- Email: [email protected]
Bleeding risk in thrombocytopenic patients after dental extractions: a retrospective single-center study
ARTICLE IN PRESS Vol. 00 No. 00 && 2020
Bleeding risk in thrombocytopenic patients after dental extractions: a retrospective single-center study Shaiba Sandhu, BDS, DDS,a,b Vidya Sankar, DMD, MHS,a,b and Alessandro Villa, DDS, PhD, MPHa,b Objective. The aim of the present study was to assess the clinical safety profile of dental extractions in patients with thrombocytopenia and explore the effectiveness of platelet transfusion before dental extractions. Study Design. This is a retrospective cohort study of patients with moderate to severe (100,000/mL) thrombocytopenia who underwent dental extractions in the Oral Medicine and Dentistry Clinic at Brigham and Women’s Hospital from 2003 to 2019. Patients with a platelet count <30,000/mL received prophylactic preprocedure platelet transfusion. Risk and type of bleeding complication (prolonged postoperative bleeding requiring intervention with topical hemostatic agents and/or therapeutic platelet transfusions) was assessed. Results. Eighty-nine thrombocytopenic patients were identified. Postextraction bleeding complications occurred in 4 patients (4.4%). Surgical extractions and multiple number of extractions were significantly associated with an increased bleeding risk (P < .05), whereas prophylactic platelet transfusion and post-transfusion platelet count were not. Conclusions. Dental extractions in patients with thrombocytopenia may be performed with a positive safety profile by following a comprehensive medical evaluation, thorough treatment planning, adequate surgical management, use of local hemostatic measures, and, importantly, coordination of care with the patient’s medical team. (Oral Surg Oral Med Oral Pathol Oral Radiol 2020;000:16)
Thrombocytopenia is defined as a platelet count less than 150,000/mL and can be categorized as mild (100,000/mL150,000/mL), which is usually clinically insignificant, moderate (50,000/mL100,000/mL), and severe (<50,000/mL).1-3 Dental extractions in medically complex patients, particularly those with congenital or acquired thrombocytopenia, may present with several challenges, including postoperative prolonged or uncontrolled bleeding. Platelet transfusion is often used in clinical practice as a prophylactic or therapeutic measure to prevent or manage bleeding in thrombocytopenic patients, yet its validity remains controversial.4,5 The most commonly accepted platelet count threshold before dental extractions below which prolonged bleeding is anticipated is 50,000/mL. This threshold was determined based on general surgery guidelines and expert opinion.6-8 A recent systematic review challenged this threshold but noted that the studies available for review were of small sample size, with the largest one including 69 patients, and not all the studies were restricted to thrombocytopenic patients.5 Studies indicate that minor general surgical procedures can be performed with a positive safety profile in patients with platelet counts between 20,000/mL and 30,000/mL,9,10 which suggests that platelet threshold of 50,000/mL may be an a
Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, Boston, MA, USA. b Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA. Received for publication Sep 6, 2019; returned for revision Dec 26, 2019; accepted for publication Dec 27, 2019. Ó 2020 Elsevier Inc. All rights reserved. 2212-4403/$-see front matter https://doi.org/10.1016/j.oooo.2019.12.010
overestimation leading to unnecessary platelet transfusions, increased costs, and possibly delayed dental treatment. The aim of this retrospective study was to (1) evaluate the risk of postoperative bleeding after dental extractions in patients with moderate to severe thrombocytopenia, (2) explore whether prophylactic platelet transfusion was associated with avoidance of postoperative bleeding, and (3) identify other factors associated with postoperative bleeding.
MATERIALS AND METHODS Patient characteristics and study design This retrospective cohort study was conducted to identify all patients who underwent a dental extraction in the Oral Medicine and Dentistry Clinic at Brigham and Women’s Hospital from January 2003 to October 2019. Records of patients with platelet count 100,000/mL before the extractions were identified. The Partners Healthcare Institutional Review Board approved this study. Inclusion and exclusion criteria Patients with mild (100,000/mL150,000/mL), moderate (50,000/mL100,000/mL), and severe (<50,000/mL) thrombocytopenia were identified.1-3 Only patients with
Statement of Clinical Relevance The safety of dental extractions in thrombocytopenic patients may be indicated by successful management of postextraction bleeding by hemostatic measures with the reservation of therapeutic platelet transfusion in cases of severe bleeding. 1
ARTICLE IN PRESS ORAL MEDICINE 2 Sandhu et al.
moderate or severe thrombocytopenia were evaluated. Thrombocytopenic patients with concurrent coagulopathy were excluded from the study. Patients on anticoagulation were not excluded because their international normalized ratio (INR) and prothrombin time laboratory values were within the effective therapeutic range for performing dental extractions; as a result, anticoagulation in our patient population was not likely to confound the bleeding outcome as a result of low platelets. Electronic medical records were reviewed, and study variables collected included demographic data (age, sex, and race), tobacco smoking and alcohol consumption, pertinent medical history, use of anticoagulant therapy, and laboratory studies (INR, pre-extraction platelet count within 24 hours of the extraction, and post-transfusion platelet count measured immediately after transfusion in those who received platelets). Other information recorded included periodontal health status (gingivitis vs periodontitis- assessed by evidence of bone loss radiographically), the number of dental extractions, extraction technique (simple vs surgical extraction), postextraction bleeding complication, and management. Primary outcome The primary outcome was any postextraction bleeding complication occurring 2448 hours after the extraction. Bleeding complications were classified as minor and major depending on the intervention required. A minor bleeding complication required topical thrombin 1200 IU/mL (THROMBIN-JMI; GenTrac, Inc., Middleton, WI, USA) or topical antifibrinolytic agents such as aminocaproic acid 0.25 g/mL (Amicar; Xanodyne Pharmaceutica, Florence, KY, USA) or tranexamic acid 0.1 g/mL (Cyklokapron; Pharmacia and Upjohn, Kalamazoo, MI, USA) to arrest bleeding from the extraction sites. Postextraction hemorrhagic complications were deemed to be major if a postextraction platelet transfusion was needed for hemostasis.
DENTAL EXTRACTIONS: CLINIC PROTOCOL It is our clinical practice that patients with a platelet count less than 30,000/mL receive platelet transfusion before the dental extraction. Extractions were performed in a nontraumatic manner under local anesthesia with 2% lidocaine with 1:100,000 epinephrine. If a surgical flap was raised or osseous recontouring needed, the procedure was considered a surgical extraction. After the procedure, all extraction sockets were packed with absorbable gelatin sponge (Gelfoam, Pfizer, New York, NY, USA), followed by placement of resorbable sutures. Detailed written and verbal postoperative instructions were given to every patient. Postoperative phase In the postextraction period (2448 hours after the extraction), the medical care team knew to contact the
OOOO && 2020
oral medicine on-call service in case of any postextraction complication for the inpatients. The inpatient nurses were instructed to use a gauze soaked in thrombin 1200 IU/mL or antifibrinolytic agent (aminocaproic acid 0.25 g/mL or tranexamic acid 0.1 g/mL), as an external pressure packing, if any abnormal bleeding occurred from the extraction sockets. All the outpatients were provided with contact information in case of any complication after the extraction, including bleeding not controlled with gauze pressure, pain, swelling, or purulent discharge. Statistical analysis To summarize the data, descriptive statistics such as median and range were used for continuous variables, and frequency (%) was used for categorical variables. Differences between patients who developed bleeding complications versus those who did not were calculated using the Pearson and Wilcoxon tests. P values were considered statistically significant at P < .05. Statistical analyses were performed using JMP Pro-14 (SAS Institute, Cary, NC, USA).
