This presentation gives general overview of Von willebrand disease.

1. Von Willebrand Disease

2. What is VWD?
• Von Willebrand disease (VWD) is a genetic disorder caused by missing or
defective Von Willebrand factor (VWF), a clotting protein. VWF binds factor
VIII, a key clotting protein, and platelets in blood vessel walls, which help
form a platelet plug during the clotting process.
• VWD is the most common bleeding disorder
• It is carried on chromosome 12 and occurs equally in men and women.

5. Symptoms
• People with VWD experience frequent nosebleeds,
easy bruising and excessive bleeding during and after
invasive procedures, such as tooth extractions and
surgery. Women often experience menorrhagia, heavy
menstrual periods that last longer than average, and
hemorrhaging after childbirth.

6. Clinical Screening for an Underlying Disorder of
Hemostasis in the Adult Patient With Excessive
Menstrual Bleeding*
• Initial screening for an underlying disorder of hemostasis in patients with excessive menstrual bleeding
should be structured by the medical history. A positive screening result* comprises the following
circumstances:
• Heavy menstrual bleeding since menarche
• One of the following conditions:
 Postpartum hemorrhage
 Surgery-related bleeding
 Bleeding associated with dental work
• Two or more of the following conditions:
 Epistaxis, one to two times per month
 Frequent gum bleeding
 Family history of bleeding symptoms

7. TYPES
• There are three main types of VWD based on qualitative or quantitative defects
inVWF. A fourth type, acquiredVWD, is not hereditary.
• Type 1 VWD is found in 60%-80% of patients. People with type 1 VWD have a quantitative deficiency
of VWF. Levels of VWF in the blood range from 20%-50% of normal. The symptoms are usually mild.
• Type 2 VWD is found in 15%-30% of patients. People with type 2 VWD have a qualitative deficiency in
their VWF. Type 2 is broken down into four subtypes: type 2A, type 2B, type 2M and type 2N,
depending on the presence and behavior of multimers, molecular chains of VWF. Symptoms are mild
to moderate.
• Type 3 VWD is found in 5%-10% of patients. People with type 3 VWD have a quantitative deficiency of
VWF. Symptoms are typically severe, and include spontaneous bleeding episodes, often into their joints
and muscles.
• Acquired VWD. This type of VWD in adults results after a diagnosis of an autoimmune disease, such as
lupus, or from heart disease or some types of cancer. It can also occur after taking certain medications.

10. DIAGNOSIS
• When VWD is suspected, blood plasma of a patient must be investigated for quantitative and
qualitative deficiencies of VWF. This is achieved by measuring the amount of VWF in a VWF antigen
assay and the functionality of VWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay,
or a ristocetin cofactor activity (RiCof) or ristocetin induced platelet agglutination (RIPA) assays.
• Factor VIII levels are also performed because factor VIII is bound to VWF which protects the factor VIII
from rapid breakdown within the blood. Deficiency of VWF can then lead to a reduction in factor VIII
levels, which explains the elevation in PTT time. Normal levels do not exclude all forms of VWD,
particularly type 2, which may only be revealed by investigating platelet interaction with
subendothelium under flow, a highly specialized coagulation study not routinely performed in
most medical laboratories. A platelet aggregation assay will show an abnormal response to ristocetin
with normal responses to the other agonists used. A platelet function assay may give an abnormal
collagen/adrenaline closure time, and in most cases, a normal collagen/ADP time. Type 2N may be
considered if factor VIII levels are disproportionately low, but confirmation requires a "factor VIII
binding" assay. Detection of VWD is complicated by VWF being an acute phase reactant with levels
rising in infection, pregnancy, and stress.

11. • Other tests performed in any patient with bleeding problems are a complete
blood count (especially platelet counts), activated partial thromboplastin
time, prothrombin time, thrombin time, and fibrinogen level. Testing for factor
IX may also be performed if hemophilia B is suspected. Other coagulation
factor assays may be performed depending on the results of a coagulation
screen. Patients with von Willebrand disease typically display a normal
prothrombin time and a variable prolongation of partial thromboplastin time.

