The Platelet Function Analyzer (PFA-100) may not be suitable for monitoring the therapeutic efficiency of von Willebrand concentrate in type III von Willebrand disease

Abstract

We describe a type-III von Willebrand patient who was admitted to the hospital with severe deformity and functional deficit of the left knee joint due to recurrent hemarthrosis. Orthopedic intervention was necessary. To prevent bleeding episodes, von Willebrand factor (vWF) replacement therapy was given during and after surgery. APTT, plasma FVIII activity (FVIIIc), vWF antigen (vWF Ag), and vWF ristocetin cofactor (vWF Rco) were measured. Primary hemostasis was monitored using the PFA-100. This "Platelet Function Analyzer" is designed to measure platelet adhesion and aggregation capacities. Whole blood is aspirated through a capillary and is forced to flow through the central hole of a membrane coated with collagen and epinephrine (COL/EPI) or ADP (COL/ADP) as platelet activators. Irreversible platelet aggregation results in the formation of a stable platelet plug, closing the central hole. The result is expressed as "closure time" (CT), i.e., time necessary to stop the blood flow, and is a measure of platelet hemostasis capacity. Laboratory investigations during substitution therapy revealed no shortening of closure times with both COL/EPI and COL/ADP cartridges despite normalization of plasma vWF Ag, vWF Rco, and FVIIIc levels. These observations suggest that intraplatelet vWF, which is totally absent in type-III von Willebrand disease, plays an important function in the adhesion of platelets to the collagen-coated membrane of the PFA-100 system, simulating an injured vessel wall. Consequently, we conclude that the PFA-100 may not be suitable for monitoring the therapeutic efficacy of von Willebrand concentrate in type-III von Willebrand patients during substitution therapy.

Platelet function analyzer (PFA)‐100® closure time in the evaluation of platelet disorders and platelet function

“…PFA‐100 CT are approximately 10–20% longer in individuals with group O, probably because of their lower plasma VWF [37,41–43]. There is evidence that platelet VWF, and the profile of VWF multimers in plasma, influences the PFA‐100 CT, based on observations of prolonged CT in type 1 ‘platelet low’, type 1 ‘platelet discordant’, type 2A and type 3 VWD, and their failure to correct with VWF replacement [13,44,45]. In patients with severe aortic stenosis and an acquired VWD characterized by the loss of the largest multimers, the PFA‐100 CT is prolonged and shortens rapidly after surgery, along with the recovery of the largest multimers [46].…”

“…In type 1 VWD, prolonged CEPI and/or CADP CT show correction after DDAVP‐induced increases in plasma VWF but not in patients with discordant or low levels of platelet VWF [11,13,44,87]. In severe VWD, PFA‐100 CT often does not correct with VWF replacement, possibly because of abnormalities in concentrate multimer profile and/or lack of intraplatelet VWF [11,13,44,45].…”

Utility of the PFA‐100® for assessing bleeding disorders and monitoring therapy: a review of analytical variables, benefits and limitations

“…The potential utility of the PFA‐100 ® in this process has been evaluated by a small number of workers [30,33,36,43]. In a large French study [36], 41 vWD patients were assessed pre‐ and post‐DDAVP ( n =34; 23 type 1, five type 2M, three type 2 A, three type 2B) or factor concentrate ( n =9; four type 3, two type 2M, two type 2 A, one type 1 platelet‐low).…”

PFA-100®: Globaltest der primären Hämostase?/PFA-100®: Global Test for Primary Haemostasis?

“…Die Frage stellt sich deshalb, ob der PFA-100 â ein geeignetes Instrument ist, Patienten mit einem von-Willebrand-Ju Èrgens-Syndrom zu screenen. B. Typ-3-Patienten verabreicht, verku Èrzten sich die Verschlusszeiten nicht, obwohl Ristocetin-Cofaktor und von Willebrand-Faktor-Konzentration ada Èquat anstiegen[17,19, 20,24]. Die Konzentration des von-Willebrand-Faktor entspricht in diesem Fall meist der Norm.…”

“…Wurde aber ein Faktor-VIII-Konzentrat z. B. Typ-3-Patienten verabreicht, verku Èrzten sich die Verschlusszeiten nicht, obwohl Ristocetin-Cofaktor und von Willebrand-Faktor-Konzentration ada Èquat anstiegen[17,19, 20,24]. Die Collagenbindungsaktivita Èt sprach in diesen Fa Èllen ebenso nicht an.…”