What labs are recommended prior to initiating DDAVP (Desmopressin) therapy in a patient with a history of bleeding or endocrine disorders, such as diabetes insipidus, hemophilia A, or von Willebrand disease?

Laboratory Testing Prior to DDAVP Initiation

Before initiating DDAVP therapy, you must obtain serum sodium, complete blood count with platelet count, PT, PTT, and disease-specific coagulation studies including VWF antigen, VWF ristocetin cofactor activity, and factor VIII coagulant activity to establish baseline hemostatic function and exclude contraindications. 1

Essential Pre-Treatment Laboratory Assessment

Mandatory Baseline Labs for All Patients

• Serum sodium concentration must be measured and confirmed normal before starting DDAVP, as hyponatremia is the most serious adverse effect and can lead to seizures, coma, respiratory arrest, or death 1, 2
• Complete blood count (CBC) with platelet count to identify thrombocytopenia or thrombocytosis that could contribute to bleeding 3
• Prothrombin time (PT) to screen for coagulation factor deficiencies 3
• Activated partial thromboplastin time (PTT) to detect intrinsic pathway abnormalities 3

Disease-Specific Coagulation Studies

For Von Willebrand Disease

The 2008 NHLBI guidelines specify three mandatory initial VWD assays before DDAVP use 3:

• VWF antigen (VWF:Ag) - quantifies total VWF protein
• VWF ristocetin cofactor activity (VWF:RCo) - measures functional VWF activity
• Factor VIII coagulant activity (FVIII) - must be >5% for DDAVP to be indicated 1

Critical determination: Calculate the ratio of VWF:RCo to VWF:Ag. If this ratio is abnormally low (below 0.5-0.7), specialized VWD assays including multimer analysis should be performed to identify VWD subtypes, as DDAVP is contraindicated in Type 2B 3, 4, 5

For Hemophilia A

• Factor VIII coagulant activity levels must be verified to be >5% before DDAVP use 1
• Exclude the presence of factor VIII autoantibodies prior to treatment 1
• Patients with factor VIII levels between 2-5% may be considered for DDAVP trial but require careful monitoring 1

Critical Exclusion Criteria Based on Laboratory Results

Absolute Contraindications

DDAVP is contraindicated in Type 2B von Willebrand disease because it can cause severe thrombocytopenia 4, 5, 6. The American Heart Association recommends VWF/FVIII concentrates rather than DDAVP as first-line therapy for Type 2B VWD 4

Identifying Type 2B VWD Pre-Treatment

• If VWF:RCo to VWF:Ag ratio is <0.5-0.7, perform VWF multimer analysis to exclude Type 2B before administering DDAVP 3
• Isolated decreased platelets may occur in VWD Type 2B, making baseline platelet count essential 3

On-Treatment Monitoring Requirements

Sodium Monitoring Protocol

The FDA mandates specific sodium monitoring intervals 1:

• Within 7 days after initiating therapy
• Approximately 1 month after initiating therapy
• Periodically during treatment
• More frequently in patients ≥65 years and those at increased risk of hyponatremia

Hemostatic Monitoring During Treatment

For von Willebrand disease patients receiving repeated doses 1:

• Bleeding time assessment
• Factor VIII coagulant activity levels
• Ristocetin cofactor activity
• Von Willebrand antigen levels

These ensure adequate hemostatic levels are being achieved during treatment 1

Important Pre-Treatment Considerations

Patient-Specific Factors Affecting Laboratory Values

Several conditions can falsely elevate VWF and FVIII levels, potentially masking underlying deficiency 3:

• Acute or chronic inflammatory illness elevates VWF and FVIII
• Pregnancy or estrogen/oral contraceptive use increases levels
• Patient stress, anxiety, or recent exercise can elevate VWF levels
• Blood group O individuals have VWF levels 25% lower than other ABO groups
• African-Americans have higher baseline VWF levels than Caucasians

Ensure blood draw is atraumatic and patient is calm to avoid falsely elevated results 3

Sample Processing Requirements

• Blood samples for VWF assays must be transported at room temperature to prevent cryoprecipitation 3
• Plasma should be separated promptly at room temperature and centrifuged thoroughly to remove platelets 3
• Avoid lipemia as it interferes with photo-optical testing methods used for VWF:RCo assay 3

Common Pitfalls to Avoid

• Never initiate DDAVP without confirming normal serum sodium - hyponatremia is life-threatening and occurred even with appropriate fluid restriction in pediatric studies 2
• Do not assume Type 1 VWD without multimer analysis if VWF:RCo/VWF:Ag ratio is low - Type 2B requires different treatment and DDAVP is contraindicated 4, 5
• Avoid testing during acute illness or stress - inflammatory conditions and anxiety falsely elevate VWF and FVIII, potentially leading to missed diagnoses 3
• In severe VWD (Type 3), DDAVP is completely ineffective due to virtually complete absence of VWF; these patients require VWF/FVIII concentrates 5