Off-label therapy helps control severe bleeding in acquired VWS case
Emicizumab was added after conventional hemostatic treatments had failed
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A multimodal treatment approach that included off-label emicizumab, a drug approved for hemophilia A, stopped severe, hard-to-treat gastrointestinal bleeding in a 72-year-old woman with acquired von Willebrand syndrome (VWS) caused by multiple myeloma, a type of blood cancer.
Case details were described in the study, “Multimodal management of refractory gastrointestinal bleeding in myeloma-associated acquired von Willebrand syndrome: a role for emicizumab prophylaxis,” published in the Journal of Thrombosis and Haemostasis.
Acquired VWS is most commonly associated with disorders involving abnormal growth of immune cells, including some blood cancers such as multiple myeloma. In plasma cell disorders such as multiple myeloma, abnormal immunoglobulins can bind to von Willebrand factor (VWF), a protein needed for normal blood clotting, or speed its removal from the body, reducing the amount of functional VWF available.
Rapid VWF clearance can make acquired VWS difficult to treat
Treating acquired VWS can be challenging because the body often clears infused VWF too quickly for replacement therapy to work. Treating the underlying disease leads to an acquired VWS response in about 71% of cases linked to plasma cell disorders.
Emicizumab, sold as Hemlibra, is an antibody-based therapy that’s approved to prevent or reduce bleeds in people with hemophilia A, a genetic bleeding disorder.
Researchers in Croatia described what they said is the first reported case of emicizumab use in acquired VWS caused by multiple myeloma.
A 72-year-old woman had no personal or family history of bleeding problems when recurrent nosebleeds began in 2013. In 2017, a severe episode required surgery, nasal packing, and blood transfusions.
She was also diagnosed with Hashimoto’s hypothyroidism, an autoimmune disorder that affects the thyroid gland. The condition, the authors note, may have contributed to her acquired VWS by reducing VWF production, though this effect is typically mild.
In October 2019, gum bleeding led to a blood test showing low levels of the blood-clotting factors VIII and VWF. Treatment with concentrated VWF/factor VIII produced only a minimal response, and genetic testing ruled out inherited von Willebrand disease.
She had intermittent bleeding between 2019 and 2024 that was managed with tranexamic acid, along with episodes of melena (dark, tarry stools from intestinal bleeding) accompanied by iron deficiency anemia, which occurs when the body does not have enough iron to make healthy red blood cells. In April 2023, she was hospitalized with melena, low hemoglobin levels — hemoglobin is the protein in red blood cells that carries oxygen — and a heart murmur. She received red blood cell transfusions and intravenous (into-the-vein) iron.
In July 2024, a pathologic collarbone fracture led to the diagnosis of multiple myeloma, with plasma cells accounting for an abnormal 70% of her bone marrow. First-line myeloma treatment markedly reduced markers of the disease after two cycles.
GI bleeding worsens despite response to myeloma treatment
Despite this response, she experienced worsening gastrointestinal bleeding from December 2024 through July 2025. She was hospitalized seven times, had very low hemoglobin levels, and required repeated blood transfusions.
During this period, doctors tried multiple treatments to control the bleeding, but with minimal or short-lived effect. These included VWF/factor VIII concentrates, factor VIIa, desmopressin, tranexamic acid, and therapeutic plasmapheresis, a procedure that filters the blood.
Imaging repeatedly traced the bleeding to the jejunum, part of the small intestine, where an actively bleeding abnormal blood vessel was identified. Doctors treated the vessel during an endoscopic procedure, but the bleeding later returned. A second endoscopic procedure was needed in July 2025.
Myeloma treatment was then switched in April 2025 because of the ongoing bleeding and neutropenia, or low levels of neutrophils, a type of white blood cell. After nine cycles, the woman had reached a very good partial response to the cancer treatment.
In July 2025, she began treatment with off-label emicizumab, given as an under-the-skin injection, along with octreotide, a drug that reduces blood flow to the gut. The researchers described this decision as a risk-benefit assessment, weighing the patient’s severe bleeding against an uncertain risk of blood clots associated with emicizumab.
Within weeks, the gastrointestinal bleeding stopped completely. One year after starting emicizumab, her hemoglobin levels were normal, tests for blood in the stool were negative, and she had no bruising or further need for blood transfusions. Her myeloma remained in very good partial response, though her VWF activity remained low. Because several treatments were used together, the researchers noted that the individual contribution of each intervention could not be determined from this single case.
“Emicizumab may represent a valuable component of such a strategy when conventional hemostatic measures fail. Further studies are needed to define its optimal role in this setting,” the scientists concluded.
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