Protocol for Oral Implant Rehabilitationin a Hemophilic HIV-Positive Patient With

Type C HepatitisLizett Castellanos-Cosano, DDS,* Ramiro-José Núñez-Vázquez, MD, PhD,† Juan-José Segura-Egea, MD, DDS, PhD,‡

Daniel Torres-Lagares, DDS, PhD,‡ José-Ramón Corcuera-Flores, DDS, PhD,*and Guillermo Machuca-Portillo, MD, DDS, PhD§

Hereditary hemostasis and coag-ulation disorders are very prev-alent diseases, von Willebrand’s

disease and hemophilia being the mostcommon.1 Hemophilia is an inheritedX-linked bleeding disorder caused bydeficiencies of clotting factors VIII(hemophilia A) or IX (hemophilia B).Mutations in the factor VIII or IX genesmanifest as hemophilia in males and asthe carrier state in females. In carrierfemales, levels of factors VIII and IXvary widely and may sometimes be lowenough to result in clinical bleedingproblems.2 Factors VIII and IX are bothinitially required for the activation offactor X in the coagulation cascade thatleads to the formation of a fibrin clot.The pivotal role played by these 2 fac-tors is underlined by the significanthemorrhagic diathesis caused by defi-ciency of either protein.

Hemophilia A and B are clinicallyindistinguishable; they are character-ized by easy bruising, spontaneous

muscle and joint hemorrhage, andexcessive bleeding after trauma andsurgical procedures. Diagnosis mustbe confirmed by specific laboratoryassay. The severity of bleeding isrelated to the measured residual factorconcentration and is classified as mild,moderate, or severe.3 Severe hemo-philia is normally defined as a plasmalevel of coagulation factor activity lessthan 1% of that in healthy individuals.Moderate disease is between 1% and5%, and mild disease is more than 5%to 40% of normal activity.4

Since the 1960s, hemophilia pa-tients have received intravenous factorVIII and IX replacement therapy.5 Inthe years that followed, it becameapparent that viruses like HIV and hep-atitis C virus (HCV) were transmitted

due to transfusion of infected plasmaproducts.6,7 The 2011 global survey ofthe World Federation of Hemophiliashowed that 2.4% of hemophiliacswere infected by HIV, and 8.2% wereinfected by HCV.8 HIV infection ina hemophiliac could aggravate thebleeding tendency due to thrombocy-topenia and the effects of drugs such asprotease inhibitors.9 Untreated HCVinfectionmay progress to liver fibrosis,cirrhosis, or hepatocellular carci-noma.10,11 Liver disease caused byHCV is now recognized as an impor-tant cause of morbidity in hemophiliapatients.12

To the best of our knowledge,implant surgery has not been describedpreviously in these patients. This articlereports implant-supported prosthesis

*Associate Professor, Department of Stomatology, School ofDentistry, University of Seville, Seville, Spain.†Chairman, Hemophilia Unit, Hematology Service, Virgen delRocío University Hospital, Seville, Spain.‡Professor, Department of Stomatology, School of Dentistry,University of Seville, Seville, Spain.§Professor and Chairman, Special Care Dentistry, Departmentof Stomatology, School of Dentistry, University of Seville, Seville,Spain.

Reprint requests and correspondence to: GuillermoMachuca-Portillo, MD, DDS, PhD, Professor andChairman of Special Care Dentistry, School ofDentistry, University of Sevilla, C/Avicena s/n, 41009Sevilla, Spain, Phone: +34 954 481128, Fax: +34 954481128, E-mail: gmachuca@us.es

ISSN 1056-6163/14/02305-622Implant DentistryVolume 23 � Number 5Copyright © 2014 by Lippincott Williams & Wilkins

DOI: 10.1097/ID.0000000000000145

Case report: A 46-year-old manwith severe hemophilia A, stage A2HIV infection and chronic hepatitis Cgenotype 1A, for whom the treatmentplan included implant-supportedprostheses in 2 mandibular edentu-lous sections. The protocol followedincluded factor VIII replacement con-centrate and oral antifibrinolytictherapy. The right mandibular sec-tion was fitted with 3 Straumannimplants (Ø 4.1 mm, length 10 mm),and the left mandibular sectionreceived 2 implants of the same char-acteristics. The patient showed nopostoperative complications. After

implant placement, the patient at-tended scheduled review appoint-ments. After a 3-month period ofosseointegration, the prosthesis wasfitted.

