How to approach a 32-year-old female with abnormal platelet function assay results (COL/EPI and COL/ADP), low von Willebrand activity (30%) and factor VIII levels (43%), and normal multimers, who is scheduled for major spinal surgery and is currently taking Selective Serotonin Reuptake Inhibitors (SSRIs)?

From the Guidelines

I would recommend treating this patient with tranexamic acid (TXA) as the primary prophylactic agent for her upcoming spinal surgery, given her abnormal platelet function assay and borderline von Willebrand disease (vWD) parameters, in order to minimize her bleeding risk. The patient's laboratory findings, including vWF activity 30%, antigen 43%, factor VIII 43%, and abnormal platelet function assay, suggest a possible bleeding disorder of unknown cause (BDUC) 1. Although she does not meet the strict diagnostic criteria for vWD, her results are at the cusp, and the planned surgery is a major one, which increases her bleeding risk.

Given the lack of consensus on the management of BDUC patients, as evident from the survey results 1, a pragmatic approach would be to use TXA, which is inexpensive, widely available, and effective as an adjunct in a range of bleeding disorders 1. The addition of desmopressin (DDAVP) could be considered, but the evidence for its use in this context is limited 1. Antifibrinolytics like TXA have been shown to be effective in managing bleeding in patients with BDUC, with a hemostatic efficacy of >90% 1.

Some key points to consider in the management of this patient include:

• The use of TXA as the primary prophylactic agent, given its efficacy and safety profile 1
• The potential addition of DDAVP, although the evidence for its use in this context is limited 1
• Close monitoring for bleeding postoperatively, with laboratory assessment of vWF levels if therapy is continued beyond the initial dose 1
• A hematology follow-up should be scheduled after recovery to reassess her diagnosis and discuss implications for future procedures 1
• The patient's SSRI use may further contribute to bleeding risk by affecting platelet function, and this should be taken into account when managing her perioperatively 1.

From the FDA Drug Label

Desmopressin acetate injection 4 mcg/mL is indicated for patients with mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5% Desmopressin acetate injection will often maintain hemostasis in patients with mild to moderate von Willebrand’s disease during surgical procedures and postoperatively when administered 30 minutes prior to the scheduled procedure

The patient has Von Willebrand activity 30%, antigen 43%, factor VIII 43%, which suggests mild to moderate von Willebrand’s disease. Given the patient's planned major surgery, desmopressin acetate injection may be considered to maintain hemostasis. However, it is essential to monitor the patient's factor VIII coagulant activity, ristocetin cofactor activity, and von Willebrand factor antigen during administration of desmopressin acetate injection to ensure adequate levels are being achieved 2. Additionally, caution should be exercised due to the patient's use of SSRIs, which may increase the risk of water intoxication with hyponatremia 2. Key considerations for the patient's management include:

• Monitoring of factor VIII and von Willebrand factor levels
• Caution with fluid intake to prevent hyponatremia and water intoxication
• Careful monitoring of the patient's response to desmopressin acetate injection It is crucial to weigh the therapeutic advantages against the possible risks in this case 2.

From the Research

Approach to the Patient

The patient presents with abnormal platelet function assay results, including COL/EPI 221 ULN 178s and COL/ADP 217 ULN 112s, which suggests a potential issue with primary hemostasis. The patient's von Willebrand activity is 30%, antigen 43%, and factor VIII 43%, with normal multimers.

Diagnostic Considerations

• The patient's results do not fulfill the criteria for a "definite" diagnosis of von Willebrand disease (VWD), but the numbers are at the cusp, and the planned surgery is a major one 3.
• The platelet function analyser (PFA-100) is a reliable tool for detecting VWF deficiency, with a high negative predictive value (0.98) and sensitivity (0.98) 4.
• The concentration and activity of plasma von Willebrand factor are routine parameters in the assessment of hemostasis disorders, and platelet von Willebrand factor is also an important contributor to primary hemostasis 5.

Management Options

• Given the patient's abnormal platelet function assay results and the planned major surgery, it is essential to carefully evaluate the patient's risk of bleeding and consider management options to minimize this risk.
• The use of desmopressin or factor VIII concentrates may be considered to increase the patient's von Willebrand factor levels and improve hemostasis 3, 6.
• The PFA-100 test can be used to monitor the patient's response to treatment and adjust management accordingly 4, 7.

Key Points

• The patient's abnormal platelet function assay results and low von Willebrand activity levels suggest a potential issue with primary hemostasis.
• The PFA-100 test is a reliable tool for detecting VWF deficiency and can be used to monitor the patient's response to treatment.
• Management options, such as desmopressin or factor VIII concentrates, may be considered to minimize the patient's risk of bleeding during surgery 3, 4, 5, 6, 7.