eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders
Factor IX: Treatment & Medication
Updated: Aug 30, 2007
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Treatment
Medical Care
A review of the global experience with plasma derived factor IX (pdFIX; Immunine and Mononine) products or rFIX showed that the 2 types of products are comparable with regards to reliability, tolerability, and clinical efficacy, with rare occurrences of serious adverse effects in either product. The major difference was variable pharmacokinetics, with a similar half-life but an approximately 25-30% lower in vivo recovery after rFIX, particularly in younger children (in children <16 y according to Poon, 20018 ; in children <15 y according to Roth, 20019 ).
Data obtained from a survey of several French hemophilia centers and presented at the International Society of Thrombosis and Haemostasis meeting in July 2001 showed an average recovery of 61% for rFIX use versus 85% for pdFIX. Initial dosing of FIX for both inpatient and outpatient treatment is on the basis of standard guidelines (Indiana Hemophilia & Thrombosis Center).
Worldwide, only 25 patients with allergic reactions have been reported to the manufacturer of rFIX, with mild-to-moderate skin and respiratory reactions in most of the patients. Of 5 patients with anaphylaxis, some developed an inhibitor, and no fatalities were reported. Three thrombotic events were reported, of which 2 were catheter related and the third patient, aged 14 years, had a transient ischemic event but did well when continued on rFIX. Seventeen of 4500 patients had red cell agglutination when blood was withdrawn into the catheter or syringe containing rFIX; this practice must be avoided.
Although many reports exist of the successful use of different continuous infusion regimens of FIX, ongoing data collection and studies will allow development of a standardized regimen in the future. Potential benefits include the ability to mimic the physiologic state and reduction in product usage, providing much-needed economic savings.
Both pdFIX and rFIX are highly effective, but rFIX is believed to be free of blood-borne pathogens.
In children who are starting therapy for the first time or in persons with hemophilia who are HIV negative, recombinant products are used whenever possible because of their presumed higher viral safety. Note that approximately 25% of the lots of human albumin containing first-generation recombinant factor VIII (rFVIII) concentrates have been found to be positive for transfusion transmitted virus (TTV) from contaminated human serum albumin. All of the second-generation rFVIII preparations (free from human albumin) were negative for the virus.10
It is important to understand the pharmacokinetics of factor IX.11 Factor IX in vivo recovery is also relatively short possibly due to its reversible binding to endothelium and possibly to platelets. There is considerable pharmacokinetic variability of factor IX between products (particularly between plasma-derived factor IX and recombinant factor IX), and between individuals.
- Factor replacement in patients with hemophilia B should be guided by an experienced hematologist who is familiar with treating patients with coagulation disorders.
- The location and severity of bleeding determine the dose and duration of factor replacement therapy. Highly purified FIX concentrates (monoclonal antibody purified FIX or rFIX) are now available (first dose: 20-80 IU/kg depending on FIX level necessary to treat the specific clinical condition).
- Approximately 50% of the first dose is administered approximately every 24 hours to maintain the initial level of FIX.
- If therapy is to last for more than 2 days or is occurring for the first time, FIX levels should be obtained immediately after the first dose, with a subsequent trough level taken to determine appropriate dose and frequency of replacement therapy based on in vivo response to a specific product. Children and surgical patients require closer monitoring of FIX levels because of known variable pharmacokinetics and a lack of a steady state, respectively.
- Preservation of the hemostatic plug formed in the presence of adequate levels of FIX at the time of surgery (ie, dental extraction) can be achieved by inhibiting fibrinolysis with EACA or tranexamic acid (Cyklokapron) administered orally or IV as needed. Inhibitors of fibrinolysis, such as EACA or tranexamic acid, can be used in combination with factor replacement to prevent bleeding from mucosal sites, including after dental extractions or sinus surgery. Following the surgical procedure, the drugs are continued, then tapered as the wound heals. Such treatment allows use of a single dose to prevent bleeding from minor procedures. However, fibrinolytic inhibitors are not of value in the treatment of hemarthroses or deep-seated bleeding. The prolonged use of fibrinolytic inhibitors in joint and deep hematomas can lead to persistence (lack of absorption) of the clot with negative consequences.
