- Email: [email protected]
A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction in myelodysplastic syndromes patient
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction in myelodysplastic syndromes patient ⁎
Tomoya Somaa, Seiji Asodaa, , Ryotaro Iwasakia, Hidetaka Miyashitaa, Mariko Inouea, Yuka Yamadaa, Kimio Uchiyamab, Taneaki Nakagawaa, Hiromasa Kawanaa a b
Division of Oral and Maxillofacial Surgery, Departmant of Dentistry and Oral Surgery, School of Medicine, Keio Universitiy, Tokyo, Japan Department of Dentistry and Oral Surgery, National Hospital Organization Tochigi Medical Center, Tochigi, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Myelodysplastic syndrome Platelet transfusion refractoriness Tooth extraction Platelet concentrate-HLA Platelet transfusion
Myelodysplastic syndrome is an acquired hematopoietic disorder showing symptoms of pre-leukemia and refractory anemia. In the tooth extraction process of such cases, bleeding tendency due to pancytopenia, infection etc., becomes a problem. As such, a cautious approach is required. We have confirmed platelet transfusion refractoriness prior to tooth extraction in a myelodysplastic syndrome patient, and hereby report a case of tooth extraction following human leukocyte antigen (HLA)-compatible concentrated platelet transfusion. The patient was a 55-year-old female who was examined at our department due to a request for the extraction of tooth No. 36. Following consultation at the Hematology Department, platelet transfusion was performed as a pretreatment upon hospitalization. Increased body temperature, chills, shivers, and feelings of discomfort in the pharynx were observed. A close examination was performed due to a lack of increase in platelet count, and revealed platelet transfusion refractoriness caused by anti-HLA antibodies. Therefore, the patient was re-hospitalized and transfused with a platelet concentrate-HLA preparation. One hour later, an increase in platelet count was confirmed and the tooth extraction was performed. There was no evidence of bleeding or infection following extraction, and the prognosis was good.
1. Introduction
2. Case report
Myelodysplastic syndrome (MDS) is a clonal acquired hematopoietic disorder comprising of refractory anemia that progresses to the chronic state. It has a latent malignant nature that readily transitions to acute myelocytic leukemia resulting in a bone marrow disease with a poor prognosis [1]. Patients with thrombocytopenia undergo blood transfusion when an invasive procedure such as tooth extraction is to be performed. Frequent exposure to alloantigens may induce the production of anti-platelet antibodies, such as anti-human leukocyte antigen (HLA). Moreover, even if platelet transfusion is performed, the platelet count does not increase due to these antibodies, and a state of platelet transfusion refractoriness (PTR) manifests [2]. In this study, we took the opportunity to confirm PTR in an MDS patient who underwent platelet transfusion prior to tooth extraction, and experienced a case of tooth extraction following platelet concentrate-HLA (PC-HLA) transfusion. Here we report the outline with a literature-based discussion.
The patient was a 55-year-old female who was examined in June 2016 at a private dental clinic due to pain in left mandibular first molar (tooth No. 36). The attending dentist concluded that conserving the tooth would be difficult. The patient was referred to our department for extraction of the same tooth in August 2016. The patient’s history showed that she was diagnosed with aplastic anemia 30 years prior and developed hemachromatosis due to a massive transfusion performed at that time. In December 2014, she was examined at the Hematology Department of another hospital for detailed tests related to the hemachromatosis. Thereafter, she was on follow-up observation while on oral treatment with the iron chelating agent, deferasirox. However, the results from a bone marrow biopsy (performed due to worsened hemocytopenia) indicated MDS (refractory cytopenia with multilineage dysplasia). From March 2016, the patient underwent a total of 5 transfusions with 10 units of platelets each time and the response was good. With regard to invasive procedures, the patient experienced tooth extraction in 1996 following platelet infusion
⁎ Corresponding author at: Division of Oral and Maxillofacial Surgery, Departmant of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail address: [email protected] (S. Asoda).
https://doi.org/10.1016/j.ajoms.2018.05.003 Received 25 December 2017; Received in revised form 16 April 2018; Accepted 10 May 2018 2212-5558/ © 2018 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Soma, T., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2018), https://doi.org/10.1016/j.ajoms.2018.05.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
Fig. 1. Photograph of the oral examination. Tooth No. 36 had stage II shaking and produced pain with mild percussion.
