Fibrin degradation product kit March 2010 (Ist version) -Manufacturing/Marketing License No, 21700AMZ00594000 Class Il blod test series Factor Auto Series For measurement of plasma fibrin degradation product (D-dimer) Factor Auto D-dimer Dedimers desribed here refer to fibrin degradation produets (XDPs) in general produced when fibrin produced accompanying sctvation of blood coagulation mechanism in blood vessels is ‘decomposed by plasmin produced subsequently in blond vessels by activation of the fibrinolysis system, i, early degradation product (Stage 1 XDP: no!y containing P-X-D/V-Y. ete). middle degradation product (Stage 2 XDP: mainly containing Y-DD-Y, ete) an Inte degradation product (Stage 3 XDP: mainly containing DDm, Presence of fibrivfibrinogen degradation products (FDPs) in blood vessels mean occurence of fibrinolysis in the body and the measurement ofthese biomarkers is useful as an indicator for diagnosis, teatment and course observation of disseminated intravascular coagulation (DIC) and various thromnotic diseases. ‘Ofthom, D-dimer isa spositic product appearing only inthe secondary fibrinolysis (fibrin degradation: it enables the liserimination to some extent whether the fibrinolytic phenomenon ‘occurring inthe blood vessel derives from primary Hibrinolsis (degradation of fibrinogen) or secondary fibrinolysis by measuring ‘the total FDP in serum and D-dimer in plasma simultaneously and comparing them, Feature) ‘his product is the reagent ki Tor measuremen’OF D-imers that can detect Stage 1 XDP, Stage 2 XDP, and Stage 3 XDP with almost ‘equal affinities and, therefore its possible to obtain the strength of secondary fibrinolysis inthe blood vessel more accurately: Refer to References 2) and 3). {General precautions} 1. This product san in vitro diagnostics and should not be used far other purposs. 2. Diagnosis should be mace comprehensively based on the ‘other related test resuls, clinical symptoms and so on 3. The kit snot guaranteed when iis used for purposes other ‘than that specified in the package inser. 44. Before use, read earefillythe package inser and handling ‘manual ofthe device to be used 5. This product contains sodium azide as. preservative. Ifthe ‘product enters in dhe mouth or eyes oraeres on the skin by mistake, ake emergent measures such 2s washing thoroughly with water and visita physioian according to necessity {Shape, structure, ete. composition ofthe ki] 1. Buffer RI): Tes butter 2. Latex reagent (R2); Suspension of latex particles sensitized with the monoclonal antibody (mouse) to human D-dimer. 500 mem [Purposes of use) “Measurement of plasma fibrin degradation product (D-dimer) Ta is a Sol TTT [Measurement principle} This product quantitatively determines D-dimers in plasma according tothe latex turbidimetric immunoassay. When a specimen is allowed to react with latex particles sensitized with ‘mouse anti-human D-dimer monoclonal antibody, Dimer inthe specimen reacts with the latex particles, which aggregate ‘eansequentl in proportion to the D-dimer concentration inthe specimen, The intensity of ageregation is measured between 500 and ‘800 nm and the D-dimer concentration in the specimen is {determined from the calibration curve prepared witha calibrator solution by a similar reaction. [Precautions during operation] 1. Proeautons eonceming a specimen (2) Use plasma asa measure ple : (2) A specimen is stable for 8 hours at temperature between 15 and 28°C and for 2 months at 20°C (6) Handle the specimen as a material witha risk of infections by viruses, tc. and autoclave the specimen and apparatuses wed in the test at 121°C for I our a disinfect them by ‘immersing in 1% sodium hypochlorite solution, ete Inetivate the waste solution by neutralization and mixing ‘with sodium hypochlorite to give 1% concentration and leaving for 30 minutes 2 Interfering substances “Measurement isnot affected by the following substances a up othe following eoncentations; bilirubin at 20 mid, hemoglobin a 460 mgd, chyle at 2400 formazin turbidity units, rheumatic Faetor at $00 TLL, and heparin at $0 units. [Dosage and administration (operating procedure) 1. Preparation of reagents i: Use the buffer as itis RD: Use the latex reagent as itis Diluent: Use the special Diluent (sold separately). Calibrator solution: Use D-dimer Calibrator (sold separately), 2, Operating procedure (measurement with TOSHIBA Aceute TBA-4OFR) (1) Measure 140 iL oF RI (2) Add 4 ji. Gach ofthe calibrator sok concentrations prepared by successive doubling dilution of the stock solution of D-dimer