Class: Hemostatics
VA Class: BL500
CAS Number: 9001-27-8
Brands: Alphanate, Hemofil-M, Humate-P, Koate-DVI, Monarc-M, Monoclate-P
Introduction
Preparation of antihemophilic factor (blood coagulation factor VIII) prepared from pooled human plasma from suitable whole-blood donors.122 133 152 153 158 167
Uses for Antihemophilic Factor (Human)
Hemophilia A
Prevention and control of hemorrhagic episodes in individuals with a deficiency of coagulation factor VIII (antihemophilic factor) associated with hemophilia A (classic hemophilia).122 133 152 153 158 167
Maintenance of hemostasis in patients with hemophilia A undergoing emergency or elective surgery.122 133 152 153 158 167
Because of an increased risk of transmission of human viruses (e.g., HIV, hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV]) and other transmissible disease agents (e.g., agents for Creutzfeldt-Jakob disease [CJD], variant CJD [vCJD]) with plasma-derived antihemophilic factor compared with antihemophilic factor (recombinant), the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation and other experts recommend antihemophilic factor (recombinant) as the preparation of choice in patients with hemophilia A.103 111 134 170 176 218 Recombinant and plasma-derived preparations of antihemophilic factor are similar and produce comparable hemostatic effects.134 170
Antihemophilic factor replacement therapy generally is required in patients with mild to moderate hemophilia A who do not respond adequately to desmopressin or those with moderate to severe hemophilia A and factor VIII levels <5% of normal.111 154 160 175 177 183 215
Also used for routine prophylaxis (i.e., administration at regular intervals) to prevent or reduce frequency of hemorrhagic events and preserve joint function.158 215 224 225 226 231 MASAC recommends prophylaxis in patients with severe hemophilia A (factor VIII activity <1%) after careful consideration of risks versus benefits.218
Hemophilia A with Inhibitors to Antihemophilic Factor
Prevention and treatment of bleeding in patients with hemophilia A who have developed relatively low levels of inhibitors (alloantibodies) to factor VIII.152 153 154 160 176 179 180 181 182 184 186 215 (See Development of Inhibitors to Antihemophilic Factor under Cautions.) May be effective in those whose inhibitor levels have historically remained <5–10 Bethesda units/mL.154 160 182 184 186 Some manufacturers state antihemophilic factor may be effective in patients with inhibitor levels ≤10 Bethesda units/mL;152 153 other clinicians recommend use of these preparations in those with inhibitor levels <5 Bethesda units/mL.215 239 240
Has been used to induce immune tolerance as a long-term strategy to eradicate or suppress further antibody production†.158 160 188 189 190 191 222 227 Such therapy eliminates risk of anamnesis with continued use of antihemophilic factor (human).160 188 189 190 191 While some experts state there is insufficient evidence to recommend use of immune tolerance therapy in patients with inhibitors,227 MASAC recommends such therapy for eradication of high-titer inhibitors.111
Other therapeutic options for patients with inhibitors include bypassing agents such as anti-inhibitor coagulant complex (activated prothrombin complex concentrate [APCC]), factor VIIa (recombinant), or certain factor IX complex preparations (prothrombin complex concentrates [PCCs]).111 134 154 160 176 180 182 213 216 217 220 227 MASAC currently recommends use of a bypassing agent in hemophilia A patients with inhibitors to prevent or control bleeding in settings where antihemophilic factor preparations would otherwise be used, including before and after surgery and physical therapy.220
Management of hemophilia A in patients with inhibitors may be difficult and consultation with a hemophilia treatment center is strongly recommended.154 160 176 184 215
Acquired Hemophilia
Has been used to control bleeding in patients without hemophilia A who spontaneously acquire inhibitors (autoantibodies) to factor VIII.122 152 153 Autoantibodies are similar to but more heterogeneous than the alloantibodies that develop in patients with hemophilia A.176 180 182 185