December 2016, the in-hospital blood tests identified the platelet count to be 9,000/μL, and the patient was transfused with 10 units of platelets. However, 20 min after the transfusion was completed, the body temperature rose to 38.0 °C; chills and shaking were also observed. Although skin symptoms, hypotension etc. were absent, the patient complained of discomfort in the pharynx and mild dyspnea. Hydrocortisol 100 mg and chlorpheniramine maleate 10 mg were administered intravenously and the symptoms subsided. Blood tests performed the following day also revealed platelet counts of 8,000/μL with no adequate increase, therefore the tooth extraction was rescheduled (Fig. 3). Corrected count increment (CCI) (Fig. 4) was below the standard and PTR was suspected. In typical cases, CCI is ≥4,500/μL on the following morning or after 24 h. The Transfusion Medicine Department was consulted, and accelerated destruction of transfused platelets due to alloantibodies such as anti-HLA antibodies was suggested to be the cause, provided there was no evidence of infection. The blood culture performed immediately after the fever was negative and blood tests performed the following day revealed a leukocyte count of 2,000/μL, ruling out infection and disseminated intravascular coagulation(DIC). A request was made to the Japanese Red Cross Kanto-Koshinetsu Block
at another hospital. Her progress at the time was good, and there were no problems with hemostasis. At the initial examination, tooth No. 36 had stage II shaking and produced pain with mild percussion (Fig. 1). Panoramic radiograph revealed a transparent image in the alveolar bone of the distal root and surroundings of the furcation area (Fig. 2). The blood test results revealed decreased leukocyte count, erythrocyte count, platelet count, and total protein, and platelet count in particular was observed at a low of 7,000/μL. Ferritin was markedly high at 3251 ng/mL (Table 1). Extraction of tooth No. 36 was considered necessary; however, the blood tests at the initial examination showed that platelet count was low at 7,000/μL. The patient then sought consultation at the other hospital that had treated her for MDS. It was concluded that the patient had abnormally high ferritin levels due to the hemochromatosis, leading to mild hepatic dysfunction in addition to pancytopenia and thrombocytopenia. The Hematology and Transfusion Medicine Departments of this hospital were consulted, and the patient received a total of 20 units of platelets; 10 were transfused on the day of hospitalization and the remaining 10 on the following day, prior to the tooth extraction. The tooth extraction was scheduled to be performed. In
Fig. 2. Panoramic radiograph. A transparent image in the alveolar bone of the distal root and surroundings of the furcation area. 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
transfusion may be necessary when an invasive procedure such as tooth extraction is to be performed on patients with a decreased platelet count. However, frequent platelet transfusion is associated with a gradual weakening of the efficacy of platelet transfusion, and PTR may be induced [4]. The cause of PTR may be attributed to either immunological or nonimmunological mechanisms, with the latter accounting for 70–80% of onsets [5]. The non-immunological mechanisms include DIC, fever, serious infection, active major bleeding, enlarged spleen etc. [6], which enhance platelet consumption. In the absence of these factors, induction of PTR by an immunological mechanism is suspected. In this patient, infection and DIC were negative in the blood tests and blood culture, thereby ruling out the possibility of a non-immunological mechanism. With regard to immunological mechanisms, anti-HLA antibodies or antibodies towards human platelet antigens (HPA), or both, may be involved as the trigger [6]. Anti-HLA antibodies have been reported to be involved in 90% of cases, and anti-HPA antibodies in 5–10% of cases [5]. As a rule in Japan, ABO blood type compatible platelet transfusion is performed. However, as HLA and HPA are incompatible, frequent transfusion yields the establishment of alloimmunity resulting in PTR [4]. The present patient had received at least 6 platelet transfusions in other hospitals. Thus, it was presumed that anti-HLA antibodies were generated by an alloimmunity mechanism at the time of the transfusions. After completing the platelet transfusion, transfusion efficacy is