A delay could put your patients at riskPrompt diagnosis of acquired hemophilia may impact lives

Stop the bleed with the only bypassing agent FDA approved for acquired hemophilia7

Please see additional Important Safety Information, including Boxed Warning, throughout.Please see accompanying Prescribing Information.

References: 1. Huth-Kühne A, Baudo F, Collins P, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica. 2009;94(4):566-575. 2. Collins PW, Hirsch S, Baglin TP, et al; for UK Haemophilia Centre Doctors’ Organisation. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood. 2007;109(5):1870-1877. 3. Bitting RL, Bent S, Li Y, Kohlwes J. The prognosis and treatment of acquired hemophilia: a systematic review and meta-analysis. Blood Coagul Fibrinolysis. 2009;20(7):517-523. 4. Knoebl P, Marco P, Baudo F, et al; EACH2 Registry Contributors. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622-631. 5. Collins PW, Percy CL. Advances in the understanding of acquired haemophilia A: implications for clinical practice. Br J Haematol. 2010;148(2):183-194. 6. Collins P, Baudo F, Huth-Kühne A, et al. Consensus recommendations for the diagnosis and treatment of acquired hemophilia A. BMC Res Notes. 2010;3:161. 7. NovoSeven® RT [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; 2015. 8. Sumner MJ, Geldziler BD, Pedersen M, Seremetis S. Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal. Haemophilia. 2007;13(5):451-461. 9. Centers for Disease Control and Prevention. International Classi� cation of Diseases, Ninth Revision, Clinical Modi� cation (ICD-9-CM). ftp://ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/ICD9-CM/2011/. Updated September 8, 2011. Accessed February 28, 2017. 10. Centers for Disease Control and Prevention. International Classi� cation of Diseases, Tenth Revision, Clinical Modi� cation (ICD-10-CM). http://www.cdc.gov/nchs/data/icd/icd10cm/2016/ICD10CM_FY2016_Full_PDF.ZIP. Updated May 29, 2015. Accessed February 28, 2017.

Spot it. Stop it.Spot it. Stop it.Acquired hemophilia

A rare, spontaneous, and potentially deadly condition1

• Only 1 to 1.5 per million people are affected yearly2

• Characterized by an inhibitory autoantibody to FVIII that appears spontaneously1

Associated with severe and life-threatening bleeding1

• Up to 21% mortality rate3

Often involving a delayed diagnosis

• 35% of patients go undiagnosed for more than 7 days4

Who “acquires” acquired hemophilia? • Underlying conditions include autoimmune disorders, malignancies,

dermatologic disorders, and pregnancy; however, in approximately 50% to 60% of patients, the cause is unknown4

Signs include:

• Isolated prolonged aPTT5

• Purpura and soft-tissue hemorrhage5

• Gastrointestinal, urological, retroperitoneal, or postpartum bleeding1,2

• Prolonged bleeding following surgery5

Patients usually present to physicians who are not specialists in the � eld and have not previously managed a case....

Lack of familiarity with the disorder may lead to delayed diagnosis and suboptimal treatment....6

— Collins et al, BMC Res Notes, 2010

Model is used for illustrative purposes only.

Indications and UsageNovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is a coagulation factor indicated for:

• Treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) de� ciency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets

• Treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia

Important Safety Information

WARNING: THROMBOSIS

• Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported.

• Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT.

• Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.

Please see additional Important Safety Information throughout.Please see accompanying Prescribing Information.

Important Safety Information (cont’d)

Adverse Reactions

• The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia.

Indications and Usage

NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is a coagulation factor indicated for:

• Treatment of bleeding episodes and peri-operative management in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) de� ciency, and Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets

• Treatment of bleeding episodes and peri-operative management in adults with acquired hemophilia

Important Safety Information

WARNING: THROMBOSIS

• Serious arterial and venous thrombotic events following administration of NovoSeven® RT have been reported.

• Discuss the risks and explain the signs and symptoms of thrombotic and thromboembolic events to patients who will receive NovoSeven® RT.

• Monitor patients for signs or symptoms of activation of the coagulation system and for thrombosis.

Warnings and Precautions

• Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance.

• Exercise caution when administering NovoSeven® RT to patients with an increased risk of thromboembolic complications, such as those with disseminated intravascular coagulation (DIC), advanced atherosclerotic disease, crush injury, septicemia, uncontrolled post-partum hemorrhage, history of coronary heart disease, liver disease, post-operative immobilization, in elderly patients, in neonates, or in patients receiving concomitant treatment with aPCCs/PCCs (activated or nonactivated prothrombin complex concentrates).

• Hypersensitivity reactions, including anaphylaxis, have been reported with NovoSeven® RT. Administer only if clearly needed in patients with known hypersensitivity to NovoSeven® RT, any of its components, or mouse, hamster, or bovine proteins. Should symptoms occur, discontinue NovoSeven® RT and administer appropriate treatment.

• Factor VII de� cient patients should be monitored for prothrombin time (PT) and factor VII coagulant activity (FVII:C). If FVII:C fails to reach the expected level, or PT is not corrected, or bleeding is not controlled after treatment with the recommended doses, antibody formation may be suspected and analysis for antibodies should be performed.

• Laboratory coagulation parameters (PT/INR, aPTT, FVII:C) have shown no direct correlation to achieving hemostasis.

Adverse Reactions

• The most common and serious adverse reactions in clinical trials are thrombotic events. Thrombotic adverse reactions following the administration of NovoSeven® RT in clinical trials occurred in 4% of patients with acquired hemophilia and 0.2% of bleeding episodes in patients with congenital hemophilia.

