Background: The management of congenital rare bleeding disorders (RBDs) and of von Willebrand disease (VWD) is difficult due to the wide spectrum of clinical phenotypes and to several procoagulant responses to different treatments.

Aims: We aimed to test the usefulness of a microchip flow-chamber system (T-TAS®) for analyzing hemostatic and coagulation status in RBDs and type-3 VWD, and the response to treatments with replacement factor and with a non-factor therapy, an anti-TFPI neutralizing antibody (clone-2021).

Methods: We recruited one patient with FVII deficiency (5% FVII), one with FXI deficiency (<15% FXI), and one with FX deficiency (5% FX), representative, respectively, of anomalous extrinsic, intrinsic and common coagulation pathways. One patient with deficit of FXIII (5% FXIII), other with type-3 VWD (0% VWF / 0.4% FVIII) and five healthy controls were also included.
Microchips coated with either collagen/thromboplastin [atherome (AR)-chip] or collagen [platelet (PL)-chip] were used to evaluate fibrin-rich platelet thrombus formation or platelet thrombus formation.

Results: Using AR-chips, deficiencies of FVII (Fig.1A) and FXI (Fig.1B) caused an anomalous clot formation. In vitro treatment of samples with the corresponding replacement factor restored coagulation profile in FVII and FXI deficiencies. Anti-TFPI corrected the deficiencies of these factors although less effectively. FX deficiency practically prevented clot development and treatment with PCC or anti-TFPI scarcely improved it (Fig.1C). Lack of FXIII did not affect clot formation (Fig. 1D).
The impairment in coagulation (Fig.2A) and primary haemostasis (Fig.2B) observed in type-3 VWD was partially corrected by pdFVIII/VWF, whereas anti-TFPI was almost ineffective.

Time/pressure curves of T-TAS assay using AR-chips with healthy controls or RBDs patients: (A) FVII deficiency, (B) FXI deficiency, (C) FX deficiency, or (D) FXIII deficiency, before or after spiking with indicated treatment.

Time/pressure curves of T-TAS assay using AR-chip (A) or PL-chip (B) with healthy controls or type-3 VWD patient, before or after spiking with indicated treatment.

Conclusions: Analysis with a flow chamber‐based assay to measure thrombus formation in vitro may be useful for the evaluation of the coagulation profile in RBDs and VWD and for monitoring effects of therapeutic treatments. Anti-TFPI was effective for correcting FVII and FXI deficiencies but have poor effects for amending FX deficiency and VWD.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/monitoring-rare-bleeding-disorders-and-their-response-to-therapeutic-treatments-with-a-microchip-flow-chamber-assay/