evaluated based on the status of improvement in clinical symptoms, and extent of increase in platelet count. Platelet transfusion is evaluated at approximately 1 h or the morning after the transfusion, or at 24 h after the corrected count increment (CCI) is measured [6]. In typical cases, CCI is ≥7,500/μL at approximately 1 h after platelet transfusion and ≥4,500/μL on the following morning or after 24 h [7]. In the present case, CCI was below the standard value at 24 h following platelet transfusion during the initial hospitalization; therefore, the tooth extraction was rescheduled. However, during the PC-HLA transfusion, CCI and platelet count increased adequately and the tooth extraction procedure could be performed safely. PTR already exists in 20–50% of patients with hematopoietic diseases who require platelet transfusion, and 1–2 weeks is required for the supply of PC-HLA preparations. Therefore, for patients found to have PTR prior to initiating treatment, PC-HLA needs to be made available prior to surgery. On the other hand, as in this patient, when the presence of PTR is unknown prior to surgery, PC-HLA cannot be made available at the time of the intervention. Based on such facts, when platelet transfusion is judged as necessary, one should always consider the possibility of PTR occurrence [8]. Details regarding the underlying disease, history, and frequency of transfusions should be obtained from patients by interview, and one needs to become acquainted with countermeasures for adverse events occurring in platelet transfusion. Typically, when platelet count is below 50,000/μL, hemostasis becomes a problem. However, there are reports stating that in
Table 1 Blood test findings. WBC RBC Hemoglobin Hematocrit Platelet Prothrombin time Prothrombin activity PT-INR APTT TP ALB T-Bil AST ALT γ-GTP ALP LDH BUN Cre Fe Ferritin
2000/μL 196 × 10４/μL 8.2 g/dL 24.70% 7.0 × 103/μL 10.6 sec > 100％ 0.99 26.3 sec 6.5 g/dL 4.0 g/dL 0.8 mg/dL 19 U/L 10 U/L 10 U/L 547 U/L 218 U/L 11.5 mg/dL 0.87 mg/dL 260 μg/dL 3251 ng/mL
(3500 ∼ 8500/μL) (370 ∼ 490 × 10４/μL) (11.5 ∼ 15 g/dL) (35 ∼ 45％) (150 ∼ 350 × 103/μL) (70 ∼ 140％) (0.8 ∼ 1.2) (23 ∼ 36 sec) (6.7 ∼ 8.2 g/dL) (3.9 ∼ 5.2 g/dL) (0.4 ∼ 1.3 mg/dL) (10 ∼ 35 U/L) (5 ∼ 40 U/L) (5 ∼ 40 U/L) (100 ∼ 320 U/L) (5 ∼ 40 U/L) (8 ∼ 20 mg/dL) (0.4 ∼ 0.8 mg/dL) (29 ∼ 164 μg/dL) (10 ∼ 120 ng/mL)
We show the remarkable decrease in panhemocyte particularly platelet and a reduction in total protein. And we recognize high level of the ferritin due to the hemochromatosis.
Blood Center to perform HLA and platelet antibody tests on the patient. Tests utilizing an immunofluorescent beads microarray system confirmed the presence of anti-HLA antibodies. Thus, PTR due to anti-HLA antibodies was diagnosed. Tooth extraction following transfusion of 20 units of PC-HLA was scheduled. In January 2017, the platelet count had increased to 11,000/μL. The patient was transfused with 10 units of PCHLA on the day of hospitalization and an additional 10 units the following day. With the PC-HLA transfusion, CCI at 1 h and 24 h posttransfusion was 24488/μL and 17,707/μL, respectively. Moreover, platelet count at 1 h post-transfusion was confirmed to have increased to 76,000/μL and the tooth extraction was subsequently performed. The procedure was uneventful, and the cavity following the extracting was filled with a hemostatic gelatin sponge as a hemostatic intervention and close suture of the gum. Moreover, the patient orally administered AMPC 750 mg/day for 3 days following tooth extraction to prevent infection. Post-surgical hemostasis was good; the following day, presence of a formed blood clot in the cavity was confirmed, and the patient was discharged (Fig. 5). There was no sign of post-surgical infection or abnormal bleeding, and the prognosis was good. 3. Discussion MDS is a hematopoietic tumor originating from hematopoietic stem cells. The important prognostic factors are events associated with the development of leukemia and hematocytopenia, in particular infection and bleeding [3]. As was the case with this patient, pre-surgical platelet
Fig. 3. Formulae used in the determination of platelet refractoriness. 3
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
Fig. 4. Treatment course at first hospitalization and transition of platelet count. Blood transfusion of 10 units of platelets on the first day of hospitalization. There was no increase in platelet count and treatment was discontinued.
