Hemophilia A Medication
- Author: Robert A Zaiden, MD; Chief Editor: Steven C Dronen, MD, FAAEM more...
Medication Summary
Factor VIII is the treatment of choice for acute or potential hemorrhage. Recombinant factor VIII concentrate is the preferred source of factor VIII. The factor VIII activity level should be corrected to 100% of normal for potentially serious hemorrhage (eg, CNS, trauma related, GI, genitourinary [GU], epistaxis) and to 30-50% of normal for minor hemorrhage (eg, hemarthrosis, oral mucosal, muscular).
One unit of factor VIII is the amount of factor VIII in 1 mL of plasma (1 U/mL or 1%). The volume of distribution of factor VIII is that of plasma, approximately 50 mL/kg. The difference between the desired factor VIII activity level and the patient's native factor VIII activity level can be calculated by simple subtraction and expressed as a fraction (eg, 100% - 5% = 95% or 0.95).
To find the number of units of factor VIII needed to correct the factor VIII activity level, use the following formula:
Units factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus the native factor VIII level)
As an example, an 80-kg individual diagnosed with hemophilia with known 1% factor VIII activity level presents to the emergency department with a severe upper GI bleed. The correct dose of factor VIII to administer to the patient would be calculated as follows:
Units factor VIII = (80 kg)(50 mL/kg)(1 U factor VIII/mL)(.99) = 3960
The next dose should be administered 12 hours after the initial dose and is one half the initial calculated dose. Minor hemorrhage requires 1-3 doses of factor VIII. Major hemorrhage requires many doses and continued factor VIII activity monitoring with the goal of keeping the trough activity level at least 50%. Continuous infusions of factor VIII may be considered for major hemorrhage.
The specific factor product patients use is often part of their individualized treatment plan. Patients will usually be well educated on their dosing/products. This information also can be found on institutional treatment center/blood bank databases.
Prophylactic administration of factor VIII is often recommended for pediatric patients with severe disease.
Other medicinal adjuncts to factor VIII (eg, desmopressin acetate [DDAVP], antifibrinolytics) often are useful in achieving hemostasis and can lessen the need for factor VIII infusion.
Antifibrinolytic agents, such as aminocaproic acid and tranexamic acid, are contraindicated as initial therapies for hemophilia-related hematuria originating from the upper urinary tract because they can cause obstructive uropathy or anuria.
Factor VIII-Containing Products
Class Summary
These agents replace deficient FVIII in patients with hemophilia A, with the goals of achieving a normal hematologic response to hemorrhage or preventing hemorrhage. Recombinant products should be used initially and subsequently in all newly diagnosed cases of hemophilia that require factor replacement.
Factor VIII, human plasma derived (Monarc M, Monoclate, Hemofil M, Koate-DVI)
This is a pooled plasma product (high purity).
Factor VIII, human plasma derived (Recombinate, Kogenate, Helixate, Advate, Xyntha)
These are synthetic products and are the most commonly used treatment when the administration of factor is indicated.
Fresh frozen plasma (FFP)
This blood product is no longer used in hemophilia A because of the lack of safe viral elimination and concerns regarding volume overload.
Antifibrinolytics
Class Summary
These agents are used in addition to factor VIII replacement for oral mucosal hemorrhage and prophylaxis, as the oral mucosa is rich in native fibrinolytic activity. Their use is contraindicated as initial therapies for hemophilia-related hematuria originating from the upper urinary tract because they can cause obstructive uropathy or anuria. They should not be used in combination with prothrombin complex concentrate (PCC).
Epsilon aminocaproic acid (Amicar)
This lysine inhibits fibrinolysis by inhibiting plasminogen activator substances and, to a lesser degree, antiplasmin activity. The principal drawbacks of this agent are that thrombi formed during treatment are not lysed, and its effectiveness is uncertain. It has been used to prevent recurrence of subarachnoid hemorrhage.
This agent is widely distributed. Its half-life is 1-2 h. Peak effect occurs within 2 h. Hepatic metabolism is minimal.
Tranexamic acid (Cyklokapron)
This agent is an alternative to aminocaproic acid. It inhibits fibrinolysis by displacing plasminogen from fibrin.