12. Gynecologic Considerations
• The association of von Willebrand disease with other gynecologic
problems—including ovarian cysts, endometriosis, and leiomyoma—is
uncertain. Heavy menstrual bleeding or hemorrhagic ovarian cysts may be
managed with combined hormonal contraceptives, which can address both
the bleeding and the development of hemorrhagic cysts. For the acute
presentation of a ruptured ovarian cyst, patients with von Willebrand disease
may require surgical intervention for hemostasis.

13. Hormonal Treatments
• Levonorgestrel-releasing intrauterine system may be effective for this population. Use of
progestin-only contraceptives, such as medroxyprogesterone acetate; progestin-only pills;
and the progestin implant, also may reduce menstrual flow in the setting of bleeding
disorders.
• For women without bleeding disorders, use of combined oral contraceptives or the
levonorgestrel-releasing intrauterine system reduce menstrual bleeding. Limited studies in
women with von Willebrand disease and heavy menstrual bleeding suggest these
treatments also may be effective for this population. Although oral progestins (taken for 21
days of the cycle) and depot medroxyprogesterone acetate are effective for women with
heavy menstrual bleeding without bleeding disorders and may be effective for women with
bleeding disorders as well.

14. Nonhormonal Treatments
• Nonhormonal treatment options include antifibrinolytic agents, such as tranexamic
acid and ε-aminocaproic acid .Therapies generally prescribed in conjunction with a
hematologist once a diagnosis of von Willebrand disease is established include
desmopressin acetate, recombinant factor VIII, and VWF complex infusion.
Desmopressin acetate is a synthetic derivative of the antidiuretic hormone
vasopressin and works by stimulating the release of VWF from endothelial cells.
Recombinant factor VIII and VWF complex infusion are plasma-derived concentrates
used to replace factor VIII and VWF, respectively.

15. Obstetric Considerations
• Obstetric concerns regarding patients with bleeding disorders include spontaneous
abortion, mode of delivery, epidural management, operative delivery techniques, and
postpartum hemorrhage. Patients with an underlying bleeding disorder are at a high risk of
epidural or spinal hematoma. Many experts advocate that women with von Willebrand
disease may have a vaginal delivery safely, with cesarean delivery reserved for standard
indications. Because von Willebrand disease can be transmitted as an autosomal dominant
or recessive trait, the fetus can have up to a 50% risk of being affected. Procedures, such as
fetal scalp electrode or fetal scalp sampling, are better avoided, and circumcision should be
postponed until the newborn’s VWD status is determined. Operative vaginal deliveries, in
which there may be an increased risk of trauma to the newborn, should be avoided because
of the potential risk of intracranial hemorrhage.

16. Safety steps to take during
pregnancy
• For prenatal care and delivery, consider using a medical center that specializes in high-risk
obstetrics and has a hematologist on staff.
• preventing serious blood loss before any invasive procedure, such as amniocentesis.
• During third trimester,blood tests to measure von Willebrand factor and factor VIII again to
help plan for delivery.
• anesthesiologist consultation before delivery to review choices for anesthesia and to discuss
taking medicine to reduce bleeding risk.
• Consultation with pediatric hematologist regarding the evaluation of the baby after delivery. If
there is boy and plan for circumcision, consider waiting until he has been tested and it is
deemed safe to perform the procedure.

17. Treatment
• Treatment for VWD depends on the diagnosis and severity. The mainstay of treatment is
DDAVP (desmopressin acetate), the synthetic version of a natural hormone vasopressin,. It
stimulates the release of VWF from cells, which also increases FVIII.DDAVP comes in two
forms: injectable and nasal spray. Because DDAVP is an antidiuretic, causing the body to
retain water, fluid restrictions are important so patients don’t develop hyponatremia,
reduced sodium in the bloodstream.
• There are a few clotting factor concentrates that are rich in VWF, and are recommended for
patients with VWD. These therapies are given by intravenous infusion.