Fig. 5. Treatment course at the second hospitalization and transition of platelet count. The patient was transfused with 10 units of PC-HLA on the day of hospitalization and an additional 10 units the following day. Tooth extraction was subsequently performed.
procedures where local hemostasis is possible, such as in tooth extraction, the procedure can be performed even when platelet count is in the range of 10,000–20,000/μL [7]. When tooth extraction is being performed, if the platelet count is below 10,000/μL, which is a very low value, hemostasis will likely become difficult, and the treatment will be highly invasive. Blood transfusion is restricted to only such cases, and the requirement for blood transfusion must be carefully evaluated. If blood transfusion is performed, measures for local hemostasis by closestitch suturing and use of a hemostasis splint must be examined.
[2] [3] [4] [5] [6]
Conflict of interest
[7]
The authors have no conflict of interest to disclose regarding this paper.
[8]
References [1] Nakamura N, Sadatani K, Nakano M, Sasaki K, Habara T, Tozi T, et al. Two cases of
4
hypoplastic myelodysplastic syndromes without abnormalities in bone marrow cells morphological abnormalities in bone marrow cells. Hiroshima MLT 2016;5:20–3. Hod E, Schwartz J. Platelet transfusion refractoriness. Br J Haematol 2008;142:348–60. Matsuda A. The management of the myelodysplastic syndrome. 1st ed. Tokyo: Iyaku (Medicine and Drug) Journal Co., Ltd.; 2011. P. 9. Amemiya Y. Platelet transfusion refractoriness and effective management of platelet alloimmunization. Jpn J Clin Med 1997;55:2392–8. Takahashi D. The clinical significance of HLA antibody in platelet transfusion refractoriness. Major Histocompat Complex 2016;23:96–107. Lee E, Shinohara K, Watanabe H, Hirose M, Kitazoe K, Fukui M, et al. Anti-HPA-5a antibody as a possible cause of platelet transfusion refractoriness in a patient with acute myelogenous leukemia. Jpn J Transfus Med 1999;45(1):32–7. Use guideline of the blood products in Japan. The Ministry of Health, Labour and Welfare; 2019 (Accessed 5 November 2017). http://www.mhlw.go.jp/stf/ seisakunitsuite/bunya/0000159893.html. Tanaka H, Kurashina K, Hayashi K, Nishizawa R, Miyazawa H, et al. A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction. Jpn J Oral Maxillofac Surg 2015;61(1):41–4.
Contents lists available at ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case Report
A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction in myelodysplastic syndromes patient ⁎
Tomoya Somaa, Seiji Asodaa, , Ryotaro Iwasakia, Hidetaka Miyashitaa, Mariko Inouea, Yuka Yamadaa, Kimio Uchiyamab, Taneaki Nakagawaa, Hiromasa Kawanaa a b
Division of Oral and Maxillofacial Surgery, Departmant of Dentistry and Oral Surgery, School of Medicine, Keio Universitiy, Tokyo, Japan Department of Dentistry and Oral Surgery, National Hospital Organization Tochigi Medical Center, Tochigi, Japan
A R T I C LE I N FO
A B S T R A C T
Keywords: Myelodysplastic syndrome Platelet transfusion refractoriness Tooth extraction Platelet concentrate-HLA Platelet transfusion
Myelodysplastic syndrome is an acquired hematopoietic disorder showing symptoms of pre-leukemia and refractory anemia. In the tooth extraction process of such cases, bleeding tendency due to pancytopenia, infection etc., becomes a problem. As such, a cautious approach is required. We have confirmed platelet transfusion refractoriness prior to tooth extraction in a myelodysplastic syndrome patient, and hereby report a case of tooth extraction following human leukocyte antigen (HLA)-compatible concentrated platelet transfusion. The patient was a 55-year-old female who was examined at our department due to a request for the extraction of tooth No. 36. Following consultation at the Hematology Department, platelet transfusion was performed as a pretreatment upon hospitalization. Increased body temperature, chills, shivers, and feelings of discomfort in the pharynx were observed. A close examination was performed due to a lack of increase in platelet count, and revealed platelet transfusion refractoriness caused by anti-HLA antibodies. Therefore, the patient was re-hospitalized and transfused with a platelet concentrate-HLA preparation. One hour later, an increase in platelet count was confirmed and the tooth extraction was performed. There was no evidence of bleeding or infection following extraction, and the prognosis was good.
