Human platelets lacking CalDAG GEFI do not form “clots” on immobilized collagen. Blood from a healthy human control or from a patient lacking CalDAG GEFI was perfused over immobilized collagen at a high shear rate intended to mimic arterial blood flow. Control platelets (left image) adhere directly to the collagen surface via multiple receptors and coalesce normally into islands of three-dimensional clotlike structures as a result of primary and secondary signaling pathways that converge upon the αIIbβ3 integrin. In contrast, the patient’s platelets (right image) adhere normally but do not form three-dimensional structures because of a lack of αIIbβ3 activation caused by the absence of CalDAG GEFI. Cross-sectional images of these adherent platelets (bottom images) demonstrate fewer platelets and smaller aggregates in the patient. Platelet numbers are clearly reduced in the patient’s clots as depicted by the plot of total fluorescence intensity (volume) on the left. See Figure 2G in the article by Kato et al that begins on page 2729.