Prevalence and Clinical Implications of Heparin-Associated False Positive Tests for Serum Fibrin(ogen) Degradation Products

Connaghan, D G; Francis, Charles W.; Ryan, D. H.; Marder, Victor J.

doi:10.1093/ajcp/86.3.304

Cited by 16 publications

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“…Elevated plasma and serum FDPs are seen in patients with increased fibrin(ogen)olysis due to disseminated intravascular coagulation and many other disorders (Garvey & Black, 1972;Kroneman et al, 1990;Mirshahi et al, 1986;Wilde et al, 1989). The polyclonal antibodies used in the serum FDP assay also recognize fibrinogen, and false-positive results can occur with incomplete clotting of the sample, dysfibrinogenaemia, and if the serum contains rheumatoid factor (noted in one of our controls) (Connaghan et al, 1986;Elms et al, 1986;Gaffney & Perry, 1985;Garvey & Black, 1972;Mirshahi et al, 1986;Nieuwenhuizen, 1988;Rutstein et al, 1978). Treating samples with reptilase can minimize false positives due to incomplete clotting (Connaghan et al, 1986).…”

Section: Discussionmentioning

confidence: 76%

“…The polyclonal antibodies used in the serum FDP assay also recognize fibrinogen, and false-positive results can occur with incomplete clotting of the sample, dysfibrinogenaemia, and if the serum contains rheumatoid factor (noted in one of our controls) (Connaghan et al, 1986;Elms et al, 1986;Gaffney & Perry, 1985;Garvey & Black, 1972;Mirshahi et al, 1986;Nieuwenhuizen, 1988;Rutstein et al, 1978). Treating samples with reptilase can minimize false positives due to incomplete clotting (Connaghan et al, 1986). The FDP levels detected in the Quebec patients were identical in samples clotted using reptilase or thrombin, indicating either enzyme can be used to prepare serum for testing.…”

Section: Discussionmentioning

confidence: 90%

“…Polyclonal serum FDP assays are sensitive tests for fibrinogen/fibrin degradation but these tests have been criticized for their lack of specificity (Amiral et al, 1990;Connaghan et al, 1986;Gaffney & Perry, 1985;Niewenhuizen, 1988;Prisco et al, 1990). Elevated plasma and serum FDPs are seen in patients with increased fibrin(ogen)olysis due to disseminated intravascular coagulation and many other disorders (Garvey & Black, 1972;Kroneman et al, 1990;Mirshahi et al, 1986;Wilde et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

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Fibrinogen degradation products in patients with the Quebec platelet disorder

et al. 1997

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Summary. The Quebec platelet disorder is a serious bleeding disorder associated with proteolysis of a-granular proteins, including fibrinogen. We evaluated fibrinogen degradation product (FDP) assays as screening tests for this disorder. Patients with the Quebec platelet disorder (13/13) had elevated serum FDPs (P < 0 . 01) due to secreted degraded platelet fibrinogen, but normal plasma FDPs and D-dimers. Unrelated controls with bleeding disorders (32/34) had undetectable FDPs, and controls with FDPs due to disseminated intravascular coagulation (DIC) and other illnesses (11/11) had elevated FDPs in all assays (P < 0 . 01). Immunoblot analyses indicated plasma fibrinogen was normal in the Quebec patients and platelet FDPs were found in their platelet lysates, releasates and serum samples. Their platelet FDPs were not altered by treatment with fibrinolytic inhibitors and were different from the FDPs in DIC and in plasmin-digested fibrinogen. Tests for serum FDPs may provide a simple rapid way to screen for the Quebec platelet disorder.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Fibrinogen degradation products in patients with the Quebec platelet disorder

et al. 1997

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“…This identifies fibrinogen fragments E, D, and Y and smaller degradation products of cross-linked fibrin. Incomplete clotting because of poor sample preparation or the presence of heparin 37 can give a falsepositive and misleading result. The widely used D-dimer assays employ monoclonal antibodies to neoepitopes resulting from ␥ chain cross-linking of D-domains, and it therefore specifically detects fibrin degradation products as opposed to fibrinogen degradation products.…”

Section: Assay Methodsmentioning

confidence: 99%

Fibrin Degradation Products, Fibrin Monomer and Soluble Fibrin in Disseminated Intravascular Coagulation