Antihemophilic Agents
Class Summary
These agents raise endogenous FVIII levels in mild hemophilia A. Increases as much as 3-fold from the baseline are observed, with peak responses at 30-60 minutes after infusion.[29] These agents are used to prevent and/or control bleeding in patients with hemophilia A and inhibitors to FVIII.
Plasma-derived prothrombin complex concentrates/Factor IX complex concentrates (Bebulin, Profilnine SD)
These replace deficient FIX and other factors in the complex.
Desmopressin (DDAVP, Stimate)
Desmopressin causes a transient increase (up to 4-fold) in factor VIII plasma levels of those patients with mild disease. It also produces a dose-dependent increase in plasminogen activator. It is useful for minor hemorrhage episodes only. It may be useful in patients with factor VIII inhibitors.
Desmopressin Increases the cellular permeability of the collecting ducts, resulting in renal reabsorption of water. Tachyphylaxis may occur even after first dose, but drug can be effective again after several days.
Anti-inhibitor coagulant complex (FEIBA VH)
This agent is a freeze-dried sterile human plasma fraction with factor VIII inhibitor bypassing activity. It contains factors II, IX, and X, mainly nonactivated; and factor VII, mainly in the activated form.
Plasma-derived coagulation factor IX concentrate (Alpha Nine SD, Mononine, BeneFIX)
This replaces deficient FIX and other factors in the complex. AlphaNine SD and Mononine contain only FIX. BeneFIX is a recombinant product.
Coagulation Factor VIIa, Recombinants
Class Summary
These agents can activate coagulation factor X to factor Xa, as well as coagulation factor IX to IXa, increasing local formation of thrombin and fibrin, to facilitate the formation of a hemostatic plug.
Factor VIIa, recombinant (NovoSeven)
Recombinant factor VIIa is indicated for the treatment of bleeding episodes in patients with hemophilia A and inhibitors. When complexed with tissue factor, this agent can activate coagulation factor X to factor Xa as well as coagulation factor IX to IXa. Factor Xa, in complex with other factors then converts prothrombin to thrombin, which leads to the formation of a hemostatic plug by converting fibrinogen to fibrin and thereby inducing local hemostasis. This process may also occur on the surface of activated platelets.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies are used to bind to specific antigens, thereby stimulating the immune system to target these antigens.
Rituximab (Rituxan)
This agent is a monoclonal antibody directed against the CD20 antigen on B-lymphocytes. It is recommended as second-line therapy in the treatment of factor VIII inhibitors, especially in cases with high inhibitor titers.
Rituximab binds to, and mediates destruction of, B-cells, thereby decreasing production of FVIII inhibitors and autoimmunization.
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| Classification | Factor Activity, % | Cause of Hemorrhage |
| Mild | >5-40 | Major trauma or surgery |
| Moderate | 1-5 | Mild-to-moderate trauma |
| Severe | < 1 | Spontaneous, hemarthrosis |
| Indication or Site of Bleeding | Factor level Desired, % | FVIII Dose, IU/kg* | Comment |
| Severe epistaxis; mouth, lip, tongue, or dental work | 20-50 | 10-25 | Consider aminocaproic acid (Amicar), 1-2 d |
| Joint (hip or groin) | 40 | 20 | Repeat transfusion in 24-48 h |
| Soft tissue or muscle | 20-40 | 10-20 | No therapy if site small and not enlarging (transfuse if enlarging) |
| Muscle (calf and forearm) | 30-40 | 15-20 | None |
| Muscle deep (thigh, hip, iliopsoas) | 40-60 | 20-30 | Transfuse, repeat at 24 h, then as needed |
| Neck or throat | 50-80 | 25-40 | None |
| Hematuria | 40 | 20 | Transfuse to 40% then rest and hydration |
| Laceration | 40 | 20 | Transfuse until wound healed |
| GI or retroperitoneal bleeding | 60-80 | 30-40 | None |
| Head trauma (no evidence of CNS bleeding) | 50 | 25 | None |
| Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs) | 100 | 50 | Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented† |
| Trauma with bleeding, surgery† | 80-100 | 50 | 10-14 d |
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