Management of acquired hemophilia not well established.154 176 179 180 181 182 184 185 Antihemophilic factor (human or recombinant) may be effective in patients with low levels of inhibitors.152 153 160 184 185 Other treatment options include immunosuppressive therapy, desmopressin, or bypassing agents.160 176 179 180 181 182 184 185 186 213 214
von Willebrand Disease
Used when necessary to prevent or control bleeding in certain individuals with von Willebrand disease.111 122 133 161 201 244 Only preparations of antihemophilic factor (human) containing both factor VIII and von Willebrand factor should be used.111 122 133 161 201 Generally recommended in patients with type 2 or type 3 von Willebrand disease and those with type 2A, 2M, or 2N disease who are unresponsive to desmopressin.111 161 201 244
Humate-P is indicated for the management of spontaneous or trauma-induced bleeding episodes and for prevention of excessive bleeding during and after surgery in adult and pediatric patients with severe von Willebrand disease, and in those with mild to moderate von Willebrand disease when use of desmopressin is known or suspected to be inadequate.133 Designated an orphan drug by FDA for treatment of von Willebrand disease.169
Alphanate is indicated in adult and pediatric patients with von Willebrand disease who are undergoing surgical and/or invasive procedures and cannot receive desmopressin because the drug is ineffective or contraindicated;122 designated an orphan drug by FDA for this use.169 Alphanate is not indicated for patients with type 3 von Willebrand disease undergoing major surgery.122 232
Limited data suggest that certain other intermediate- or high-purity antihemophilic factor (human) preparations (i.e., Koate-DVI) that contain sufficient quantities of von Willebrand factor: Ristocetin cofactor (vWF:RCo) and von Willebrand factor antigen (wWF:AG) may be effective in the management of von Willebrand disease†.111 161 201 244
Very high purity preparations (Hemofil-M, Monarc-M, Monoclate-P) of antihemophilic factor (human) prepared using immunoaffinity purification should not be used in the treatment of von Willebrand disease; such preparations do not contain adequate amounts of von Willebrand factor.111 152 153 161 167 201 244
Antihemophilic Factor (Human) Dosage and Administration
General
In patients with hemophilia A, confirm deficiency of factor VIII prior to initiating therapy;133 152 153 158 continue monitoring factor VIII levels periodically during treatment to individualize dosage and assess response to therapy.122 133 158 (See Laboratory Monitoring under Cautions.)
In patients with von Willebrand disease, confirm deficiency of vWF:RCo prior to initiating therapy;133 continue monitoring vWF:RCo levels periodically during treatment to individualize dosage and assess response to therapy.133 (See Laboratory Monitoring under Cautions.)
Correct factor VIII and/or vWF:RCo deficiency prior to surgical procedures.158 167 215
Administration
IV Administration
Administer by slow IV injection or by IV infusion over several minutes.122 133 152 153 158 167
Has been given as a continuous IV infusion†.228 229 230
Administer using plastic syringes only; antihemophilic factor (human) may adhere to glass.122 133 152 153 167
Filter solution prior to administration.122 133 152 153 158 215
Instructions on reconstitution, dilution, and administration vary according to preparation; consult manufacturer’s labeling for specific information on each antihemophilic factor (human) product.122 133 152 153 158 167
Reconstitution
Prior to reconstitution, allow injection concentrate and diluent to warm to room temperature; do not exceed 37°C.122 133 152 153 158 167 Solution may precipitate if administered below room temperature.a
Reconstitute antihemophilic factor (human) concentrate with diluent provided by manufacturer.122 133 152 153 158 167
Gently swirl solution to dissolve powder completely; do not shake.122 133 152 153 167
Rate of Administration
Individualize infusion rates according to patient response and comfort.158 167 Monitor pulse rate before and during infusion.152 153 Slow infusion rate or temporarily discontinue therapy if there is a substantial increase in pulse rate.152 153
Alphanate, Hemofil-M, Monarc-M: Administer at a rate ≤10 mL/minute.122 152 153
Humate-P: Administer at a rate ≤4 mL/minute.133
