Hematology Reports 2019; volume 11:7912

Use of Catridecacog in a disorders4 and are at high risk of intraoper- patient with severe Factor XIII ative and delayed postoperative Correspondence: Alessandra Di Lelio, Center bleeds.3These patients require FXIII for Outcomes Research and Clinical deficiency undergoing surgery replacement to treat bleeds and, even more Epidemiology – CORESEARCH, Via Tiziano importantly, to prevent them (prophylaxis). Vecellio 2, 65124 Pescara, Italy. Gianluca Sottilotta,1 Francesca Luise,1 Until recently, only plasma-derived Tel.: +39.085.9047114 – Fax: +39.085.9047113. E-mail: [email protected] Vincenzo Oriana,1 Angela Piromalli,1 sources of FXIII have been available (fresh 2 3 frozen plasma, cryoprecipitate and plasma- Rosa Santacroce, Alessandra Di Lelio Key words: Recombinant FXIII, congenital derived FXIII concentrate). Nowadays, a 1UOSD Microcitemie – Centro Emofilia FXIII deficiency, surgery. recombinant factor XIII (rFXIII) is avail- – Servizio Emostasi e Trombosi, Grande able: Catridecacog is efficient in patients Acknowledgements: The editorial assistance Ospedale Metropolitano Bianchi- with congenital factor XIII A-subunit defi- was provided by Airon Communication Melacrino-Morelli, Reggio Calabria; ciency: a dose of 35 UI/kg every 28±2 days through a Novo Nordisk S.p.A. unconditional 2 Servizio di Genetica Medica, Azienda is recommended for prophylaxis6 and a grant. The authors of the publication are fully Ospedaliero-Universitaria Ospedali trough level of greater than 5% FXIII activ- responsible for the contents and conclusions. 3 Riuniti di Foggia; Center for Outcomes ity should be aimed for.7 Novo Nordisk S.p.A. did not influence and Research and Clinical Epidemiology - has not been involved in the data interpreta- CORESEARCH, Pescara, Italy tion and statistical analysis presented in the manuscript.

Case Report Contributions: GS, FL, VO, AP, RS: substan- tial contributions to conception and design, We report a case of a Caucasian 47- Abstract drafting and writing the case report; final year-old male patient with severe FXIII approval of the version to be published. ADL: Despite many articles regarding the subunit A congenital deficiency (FXIII drafting and writing the case report, final antihemorrhagic treatment and prophylaxis, <1%). The genetic mutation which caused approvalonly of the version to be published. GS is there is a lack of experience about how to FXIII deficit is Gly563Arg in homozygosi- the guarantor of this work, accountable for all best conduct major surgical procedures in ty. He has two sisters with the same bleed- aspects of the work in ensuring that questions patients with congenital factor XIII (FXIII) ing disorder and the same level of severity. related to the accuracy or integrity of any part of the work are appropriately investigated and deficiency. His disease was diagnosed at the age of useresolved. Here we report a case of surgery (right 4 years after a surgery for left inguinal her- nia complicated by postoperative hemor- inguinal hernia, complicated by heaviness Conflict of interest: the authors declare no rhage with need for blood transfusion. and pain) performed in a patient with FXIII potential conflict of interest. deficiency, receiving recombinant FXIII This patient had been in prophylaxis prophylaxis (Catridecacog 35 UI/kg every first with FXIII plasma concentrate (1250 Funding: None 28±2 days). Our experience shows that UI every 21 days from November 1985 to Catridecacog can be used safely and effec- October 1987). It was then withdrawn from Received for publication: 17 October 2018. tively not only for continued prophylaxis the market, so he was treated with fresh Accepted for publication: 17 January 2019. but also in surgery and adds to the very lim- frozen plasma in prophylaxis every 21 days This work is licensed under a Creative ited body of evidence currently available on (from November 1987 to October 2013). Then, the patient restarted prophylaxis Commons Attribution-NonCommercial 4.0 surgery in this bleeding disorder. International License (CC BY-NC 4.0). with FXIII plasma concentrate 1500 UI (18 UI/kg) since this drug was reintroduced. ©Copyright G. Sottilotta, et al., 2019 nd From July 22 , 2014, when the patient was Licensee PAGEPress, Italy Introduction 44 years old, he started prophylaxis with Hematology Reports 2019; 11:7912 rFXIII: Catridecacog 30 UI/kg every 30 doi:10.4081/hr.2019.7912 Factor XIII (FXIII) is the terminalNon-commercialdays. That was the first time that enzyme in the blood coagulation cascade Catridecacog was administered in Italy. and essential for cross-linking fibrin mole- During the prophylaxis period with cules to form an effective and stable clot. In Catridecacog, the patient did not report any Dosages for FXIII showed a 50.7% and plasma, FXIII circulates as an inactive het- hemorrhagic episode even in work-related 41.1% level at 39 and 66 hours after sur- erotetramer composed of two catalytic traumas (except for a post-traumatic subcu- gery, respectively (immunoassay). No intra- FXIII A-subunits and two carrier FXIII B- taneous hematoma, which regressed after operative or post-surgical bleeding 1,2 occurred. Hemoglobin levels were available subunits (FXIII-A2B2). A deficiency or three days from the treatment administra- dysfunction of either the A or B subunit can tion). Prophylaxis was successful, without before (13.6 g/dL) and after surgery (12.2 result in FXIII deficiency. Congenital FXIII adverse events. A right inguinal hernia, g/dL). No other intraoperative or postopera- deficiency is a rare and serious autosomal complicated by heaviness and pain, was tive complications occurred. No further recessive coagulation disorder with a high diagnosed in July 2017. Because of the risk administration of Catridecacog or any other risk of life-threatening bleeding complica- of a strangulated hernia or obstruction, the anti-hemorrhagic drug was required. tions.3 The prevalence is estimated to be patient was scheduled to have surgery. The The patient was discharged 3 days after approximately 1 in 1 to 2 million people surgery was performed 2 weeks after the the surgery. In the postoperative period, no worldwide.4,5 Patients with congenital last prophylaxis infusion: the pre-operative hemorrhage or surgical wound healing FXIII deficiency experience major sponta- FXIII dosage showed levels of 21.5% delay occurred. After the surgery, the neous bleeding episodes more frequently (immunoassay). Catridecacog 29.7 UI/Kg patient regularly resumed his prophylactic than patients with most other rare bleeding was infused 4 hours before surgery. program every 30 days.

