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LETTERS TO THE EDITORTurk J Hematol 2018;35:75-93apparent only after 10 days of antimicrobial therapy and thefibrinogen level increased after the withdrawal of tigecycline.Life-threatening coagulopathy and hypofibrinogenemiacases induced by tigecycline were reported by Rossitto et al.[5], Pieringer et al. [7], and Sabanis et al. [1]; clinical studieswere reported by Routsi et al. [6] and Zhang et al. [2] in theliterature. However, the main mechanism by which tigecyclineprovokes hypofibrinogenemia is ambiguous [1,5]. It could beby intestinal microflora or by hepatic dysfunction [1,5,7]. Theposttranscriptional regulation of the fibrinogen gene by miRNAscould be the cornerstone in this field [1].We suggest routine strict monitoring of coagulation parameters inpatients receiving tigecycline. If patients develop hypofibrinogenemia,one should consider discontinuation of the drug.Keywords: Hypofibrinogenemia, Tigecycline, Hemoglobine levelAnahtar Sözcükler: Hipofibrinojenemi, Tigesiklin, HemoglobinseviyesiConflict of Interest: The authors of this paper have no conflictsof interest, including specific financial interests, relationships,and/or affiliations relevant to the subject matter or materialsincluded.References1. Sabanis N, Paschou E, Gavriilaki E, Kalaitzoglou A, Vasileiou S.Hypofibrinogenemia induced by tigecycline: a potentially life-threateningcoagulation disorder. Infect Dis (Lond) 2015;47:743-746.2. Zhang Q, Zhou S, Zhou J. Tigecycline treatment causes a decrease infibrinogen levels. Antimicrob Agents Chemother 2015;59:1650-1655.3. Martis N, Chirio D, Queyrel-Moranne V, Zenut MC, Rocher F, Fuzibet JG.Tocilizumab-induced hypofibrinogenemia: a report of 7 cases. Joint BoneSpine 2017;84:369-370.4. Zhou HB. Hypofibrinogenemia caused by hemocoagulase after colon polypsexcision. Am J Case Rep 2017;18:291-293.5. Rossitto G, Piano S, Rosi S, Simioni P, Angeli P. Life-threatening coagulopathyand hypofibrinogenaemia induced by tigecycline in a patient with advancedliver cirrhosis. Eur J Gastroenterol Hepatol 2014;26:681-684.6. Routsi C, Kokkoris S, Douka E, Ekonomidou F, Karaiskos I, Giamarellou H.High-dose tigecycline-associated alterations in coagulation parametersin critically ill patients with severe infections. Int J Antimicrob Agents2015;45:90-93.7. Pieringer H, Schmekal B, Biesenbach G, Pohanka E. Severe coagulationdisorder with hypofibrinogenemia associated with the use of tigecycline.Ann Hematol 2010;89:1063-1064.Address for Correspondence/Yazışma Adresi: Fulya YILMAZ DURAN, M.D.,Bozyaka Training and Research Hospital, Clinic of Anesthesiology and Reanimation, İzmir, TurkeyPhone : +90 232 250 50 50E-mail : drfulya@mynet.com ORCID-ID: orcid.org/0000-0002-6901-7404Received/Geliş tarihi: August 16, 2017Accepted/Kabul tarihi: December 06, 2017DOI: 10.4274/tjh.2017.031084
Turk J Hematol 2018;35:75-93LETTERS TO THE EDITOREffectiveness of Ankaferd BloodStopper in Prophylaxis andTreatment of Oral Mucositis in Childhood Cancers Evaluated withPlasma Citrulline LevelsÇocukluk Çağı Kanserlerinde Oral Mukozit Tedavi ve Profilaksisinde Ankaferd BloodStopperEtkinliği ve Plazma Sitrülin Seviyeleri ile DeğerlendirilmesiTürkan Patıroğlu 1 , Nagihan Erdoğ Şahin 2 , Ekrem Ünal 1 , Mustafa Kendirci 3 , Musa Karakükcü 1 , Mehmet Akif Özdemir 11Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Kayseri, Turkey2Erciyes University Faculty of Medicine, Department of Pediatrics, Kayseri, Turkey3Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Metabolism, Kayseri, TurkeyTo the Editor,Oral mucositis is one of the toxic effects of chemotherapy [1].Ankaferd BloodStopper (ABS) is an herbal product that is used as ahemostatic agent in traditional Turkish medicine. ABS affects theendothelium, blood cells, angiogenesis, cellular reproduction, andvascular dynamics and stimulates the mediators that lead to rapidlyprogressive wound healing [2]. Additionally, antiinflammatory,antimicrobial, antifungal, and antioxidative effects have beenattributed to ABS in previous studies [3,4,5].In this study, we aimed to investigate the effectiveness of ABSin the prophylaxis and treatment of oral mucositis in patientsreceiving chemotherapy in childhood. In addition, plasma levelsof citrulline, which are a biochemical marker for mucosal barrierinjury, were measured and the effectiveness of ABS therapyin mucositis was correlated by quantitative data in addition toclinical assessment.This is a case-control study. The study included 31 patients aged4-17 years receiving chemotherapy regimens with strong mucotoxiceffects. The standard oral care (SOC) protocol consisted of toothbrushing and use of 5% sodium bicarbonate, 0.2% chlorhexidinemouthwash, and nystatin. The patients were asked to perform SOCstarting on the first day of a course of chemotherapy, lasting for14 days, and oral mucosa was assessed daily upon completion ofchemotherapy based on the World Health Organization scale fororal mucositis. In addition, blood samples were drawn to measurecitrulline levels immediately before initiation of chemotherapyand in the period in which mucositis became most severe. Thesame patients receiving the same chemotherapeutic agents in thesecond course of chemotherapy were asked to gargle with ABS(3-4 mL, liquid form) four times daily in addition to SOC. Mucosaratings were performed before the second chemotherapy courseand in the period in which mucositis became most severe. Of thepatients included, 17 (55%) were male and 14 (45%) were female.The mean age was 9.3±4.5 years (range: 4-17 years). When thestages of oral mucositis before and after chemotherapy wereassessed, it was found that there was no significant differencebetween chemotherapy sessions given with SOC and with ABS plusSOC before chemotherapy, while there was a significant differencebetween these sessions after chemotherapy regarding stagesof oral mucositis (p=0.004) (Figure 1). When the extent of thedecrease in plasma citrulline levels was compared, it was higher inchemotherapy sessions with SOC than in those with SOC plus ABS,indicating a significant difference (p<0.008).In conclusion, our study is a prospective, clinical trial demonstratingthat ABS is effective in the prophylaxis and treatment of oralmucositis secondary to chemotherapy in childhood cancers.Moreover, adding ABS to SOC limits the decrease in plasmacitrulline levels. Further randomized studies with larger sampleswill allow the introduction of ABS in the prophylaxis and treatmentprotocols of oral mucositis.Figure 1. Change in oral mucositis grade before and afterchemotherapy treatment between groups. A value of p<0.05 wasconsidered statistically significant.SOC: Standard oral care, CT: chemotherapy.85
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