RESULTS Patient characteristics Eighty-nine patients were identified with moderate (50,000/mL100,000/mL) to severe thrombocytopenia (<50,000/mL) receiving dental extractions. The median age was 56 years (range: 2086 years), and 55% of participants were male. Fourteen patients (15.7%) were current smokers, and 21 (23.5%) were current alcohol users at the time of extraction. Chronic periodontal disease was present in 46 patients (51.6%). The causes of thrombocytopenia were hematologic malignancy (n = 69; 77.5%), metastatic solid tumors (n = 4; 4.4%), hepatic disorders (n = 6; 6.7%), iatrogenic (n = 4; 4.4%), platelet disorders (n = 5; 5.6%) and congenital (n = 1; 1.1%) (Table I). Out of the 7 patients who were on anticoagulants, 6 received heparin infusion and 1 was on apixaban. The median INR of all patients was 1.1 (range: 0.91.9), including those with hepatic disorders. Out of the 6 patients with hepatic disorders (3 with hepatitis C, 2 with liver cirrhosis, and 1 with liver transplant), only 1 patient had a slightly increased prothrombin time of 37.6 seconds (reference range: 23.836.6 seconds) (Table II). Dental extractions Each patient received a median of 2 dental extractions (range: 121). Seventy-seven patients received 14 extractions (86.5%), 7 received 58 extractions (7.8%), 3 received 912 (3.3%), 1 received 1316 extractions (1.1%), and 1 had 21 dental extractions (1.1%). A total of 29 patients (32.5%) had a pre-extraction platelet count <30,000/mL. Of these, the 2 patients (2.2%) with platelet
ARTICLE IN PRESS OOOO Volume 00, Number 00
ORIGINAL ARTICLE Sandhu et al. 3
Table I. Patient characteristics Baseline characteristics
Table II. Primary diagnosis causing thrombocytopenia Total patients (N = 89)
Age (y) Median (range) 56 (2086) Gender, n (%) Male 55 (61.7) Female 34 (38.2) Race, n (%) White 68 (76.4) Black 8 (8.9) Asian 4 (4.5) Other 9 (10.1) Smoking status, n (%) Never 50 (56.1) Former 25 (28.0) Current 14 (15.7) Alcohol consumption, n (%) Never 23 (25.8) Former 45 (50.5) Current 21 (23.5) Platelet count/mL, n (%) 50,000100,000 44 (49.4) 30,00050,000 16 (17.9) 10,00030,000 24 (26.9) <10,000 5 (5.6) Median (range) 49,000 (500098,000) Patients transfused, n (%) 27 (30.3) Post-transfusion platelet count/mL, n (%) >100,000 6 (22.2) 50,000100,000 11 (40.7) 30,00050,000 8 (29.6) 10,00030,000 1 (3.7) <10,000 1 (3.7) Median (range) 59,000 (6000166,000) Teeth extracted, n (%) 14 77 (86.5) 58 7 (7.8) 912 3 (3.3) 1316 1 (1.1) >16 1 (1.1) Median (range) 1 (116) Site of extraction, n (%) Anterior 13 (14.6) Posterior 66 (74.1) Both anterior and posterior 10 (11.2) Primary diagnosis causing thrombocytopenia, n (%) Malignancy 73 (82.0) Other 16 (17.9) Periodontal bone loss, n (%) 46 (51.6) Use of an anticoagulant,* n (%) 7 (7.8) INR Median (range) 1.1 (0.91.9) INR, international normalized ratio. *Out of the seven patients on anticoagulation, one was on apixaban, and six were on heparin.
counts of 11,000/mL and 15,000/mL had simple single tooth extraction without prophylactic platelet transfusion at the decision of the patient’s medical team. The remaining 27 patients (30.3%) received a platelet transfusion just before the extraction(s) and had a median post-transfusion
Diagnosis
Patients, n (%)
Congenital Dyskeratosis Congenita Hematologic malignancy Acute myeloid leukemia Acute lymphoid leukemia Chronic myeloid leukemia Chronic lymphoid leukemia Aplastic anemia Non-Hodgkin’s lymphoma Hodgkin’s lymphoma Multiple myeloma Myelodysplastic syndrome Large granular lymphocytic leukemia Waldenstrom macroglobulinemia Metastatic solid tumor Hepatic conditions Liver cirrhosis Hepatitis C Liver transplant Platelet disorder Immune thrombocytopenic purpura Thrombotic event Iatrogenic Chemotherapy for sinonasal carcinoma Hemodialysis-related Drug-induced liver injury
1 (1.1) 69 (77.5) 32 (35.9) 3 (3.3) 2 (2.2) 1 (1.1) 2 (2.2) 4 (4.4) 4 (4.4) 7 (7.8) 11 (12.3) 2 (2.2) 1 (1.1) 4 (4.4) 6 (6.7) 2 (2.2) 3 (3.3) 1 (1.1) 5 (5.6) 4 (4.4) 1 (1.1) 4 (4.4) 1 (1.1) 2 (2.2) 1 (1.1)
platelet count of 59,000/mL (range: 6000160,000/mL). Despite the transfusion, platelet count of 3 patients (3.4%) remained <30,000/mL. These 27 patients had a median of 1 dental extraction (range: 116). There were 16 patients (17.9%) with a platelet count between 30,000/mL and 50,000/mL (median: 43,000/mL; range: 32,00050,000/mL) who did not receive prophylactic platelet transfusion in compliance with the clinical protocol. Post-dental extractions sequelae Three patients (3.3%) developed minor bleeding after dental extractions managed with topical thrombin or antifibrinolytic agents and pressure with gauze. Of these 3, one patient, whose medical history was significant for end-stage renal disease requiring hemodialysis, essential hypertension, and insulin-dependent diabetes mellitus type 2, was hospitalized with sepsis, deep vein thrombosis, and gastrointestinal bleeding. During her inpatient admission, she developed a submental abscess secondary to odontogenic infection requiring source control. She had a platelet count of 75,000/mL and underwent simple extractions of 3 grossly carious mandibular anterior teeth. The medical history of the other 2 patients was pertinent for hematologic malignancies (acute myeloid leukemia and myelodysplastic syndrome [MDS]), contributing to the underlying thrombocytopenia (platelets <30,000/mL) requiring
ARTICLE IN PRESS ORAL MEDICINE 4 Sandhu et al.
