sign in sign up
<<
Home , Anagrelide, Bleeding, Factor VIII (medication), Von Willebrand disease

Bleeding disorders

ER guide to disorders

1 Table of contents

4 General guidelines 4–5 National Hemophilia Foundation guidelines 5–10 Treatment options 10 Hemophilia A Name:______10–11 National Hemophilia Foundation guidelines Address:______12 Dosage chart Phone:______14–15 Treatment products 16 Hemophilia B In case of emergency, contact: ______16 National Hemophilia Foundation guidelines

Relation to patient:______17 Dosage chart 18 Treatment products 19 Hemophilia A or B with inhibitors Diagnosis:  Hemophilia A:  Mild  Moderate  Severe 20 National Hemophilia Foundation guidelines  Inhibitors  Inhibitors Bethesda units (if known) ______21 Treatment products  Hemophilia B:  Mild  Moderate  Severe 22–23   Inhibitors Inhibitors Bethesda units (if known) ______23–24 National Hemophilia Foundation guidelines  von Willebrand disease:  Type 1  Type 2  Type 3  type 25 Treatment products 27 Bibliography

Preferred product:______

Dose for life-threatening bleed:______This ER guide to bleeding disorders rendering of medical care. The treatment. The diagnosis and contains general educational recommendations were developed treatment of bleeding disorders If inhibitor, bypassing agent product name and dose:______materials to assist emergency room by the Medical and Scientific should only be undertaken by, or Allergies:______staff in handling an emergency Advisory Council (MASAC) of the under the direction of, a qualified involving a patient with hemophilia National Hemophilia Foundation doctor. Any questions should be or von Willebrand disease. This (NHF). The patient’s hematologist directed to a qualified hematologist. document is not intended to should always be consulted with Primary care physician:______Phone:______constitute medical advice or the regard to the patient’s medical Hematologist or HTC:______Phone:______