Koate-DVI: Generally well-tolerated when given over 5–10 minutes.158
Monoclate-P: Administer at a rate of approximately 2 mL/minute.167
Dosage
Dosage (potency) expressed in terms of international units (IU, units).122 133 152 153 158 167 168 One unit is approximately equivalent to amount of factor VIII or von Willebrand factor:Ristocetin cofactor (vWF:RCo) in 1 mL of fresh pooled human plasma.122 133 158 167
Individualize dosage and duration of therapy based on degree of factor VIII deficiency (measuring factor VIII levels prior to and at regular intervals during therapy), desired factor VIII levels, patient’s weight, type and severity of bleeding, presence of factor VIII inhibitors, and clinical response.122 133 158 167 215
Use the following calculations and dosage guidelines (based on the degree of hemorrhage or type of surgery) for administering the drug in patients with hemophilia A.122 133 152 153 158 167
These calculations and suggested dosage regimens are only approximations and should not preclude appropriate clinical monitoring, laboratory determinations, and individualization of dosage based on the hemostatic requirements of patients.122 133 152 153 158 167 Perform serial assays of factor VIII at suitable intervals to ensure that adequate levels have been attained and maintained.122 133 152 153 158 167 Consult manufacturers’ prescribing information for specific dosage recommendations for each antihemophilic factor (human) preparation.122 133 152 153 158 167
Careful control of the dose is especially important in cases of life-threatening bleeding or major surgery.152 153 If calculated dosage is ineffective in achieving adequate factor VIII levels or if bleeding is not controlled, consider the possibility that inhibitors to antihemophilic factor may have developed.122 152 153 215 (See Development of Inhibitors to Antihemophilic Factor under Cautions.) Some patients with inhibitors may require higher or more frequent doses.122 152 153 158
Administration of 1 unit/kg antihemophilic factor (human) generally increases factor VIII level by approximately 2% and vWF:Co by approximately 5%.133 154 160 167 176 194 215
Dosage required to achieve desired factor VIII levels:122 152 153 158 167
Dose (units) = body weight (in kg) × 0.5 × desired factor VIII increase (in % of normal)
Approximate % increase in factor VIII levels expected from a given dosage:122 152 153 158 167
Expected factor VIII increase (in % of normal) = [dose (units)/body weight (in kg)] × 2
Pediatric Patients
Hemophilia A
Alphanate
IV
Pediatric patients >16 years of age with minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 15 units/kg twice daily to achieve a plasma factor VIII level of 30% of normal; usually for 1–2 days (until hemorrhage stops and healing achieved).122
Pediatric patients >16 years of age with moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25 units/kg twice daily to achieve a plasma factor VIII level of 50% of normal; usually for 2–7 days (until healing achieved).122
Pediatric patients >16 years of age with major hemorrhage (e.g., joint or muscle bleeding, major trauma, hematuria, intracranial and intraperitoneal bleeding): Initially, 40–50 units/kg twice daily to achieve a plasma factor VIII level of 80–100% of normal for at least 3–5 days; give additional doses of 25 units/kg twice daily for up to 10 days (until healing is achieved) to maintain a plasma factor VIII level of 50% of normal.122
Pediatric patients >16 years of age undergoing surgery: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal prior to surgery.122 Give additional doses of 25–50 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a plasma factor VIII level of 60–100% of normal.122
Hemofil-M, Monarc-M
The manufacturer of Hemofil-M and Monarc-Mstates that there are no clear indications in labeling concerning use of Hemofil-M and Monarc-M in pediatric patients.152 153 234
Humate-P
IV
Adequate and well-controlled studies evaluating use in pediatric patients with hemophilia A not available.133 When immediate control of bleeding is necessary in a pediatric patient, manufacturer recommends that the general recommendations for dosage and administration in adults be considered.133 (See Humate-P dosage recommendations for adults under Dosage and Administration.)