prophylactic platelets. One patient (1.1%) with acute myeloid leukemia developed a major bleeding complication requiring therapeutic platelet transfusion to achieve hemostasis in addition to antifibrinolytics. Local operative site infection developed in 2 patients (2.3%) with hematologic malignancy. Interestingly, the patients who developed a bleeding complication had platelet counts >30,000/mL at the time of dental extraction. The median platelet count at the time of extraction in patients exhibiting prolonged bleeding was 59,000/mL (range: 39,00075,000/mL) compared with those who did not develop any bleeding complication (62,000/mL; range: 6000166,000/mL) (Table III). The platelet count at the time of extraction did not have a statistically significant effect on the bleeding outcome (P = .42). Patients who underwent surgical extractions were at a higher risk of bleeding complications compared with those who had simple extraction (P < .01). Additionally, multiple dental extractions (2 or more) were significantly associated with an increased risk of postextraction bleeding (P < .05). Prophylactic platelet transfusion was not associated with a reduction in oral bleeding complication (P = .79). The lowest platelet count at which a dental extraction was carried out was 6000/mL. This patient’s underlying primary diagnosis was MDS. He had an odontogenic infection and required an urgent extraction for dental clearance before allogeneic stem cell transplant. Thus, after discussion with the oncology team, it was decided to proceed with the extraction. He received 2 units of platelets before the procedure; however, the platelet transfusion failed to increase his platelet count. Interestingly, his pre-extraction platelet count reduced from 9000/mL to 6000/mL after the transfusion. As per his oncologist, he was on systemic tranexamic acid 1300 mg TID. This patient had an atraumatic, simple extraction and did not experience any bleeding complications.
DISCUSSION Thrombocytopenic patients are considered at risk of prolonged bleeding after dental extraction. To date, there is no definite platelet count required for performing dental extractions.5 The commonly followed threshold of 50,000 platelets/mL is based on general surgery guidelines.6-8 Recently, a systematic review challenged this threshold for carrying out invasive dental procedures safely and found inadequate evidence to support that a platelet count >50,000/mL would diminish the risk of postoperative bleeding complications.5 However, this review included small scale studies with a median sample size of 13 (range: 469), and all the studies incorporated were not specific for thrombocytopenic patients.5 According to Watson-Williams, minor surgery can be performed “without undue risk” at 30,000 platelets/mL.9 As such, our clinical protocol has
OOOO && 2020
Table III. Primary outcome: postextraction bleeding complication Variable
Bleeding complication Yes (n = 4)
Age (y) Median (range) 54.5 (2374) Sex, n (%) Male 2 (2.2) Female 2 (2.2) Platelet count at the time of extraction/mL* Median (range) 50,000 (39,00075,000) Prophylactic platelet transfusion, n (%) No 2 (2.2) Yes 2 (2.2) Extraction type, n (%) Simple 3 (3.3) Surgical 1 (1.1) No. of extractions, n (%) Single extraction 0 Multiple extractionsy 4 (4.4) Median (range) 3 (221) Site of extraction, n (%) Anterior 1 (1.1) Posterior 2 (2.2) Both 1 (1.1) INR Median (range) 1.3 (1.11.5) Chronic periodontitis, n (%) Yes 5 (5.7) No 0 (0.0) Smoking status, n (%) Never 3 (3.3) Former 0 Current 1 (1.1)
Bleeding complication No (n = 85)
P
56 (2086)
.78
53 (62.3) 32 (37.6)
.62
62,000 (6000 166,000)
.42
61 (68.5) 24 (26.9)
.79
84 (1.1) 1 (1.1)
<.01
44 (50.5) 41 (46.0) 1 (116)
<.05
12 (13.4) 64 (71.9) 9 (10.1)
.51
1.1 (0.91.9)
.12
39 (44.8) 43 (49.4)
.32
47 (52.8) 25 (28.0) 13 (14.6)
.43
INR, international normalized ratio. *Including post-transfusion platelet count. yMultiple extractions were considered when 2 or more teeth were extracted.
been to recommend platelet transfusion before dental extraction if the platelet count is <30,000/mL. The majority of patients (95.5%) with moderatesevere thrombocytopenia did not develop any bleeding complication after extractions. One patient (1.1%), who developed a major bleeding complication, had a platelet count of 58,000/mL at the time of extraction and underwent multiple extractions of anterior and posterior teeth (21 teeth). His bleeding complication was likely a result of his poor periodontal health and a large number of extractions. He developed poorly organized protruding clots (also known as liver clots11) at the maxillary extraction sites postoperatively. Once these clots were removed, no further complications occurred. Three patients (3.3%) experienced minor bleeding episodes in the 24-hour postoperative period, which were well controlled with gauze pressure packs soaked in topical thrombin and/or antifibrinolytic agents. The
ARTICLE IN PRESS OOOO Volume 00, Number 00
two patients with hematologic malignancies received multiple surgical and simple posterior teeth extractions (median 3; range 26) at the platelet count of 39,000/ mL and 41,000/mL, respectively. The association between the platelet count and postextraction bleeding complication was not found to be statistically significant. The patient with the lowest platelet count at the time of extraction (6000/mL) received simple tooth extraction of a mandibular molar without any postoperative complications. A retrospective study conducted by Fillmore et al.12 indicated that the mean platelet count of 25,000/mL was associated with postoperative bleeding. Our study did not find such an association. However, surgical extraction and a multiple number of extractions were found to be the 2 significant factors related to an increased risk of postextraction bleeding. The results of our study indicated that with atraumatic extraction technique, postextraction management of the socket by packing absorbable hemostatic matrix with suturing, and good communication among the dental team, the patient, and the medical care team, extractions can be successfully performed in patients with moderate to severe thrombocytopenia without significant postoperative complications. The widely accepted platelet threshold of 50,000/mL for dental extraction may be an overestimation leading to unnecessary platelet transfusions. Platelet transfusions increase health care costs; in 2017 the total direct cost of a platelet transfusion in a patient was estimated to be in the range of $5258 to $13,117 in the United States.13 One unit of platelets typically boosts the platelet count by an average of 5000 to 8000/mL. Six whole blood donations are needed for a single platelet transfusion, and platelets have a limited storage life of 5 days. Hence, platelet donations are needed every day.13 It is essential to recognize that platelet transfusion is not entirely benign, and there are several risks related to the transfusion.14 Adverse reactions include the development of refractoriness, hemolysis from ABOmismatched transfusions, acute lung injury, and bacterial sepsis.14,15 Recurrent transfusion can result in human leukocyte antigen alloimmunization causing platelet refractoriness, which requires additional platelet transfusion with human leukocyte antigenmatched platelets leading to additional cost. Thus, some authors recommend that the platelet transfusion should be reserved for major bleeding episodes because minor bleeding can be effectively controlled with local measures.4 None of the patients included in this study who received pre-extraction platelets developed any acute transfusion complication; however, one of the patients with MDS was suspected of having developed platelet refractoriness because his platelets failed to increase from 6000/mL despite repeated platelet transfusions.
ORIGINAL ARTICLE Sandhu et al. 5
The benefit of prophylactic transfusion, even in cases of marked thrombocytopenia, remains controversial.16 A meta-analysis conducted in 2018 to evaluate the clinical efficacy of prophylactic transfusion of platelets in thrombocytopenic patients requiring general surgery found that there was insufficient evidence in the literature to establish that preprocedure transfusion results in a reduction in postoperative bleeding.16 Consequently, some authors advocate for therapeutic platelet transfusion instead.10 Similarly, our study did not find a statistically significant impact of prophylactic platelet transfusion on the clinical outcome. As a result, more attention should be placed on treating the bleeding rather than aggressively transfusing platelets preoperatively. In patients with quantitative and qualitative platelet disorders, postextraction bleeding can be efficiently controlled with local hemostatic measures without correcting the underlying hemorrhagic defect.17,18 Hemostatic matrices such as absorbable gel foam, oxidized cellulose, or collagen act as a 3-dimensional scaffold and play a role in clot organization, but their hemostatic properties are dependent on a functional coagulation cascade.18 Antifibrinolytic agents inhibit the conversion of plasminogen into plasmin and thus prevent lysis of the clot.19,20 A meta-analysis conducted to evaluate the role of topical tranexamic acid or aminocaproic acid in major surgical procedures concluded that these antifibrinolytics were effective in reducing postoperative bleeding.21 Life-threatening bleeding complications after dental extraction are uncommon but may occur, especially in the cases of combined thrombocytopenia and coagulopathy. If both the primary and secondary hemostatic pathways are compromised, the risk of hemorrhage increases. A case report by Lieberman et al.22 presented a patient who underwent a surgical extraction (later found to have severe thrombocytopenia with concurrent factor VII deficiency) and developed a hematoma in the submandibular space necessitating intubation to protect the airway. In thrombocytopenia, because the coagulation pathway (secondary hemostatic pathway) is functional, local measures of hemostasis are successful in contributing to the formation and stabilization of the primary hemostatic plug and stimulating the coagulation cascade.19 In this study population, the INR was within normal limits for all the patients, including those on anticoagulation, suggesting that the coagulation pathway was unimpaired. There were limitations to this study. First, all patients received an absorbable hemostat, followed by the placement of sutures after the extraction. This is a measure that may not be practiced routinely after all dental extractions at other institutions. This study did not address the bleeding complication risk if compression with gauze after extraction was the only measure used to control any bleeding. Second, our sample size was too small to
ARTICLE IN PRESS ORAL MEDICINE 6 Sandhu et al.
comment on the influence of anticoagulation on postoperative bleeding complications. Additionally, because of the retrospective nature of this chart review, there were insufficient details about the extent and severity of the periodontal disease in the medical records, which may have influenced postoperative bleeding in the setting of increased inflammation. Finally, although a retrospective study lacks the strength to establish a declarative statement, we intended to add more evidence to the literature for the development of better guidelines related to prophylactic platelet transfusions for thrombocytopenic patients in dentistry. A prospective study may be better suited to establish a threshold for platelet transfusion. But to our knowledge, our study offers the largest sample size with a wide array of primary diagnoses ranging from hematologic malignancies and hepatic disorders to primary platelet disorders leading to congenital and acquired thrombocytopenia. In conclusion, our results indicate that dental extractions, incorporating comprehensive medical evaluation, thorough treatment planning, adequate surgical management, use of local hemostatic measures, and coordination of care with the patient’s medical team may be performed with a positive safety profile in thrombocytopenic patients regardless of the preoperative platelet count. Randomized clinical trials are required for the establishment of more evidence-based guidelines.
DISCLOSURE We do not have conflicts of interest associated with this publication, and there has been no financial support for this work that could have influenced its outcome. This manuscript is original, has not been previously published and is not currently under consideration by another journal. REFERENCES 1. Erkurt, Kaya E, Berber I, Koroglu M, Kuku I. Thrombocytopenia in adults: review article. J Hematol. 2012. 1 Jul. 2. Nagrebetsky A, Al-Samkari H, Davis NM, Kuter DJ, WienerKronish JP. Perioperative thrombocytopenia: evidence, evaluation, and emerging therapies. Br J Anaesth. 2019;122:19-31. 3. Williamson DR, Albert M, Heels-Ansdell D, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013; 144:1207-1215. 4. Patel IJ, Davidson JC, Nikolic B, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 2012;23:727-736. 5. 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 1):174-181.
OOOO && 2020 6. Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surg Oral Med Oral Pathol. 1988;66:297-303. 7. Henderson JM, Bergman S, Salama A, Koterwas G. Management of the oral and maxillofacial surgery patient with thrombocytopenia. J Oral Maxillofac Surg. 2001;59:421-427. 8. Forbes CD, et al. Management of Bleeding Disorders in Surgical Practice. Oxford: Blackwell Scientific; 1993. 9. Watson-Williams EJ. Hematologic and hemostatic considerations before surgery. Med Clin North Am. 1979;63:1165-1189. 10. Wandt H, Sch€afer-Eckart K, Greinacher A. Platelet transfusion in hematology, oncology and surgery. Dtsch Aerzteblatt Int. 2014;111:809-815. 11. Druckman RF, Fowler EB, Breault LG. Post-surgical hemorrhage: formation of a “liver clot” secondary to periodontal plastic surgery. J Contemp Dent Pract. 2001;2:62-71. 12. Fillmore WJ, Leavitt BD, Arce K. Dental extraction in the thrombocytopenic patient is safe and complications are easily managed. J Oral Maxillofac Surg. 2013;71:1647. 1652. 13. Barnett CL, Mladsi D, Vredenburg M, Aggarwal K. Cost estimate of platelet transfusion in the United States for patients with chronic liver disease and associated thrombocytopenia undergoing elective procedures. J Med Econ. 2018;21:827-834. 14. Refaai MA, Phipps RP, Spinelli SL, Blumberg N. Platelet transfusions: impact on hemostasis, thrombosis, inflammation and clinical outcomes. Thromb Res. 2011;127:287-291. 15. Schmidt AE, Henrichs KF, Kirkley SA, Refaai MA, Blumberg N. Prophylactic preprocedure platelet transfusion is associated with increased risk of thrombosis and mortality. Am J Clin Pathol. 2018;149:87-94. 16. Estcourt LJ, Malouf R, Doree C, Trivella M, Hopewell S, Birchall J. Prophylactic platelet transfusions prior to surgery for people with a low platelet count. Cochrane Database Syst Rev. 2018:CD012779. 17. Lucas, et al. Oral surgery in thrombocytopenic patients. Oral Surg Oral Med Oral Pathol. 1964;17:572-580. 18. Aldridge E, Cunningham LL. Current thoughts on treatment of patients receiving anticoagulation therapy. J Oral Maxillofac Surg. 2010;68:2879-2887. 19. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006;40:2205-2210. 20. Ward BB, Smith MH. Dentoalveolar procedures for the anticoagulated patient: literature recommendations versus current practice. J Oral Maxillofac Surg. 2007;65:1454-1460. 21. Ipema HJ, Tanzi MG. Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures. Ann Pharmacother. 2012;46:97-107. 22. Lieberman BL, Kennedy MK, Lorenzo DR, et al. Control of lifethreatening head and neck hemorrhage after dental extractions: a case report. J Oral Maxillofac Surg. 2010;68:2311-2319.
Reprint requests: Shaiba Sandhu, BDS, DDS 1620 Tremont St. Suite BC-3-028. Boston MA 02120 USA. [email protected]
Bleeding risk in thrombocytopenic patients after dental extractions: a retrospective single-center study Shaiba Sandhu, BDS, DDS,a,b Vidya Sankar, DMD, MHS,a,b and Alessandro Villa, DDS, PhD, MPHa,b Objective. The aim of the present study was to assess the clinical safety profile of dental extractions in patients with thrombocytopenia and explore the effectiveness of platelet transfusion before dental extractions. Study Design. This is a retrospective cohort study of patients with moderate to severe (100,000/mL) thrombocytopenia who underwent dental extractions in the Oral Medicine and Dentistry Clinic at Brigham and Women’s Hospital from 2003 to 2019. Patients with a platelet count <30,000/mL received prophylactic preprocedure platelet transfusion. Risk and type of bleeding complication (prolonged postoperative bleeding requiring intervention with topical hemostatic agents and/or therapeutic platelet transfusions) was assessed. Results. Eighty-nine thrombocytopenic patients were identified. Postextraction bleeding complications occurred in 4 patients (4.4%). Surgical extractions and multiple number of extractions were significantly associated with an increased bleeding risk (P < .05), whereas prophylactic platelet transfusion and post-transfusion platelet count were not. Conclusions. Dental extractions in patients with thrombocytopenia may be performed with a positive safety profile by following a comprehensive medical evaluation, thorough treatment planning, adequate surgical management, use of local hemostatic measures, and, importantly, coordination of care with the patient’s medical team. (Oral Surg Oral Med Oral Pathol Oral Radiol 2020;000:16)
Thrombocytopenia is defined as a platelet count less than 150,000/mL and can be categorized as mild (100,000/mL150,000/mL), which is usually clinically insignificant, moderate (50,000/mL100,000/mL), and severe (<50,000/mL).1-3 Dental extractions in medically complex patients, particularly those with congenital or acquired thrombocytopenia, may present with several challenges, including postoperative prolonged or uncontrolled bleeding. Platelet transfusion is often used in clinical practice as a prophylactic or therapeutic measure to prevent or manage bleeding in thrombocytopenic patients, yet its validity remains controversial.4,5 The most commonly accepted platelet count threshold before dental extractions below which prolonged bleeding is anticipated is 50,000/mL. This threshold was determined based on general surgery guidelines and expert opinion.6-8 A recent systematic review challenged this threshold but noted that the studies available for review were of small sample size, with the largest one including 69 patients, and not all the studies were restricted to thrombocytopenic patients.5 Studies indicate that minor general surgical procedures can be performed with a positive safety profile in patients with platelet counts between 20,000/mL and 30,000/mL,9,10 which suggests that platelet threshold of 50,000/mL may be an a
Division of Oral Medicine and Dentistry, Brigham and Women’s Hospital, Boston, MA, USA. b Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA. Received for publication Sep 6, 2019; returned for revision Dec 26, 2019; accepted for publication Dec 27, 2019. Ó 2020 Elsevier Inc. All rights reserved. 2212-4403/$-see front matter https://doi.org/10.1016/j.oooo.2019.12.010
overestimation leading to unnecessary platelet transfusions, increased costs, and possibly delayed dental treatment. The aim of this retrospective study was to (1) evaluate the risk of postoperative bleeding after dental extractions in patients with moderate to severe thrombocytopenia, (2) explore whether prophylactic platelet transfusion was associated with avoidance of postoperative bleeding, and (3) identify other factors associated with postoperative bleeding.
MATERIALS AND METHODS Patient characteristics and study design This retrospective cohort study was conducted to identify all patients who underwent a dental extraction in the Oral Medicine and Dentistry Clinic at Brigham and Women’s Hospital from January 2003 to October 2019. Records of patients with platelet count 100,000/mL before the extractions were identified. The Partners Healthcare Institutional Review Board approved this study. Inclusion and exclusion criteria Patients with mild (100,000/mL150,000/mL), moderate (50,000/mL100,000/mL), and severe (<50,000/mL) thrombocytopenia were identified.1-3 Only patients with
Statement of Clinical Relevance The safety of dental extractions in thrombocytopenic patients may be indicated by successful management of postextraction bleeding by hemostatic measures with the reservation of therapeutic platelet transfusion in cases of severe bleeding. 1
ARTICLE IN PRESS ORAL MEDICINE 2 Sandhu et al.
moderate or severe thrombocytopenia were evaluated. Thrombocytopenic patients with concurrent coagulopathy were excluded from the study. Patients on anticoagulation were not excluded because their international normalized ratio (INR) and prothrombin time laboratory values were within the effective therapeutic range for performing dental extractions; as a result, anticoagulation in our patient population was not likely to confound the bleeding outcome as a result of low platelets. Electronic medical records were reviewed, and study variables collected included demographic data (age, sex, and race), tobacco smoking and alcohol consumption, pertinent medical history, use of anticoagulant therapy, and laboratory studies (INR, pre-extraction platelet count within 24 hours of the extraction, and post-transfusion platelet count measured immediately after transfusion in those who received platelets). Other information recorded included periodontal health status (gingivitis vs periodontitis- assessed by evidence of bone loss radiographically), the number of dental extractions, extraction technique (simple vs surgical extraction), postextraction bleeding complication, and management. Primary outcome The primary outcome was any postextraction bleeding complication occurring 2448 hours after the extraction. Bleeding complications were classified as minor and major depending on the intervention required. A minor bleeding complication required topical thrombin 1200 IU/mL (THROMBIN-JMI; GenTrac, Inc., Middleton, WI, USA) or topical antifibrinolytic agents such as aminocaproic acid 0.25 g/mL (Amicar; Xanodyne Pharmaceutica, Florence, KY, USA) or tranexamic acid 0.1 g/mL (Cyklokapron; Pharmacia and Upjohn, Kalamazoo, MI, USA) to arrest bleeding from the extraction sites. Postextraction hemorrhagic complications were deemed to be major if a postextraction platelet transfusion was needed for hemostasis.
DENTAL EXTRACTIONS: CLINIC PROTOCOL It is our clinical practice that patients with a platelet count less than 30,000/mL receive platelet transfusion before the dental extraction. Extractions were performed in a nontraumatic manner under local anesthesia with 2% lidocaine with 1:100,000 epinephrine. If a surgical flap was raised or osseous recontouring needed, the procedure was considered a surgical extraction. After the procedure, all extraction sockets were packed with absorbable gelatin sponge (Gelfoam, Pfizer, New York, NY, USA), followed by placement of resorbable sutures. Detailed written and verbal postoperative instructions were given to every patient. Postoperative phase In the postextraction period (2448 hours after the extraction), the medical care team knew to contact the
OOOO && 2020
oral medicine on-call service in case of any postextraction complication for the inpatients. The inpatient nurses were instructed to use a gauze soaked in thrombin 1200 IU/mL or antifibrinolytic agent (aminocaproic acid 0.25 g/mL or tranexamic acid 0.1 g/mL), as an external pressure packing, if any abnormal bleeding occurred from the extraction sockets. All the outpatients were provided with contact information in case of any complication after the extraction, including bleeding not controlled with gauze pressure, pain, swelling, or purulent discharge. Statistical analysis To summarize the data, descriptive statistics such as median and range were used for continuous variables, and frequency (%) was used for categorical variables. Differences between patients who developed bleeding complications versus those who did not were calculated using the Pearson and Wilcoxon tests. P values were considered statistically significant at P < .05. Statistical analyses were performed using JMP Pro-14 (SAS Institute, Cary, NC, USA).