2 3 ER guide to bleeding Assessment hemorrhage. For routine joint 7. Any invasive procedure or . In general, follow bleeding, no radiographic studies disorders 1. Treatment for a suspected 8. Heavy or persistent bleeding from these guidelines: are indicated. Inherited bleeding disorders, such bleeding episode is based on any site. • Do not keep this patient waiting. as hemophilia and von Willebrand clinical history. Physical exam 2. For patients with hemophilia 9. Gastrointestinal bleeding. disease, present unique challenges • A bleeding episode requires findings tend to be normal in the who have illnesses or disorders 1 0 . Acute fractures, dislocations for patients and caregivers in the immediate attention. early phases of most hemophilic that necessitate an invasive and sprains. emergency room (ER). Because bleeds. Spontaneous bleeding is procedure (, • Infuse promptly. hemophilia is rare — approximately common in individuals with severe arterial gas, arthrocentesis, • Therapeutic infusions TREATMENT 20,000 people in the United States disease (factor levels <1%). When etc.) or surgery, factor should precede radiographic have this bleeding disorder —­ many in doubt, administer clotting replacement therapy must be Hemophilia A without inhibitor studies, invasive procedures doctors may not have treated a factor replacement therapy. administered in the emergency The treatment of choice for patients with hemophilia A (factor VIII deficiency) 1,2 or complex evaluations. department beforehand. patient with a bleeding disorder. 2. Treatment decisions should be is recombinant factor VIII or the patient’s product of choice. Plasma-derived • Listen to the patient. 3. For an individual with known concentrate is a suitable alternative in an emergency situation when This educational guide provides based on the suspicion of a • These patients are generally hemophilia, routine laboratory recombinant factor VIII is not available. and fresh frozen general recommendations and bleeding-related problem, not the quite knowledgeable about the studies (PT, PTT, factor levels) plasma are no longer recommended for treatment of people with hemophilia. guidelines to assist emergency documentation of one. disease. Be prepared to work are not indicated in the treatment room staff in handling an 3. Believe the patient or the parent When bleeding is severe, the appropriate dose of factor VIII is 50 units/kg. in collaboration with them. of a routine bleeding episode emergency involving a patient of a patient. If in their experience This should result in a factor VIII level of 80%–100%. unless requested by the patient’s with hemophilia or von Willebrand • Contact the patient’s they suspect occult bleeding hematologist. The clinical severity disease and is not intended to hematologist. is occurring, administer clotting Mild hemophilia A with non-life- or limb-threatening bleeding of a patient’s hemophilia is replace standard medical practices. factor replacement. Patients often Individuals with mild hemophilia A (factor VIII greater than 5%) who gauged by his or her baseline Guidelines for Emergency are instructed in and/or carry with are experiencing non-life- or limb-threatening bleeding may respond to Diagnosis and treatment of Department Management clotting factor level, a value that them appropriate factor if they have been shown to respond to this treatment previously. bleeding disorders are the ultimate of Individuals with remains fairly constant replacement dosing guidelines Otherwise, treatment is the same as for other individuals with hemophilia A. responsibility of the attending throughout that person’s life. Hemophilia as advised by their treating doctor. However, in many cases, the MASAC recommendation #175 Hemophilia B without inhibitor hematologist. Indications for factor patients and caregivers are very The following guidelines were approved by the Medical and Scientific Advisory Council (MASAC) replacement therapy The treatment of choice for patients with hemophilia B (factor IX deficiency) knowledgeable about treatment. 4. Consultation with the patient’s of the National Hemophilia Foundation on is recombinant factor IX or the patient’s product of choice. Plasma-derived Any questions should be directed October 14, 2006, and adopted by the NHF hematologist or a regional 1. Suspected bleeding into a joint Board of Directors on October 15, 2006. concentrate is a suitable alternative in an emergency situation when to a qualified hematologist. hemophilia treatment center or muscle. recombinant factor IX is not available. is no longer Individuals with bleeding disorders professional is strongly advised; 2. Any significant injury to the head, recommended for treatment of individuals with hemophilia B. Note that who present to an emergency however, this should not delay neck, mouth or eyes, or evidence cryoprecipitate does not contain factor IX. When bleeding is severe, the department for care should receive giving clotting factor replacement of bleeding in those areas. appropriate dose of factor IX is 100–120 units/kg. This should result in a appropriate, expeditious management. to the patient. factor IX level of 80%–100%. To this end, MASAC has developed the 3. Any new or unusual , Diagnostic studies following guidelines. particularly one following trauma. 1. If a patient with hemophilia 1. Clotting factor replacement whenever possible. Individuals 4. Severe pain or swelling at any site. or the parent of a patient with Triage therapy should be given before any with bleeding disorders are 5. All open requiring hemophilia brings clotting encouraged to have an Triage should be urgent because delays diagnostic studies (X-rays, surgical closure, adhesive factor with them to the emergency dose of factor in administering factor concentrate CAT scans, etc.) are performed or steri-strips. emergency department, allow concentrate or DDAVP in their treatment significantly affect morbidity in the evaluation of a suspected them to utilize it. They should home and to take it with them and mortality in individuals with bleeding problem, especially in 6. History of an accident or trauma be permitted to reconstitute the when they travel. In those hemophilia. the case of head trauma or that might result in . product and administer it situations where a patient does 4 suspected intracranial 5 not bring their own clotting FEIBA® VH at 75–100 units/kg. The 9. In situations in which patients Treatment options and full vials, rather than a portion of a Please refer to pages 14 and 15 for a factor concentrate, emergency patient or family can also provide are hemodynamically stable and general guidelines vial, are administered for prescribed list of factor VIII products and page departments must be prepared to information on response to are not requiring volume Clotting factor factor doses. A moderate excess of 18 for a list of factor IX products provide clotting factor therapeutic bypassing agents. replacement, the smallest gauge replacement therapy recombinant factor will prolong available in the United States. replacement. Emergency 5. When treating an individual with needle should be utilized for a therapeutic hemostatic level of departments must have ready obtaining IV access (25-gauge An intravenous infusion of the treatment. Try to match the Treatment regimens mild hemophilia A who is replacement clotting factor access to factor replacement responsive to desmopressin, butterfly needles in young infants, assays with the calculated dosage A patient’s hematologist will concentrate will elevate factor levels prescribe a treatment regimen to products so they are available the dose and prior responsiveness 23-gauge butterfly needles in as closely as possible. Overfilling within 1 hour of the patient’s older children and adults). enough to allow the body to form a increases drug utilization costs manage hemophilia: are usually known. The dose clot and stop the bleeding. Clotting arrival. In an effort to expedite while underfilling may cause • Episodic treatment (also called of desmopressin is 0.3 mcg/kg 10. Tourniquets should not be applied factor concentrate comes as a freeze- care, emergency doctors should breakthrough or continuing bleeds, on-demand or PRN) occurs when subcutaneously, or intravenously tightly to extremities because they dried powder that is reconstituted order unreconstituted factor requiring follow-up infusions. Please factor is given only when a in 30 mL normal over 30 may cause bleeding. with sterile water prior to infusion. from their pharmacy or blood refer to the dosage charts on pages bleeding episode occurs. minutes. It may also be 11. and aspirin-containing bank and reconstitute the Factor must be used within 3 hours 12 and 17 as a calculation guide. administered as an ultra • Prophylaxis is the practice of product in the emergency products are contraindicated of reconstitution. Each box of factor concentrated nasal spray in individuals with hemophilia A. has a lot number, expiration date and Possible side effects giving factor on a regular basis department. (Stimate®) at a dose of one spray Acetaminophen and/or codeine a specific number of units (assays). All If infused too rapidly, side effects (usually several times a week) to 2. Factor replacement must be in one nostril for individuals <50 may be used for analgesia. Non- this information should be included in raise factor levels to prevent bleeds. administered intravenously by kg and one spray in each nostril include tingling at the site or in steroidal anti-inflammatory the patient’s chart when administered. • Planned preventive treatment IV push over 1–2 minutes (or per for individuals >50 kg. the hands or lips, lightheadedness, drugs (NSAIDs) may be carefully Refer to the product manufacturer’s involves infusing factor before an manufacturer’s recommendation). shortness of breath and burning 6. The most experienced IV administered to select patients, package insert for specific mixing at the infusion site. Allergic event or activity that may 3. Dose factor up to the “closest vial,” therapist or phlebotomist should such as individuals with chronic and dosing guidelines, administration reactions include chills, fever, potentially cause a bleed. and infuse the full content of each perform any venipuncture. arthritic pain who are not actively rate and dosing calculations. hives and difficulty breathing. • Continuous infusion is when reconstituted vial. A moderate Traumatic venipunctures and bleeding or being treated for a factor is delivered through a excess of factor concentrate will repeated needle sticks cause recent bleeding problem. Reconstituted factor is injected into the Clotting factor concentrate body through a vein or a central venous continuous ambulatory infusion not create a hypercoaguable state painful that may There are two forms of clotting 12. If an individual with hemophilia access device. The smallest gauge pump. This delivery mode is often but will prolong the therapeutic limit further IV access. factor concentrates, depending on A is bleeding and requires needle should be utilized for obtaining used to stop bleeding for level of the product administered. the source from which it is made: 7. In any suspected bleeding transportation to another facility IV access—25-gauge butterfly needles hemophilia patients who Thus, it is prudent to “round up.” plasma-derived or recombinant. emergency in which the clotting for definitive care, all efforts work well in young infants. Additionally, face surgery, trauma or serious Recombinant clotting factors are 4. For individuals with inhibitors factor level of an individual with should be made to replace the most adults and older children prefer hemorrhage. Studies have shown preferable and considered the (antibodies to factor VIII), hemophilia is unknown, the deficient clotting factor before butterfly needles for IV access— that continuous infusion standard treatment. Because treatment decisions may be more factor level should be assumed to transport. 23-gauge needles are frequently used. maintains factor level in a complicated. The care of inhibitor be 0 percent. This material is provided for your general recombinant products contain therapeutic range and provides information only. NHF does not give medical advice few or no proteins from human patients should be urgently 8. Intramuscular injections should or engage in the practice of medicine. NHF under Dosage effective compared discussed with the patient’s no circumstance recommends particular treatment blood, the risk of contracting be avoided if at all possible. If they for specific individuals and in all cases recommends Factor dosage or number of units with bolus injection. However, viruses is minimal or absent. hematologist. If an individual must be given, factor replacement that you consult your doctor or local treatment infused is based on the patient’s continuous infusion of factor with an inhibitor presents in a center before pursuing any course of treatment. therapy should precede the weight and the percentage of Cryoprecipitate, once regarded requires different dosing life- or limb-threatening Reprinted with permission from the National injection. Parenteral agents Hemophilia Foundation. Please visit the NHF website circulating factor VIII desired. Factor as the treatment of choice for calculations. Please consult a scenario, the safest immediate at www.hemophilia.org for more information. should be given intravenously concentrates are manufactured people with hemophilia, is no hematologist for more information. action is to prescribe recombinant or subcutaneously. Tetanus in vials with varying ranges. longer recommended because it is Note: Continuous infusion is factor VIIa (rFVIIa) at a dose of immunizations may be Often, a factor prescription is written considered less safe than currently currently used off-label and is not 90 mcg/kg or activated administered subcutaneously. as +/- 10 percent of a target dose. available clotting factor concentrates. approved by the FDA. prothrombin complex concentrates 6 To prevent costly waste of factor, 7 Medications including herbs, vitamins and over- complications directly, continued cause bleeding. Aspirin should Natural products Anti-platelet agents the-counter drugs. Certain drugs may use may lead to a decrease in the not be taken by a person with a (Pletal®) Desmopressin, A number of herbal products may interact with each other or make it absorption of , which is bleeding disorder. Aspirin can also (Plavix®) Stimate, Amicar® affect bleeding time, the formation harder for blood to clot. A complete needed for effective clotting. prevent from working Ticlopidine (Ticlid®) of a clot or the ability of platelets Patients with mild hemophilia A medication profile will allow you to properly and worsen a patient’s Anagrelide (Agrylin®) to stick together to form a clot. (baseline clotting factor of at least check for any possible interactions. COX-2 inhibitors underlying tendency to bleed. (Persantine,® 5 percent) who have non-life– A COX-2 inhibitor, such as , Pain management Aggrenox®) threatening bleeding may be given Acetaminophen is a type of NSAID that causes Interferon and ribavirin When treating the pain that typically Bile acid sequestrants desmopressin either intravenously, Because aspirin can be harmful fewer bleeding problems than Interferons are used to treat viral accompanies a hemorrhage, avoid Cholestyramine (Questran,® subcutaneously, or intranasally. to people with bleeding disorders, traditional NSAIDs. COX-2 inhibitors infections and various types of giving drugs that inhibit platelet Lo Cholest®) Because desmopressin is a potent many hematologists recommend are often used to treat arthritis and cancer. Gastrointestinal bleeding aggregation. Never give aspirin, Colestipol (Colestid®) antidiuretic agent, the patient must acetaminophen for their patients. are not associated with causing has been associated with alpha agents that contain aspirin or Colesevelam (Welchol™) restrict fluid intake, and serum platelets to malfunction. The interferon. has been other NSAIDs that inhibit platelet sodium levels should be monitored and National Hemophilia Foundation associated with the use of both Herbal Products 1 aggregation. Acetaminophen and during repeated doses of the drug. anti-platelet agents recommends the potential risk interferon and ribavirin, which is Anise opiate agents are preferable. Anticoagulants, or blood thinners, of bleeding be weighed against also used to treat .6 Astragalus Amicar (aminocaproic acid) is often by their very nature may lead to the potential benefit in patients Bilberry used to treat mouth bleeds. It is The following is a list of specific bleeding complications if not closely with bleeding disorders.4, 5 Protease inhibitors Bromelain available in injectable, tablet and drugs that affect clotting. monitored. If these medications are Protease inhibitors are used in Dong quai liquid forms. This product should This is not a complete list. needed, monitoring by a doctor is Non-steroidal anti- combination with other antiretroviral Fish oils (omega 3 fatty acids) not be used in conjunction with Anti-coagulants essential. inflammatory drugs medications in the treatment of HIV Flax seed anti-inhibitor or factor IX products or Dalteparin (Fragmin®) (NSAIDs) and salicylates infection. These medications can Fucus bypassing agents, such as FEIBA VH. Enoxaparin (Lovenox®) Bile acid sequestrants These medications are used for pain be used in patients with bleeding Garlic Fondaparinux (Arixtra®) These drugs lower cholesterol by and inflammation. They have the disorders under the supervision Ginger Prescriptions, over-the- Heparin binding to bile acids and decreasing potential to prolong bleeding by of a doctor. Some patients taking Ginko biloba counter medications and Tinzaparin (Innohep®) herbal supplements the amount of fat and lipid material preventing platelets from sticking these medications have reported Ginseng (Coumadin®) Guarana It is important to know what absorbed by the body. While these to one another. These medications spontaneous bleeding. Horse chestnut medications the patient is taking, drugs do not cause bleeding can also irritate the stomach and

