The disguise of dyscrasia: Hereditary von Willebrand disease unmasked by MGUS-associated acquired VWD Free

Introduction: A 70-year-old male initially underwent evaluation for suspected multiple myeloma and was found to have IgG monoclonal gammopathy of undetermined significance (MGUS). He subsequently developed a spontaneous intracranial hemorrhage and was diagnosed with Type 1 Hereditary Von Willebrand Disease (VWD). This case highlights how acquired VWD, often associated with plasma cell disorders like MGUS, can unmask underlying hereditary VWD, emphasizing the importance of comprehensive evaluation in atypical bleeding presentations.

Case Presentation: A 70-year-old male with no significant past medical history presented to the emergency department for severe non-radiating neck pain minimally responsive to analgesics. Laboratory work-up was relatively unremarkable. CT Cervical Spine without contrast was obtained which demonstrated no acute bony findings, however, multiple small lucencies throughout the vertebral bodies, nonspecific, but multiple myeloma can have this appearance. As such, MRI Cervical Spine with and without contrast was obtained which was significantly limited by artifact as patient was not cooperating. Patient was referred to outpatient Orthopedics. On follow-up visit, it was recommended that the patient pursue further work-up for multiple myeloma with primary care physician (PCP) due to concern for multiple myeloma on CT scan.

Multiple Myeloma work-up demonstrated M spike 0.2g.dl, IgG kappa free light chain 24.8 mg/L(H), free lambda light chain 15.3 mg/L, kappa lambda ratio 1.62, IgG 577 mg/dL (L), IgA 272 mg/dL, IgM 90 mg/dL, IgE 6 mg/dL, total protein in urine 4.5 mg/dl with albumin 100%, serum calcium 8.6. Bone marrow biopsy revealed <5% plasma cells and cytogenetics and fish panel were negative. As such, patients' clinical picture was consistent with IgG MGUS.

Patient then presented to the hospital due to worsening headache and left upper extremity weakness. MRI brain with and without contrast demonstrated a right parietal subdural hematoma and adjacent subarachnoid hemorrhage in right postcentral gyrus. He has no past medical history major bleeding or family history of bleeding diathesis. He was conservatively managed. Outpatient, a Von Willebrand profile was performed which showed factor VIII activity 21%, Von Willebrand activity <10%, and Von Willebrand factor antigen (vWF Ag) 24% which was consistent with Von Willebrand Disease (VWD). Platelet function analysis showed delayed aggregation. Ristocetin induced platelet aggregation was normal. Von Willebrand profile was repeated twice demonstrating consistent decrease in Von Willebrand panel. Patient received DDAVP challenge with repeat Von Willebrand panel at 0, 4, and 8 hours. Factor VIII activity was 15%, 32%, 40% respectively, VWF Ag at 19%, 30%, 44% respectively, and vWF activity <10%, 10%, 25% respectively. As such, patients' clinical picture was consistent with Type 1 Von Willebrand Disease. Patient's son and daughter were tested and laboratory work-up was consistent with Type 1 Von Willebrand Disease solidifying a diagnosis of Type 1 Hereditary Von Willebrand Disease.

Discussion: Type 1 VWD is characterized by partial quantitative deficiency through impaired synthesis, secretion, or increased clearance of VWF. Acquired VWD is characterized by qualitative or quantitative defects secondary to an underlying condition, most notably a complication of plasma cell dyscrasias such as MGUS. In MGUS, there is accelerated clearance or functional inhibition of VWF that can mimic labs and clinical presentation like that of Hereditary VWD. However, although rare, Acquired VWD has the propensity to unmask Hereditary VWD, which is seen in this case. This patient had a mild or subclinical disease which was likely exacerbated by increased clearance of VWF secondary to MGUS. What appeared to be Acquired VWD as a complication of MGUS exposed underlying Hereditary VWD.

Conclusion: This case underscores the complex interplay between MGUS and bleeding disorders, where acquired VWD may mimic or reveal underlying hereditary VWD. The patient's diagnosis of Type 1 Hereditary VWD, uncovered during evaluation for spontaneous hemorrhage and initially suspected as acquired VWD from MGUS, illustrates the importance of thorough hematologic assessment and familial testing. Recognition of hereditary bleeding disorders in the setting of monoclonal gammopathies is essential for accurate diagnosis and tailored management.