Emicizumab for Severe Von Willebrand Disease (VWD) and VWD/Hemophilia A

Inclusion Criteria:

• Signed informed consent
• age >/= 2
• ability to comply with protocol in investigators judgement
• diagnosis of: severe VWD type 3, or VWD with VWF antigen, activity or collagen binding
• diagnosis of VWD/hemophilia A defined as VWF:ag, activity or CB <50 U/dl, and mildmoderate or severe hemophilia A(defined by ISTH criteria) based on historical medicalrecords of the study site.
• plan to be adherent to emicizumab prophylaxis during the study
• Patient's bleeding phenotype necessitating prophylaxis per treating providerrecommendations.
• Patient on current prophylaxis for VWD or VWD/hemophilia A may enroll if they arecurrently on a ono-emicizumab agent, and if it has been > 18 months since lastoff-label dose of emicizumab, and are willing to discontinue current prophylaxis.
• For menstruating individuals: agreement to remain abstinent (refrain from heterosexualintercourse) or use contraceptive methods that result in a failure rate of < 1% peryear during the study period. A mensturating individual is considered to be ofchildbearing potential if they are post-menarchal, have not reached a postmenopausalstate (12 continuous months of amenorrhea with no identified cause other thanmenopause), and have not undergone surgical sterilization (removal of ovaries and/oruterus). Examples of highly effective contraceptive methods with a failure rate of < 1% per yearinclude proper use of combined oral or injected hormonal contraceptive, bilateral tuballigation, male sterilization, hormone-releasing intrauterine devices, and copperintrauterine devices. The reliability of sexual abstinence should be evaluated in relationto the duration of the clinical trial and the preferred and usual lifestyle of the patient.Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods)and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

• Patients age <2 years of age.
• Patients with low VWF or non-severe VWD (ie.not meeting the above criteria)
• Other concomitant bleeding disorders including coagulopathy from liver cirrhosis.
• Current treatment with emicizumab or emicizumab therapy in the previous 18 months.
• Previous (in the past 12 months) or current treatment for thromboembolic disease (withthe exception of previous catheter-associated thrombosis for which anti-thrombotictreatment is not currently ongoing) or current signs of thromboembolic disease
• Other conditions (e.g., certain autoimmune diseases, including, but not limited todiseases such as systemic lupus erythematosus, inflammatory bowel disease, andantiphospholipid syndrome) that may increase the risk of bleeding or thrombosis
• Patients who are at high risk for thrombotic microangiopathy (TMA; e.g., have aprevious medical or family history of TMA), in the investigator's judgment
• Would refuse treatment with blood or blood products, if necessary.
• Any serious medical condition or abnormality in clinical laboratory tests that, in theinvestigator's judgment, precludes the patient's safe participation in and completionof the study
• Treatment with any of the following: An investigational drug to treat or reduce the risk of hemophilic bleeds within 5half-lives of last drug administration before Study Day 1 A non-hemophilia-relatedinvestigational drug within the last 30 days or 5 halflives- before Study Day 1, whicheveris longer An investigational drug concurrently
• History of clinically significant hypersensitivity associated with monoclonal antibodytherapies or components of the emicizumab injection
• Pregnant or lactating, or intending to become pregnant during the study
• Women of childbearing potential must have a negative serum pregnancy test resultwithin 7 days before Study Day 1
• Illicit drug or alcohol abuse within 12 months prior to screening, in theinvestigator's judgment
• Serious infection requiring oral or IV antibiotics within 30 days prior to screening