Is multimer testing recommended for a patient with recurrent thrombocytopenia, a history of delayed post-surgical hemorrhages, and a von Willebrand factor (VWF) ratio of 0.7, similar to her mother's ratio?

Von Willebrand Factor Multimer Testing in Recurrent Thrombocytopenia with Delayed Post-Surgical Hemorrhages

Von Willebrand factor multimer testing is strongly recommended for this patient with recurrent thrombocytopenia, delayed post-surgical hemorrhages, and a VWF ratio of 0.7, especially given the similar ratio in her mother. 1

Diagnostic Significance of VWF Ratio of 0.7

A VWF activity to antigen ratio of 0.7 is a critical diagnostic threshold that indicates:

• Presence of qualitative VWF defects consistent with acquired von Willebrand syndrome (AVWS) or type 2 von Willebrand disease (VWD) 1
• Loss of high-molecular-weight (HMW) VWF multimers, which are most effective in supporting platelet-subendothelial matrix interaction 2
• Significantly increased risk of bleeding, particularly during surgical procedures 1

The familial pattern (mother also having a ratio of 0.7) strongly suggests hereditary type 2 VWD rather than acquired VWS.

Clinical Correlation with Patient's Presentation

The patient's clinical presentation aligns perfectly with type 2 VWD:

• Recurrent thrombocytopenia - common in type 2B VWD due to increased binding of platelets to abnormal VWF 3
• History of delayed post-surgical hemorrhages - characteristic of VWF deficiency 1
• VWF ratio of 0.7 - indicates loss of HMW multimers 1
• Family history (mother with similar ratio) - supports hereditary nature 3

Recommended Diagnostic Algorithm

1. Perform VWF multimer analysis to confirm loss of HMW multimers and determine specific subtype 1
2. Measure VWF:RCo (ristocetin cofactor activity) and VWF:CB (collagen binding) to further characterize the defect 2
3. Consider ristocetin-induced platelet aggregation (RIPA) to differentiate type 2B from other subtypes 1
4. Genetic testing to confirm specific mutation, particularly if type 2B is suspected 1

Management Implications

Confirming the specific VWD subtype through multimer testing has critical treatment implications:

• Type 2A vs 2B differentiation is crucial as management differs significantly 2
• Desmopressin is contraindicated in type 2B VWD as it can worsen thrombocytopenia 1
• VWF concentrate is the preferred treatment for type 2 VWD, especially for surgical procedures 1
• Target VWF:RCo levels should be >50 IU/dL for minor procedures and >100 IU/dL for major surgery 1

Potential Pitfalls to Avoid

• Misdiagnosis risk: Without multimer testing, the specific VWD subtype cannot be accurately determined, leading to potentially harmful treatment decisions 1
• Treatment errors: Using desmopressin in type 2B VWD can worsen thrombocytopenia and increase bleeding risk 2
• Surgical complications: Failure to identify and properly manage VWD before surgery can result in significant hemorrhagic complications 1

Additional Considerations

• The patient's recurrent thrombocytopenia could be a manifestation of type 2B VWD, which is characterized by enhanced binding of abnormal VWF to platelets, leading to their clearance from circulation 3
• The delayed post-surgical hemorrhages are consistent with defective primary hemostasis due to dysfunctional VWF 1
• The familial pattern strongly suggests hereditary VWD rather than acquired VWS 3

Multimer testing is essential not only for diagnosis but also for guiding appropriate management to prevent future bleeding complications, particularly during surgical procedures.