Periodontal diseases commonly result in gum tissue bleeding and tooth mobility, with increased complexity observed in patients with hemophilia due to heightened bleeding severity stemming from low clotting factor concentrations in the blood. Consequently, individuals with hemophilia often exhibit reduced levels of oral hygiene at home and frequent visits to dental clinics, accompanied by increased factor concentrate intake for bleeding control. However, this self-treatment approach often needs to be revised.

​

Hemophilia encompasses a spectrum of hereditary disorders characterized by deficiencies in clotting factors, leading to prolonged clotting times and a predisposition to excessive bleeding.1 Hemophilia is categorized into types A, B, and C, corresponding to deficiencies in factors VIII, IX, and XI. Hemophilia A is the most prevalent X-linked recessive disorder.

​

In general, the symptoms are internal or external bleeding episodes. People with more severe hemophilia suffer more severe and more frequent bleeds, while people with mild hemophilia usually suffer more minor symptoms except after surgery or severe trauma. In cases of moderate hemophilia, symptoms are variable and manifest along a spectrum between severe and mild forms.2,3    

​

Periodontitis, an inflammation of the tooth-supporting tissues, arises from various etiological factors such as bacteria, poor oral hygiene, genetics, environmental factors, and systemic health conditions (e.g., diabetes, cardiovascular diseases, viral infections, digestive disorders). The initial stage of periodontitis, gingivitis, is characterized by gum tissue swelling, plaque accumulation, and severe bleeding. In advanced cases, periodontitis extends to surrounding tissues, including the periodontal ligament and alveolar bone, resulting in significant local or generalized gum and bone recession, tooth mobility, and occlusal trauma.4

​

Periodontitis in individuals with hemophilia follows a more complex course, perpetuating a vicious cycle wherein gingivitis-induced gum tissue bleeding exacerbates due to the underlying hemophilia. Reduced oral hygiene practices further contribute to bacterial accumulation, a primary etiological factor in periodontitis development.

​

Adequate dental care for individuals with hemophilia necessitates minimal traumatic interventions. While treatment for periodontitis typically involves hygienic procedures or surgery, both interventions can induce bleeding, albeit controllable with factor concentrate administration. Nevertheless, repetitive bleeding remains a common challenge in managing periodontitis in individuals with hemophilia.5,6

 

Bacteriophages, viruses that infect and replicate within bacteria and archaea, are composed of proteins that encapsulate a DNA or RNA genome and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes (e.g., MS2) and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.7,8

 

The objective of this study is to propose phage therapy as an alternative non-invasive treatment modality for periodontal disease in individuals with hemophilia.

​

In our case, all patients received oversight from their hematologist. However, for patients with hemophilia, the sole treatment method comprised an infusion of antihemophilic factor concentrate and tranexamic acid. Given the objective of our trial to assess the efficacy of phages in reducing bleeding episodes from the oral cavity, administering factor concentrates could confound the results. Therefore, in consultation with the hematologist, factor concentrate infusions were withheld from the patients during the study.

​

Seven patients with hemophilia and severe periodontitis were selected for inclusion in the study. Bacteriological and phage resistance testing was conducted on all patients by obtaining oral cavity biopsies, revealing no phage resistance among the patient cohort. None of the patients received antihemophilic factor concentrate therapy during the study period.

​

After four patients were excluded, all participants were provided with PHAGIO® as the sole mouthwash for regular use over four weeks. Standard dental procedures were uniformly applied to all patients, including professional dental hygiene consisting of teeth scaling and polishing, prescription of anti-inflammatory toothpaste and mouthwash, and provision of a medium toothbrush after professional cleaning.

​

PHAGIO® was exclusively used as the mouthwash for the targeted patients throughout the study period. Each milliliter of the drug contained a mixture of sterile filtrates of bacteria including Streptococcus, Staphylococcus, E. coli, Pseudomonas aeruginosa, and Proteus phagolysates, with a phage titer not less than 1X105.

​

PHAGIO® comprises virulent phages selected from bacteria (Streptococcus, Staphylococcus, E. coli, Pseudomonas aeruginosa, and Proteus), ensuring the drug's high activity and efficacy. Regardless of the route of administration, bacteriophage preparations are rapidly absorbed into the bloodstream and lymphatic system, facilitating their delivery to the site of infection.

​

All observed patients were distributed among two groups:

• Group 1: Patients received professional oral cavity cleaning and were treated solely with PHAGIO® at an appropriate dosage (10-20 ml orally once daily for four weeks);

• Group 2: Patients underwent standard professional oral hygiene procedures at the dental office without a PHAGIO® prescription. Their toothbrushes were replaced, and they were provided with anti-inflammatory toothpaste and chlorhexidine-containing mouthwash at appropriate dosages for four weeks.