Questions: Platelet Function and Von Willebrand Disease

Question 1

A 24-year-old woman reports frequent nosebleeds, heavy menstrual periods, and prolonged bleeding after dental extractions since childhood. Family history is positive for similar symptoms. Labs show normal PT, slightly prolonged PTT, and a prolonged PFA-100 closure time. What is the most likely diagnosis?

• A. Hemophilia A (Factor VIII deficiency)
• B. Immune thrombocytopenic purpura (ITP)
• C. Von Willebrand disease
• D. Disseminated intravascular coagulation (DIC)

Answer: (C)

The pattern of mucocutaneous bleeding — epistaxis, menorrhagia, prolonged wound bleeding — is the hallmark of a primary hemostasis defect, specifically defective platelet adhesion. The prolonged PFA-100 (a test of platelet plug formation) with normal PT confirms that the coagulation cascade is intact and the defect lies in the platelet plug. The slightly prolonged PTT may reflect reduced factor VIII, since vWF normally carries and protects factor VIII. Hemophilia A causes deep tissue bleeding (hemarthroses, muscle hematomas), not mucocutaneous bleeding — a critical distinguishing feature.

Question 2

Why is von Willebrand factor particularly critical for platelet adhesion in arteries compared to veins?

• A. Arteries contain more collagen in the subendothelium, requiring a stronger adhesive bridge
• B. Arterial blood flows at higher shear stress, which would dislodge platelets before direct collagen binding can occur without a bridging molecule
• C. Veins produce their own platelet-adhesion molecule that makes vWF redundant in the venous circulation
• D. vWF is synthesized only by arterial endothelial cells, not venous endothelium

Answer: (B)

At the high shear rates of arterial blood flow, simple diffusion-based platelet-collagen contact would be too slow and too weak — platelets would be swept past before they could adhere. vWF solves this: it unfolds under high shear stress and simultaneously binds exposed collagen and platelet GPIb receptors, physically bridging the gap and decelerating platelets enough for stable adhesion. In the slower-flow venous circulation, direct platelet-collagen binding is sufficient. This explains why vWD causes more arterial-type bleeding problems.

Question 3

Von Willebrand disease prolongs the prothrombin time (PT), because vWF deficiency impairs the extrinsic coagulation pathway.

• T. True
• F. False

Answer: False

vWD prolongs the bleeding time and PFA-100 closure time, which are tests of primary hemostasis (platelet plug formation). The PT, which tests the extrinsic coagulation pathway (factor VII, X, V, prothrombin, fibrinogen), is unaffected by vWF deficiency. In severe vWD, the PTT may be prolonged because vWF normally carries and protects factor VIII from proteolytic degradation — but even then, it is the secondary effect on factor VIII that prolongs the PTT, not a direct effect on the coagulation cascade.

Question 4

In addition to mediating platelet adhesion, vWF serves as a carrier protein for factor VIII in circulation, protecting it from premature proteolysis.

• T. True
• F. False

Answer: True

This dual role explains why severe vWF deficiency (Type 3 vWD) can cause both primary hemostasis failure and reduced factor VIII levels, leading to a combined bleeding phenotype that partially overlaps with mild hemophilia A. In vWD patients with very low vWF, the factor VIII that is not bound to vWF is rapidly degraded, shortening its half-life and reducing plasma levels below the normal range.

Question 5

How does the clinical bleeding pattern of von Willebrand disease differ from that of hemophilia A, and what explains this difference mechanistically?

Model answer: Von Willebrand disease causes mucocutaneous bleeding — nosebleeds, gum bleeding, heavy menstrual periods, and prolonged oozing from minor cuts — because vWF mediates platelet adhesion, which is the first step of primary hemostasis (the platelet plug). Hemophilia A causes deep tissue bleeding — hemarthroses, intramuscular hematomas — because factor VIII is required for tenase complex assembly in the intrinsic coagulation pathway, which is secondary hemostasis (fibrin clot formation). The platelet plug forms normally in hemophilia A and can stop capillary-level bleeding; it is the fibrin reinforcement that fails. In vWD, the platelet plug itself cannot form properly, so even minor trauma causes prolonged surface bleeding.

This distinction is clinically crucial: a patient with joint bleeds after minor trauma likely has a coagulation factor deficiency; a patient with nosebleeds and heavy periods likely has a primary hemostasis defect. The lab also reflects this — vWD prolongs the PFA-100 but not the PT; hemophilia A prolongs the PTT but not the PFA-100.