Subscribe to RSS
![](/products/assets/desktop/img/oa-logo.png)
DOI: 10.1055/a-1641-7770
Dentoalveolar Procedures in Immune Thrombocytopenia; Systematic Review and an Institutional Guideline
![](https://www.thieme-connect.de/media/10.1055-s-00033990/202104/lookinside/thumbnails/10-1055-a-1641-7770_210030-1.jpg)
Abstract
Background Dentoalveolar procedures in immune thrombocytopenia (ITP) pose a risk of bleeding due to thrombocytopenia and infection due to immunosuppressive treatments. We aimed to systematically review the safety and management of dentoalveolar procedures in ITP patients to create practical recommendations.
Methods PubMed, Embase, Cochrane, and Cinahl were searched for original studies on dentoalveolar procedures in primary ITP patients. We recorded bleeding- and infection-related outcomes and therapeutic strategies. Clinically relevant bleeding was defined as needing medical attention.
Results Seventeen articles were included, of which 12 case reports/series. Overall, the quality of the available evidence was poor. Outcomes and administered therapies (including hemostatic therapies and prophylactic antibiotics) were not systematically reported. At least 73 dentoalveolar procedures in 49 ITP patients were described. The range of the preoperative platelet count was 2 to 412 × 109/L. Two clinically relevant bleedings (2%) were reported in the same patient of which one was life-threatening. Strategies used to minimize the risk of bleeding were heterogeneous and included therapies to increase platelet count, antifibrinolytics, local measures, and minimally invasive techniques. Reports on the occurrence of bleedings due to anesthetics or infection were lacking.
Conclusion Based on alarmingly limited data, clinically relevant bleedings and infections after dentoalveolar procedures in ITP patients seem rare. Awaiting prospective and controlled studies to further evaluate these risks and the efficacy of therapeutic interventions, we provided our institutional guideline to guide the management of dentoalveolar procedures in ITP patients.
Publication History
Received: 18 February 2021
Accepted: 07 September 2021
Accepted Manuscript online:
09 September 2021
Article published online:
16 November 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Israels S, Schwetz N, Boyar R, McNicol A. Bleeding disorders: characterization, dental considerations and management. J Can Dent Assoc 2006; 72 (09) 827
- 2 Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology (Am Soc Hematol Educ Program) 2015; 2015 (01) 237-242
- 3 Ghoshal K, Bhattacharyya M. Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis. ScientificWorldJournal 2014; 2014: 781857
- 4 Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood 2017; 129 (21) 2829-2835
- 5 Rodeghiero F, Stasi R, Gernsheimer T. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113 (11) 2386-2393
- 6 Neunert C, Terrell DR, Arnold DM. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3 (23) 3829-3866
- 7 Al-Samkari H, Kuter DJ. Immune thrombocytopenia in adults: modern approaches to diagnosis and treatment. Semin Thromb Hemost 2020; 46 (03) 275-288
- 8 Hicks SM, Coupland LA, Jahangiri A, Choi PY, Gardiner EE. Novel scientific approaches and future research directions in understanding ITP. Platelets 2020; 31 (03) 315-321
- 9 Karasneh J, Christoforou J, Walker JS. et al. World Workshop on Oral Medicine VII: Platelet count and platelet transfusion for invasive dental procedures in thrombocytopenic patients: A systematic review. Oral Dis 2019; 25 (Suppl. 01) 174-181
- 10 Iwabuchi H, Imai Y, Asanami S. et al. Evaluation of postextraction bleeding incidence to compare patients receiving and not receiving warfarin therapy: a cross-sectional, multicentre, observational study. BMJ Open 2014; 4 (12) e005777
- 11 Wells D, Capes J, Powers M. Complications of dentoalveolar surgery. Oral and Maxillofacial Surgery 2000; 1: 421-438
- 12 Lockhart PB, Gibson J, Pond SH, Leitch J. Dental management considerations for the patient with an acquired coagulopathy. Part 1: coagulopathies from systemic disease. Br Dent J 2003; 195 (08) 439-445
- 13 Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surg Oral Med Oral Pathol 1988; 66 (03) 297-303
- 14 Malmquist JP. Complications in oral and maxillofacial surgery: management of hemostasis and bleeding disorders in surgical procedures. Oral Maxillofac Surg Clin North Am 2011; 23 (03) 387-394
- 15 Portielje JE, Westendorp RG, Kluin-Nelemans HC, Brand A. Morbidity and mortality in adults with idiopathic thrombocytopenic purpura. Blood 2001; 97 (09) 2549-2554
- 16 Givol N, Goldstein G, Peleg O. et al. Thrombocytopenia and bleeding in dental procedures of patients with Gaucher disease. Haemophilia 2012; 18 (01) 117-121
- 17 Rebulla P. Platelet transfusion trigger in difficult patients. Transfus Clin Biol 2001; 8 (03) 249-254
- 18 Hato T, Shimada N, Kurata Y. et al. Risk factors for skin, mucosal, and organ bleeding in adults with primary ITP: a nationwide study in Japan. Blood Adv 2020; 4 (08) 1648-1655
- 19 Cohen SG. Thrombocytopenia. In: Rose LF, Kaye D. eds. Internal Medicine for Dentistry. Mosby; 1983: 425-426 , Toronto
- 20 Webster WP, Roberts HR, Penick GD. Dental care of patients with hereditary disorders of blood coagulation. Mod Treat 1968; 5 (01) 93-110
- 21 British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003; 120 (04) 574-596
- 22 Estcourt LJ, Birchall J, Allard S. et al; British Committee for Standards in Haematology. Guidelines for the use of platelet transfusions. Br J Haematol 2017; 176 (03) 365-394
- 23 Franz MG, Steed DL, Robson MC. Optimizing healing of the acute wound by minimizing complications. Curr Probl Surg 2007; 44 (11) 691-763
- 24 Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res 2010; 89 (03) 219-229
- 25 Sonbol H, Pelargidou M, Lucas VS, Gelbier MJ, Mason C, Roberts GJ. Dental health indices and caries-related microflora in children with severe haemophilia. Haemophilia 2001; 7 (05) 468-474
- 26 Foster H, Fitzgerald J. Dental disease in children with chronic illness. Arch Dis Child 2005; 90 (07) 703-708
- 27 Semple JW, Italiano Jr JE, Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011; 11 (04) 264-274
- 28 Douketis JD, Berger PB, Dunn AS. et al. The perioperative management of antithrombotic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133 (6, suppl): 299S-339S
- 29 Baudo F, de Cataldo F, Gatti R, Landonio G, Muti G, Scolari G. Local hemostasis after tooth extraction in patients with abnormal hemostatic function. Use of human fibrinogen concentrate. Haemostasis 1985; 15 (06) 402-404
- 30 Rakocz M, Mazar A, Varon D, Spierer S, Blinder D, Martinowitz U. Dental extractions in patients with bleeding disorders. The use of fibrin glue. Oral Surg Oral Med Oral Pathol 1993; 75 (03) 280-282
- 31 Suwannuraks M, Chuansumrit A, Sriudomporn N. The use of fibrin glue as an operative sealant in dental extraction in bleeding disorder patients. Haemophilia 1999; 5 (02) 106-108
- 32 Bartholomew JR, Salgia R, Bell WR. Control of bleeding in patients with immune and nonimmune thrombocytopenia with aminocaproic acid. Arch Intern Med 1989; 149 (09) 1959-1961
- 33 Lee S-T, Kim J-W, Kwon T-G. Life-threating outcomes after dental implantation in patient with idiopathic thrombocytopenic purpura: a case report and review of literature. Maxillofac Plast Reconstr Surg 2018; 40 (01) 39
- 34 McKelvy B, Satinover F, Sanders B. Idiopathic thrombocytopenic purpura manifesting as gingival hypertrophy: case report. J Periodontol 1976; 47 (11) 661-663
- 35 Engelen ET, Schutgens RE, Mauser-Bunschoten EP, van Es RJ, van Galen KP. Antifibrinolytic therapy for preventing oral bleeding in people on anticoagulants undergoing minor oral surgery or dental extractions. Cochrane Database Syst Rev 2018; 7 (07) CD012293
- 36 Vavricka SR, Walter RB, Irani S, Halter J, Schanz U. Safety of lumbar puncture for adults with acute leukemia and restrictive prophylactic platelet transfusion. Ann Hematol 2003; 82 (09) 570-573
- 37 Owattanapanich D, Ungprasert P, Owattanapanich W. Efficacy of local tranexamic acid treatment for prevention of bleeding after dental procedures: a systematic review and meta-analysis. J Dent Sci 2019; 14 (01) 21-26
- 38 de Vasconcellos Sde A, de Santana Santos T, Reinheimer DM, Faria-E-Silva AL, de Melo MF, Martins-Filho PR. Topical application of tranexamic acid in anticoagulated patients undergoing minor oral surgery: a systematic review and meta-analysis of randomized clinical trials. J Craniomaxillofac Surg 2017; 45 (01) 20-26
- 39 Forbes CD, Barr RD, Reid G. et al. Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease. BMJ 1972; 2 (5809): 311-313
- 40 van Galen KP, Engelen ET, Mauser-Bunschoten EP, van Es RJ, Schutgens RE. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or von Willebrand disease undergoing minor oral surgery or dental extractions. Cochrane Database Syst Rev 2019; 4 (04) CD011385
- 41 Deshayes S, Khellaf M, Zarour A. et al. Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: results at 5 years from the French prospective registry ITP-ritux. Am J Hematol 2019; 94 (12) 1314-1324
- 42 Randall KL. Rituximab in autoimmune diseases. Aust Prescr 2016; 39 (04) 131-134
- 43 Provan D, Butler T, Evangelista ML, Amadori S, Newland AC, Stasi R. Activity and safety profile of low-dose rituximab for the treatment of autoimmune cytopenias in adults. Haematologica 2007; 92 (12) 1695-1698
- 44 Lo JC, O'Ryan FS, Gordon NP. et al; Predicting Risk of Osteonecrosis of the Jaw with Oral Bisphosphonate Exposure (PROBE) Investigators. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010; 68 (02) 243-253
- 45 Franken AAM, van Blijderveen NJC, Witjes MJH, Netelenbos CJC. Bisfosfonaatgerelateerde osteonecrose van de kaak. Ned Tijdschr Geneeskd 2011; 155: A3077
- 46 Mokhtari DH, Roosendaal G, Koole R, Mauser-Bunschoten EP, van den Berg HM. Bloedige orale ingrepen bij patiënten met hemofilie. Ned Tijdschr Tandheelkd 2003; 110: 74-77
- 47 Aldridge E, Cunningham Jr LL. Current thoughts on treatment of patients receiving anticoagulation therapy. J Oral Maxillofac Surg 2010; 68 (11) 2879-2887
- 48 Douketis JD, Spyropoulos AC, Spencer FA. et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, suppl): e326S-e350S
- 49 Fillmore WJ, Leavitt BD, Arce K. Dental extraction in the thrombocytopenic patient is safe and complications are easily managed. J Oral Maxillofac Surg 2013; 71 (10) 1647-1652
- 50 Tosetto A, Balduini CL, Cattaneo M. et al; Italian Society for Haemostasis and Thrombosis. Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 2009; 124 (05) e13-e18
- 51 Arnold DM, Heddle NM, Cook RJ. et al. Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial. Lancet Haematol 2020; 7 (09) e640-e648
- 52 Marshall AL, Goodarzi K, Kuter DJ. Romiplostim in the management of the thrombocytopenic surgical patient. Transfusion 2015; 55 (10) 2505-2510
- 53 Ramakrishna R, Rehman A, Ramakrishna S, Alexander W, Yeo WW. Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period. Intern Med J 2015; 45 (07) 718-724
- 54 Zaja F, Barcellini W, Cantoni S. et al. Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study. Am J Hematol 2016; 91 (05) E293-E295
- 55 Tarantino MD, Fogarty PF, Shah P, Brainsky A. Dental procedures in 24 patients with chronic immune thrombocytopenia in prospective clinical studies of eltrombopag. Platelets 2015; 26 (01) 93-96
- 56 Tarantino MD, Bakshi KK, Brainsky A. Hemostatic challenges in patients with chronic immune thrombocytopenia treated with eltrombopag. Platelets 2014; 25 (01) 55-61
- 57 Landete E, Domingo A, Pérez-Rus G. et al. Perioperative use of eltrombopag in patients with chronic thrombocytopenia. A single-center experience. HemaSphere 2018; 2 (Suppl. 01) 1041
- 58 Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica 2019; 104 (06) 1112-1123
- 59 Hsia CC, Liu Y, Eckert K, Monga N, Elia-Pacitti J, Heddle NM. Intravenous immunoglobulin (IVIg) utilization in immune thrombocytopenia (ITP): a multi-center, retrospective review. Drugs Real World Outcomes 2015; 2 (01) 35-42
- 60 Caress JB, Kennedy BL, Eickman KD. Safety of intravenous immunoglobulin treatment. Expert Opin Drug Saf 2010; 9 (06) 971-979
- 61 Ramírez E, Romero-Garrido JA, López-Granados E. et al. Symptomatic thromboembolic events in patients treated with intravenous-immunoglobulins: results from a retrospective cohort study. Thromb Res 2014; 133 (06) 1045-1051
- 62 Provan D, Stasi R, Newland AC. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115 (02) 168-186
- 63 Padmore RF. Hemolysis upon intravenous immunoglobulin transfusion. Transfus Apheresis Sci 2012; 46 (01) 93-96
- 64 Bharath V, Eckert K, Kang M, Chin-Yee IH, Hsia CC. Incidence and natural history of intravenous immunoglobulin-induced aseptic meningitis: a retrospective review at a single tertiary care center. Transfusion 2015; 55 (11) 2597-2605
- 65 Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol 2006; 6 (04) 535-542
- 66 Bonilla FA. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol 2008; 122 (06) 1238-1239
- 67 Cherin P, Marie I, Michallet M. et al. Management of adverse events in the treatment of patients with immunoglobulin therapy: a review of evidence. Autoimmun Rev 2016; 15 (01) 71-81
- 68 Mohamed M. Intravenous immunoglobulin-associated hemolysis: risk factors, challenges, and solutions. Int J Clin Transfus Med. 2016; 4: 121-131
- 69 Daniel GW, Menis M, Sridhar G. et al. Immune globulins and thrombotic adverse events as recorded in a large administrative database in 2008 through 2010. Transfusion 2012; 52 (10) 2113-2121
- 70 Godeau B, Caulier M-T, Decuypere L, Rose C, Schaeffer A, Bierling P. Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 0.5 and 1 g/kg b.w. Br J Haematol 1999; 107 (04) 716-719
- 71 Godeau B, Chevret S, Varet B. et al; French ATIP Study Group. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet 2002; 359 (9300): 23-29
- 72 Min KH, Rhee C-K, Jung JY, Suh M-W. Characteristics of adverse effects when using high dose short term steroid regimen. Korean J Audiol 2012; 16 (02) 65-70
- 73 Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. II. Relation between steroid dose and steroid associated side effects. Ann Rheum Dis 1989; 48 (08) 662-666
- 74 Broadbent C, Pfeffer P, Steed L, Walker S. Patient-reported side effects of oral corticosteroids. Eur Respir J 2018; 52: 3144
- 75 Zorginstituut Nederland. Farmacotherapeutisch Kompas. Accessed September 28, 2021 at: https://farmacotherapeutischkompas.nl
- 76 Waljee AK, Rogers MAM, Lin P. et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017; 357: j1415
- 77 Salama A, Kiesewetter H, Kalus U, Movassaghi K, Meyer O. Massive platelet transfusion is a rapidly effective emergency treatment in patients with refractory autoimmune thrombocytopenia. Thromb Haemost 2008; 100 (05) 762-765
- 78 Gibson N, Ferguson JW. Steroid cover for dental patients on long-term steroid medication: proposed clinical guidelines based upon a critical review of the literature. Br Dent J 2004; 197 (11) 681-685
- 79 Cronberg S, Wallmark E, Söderberg I. S C. Effect on platelet aggregation of oral administration of 10 non-steroidal analgesics to humans. Scand J Haematol 1984; 33 (02) 155-159