Monoclate-P
IV
Mild hemorrhage: A single infusion may be sufficient to achieve a plasma factor VIII level of ≥30% of normal.167
Moderate hemorrhage: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167
Severe hemorrhage (e.g., neck, throat, subperitoneal bleeding): Initially, 40–50 units/kg and a maintenance dosage of 20–25 units/kg given every 8–12 hours to achieve a plasma factor VIII level of 80–100% of normal.167
Minor surgery: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167
Major surgery: Administer an appropriate dose to achieve a plasma factor VIII level of 80–100% of normal 1 hour before surgery; administer a second dose equal to 50% of the initial dose 5 hours later.167 Maintain a plasma factor VIII level of ≥30% of normal for 10–14 days after surgery.167
Routine Prophylaxis
IV
Various dosing regimens have been recommended; optimal dosage remains to be established.215 218 225 231 Dosages of 25–40 units/kg every other day (minimum 3 times a week) usually recommended.215 231 MASAC states that an antihemophilic factor dosage of 25–50 units/kg 3 times a week or every other day usually is sufficient to maintain trough factor VIII concentrations >1% between infusions.218
Evaluate patients periodically to determine continued need for prophylaxis; some patients may require life-long prophylaxis.218
von Willebrand Disease (Alphanate)
Amount of von Willebrand factor:Ristocetin cofactor (vWF:RCo) and factor VIII contained in each vial of Alphanate is indicated on the label.122 Ratio of vWF:RCo to factor VIII varies depending on the manufacturing lot; therefore, reevaluate dosage of Alphanate for management of von Willebrand disease should be reevaluated whenever a different manufacturing lot is indicated on the vial.122
IV
Surgical or invasive procedures: Initially, 75 units/kg of vWF:RCo prior to procedure; follow with additional doses of 50–75 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 May reduce dosage after third postoperative day; continue treatment until healing is complete.122
von Willebrand Disease (Humate IV-P)
IV
Adjust dosage according to extent and location of bleeding.133 Usually administer doses of 40–80 units/kg of vWF:RCo (corresponding to 17–33 units/kg of antihemophilic factor) every 8–12 hours; repeat doses for as long as needed based on repeated monitoring of appropriate clinical and laboratory measures.133
Expected levels of vWF:RCo based on expected in vivo recovery of 2% increase per unit/kg of vWF:RCo administered.133 Administration of 1 unit/kg of antihemophilic factor can be expected to result in an increase in circulating vWF:RCo of approximately 5%.133
Monitor and maintain factor VIII levels according to the usual guidelines for patients with hemophilia A.133
Type 1 (Mild) von Willebrand Disease (Baseline vWF:RCo Activity Typically >30%)
IV
Pediatric patients (excluding neonates) with major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic hemorrhage) and when use of desmopressin is inappropriate: Initially, 40–60 units/kg of vWF:RCo, followed by 40–50 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a trough vWF:RCo level of >50%.133 Continue with 40–50 units/kg vWF:RCo daily for up to 7 days.133
Type 1 (Moderate or Severe) von Willebrand Disease (Baseline vWF:RCo Activity Typically <30%)
IV
Pediatric patients (excluding neonates) with minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133
Pediatric patients (excluding neonates) with major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): Initially, 50–75 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133
Type 2 (All Variants) and Type 3 von Willebrand Disease
IV
Pediatric patients (excluding neonates) with minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133
Pediatric patients (excluding neonates) with major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): Initially, 60–80 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133
Prevention of Excessive Bleeding During and After Surgery
Whenever possible, calculate dosages for surgical prophylaxis based on incremental in vivo recovery (IVR) values.133 If individual IVR values not available, assume IVR of 2% per unit/kg of vWF:RCo.133 In case of emergency surgery, administer a loading dose of 50–60 units/kg of vWF:RCo and closely monitor trough coagulation factor levels.133