Horan¹,

Francis²

2001

Semin Thromb Hemost

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102

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Disseminated intravascular coagulation (DIC) is characterized by activation of hemostasis and fibrinolysis resulting in the formation of thrombin and plasmin, and the characteristic effects of these enzymes on plasma fibrinogen can be useful in diagnosis. Thrombin cleaves fibrinopeptides from fibrinogen, forming fibrin monomer that rapidly polymerizes to form a clot. Small amounts can circulate in plasma as "soluble fibrin," which may have a complex composition and include fibrinogen and a variable amount of cross-linking. Plasmic degradation of cross-linked fibrin forms a heterogeneous group of degradation products reactive in assays for D-dimer, and their levels provide a measure of the amount of fibrin formation and lysis. Caution should be exercised in comparing quantitative results using different assays because of problems with standardization and variable reactivity with different molecular forms. Marked elevations of fibrin(ogen) degradation products are a constant finding in experimental animal models of DIC. In human models of DIC resulting from endotoxin infusion, D-dimer is elevated early and high levels persist, reflecting lysis of microvascular fibrin deposits. Elevated levels of D-dimer and soluble fibrin are very sensitive for the diagnosis of DIC, and a normal level has a high negative predictive value. Serial monitoring of soluble fibrin or D-dimer assays may be of value in evaluating the response to therapy and possibly in identifying at-risk patients.Objectives: Upon completion of this article, the reader should be able to (1) summarize the biochemical steps involved in the formation of soluble fibrin and fibrin(ogen) degradation products and (2) understand the clinical application of soluble fibrin and D-dimer assays in the diagnosis and management of DIC. Accreditation: Tufts University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. TUSM takes full responsibility for the content, quality, and scientific integrity of this continuing education activity. Credit: Tufts University School of Medicine designates this education activity for a maximum of 1.0 hours credit toward the AMA Physicians Recognition Award in category one. Each physician should claim only those hours that he/she actually spent in the educational activity.

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“…The venom causes complete clotting of fibrinogen in vitro, and eliminates these false-positive results. 9 Currently, all collection tubes provided with com-mercial serum FDP kits contain Reptilase. The TW serum FDP kit, using thrombin-based collection tubes, has been the traditional standard for FDP detection in dogs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Kits for the Detection of Fibrin(ogen) Degradation Products in Dogs

Stokol¹,

Brooks²,

Erb³

et al. 1999

J Vet Int Med

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The sensitivities and specificities of 3 commercial serum fibrin(ogen) degradation product (FDP) kits and 1 plasma FDP kit for the detection of FDPs in dogs were determined. Blood was collected for measurement of serum and plasma FDP concentrations from 30 healthy dogs and from 20 dogs that fulfilled clinical and laboratory criteria for disseminated intravascular coagulation. To determine the effect of hemolysis on FDP results, blood was collected simultaneously into Bothrops atrox venom-based and thrombin-based serum collection tubes for measurement of FDPs using a single serum FDP kit. The sensitivity (80-95%) and specificity (90-100%) for a positive or negative FDP result, regardless of concentration, was similar for all kits. Kits yielded discordant results in individual dogs and FDP concentrations obtained from 1 serum FDP kit were consistently higher than those from the other kits. Serum prepared from venom-based collection tubes was significantly more hemolyzed than serum prepared from thrombin-based collection tubes or citrated plasma. Hemolysis did not affect the FDP results. On the basis of these results, we conclude that commercial latex agglutination kits for detection of FDPs in serum and plasma samples from human patients are valid for use in dogs. The plasma FDP assay is a viable alternative to currently used serum FDP assays and has the advantage of using a single (citrated plasma) sample for measuring coagulation parameters and FDP concentration.

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Prevalence and Clinical Implications of Heparin-Associated False Positive Tests for Serum Fibrin(ogen) Degradation Products

Cited by 16 publications

References 0 publications

Fibrinogen degradation products in patients with the Quebec platelet disorder

Fibrinogen degradation products in patients with the Quebec platelet disorder

Fibrin Degradation Products, Fibrin Monomer and Soluble Fibrin in Disseminated Intravascular Coagulation

Evaluation of Kits for the Detection of Fibrin(ogen) Degradation Products in Dogs

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