1. Introduction
2. Case report
Myelodysplastic syndrome (MDS) is a clonal acquired hematopoietic disorder comprising of refractory anemia that progresses to the chronic state. It has a latent malignant nature that readily transitions to acute myelocytic leukemia resulting in a bone marrow disease with a poor prognosis [1]. Patients with thrombocytopenia undergo blood transfusion when an invasive procedure such as tooth extraction is to be performed. Frequent exposure to alloantigens may induce the production of anti-platelet antibodies, such as anti-human leukocyte antigen (HLA). Moreover, even if platelet transfusion is performed, the platelet count does not increase due to these antibodies, and a state of platelet transfusion refractoriness (PTR) manifests [2]. In this study, we took the opportunity to confirm PTR in an MDS patient who underwent platelet transfusion prior to tooth extraction, and experienced a case of tooth extraction following platelet concentrate-HLA (PC-HLA) transfusion. Here we report the outline with a literature-based discussion.
The patient was a 55-year-old female who was examined in June 2016 at a private dental clinic due to pain in left mandibular first molar (tooth No. 36). The attending dentist concluded that conserving the tooth would be difficult. The patient was referred to our department for extraction of the same tooth in August 2016. The patient’s history showed that she was diagnosed with aplastic anemia 30 years prior and developed hemachromatosis due to a massive transfusion performed at that time. In December 2014, she was examined at the Hematology Department of another hospital for detailed tests related to the hemachromatosis. Thereafter, she was on follow-up observation while on oral treatment with the iron chelating agent, deferasirox. However, the results from a bone marrow biopsy (performed due to worsened hemocytopenia) indicated MDS (refractory cytopenia with multilineage dysplasia). From March 2016, the patient underwent a total of 5 transfusions with 10 units of platelets each time and the response was good. With regard to invasive procedures, the patient experienced tooth extraction in 1996 following platelet infusion
⁎ Corresponding author at: Division of Oral and Maxillofacial Surgery, Departmant of Dentistry and Oral Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. E-mail address: [email protected] (S. Asoda).
https://doi.org/10.1016/j.ajoms.2018.05.003 Received 25 December 2017; Received in revised form 16 April 2018; Accepted 10 May 2018 2212-5558/ © 2018 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd All rights reserved.
Please cite this article as: Soma, T., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology (2018), https://doi.org/10.1016/j.ajoms.2018.05.003
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
Fig. 1. Photograph of the oral examination. Tooth No. 36 had stage II shaking and produced pain with mild percussion.
December 2016, the in-hospital blood tests identified the platelet count to be 9,000/μL, and the patient was transfused with 10 units of platelets. However, 20 min after the transfusion was completed, the body temperature rose to 38.0 °C; chills and shaking were also observed. Although skin symptoms, hypotension etc. were absent, the patient complained of discomfort in the pharynx and mild dyspnea. Hydrocortisol 100 mg and chlorpheniramine maleate 10 mg were administered intravenously and the symptoms subsided. Blood tests performed the following day also revealed platelet counts of 8,000/μL with no adequate increase, therefore the tooth extraction was rescheduled (Fig. 3). Corrected count increment (CCI) (Fig. 4) was below the standard and PTR was suspected. In typical cases, CCI is ≥4,500/μL on the following morning or after 24 h. The Transfusion Medicine Department was consulted, and accelerated destruction of transfused platelets due to alloantibodies such as anti-HLA antibodies was suggested to be the cause, provided there was no evidence of infection. The blood culture performed immediately after the fever was negative and blood tests performed the following day revealed a leukocyte count of 2,000/μL, ruling out infection and disseminated intravascular coagulation(DIC). A request was made to the Japanese Red Cross Kanto-Koshinetsu Block