8 9 Pennyroyal Ritonavir (Norvir®) I. Recommendation for doctors thus, recombinant factor VIII technology and thus theoretically St. John’s wort Saquinavir mesylate treating patients with hemophilia A products are the recommended do not transmit human Tumeric (Invirase,® Fortovase®) A. Treatment of hemophilia A treatment of choice for patients viruses. Moreover, methods of Vitamin E Tipranavir (Aptivus®) with hemophilia A. (Table I.A.) viral inactivation (pasteurization, 1. Recombinant factor VIII NSAIDs Salicylates 2. Plasma-derived factor VIII solvent-detergent treatment, concentrates: Recombinant (r) immunoaffinity purification) Celecoxib (Celebrex®) Aspirin (Bufferin,® Excedrin, FVIII is produced by well- concentrates: Improved Diclofenac (Cataflam,® Voltaren,® Anacin,,® and many others) viral-depleting processes and have resulted in a reduced established hamster cell lines risk of HIV and hepatitis B and C Arthrotec®—combination with Magnesium salicylate that have been transfected with donor screening practices have misoprostol) (Extra Strength Doan’s®) resulted in plasma-derived (pd) transmission with plasma-derived the gene for human FVIII(1,2). Two factor VIII concentrates Diflunisal (Dolobid®) Salicylate combinations (Trilisate®) recombinant factor VIII products FVIII products that have greatly (Lodine,® Lodine® XL) reduced risk for transmission of ( 5–6, 11–13). For these reasons, Hemophilia A have the B domain deleted cryoprecipitate should not be Flurbiporfen (Ansaid®) from the factor VIII gene before human immunodeficiency virus Hemophilia A is rare, affecting only used as a treatment alternative. Ibuprofen (Motrin,® Advil,® Nuprin®) it is inserted into Chinese and hepatitis B and C. No 12,000 people in the United States.7 Despite donor screening by Indomethacin (Indocin,® Indocin® SR) hamster cells (3). First seroconversions to HIV, HBV or Ketoprofen (Orudis,® Orudis® KT, HCV have been reported with nucleic acid testing (NAT) for What is hemophilia A? generation rFVIII contains animal HIV-1, HBV and HCV, Oruvail®) and/or human plasma-derived any of the pdFVIII products People who are missing or have cryoprecipitate might still Ketorolac (Toradol®) proteins in the cell culture medium currently marketed in the United a low amount of factor VIII have be infectious. While the current Meloxicam (Mobic®) and in the final formulation vial. States, including products that hemophilia A. There are different estimate for the risk of HIV Nabumetone (Relafen®) Second generation rFVIII contains are heated in aqueous solution levels of severity of hemophilia, infection from a single unit of Naproxen (Aleve,® Anaprox,® animal or human plasma proteins (pasteurized), solvent-detergent determined by the amount of factor blood is one in 1,000,000 Naprosyn®) in the medium but not in the final treated and/or immunoaffinity a person has in his blood. Severity donations, the risk of HCV Oxaprozin (Daypro®) formulation, while third generation purified. Thus, each of these levels do not change over time. transmission is somewhat higher, Piroxicam (Feldene®) rFVIII does not contain any animal methods appears to have greatly Sulindac (Clinoril®) reduced the risk of viral approximately 1 in 900,000 (14). MASAC recommendations or human plasma-derived proteins Tolmentin (Tolectin®) transmission compared with 4. Treatment of mild hemophilia A: concerning the treatment in the culture medium or in the older methods of viral inactivation Desmopressin (DDAVP®) should be Protease inhibitors of hemophilia A final formulation vial. The risk of (4–6). There remains the possibility used whenever possible for Amprenavir (Agenerase®) MASAC recommendation #187 human viral contamination of HIV-1, HIV-2 or hepatitis B or C patients with mild hemophilia A. Atazanavir sulfate (Reyataz®) (Replaces document #182) associated with recombinant FVIII virus transmission with the use of DDAVP is available in both a Darunavir (Prezista®) (Revised November 2008) is definitely much lower than for currently marketed, viral-inactivated, parenteral form (DDAVP injection) Fosamprenavir (Lexiva®) The following recommendation was approved plasma-derived FVIII products. by the Medical and Scientific Advisory Council plasma-derived products. The and a highly concentrated Indinivir sulfate (Crixivan®) (MASAC) on November 15, 2008, and adopted by the No seroconversions to HIV, HBV or Lopinavir/ritonavir (Kaletra®) NHF Board of Directors on November 16, 2008. HCV have been reported with any non-lipid enveloped viruses human intranasal spray formulation Nelfinavir mesylate (Viracept®) of the currently available products; parvovirus B19 and hepatitis A (Stimate nasal spray). (Table III.A.) virus were also transmitted by Desmopressin should not be This material is provided for your general information only. NHF does not give medical advice 8 pdFVIII (7–9); additional steps used in certain categories of Classification Factor level what to expect or engage in the practice of medicine. NHF under such as viral filtration have been patients. Children under the age no circumstance recommends particular treatment Less than Bleeding after a minor injury, major trauma or surgery is common. Bleeding may for specific individuals and in all cases recommends Severe added to reduce these risks as of 2, pregnant women and you consult your doctor or local treatment center 1% occur without an obvious injury (spontaneous bleeding). well. (Table I.B.). patients with mild hemophilia before pursuing any course of treatment. Bleeding after minor injury is possible, as well as after major trauma or surgery. A in whom desmopressin does Reprinted with permission from the National Moderate 1 to 5% Occasional spontaneous bleeding may occur but is usually associated with 3. Cryoprecipitate not not provide adequate factor Hemophilia Foundation. This material is an excerpt of prolonged or serious bleeding in a joint. recommended: FVIII products “MASAC Recommendations Concerning the Treatment VIII levels should be treated as per of Hemophilia and Other Bleeding Disorders” (#187). 5 to 30 percent. Prolonged bleeding usually occurs only after serious injury, are available that are Mild 5 to 30% section I.A.1 or I.A.2. Please visit the NHF website at www.hemophilia.org to major trauma or surgery. manufactured by recombinant see the recommendation in its entirety. 10 Normal 50 to 150% 50 to 150 percent. No abnormal bleeding. 11 455 682 909 1591 1136 1818 3182 2727 100% 5227 5455 4773 2273 4318 1364 2955 4545 4091 5682 2045 3636 2500 3864 3409 5000 818 614 90% 409 5114 1227 1841 1432 1023 3273 3477 2455 1636 4705 2250 4091 4295 2045 2659 3682 3886 2864 4500 3068 4909 727 545 80% 364 909 1273 1818 1455 1091 2182 2727 3273 3818 4182 3455 2545 1636 3091 4545 2364 3636 4364 2909 2000 4000 318 477 795 955 70% 1114 636 1591 1273 1750 3341 1432 3182 3818 2227 2545 3977 2705 3023 1909 3659 2386 3500 2864 2068 273 818 545 955 682 60% 409 1773 1227 1091 2318 2591 3136 2182 2727 3273 1364 2455 1500 1636 2045 1909 2864 3409 3000 341 227 455 795 50% 568 682 909 1591 1136 1477 1818 1705 1250 2159 2727 1023 1932 2273 2841 1364 2614 2045 2386 2500 182 727 273 818 455 545 364 636 40% 909 1182 1727 1273 1818 1455 1545 1091 2182 2273 1364 1636 2091 1909 1000 2000 Example using dosage chart: using dosage Example 1455 require he would Using this chart, 40% . to level his factor needs raise to 160 lbs. A man weighing 730 units each, bottles on hand contain VIII If concentrate the factor VIII concentrate. units of factor bottles. two the man will receive 341 136 273 477 818 545 614 750 955 205 682 30% 886 409 1159 1227 1705 1091 1432 1295 1023 1568 1364 1500 1636 511 114 341 170 227 455 795 852 739 625 568 25% 284 398 682 966 909 1136 1193 1307 1250 1023 1364 1420 1080 91 318 591 773 182 727 136 273 227 818 455 545 955 364 682 500 636 864 409 20% 909 1136 1091 1045 1000 68 511 716 341 170 375 136 102 273 477 818 545 614 15% 750 852 307 205 784 239 443 580 682 648 409 ercentage of circulating III desired factor of circulating ercentage 91 45 68 114 P 341 318 159 182 136 273 477 523 227 455 545 432 295 205 250 568 364 386 500 10% 409 50 9.1 kgs 100 77.3 59.1 27.3 31.8 72.7 18.2 13.6 22.7 45.5 81.8 54.5 95.5 68.2 63.6 36.4 40.9 86.4 90.9 113.6 109.1 104.5 eight 70 50 30 20 40 80 60 90 lbs 110 170 150 130 120 210 140 180 160 100 190 W 250 230 220 240 200 The above dosage chart is for people who have hemophilia A (factor VIII deficiency). hemophilia A (factor chart dosage people who have The above is for contact a needed, clotting factor of circulating percentage determine the appropriate To or hematologist. center hemophilia treatment with units per bottle. correspond to (number of units) in assays given are Dosages not be exact (units per bottle) may chart. If dosage to assays the amount mixed Available please contact a hematologist. of +/- 10 %, has a variance bottle should be used within 3 hours of mixing. factor of reconstituted contents Entire 12 V III chartD osage (hemophilia A only) factor for 13 Viral safety studies safety Viral in humans with this product Yes Yes Yes Yes Yes Yes 9,900 13,700 – 19 – – 4,000–10,000 4,000 4,000 9,110 5,500 1.65 S pecific activity of final V IIIproduct ( IU / factor after mg protein total addition of stabilizer) Viral safety studies in safety Viral humans with another but similar viral product, method inactivation No Yes Yes Generation Third Second Second First Second (B-domain deleted) Third (B-domain deleted) Viral safety studies safety Viral in humans with this product Yes No Yes None Human plasma solution protein Human plasma solution protein serum Bovine albumin Human serum albumin by (manufactured Instituto Grifols, OctaPharma, Spain, Sweden) None Human or animal plasma-derived used in protein medium culture