- A dose of EACA, 5 g orally or IV, is administered immediately before the surgical procedure along with a dose of FIX, followed by 1 g per hour postoperatively until the decision is made to taper the dose over the next 5 days.
- Tranexamic acid can be administered in a dose of 1.5 g every 6-8 hours for 5 days; this drug is not available in the United States.
- Administration of these fibrinolytic inhibitors is contraindicated in patients with hematuria who are receiving or have recently received FIX product because of the risk of an acute persistent thrombus obstructing the ureters and causing acute hydronephrosis.
- Nonnarcotic and narcotic analgesics are used to relieve pain. Narcotic analgesics are used to manage severe acute pain, such as occurs with joint bleeding or perioperatively. Chronic persistent pain of chronic joint disease can be difficult to manage. Ideally, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided in patients with a bleeding disorder because the addition of platelet dysfunction caused by the drugs can potentiate bleeding. However, because of the persistent demand by individuals with hemophilia, cyclooxygenase 2 (COX-2) inhibitors are being tried with caution because of a lack of efficacy of nonnarcotic pain relievers in severe arthritis. Use of NSAIDs by individuals with hemophilia has increased in an attempt to relieve the severe joint pain of chronic arthritis.
- Several approaches to gene therapy have been undertaken in treating patients with hemophilia B or A with severe deficiency. Basal levels of 5-10% significantly ameliorate bleeding in persons with severe hemophilia.
- The most successful and least toxic method of introducing the gene remains to be determined. The use of an attenuated adenoviral vector, although associated with high short-term expression in a canine model of hemophilia, led to liver toxicity, thrombocytopenia, and an antibody to the factor due to an immunologic response to the vector.
- An additional question is the appropriate in vivo–vector dose to be administered; evidence is emerging for the need for a minimum threshold dose.
- Short-term correction resulting from high gene expression in the neonatal period following in utero injection of an adenoviral murine vector has been accomplished with FVIII.
- Use of a parvovirus, use of transduced endothelial cells, or the possibility of cutaneous gene therapy are being explored in animal models and in humans.
- Development of antibodies to replaced proteins is a major problem, and the possibility of using CTLA4-Ig to block T-cell function to prevent antibody response has been explored in murine models of hemophilia A.
- Several possible approaches to gene therapy include ex vivo gene therapy, in which the cells to be injected are modified to secrete FIX or FVIII and then are reimplanted into the recipient, and in vivo gene therapy, in which cells modified to secrete the missing factor are packaged in immunoprotected devices and implanted in recipients.
- Gene therapy with a variety of vectors has been tested in humans, with the most successful method still to be determined. Gene therapy studies were halted following the death of a patient treated for a metabolic disorder. Reevaluation of the type of vector, dose, route, and toxicity of the different approaches to gene therapy was undertaken. Oligonucleotides possibly can be used in vivo to correct point mutations. Advantages and disadvantages of several approaches to gene therapy in individuals with hemophilia and other patients have been updated in two recent publications.12,13
Gene therapy remains promising.14 In humans, one hemophilia B patient achieved 10% of normal activity after liver-directed gene therapy with a single-stranded adeno-associated virus vector expressing human factor IX, but expression fell at 1 month. Thus, gene therapy may be viewed as successful in a patient with hemophilia B, but expression was unstable probably due to an immune response. Abrogating immune responses may be the next important hurdle for achieving long-lasting gene therapy.
Surgical Care
Appropriate preoperative evaluation includes an aPTT mixing test after incubation for 1-2 hours at 37°C with pooled normal plasma to exclude an inhibitor, followed by administration of an appropriate preoperative dose of concentrate, followed by appropriate postoperative treatment.
