Background: von Willebrand factor (VWF) multimers (VWF:MM) methodologies are technically difficult, laborious, time consuming, non-standardized and results vary between laboratories. A new semi automated VWF:MM assay is available for routine use (Sebia). Due to lack of reference values for VWF:MM fractions, results interpretation can be challenging in some cases. The aim of this study was to determine reference intervals for low molecular weight (LMWM), intermediate molecular weight (IMWM) and high molecular weight (HMWM) multimers.
Methods: By the international cooperation initiated between 4 countries (Estonia, Latvia, France, and USA) 131 samples of relatively healthy individuals were analyzed for VWF:MM (in total 51 males and 80 non-pregnant females aged 17-69 years). Reference intervals were calculated according to CLSI C28-A3 standard.
Results: The proposed reference intervals for VWF:MM were calculated for LMWM 10.4-22.5%, IMWM 22.6-37.6%, HMWM 45.6-66.6%. Age related differences were seen in IMWM and HMWM (p<0.001 and 0.038). There was no gender related difference observed. Geographically LMWM results of France were different from the other regions (p<0.05).
Conclusions: Quantification of VWF:MM fractions, in addition to qualitative assessment of VWF:MM patterns, has the potential to aid in differential diagnosis of von Willebrand disease (VWD) subtypes. The reference values calculated in this study can be used in future research to establish clinical decision limits.
Uvod: Metodologija multimera (VWF:MM) von Willebrand faktora (VWF) tehnički je teška, naporna, digotrajna, nestandardizovana i rezultati se razlikuju u različitim laboratorijama. Novi poluautomatski VWF:MM test (Sebia) dostupan je za rutinsku upotrebu. Zbog nedostatka referentnih vrednosti za VWF:MM frakcije, tumačenje rezultata može u nekim slučajevima biti izazovno. Cilj ove studije bio je da se odrede referentni intervali za multimere niske molekularne mase (LMWM), srednje molekularne mase (IMWM) i visoke molekularne težine (HMWM).
Metode: Međunarodnom saradnjom započetom između 4 zemlje (Estonija, Letonija, Francuska i SAD) 131 uzorak relativno zdravih pojedinaca analiziran je na VWF:MM (ukupno 51 muškarac i 80 žena koje nisu bile trudne u dobi od 17-69 godina). Referentni intervali su izračunati prema CLSI C28-A3 standardu.
Rezultati: Predloženi referentni intervali za VWF:MM izračunati su za LMWM 10,4-22,5%, IMWM 22,6-37,6% i HMWM 45,6-66,6%. Starosne razlike su primećene u IMWM i HMWM (p < 0,001 i 0,038). Nije uočena razlika vezana za pol. Geografski rezultati LMWM iz Francuske bili su različiti od ostalih regiona (p < 0,05).
Zaključak: Kvantifikovanje frakcija VWF:MM, pored kvalitativne procene VWF:MM uzoraka, može da pomogne i u diferencijalnoj dijagnozi podtipova von Willebrandove (VWD) bolesti. Referentne vrednosti izračunate u ovoj studiji mogu se koristiti u budućim istraživanjima za utvrđivanje granica kliničkih odluka.
Keywords: quantitative analysis; reference intervals; von Willebrand factor; von Willebrand factor multimers.
2022 Marika Pikta, Marc Vasse, Kristi J. Smock, Karen A. Moser, Dievoet Marie-Astrid van, Sandra Lejniece, Timea Szanto, Hector Bautista, George Nouadje, Valdas Banys, published by CEON/CEES.