2–20 2–20 5–10 S pecific activity of final product factor V III protein total ( IU /mg factor addition of stabilizer) after Heparin in final vial None None None None None None Heparin in final vial None None None S tabilizer in final vial Trehalose Sucrose, 28 mg/vial Sucrose, 28 mg/vial Human albumin Sucrose Sucrose 10 h) C, Polysorbate 80 ) Polysorbate (TNBP/Octoxynol 9 ) (TNBP/Octoxynol 9 ) (TNBP/Octoxynol chromatography chromatography chromatography Immunoaffinity Immunoaffinity Immunoaffinity (TNBP/Polysorbate 80 ) (TNBP/Polysorbate 80 ) (TNBP/Polysorbate 80 ) (TNBP/Polysorbate 100 ) X- (TNBP/Triton (TNBP/ Solvent/detergent chromatography chromatography chromatography chromatography chromatography Immunoaffinity Immunoaffinity Immunoaffinity Immunoaffinity Immunoaffinity 1. 2. Solvent/detergent 1. 2. Solvent/detergent 1. ( 60° 2. Pasteurization M ethod of inactivation viral 1. 2. 1. 2. Solvent/detergent 1. 2. Solvent/detergent 1. 1. 2. Solvent/detergent 1. Solvent/detergent 2. Nanofiltration #187 ) recommendation to hemophilia A ( MASAC treat . #187 ) recommendation to hemophilia A ( MASAC treat . ethod of viral M ethod of viral depletion or inactivation . S . S M anufacturer M anufacturer Baxter by (distributed CSL Behring) Baxter Bayer Wyeth Wyeth Baxter Baxter (from American Red Cross—collected plasma) CSL Behring roducts licensed in licensed P roducts the U LE I . in licensed P roducts the U LE I . ecombinant factor V III products factor ecombinant Advate™ FS Helixate® FS Kogenate® Recombinate™ ReFacto® ™ Xyntha Hemofil® M Monarc-M® P Monoclate® P roduct name P roduct name A B A B T T 14 R A . V III human plasma factor from derived products purified I mmunoaffinity B. 15 909 1818 7727 3182 7273 2727 100% 5455 2273 8182 1364 4545 6818 9545 4091 9091 3636 6364 8636 5909 5000 11364 10455 10909 10000 818 90% 1227 7773 5318 5727 3273 8591 8182 2455 1636 6136 9818 6545 4091 7364 6955 2045 3682 2864 4500 9409 4909 9000 10227 Hemophilia B It is stabilized with sucrose products remains. Transmission of (third generation product). Thus, human parvovirus B19 and Hemophilia B is rare, affecting only 727 80% 1818 1455 1091 7273 2182 5818 3273 5455 4727 8727 2545 the risk of human blood-borne viral hepatitis A virus by these products 5091 6182 6545 7636 9091 3636 4364 9 8364 2909 4000 8000 5,000 people in the United States. 6909 contamination is essentially did occur, but the risk has been What is hemophilia B? zero (15). Recombinant factor IX reduced with additional viral is considered to be the treatment attenuation methods such as People who are missing or have a low 955 70% 636 1591 1273 7318 5727 3182 4773 3818 2227 7955 4136 2545 5091 4455 7636 1909 3500 6045 2864 5409 6364 6682 of choice for patients with ultrafiltration. (Table II. B.) 7000 amount of factor IX have hemophilia B. hemophilia B. (Table II. A.) There are different levels of severity 3. Reduction of thromboembolic of hemophilia B determined by the 2. Plasma-derived factor IX risk during surgery: The use 818 545 60% 5182 5727 1091 2182 2727 3273 5455 3818 3545 1364 2455 1636 6273 6818 6545 4091 1909 4364 4636 3000 4909 amount of factor a person has in concentrates: Improved viral of recombinant factor IX or pd 6000 his/her blood. Severity levels do not depleting processes and donor FIX concentrates change over time. screening practices have resulted rather than pd-prothrombin in plasma-derived (pd) FIX complex concentrates (PCCs) is 455 50% 682 909 1591 1136 1818 3182 2727 5227 5455 4773 2273 4318 1364 2955 4545 4091 5682 2045 3636 2500 3864 3409 MASAC recommendations products with greatly reduced risk recommended in certain 5000 concerning the treatment for HIV, HBV and HCV situations associated with a of hemophilia B transmission (16). Viral attenuation higher risk of thromboembolic MASAC recommendation #187 727 545 364 40% 909 1273 1818 1455 1091 2182 2727 3273 3818 4182 3455 2545 1636 3091 4545 2364 3636

