Platelet Adhesion to Subendothelial Collagen Requires von Willebrand Factor
The adhesion of platelets to subendothelial collagen is impaired in the absence of von Willebrand factor (option 1). This is the correct answer, as vWF serves as the essential bridge between exposed collagen and platelet receptors, particularly under high shear stress conditions.
Mechanism of vWF-Mediated Platelet Adhesion
von Willebrand factor plays a key role in primary hemostasis by mediating platelet adhesion to the subendothelium, especially at high shear rates that prevail in the microcirculation 1. The mechanism operates as follows:
vWF binds first to subendothelial collagen (particularly collagen VI) before platelet adhesion occurs 2. This binding occurs via the A1 domain of vWF 3.
Under high shear stress conditions (>1000 s⁻¹), vWF undergoes conformational changes from a globular to an unfolded state, exposing binding sites for platelet glycoprotein Ib (GPIb) 1. At low shear rates (<1000 s⁻¹), vWF circulates in a globular conformation that poorly interacts with platelets 1.
The high-molecular-weight (HMW) multimers of vWF (5500-10,000 kDa) are the most effective in promoting platelet adhesion under high shear rates at sites of vascular injury 1.
vWF forms a "bridge" between the platelet membrane (via GPIb/IX complex) and subendothelial collagen 2, 4.
Clinical Evidence from von Willebrand Disease
Patients with von Willebrand disease demonstrate markedly decreased platelet adhesion (57.3 ± 3.4% surface coverage) compared to normal subjects (83.3 ± 1.9%) 5. This adhesion defect is corrected by the addition of vWF 2.
Studies using monoclonal antibodies to vWF in normal blood confirm decreased platelet adhesion to subendothelium, validating vWF's essential role 2.
Why the Other Options Are Incorrect
Plasmin (option 2): This is a fibrinolytic enzyme that degrades fibrin clots; it does not mediate platelet adhesion to collagen.
Heparin (option 3): This is an anticoagulant that enhances antithrombin activity; it does not facilitate platelet adhesion.
Antithrombin III (option 4): This is a serine protease inhibitor that inactivates thrombin and other coagulation factors; it has no role in platelet adhesion to collagen.
Shear Rate Dependency
The importance of vWF in platelet adhesion is particularly pronounced under high shear conditions characteristic of arterial circulation 4, 3. At lower shear rates, direct platelet-collagen interactions via GPIIb-IIIa and α₂β₁ integrin receptors may partially compensate for vWF absence 6.