at another hospital. Her progress at the time was good, and there were no problems with hemostasis. At the initial examination, tooth No. 36 had stage II shaking and produced pain with mild percussion (Fig. 1). Panoramic radiograph revealed a transparent image in the alveolar bone of the distal root and surroundings of the furcation area (Fig. 2). The blood test results revealed decreased leukocyte count, erythrocyte count, platelet count, and total protein, and platelet count in particular was observed at a low of 7,000/μL. Ferritin was markedly high at 3251 ng/mL (Table 1). Extraction of tooth No. 36 was considered necessary; however, the blood tests at the initial examination showed that platelet count was low at 7,000/μL. The patient then sought consultation at the other hospital that had treated her for MDS. It was concluded that the patient had abnormally high ferritin levels due to the hemochromatosis, leading to mild hepatic dysfunction in addition to pancytopenia and thrombocytopenia. The Hematology and Transfusion Medicine Departments of this hospital were consulted, and the patient received a total of 20 units of platelets; 10 were transfused on the day of hospitalization and the remaining 10 on the following day, prior to the tooth extraction. The tooth extraction was scheduled to be performed. In
Fig. 2. Panoramic radiograph. A transparent image in the alveolar bone of the distal root and surroundings of the furcation area. 2
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
transfusion may be necessary when an invasive procedure such as tooth extraction is to be performed on patients with a decreased platelet count. However, frequent platelet transfusion is associated with a gradual weakening of the efficacy of platelet transfusion, and PTR may be induced [4]. The cause of PTR may be attributed to either immunological or nonimmunological mechanisms, with the latter accounting for 70–80% of onsets [5]. The non-immunological mechanisms include DIC, fever, serious infection, active major bleeding, enlarged spleen etc. [6], which enhance platelet consumption. In the absence of these factors, induction of PTR by an immunological mechanism is suspected. In this patient, infection and DIC were negative in the blood tests and blood culture, thereby ruling out the possibility of a non-immunological mechanism. With regard to immunological mechanisms, anti-HLA antibodies or antibodies towards human platelet antigens (HPA), or both, may be involved as the trigger [6]. Anti-HLA antibodies have been reported to be involved in 90% of cases, and anti-HPA antibodies in 5–10% of cases [5]. As a rule in Japan, ABO blood type compatible platelet transfusion is performed. However, as HLA and HPA are incompatible, frequent transfusion yields the establishment of alloimmunity resulting in PTR [4]. The present patient had received at least 6 platelet transfusions in other hospitals. Thus, it was presumed that anti-HLA antibodies were generated by an alloimmunity mechanism at the time of the transfusions. After completing the platelet transfusion, transfusion efficacy is evaluated based on the status of improvement in clinical symptoms, and extent of increase in platelet count. Platelet transfusion is evaluated at approximately 1 h or the morning after the transfusion, or at 24 h after the corrected count increment (CCI) is measured [6]. In typical cases, CCI is ≥7,500/μL at approximately 1 h after platelet transfusion and ≥4,500/μL on the following morning or after 24 h [7]. In the present case, CCI was below the standard value at 24 h following platelet transfusion during the initial hospitalization; therefore, the tooth extraction was rescheduled. However, during the PC-HLA transfusion, CCI and platelet count increased adequately and the tooth extraction procedure could be performed safely. PTR already exists in 20–50% of patients with hematopoietic diseases who require platelet transfusion, and 1–2 weeks is required for the supply of PC-HLA preparations. Therefore, for patients found to have PTR prior to initiating treatment, PC-HLA needs to be made available prior to surgery. On the other hand, as in this patient, when the presence of PTR is unknown prior to surgery, PC-HLA cannot be made available at the time of the intervention. Based on such facts, when platelet transfusion is judged as necessary, one should always consider the possibility of PTR occurrence [8]. Details regarding the underlying disease, history, and frequency of transfusions should be obtained from patients by interview, and one needs to become acquainted with countermeasures for adverse events occurring in platelet transfusion. Typically, when platelet count is below 50,000/μL, hemostasis becomes a problem. However, there are reports stating that in
Table 1 Blood test findings. WBC RBC Hemoglobin Hematocrit Platelet Prothrombin time Prothrombin activity PT-INR APTT TP ALB T-Bil AST ALT γ-GTP ALP LDH BUN Cre Fe Ferritin
2000/μL 196 × 10４/μL 8.2 g/dL 24.70% 7.0 × 103/μL 10.6 sec > 100％ 0.99 26.3 sec 6.5 g/dL 4.0 g/dL 0.8 mg/dL 19 U/L 10 U/L 10 U/L 547 U/L 218 U/L 11.5 mg/dL 0.87 mg/dL 260 μg/dL 3251 ng/mL
(3500 ∼ 8500/μL) (370 ∼ 490 × 10４/μL) (11.5 ∼ 15 g/dL) (35 ∼ 45％) (150 ∼ 350 × 103/μL) (70 ∼ 140％) (0.8 ∼ 1.2) (23 ∼ 36 sec) (6.7 ∼ 8.2 g/dL) (3.9 ∼ 5.2 g/dL) (0.4 ∼ 1.3 mg/dL) (10 ∼ 35 U/L) (5 ∼ 40 U/L) (5 ∼ 40 U/L) (100 ∼ 320 U/L) (5 ∼ 40 U/L) (8 ∼ 20 mg/dL) (0.4 ∼ 0.8 mg/dL) (29 ∼ 164 μg/dL) (10 ∼ 120 ng/mL)
We show the remarkable decrease in panhemocyte particularly platelet and a reduction in total protein. And we recognize high level of the ferritin due to the hemochromatosis.
Blood Center to perform HLA and platelet antibody tests on the patient. Tests utilizing an immunofluorescent beads microarray system confirmed the presence of anti-HLA antibodies. Thus, PTR due to anti-HLA antibodies was diagnosed. Tooth extraction following transfusion of 20 units of PC-HLA was scheduled. In January 2017, the platelet count had increased to 11,000/μL. The patient was transfused with 10 units of PCHLA on the day of hospitalization and an additional 10 units the following day. With the PC-HLA transfusion, CCI at 1 h and 24 h posttransfusion was 24488/μL and 17,707/μL, respectively. Moreover, platelet count at 1 h post-transfusion was confirmed to have increased to 76,000/μL and the tooth extraction was subsequently performed. The procedure was uneventful, and the cavity following the extracting was filled with a hemostatic gelatin sponge as a hemostatic intervention and close suture of the gum. Moreover, the patient orally administered AMPC 750 mg/day for 3 days following tooth extraction to prevent infection. Post-surgical hemostasis was good; the following day, presence of a formed blood clot in the cavity was confirmed, and the patient was discharged (Fig. 5). There was no sign of post-surgical infection or abnormal bleeding, and the prognosis was good. 3. Discussion MDS is a hematopoietic tumor originating from hematopoietic stem cells. The important prognostic factors are events associated with the development of leukemia and hematocytopenia, in particular infection and bleeding [3]. As was the case with this patient, pre-surgical platelet
Fig. 3. Formulae used in the determination of platelet refractoriness. 3
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology xxx (xxxx) xxx–xxx
T. Soma et al.
Fig. 4. Treatment course at first hospitalization and transition of platelet count. Blood transfusion of 10 units of platelets on the first day of hospitalization. There was no increase in platelet count and treatment was discontinued.
Fig. 5. Treatment course at the second hospitalization and transition of platelet count. The patient was transfused with 10 units of PC-HLA on the day of hospitalization and an additional 10 units the following day. Tooth extraction was subsequently performed.
procedures where local hemostasis is possible, such as in tooth extraction, the procedure can be performed even when platelet count is in the range of 10,000–20,000/μL [7]. When tooth extraction is being performed, if the platelet count is below 10,000/μL, which is a very low value, hemostasis will likely become difficult, and the treatment will be highly invasive. Blood transfusion is restricted to only such cases, and the requirement for blood transfusion must be carefully evaluated. If blood transfusion is performed, measures for local hemostasis by closestitch suturing and use of a hemostasis splint must be examined.
[2] [3] [4] [5] [6]
Conflict of interest
[7]
The authors have no conflict of interest to disclose regarding this paper.
[8]
References [1] Nakamura N, Sadatani K, Nakano M, Sasaki K, Habara T, Tozi T, et al. Two cases of
4
hypoplastic myelodysplastic syndromes without abnormalities in bone marrow cells morphological abnormalities in bone marrow cells. Hiroshima MLT 2016;5:20–3. Hod E, Schwartz J. Platelet transfusion refractoriness. Br J Haematol 2008;142:348–60. Matsuda A. The management of the myelodysplastic syndrome. 1st ed. Tokyo: Iyaku (Medicine and Drug) Journal Co., Ltd.; 2011. P. 9. Amemiya Y. Platelet transfusion refractoriness and effective management of platelet alloimmunization. Jpn J Clin Med 1997;55:2392–8. Takahashi D. The clinical significance of HLA antibody in platelet transfusion refractoriness. Major Histocompat Complex 2016;23:96–107. Lee E, Shinohara K, Watanabe H, Hirose M, Kitazoe K, Fukui M, et al. Anti-HPA-5a antibody as a possible cause of platelet transfusion refractoriness in a patient with acute myelogenous leukemia. Jpn J Transfus Med 1999;45(1):32–7. Use guideline of the blood products in Japan. The Ministry of Health, Labour and Welfare; 2019 (Accessed 5 November 2017). http://www.mhlw.go.jp/stf/ seisakunitsuite/bunya/0000159893.html. Tanaka H, Kurashina K, Hayashi K, Nishizawa R, Miyazawa H, et al. A case of platelet transfusion refractoriness occurring after platelet transfusion for tooth extraction. Jpn J Oral Maxillofac Surg 2015;61(1):41–4.