Patient case (clinical description): A 23-year-old female has prolonged oral bleeding immediately after a tooth extraction.  Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration.  The patient has heavy menstrual cycles each month.  She has no other medical problems and takes no medications.  Her mother and grandmother have also had excessive bleeding during menstrual period.  Review of systems is positive for mild bruising on his legs. Laboratory findings reveal a normal platelet count and an abnormal ristocetin cofactor assay, as well as CB <= 0.30 IU/mL and FVIII:C <= 0.40 IU/mL.

Patient's own account: I'm a 23 woman and I went to the ER because of non-stop bleeding after my tooth extraction. I tried to make the bleeding stop but it just kept going for hours and it finally stopped when I took some medication called DDAVP. I usually have heavy periods, just like my mom and grandma had. I don't have any other medical condition and I don't take any other medication. The doctor noticed the bruises on my legs. I had to do some lab tests. I had a normal platelet count but an abnormal ristocetin cofactor assay. I had low CB and FVIII:C levels.

Clinical trial: BAX 111 rVWF in Pediatrics

Eligibility criteria:
Inclusion Criteria:

          -  Diagnosis of severe von Willebrand disease (VWD) (defined as von Willebrand factor:
             ristocetin cofactor [VWF:RCo] less than [<] 20 percent [%]):

               1. Type 1 (VWF:RCo < 20 International Units per deciliter [IU/dL]); or

               2. Type 2A (VWF:RCo < 20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor
                  VIII coagulation activity [FVIII:C] < 10 % and historically documented genetics),
                  Type 2M; or

               3. Type 3 (VWF:Ag less than or equal to [=<] 3 IU/dL).

          -  Age 0 to < 18 years at the time of Screening.

          -  The participant has provided assent (if appropriate) and legally authorized
             representative(s) has provided informed consent.

          -  If female of childbearing potential, participant presents with a negative serum
             pregnancy test.

          -  If applicable, participant agrees to employ adequate birth control measures for the
             duration of the study.

          -  The participant and/or the legally authorized representative are willing and able to
             comply with the requirements of the protocol, which should also be confirmed based on
             a pre-screening evaluation held between the Investigator and the Sponsor, to ensure no
             eminent risk is present that could challenge the participants compliance with the
             study requirements.

        Additional inclusion criteria for previously treated participants and participants
        undergoing surgery are as follows:

          -  Unable to tolerate or are inadequately responsive to deamino-delta-D-arginine
             vasopressin.

          -  The participant has had a minimum of 1 documented bleed requiring VWF coagulation
             factor replacement therapy (i.e. treatment with a VWF product) during the previous 12
             months prior to enrollment and overall historically 3 or more exposure days (EDs) to
             plasma-derived von Willebrand disease (pdVWF).

        Additional inclusion criterion for previously untreated participants are as follows:

          -  The participant has not received prior VWF coagulation factor replacement therapy.

          -  Pediatric participants in the continuation study (SHP677-304 [NCT03879135]) that
             require elective or emergency surgical/invasive treatment during their participation
             in the continuation study may be considered for enrollment in this study's surgery arm
             to receive treatment with the study drug (rVWF) for peri-operative management of
             surgery related bleeds/bleeding tendency, if they continue meeting all other
             eligibility criteria for the surgery arm in this Pediatric On-Demand and Surgery
             study, 071102.

        Exclusion Criteria:

          -  Diagnosis of pseudo-VWD or another hereditary or acquired coagulation disorder (eg,
             qualitative and quantitative platelet disorders or elevated prothrombin time
             [PT]/international normalized ratio [INR] greater than [>] 1.4).

          -  History or presence of a VWF inhibitor at Screening.

          -  History or presence of a Factor VIII (FVIII) inhibitor with a titer greater than or
             equal [>=] 0.4 Bethesda units (BU) (by Nijmegen assay) or >= 0.6 BU (by Bethesda
             assay).

          -  Documented history of a VWF: RCo half-life < 6 hours.

          -  Known hypersensitivity to any of the components of the study drug, such as mouse or
             hamster proteins.

          -  Medical history of immunological disorders, excluding seasonal allergic
             rhinitis/conjunctivitis/asthma, food allergies, or animal allergies.

          -  Medical history of a thromboembolic event.

          -  Human immunodeficiency virus (HIV) positive, with an absolute CD4 count < 200/ cubic
             millimeter (mm^3).

          -  In the judgment of the Investigator, the participant has another clinically
             significant concomitant disease (e.g. uncontrolled hypertension, cancer) that may pose
             additional risks for the participant.

          -  Diagnosis of significant liver disease, as evidenced by, but not limited to, any of
             the following: serum alanine aminotransferase (ALT) of 5 times the upper limit of
             normal; hypoalbuminemia; portal vein hypertension (e.g. presence of otherwise
             unexplained splenomegaly, history of esophageal varices) or liver cirrhosis classified
             as Child B or C.

          -  Diagnosis of renal disease, with a serum creatinine level >= 2.5 milligram per
             deciliter (mg/dL).

          -  Immunomodulatory drug treatment other than anti-retroviral chemotherapy (e.g.
             α-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater
             than 10 milligram per day [mg/day] (excluding topical treatment [e.g. ointments, nasal
             sprays]), within 30 days prior to signing the informed consent (or assent, if
             appropriate).

          -  If female, participant is pregnant or lactating at the time informed consent (or
             assent, if appropriate) is obtained.

          -  Participant has participated in another clinical study involving an investigational
             product (IP), other than recombinant von Willebrand Factor (rVWF) with or without
             ADVATE, or investigational device within 30 days prior to enrollment or is scheduled
             to participate in another clinical study involving an IP other than rVWF or
             investigational device during the course of this study.

          -  Participant's legal representative is a family member or employee of the Investigator.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.

Subject must be at most 17 Years

Eligibility (NLI label): Contradiction