methods used in the production complications, such as surgery 4364 2909 2000 (Replaces document #182) 4000 of pdFIX products that appear or severe hemorrhage requiring (Revised November 2008) chart: using dosage Example 2909 require he would Using this chart, 40 %. to level his factor needs raise to 160 lbs. A man weighing the 1450 units each, bottles on hand contain IX concentrate If the factor IX concentrate. units of factor bottles. two man will receive to be effective for reducing the treatment one to two times per The following recommendation was approved by the Medical and Scientific Advisory Council risk of HIV and hepatitis are day. (Table II. A. Table II. B.) 273 818 545 955 682 30% 409 1773 1227 1091 2318 2591 2182 3136 2727 3273 2455 1364 1500 1636 2045 1909 2864 3409 (MASAC) on November 15, 2008, and adopted by the dry heating at 60°C for 144 hours, This material is provided for your general 3000 NHF Board of Directors on November 16, 2008. information only. NHF does not give medical advice solvent-detergent treatment, or engage in the practice of medicine. NHF under I. Recommendation for doctors vapor treatment and sodium no circumstance recommends particular treatment for specific individuals and in all cases recommends 341 227 455 795 568 25% 682 909 1591

thiocyanate plus ultrafiltration. 1136 1477 1818 1705 1250 2159 2727 1023 1932 2273 2841 1364 treating patients with hemophilia B you consult your doctor or local treatment center 2614 2045 2386 2500 Purification steps involved in the before pursuing any course of treatment. B. Treatment of hemophilia B preparation of the more purified Reprinted with permission from the National Hemophilia Foundation. This material is an excerpt of 1. Recombinant factor IX pd-coagulation FIX products “MASAC Recommendations Concerning the Treatment 182 727 273 818 455 545 364 636 20% 909 1182 1727 1273 1818 1455 1545 1091 2182

of Hemophilia and Other Bleeding Disorders” (#187). 2273 1364 1636 2091 1909 1000 concentrate: Recombinant factor are associated with loss of several 2000 Please visit the NHF website at www.hemophilia.org to IX (rFIX) is produced in Chinese additional logs of virus. A slight see the recommendation in its entirety. hamster ovary cells; no human possibility of viral transmission or animal plasma-derived with the currently marketed viral 341 136 273 477 818 545 614 750 955 15% 205 682 886 409 1159 1227 1705 1091 1432 1295 1023 1568 1364 1500 1636 proteins are used in the inactivated, plasma-derived manufacturing process.

8 ercentage of circulating factor I X desired factor of circulating ercentage

Factor level what to expect 91 P 318 591 773 182 727 136 273 227 818 Classification 455 545 955 364 682 500 636 10% 864 409 909 1136

1091 1045 1000 Less than Bleeding after a minor injury, major trauma or surgery is common. Bleeding may Severe 1% occur without an obvious injury (spontaneous bleeding). Bleeding after minor injury is possible, as well as after major trauma or surgery. 50 9.1 kgs 100 77.3 59.1 27.3 31.8 72.7 18.2 13.6 22.7 45.5 81.8 54.5 95.5 68.2 63.6 36.4 40.9 86.4 90.9 113.6 109.1 Moderate 1 to 5% Occasional spontaneous bleeding may occur but is usually associated with 104.5 prolonged or serious bleeding in a joint.

5 to 30 percent. Prolonged bleeding usually occurs only after serious injury, major Mild 5 to 30%

trauma or surgery. eight 70 50 30 20 40 80 60 90 lbs W 110 170 150 130 120 210 140 180 160 190 100 250 230 220 240 200 Normal 50 to 150% 50 to 150 percent. No abnormal bleeding. osage chart for factor I X (hemophilia B only) chartD osage factor for 16 IX deficiency). hemophilia B (factor chart dosage people who have The above is for contact a needed, clotting factor of circulating percentage determine the appropriate To or hematologist. center hemophilia treatment with units per bottle. correspond to (number of units) in assays given are Dosages not be exact (units per bottle) may chart. If dosage to assays the amount of Available please contact a hematologist. of +/- 10 %, has a variance mixed factor bottle should be used within 3 hours of mixing. factor of reconstituted contents Entire 17 Yes Viral safety studies safety Viral in humans with this product Yes No Viral safety studies in safety Viral humans with another but similar viral product, method inactivation Hemophilia A and B with Because of these complications, High-responding inhibitors 10 many healthcare providers believe inhibitors For people with high-responding ridding the body of inhibitors is the For patients with inhibitors inhibitors, utilizing standard factor is, best option, using a course of therapy (antibodies to factor VIII and factor in many cases, not possible because known as “immune tolerance.” There IX), treatment decisions are more the inhibitor neutralizes even the 200–360 S pecific activity of final product X/mg protein) total ( IU I X/mg factor are different immune tolerance

Viral safety safety Viral studies in humans with this product complicated. The care of inhibitor

Yes Yes largest possible dose of factor. treatment programs, but most patients should be urgently discussed Specialty products that bypass factor require repeated exposure to the with the patient’s hematologist. VIII and factor IX in the clotting deficient clotting factor. People who Treating a person who has inhibitors cascade are generally needed. In opt for immune tolerance infuse Generation

Third can be a challenging experience for these cases, treatment is based daily doses of factor over a period of both the patient and the healthcare on the type of hemophilia and the weeks or, in some cases, years. Some team. Often the treatment is a

nature of the bleed. people using this therapy also receive twofold process: managing bleeding immunosuppressive drugs, which can episodes first, while dealing with the > 150 > 190 S pecific activity of final product after protein total ( IU I X/mg factor addition of stabilizer) predispose them to infections. The inhibitor itself secondly. Dealing with Human or animal plasma-derived used in protein medium culture None risks and benefits of each treatment the presence of inhibitors can take program should be discussed in months or even years of treatment. detail with a healthcare provider. The What are inhibitors? goal of immune tolerance therapy 0.04 None ( U nits/ IU I X) factor Heparin in final vial is to “teach” the body to tolerate the None Heparin in final vial In some cases when a patient receives replacement factor, the factor, rather than mount an immune body’s immune system will perceive response, so normal replacement the normal clotting factor as therapy can be used to prevent or foreign or as an antigen to which control bleeding. Overall, immune S tabilizer in final vial Sucrose an antibody is produced. These tolerance treatment is thought to antibodies are called inhibitors. work 60–80 percent of the time. The inhibitor binds to the infused Low-responding inhibitors clotting factor, making it difficult— For patients who have low- if not impossible—to obtain a responding inhibitor levels (i.e., level sufficient to control bleeding. low levels of inhibitor in the blood), Treatment with replacement clotting continued therapy with factor factor does not have the same Nanofiltration (viral retention filter) retention (viral Nanofiltration Ultrafiltration 80) (TNBP/Polysorbate Solvent/detergent Sodium thiocyanate Dual affinity chromatography Dual affinity chromatography Immunoaffinity Affinity chromatography Affinity

ethod of viral depletion M ethod of viral or inactivation replacement is often possible. This 1. 2. 3. 1. 2. 3. 187) # recommendation to hemophilia B ( MASAC treat . # 187) recommendation to hemophilia B ( MASAC treat .

