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Coagulation Disorders: Common Clotting Factor Deficiency Disease States, Associated Systemic and/or Local Hemostasis Adjuncts, and Dental Management Guidelines

HEMOPHILIA A AND HEMOPHILIA B: OVERVIEW, FACTS, AND MANAGEMENT

Hemophilia A and Hemophilia B

Hemophilia A, hemophilia B, and von Willebrand Disease (vWD) are the three most common inherited bleeding disorders. Hemophilia A and hemophilia B (Christmas disease) are x-linked recessive traits that affect only males. Females are often carriers unless both parents carry the hemophilia gene. Either hemophilia is often diagnosed in childhood, though mild hemophiliacs may remain undiagnosed until adulthood. Clinical history is often positive for joint hemorrhage (hemarthroses) with joint deformities, gingival hemorrhage, persistent oral bleeding, and bleeding into soft tissues.

Hemophilia A is associated with Factor VIII deficiency, and hemophilia B is associated with Factor IX deficiency. Factor VIII has a half-life activity of 8–12 hours. Factor IX has a half-life activity of 12–24 hours. Factor VIII and Factor IX are part of the “intrinsic” pathway, and patients with hemophilia will present with a prolonged APTT test. The PT is normal because the extrinsic pathway is not affected; the bleeding time (BT) and the platelet count are also normal because platelets are not affected with either hemophilia. It is important to remember that patients with hemophilia A and B can have mild, moderate, or severe disease depending on the factor activity levels of Factors VIII or IX, respectively.

Hemophilia Severity Classification

Hemophilia can be of mild, moderate, or severe intensity:

Hemophilia A and B Treatment

Factor replacement therapy with the specific clotting factor is the treatment of choice for hemophilias A and B. Most patients with mild hemophilia A can be treated with desmopressin (DDAVP/Stimate). DDAVP/Stimate is a synthetic analogue of vasopressin. It stimulates the release of Factor VIII, von Willebrand’s Factor (vWF), and tissue plasminogen activator from the endothelial storage sites. There is a two- to threefold increase of Factor VIII from baseline level. At least 25–30% Factor VIII activity is needed for adequate hemostasis.

DDAVP/Stimate Therapy for Hemophilia A

DDAVP/Stimate is given orally, intravenously, or intranasally prior to a planned dental procedure to prevent bleeding. DDAVP should not be used too frequently because it can deplete the storage pools. Do not use DDAVP more than twice or three times over a 48-hour period.

DDAVP Dosing

Note that DDAVP is not used in the management of hemophilia B because it does not stimulate the release of Factor IX.

Hemophilia A and B Clotting Factor Replacement Therapy

The moderate and severe hemophilia A or B patient will always need specific Factor replacement prior to any major or minor dental procedure, and this includes probing or local anesthesia injection. One unit of Factor VIII/kg provides a 2% rise in Factor VIII level. To provide recombinant Factor VIII replacement, the clinician needs to obtain baseline Factor VIII activity and then correct to the desired percentage of factor activity. The factor activity level must be rechecked to confirm adequate replacement. The replacement formula for Factor VIII is as follows: {(% Desired − % Actual)/2%} × Wt (kg) = # units. One unit Factor IX/kg provides a 1% rise in Factor IX level. Here, too, the clinician needs to obtain baseline Factor IX activity and correct to desired percentage factor activity. Recheck factor activity to confirm adequate replacement. Factor IX replacement formula is as follows: (% Desired − % Actual) × Wt (kg) = # units. Clearly, in both cases, the clotting Factor dose prior to surgery will depend on the severity of bleeding expected and is decided by the patient’s physician: 50% Factor activity is a must for block anesthesia.

The commercial Factors are powders that need to be dissolved in sterile water prior to use. Often it is the patient who injects the factor intravenously (IV), approximately 15 minutes prior to a planned procedure.

Repeat infusions every 8–12 hours for Factor VIII and every 12–24 hours for Factor IX; this will depend on the planned dental procedure, the extent of postop bleeding, and if antifibrinolytic drugs tranexamic acid (Cyklokapron) or epsilon aminocaproic acid (Amicar) have been prescribed. The antifibrinolytic drugs prevent fibrinolysis/clot breakdown by inhibiting the activation of plasminogen to plasmin.

Factors VIII and IX Sources

Factors VIII and IX are obtained from two sources:

Factor VIII Products for Hemophilia A

The Factor VIII products available for hemophilia A are: