Understanding Acquired von Willebrand Syndrome (AVWS)
Most people associate von Willebrand disease (VWD) with an inherited genetic condition. It is true that the hereditary form is far more prevalent, affecting approximately 1 in 100 people in the United States, although many cases are mild and undiagnosed. However, a much rarer form, known as acquired von Willebrand syndrome (AVWS), can develop in individuals who have no prior personal or family history of the disorder. AVWS is not a birth defect, but rather a bleeding disorder that emerges later in life, typically in adulthood, and is often a direct consequence of another underlying medical issue.
How AVWS Differs from Inherited VWD
Acquired von Willebrand syndrome shares many clinical and laboratory features with its hereditary counterpart, including excessive bleeding and low levels or dysfunction of the von Willebrand factor (VWF) protein. VWF is crucial for blood clotting, as it helps platelets stick to the site of an injury and carries another important clotting protein, Factor VIII. In inherited VWD, a genetic mutation is responsible for the VWF abnormality. In contrast, AVWS is caused by other health problems that lead to the destruction, clearance, or reduced function of a person's previously normal VWF.
The key differences between acquired and inherited VWD are summarized in the table below:
| Feature | Acquired von Willebrand Syndrome (AVWS) | Inherited von Willebrand Disease (VWD) |
|---|---|---|
| Onset | Typically later in life (adulthood) | Present from birth |
| Family History | Negative for bleeding disorders | Often positive for a bleeding disorder |
| Cause | Associated with other medical conditions | Genetic mutation affecting VWF gene |
| Curability | Potentially reversible if underlying condition is treated | A lifelong condition that is managed |
| Inheritance | Not passed to offspring | Can be passed to offspring |
Underlying Conditions Associated with AVWS
AVWS is a complex condition, and its development is strongly linked to a variety of other diseases. The mechanisms vary depending on the underlying cause, but they all disrupt the body's normal production or function of VWF. Some of the most common associated conditions include:
- Lymphoproliferative and Myeloproliferative Disorders: This category includes several types of blood cancers, such as chronic lymphocytic leukemia, multiple myeloma, and essential thrombocythemia. These conditions can cause an overproduction of abnormal cells, which may either create antibodies that attack VWF or directly adsorb the factor from the blood.
- Autoimmune Diseases: Conditions in which the immune system mistakenly attacks the body's own tissues, such as systemic lupus erythematosus, are a recognized cause of AVWS. The autoantibodies produced by the immune system can target and neutralize the von Willebrand factor.
- Cardiovascular Disorders: Certain heart conditions, most notably aortic valve stenosis and the use of ventricular assist devices, can cause increased shear stress on the blood as it flows through the heart. This mechanical stress can cause large, functional VWF multimers to break down, leading to a bleeding tendency.
- Solid Tumors: Some solid tumors, including Wilms' tumor and lung cancer, can also be associated with AVWS. The exact mechanism is not always clear, but it is thought to involve the adsorption of VWF onto the surface of the tumor cells.
- Other Conditions: Other associated conditions can include hypothyroidism and certain medications. Some drugs, like valproic acid or ciprofloxacin, have been linked to the development of AVWS, with the condition often resolving once the medication is stopped.
Diagnosing Acquired von Willebrand Syndrome
Diagnosing AVWS can be challenging because its symptoms often mimic those of inherited VWD. A doctor will typically start with a physical exam and a detailed medical and family history. If a patient presents with bleeding symptoms but no family history of a bleeding disorder, the possibility of AVWS should be considered, especially if an underlying disease is present. Blood tests will then be performed to measure the levels and function of von Willebrand factor. For example, tests might show decreased VWF antigen levels or reduced ristocetin cofactor activity. A key diagnostic indicator is the absence of a prior bleeding history and the presence of a co-existing medical condition known to cause AVWS.
Management and Treatment of AVWS
Managing AVWS is a dual-pronged approach that focuses on controlling or preventing bleeding episodes and treating the underlying condition. The cornerstone of treatment is addressing the root cause, as this is the only potentially curative strategy. For example, treating the underlying blood cancer or autoimmune disease may lead to a resolution of the bleeding disorder.
Various therapies are used to manage bleeding in the interim:
- Desmopressin (DDAVP): This synthetic hormone can increase VWF levels in some patients, though its effectiveness varies depending on the underlying cause. It's often used for mild bleeding episodes or to prevent bleeding during minor procedures.
- von Willebrand Factor (VWF) Concentrates: These are infusions of VWF derived from human plasma, providing a temporary boost to clotting factor levels. They are typically reserved for more severe bleeding or major surgeries.
- Intravenous Immunoglobulin (IVIG): This therapy is particularly effective in cases of AVWS linked to certain autoimmune and lymphoproliferative disorders. It can help counteract the autoantibodies that are targeting and destroying VWF.
- Antifibrinolytic Agents: Medications like tranexamic acid can be used to stabilize blood clots and prevent their breakdown, especially for mucocutaneous bleeding.
For more detailed information on bleeding disorders and their management, you can visit the National Hemophilia Foundation.
Conclusion
While acquired von Willebrand syndrome is a rare condition, it is a crucial diagnosis to consider in a patient presenting with bleeding symptoms later in life and no prior history of bleeding disorders. Unlike inherited von Willebrand disease, AVWS is not a genetic condition but a secondary complication of another illness. The successful treatment of the underlying cause offers the best chance for reversing the bleeding disorder and restoring normal clotting function.
