For Patients & Caregivers

Retrospective Surgery Experience

Surgical experience
Minor surgical experience
Major surgical experience

Learn more about HEMLIBRA and treating breakthrough bleeds.

Surgical experience in HAVEN 1-4

Surgical experience in pediatric, adult, and adolescent patients with hemophilia A with or without FVIII inhibitors taking HEMLIBRA for routine prophylaxis26

  • Approximately one-third (126/399) of people with hemophilia A on HEMLIBRA in the HAVEN 1-4 trials had at least one surgery, and 11% (43/399) had at least 2 surgeries
  • HAVEN 1-4 studies were not designed to analyze the management and outcomes of surgeries in patients taking HEMLIBRA. These analyses are descriptive; therefore, no conclusions should be drawn
  • Patients with planned major surgical interventions were excluded from HAVEN 1-4. The data presented here depict unplanned surgeries
  • Some of the surgeries were limited by small numbers
  • There was no protocol-specified guidance provided. Perioperative management was determined based on the investigators’ discretion
  • The cutoff dates for the data were in October 2018. Overall, the median IQR exposure time before surgery was 278 (177-431) days
Benefit conclusions with HEMLIBRA cannot be drawn from this analysis.

FVIII=factor VIII; IQR=interquartile range; PwHA=patients with hemophilia A.

Minor surgical experience in HAVEN 1-4

A descriptive analysis of minor surgeries managed with or without preventative factor concentrate from HAVEN 1-426

  • Among the 215 minor surgeries, 34% (74/215) were managed with additional preventative factor concentrate, and of those, 74% (55/74) were not associated with a postoperative bleed
    • Of the 19 postoperative bleeds that occurred, 47% (9/19) were treated with additional factor concentrate
  • Of the 141 surgeries managed without additional preventative factor concentrate, 86% (121/141) were not associated with a postoperative bleed
    • Of the 20 postoperative bleeds that occurred, 65% (13/20) were treated with additional factor concentrate

Minor surgical procedures included:26

  • 62 dental*
  • 25 joint†
  • 36 central venous access device (CVAD)‡
  • 30 endoscopic§
  • 62 other proceduresII

*The most common dental procedures were tooth extraction, endodontic procedure, dental implantation, and dental prosthesis placement.
†The most common joint procedures were joint injection, synoviorthesis, and joint aspiration.
‡The most common CVAD procedures were central venous catheter removal, central venous catheterization, and catheter placement.
§The most common endoscopic procedures were upper gastrointestinal endoscopy, esophagogastroduodenoscopy, colonoscopy, biopsy or biopsy colon, large intestinal polypectomy, cystoscopy, and sigmoidoscopy.
IIThe most common other procedures were aspiration of serum, suture removal, biopsy or biopsy skin, ear tube insertion, hematoma evacuation, mole excision, nasal septal operation, and retinal laser coagulation.

Major surgical experience in HAVEN 1-4

A descriptive analysis of major surgeries managed with or without preventative factor concentrate from HAVEN 1-426

  • The majority, 83% (15/18), of major surgeries were managed with additional preventative factor concentrate. 80% (12/15) were associated with no intraoperative or postoperative bleeds

Major surgical procedures included:26,27

  • 4 synovectomy
  • 3 hip arthroplasty
  • 2 muscle suture#
  • 1 ankle arthroplasty
  • 1 knee arthroplasty
  • 1 removal of right femoral retained orthopedic hardware
  • 1 open reduction of fracture
  • 1 appendectomy
  • 1 epidural injection
  • 1 cholecystectomy
  • 1 incisional hernia repair
  • 1 tonsillectomy

One synovectomy was a compound procedure, also involving arthrofibrosis, chondroplasty, and joint debridement.27
#Classified as a major procedure because a fascial plane was breached.27

A descriptive analysis of minor and major surgeries in patients with and without inhibitors across HAVEN 1-426

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In Patients Without FVIII Inhibitors

HEMLIBRA has been shown to work for adults and adolescents without FVIII inhibitors.

See the Results

In Patients With FVIII Inhibitors

Learn more about zero treated bleed data in adults and adolescents with FVIII inhibitors.

See the Results
NEXT: Important Safety Information

Indication & Important Safety Information

Indication
HEMLIBRA is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A with or without factor VIII inhibitors.

Important Safety Information
Boxed WARNING: THROMBOTIC MICROANGIOPATHY and THROMBOEMBOLISM
Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of HEMLIBRA if symptoms occur. 