Recent small studies have established the efficacy of using lower than usually recommended doses of FIX concentrate, administered as an intermittent bolus infusion after major surgical procedures. Preoperatively, FIX was used in a dose of 77 U/kg to achieve a presurgical level of 107% (range 50-104%). Between days 1 and 3 after surgery, an average of 23 U/kg/d was used with an average trough value of FIX of 34% (range 11-52%). After day 4, an average of 18 U/kg/d of FIX was used until wound healing occurred. This resulted in a significant reduction in overall factor used without hemostatic inadequacy. Such data underscore the importance of defining the least amount of factor replacement necessary to obtain and maintain adequate hemostasis.
- The use of fibrin sealants (ie, fibrin glue, fibrin adhesive), which consist of fibrinogen and thrombin with variable incorporation of factor XIII (FXIII) and fibrinolytic inhibitors, has helped improve surgical hemostasis markedly, thereby permitting necessary high-risk surgery (eg, pseudotumors, surgery in patients with hemophilia with inhibitors). This technology reduces or eliminates the need for prolonged replacement using expensive clotting factor concentrates and may eliminate or reduce the need for hospitalization. In total, the measures result in improved quality of life in patients with hemophilia, while achieving a reduction in medical care costs. Bovine thrombin used in these preparations may result in development of inhibitors to several factors, including thrombin and FV, as it has in other postoperative states.
- Warn patients to avoid any antiplatelet drug starting 1 week prior to surgery and in the immediate postoperative period to minimize the risk of bleeding.
- The use of ice packs at surgical sites may be beneficial to reduce the size of the surgical site hematoma.
Consultations
- Hematologist, including general medical evaluation
- Orthopedist
- Physical therapist
- Dentist
- Surgeon
- Social worker
- Psychiatrist, particularly in the management of HIV-related issues15
- Geneticist for genetic testing and counseling for family members
Diet
Encourage a generally healthy and nutritious diet.
Activity
- Activity recommendations depend on such factors as joint disease and resolution of bleed into joints and muscles.
- Appropriate use of physical therapy is advised.
Medication
Currently, highly purified preparations, ie, rFIX or purified monoclonal antibody and solvent-detergent–treated FIX products are used. rFIX products are free of the usual viral contaminants and are the only products free of Parvovirus B 19. These products have significantly reduced risks of viral transmission; however, a recent report exists of contamination of first-generation recombinant products with TTV due to the use of human serum albumin.10Recombinant products result in 20-30% less factor recovery, possibly because of the presence of nonneutralizing antibodies. These products can cause severe allergic reactions, especially in patients who are severely deficient in FIX. These potentially life-threatening reactions are associated with development of inhibitors. Young children can experience such reactions, especially at the start of treatment.
Serious allergic reactions to FIX preclude further use of FIX or prothrombin-complex concentrates (PCCs) or activated prothrombin-complex concentrates (aPCCs); desensitization may be attempted. PCCs/aPCCs are crude plasma preparations containing concentrates of vitamin K–dependent factors, some in an activated form. Liver disease diminishes clearance of activated coagulation factors and synthesis of physiologic inhibitors. Rapid infusion increases risk of thromboembolic complications, especially DIC, in patients with liver disease. The addition of very small amounts of heparin (1 U of heparin for every 100 U of FIX activity) has been used to minimize the effect of activators present in the aPCCs.
Most data suggest an approximate 50% drop in FIX level within approximately 24 hours. However, the actual in vivo FIX level that is achieved varies. Peak and trough levels following bolus dosing dictate the amount and timing of subsequent doses. Generally, an appropriate second dose is approximately one half of the initial dose, which is administered every 24 hours for moderate or minor bleeds and more often for severe or life-threatening bleeds. Ideally, FIX levels should be monitored in any serious situation to assess adequacy of dose and response.
Home care on-demand factor replacement therapy doses depend on the individual's response to the product and on the type of bleed. The goal of prophylactic therapy is to maintain the basal FIX level in an approximate 5% range, which reduces frequency and risk of spontaneous bleeding. Attempts are underway to determine the lowest level of FIX necessary for adequate hemostasis and to reduce dose requirements by using continuous infusion of FIX concentrates.