To calculate IVR, use the following formula.133 Measure plasma vWF:RCo level at baseline and 30 minutes following a dose of 60 units/kg of vWF:RCo.133
IVR = (Plasma vWF:RCotime + 30 minutes - Plasma vWF:RCobaseline) / 60 units/kg
Calculate loading dose (administered 1–2 hours prior to surgery) using the following formula:133
Dose required (units of vWF:RCo) = [(Target peak plasma vWF:RCo - baseline plasma vWF:RCo) x body weight (in kg)]/IVR
Administer loading doses to achieve specific target peak vWF:RCo and factor VIII levels.133 Additional doses may be necessary to achieve recommended factor VIII levels; because of a higher ratio of vWF:RCo to factor VIII (2.4 to 1), vWF:RCo will increase proportionally more than factor VIII with increasing doses.133
Administer initial maintenance dose equal to one-half the loading dose (irrespective of any additional loading doses given to meet target factor VIII goals); follow with additional maintenance doses based on trough plasma vWF:RCo and factor VIII levels.133 Frequency of administration depends on individual pharmacokinetic parameters; in the absence of such data, administer every 8 hours initially.133
Monitor trough vWF:RCo and factor VIII levels at least once daily, and during and after surgery.133 Modify dose and/or frequency of antihemophilic factor administration if hemostasis is insufficient or measured trough coagulation factor levels are not within recommended range.133 Because factor VIII is the main predictor of surgical hemostasis, some clinicians recommend monitoring factor VIII levels every 12 hours on the day a dose is administered, then every 24 hours thereafter.244 Determine duration of therapy based on hemostatic response.133
IV
Pediatric patients (excluding neonates) undergoing major surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 100% and a peak plasma factor VIII level of 80–100%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of >50% (>50% of factor VIII activity) for up to 3 days following surgery and target trough vWF:RCo levels of >30% (>30% of factor VIII activity) after day 3.133 Minimum duration of treatment is 72 hours.133
Pediatric patients (excluding neonates) undergoing minor surgery: Administer appropriate loading dose to achieve a target peak plasma vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough plasma vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 48 hours.133
Pediatric patients (excluding neonates) undergoing oral surgery: Administer appropriate loading dose to achieve a target peak vWF:RCo level of 50–60% and a peak plasma factor VIII level of 40–50%.133 Give initial maintenance dose equal to one-half the loading dose and subsequent doses to achieve target trough vWF:RCo levels of ≥30% for up to 3 days following surgery and target trough factor VIII levels >30% after day 3.133 Minimum duration of treatment is 8–12 hours.133
Adults
Hemophilia A
Alphanate
IV
Minor hemorrhage (e.g., bruises, cuts, scrapes, uncomplicated joint hemorrhage): 15 units/kg twice daily to achieve a plasma factor VIII level of 30% of normal; usually for 1–2 days (until hemorrhage stops and healing achieved).122
Moderate hemorrhage (e.g., epistaxis, mouth and gum bleeding, tooth extraction, hematuria): 25 units/kg twice daily to achieve a plasma factor VIII level of 50% of normal; usually for 2–7 days, until healing achieved.122
Major hemorrhage (e.g., joint or muscle bleeding, major trauma, hematuria, intracranial and intraperitoneal bleeding): Initially, 40–50 units/kg twice daily to achieve a plasma factor VIII level of 80–100% of normal for at least 3–5 days.122 Give additional doses of 25 units/kg twice daily for up to 10 days (until healing is achieved) to maintain a plasma factor VIII level of 50% of normal.122
Surgery: Initially, 40–50 units/kg to achieve a plasma factor VIII level of 80–100% of normal prior to surgery.122 Give additional doses of 25–50 units/kg twice daily for 7–10 days (or until healing achieved) to maintain a plasma factor VIII level of 60–100% of normal.122
Humate-P
IV
Minor hemorrhage (e.g., early joint or muscle bleeding, severe epistaxis): Initially, 15 units/kg to achieve a plasma factor VIII level of approximately 30% of normal.133 A single dose may be sufficient; if necessary, administer additional doses equal to 50% of the loading dose once or twice daily for 1–2 days.133