Warnings and Precautions
Thrombotic Microangiopathy (TMA) and Thromboembolism Associated With HEMLIBRA and aPCC
In clinical trials, TMA was reported in 0.8% of patients (3/391) and thrombotic events were reported in 0.5% of patients (2/391). In patients who received at least one dose of aPCC, TMA was reported in 8.1% of patients (3/37) and thrombotic events were reported in 5.4% of patients (2/37). Patients with TMA presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13.

Consider the benefits and risks if aPCC must be used in a patient receiving HEMLIBRA prophylaxis. Due to the long half-life of HEMLIBRA, the potential for an interaction with aPCC may persist for up to 6 months after the last dose. Monitor for the development of TMA and/or thromboembolism when administering aPCC. Immediately discontinue aPCC and interrupt HEMLIBRA prophylaxis if clinical symptoms, imaging, or laboratory findings consistent with TMA and/or thromboembolism occur, and manage as clinically indicated. Consider the benefits and risks of resuming HEMLIBRA prophylaxis following complete resolution of TMA and/or thrombotic events on a case-by-case basis.

Immunogenicity
Treatment with HEMLIBRA may induce anti-drug antibodies. Anti-emicizumab-kxwh antibodies were reported in 5.1% of patients (34/668) treated with HEMLIBRA in clinical trials. Most patients with anti-emicizumab-kxwh antibodies did not experience a change in HEMLIBRA plasma concentrations or an increase in bleeding events; however, in uncommon cases (incidence <1%), the presence of neutralizing antibodies with decreasing plasma concentration may be associated with loss of efficacy.

Monitor for clinical signs of loss of efficacy (eg, increase in breakthrough bleeding events) and if observed, promptly assess the etiology and consider a change in treatment if neutralizing anti-emicizumab-kxwh antibodies are suspected.

Laboratory Coagulation Test Interference
HEMLIBRA affects intrinsic pathway clotting-based laboratory tests, including activated clotting time (ACT); activated partial thromboplastin time (aPTT); and all assays based on aPTT, such as one-stage, factor VIII (FVIII) activity. Therefore, intrinsic pathway clotting-based coagulation laboratory test results in patients who have been treated with HEMLIBRA prophylaxis should not be used to monitor HEMLIBRA activity, determine dosing for factor replacement or anti-coagulation, or measure FVIII inhibitor titers.

Results affected by HEMLIBRA: aPTT; Bethesda assays (clotting-based) for FVIII inhibitor titers; one-stage, aPTT-based single-factor assays; aPTT-based Activated Protein C Resistance (APC-R); ACT.

Results unaffected by HEMLIBRA: Bethesda assays (bovine chromogenic) for FVIII inhibitor titers; thrombin time (TT); one-stage, prothrombin time (PT)-based single-factor assays; chromogenic-based single-factor assays other than FVIII (see Drug Interactions for FVIII chromogenic activity assay considerations); immuno-based assays (ie, ELISA, turbidimetric methods); genetic tests of coagulation factors (eg, Factor V Leiden, Prothrombin 20210).

Most Common Adverse Reactions
The most common adverse reactions (incidence ≥10%) are injection site reactions, headache, and arthralgia.

Adverse Reactions
Characterization of aPCC Treatment in Pooled Clinical Trials
There were 130 instances of aPCC treatment in 37 patients, of which 13 instances (10%) consisted of on average a cumulative amount of >100 U/kg/24 hours of aPCC for 24 hours or more; 2 of the 13 were associated with thrombotic events and 3 of the 13 were associated with TMA. No TMA or thrombotic events were associated with the remaining instances of aPCC treatment.

Injection Site Reactions
In total, 85 patients (22%) reported injection site reactions (ISRs). All ISRs observed in HEMLIBRA clinical trials were reported as mild to moderate intensity and 93% resolved without treatment. The commonly reported ISR symptoms were injection site erythema (11%), injection site pruritus (4%), and injection site pain (4%).

Other Less Common (<1%) Reactions
Rhabdomyolysis was reported in 2 adult patients with asymptomatic elevations in serum creatine kinase without associated renal or musculoskeletal symptoms. In both instances, the event occurred following an increase in physical activity.

Drug Interactions
Clinical experience suggests that a drug interaction exists with HEMLIBRA and aPCC.

