A 26-year-old woman is evaluated for a lifelong history of easy bruising and heavy menstrual bleeding. She has a strong family history of bleeding tendencies affecting both her mother and maternal grandfather. Physical examination shows scattered petechiae and ecchymoses on her extremities.
Laboratory results are as follows:
| Test | Result | Reference Range |
|---|---|---|
| Platelet count | 110,000/mm³ | 150,000 - 400,000/mm³ |
| Prothrombin time (PT) | 11.5 s | 11.0 - 14.0 s |
| Activated partial thromboplastin time (aPTT) | 32 s | 25 - 40 s |
| Factor VIII coagulant activity | 70% | 50% - 150% |
| von Willebrand factor antigen (vWF:Ag) | 85% | 50% - 150% |
| vWF ristocetin cofactor activity (vWF:RCo) | 25% | 50% - 150% |
Additional specialized hematologic testing reveals the absence of high-molecular-weight vWF multimers. A low-dose ristocetin-induced platelet aggregation (RIPA) assay shows enhanced brisk platelet aggregation.
To further delineate the etiology, a RIPA mixing study is performed:
- Patient plasma + normal washed platelets + low-dose ristocetin: Brisk aggregation occurs
- Normal plasma + patient washed platelets + low-dose ristocetin: No aggregation occurs
Which of the following best describes the underlying pathophysiology of this patient's laboratory findings?
- Gain-of-function mutation in the von Willebrand factor molecule increasing its affinity for plateletsCevap
- BGain-of-function mutation in the platelet glycoprotein Ib receptor increasing its affinity for von Willebrand factor
- CIncreased susceptibility of von Willebrand factor to proteolytic cleavage by ADAMTS13
- DMarkedly decreased binding affinity of von Willebrand factor for Factor VIII
- EDefective endothelial synthesis and secretion of Weibel-Palade body contents