Moderate hemorrhage (e.g., advanced joint or muscle bleeding; neck, tongue, or pharyngeal hematoma without airway compromise; severe abdominal pain; tooth extraction): Initially, 25 units/kg to achieve a plasma factor VIII level of approximately 50% of normal,133 followed by 15 units/kg every 8–12 hours for the first 1–2 days to maintain a plasma factor VIII level of 30% of normal.133 Thereafter, the same dose may be given once or twice daily for up to 7 days or until adequate wound healing.133
Life-threatening hemorrhage (e.g., major surgery, GI bleeding; neck, tongue, or pharyngeal hematoma with potential for airway compromise; intracranial, intra-abdominal, or intrathoracic bleeding; fractures): Initially, 40–50 units/kg followed by 20–25 units/kg every 8 hours to maintain a plasma factor VIII level of 80–100% of normal for 7 days.133 Thereafter, the same dose may be given once or twice daily for another 7 days to maintain a plasma factor VIII level of 30–50% of normal.133
Hemofil-M, Monarc-M
IV
Early hemarthrosis, muscle bleeding or oral bleeding: Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 20–40% of normal.152 153 To maintain an adequate level, administer doses every 12–24 hours for 1–3 days until bleeding resolves (indicated by relief of pain) or healing achieved.152 153
More extensive hemarthrosis, muscle hemorrhage, or hematoma: Administer appropriate dosage to achieve peak plasma factor VIII postinfusion level of 30–60% of normal.152 153 Give doses every 12–24 hours for 3 days or longer until pain and disability resolve.152 153
Life-threatening bleeding (e.g., head injury, throat bleeding, severe abdominal pain): Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 60–100% of normal.152 153 Give doses every 8–24 hours until bleeding resolves.152 153
Minor surgery (e.g., tooth extraction): Administer appropriate dosage to achieve a peak plasma factor VIII postinfusion level of 60–80% of normal.152 153 A single infusion given in conjunction with an oral antifibrinolytic agent usually is sufficient in about 70% of patients.152 153
Major surgery: Administer appropriate dosage to achieve peak plasma factor VIII pre- and postoperative levels of 80–100% of normal.152 153 Repeat doses every 8–24 hours depending on state of healing.152 153
Koate-DVI
IV
Mild hemorrhage (superficial or early hemorrhage): A single 10-unit/kg dose may be sufficient to achieve an in vivo factor VIII level of approximately 20% of normal.158 Repeat only if evidence of further bleeding.158
Moderate hemorrhage (more serious bleeding episodes including definite hemarthroses, known trauma): Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.158 If additional therapy is required, give additional doses of 10–15 units/kg every 8–12 hours.158
Severe hemorrhage (life-threatening bleeding or possible hemorrhage involving vital structures [e.g., CNS, retropharyngeal and retroperitoneal spaces, iliopsoas sheath]): Increase plasma factor VIII level to 80–100% of normal with an initial dose of 40–50 units/kg and a maintenance dosage of 20–25 units/kg every 8–12 hours.158
Major surgery: Increase plasma factor VIII level to approximately 100% with a preoperative 50-unit/kg dose.158 Check plasma factor VIII levels to verify that the expected level is achieved prior to surgery.158 Give additional doses if necessary, every 6–12 hours initially, and for a total of 10–14 days until healing complete.158
Intensity of antihemophilic factor therapy required depends on the type of surgery and postoperative regimen employed; less intensive treatment schedules may provide adequate hemostasis for minor surgical procedures.158
Monoclate-P
IV
Mild hemorrhage: A single infusion may be sufficient to achieve a plasma factor VIII level of ≥30% of normal.167
Moderate hemorrhage: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal.167 If needed, give additional doses of 10–15 units/kg every 8–12 hours.167
Severe hemorrhage (e.g., neck, throat, subperitoneal bleeding): Initially, 40–50 units/kg and a maintenance dosage of 20–25 units/kg given every 8–12 hours may be sufficient to achieve a plasma factor VIII level of 80–100% of normal.167
Minor surgery: Initially, 15–25 units/kg to achieve a plasma factor VIII level of 30–50% of normal; maintenance doses of 10–15 units/kg may be given every 8–12 hours if needed.167