Conclusions: Although, in thiscase, the treatment proved successful2 years postrehabilitation and theprotocol used seems safe and effec-tive, long-term prospective studiesare needed to evaluate the implantsuccess rate in these patients.(Implant Dent 2014;23:622–625)Key Words: hemophilia A, dentalimplant, HIV infection, hepatitis Cinfection

622 PROTOCOL FOR IMPLANTS IN HIV PATIENTS � CASTELLANOS-COSANO ET AL

treatment in a hemophiliac with HIVand hepatitis C infection, and the devel-opment of a protocol agreed with theHemophilia Unit of Virgen del RocíoHospital, Seville, for managing thesecases.

CASE REPORT

The patient, a 46-year-oldmanwithsevere hemophilia A ([factor VIII] ¼0.7 U/dL), stage A2 HIV infection(HIV RNA 400 [2.6]; CD4: 489 cellsper microliter [30.93%]) and chronichepatitis C genotype 1A, was on highlyactive antiretroviral therapy with efavir-enz-emtricitabine-tenofovir. The patientreceived routine dental care at theDentistry Unit of Virgen del RocíoUniversity Hospital, Seville since thediscovery of his hereditary coagulationdisorder. His principle request wasto replace his missing teeth witha fixed-prosthesis dental treatment.Oral examination revealed 2 mandibu-lar edentulous sections and poor oralhygiene (Figs. 1–3). A digital pano-ramic radiograph of the jaws was per-formed to evaluate bone support forimplant placement in the edentulouszone and to rule out other underlyingconditions (Fig. 4). This was followedby a computerized tomography. Treat-ment objectives were to improve oralhygiene and to achieve adequate oralmasticatory function.

Protocol DesignAfter consultation with the pa-

tient’s hematologist, a protocol(Table 1) was followed to avoid com-plications caused by bleeding into thesurgical sites that would have compro-mised the osseointegration of theimplants.

Surgical TreatmentSurgical treatment was performed

under local infiltrative anesthesiawith vasoconstrictor (articaine plus1:100,000 epinephrine) by periapicalinjection. A mucoperiosteal flap wasmade along the crestal bone of theedentulous space. The previous drugtherapy regimen for treatment, per-formed before each of 2 surgical proce-dures, along with local hemostasis,effectively controlled the bleeding.The right edentulous mandibularsection was fitted with 3 Straumann

Fig. 1. Frontal view of patient’s closed mouth at the beginning of treatment. Note poorhygiene and gingival inflammation.

Fig. 2. Lateral view of right side of closed mouth at the beginning of treatment.

Fig. 3. Lateral view of left side of closed mouth at the beginning of treatment.

Fig. 4. Panoramic radiograph of the patient’s initial condition. No particular atrophy of themandibular bone and no specific injuries are present.

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Standard Plus Regular Neck implants(Ø 4.1 mm, length 10 mm) in the rightfirst mandibular premolar, the right firstmandibular molar, and the right secondmandibular molar. Eight months later,2 implants of the same characteristicswere placed in the left second mandib-ular premolar (Ø 4.1 mm, length8 mm) and left first mandibular molar(Ø 4.1 mm, length 10 mm). Postoper-atively, administration of factor VIII

clotting factor, antibiotic and analge-sic treatment was prescribed for bothsurgical procedures, as described inthe protocol (Table 1). The patientshowed no postoperative complica-tions and no additional need for factorVIII concentrate or other blood prod-ucts, and there was no bleeding oncethe course of tranexamic acid was

completed. The patient never requiredblood transfusions.

Prosthetic TreatmentAfter implant placement, the

patient attended scheduled review ap-pointments. After a 3-month period ofosseointegration, the rehabilitativeprosthesis was fitted. The patient wasreviewed every 6 months for 2 years.Figures 5–8 show his clinical and radio-logical treatment status at the end of 2years.