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in consumptive processes such as surgery. activation, and cross-linking of Discussion Only one infusion was sufficient to achieve fibrinogen and fibrin. J Biol Chem the anti-hemorrhage efficacy as was also 1973;248:1395-407. Little is known about how to best con- evidenced by elevated FXIII levels even 3. Muszbek L, Katona É. Diagnosis and duct major surgical procedures in patients three days after the surgery. No other anti- Management of Congenital and with congenital FXIII deficiency. hemorrhagic therapy was required. Acquired FXIII Deficiencies. Semin To date, the only published data on the Thromb Hemost 2016;42:429-39. effectiveness of rFXIII in the surgical set- 4. Peyvandi F, Palla R, Menegatti M, et al. ting derive from the Mentor™2 trial, a trial on efficacy and safety of monthly replace- European Network of Rare Bleeding ment therapy with rFXIII. As elective sur- Conclusions Disorders Group. Coagulation factor activity and clinical bleeding severity in gery was permitted, the trial provided the Our case report shows that rare bleeding disorders: results from the first data on minor surgical procedures per- Catridecacog can be used safely and effec- European Network of Rare Bleeding formed in patients receiving rFXIII prophy- tively not only for continued prophylaxis7 Disorders. J Thromb Haemost 2012;10: laxis. All 12 minor procedures were per- but also in surgery and add to the very lim- 615-21. formed within 1 to 21 days of the last sched- ited body of evidence currently available on 5. Anwar R, Minford A, Gallivan L, et al. uled rFXIII dose (8 procedures were per- surgery in FXIII-deficiency patients. formed within 7 days of patient’s last sched- Delayed umbilical bleeding: a uled dose and 4 were performed 10 to 21 presenting feature for factor XIII days after the dose) and additional FXIII deficiency: clinical features, genetics, and management. Pediatrics 2002; substitution was not administered for any of References these procedures These findings suggest 109:E32. that prophylaxis with 35 UI/kg rFXIII every 1. Chung SI, Lewis MS, Folk JE. 6. Carcao M, Altisent C, Castaman G, et 4 weeks provides sufficient hemostatic cov- Relationships of the catalytic properties al. Recombinant FXIII (rFXIII-A(2)) erage for the perioperative management of of human plasma and platelet Prophylaxis Prevents Bleeding and minor surgical procedures in patients with transglutaminases (activated blood onlyAllows for Surgery in Patients with congenital FXIII deficiency, without the coagulation factor XIII) to their subunit Congenital FXIII A-Subunit need for additional FXIII treatment.6 structures. J Biol Chem 1974;249:940- Deficiency. Thromb Haemost In our case, despite the pre-surgery 50. 2018;118: 451-60. FXIII level was above the hemostatic 2. Schwartz ML, Pizzo SV, Hilluse RL, 7. Muszbek L, Katona É. Diagnosis and threshold, we decided to infuse McKee PA. Human factor XIII from Management of Congenital and Catridecacog to prevent bleedings because plasma and platelets. Molecular Acquired FXIII Deficiencies. Semin of the well-known FXIII half-life reduction weights, subunit structures, proteolytic Thromb Hemost 2016;42:429-39.

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