Pregnancy, Lactation, Females and Males of Reproductive Potential
Women of childbearing potential should use contraception while receiving HEMLIBRA. It is not known whether HEMLIBRA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HEMLIBRA should be used during pregnancy only if the potential benefit for the mother outweighs the risk to the fetus. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HEMLIBRA and any potential adverse effects on the breastfed child from HEMLIBRA or from the underlying maternal condition.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the HEMLIBRA full Prescribing Information for additional Important Safety Information, including Boxed WARNING.

    • HEMLIBRA package insert. South San Francisco, CA: Genentech, Inc.; 2023.

      HEMLIBRA package insert. South San Francisco, CA: Genentech, Inc.; 2023.

    • Data on File. Genentech, Inc.

      Data on File. Genentech, Inc.

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      Shima M, Nagao A, Taki M, et al. Long-term safety and efficacy of emicizumab for up to 5.8 years and patients’ perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A. Haemophilia. 2021;27(1):81​-89. doi:10.1111/hae.14205

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      Shima M, Nogami K, Nagami S, et al. A multicentre, open-label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors. Haemophilia. 2019;25(6):979​-987. doi:10.1111/hae.13848

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      Négrier C, Mahlangu J, Lehle M, et al. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023;10(3):e168-e177. doi:10.1016/S2352​-3026(22)00377-5

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      Pipe S, Collins P, Dhalluin C, et al. Emicizumab prophylaxis for the treatment of infants with severe hemophilia A without factor VIII inhibitors: results from the primary analysis of the HAVEN 7 study. Slide deck presented at: 65th Ash Annual Meeting, December 9-12, 2023.

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      Jiménez-Yuste V, Peyvandi F, Klamroth R, et al. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022;6(8):e12837. Published 2022 Nov 14. doi:10.1002/rth2.12837

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      https://clinicaltrials.gov/ct2/show/NCT03315455. NLM identifier: NCT03315455. Accessed February 28, 2023.

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      Kitazawa T, Esaki K, Tachibana T, et al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017:117(7):1348​-1357. doi:10.1160/TH17-01-0030

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      Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Supplementary materials. Blood. 2021;137(16):2231​​-2242. doi:10.1182/blood.2020009217

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      Callaghan MU, Negrier C, Paz-Priel I, et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231​​-2242. doi:10.1182/blood.2020009217

    • National Bleeding Disorders Foundation. MASAC Document 268: Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA) for hemophilia A with and without inhibitors. April 27, 2022; New York, NY.

      National Bleeding Disorders Foundation. MASAC Document 268: Recommendation on the use and management of emicizumab-kxwh (HEMLIBRA) for hemophilia A with and without inhibitors. April 27, 2022; New York, NY.

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      Mahlangu J, Jiménez-Yuste V, Ventriglia G, et al. Long-term outcomes with emicizumab prophylaxis for severe haemophilia A without FVIII inhibitors: safety and efficacy analyses from HAVEN 3 & 4. Poster presented at: The European Association for Haemophilia and Allied Disorders (EAHAD) Annual Meeting 2023; February 7​-10, 2023; Manchester, United Kingdom.

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      Callaghan M, Negrier C, Paz-Priel I, et al. Emicizumab treatment is efficacious and well tolerated long term in persons with haemophilia (PwHA) with or without FVIII inhibitors: pooled data from four HAVEN studies. Slide deck presented at: International Society on Thrombosis and Haemostasis 2019 Congress; July 6​–10, 2019; Melbourne, Australia.

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      National Bleeding Disorders Foundation. MASAC Document 267: MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. April 27, 2022; New York, NY.

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    • HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2022.

      HEMLIBRA Summary of Product Characteristics. Roche Registration Limited; 2022.

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      Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Blood Adv. 2022;6(24):6140​​-6150. doi:10.1182/bloodadvances.2022007458

    • Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Supplementary materials. Blood Adv. 2022;6(24):6140​​-6150. doi:10.1182/bloodadvances.2022007458

      Kruse-Jarres R, Peyvandi F, Oldenburg J, et al. Surgical outcomes in people with hemophilia A taking emicizumab prophylaxis: experience from the HAVEN 1-4 studies. Supplementary materials. Blood Adv. 2022;6(24):6140​​-6150. doi:10.1182/bloodadvances.2022007458

    • HEMLIBRA Instructions For Use. Roche Registration Limited; 2022.

      HEMLIBRA Instructions For Use. Roche Registration Limited; 2022.

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