Effective Hemostasis

The process of blood coagulation has two distinct phases: primary hemostasis and secondary hemostasis. While factor VIII (FVIII) has a role in secondary hemostasis, von Willebrand factor (VWF) protein is the key component in primary hemostasis.

People with VWD have an insufficient amount of VWF protein in the blood, or VWF that is defective. Because VWF is essential in primary hemostasis, an insufficient amount or a supply of defective VWF interferes with proper platelet adherence or aggregation. The mainstay of VWD treatment is the replacement of the deficient VWF protein. This results in shortened bleeding time and correction of the coagulation abnormality.

Stages of Hemostasis

Slides 1, 2, and 3 illustrate the crucial role of VWF in primary hemostasis, while Slide 4 shows the process of secondary hemostasis. Slide 5 illustrates how LMW-VWF forms an impaired hemostatic plug.

When the vessel is injured, several actions occur to form the initial hemostatic plug:

VWF unfolds from its inactivated pretzel-like shape, exposing A1 domains (platelet receptors)
Collagen binds with A3 domains (collagen-binding sites)

HMW-VWF has more A3 domains and A1 domains than LMW-VWF, allowing more bonds to form.¹

At the same time, platelets rush to the injury site, forming bonds with A1 domains

On Slide 3, we see how platelet aggregation occurs when platelet thrombi, or bridges, form. The platelet bridges and VWF form layers, known as the initial hemostatic plug, which stops the bleeding at the injury site.¹

Secondary hemostasis occurs when a chain reaction of clotting factor proteins occurs (the clotting cascade), leading to additional platelet binding and the release of fibrin. The result is the formation of a stable hemostatic plug.¹

In comparison, LMW-VWF, which has few A1 and A3 domains, forms an impaired hemostatic plug, making long-term blood clotting difficult or impossible.

Successful completion of both stages of hemostasis results in the final step of the clotting process, the formation of a stable hemostatic plug.

Important Safety Information

Humate-P is indicated for treatment and prevention of bleeding in adult patients with hemophilia A (classical hemophilia). Humate-P is also indicated in adult and pediatric patients with von Willebrand disease (VWD) for (1) treatment of spontaneous and trauma-induced bleeding episodes, and (2) prevention of excessive bleeding during and after surgery. This applies to patients with severe VWD, and patients with mild and moderate VWD for whom use of desmopressin is known or suspected to be inadequate. Humate-P is not indicated for the prophylaxis of spontaneous bleeding episodes.

Humate-P is contraindicated in individuals with a history of anaphylactic or severe systemic response to antihemophilic factor or von Willebrand factor preparations.

Monitor for intravascular hemolysis and decreasing hematocrit values in patients with A, B, and AB blood groups who are receiving large or frequent doses. Also monitor VWF:RCo and FVIII levels in VWD patients, especially those undergoing surgery.

Thromboembolic events have been reported in VWD patients receiving coagulation factor replacement. Caution should be exercised and antithrombotic measures considered, particularly in patients with known risk factors for thrombosis.

Humate-P is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.

In patients receiving Humate-P in clinical studies for treatment of VWD, the most commonly reported adverse reactions observed by >5% of subjects are allergic-anaphylactic reactions, including urticaria (hives), chest tightness, rash, pruritus (itching), and edema (swelling). For patients undergoing surgery, the most common adverse reactions are postoperative wound or injection-site bleeding, and epistaxis (nosebleed).

Please see full prescribing information.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

The information provided herein is solely for use by physicians and healthcare professionals in the United States. The CSL Behring product listed may not have been approved in other countries and may not be available everywhere.

Reference

Data on file, 2005, CSL Behring LLC.