- 80 Schafer AI. Effects of nonsteroidal antiinflammatory drugs on platelet function and systemic hemostasis. J Clin Pharmacol 1995; 35 (03) 209-219
- 81 Goldenberg NA, Jacobson L, Manco-Johnson MJ. Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med 2005; 142 (07) 506-509
- 82 Ruggiero SL, Dodson TB, Fantasia J. et al; American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw–2014 update. J Oral Maxillofac Surg 2014; 72 (10) 1938-1956
- 83 Abed H, Alhabshi M, Alkhayal Z, Burke M, Nizarali N. Oral and dental management of people with myelodysplastic syndromes and acute myeloid leukemia: a systematic search and evidence-based clinical guidance. Spec Care Dentist 2019; 39 (04) 406-420
- 84 Alonso-Coello P, Oxman AD, Moberg J. et al; GRADE Working Group. GRADE evidence to decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: clinical practice guidelines. BMJ 2016; 353: i2089
- 85 Atkins D, Eccles M, Flottorp S. et al; GRADE Working Group. Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches the GRADE working group. BMC Health Serv Res 2004; 4 (01) 38
- 86 Guyatt G, Oxman AD, Akl EA. et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64 (04) 383-394
- 87 Guyatt GH, Oxman AD, Vist GE. et al; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336 (7650): 924-926
- 88 Schünemann HJ, Mustafa R, Brozek J. et al; GRADE Working Group. GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. J Clin Epidemiol 2016; 76: 89-98
- 89 Finucane D, Fleming P, Smith O. Dentoalveolar trauma in a patient with chronic idiopathic thrombocytopenic purpura: a case report. Pediatr Dent 2004; 26 (04) 352-354
- 90 Guzeldemir E. The role of oral hygiene in a patient with idiopathic thrombocytopenic purpura. Int J Dent Hyg 2009; 7 (04) 289-293
- 91 Harms RE, Cornelissen JJ, Visch LL. Orthodontic tooth extraction in a patient with idiopathic thrombocytopenia [in Dutch]. Ned Tijdschr Tandheelkd 1996; 103 (03) 92-93
- 92 Inchingolo F, Crincoli V, Dipalma G, Inchingolo AM. Patient at high hemorrhagic risk. Surgical management of three cases and review of the literature. Minerva Stomatol 2005; 54 (04) 247-253
- 93 Larionova E, Tarasenko S, Morozova E, Diachkova E. Use of erbium laser in the treatment of a patient with acute purulent periostitis and a resistant form of primary immune thrombocytopenia. Case Rep Dent 2019; 2019: 8260605
- 94 Martin AA, Manton SL, Kerr R. Case reports: extraction of teeth in patients with primary immune thrombocytopenia using the drug eltrombopag. J Disabil Oral Heal. 2013; 14 (03) 111-113
- 95 Oda Y, Kagami H, Tohnai I, Ueda M. Asynchronously occurring bilateral mandibular hemorrhagic bone cysts in a patient with idiopathic thrombocytopenic purpura. J Oral Maxillofac Surg 2002; 60 (01) 95-99
- 96 Sangwan A, Tewari S, Narula SC, Sharma RK, Sangwan P. Significance of periodontal health in primary immune thrombocytopenia- a case report and review of literature. J Dent (Tehran) 2013; 10 (02) 197-202
- 97 Tay S, Szabo F, Spain B. Dental extraction in a child with chronic idiopathic thrombocytopenia purpura: are preoperative platelet transfusions necessary?. A A Case Rep 2013; 1 (01) 3-4
- 98 Vaisman B, Medina AC, Ramirez G. Dental treatment for children with chronic idiopathic thrombocytopaenic purpura: a report of two cases. Int J Paediatr Dent 2004; 14 (05) 355-362
- 99 Heidbuchel H, Verhamme P, Alings M. et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015; 17 (10) 1467-1507
- 100 Madrid C, Sanz M. What influence do anticoagulants have on oral implant therapy? A systematic review. Clin Oral Implants Res 2009; 20 (Suppl. 04) 96-106
- 101 Oliver RJ, Sloan P, Pemberton MN. Oral biopsies: methods and applications. Br Dent J 2004; 196 (06) 329-333 , quiz 362