1. filtration Viral 2. long-term, positive outcomes as in M ethod of inactivation viral . S . S therapeutic approach provides patients without inhibitors. These control of both minor and more less-than-optimal treatments can serious bleeds. To overcome the also lead to secondary problems, such presence of inhibitors in these as infections, bleeding into joints and

Grifols CSL Behring cases, doctors may use larger doses M anufacturer M anufacturer

Wyeth organ damage. of factor and may need to provide additional doses.

roducts licensed in licensed P roducts the U LE II . in licensed P roducts U the LE II . ecombinant factor I X products factor ecombinant X products derived from human plasma from derived I X products factor oagulation AlphaNine® SD Mononine® BeneFIX® P roduct name P roduct name A B A B . R A . C B. 18 T T 19 Yes Viral safety studies safety Viral in humans with this product Yes Viral safety studies in safety Viral humans with another but similar viral product, method inactivation Second Generation Yes Viral safety studies safety Viral in humans with this product Newborn calf serum Human or animal plasma-derived used in culture protein medium L ) (units/m

a hemophilia treatment center This material is provided for your general information MASAC recommendations only. NHF does not give medical advice or engage in 0.8 None Heparin in final vial concerning the treatment is strongly recommended. the practice of medicine. NHF under no circumstance S pecific activityproduct of final addition after protein total ( IU factor/mg of stabilizer) recommends particular treatment for specific of patients with inhibitors 1. Activated prothrombin complex individuals and in all cases recommends you consult to factor VIII or IX concentrate (aPCC): aPCC contains your doctor or local treatment center before pursuing any course of treatment. MASAC recommendation #187 activated factors IIa, VIIa, and Xa. L ) (units/m (Replaces document #182) Reprinted with permission from the National These factors are able to bypass Hemophilia Foundation. This material is an excerpt of (Revised November 2008) “MASAC Recommendations Concerning the Treatment None Mannitol

an inhibitor to factor VIII or Heparin in final vial S tabilizer in final vial The following recommendation was approved of Hemophilia and Other Bleeding Disorders” (#187). by the Medical and Scientific Advisory Council factor IX to promote hemostasis. Please visit the NHF website at www.hemophilia.org to (MASAC) on November 15, 2008, and adopted by the This product is derived from see the recommendation in its entirety. NHF Board of Directors on November 16, 2008. human plasma and is treated I. Recommendation for doctors with vapor (steam) heat to 190 mbar treating patients with

eliminate viruses (22). (Table IV. A.) 60 °C,

hemophilia with inhibitors. 375 mbar) 2. Recombinant factor VIIa D. Treatment of patients with concentrate: Recombinant factor 80 °C, inhibitors to factor VIII or IX: VIIa is licensed for use in patients (TNPB/polysorbate 80 ) (TNPB/polysorbate . Affinity chromatography Affinity . The following products have been with inhibitors to factor VIII or # 187) recommendations ( MASAC patients to inhibitor treat . # 187) recommendations ( MASAC patients to inhibitor treat . Vapor heat ( 10 h, Vapor plus 1 h, 1 Solvent/detergent 2 . ethod of viral M ethod of viral depletion or inactivation M ethod of viral depletion or inactivation . S . S licensed for use in patients with IX. It is produced by baby hamster inhibitors. However, the products kidney cells; animal—not human are not interchangeable. Choice proteins—are used in its of product depends on multiple production. It is stabilized with mannitol (second-generation

factors, including type of inhibitor M anufacturer M anufacturer Baxter (Vienna) Novo Nordisk Novo (Bagsvaerd, Denmark) (low- or high-responding), current recombinant product). Thus, the titer of inhibitor, location of the risk of transmission of human bleed and availability of these viruses is essentially zero (23).

