Pathological mechanism for FLNa-deficient MKs. (A) In the presence of FLNa, the interaction between fibrinogen and its receptor α_IIbβ₃ does not trigger RhoA pathway activation. No anomalies in proplatelet formation could be observed. (B) In the absence of FLNa, the interaction between fibrinogen and α_IIbβ₃ leads to an increase in RhoA activity. Consequently, the normal actomyosin contractility is disrupted via ROCK1/2 activity, and this leads to deeply flawed proplatelet formation. This increased RhoA activity in the absence of FLNa is specifically dependent on fibrinogen and absent in the presence of other extracellular matrices like fibronectin, vitronectin, collagen 1, or VWF.