Dosing guidelines relate to the in vivo level of FIX needed. Different products have different in vivo recovery. Dosing guidelines require verification for each patient. Educating patients regarding their response to specific products is important so that the information does not have to be generated repeatedly, and patients can advise an emergency department physician regarding personal dose response to a specific product.
Current products are safer in regards to viral and HIV infection. However, contamination with previously unknown pathogens may occur. Currently, blood from donors who have new variant Creutzfeldt-Jacob disease (nvCJD) has been withdrawn from the manufacturing process. Potential risk of nvCJD or transmissible spongiform encephalopathies remains a concern when plasma-derived products are used. Patients should be vaccinated for hepatitis A and B.
DIC and thromboembolism are complications that have occurred using PCCs and aPCCs. Fibrinolytic inhibitors should not be used concomitantly with these products because of the risk of accelerating thrombosis.
FIX inhibitors develop in 3-5% of patients with hemophilia B who are receiving concentrates. An inhibitor should be suspected if FIX levels do not rise to predicted (expected) levels following treatment with concentrates, a hemorrhage does not respond to previously adequate doses, or severe allergic reactions occur soon after starting a patient on a replacement product. Laboratory confirmation of the presence of an inhibitor is essential.
Treatment of patients with FIX inhibitors is complex, requiring the services of a competent hematologist. Patients with low titers of inhibitors of 10 Bethesda units can be treated using PCCs, starting with a dose of 75 U/kg q6-12h, or recombinant activated factor VIIa (rFVIIa) can be used to treat patients with FIX inhibitors; doses vary from 30-90 mcg/kg IV q2-3h, with 1 additional dose after hemostasis is achieved.
Availability of rFVIIa resulted in another leap forward in the ability to treat patients with inhibitors to FIX or factor VIII coagulant activity (FVIII-C), allowing them to undergo previously impossible major surgical procedures, such as joint replacements or pseudocyst excisions, which require extensive procedures. As a result of its cost, rFVIIa previously was used as backup therapy when other products failed, but as experience with this product grows, it is being used more often as first-line therapy. The starting dose can vary from 30-90 mcg/kg IV every 2-3 hours.
Excellent or effective response may be seen in patients with inhibitors within 12 hours of starting therapy. Data from compassionate-use experience shows that hemostasis was obtained in approximately 92% of patients with inhibitors within 2-3 doses using 90 mcg/kg, suggesting an up-front use of the larger dose.
A decline of inhibitor titer to approximately one third of the original level was seen in patients who had received repeated doses of rFVIIa for treatment of bleeding. A continuous infusion regimen, rather than administration of an intermittent bolus, has been used successfully in patients with inhibitors. Since FVIIa in concert with TF, phospholipids, and calcium activates FX to FXa, thereby leading to thrombin generation, fibrinogen levels were monitored in treated patients and found to be similar to baseline values in the majority.
Additionally, follow-up samples obtained in patients treated with rFVIIa did not detect any antibody levels above the cutoff value, and no new antibodies were found to baby hamster kidney cells or to murine IgG. Despite these data, further studies are needed to refine dosing for the treatment of different types of bleeding in patients with inhibitors. Duration of therapy depends on adequacy of control of bleeding as balanced against possible adverse effects. Thromboembolic complications are infrequent, based on currently available information.
Advantages of rFVIIa are that it is a recombinant protein with no risk of transmission of the usual viruses, hemostasis is localized to the site(s) of injury, anaphylactic reactions have not occurred in patients with FIX deficiency, and rFVIIa does not induce an anamnestic rise in FIX antibody titer. rFVIIa can be used at home, postoperatively. Disadvantages are its expense, the need for good venous access, frequent repetitive administration, and activation of coagulation with possible DIC and rare thromboembolic events.
Immune tolerance induction (ITI) using prolonged gradually increasing doses of IV FIX concentrate, IV IgG, Cytoxan, other immunosuppressives, and inhibitor-antibody column has been used to treat patients with FIX inhibitors. ITI can be associated with development of nephrotic syndrome, which usually is steroid resistant and requires withdrawal of the antigenic protein. Disadvantages of ITI are that it is time intensive (6-24 mo), requires a high degree of patient compliance and daily venous access, is expensive, and has a significant failure rate.
