Heterophilic antibodies leading to falsely positive D-dimer concentration in an adolescent

Verboogen, Daniëlle R J; Granzen, Bernd; Hudig, Ciska; Kerkhof, Daan van de; Verhezen, Paul W M; Boer, Douwe de; Henskens, Yvonne

doi:10.1016/j.rpth.2022.100017

Research and Practice in Thrombosis and Haemostasis

2023

DOI: 10.1016/j.rpth.2022.100017

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Heterophilic antibodies leading to falsely positive D-dimer concentration in an adolescent

Daniëlle R J Verboogen

Bernd Granzen

Ciska Hudig

et al.

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Cited by 2 publications

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“…The D -dimer test sensitivity can also be reduced, in fact, it can be false -negative if it is measured more than 7-10 days after the onset of symptoms, 8,9 if a reagent has low sensitivity, or during anticoagulant treatment. 4, 10,11 In addition, naturally occurring polyreactive antibodies, autoantibodies, human antianimal antibodies, or rheumatoid factor, also known as heterophilic antibodies, can interfere with immunoassays, especially latex-enhanced immunoturbidimetric D -dimer tests, 12 producing false -positive results. The Food and Drug Administration has approved commercial clinical tests for VTE exclusion on the basis of management studies.…”

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confidence: 99%

D-dimer in diagnosis and prevention of venous thrombosis: recent advances and their practical implications

Cosmi,

Legnani,

Libra

et al. 2023

Polish Archives of Internal Medicine

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D -Dimers and venous thromboembolism 1 extent of fibrinolysis, and clearance of fibrin degradation products.D -Dimer level increases physiologically with age and during pregnancy and puerperium; it may be higher in African -Americans and in smokers. Increased D -dimer level is also observed in several pathologic conditions, in which stabilized fibrin is formed and subsequently degraded, such as in venous and arterial thrombosis, infectious diseases, neoplasms, trauma, surgery, liver disease, renal insufficiency, fibrinolytic therapy, disseminated intravascular coagulation (DIC), acute coronary syndromes, acute cerebrovascular events, subarachnoid hemorrhage, obstetric complications, or autoimmune disorders. 3 D -Dimer measurement D -Dimer level measurement was proposed as a laboratory test for the diagnosis of DIC in the 1970s; since then considerable advances have been made regarding its measurement, and its main clinical role is that in venous thromboembolism (VTE) diagnosis. 2 Introduction During hemostasis, activation of coagulation leads to the production of thrombin, which cleaves fibrinogen into fibrin monomers that finally form fibrin polymer. Thrombin also activates factor XIII, which stabilizes fibrin polymers with cross -linked covalent bonds. Activation of fibrinolysis leads to the production of plasmin, which cleaves cross -linked fibrin into various fragments, including D -dimers 1 (FIguRE 1). Plasmin produces several different degradation products with molecular weight (MW) ranging from 190 to over 10 000 kDa, and MW of D -dimers is about 180 kDa. 1 D -Dimers are mainly cleared by the kidney and reticulo -endothelial system, with a plasma half -life of 6 to 8 hours. 1,2 In physiological conditions, approximately 2%-3% of fibrinogen is converted into fibrin, which is then degraded by the fibrinolytic system. 1,2 As a result, D -dimers can be detected in low amounts in healthy individuals under physiological conditions. Plasma D -dimer concentration depends on the extent of factor XIIIa -stabilized fibrin formation,

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mentioning

confidence: 99%

D-dimer in diagnosis and prevention of venous thrombosis: recent advances and their practical implications

Cosmi,

Legnani,

Libra

et al. 2023

Polish Archives of Internal Medicine

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Interfering antibodies may contribute to elevated d-dimer: a case report

Zilstorff,

Hermann,

Rasmussen

et al. 2024

J Med Case Reports

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Background Plasma levels of d-dimer are elevated in patients with thromboembolisms. Here we investigated the existence of interfering antibodies as a potential cause for elevated d-dimer levels. Case presentation A 42-year-old white Caucasian woman with a prior history of pulmonary embolism during her first pregnancy (treated with heparin therapy for 6 weeks postnatally) and hypothyroidism had a persistent elevated d-dimer without any clinical or ultrasound-based signs of thromboembolic conditions during her second pregnancy. We obtained informed consent and plasma was obtained from the patient. d-dimer levels were measured using two different assays. We also tested for the presence of rheumatoid factor, performed dilution series, and finally used an antibody depletion strategy. The two d-dimer assays performed similarly. Using our antibody depletion technique, we observed that ~ 1/3 of the increased plasma levels of d-dimer may be attributed to interfering antibodies. Conclusions Our results identify interfering antibodies as a potential contributor to an increased d-dimer in this patient. Our case highlights the potential of heterophilic interference for increased d-dimer and provides a procedure to determine this analytically.

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Heterophilic antibodies leading to falsely positive D-dimer concentration in an adolescent

Cited by 2 publications

References 12 publications

D-dimer in diagnosis and prevention of venous thrombosis: recent advances and their practical implications

D-dimer in diagnosis and prevention of venous thrombosis: recent advances and their practical implications

Interfering antibodies may contribute to elevated d-dimer: a case report

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