Intravenous Immunoglobulin Temporarily Improves Bleeding in Patients With Acquired Von Willebrand Syndrome

Intravenous immunoglobulin (IVIG) offered temporary improvement in condition of a patient with acquired von Willebrand syndrome (AVWS) due to a monoclonal gammopathy, emphasizing the importance of a correct diagnosis of AVWS and appropriate treatment thereafter, according to a case report published in eJHaem.¹

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AVWS is a distinct bleeding order that is a subtype of von Willebrand disease (VWD), representing 1% to 5% of all cases. This form of the disease is not typically inherited but is due to underlying disease or autoimmune, lymphoproliferative, or myeloproliferative disorder.^1,2

It can be difficult to differentiate AVWS from VWD due to the laboratory and clinical similarities that could exist during the initial patient evaluation. Despite the relative rarity of fatalities from bleeding due to AVWS, it is essential that the appropriate therapy to control bleeding is selected.¹

In a review published in Thrombosis Research, authors described the importance of a thorough patient evaluation when AVWS is suspected. They wrote that recently developed diagnostic algorithms can assist clinicians with diagnosis and differentiation between AVWS and VWD.³

Additionally, they explained that AVWS should always be considered in patients with new-onset bleedings whenever laboratory results suggest VWD. This is particularly important if there are any AVWS-associated disorders in the patient.³ Incorrect diagnosis could lead to AVWS being missed, with fatal consequences possible.¹

In the current case study, the investigators treated a 69-year-old woman who was originally believed to have VWD but was later determined to have AVWS.¹ A few months after her initial presentation for presumed VWD, she was hospitalized for weakness and melena, with a work-up indicating acute anemia. Three subsequent readmissions were required for continuing gastrointestinal bleeding, necessitating red blood cell transfusions.¹

Examination by an outpatient hematologist raised concern for type 1 VWD. Upon being referred to the study investigators, she denied any major bleeding during childhood or a family history of bleeding diathesis after inquiry. Additional work-up showed persistently low von Willebrand factor (VWF):Ag, FVIII:C, and VWF:GP1bM, and a multimer analysis detected the lack of high molecular weight multimers.¹

These factors, plus the absence of childhood bleeding and the presentation of significant bleeding later in life following various procedures, led to suspected AVWS. Due to concern for an AVWS secondary caused by an underlying IgG monoclonal gammopathy, the patient was treated with IVIG at a dose of 1 g/kg over 2 days.¹

IVIG was successful in treating the patient, who had no further bleeding. IVIG was continued every 4 weeks, according to the study investigators.¹

Each patient with AVWS requires treatment that is dependent on the cause. IVIG can prevent the increased clearance of VWF in the liver that is associated with the subtype of AVWS that the patient had, leading to the initiation of IVIG treatment.¹

Based on the successful treatment, the investigators wrote that IVIG can be reasonably considered as a first-line therapeutic in patients with AVWS secondary to IgG. However, they cautioned that, for patients who need a more sustained response, alternative therapies can be simultaneously considered.¹

“Given the short duration of benefits with IVIG, it is best to plan procedures and confirm response to IVIG in advance of the procedure. Further, it would be prudent to maintain the patient on IVIG infusion every 3–4 weeks post-procedure to maintain hemostasis,” the investigators concluded.¹

Pharmacists play an essential role in determining not only the correct diagnosis in patients with suspected AVWS but must be sure to prescribe effective and proven treatments. There must be adequate supply of medications and know that patients with AVWS or VWD need substantial personalized care to improve outcomes.²

“Every speciality pharmacist should know the patient’s specific VWD subtype, bleeding history, and typical plasma levels of vWF and factor VIII,” Tim Affeldt told Pharmacy Times at the Asembia Speciality Pharmacy Summit.²

REFERENCES

1. Zablonski KG, Rajkumar A, Nayak L. Intravenous immunoglobulin offers temporary improvement in acquired von Willebrand syndrome due to monoclonal gammopathy: a case report. eJHaem. 2024. doi:10.1002/jha2.969

2. Pharmacy Times. Personalizing care in von Willebrand disease is essential. Published May 2, 2019. Accessed July 23, 2024. https://www.pharmacytimes.com/view/personalizing-care-in-von-willebrand-disease-is-essential

3. Tiede A. Diagnosis and treatment of acquired von Willebrand syndrome. Thombosis Research. 2012;130(2):S2-S6. doi:10.1016/S0049-3848(13)70003-3