The use of PCC/aPCC products in patients with inhibitors has several disadvantages. They have a poorly defined mode of action and an unpredictable hemostatic response. Since they are derived from pooled plasma, they carry a greater potential for transmission of viral and other illnesses. In addition, response is variable, frequent administration is required (at least q12h), and they are associated with significant failure rate, induce an anamnestic response with increase in antibody titer, and are not for use in patients who have developed anaphylaxis to FIX products.
Factor IX concentrates
For use in patients with FIX deficiency.
In practice, administration of concentrates must be individualized by the evaluation of the extent, site, and cause of bleeding, response to therapy, current laboratory data, and the patient's history.
Table 2. Rough Guidelines for Treatment Using Factor IX Concentrates
Open table in new window
Table
| Type of Hemorrhage | Desired FIX Activity, % of Normal | Duration of Therapy, Days |
|---|---|---|
| Minor - Uncomplicated hemarthroses superficial large hematomas | 20-30 | 1-2 |
| Moderate - Hematoma with dissection Oral/mucosal hemorrhages and epistaxis hematuria* | 25-50 | 3-7 (2-5 in oral hemorrhages) |
| Dental extraction(s)* | 50-100 | 2-5 |
| Major - Pharyngeal/retropharyngeal, retroperitoneal, GI tract bleeding, CNS bleeding surgery | ~100 until bleeding is controlled; then taper to minimum required to prevent rebleed | 7-10 (5-10 in oral hemorrhages) |
| Type of Hemorrhage | Desired FIX Activity, % of Normal | Duration of Therapy, Days |
|---|---|---|
| Minor - Uncomplicated hemarthroses superficial large hematomas | 20-30 | 1-2 |
| Moderate - Hematoma with dissection Oral/mucosal hemorrhages and epistaxis hematuria* | 25-50 | 3-7 (2-5 in oral hemorrhages) |
| Dental extraction(s)* | 50-100 | 2-5 |
| Major - Pharyngeal/retropharyngeal, retroperitoneal, GI tract bleeding, CNS bleeding surgery | ~100 until bleeding is controlled; then taper to minimum required to prevent rebleed | 7-10 (5-10 in oral hemorrhages) |
*Concomitant administration of EACA or tranexamic acid (both fibrinolytic inhibitors) can help reduce the dose of clotting factor replacement required to treat such bleeds.
Recombinant human factor IX (BeneFix)
Indicated for control and treatment of spontaneous or surgery-related bleeding or prevention of bleeding in patients proven to be deficient in FIX. Used as first-line therapy, particularly in previously untreated patients, due to safety regarding common virally transmitted illnesses.
In vivo recovery of rFIX is lower than that obtained with plasma-derived products.
Adult
In a small study, 1 IU/kg of BeneFix increased circulating FIX activity by 0.8 IU/dL (range 0.4-1.4 IU/dL)
Reasonable dosage calculation guide is as follows: FIX dose (IU) = body weight (kg) X desired FIX increase (%) X 1.2 IU/kg (see Table 2)
Pediatric
Initial dose: Administer as in adults; monitor trough and peak values to determine adequacy of dose because pharmacokinetics are different in children <16 years; safety and efficacy studies are ongoing; studies report no major adverse reactions in previously untreated children
Antiplatelet drugs (eg, NSAIDs, herbal products) can increase frequency and severity of bleeds; fibrinolytic inhibitors increase risk of acute firm clot in ureters in patients with hematuria if administered concomitantly with product replacement, leading to acute urinary obstruction
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Carefully monitor for any type of allergic reactions (eg, hives, chest tightness, chills, flushing, nausea); possible need to slow infusion rate or discontinue drug if severe allergic reactions develop; additional details listed under introduction to medications
Monoclonal antibody purified factor IX concentrate (Mononine)
Prevents and treats spontaneous or surgery-associated bleeding in patients with proven FIX deficiency. As with any factor replacement therapy, documenting actual recovery for a given dose and product is essential in every patient.
Adult
General guide to dosing derived from studies is as follows:
FIX dose (IU) = body weight (kg) X desired FIX increase (%) X 1 IU/kg
Pediatric
Administer as in adults
Fibrinolytic inhibitors (tranexamic acid, aminocaproic acid) may increase risk of acute firm clot in ureters in patients with hematuria, leading to acute urinary obstruction when administered with FIX; NSAIDs increase risk for bleeding
Documented hypersensitivity; hepatic disease if DIC or fibrinolysis suspected
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Carefully monitor for any type of allergic reactions (eg, hives, chest tightness, chills, flushing, nausea), which may be ameliorated by antihistamines, require slowing infusion rate, or discontinuation of drug; additional details listed under introduction to medications
Factor IX complex (Proplex T)
Heat-treated concentrate of vitamin K–dependent factors derived from human plasma. Prior to availability of recombinant and monoclonal antibody purified products, patients deficient in F IX were treated with such concentrates because of the ability to provide needed amounts of FIX in a smaller volume than was previously achievable with fresh frozen plasma. This product can be used to treat patients with proven FIX deficiency, if they have used plasma-derived products previously, patients with inhibitors to FVIII, and patients who are FVII deficient (note: rFVIIa is now available for use in these patients). Please note the risks involved with the use of FIX complex concentrates.
Adult
FIX deficiency dosing formula:
FIX dose (IU) = body weight (kg) X desired FIX increase (%) X 1 IU/kg
Pediatric
Not established
May decrease anticoagulant effect of warfarin; fibrinolytic inhibitors (tranexamic acid, aminocaproic acid) may increase risk of clot formation
Documented hypersensitivity; do not use in active DIC
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Carefully monitor for any type of allergic reactions (eg, hives, chest tightness, chills, flushing, nausea), which may be ameliorated by antihistamines, require slowing infusion rate, or discontinuation of drug; risk of virally transmitted disease (ie, HIV, hepatitis); risk of thrombotic complications; infuse slowly, particularly in patients with hepatitis, to avoid precipitating DIC; careful monitoring for DIC may be necessary with hepatitis; if used in emergent critical organ bleeding in patients with excess warfarin effect, follow-up testing should be performed for virally transmitted disease or other illnesses; additional details listed under introduction to medications
Factor IX concentrate (Bebulin VH)
Vapor-heated concentrate of vitamin K–dependent factors derived from human plasma. Prior to availability of recombinant and monoclonal antibody purified products, patients deficient in FIX were treated with such concentrates because of the ability to provide needed amounts of FIX in a smaller volume than was previously achievable with fresh frozen plasma.
Adult
To estimate dose of FIX when using this product:
FIX dose (IU) = body weight (kg) X desired FIX increase (%) X 1.2 IU/kg
Pediatric
Not established
May decrease anticoagulant effect of warfarin; fibrinolytic inhibitors (tranexamic acid) increase risk of clot formation; aminocaproic acid increases risk of thrombosis
Documented hypersensitivity; do not use with active DIC
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Carefully monitor for any type of allergic reactions (eg, hives, chest tightness, chills, flushing, nausea), which may be ameliorated by antihistamines, require slowing infusion rate, or discontinuation of drug; risk of virally transmitted disease (eg, HIV, hepatitis); risk of thrombotic complications; infuse slowly, particularly in patients with liver disease, to avoid precipitating DIC; careful monitoring for DIC may be necessary in such patients; if used in emergent critical organ bleeding in patients with excess warfarin effect, follow-up testing should be performed for virally transmitted disease or other illnesses; additional details listed under introduction to medications
Factor VIIa, recombinant (NovoSeven)
Used in patients with FIX inhibitors to control spontaneous or anticipated surgical bleeding. The dose range that has been used has varied from 35-120 mcg/kg. Dose generally is tapered after hemostatic efficacy has been obtained, depending on clinical context.
Adult
90 mcg/kg IV bolus q2h until hemostasis is achieved or until treatment is considered to have failed
Pediatric
Administer as in adults
Diminishes anticoagulant effect of warfarin; use with PCCs or aPCCs is not advised
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Monitor for DIC; higher risk for DIC in presence of infection, tissue injury, vessel wall damage, or sepsis (slower rate of infusion and lower starting dose may be necessary); decompensation of coagulation factors and platelet count may require discontinuation; careful balance of need for hemostasis versus extent of coagulation factor decompensation must be achieved
Antifibrinolytics
Use together with single-dose factor replacement for minor surgical procedures, such as dental extractions or sinus surgery, so that the procedures can be accomplished on an outpatient basis with the use of a single dose of product.
Aminocaproic acid (Amicar)
Hemostatic agent that diminishes bleeding by inhibiting fibrinolysis of hemostatic plug. Can be used PO or IV.
Adult
5 g PO initially, followed by 1 g/h PO for 8 doses or until active bleeding controlled, then taper (frequency of maintenance dose can be lengthened (2 g PO q2h) if needed to reduce frequency for patients taking drug at home
5 g IV over 30 min to 1 h initially, followed by 1 g/h IV; 1 g q1h or equivalent dose q2-4h PO/IV or 0.1 g/kg q4-6h IV maintenance; not to exceed 30 g/d
Pediatric
100-200 mg/kg IV over 30 min initially; followed by 30 mg/kg q1h or 100 mg/kg q6h maintenance; not to exceed 18 g/m2
Coadministration with estrogens may result in hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process (can be fatal in patients with DIC)
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Do not administer unless definite diagnosis of primary hyperfibrinolysis is made; caution in cardiac, hepatic, or renal disease (reduce dose); benzyl alcohol can cause toxicity in newborns and, therefore, is not recommended; prolonged continuous IV infusion generally not recommended; one third of patients receiving large oral doses for prolonged period of time experience adverse GI tract effects (eg, abdominal pain, nausea, diarrhea); dizziness may occur; occasional reports of myopathy and rhabdomyolysis recorded after prolonged high-dose therapy, with resolution after withdrawal of drug
Tranexamic acid (Cyklokapron)
Fibrinolytic inhibitor used with FIX replacement to reduce need for hospitalization and more than 1 dose of FIX concentrate in patients with hemophilia B requiring dental or sinus procedures. Can be used similarly in patients with hemophilia A. Also used to inhibit fibrinolysis in other conditions.
Adult
Prior to surgery: 25 mg/kg PO tid/qid 1 d prior to procedure; continue for 2-8 d prn; combine with IV dose FIX concentrate just prior to surgery
Prior to dental extraction: 10 mg/kg IV together with FIX concentrate (single dose) just prior to procedure; continue tid/qid for several days prn
Mild renal failure: Change frequency to bid
Moderate renal failure: Change frequency to 10 mg/kg IV (15 mg/kg PO) qd
Severe renal impairment: Change dose to 7.5 mg/kg IV/PO qd
Pediatric
10 mg/kg IV slowly initially, followed by 25 mg/kg IV q6-8h
Increased risk of thrombosis with anti-inhibitor coagulant complex and antifibrinolytics; increased risk of clot formation with clotting factors; increased coagulation with estrogens; reduces effectiveness of thrombolytic agents
Documented hypersensitivity; active DIC; acquired defective color vision; subarachnoid hemorrhage
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Dose reduction in renal failure; GU tract obstruction can occur when used with FIX concentrate in GU tract bleeding in patients with hemophilia B; similar problems occur with use in GU tract bleeding in patients with hemophilia A and associated with thrombosis or thromboembolism; continuous IV infusion generally not recommended
More on Factor IX |
| Overview: Factor IX |
| Differential Diagnoses & Workup: Factor IX |
 Treatment & Medication: Factor IX |
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Further Reading
Keywords
hemophilia B, Christmas disease, hemophiliac, hemophilia, blood factors, factor 9, FIX, bleeding disorder, blood disease, blood disorder, hemarthrosis, hematomas, mucocutaneous bleeding, inherited blood disease, familial bleeding disorder, familial blood disease, factor replacement therapy