Calibrator with Diluent and at O concentration (Diluent), or a specimen with light shaking. (3) Incubate for 110 S minutes at 37°C. (4) Add 40 lof R. (5) Measure the change per minute in absorbance at 48 nm from 29.7 0173.2 spoons afer edition oF 2, (6) Prepare calibration curve using the changes in absorbance of the reagent blank (Diluent) and Calibrator solutions obianed similarly as forthe specimen and determine the D-dimer concentration i the specimen from fons at SFactor Auto D-dimer the change in the absorbance of the specimen The parameters used inthe operating procedures with ther analytical instruments are also avaiable, Please make an inquiry to cour office [Judgment ofthe measurement est] Reference normal range: Not moee than 1.0 p/n? “The normal range may vary depending on the measurement ‘conditions and the standard used. Set the range upon consultation ‘with a physician at each institution. {Wsrformance) . ‘The performance data is based on Q-may's quality contol criteria I. Performance (1) Sensitivity: 0.38 g’mL. When simultaneous measurement wa performed 10 times for 0 up/miL and 0.38 yim. Calibrators, the ‘mean2SD obtained from the change in absorbance (AOD/in) f 0 ppm and 0.38 npn Calibrators does not overap, (2) Accurae: The result showed within 15% ofthe labeled «concentration when contol plasmas of known concentrations (1.5 w 24 jig) ere measured, (3) Iniea-day reproducibility The CV value was not more than 15% Within Run Inhouse Data TOSHIBA Accite TBA-WOFR Factor Auto Dimer Sample Low [High Men 425 Tae 5 3 SD 007 om ow im | 13% (4) Measurement range: Between 0.38 and 54.00 yam (6) Interday reproducibility: The CV value was not more than 15% ewe Ra Tnshose Daa ‘TOSHIBA AcoueTBAIOFR Fair Auto Dimer Sample Tow High Men 4 las 2 3s 3 SD. ox Lo a 7m | 9% 2, Results of correlation study (41) This product showed satisfactory correlation with an exiting product (Latex agsltinaion assay of Company A) about the plasma specimens obained from $5 subject. 0.977, y=0.98IWHOLIS 4: This product, x: Existing product of Company A (2) This product showed satisfactory correlation with an exiting prot (Latex agglutination assay of Company’) bout the plasma specimens obtained from 61 subject 0.965, y=1.0139%-0.0768 _y: This product, x: Existing produet of Company B [Precautions concerning use or handling] 1 The measured value of D-dimer may nt beso igh when primary TibrinolysisWenkanced. If such situation is expected, the fibrinolysis eonition of a patient shoul be judged by comparing with the measured value of total FDP if possible 2. The massed value of Dsdimer may deviate from that ofan exiting product ia plasma for measurement of D-dimer i stored under poor eontions. Measure the plasma obtained by centrifugation within the day of preparation. Or, store it under freezing at -20°C or below and complete the measurement within the day of preparation ater thawing at 37°C for 10 minutes. Do ~ not se the plasma repeatedly frozen and thawed. 3. Store the reagents 2 t0 8°C. Do not use frozen reagents or ‘reagents beyond the expiration date 4. Shake the latex reagent well before use with paying an attention to avoid bubbling, ‘5. Do not use the reagents by combining those of different ls. "Do not use the reagents by adding a product of different lo 6. Always use purified water forthe measurement system, Do not use tap wate, “1. Sau azide is contained ta tace concentration in each component reagent asa reservative. Sodium azide may react, with lead and copper pipes and produce explosive metal azide. ‘Wash witha large volume of water forts disposal {Storage condition and expiration date] 1. Storage condition: Store between 2 and 8°C. (Freezing is prohibited) 2. Expiration date: 18 masks ‘Use the prodiet within the expiration date indiated on the ‘outer eaton, [Packaging unit) I (buffer: mL x2 2 (latex reagent): 6 mL xT [References] 1) Francis,C:W.Plasmic Degradation of Crosslinked ‘Fibrin. Clin Invest. 1033-1043, 198, 2) Magari¥. otal: Usefulness of Factor Auto D-dimer newly developed for standanlization. Journal of Analytical Bio-Science Vol. 29 No. 4, 2008. 5) Mizunaga M. ot al: Basic study of factor auto D-dimer ‘measurement reagent assaying carly to lat fibrin degradation ‘products equally, Joural of Medicine and Pharmaceutical Science, Vol. $6 No. 3, 2006. 4) Journal of Medical Technology, Vol. 35 No-13;pp.1344#—1348, 2007. [Inquiry to Manufacturer/marketer] Q-may Laboratory Corporation 549-3 Aza Nagahata, Oaza Furug0, Oita-shi, Cita 870.0886 JAPAN “TEL: (81) 497-545-5051 PAX: (81) +97-846-2608 Ores