(Table IV. B.) RT. by NovoSeven has been replaced NovoSeven E : products. Consultation with in licensed P roducts the U LE I V. in licensed P roducts the U LE I V. a for use in patients with inhibitors to factor V III with inhibitors or I X factor to V II use in patients a for factor ecombinant T (for use in patients with inhibitors to factor V III with inhibitors or I X) factor to use in patients (for FEIBA VH FEIBA NovoSeven® P roduct name P roduct name A B A B 20 T human plasma from derived concentrates) complex prothrombin (activated complex coagulation A nti-inhibitor A . T R B. NO 21 References for MASAC recommendation #187 13. Mannucci PM, Zanetti AR, Colombo M and this type have reduced levels of invasive dental work, during surgical VIII concentrate that is known the Study Group of the Foundazione dell’ Von Willebrand Disease 1. Bray GL, Gomperts ED, Courter S, et al. A Emophilia: Prospective study of hepatitis . Bleeding procedures and after accident to contain the higher molecular multicenter study of recombinant factor VIII after factor VIII concentrate exposed to hot What is von Willebrand (Recombinate): safety, efficacy and inhibitor 11, 12 symptoms are usually mild. or injury. In women, excessive weight multimers of von vapour. Br J Haematol 1988; 68:427-430. disease? risk in previously untreated patients with menstrual bleeding is often the Willebrand factor and that has hemophilia A. Blood 1994; 83:2428-2435. 14. Dodd RY, Notari EP, Stamer SL. Current Von Willebrand disease (vWD) is Type 2 includes subtypes 2A, 2B, 2M prevalence and incidence of infectious disease major symptom. Women with von been virally attenuated to 2. Lusher JM, Arkin S, Abildgaard CF, Schwartz RS, and 2N. People with this type have a markers and estimated window period a hereditary bleeding disorder Group TKPUPS. Recombinant factor VIII for the Willebrand disease are also at risk of eliminate transmission of HIV risk in the American Red Cross blood donor defect in the von Willebrand factor treatment of previously untreated patients with characterized by bleeding from the population. Transfusion 2002; 42:975-979. postpartum hemorrhage, particularly and hepatitis A, B and C. hemophilia A. N Engl J Med 1993; 328:453-459. they produce, so it does not work 15. White G, Shapiro A, Ragni M, Garzone P, skin and mucous membranes (e.g., 3. Sandberg H, Almstedt A, Brandt J, et al. Structural delayed postpartum hemorrhage. Alphanate® (Grifols) and Goodfellow J, Tubridy K, Courter S. Clinical properly. People with Type 2 von and functional characteristics of the B-domain- mouth, nose, throat, gastrointestinal evaluation of recombinant factor IX. Semin Humate-P® (CSL-Behring) have deleted recombinant factor VIII protein, r-VIII Willebrand disease usually have mild Hematol. 1998; 35 (Suppl. 2):33-38. tract). The most common symptoms Recently developed products have SQ. Thromb Haemostas. 2001; 85:93-100. to moderate symptoms. Each subtype been approved by the FDA for use 16. Shapiro AD, Ragni M, Lusher JM, Culbert S, Koerper of von Willebrand disease are easy changed the treatment options for 4. Horowitz MS, Horowitz B, Rooks C, in vWD. Koate®-DVI (Talecris) may MA, Bergman, GE, Hannan MM: Safety and efficacy is treated differently, so knowing Hilgartner MW: Virus safety of solvent/ bruising, prolonged , individuals with von Willebrand of monoclonal antibody-purified factor IX in also be effective in these patients, detergent-treated antihaemophilic factor the exact subtype is important in patients previously unexposed to PCC or other heavy or prolonged menstrual disease. The following are current concentrate. Lancet 1988; 2:186-188. but it has not been approved by blood products. Thromb Haemostas 1996; 75:30-35. periods (lasting more than 7 days) determining the course of treatment. recommendations for treating 5. Schimpf K, Mannucci PM, Kreutz W, et al. the FDA for use in von Willebrand 17. Scharrer I: The treatment of von Willebrand’s Absence of hepatitis after treatment with occurs when there is an bleeding in these individuals. disease. In: Lusher JM and Kessler CM, and prolonged bleeding following Type 3 a pasteurized factor VIII concentrate in disease. eds: Hemophilia and von Willebrand’s absence or very low levels of von patients with hemophilia and no previous injury, surgery, dental procedures and 1. Persons with Type 1 von Disease in the 1990s. Elsevier Science Pulil 4. Because of the increased risk transfusions. N Engl J Med 1987; 316:918-922. Willebrand factor and factor VIII. B.V., Amsterdam, 1991; pp. 463-469. . Gastrointestinal bleeding Willebrand disease should be 6. Addiego JE, Jr., Gomperts E, Liu S-L, et al: of HIV and hepatitis A, B and C 18. Scharrer I, Vigh T, Aygoren-Pursun E: Experience can also occur. Type 3 vWD is considered severe. Treatment of hemophilia A with a highly treated with the synthetic agent with Haemate P in von Willebrand’s disease transmission, cryoprecipitate purified factor VIII concentrate prepared by In this rare type of von Willebrand in adults. Haemostasis 1994; 24:298-303. desmopressin (DDAVP injectable anti-FVIII immunoaffinity chromatography. People with von Willebrand disease should not be used except in an disease, patients can experience or Stimate nasal spray for Thromb Haemostas 1992; 67:19-27. 19. Berntorp E: Plasma product treatment in have a deficiency or defect in a blood- emergency situation where one various types of von Willebrand’s disease. frequent bleeding—including in 7. Mannucci PM, Gdovin S, Gringeri A, et al. bleeding, 1.5 mg/mL). Their Haemostasis 1994; 24:289-297. clotting protein called von Willebrand of the above-mentioned Transmission of hepatitis A to patients with the joints and muscles—similar to response at first use should be hemophilia by factor VIII concentrates treated 20. Mannucci PM: Biochemical characteristics factor (vWF). Von Willebrand disease people with hemophilia. products is not available and with solvent and detergent to inactivate of therapeutic plasma concentrates used documented for future reference. differs from hemophilia because delay of treatment would be viruses. Ann Int Med 1994; 120:1-7. in the treatment of von Willebrand’s For surgery, trauma or other disease. Haemostasis 1994; 24:285-288. it affects both males and females MASAC recommendations life- or limb-threatening. 8. Centers for Disease Control and Prevention. serious bleeding episodes, if Hepatitis A among persons with hemophilia 21. Kreuz W, et al: Haemate P in children with von equally. It is the most common regarding the treatment of 5. Desmopressin is a potent who received clotting factor concentrate Willebrand’s disease. Haemostasis 1994; 24:304-310. hemostasis is not achieved with — United States, September – December inherited bleeding disorder, affecting von Willebrand disease 22. Kasper CK, Lusher JM, and Transfusion antidiuretic agent, and 1995. MMWR 1996; 45:29-32. MASAC recommendation #186 DDAVP, a factor VIII concentrate Practices Committee, AABB: Recent evolution approximately one percent of the fluid retention is a potential 9. Azzi A, Ciappi S, Zakuyzewska K, et al. Human of clotting factor concentrates for hemophilia population. (Replaces document #173) rich in the high molecular weight parvovirus B19 infection in hemophiliacs first A and B. Transfusion 1993; 33:422-434. complication of this drug. Both The following recommendations were approved multimers of von Willebrand infused with two high-purity, virally treated factor 23. Key NS, Aledort LM, Beardsley D, et al. Home by the Medical and Scientific Advisory Council parenterally administered DDAVP VIII concentrates. Am J Hematol 1992; 39:228-230. What are the different types of factor should be used treatment of mild to moderate bleeding (MASAC) on November 15, 2008, and adopted by the and Stimate nasal spray 10. de Biasi R, Rocine A, Quirino A, Miraglia E, episodes using recombinant factor VIIa von Willebrand disease? NHF Board of Directors on November 16, 2008. (see #3 below). Ziello L: The impact of a very high purity factor (NovoSeven) in haemophiliacs with inhibitors. have been associated with the There are several types of von VIII concentrate on the immune system of Thromb Haemostas 1998; 80:912-918. Von Willebrand disease is the 2. Persons with type 2A, 2M and development of hyponatremia HIV-infected haemophiliacs: a randomized, 24. Morrison AE, Ludlam CA, Kessler C. Use of porcine Willebrand disease that are 2N von Willebrand disease should two year comparison with a high purity most common inherited bleeding factor VIII in the treatment of patients with and seizures. To minimize this risk, concentrate. 1996; 2:82-87. determined by diagnostic blood be treated with DDAVP if they acquired hemophilia. Blood 1993; 81:1513-1520. disorder. Recent studies estimate the following precautions should 11. Study Group of the UK Haemophilia tests. Because the type and subtype 2 5 . Piet MP, Chin S, Prince AM, et al. The use of tri-(n- the incidence at one to two percent have been shown by a DDAVP Center Directors on Surveillance of Virus be observed when this drug is butyl)-phosphate detergent mixtures to inactivate Transmission by Concentrates. Effect of dry determine treatment, it is important of the general population. Since it is trial to be responsive. hepatitis viruses and human immunodeficiency used at home: heating of coagulation factor concentrates virus in plasma. Transfusion 1990; 30:591-598. to know the specific type of von inherited in an autosomal dominant at 80°C for 72 hrs on transmission of non-A, 3. Persons with type 2B and type 3 Willebrand disease. a. DDAVP and Stimate should be non-B hepatitis. Lancet 1988; 2:184-186. 2 6 . Ragni MV, Lusher JM, Koerper MA, Manco-Johnson fashion, males and females are von Willebrand disease—and M, Krouse DS. Safety and immunogenicity of administered no more often 12. Shapiro A, Abe T, Aledort LM, Anderle K, et al: equally affected. Von Willebrand subcutaneous hepatitis A vaccine in children Type 1 is the most common type of those with type 1, 2A, 2M and Low risk of viral infection after administration than once every 24 hours. with haemophilia. Haemophilia 2000; 6:98-103. disease is associated with mucus of vaporheated factor VIII concentrate or factor vWD, accounting for approximately 2N who have been shown to be IX complex in first-time recipients of blood 27. Andre FE, et al. Clinical assessment of the 90 percent of all cases. People with membrane bleeding, excessive nonresponsive to DDAVP b. DDAVP and Stimate should be components. Transfusion 1995; 35:204-208 safety and efficacy of an inactivated hepatitis used for no more than 3 A vaccine: Rationale and summary of findings. bruising and bleeding from cuts. It should be treated with a factor 22 Vaccine 1992; 10 (Suppl):S160-168 can result in excessive bleeding with consecutive days unless 23 III FV F:

atio of atio 1.8–2.8:1 Unknown 0.4–1:1 R v W illebrand DA Yes No Yes F approved von for W disease

directed to do so by hemophilia treatment center medical staff. c. DDAVP and Stimate should not be used in children under the age of 2 years. Yes No Yes Viral safety studies safety Viral in humans with another product, but similar method d. DDAVP and Stimate should be used with caution in the elderly and in individuals with a history of heart disease, Viral safety safety Viral studies in humans with this product No Yes No hypertension or .

