to establish gestational age-specific reference intervals for three different DD-assays frequently used. We collected 1069 heparinized blood samples of pregnant women from 5th to 36th week of gestation. We excluded 47 women with a history of DVT. Samples were collected for routine maternal checkups as recommended in Germany. Aliquots were frozen at –20 °C the same day and analyzed in batches. For comparison of DD results obtained by heparinized and citrated specimens a conversion factor of 0.84 for heparinized plasma was used [8, 9]. Three frequently used commercially available LIAassays were chosen: Hemosil D-Dimer HS 500® (Instrumentation Laboratory), using ACL Top-analyzer; Innovance D-Dimer® (Siemens Healthcare) using BCS-analyzer and Tina-quant® (Roche) using Modular analyzer. All three assays have the same cut-off value of