Drug Interactions

• Thrombosis may occur if NovoSeven® RT is administered concomitantly with Coagulation Factor XIII.

Please see accompanying Prescribing Information.

Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, New Jersey 08536 U.S.A.

NovoSeven® is a registered trademark of Novo Nordisk Health Care AG.Novo Nordisk is a registered trademark of Novo Nordisk A/S.© 2017 Novo Nordisk Printed in the U.S.A. USA16HDM04352 April 2017

The patient

A 78-year-old woman with a swollen leg

Initial presentation

• Patient presented to her PCP with painful lower extremity swelling in one leg and was admitted to the hospital

• Doppler ultrasound was negative for DVT; D-dimers were not tested

• Anticoagulation therapy with enoxaparin sodium injection was started to treat the patient for suspected DVT

• Once on enoxaparin sodium injection, the patient developed GI bleeding

Initial evaluation

• Coagulation studies (PT/aPTT) were not performed during initial presentation

• Coagulation tests (PT/aPTT) were drawn after enoxaparin sodium injections were initiated

- Prolonged aPTT was then noted

The delay

• Patient had an incorrect diagnosis of DVT for 5 days

• Prolonged aPTT was inappropriately presumed due to anticoagulation with enoxaparin sodium injection, resulting in further delay

• Enoxaparin sodium injection was stopped and the patient was given vitamin K to reverse the anticoagulation

• When bleeding and prolonged aPTT did not improve with vitamin K, the patient received multiple units of FFP

• After 5 days, the PCP consulted a local hematologist/oncologist who immediately consulted a benign hematologist at a nearby HTC

The diagnosis

• Patient was transferred to a tertiary care hospital af� liated with the HTC

• Repeat aPTT was 75 seconds, and the 1:1 aPTT mixing study showed an aPTT of 35 seconds with immediate mix and 85 seconds after a 2-hour incubation at 37°C

• FVIII levels were <1% and inhibitor titer was 90 BUs

• Patient was diagnosed with acquired hemophilia

Management

• Patient started treatment with NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) 90 mcg/kg every 2 hours for GI bleeding until hemostasis was achieved

• Patient then began immunosuppressive treatment

Key takeaways

For nonspecialist HCPs

• Failure to do initial coagulation studies or D-dimers con� rming DVT contributed to misdiagnosis of bleeding in a limb as a DVT and thus to mismanagement of a bleeding disorder with an anticoagulant (enoxaparin sodium injection)

• Lack of knowledge of the effects of enoxaparin sodium injection on PT/aPTT led to further misdiagnosis and improper treatment with vitamin K and FFP

• Earlier hematology consult could have supported earlier diagnosis

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and contraindicated anticoagulation treatment

For hematology/oncology specialists

• PCP’s lack of knowledge of the effects of enoxaparin sodium injection on PT/aPTT contributed to misdiagnosis and further improper treatment with vitamin K and FFP

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and contraindicated anticoagulation treatment

• The immediate consult from a hematologist/oncologist to a benign hematologist at the HTC supported the eventual diagnosis

For pharmacists

• Use of multiple units of FFP could have served as a red � ag to consider the diagnosis of acquired hemophilia

• Communication between the pharmacist and health care team could support earlier diagnosis of acquired hemophilia

• Failure to properly diagnose acquired hemophilia in this case led to prolonged hospitalization and contraindicated anticoagulation treatment

An acquired hemophilia case in which delayed diagnosis put a patient at risk

C A S E S T U D Y

Spot it. Stop it.

aPTT=activated partial thromboplastin time; BU=Bethesda unit; DVT=deep venous thrombosis; FFP=fresh frozen plasma; GI=gastrointestinal; HCP=health care professional; HTC=hemophilia treatment center; PCP=primary care physician; PT=prothrombin time.

Important Safety Information (cont’d)

Warnings and Precautions

• Serious arterial and venous thrombotic events have been reported in clinical trials and postmarketing surveillance.

Please see additional Important Safety Information, including Boxed Warning, throughout.Please see accompanying Prescribing Information.

Thrombotic adverse events within clinical data7

• 4% in patients with acquired hemophilia

a Ef� cacy of NovoSeven® RT used � rst-line versus salvage therapy.

b Data were extracted from a review of experiences with rFVIIa for the treatment of acquired hemophilia in compassionate-use programs, the Hemophilia & Thrombosis Research Society (HTRS) registry, and independent published reports. Ef� cacy was de� ned as “effective” and “partially effective” treatment outcomes. “Ineffective” treatment was determined by the inability to stop the bleeding episode or by the physician describing treatment as not effective.8

cThe minimum effective dose has not been determined.

Treatment of acute bleeding episodes

Perioperative management (major or minor surgery)

70 mcg/kg to 90 mcg/kg every 2 to 3 hours until hemostasis is achieved

70 mcg/kg to 90 mcg/kg immediately before surgery and repeat every 2 to 3 hours for the duration of the surgery and until hemostasis is achieved

Recommended dosing of NovoSeven® RTfor acquired hemophilia7,c

Reimbursement

• The ICD-9-CM code for acquired hemophilia is 286.529

• The ICD-10-CM code for acquired hemophilia is D68.31110

• The appropriate code must be included on all claim forms for patients with acquired hemophilia treated with NovoSeven® RT

Model is used for illustrative purposes only.

Individual results may vary.

The only bypassing agent FDA approved for acquired hemophilia7

An international consensus recommends the use of NovoSeven® RT as � rst-line treatment1

Using NovoSeven® RT � rst-line improved ef� cacy8,a,b

95%effective

First-line treatment

80%effective

Salvage therapy