DISCUSSION

Establishing a medical protocol tocontrol bleeding represented a signifi-cant challenge. Hemostasis had to beoptimal because any bleeding wouldhave compromised the osseointegrationof the implants. The factor VIII doseneeded for replacement therapy is cal-culated as body weight (66 kg)3 factorVIII increase (80%–100%) (IU/dL) 30.5. Guidelines tailored to the individ-ual diagnosis depend on the severity ofbleeding and the type of surgeryplanned. This patient was prescribed45 U/kg. The planned replacementdose of 3000 units was calculated toraise his factor VIII level to approxi-mately 80% to 100%, ensuring the besthemostasis possible. A presurgical testfor factor VIII inhibitors (antibodies)was negative. This allowed factor VIIIconcentrates to be used, at regulardoses. In the absence of inhibitors, fac-tor VIII has a half-life of 8 to 12 hours.This meant that the second dose could

Table 1. Recommended Protocol for the Placement of Implants in PatientsWith hemophilia

Drug Therapy Treatment Regimen

Tranexamic acid 1 g (OR) 1 tablet every 6 h, from the night before theprocedure during 5–7 d

Factor VIII 3000 UI (IV) 15 min previous the procedureFactor VIII 2000 UI (IV) 12 h after surgeryFactor VIII 3000 UI (IV) 24 h after surgeryFactor VIII 2000 UI (IV) 48 and 72 h after surgeryParacetamol 500 mg Alternate every 4 hMetamizole 575 mg (OR)Amoxicilin clavulanic acid 875/

125 mg (OR)1 tablet every 8 h during 7 d

Hospital admission is recommended with observation for the first 12 to 24 hours at the discretion of the hematologist.IU indicates international units; IV, intravenous; OR, oral.

Fig. 5. Frontal view of closed mouth 2years after the end of treatment. Note cor-rect gingival status, without inflammation orplaque.

Fig. 6. Lateral view of right side of closedmouth 2 years after the end of treatment.Note the condition of the mucosa around theimplants.

Fig. 7. Lateral view of left side of closedmouth 2 years after the end of treatment.Note the condition of the mucosa around theimplants.

Fig. 8. Panoramic radiograph 2 years after completion of the case, showing osseointegratedimplants in good condition.

624 PROTOCOL FOR IMPLANTS IN HIV PATIENTS � CASTELLANOS-COSANO ET AL

be administered 12 hours later, whilethe patient was in hospital. An obser-vation period is essential to controlpossible hemorrhagic complicationsin the event of damage to importantarteries during dental implant surgery,potentially leading to compromise ofthe airway.13 Once the patient had suc-cessfully had this second dose at thehospital, he was able to continue thetreatment at home. The objective wasto maintain the factor VIII level at 80%constantly during the 24 hours aftersurgery.

Tranexamic acid was prescribed tokeep weak blood clots intact for longerand to prevent bleeding in plasmin-richareas such as the oral cavity. Tranexa-mic acid significantly reduces bloodlosses after oral surgery in patientswith hemophilia and can be used topi-cally or systemically.14 It was used sys-temically at a dose of 1 g (30 mg/kg)orally, 4 times daily, starting 24 hourspreoperatively for surgical proceduresfor 5 to 7 days. Initial factor VIIIreplacement allowed clots to form,and tranexamic acid enabled them toremain hemostatically effective fora long time. This combination resultedin outstanding bleeding control in thesurgical field.

It has been suggested that HIV-positive patients are more likely todevelop both early and late postopera-tive complications, such as septicemiaand poor wound healing. This has notbeen corroborated by more recent stud-ies, but seems to depend on the patient’slevel of CD4 cells and general condi-tion.15 Pronounced immunosuppres-sion (CD4 T cells 200/ml) has beenassociated with a higher risk of postop-erative complications.16 Several oralsurgical procedures have been per-formed in HIV-positive patients with-out a significant increase in adversepostoperative events.15,17 In this case,the patient had 489 CD4 T cells permicroliter, so the risk of infection wascontrolled. Infection also seems to

induce fibrinolysis, so antimicrobialssuch as oral amoxicillin/clavulanicacid, 875/125 mg 3 times daily, weregiven postoperatively for a full 7-daycourse to reduce the risk of secondaryinfections.

CONCLUSIONS

Only one article has describedimplant placement in a hemophilicpatientwith successful implant osseoin-tegration after a hemostasis protocol(Gornistky et al, 2005).3 The resultspresented in our case show that evenin a hemophiliac with HIV and hepatitisC infection, with a correct hemostasisprotocol and specialmanagement, com-plications after oral surgery can becontrolled and masticatory functionimproved.

DISCLOSURE

The authors claim to have nofinancial interest, either directly orindirectly, in the products or informa-tion listed in the article.

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