RESULTS Patient characteristics Eighty-nine patients were identified with moderate (50,000/mL100,000/mL) to severe thrombocytopenia (<50,000/mL) receiving dental extractions. The median age was 56 years (range: 2086 years), and 55% of participants were male. Fourteen patients (15.7%) were current smokers, and 21 (23.5%) were current alcohol users at the time of extraction. Chronic periodontal disease was present in 46 patients (51.6%). The causes of thrombocytopenia were hematologic malignancy (n = 69; 77.5%), metastatic solid tumors (n = 4; 4.4%), hepatic disorders (n = 6; 6.7%), iatrogenic (n = 4; 4.4%), platelet disorders (n = 5; 5.6%) and congenital (n = 1; 1.1%) (Table I). Out of the 7 patients who were on anticoagulants, 6 received heparin infusion and 1 was on apixaban. The median INR of all patients was 1.1 (range: 0.91.9), including those with hepatic disorders. Out of the 6 patients with hepatic disorders (3 with hepatitis C, 2 with liver cirrhosis, and 1 with liver transplant), only 1 patient had a slightly increased prothrombin time of 37.6 seconds (reference range: 23.836.6 seconds) (Table II). Dental extractions Each patient received a median of 2 dental extractions (range: 121). Seventy-seven patients received 14 extractions (86.5%), 7 received 58 extractions (7.8%), 3 received 912 (3.3%), 1 received 1316 extractions (1.1%), and 1 had 21 dental extractions (1.1%). A total of 29 patients (32.5%) had a pre-extraction platelet count <30,000/mL. Of these, the 2 patients (2.2%) with platelet
ARTICLE IN PRESS OOOO Volume 00, Number 00
ORIGINAL ARTICLE Sandhu et al. 3
Table I. Patient characteristics Baseline characteristics
Table II. Primary diagnosis causing thrombocytopenia Total patients (N = 89)
Age (y) Median (range) 56 (2086) Gender, n (%) Male 55 (61.7) Female 34 (38.2) Race, n (%) White 68 (76.4) Black 8 (8.9) Asian 4 (4.5) Other 9 (10.1) Smoking status, n (%) Never 50 (56.1) Former 25 (28.0) Current 14 (15.7) Alcohol consumption, n (%) Never 23 (25.8) Former 45 (50.5) Current 21 (23.5) Platelet count/mL, n (%) 50,000100,000 44 (49.4) 30,00050,000 16 (17.9) 10,00030,000 24 (26.9) <10,000 5 (5.6) Median (range) 49,000 (500098,000) Patients transfused, n (%) 27 (30.3) Post-transfusion platelet count/mL, n (%) >100,000 6 (22.2) 50,000100,000 11 (40.7) 30,00050,000 8 (29.6) 10,00030,000 1 (3.7) <10,000 1 (3.7) Median (range) 59,000 (6000166,000) Teeth extracted, n (%) 14 77 (86.5) 58 7 (7.8) 912 3 (3.3) 1316 1 (1.1) >16 1 (1.1) Median (range) 1 (116) Site of extraction, n (%) Anterior 13 (14.6) Posterior 66 (74.1) Both anterior and posterior 10 (11.2) Primary diagnosis causing thrombocytopenia, n (%) Malignancy 73 (82.0) Other 16 (17.9) Periodontal bone loss, n (%) 46 (51.6) Use of an anticoagulant,* n (%) 7 (7.8) INR Median (range) 1.1 (0.91.9) INR, international normalized ratio. *Out of the seven patients on anticoagulation, one was on apixaban, and six were on heparin.
counts of 11,000/mL and 15,000/mL had simple single tooth extraction without prophylactic platelet transfusion at the decision of the patient’s medical team. The remaining 27 patients (30.3%) received a platelet transfusion just before the extraction(s) and had a median post-transfusion
Diagnosis
Patients, n (%)
Congenital Dyskeratosis Congenita Hematologic malignancy Acute myeloid leukemia Acute lymphoid leukemia Chronic myeloid leukemia Chronic lymphoid leukemia Aplastic anemia Non-Hodgkin’s lymphoma Hodgkin’s lymphoma Multiple myeloma Myelodysplastic syndrome Large granular lymphocytic leukemia Waldenstrom macroglobulinemia Metastatic solid tumor Hepatic conditions Liver cirrhosis Hepatitis C Liver transplant Platelet disorder Immune thrombocytopenic purpura Thrombotic event Iatrogenic Chemotherapy for sinonasal carcinoma Hemodialysis-related Drug-induced liver injury
1 (1.1) 69 (77.5) 32 (35.9) 3 (3.3) 2 (2.2) 1 (1.1) 2 (2.2) 4 (4.4) 4 (4.4) 7 (7.8) 11 (12.3) 2 (2.2) 1 (1.1) 4 (4.4) 6 (6.7) 2 (2.2) 3 (3.3) 1 (1.1) 5 (5.6) 4 (4.4) 1 (1.1) 4 (4.4) 1 (1.1) 2 (2.2) 1 (1.1)
platelet count of 59,000/mL (range: 6000160,000/mL). Despite the transfusion, platelet count of 3 patients (3.4%) remained <30,000/mL. These 27 patients had a median of 1 dental extraction (range: 116). There were 16 patients (17.9%) with a platelet count between 30,000/mL and 50,000/mL (median: 43,000/mL; range: 32,00050,000/mL) who did not receive prophylactic platelet transfusion in compliance with the clinical protocol. Post-dental extractions sequelae Three patients (3.3%) developed minor bleeding after dental extractions managed with topical thrombin or antifibrinolytic agents and pressure with gauze. Of these 3, one patient, whose medical history was significant for end-stage renal disease requiring hemodialysis, essential hypertension, and insulin-dependent diabetes mellitus type 2, was hospitalized with sepsis, deep vein thrombosis, and gastrointestinal bleeding. During her inpatient admission, she developed a submental abscess secondary to odontogenic infection requiring source control. She had a platelet count of 75,000/mL and underwent simple extractions of 3 grossly carious mandibular anterior teeth. The medical history of the other 2 patients was pertinent for hematologic malignancies (acute myeloid leukemia and myelodysplastic syndrome [MDS]), contributing to the underlying thrombocytopenia (platelets <30,000/mL) requiring
ARTICLE IN PRESS ORAL MEDICINE 4 Sandhu et al.
