Hemophilia A (Factor VIII Deficiency) Medication

Updated: Jul 05, 2023
  • Author: Douglass A Drelich, MD; Chief Editor: Srikanth Nagalla, MD, MS, FACP  more...
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Medication Summary

Factor VIII (FVIII) is the treatment of choice for acute or potential hemorrhage. Recombinant FVIII concentrate is generally the preferred source of factor VIII. Prophylactic administration of FVIII is often recommended for patients with severe disease. The FVIII activity level should be corrected to 100% of normal for potentially serious hemorrhage (eg, central nervous system, trauma related, gastrointestinal [GI], genitourinary, epistaxis) and to 30-50% of normal for minor hemorrhage (eg, hemarthrosis, oral mucosal, muscular).

One unit of FVIII is the amount of FVIII in 1 mL of plasma (1 U/mL or 1%). The volume of distribution of FVIII is that of plasma, approximately 50 mL/kg. The difference between the desired FVIII activity level and the patient's native FVIII activity level can be calculated by simple subtraction and expressed as a fraction (eg, 100% - 5% = 95% or 0.95). 

To determine the number of units of FVIII needed to correct the FVIII activity level, use the following formula:

Units FVIII = (weight in kg)(50 mL plasma/kg)(1 U FVIII/mL plasma)(desired FVIII level minus the native FVIII level)

As an example, an 80-kg individual diagnosed with hemophilia with known 1% FVIII activity level presents to the emergency department with a severe upper GI bleed. The correct dose of FVIII to administer in this case would be calculated as follows:

Units FVIII = (80 kg)(50 mL/kg)(1 U FVIII/mL)(0.99) = 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 FVIII. Major hemorrhage requires many doses and continued monitoring of FVIII activity with the goal of keeping the trough activity level at no lower than 50%. Continuous infusions of FVIII may be considered for major hemorrhage.  It is important to recall that response to factor replacement and half-life of product varies substantially across the population and that therapy should ideally be individualized for that patient.  Peak and trough values drawn after a treatment and just prior to next treatment can be very helpful in individualizing therapy.

The specific factor product that patients use is often part of their individualized treatment plan. Patients, or parents of young children, will usually be well educated on their dosing/products. This information also can be found on institutional treatment center/blood bank databases.

Other medicinal adjuncts to factor VIII (eg, desmopressin acetate [DDAVP], antifibrinolytics) often are useful in achieving hemostasis and can lessen the need for FVIII infusion. Antifibrinolytic agents, such as aminocaproic acid and tranexamic acid, are especially useful for oral mucosal bleeds but are contraindicated as initial therapies for hemophilia-related hematuria originating from the upper urinary tract because they can cause obstructive uropathy or anuria.


Coagulation Factors

Class Summary

FVIII concentrates replace deficient FVIII in patients with hemophilia A, with the goal 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. Agents that bypass FVIII activity in the clotting cascade (eg, activated FVII) are used in patients with FVIII inhibitors.

Antihemophilic factor recombinant (Advate, Adynovate, Afstyla, Eloctate, Helixate FS, Jivi, Kogenate FS, Kovaltry, NovoEight, Nuwiq, Obizur, Recombinate, Xyntha)

These are synthetic products and are the most commonly used form of treatment when the administration of clotting protein factor VIII is indicated. In hemophilia A patients, it temporarily restores hemostasis

Factor VIII, human plasma derived (Monoclate-P, Hemofil M, Koate DVI)

These are pooled plasma products (high purity) with factor VIII, which is necessary for stable clot formation and for maintenance of hemostasis.

Anti-inhibitor coagulant complex (Feiba NF, Feiba VH Immuno)

This agent is a freeze-dried sterile human plasma fraction with FVIII inhibitor bypassing activity. It contains factors II, IX, and X, mainly nonactivated; and FVII, mainly in the activated form. It may shorten the activated partial thromboplastin time of plasma containing factor VIII inhibitors.

Anti-inhibitor coagulant complex is indicated for prevention and control of spontaneous hemorrhage or bleeding during surgical interventions in hemophilia patients who have autoantibodies or alloantibodies to coagulation factors. It is also indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.

Factor VIIa, recombinant (NovoSeven RT, Sevenfact)

Recombinant activated factor (FVIIa) is indicated for the treatment of bleeding episodes in patients with hemophilia A and inhibitors. When complexed with tissue factor, this agent can activate the conversion of 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.

Antihemophilic factor/von Willebrand factor complex (Alphanate, Humate P, Wilate)

Antihemophilic Factor (FVIII) and von Willebrand Factor (VWF) are constituents of normal plasma, which are required for clotting. Temporarily increases the plasma level of FVIII, thus minimizing the hazard of hemorrhage in patients with hemophilia A; FVIII is an essential cofactor in activation of Factor X leading to formation of thrombin and fibrin. Indicated for control and prevention of bleeding episodes for hemophilia A in adults and children (brand dependent).  These concentrates have different ratios of the the amount of Factor VIII and VWF in the product and the prescriber should familiarize themselves with these differences to optomized dosing.


Monoclonal Antibodies

Class Summary

Monoclonal antibodies are used to bind to one specific substance in the body (eg, molecules, antigens). This binding is very versatile and can mimic, block, or cause changes to enact precise mechanisms (eg, bridging molecules, replacing or activating enzymes or cofactors, immune system stimulation).

Emicizumab (Hemlibra, emicizumab-kxwh)

Emicizumab is a first-in-class bispecific monoclonal antibody that bridges activated FIX and FX to restore the function of activated FVIII. It is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients (including newborns) with hemophilia A with or without factor VIII inhibitors.

Rituximab (Rituxan)

Rituximab is a monoclonal antibody directed against the CD20 antigen on B-lymphocytes. It is recommended as second-line therapy in immune tolerance induction regimens for patients with FVIII inhibitors, especially those with high inhibitor titers. This agent binds to, and mediates destruction of, B-cells, thereby decreasing production of FVIII inhibitors and autoimmunization.



Class Summary

Desmopressin transiently increases the FVIII plasma level in patients with mild hemophilia A.

Desmopressin (DDAVP, Stimate)

Desmopressin causes a transient increase (up to 4-fold) in FVIII plasma levels of patients with mild hemophilia A. 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 FVIII inhibitors.

Desmopressin Increases the cellular permeability of the collecting ducts, resulting in renal reabsorption of water.  This can result in hyponatremia which can be severe, particularly with repeat dosing. Tachyphylaxis may occur even after first dose, but drug can be effective again after several days.


Antifibrinolytic Agents

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 blocking the binding of plasminogen to fibrin and inhibiting plasminogen and conversion to plasmin, resulting in the inhibition of fibrinolysis. 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 hours. Peak effect occurs within 2 hours. Hepatic metabolism is minimal.

Tranexamic acid (Cyklokapron, Lysteda)

This agent is an alternative to aminocaproic acid. It inhibits fibrinolysis by displacing plasminogen from fibrin. It also inhibits the proteolytic activity of plasmin.


Clotting Factors, Gene Therapies

Class Summary

These therapies are designed to introduce a functional copy of a transgene encoding the human coagulation factor VIII. 

Valoctocogene roxaparvovec (Roctavian)

Valoctocogene roxaparvovec is an adeno-associated virus serotype 5 (AAV5) based gene therapy vector, designed to introduce a functional copy of a transgene encoding the B-domain deleted SQ form of human coagulation factor VIII (hFVIII-SQ). The expressed hFVIII-SQ replaces the missing coagulation factor VIII needed for effective hemostasis. It is indicated for severe hemophilia A (congenital factor VIII deficiency with factor VIII activity <1 IU/dL) in adults without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.