Major surgery: Administer appropriate dosage to achieve plasma factor VIII level of 80–100% of normal 1 hour before surgery; administer a second dose equal to 50% of the initial dose 5 hours later.167 Maintain a plasma factor VIII level of ≥30% of normal for 10–14 days after surgery.167
Routine Prophylaxis
IV
Various dosing regimens have been recommended; optimal dosage remains to be established.215 218 231 Dosages of 25–40 units/kg every other day (minimum 3 times a week) usually recommended.215 231 MASAC states that an antihemophilic factor dosage of 25–50 units/kg 3 times a week or every other day usually is sufficient to maintain trough factor VIII concentrations >1% between infusions.218
Evaluate patients periodically to determine continued need for prophylaxis.218
Acquired Hemophilia
IV
When used in patients with acquired factor VIII inhibitors ≤10 Bethesda units/mL, dosages of antihemophilic factor (human) should be controlled by frequent monitoring of plasma factor VIII levels.152 153 Individualize treatment.122
von Willebrand Disease (Alphanate)
Amount of von Willebrand factor:Ristocetin cofactor (vWF:RCo) and factor VIII contained in each vial of Alphanate is indicated on the label.122 Ratio of vWF:RCo to factor VIII varies depending on the manufacturing lot; therefore, reevaluate dosage of Alphanate for management of von Willebrand disease whenever a different manufacturing lot is indicated on the vial.122
IV
Minor surgical or invasive procedures: Initially, 60 units/kg of vWF:RCo prior to procedure; follow with additional doses of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 Maintain a vWF level of 40–50% of normal for 1–3 days after procedure.122 May reduce dosage after third postoperative day, but continue treatment until healing is complete.122
Major surgical or invasive procedures: Initially, 60 units/kg of vWF:RCo prior to procedure; follow with additional dosages of 40–60 units/kg of vWF:RCo every 8–12 hours as clinically needed.122 Maintain a vWF level of 40–50% of normal for at least 3–7 days after procedure.122 May reduce dosage after third postoperative day, but continue treatment until healing is complete.122
von Willebrand Disease (Humate IV-P)
IV
Adjust dosage according to extent and location of bleeding.133 Usually administer dosage of 40–80 units/kg of vWF:RCo (corresponding to 17–33 units/kg of antihemophilic factor) every 8–12 hours; repeat doses for as long as needed based on repeated monitoring of appropriate clinical and laboratory measures.133
Expected levels of vWF:RCo based on expected in vivo recovery of 2% increase per unit/kg of vWF:RCo administered.133 Administration of 1 unit/kg of antihemophilic factor can be expected to result in an increase in circulating vWF:RCo of approximately 5%.133
Monitor and maintain factor VIII levels according to the usual guidelines for patients with hemophilia A.133
Type 1 (Mild) von Willebrand Disease (Baseline vWF:RCo Activity Typically >30%)
IV
Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, traumatic hemorrhage) and when use of desmopressin is inappropriate: Initially, 40–60 units/kg of vWF:RCo, followed by 40–50 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a trough vWF:RCo level of >50%.133 Continue with 40–50 units/kg of vWF:RCo daily for up to 7 days.133
Type 1 (Moderate or Severe) von Willebrand Disease (Baseline vWF:RCo Activity Typically <30%)
IV
Minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133
Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): Initially, 50–75 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133
Type 2 (All Variants) and Type 3 von Willebrand Disease
IV
Minor hemorrhage (e.g., epistaxis, oral bleeding, menorrhagia): 40–50 units/kg of vWF:RCo given as 1 or 2 doses.133
Major hemorrhage (e.g., severe or refractory epistaxis, GI bleeding, CNS trauma, hemarthrosis, traumatic hemorrhage): Initially, 60–80 units/kg of vWF:RCo, followed by 40–60 units/kg of vWF:RCo every 8–12 hours for 3 days to maintain a vWF:RCo trough level of >50%.133 Continue with 40–60 units/kg of vWF:RCo daily for up to 7 days.133
Prevention of Excessive Bleeding During and After Surgery
Whenever possible, calculate dosages for surgical prophylaxis based on incremental in vivo recovery (IVR) values.133 If individual IVR
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