prophylactic platelets. One patient (1.1%) with acute myeloid leukemia developed a major bleeding complication requiring therapeutic platelet transfusion to achieve hemostasis in addition to antifibrinolytics. Local operative site infection developed in 2 patients (2.3%) with hematologic malignancy. Interestingly, the patients who developed a bleeding complication had platelet counts >30,000/mL at the time of dental extraction. The median platelet count at the time of extraction in patients exhibiting prolonged bleeding was 59,000/mL (range: 39,00075,000/mL) compared with those who did not develop any bleeding complication (62,000/mL; range: 6000166,000/mL) (Table III). The platelet count at the time of extraction did not have a statistically significant effect on the bleeding outcome (P = .42). Patients who underwent surgical extractions were at a higher risk of bleeding complications compared with those who had simple extraction (P < .01). Additionally, multiple dental extractions (2 or more) were significantly associated with an increased risk of postextraction bleeding (P < .05). Prophylactic platelet transfusion was not associated with a reduction in oral bleeding complication (P = .79). The lowest platelet count at which a dental extraction was carried out was 6000/mL. This patient’s underlying primary diagnosis was MDS. He had an odontogenic infection and required an urgent extraction for dental clearance before allogeneic stem cell transplant. Thus, after discussion with the oncology team, it was decided to proceed with the extraction. He received 2 units of platelets before the procedure; however, the platelet transfusion failed to increase his platelet count. Interestingly, his pre-extraction platelet count reduced from 9000/mL to 6000/mL after the transfusion. As per his oncologist, he was on systemic tranexamic acid 1300 mg TID. This patient had an atraumatic, simple extraction and did not experience any bleeding complications.
DISCUSSION Thrombocytopenic patients are considered at risk of prolonged bleeding after dental extraction. To date, there is no definite platelet count required for performing dental extractions.5 The commonly followed threshold of 50,000 platelets/mL is based on general surgery guidelines.6-8 Recently, a systematic review challenged this threshold for carrying out invasive dental procedures safely and found inadequate evidence to support that a platelet count >50,000/mL would diminish the risk of postoperative bleeding complications.5 However, this review included small scale studies with a median sample size of 13 (range: 469), and all the studies incorporated were not specific for thrombocytopenic patients.5 According to Watson-Williams, minor surgery can be performed “without undue risk” at 30,000 platelets/mL.9 As such, our clinical protocol has
OOOO && 2020
Table III. Primary outcome: postextraction bleeding complication Variable
Bleeding complication Yes (n = 4)
Age (y) Median (range) 54.5 (2374) Sex, n (%) Male 2 (2.2) Female 2 (2.2) Platelet count at the time of extraction/mL* Median (range) 50,000 (39,00075,000) Prophylactic platelet transfusion, n (%) No 2 (2.2) Yes 2 (2.2) Extraction type, n (%) Simple 3 (3.3) Surgical 1 (1.1) No. of extractions, n (%) Single extraction 0 Multiple extractionsy 4 (4.4) Median (range) 3 (221) Site of extraction, n (%) Anterior 1 (1.1) Posterior 2 (2.2) Both 1 (1.1) INR Median (range) 1.3 (1.11.5) Chronic periodontitis, n (%) Yes 5 (5.7) No 0 (0.0) Smoking status, n (%) Never 3 (3.3) Former 0 Current 1 (1.1)
Bleeding complication No (n = 85)
P
56 (2086)
.78
53 (62.3) 32 (37.6)
.62
62,000 (6000 166,000)
.42
61 (68.5) 24 (26.9)
.79
84 (1.1) 1 (1.1)
<.01
44 (50.5) 41 (46.0) 1 (116)
<.05
12 (13.4) 64 (71.9) 9 (10.1)
.51
1.1 (0.91.9)
.12
39 (44.8) 43 (49.4)
.32
47 (52.8) 25 (28.0) 13 (14.6)
.43
INR, international normalized ratio. *Including post-transfusion platelet count. yMultiple extractions were considered when 2 or more teeth were extracted.
been to recommend platelet transfusion before dental extraction if the platelet count is <30,000/mL. The majority of patients (95.5%) with moderatesevere thrombocytopenia did not develop any bleeding complication after extractions. One patient (1.1%), who developed a major bleeding complication, had a platelet count of 58,000/mL at the time of extraction and underwent multiple extractions of anterior and posterior teeth (21 teeth). His bleeding complication was likely a result of his poor periodontal health and a large number of extractions. He developed poorly organized protruding clots (also known as liver clots11) at the maxillary extraction sites postoperatively. Once these clots were removed, no further complications occurred. Three patients (3.3%) experienced minor bleeding episodes in the 24-hour postoperative period, which were well controlled with gauze pressure packs soaked in topical thrombin and/or antifibrinolytic agents. The
ARTICLE IN PRESS OOOO Volume 00, Number 00
two patients with hematologic malignancies received multiple surgical and simple posterior teeth extractions (median 3; range 26) at the platelet count of 39,000/ mL and 41,000/mL, respectively. The association between the platelet count and postextraction bleeding complication was not found to be statistically significant. The patient with the lowest platelet count at the time of extraction (6000/mL) received simple tooth extraction of a mandibular molar without any postoperative complications. A retrospective study conducted by Fillmore et al.12 indicated that the mean platelet count of 25,000/mL was associated with postoperative bleeding. Our study did not find such an association. However, surgical extraction and a multiple number of extractions were found to be the 2 significant factors related to an increased risk of postextraction bleeding. The results of our study indicated that with atraumatic extraction technique, postextraction management of the socket by packing absorbable hemostatic matrix with suturing, and good communication among the dental team, the patient, and the medical care team, extractions can be successfully performed in patients with moderate to severe thrombocytopenia without significant postoperative complications. The widely accepted platelet threshold of 50,000/mL for dental extraction may be an overestimation leading to unnecessary platelet transfusions. Platelet transfusions increase health care costs; in 2017 the total direct cost of a platelet transfusion in a patient was estimated to be in the range of $5258 to $13,117 in the United States.13 One unit of platelets typically boosts the platelet count by an average of 5000 to 8000/mL. Six whole blood donations are needed for a single platelet transfusion, and platelets have a limited storage life of 5 days. Hence, platelet donations are needed every day.13 It is essential to recognize that platelet transfusion is not entirely benign, and there are several risks related to the transfusion.14 Adverse reactions include the development of refractoriness, hemolysis from ABOmismatched transfusions, acute lung injury, and bacterial sepsis.14,15 Recurrent transfusion can result in human leukocyte antigen alloimmunization causing platelet refractoriness, which requires additional platelet transfusion with human leukocyte antigenmatched platelets leading to additional cost. Thus, some authors recommend that the platelet transfusion should be reserved for major bleeding episodes because minor bleeding can be effectively controlled with local measures.4 None of the patients included in this study who received pre-extraction platelets developed any acute transfusion complication; however, one of the patients with MDS was suspected of having developed platelet refractoriness because his platelets failed to increase from 6000/mL despite repeated platelet transfusions.