e. If a patient is treated with DDAVP before surgery, the anesthesiologist should be advised to avoid fluid overload > 5 1–2 9–22 S pecific activity of final product and dilutional hyponatremia. V III total ( IU /mg factor addition after protein of stabilizer)

f. DDAVP should be used with 24 hours. after repeat May by subcutaneous injection. µ g /kg May repeat after 24 hours. after repeat May

extreme caution in pregnant and dosage ecommended mL normal saline solution, infused IV slowly over 30 minutes. infused IV slowly over in 30 mL normal saline solution, mixed µ g /kg, 1) 0.3 2 ) 0.3 USE INWOMEN. OR IN CHILDREN PREGNANTDO NOT YEARS OF 2 THE UNDER AGE = 150 µ g ). in one nostril (dose one spray give weighing < 50 kg, In patients = 300 µ g ). in each nostril (dose one spray give In those weighing > 50 kg, 24 hours. after repeat May USE INWOMEN OR IN CHILDREN PREGNANTDO NOT YEARS OF 2 THE UNDER AGE R administration women and in women who are None None 1.0 L ) (units/m immediately postpartum. Heparin in final vial 6. An adjunctive treatment for mucous membrane bleeding illebrand factor illebrand

is the antifibrinolytic agent W aminocaproic acid (Amicar). This agent can be given orally or intravenously. 10 hrs) ) per actuation. mL ( 150 µ g ) per actuation. For parenteral use (IV or SQ), parenteral For in a 10 -mL vial 4 µg/mL The 1.5 mg/mL. Nasal spray, dose pump delivers metered 0.1 2.5 mL The bottle contains pump capable of with spray 25 150 - µ g doses or delivering 12 300 - µ g doses. 7. Prior to surgery in a patient with Formulation 72 h) 72 h)

von Willebrand disease, # 187) recommendations disease ( MASAC illebrand # 187) recommendations disease ( MASAC illebrand consultation should be obtained W W with a pediatric or adult hematologist who specializes in . D istributor . Dry heat ( 80 °C, 80) (TNBP/Polysorbate Solvent/detergent the management of individuals chromatography Affinity ( 60 °C,Pasteurization 80 ) (TNBP/Polysorbate Solvent/detergent . S . to treat von to von treat . to von treat . 1. 2. 3. 1. 1. Dry heat ( 80 °C,2 . M ethod of inactivation viral Aventis Pharma Aventis CSL Behring U with inherited bleeding disorders. . S . S This consultation should cover such issues as the need for a DDAVP stimulation test; type of /fluid restriction; M anufacturer M anufacturer Ferring AB Ferring (Malmo, Sweden) AB Ferring (Malmo, Sweden) dose and duration if DDAVP is to Grifols CSL Behring GmbH (Marberg, Germany) Talecris be used; appropriate dose, timing

and duration of factor replacement therapy; and use of adjunctive roducts licensed in licensed P roducts LE IIIthe U . in licensed P roducts LE IIIthe U . DDAVP injection Stimate nasal spray bleeding for Alphanate Humate-P Koate-DVI

medications (Amicar). P roduct name P roduct name A B A B esmopressin formulations to treat type 1 and type 2 v WD formulations D esmopressin A . V III and von factor human plasma that from contain derived P roducts B. 24 T T 25 References: Bibliography 1. Mannucci PM. Desmopressin (DDAVP) for treatment of disorders of hemostasis. 1. Hemophilia of Georgia, Inc. 6. Dietary Supplements. Updated 11. National Heart Lung and Blood Prog Hemost Thromb 1986; 8: 19-45. The Hemophilia Handbook 21 August 2006. http://www Institute. http://www.nhlbi.nih. 2. Mannucci PM, Canciani MT, Rota L, Donovan BS. hemophiliagalaxy.com/patients/ gov/health/dci/Diseases/vWD/ Response of factor VIII/von Willebrand factor 2002: 182-186. to DDAVP in healthy subjects and patients living/nutritionalsupplements.html. vWD_WhatIs.html. Accessed 2. Mancano MA. Drugs that may with and von Willebrand 3/20/2009. disease. Br J Haematol 1981; 47: 283-93. affect hemostasis. HemAware 7. National Hemophilia Foundation. 3. Mannucci PM, Lusher JM. Desmopressin March/April 2002;46-51. www.hemophilia.org/bleeding_ 12. Living with von Willebrand and . Lancet 1989; 2: 675-6. disorders/hemophilia_a.htm. Disease. Hemophilia Health 4. Nilsson IM, Hethagen S. Current status of 3. National Hemophilia Foundation. Accessed 3/20/2009. Services. 2007. DDAVP formulations and their use. In Lusher JM, MASAC recommendations on use Kessler CM, eds. Hemophilia and von Willebrand disease in the 1990’s. International Congress of Cox-2 inhibitors in persons 8. Butler R, Crudder SO, Riske B, Toal S. Series/Excerpta Medica 1991; 943: 443-53. with bleeding disorders. Basic Concepts of Hemophilia This material is provided for your general information (Centers for Disease Control and only. NHF does not give medical advice or engage in 2005; MASAC Document #162. the practice of medicine. NHF under no circumstance Prevention. 2001), 1-7. recommends particular treatment for specific 4. United States Food and Drug individuals and in all cases recommends that you Administration. Use caution with 9. National Hemophilia Foundation. consult your doctor or local treatment center before pursuing any course of treatment. pain relievers. FDA Consumer www.hemophilia.org/bleeding_ Reprinted with permission from the National Jan–Feb 2003. disorders/hemophilia_b.htm. Hemophilia Foundation. Please visit the NHF website Accessed 3/20/2009. at www.hemophilia.org for more information. 5. National Hemophilia Foundation. Taking Oral Medications. http:// 10. National Hemophilia Foundation. www.hemophilia.org/wellness/ http://www.hemophilia.org/ mcdications.html. Accessed NHFWeb/MainPgs/MainNHF. 8/9/2006. aspx?menuid=227&contentid= 424. Accessed 3/20/2009.

26 27 In general, follow these guidelines: • Do not keep this patient waiting. • A bleeding episode requires immediate attention. • Infuse promptly. • Therapeutic infusions should precede radiographic studies, invasive procedures or complex evaluations. • Listen to the patient. • These patients are generally quite knowledgeable about the disease. Be prepared to work in collaboration with them. • Contact the patient’s hematologist.

800.800.6606

All rights in the product names, trade names or logos of all third-party products which appear in italics in this guide, whether or not appearing with the trademark symbol, belong exclusively to their respective owners. © 2013 Accredo Health Group, Inc. | An Express Scripts Company 28 HEM-00134-102813