ORIGINAL ARTICLE Sandhu et al. 5
The benefit of prophylactic transfusion, even in cases of marked thrombocytopenia, remains controversial.16 A meta-analysis conducted in 2018 to evaluate the clinical efficacy of prophylactic transfusion of platelets in thrombocytopenic patients requiring general surgery found that there was insufficient evidence in the literature to establish that preprocedure transfusion results in a reduction in postoperative bleeding.16 Consequently, some authors advocate for therapeutic platelet transfusion instead.10 Similarly, our study did not find a statistically significant impact of prophylactic platelet transfusion on the clinical outcome. As a result, more attention should be placed on treating the bleeding rather than aggressively transfusing platelets preoperatively. In patients with quantitative and qualitative platelet disorders, postextraction bleeding can be efficiently controlled with local hemostatic measures without correcting the underlying hemorrhagic defect.17,18 Hemostatic matrices such as absorbable gel foam, oxidized cellulose, or collagen act as a 3-dimensional scaffold and play a role in clot organization, but their hemostatic properties are dependent on a functional coagulation cascade.18 Antifibrinolytic agents inhibit the conversion of plasminogen into plasmin and thus prevent lysis of the clot.19,20 A meta-analysis conducted to evaluate the role of topical tranexamic acid or aminocaproic acid in major surgical procedures concluded that these antifibrinolytics were effective in reducing postoperative bleeding.21 Life-threatening bleeding complications after dental extraction are uncommon but may occur, especially in the cases of combined thrombocytopenia and coagulopathy. If both the primary and secondary hemostatic pathways are compromised, the risk of hemorrhage increases. A case report by Lieberman et al.22 presented a patient who underwent a surgical extraction (later found to have severe thrombocytopenia with concurrent factor VII deficiency) and developed a hematoma in the submandibular space necessitating intubation to protect the airway. In thrombocytopenia, because the coagulation pathway (secondary hemostatic pathway) is functional, local measures of hemostasis are successful in contributing to the formation and stabilization of the primary hemostatic plug and stimulating the coagulation cascade.19 In this study population, the INR was within normal limits for all the patients, including those on anticoagulation, suggesting that the coagulation pathway was unimpaired. There were limitations to this study. First, all patients received an absorbable hemostat, followed by the placement of sutures after the extraction. This is a measure that may not be practiced routinely after all dental extractions at other institutions. This study did not address the bleeding complication risk if compression with gauze after extraction was the only measure used to control any bleeding. Second, our sample size was too small to
ARTICLE IN PRESS ORAL MEDICINE 6 Sandhu et al.
comment on the influence of anticoagulation on postoperative bleeding complications. Additionally, because of the retrospective nature of this chart review, there were insufficient details about the extent and severity of the periodontal disease in the medical records, which may have influenced postoperative bleeding in the setting of increased inflammation. Finally, although a retrospective study lacks the strength to establish a declarative statement, we intended to add more evidence to the literature for the development of better guidelines related to prophylactic platelet transfusions for thrombocytopenic patients in dentistry. A prospective study may be better suited to establish a threshold for platelet transfusion. But to our knowledge, our study offers the largest sample size with a wide array of primary diagnoses ranging from hematologic malignancies and hepatic disorders to primary platelet disorders leading to congenital and acquired thrombocytopenia. In conclusion, our results indicate that dental extractions, incorporating comprehensive medical evaluation, thorough treatment planning, adequate surgical management, use of local hemostatic measures, and coordination of care with the patient’s medical team may be performed with a positive safety profile in thrombocytopenic patients regardless of the preoperative platelet count. Randomized clinical trials are required for the establishment of more evidence-based guidelines.
DISCLOSURE We do not have conflicts of interest associated with this publication, and there has been no financial support for this work that could have influenced its outcome. This manuscript is original, has not been previously published and is not currently under consideration by another journal. REFERENCES 1. Erkurt, Kaya E, Berber I, Koroglu M, Kuku I. Thrombocytopenia in adults: review article. J Hematol. 2012. 1 Jul. 2. Nagrebetsky A, Al-Samkari H, Davis NM, Kuter DJ, WienerKronish JP. Perioperative thrombocytopenia: evidence, evaluation, and emerging therapies. Br J Anaesth. 2019;122:19-31. 3. Williamson DR, Albert M, Heels-Ansdell D, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013; 144:1207-1215. 4. Patel IJ, Davidson JC, Nikolic B, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol. 2012;23:727-736. 5. 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 1):174-181.
OOOO && 2020 6. Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surg Oral Med Oral Pathol. 1988;66:297-303. 7. Henderson JM, Bergman S, Salama A, Koterwas G. Management of the oral and maxillofacial surgery patient with thrombocytopenia. J Oral Maxillofac Surg. 2001;59:421-427. 8. Forbes CD, et al. Management of Bleeding Disorders in Surgical Practice. Oxford: Blackwell Scientific; 1993. 9. Watson-Williams EJ. Hematologic and hemostatic considerations before surgery. Med Clin North Am. 1979;63:1165-1189. 10. Wandt H, Sch€afer-Eckart K, Greinacher A. Platelet transfusion in hematology, oncology and surgery. Dtsch Aerzteblatt Int. 2014;111:809-815. 11. Druckman RF, Fowler EB, Breault LG. Post-surgical hemorrhage: formation of a “liver clot” secondary to periodontal plastic surgery. J Contemp Dent Pract. 2001;2:62-71. 12. Fillmore WJ, Leavitt BD, Arce K. Dental extraction in the thrombocytopenic patient is safe and complications are easily managed. J Oral Maxillofac Surg. 2013;71:1647. 1652. 13. Barnett CL, Mladsi D, Vredenburg M, Aggarwal K. Cost estimate of platelet transfusion in the United States for patients with chronic liver disease and associated thrombocytopenia undergoing elective procedures. J Med Econ. 2018;21:827-834. 14. Refaai MA, Phipps RP, Spinelli SL, Blumberg N. Platelet transfusions: impact on hemostasis, thrombosis, inflammation and clinical outcomes. Thromb Res. 2011;127:287-291. 15. Schmidt AE, Henrichs KF, Kirkley SA, Refaai MA, Blumberg N. Prophylactic preprocedure platelet transfusion is associated with increased risk of thrombosis and mortality. Am J Clin Pathol. 2018;149:87-94. 16. Estcourt LJ, Malouf R, Doree C, Trivella M, Hopewell S, Birchall J. Prophylactic platelet transfusions prior to surgery for people with a low platelet count. Cochrane Database Syst Rev. 2018:CD012779. 17. Lucas, et al. Oral surgery in thrombocytopenic patients. Oral Surg Oral Med Oral Pathol. 1964;17:572-580. 18. Aldridge E, Cunningham LL. Current thoughts on treatment of patients receiving anticoagulation therapy. J Oral Maxillofac Surg. 2010;68:2879-2887. 19. Patatanian E, Fugate SE. Hemostatic mouthwashes in anticoagulated patients undergoing dental extraction. Ann Pharmacother. 2006;40:2205-2210. 20. Ward BB, Smith MH. Dentoalveolar procedures for the anticoagulated patient: literature recommendations versus current practice. J Oral Maxillofac Surg. 2007;65:1454-1460. 21. Ipema HJ, Tanzi MG. Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures. Ann Pharmacother. 2012;46:97-107. 22. Lieberman BL, Kennedy MK, Lorenzo DR, et al. Control of lifethreatening head and neck hemorrhage after dental extractions: a case report. J Oral Maxillofac Surg. 2010;68:2311-2319.
Reprint requests: Shaiba Sandhu, BDS, DDS 1620 Tremont St. Suite BC-3-028. Boston MA 02120 USA. [email protected]