曲妥珠单抗致重度血小板减少症一例及文献回顾

doi:10.24920/003799

摘要/Abstract

摘要：

我们报告一例29岁浸润性导管癌pT2N0M0女性患者,ER和PR均弱阳性,Her-2（3+）,患者在我中心接受化疗和曲妥珠单抗治疗。于第二周期注射曲妥珠单抗6小时后出现异常子宫出血,血小板计数急剧降至3×10⁹/L,临床确诊为曲妥珠单抗所致严重血小板减少症。给予输注血小板、糖皮质激素、缩宫素及升血小板药物治疗,11天后患者的血小板完全恢复正常。由于严重血小板减少症由曲妥珠单抗所致,患者终止并未再继续尝试曲妥珠单抗治疗。随着曲妥珠单抗在临床逐渐广泛应用,临床医生可能会越来越多地遇到由曲妥珠单抗引起的致命性严重血小板减少症。我们希望通过此病例报告和文献回顾,引起临床医生对此种情况的警惕和重视,助益提升治疗效果。

关键词: 乳腺癌, 曲妥珠单抗, 血小板, 血小板减少症

Abstract:

We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×10⁹/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.

Key words: breast cancer, trastuzumab, platelet, thrombocytopenia

基金资助: 南方医科大学南方医院院长基金(2016L007)

Xiaoqi Zeng, Shanshan Jiang, Yuanyang Peng, Minfeng Liu, Changsheng Ye, Jianyu Dong. Trastuzumab-Induced Severe Thrombocytopenia:A Case Report and Literature Review[J].Chinese Medical Sciences Journal, 2020, 35(4): 377-382.

图/表 2

参考文献 19.

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6):394-424. doi: 10.3322/caac.21492. PubMed PMID: 30207593. pmid: 30207593
2.	Feng RM, Zong YN, Cao SM, et al. Current cancer situation in China: good or bad news from the 2018 Global Cancer Statistics? Cancer Commun (Lond) 2019; 39(1):22. doi: 10.1186/s40880-019-0368-6.
3.	Guo J, Li Q, Zhang P, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients. Chin J Cancer Res 2019; 31(5):759-70. doi: 10.21147/j.issn.1000-9604.2019.05.06. doi: 10.21147/j.issn.1000-9604.2019.05.06 pmid: 31814680
4.	Hudis CA. Trastuzumab: mechanism of action and use in clinical practice. N Engl J Med 2007; 357(1):39-51. doi: 10.1056/NEJMra043186. pmid: 17611206
5.	Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. The Lancet 2017; 389(10075):1195-205. doi: 10.1016/s0140-6736(16)32616-2. doi: 10.1016/S0140-6736(16)32616-2
6.	Cathomas R, von Moos R. Severe drug-induced thrombocytopenia after treatment with trastuzumab but not with lapatinib. Ann Oncol 2009; 20(9):1606-7. doi: 10.1093/annonc/mdp370. doi: 10.1093/annonc/mdp370 pmid: 19622591
7.	Parikh O, Neave F, Palmieri C. Severe thrombocytopenia induced by a single infusion of trastuzumab. Clin Br Cancer 2008; 8(3):285-6. doi: 10.3816/CBC.2008.n.034.
8.	Jara Sanchez C, Olier Garate C, Garcia-Donas Jimenez J, et al. Drug-induced thrombocytopenia induced by trastuzumab: a special challenge in a curable disease. Ann Oncol 2009; 20(9):1607-8. doi: 10.1093/annonc/mdp374. doi: 10.1093/annonc/mdp374 pmid: 19633054
9.	Drudi F, Gianni L, Fantini M, et al. Trastuzumab-related thrombocytopenia: always a self-limiting complication? Ann Oncol 2010; 21(3):668-9. doi: 10.1093/annonc/mdp566. doi: 10.1093/annonc/mdp566 pmid: 20032121
10.	Mantzourani M, Gogas H, Katsandris A, et al. Severe thrombocytopenia related to trastuzumab infusion. Med Sci Monit 2011; 17(7):CS85-7. doi: 10.12659/msm.881846 pmid: 21709629
11.	Pino MS, Angiolini C, Fioretto L. Severe thrombocytopenia after trastuzumab retreatment: a case report. BMC Res Notes 2013; 6:400. doi: 10.1186/1756-0500-6-400. doi: 10.1186/1756-0500-6-400 pmid: 24093447
12.	Zeng RC, Dai XX, Xie FY, et al. Severe thrombocytopenia induced by second exposure to trastuzumab can be alleviated by prolonging the interval between treatments. Clin Br Cancer 2014; 14(2):e69-72. doi: 10.1016/j.clbc.2013.11.004.
13.	Miarons M, Velasco M, Campins L, et al. Gradual thrombocytopenia induced by long-term trastuzumab exposure. J Clin Pharm Therapeut 2016; 41(5):563-5. doi: 10.1111/jcpt.12416. doi: 10.1111/jcpt.12416
14.	Luo Q, Guo Z, Ye C. Thrombocytopenia induced by herceptin. Am Surg 2019; 85(4):e222-4. pmid: 31043221
15.	George JN, Raskob GE, Shah SR, et al. Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998; 129(11):886-90. pmid: 9867731
16.	Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med 2007; 357(6):580-7. doi: 10.1056/NEJMra066469. doi: 10.1056/NEJMra066469 pmid: 17687133
17.	Aster RH, Curtis BR, McFarland JG, et al. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost 2009; 7(6):911-8. doi: 10.1111/j.1538-7836.2009.03360.x. doi: 10.1111/j.1538-7836.2009.03360.x pmid: 19344362
18.	Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 2019; 3(23):3829-66. doi: 10.1182/bloodadvances.2019000966. doi: 10.1182/bloodadvances.2019000966 pmid: 31794604
19.	Liu XG, Bai XC, Chen FP, et al. Chinese guidelines for treatment of adult primary immune thrombocytopenia. Int J Hematol 2018; 107(6):615-23. doi: 10.1007/s12185-018-2445-z. doi: 10.1007/s12185-018-2445-z pmid: 29619624

Case No.	References	Year*	Age (y/o)	Cycle	Onset time	Symptom (s)	Platelet# (×10⁹/L)	Treatment	Recovery time
1	Cathomas R, et al.^[6]	2007	54	1	4 days	Nose bleeding and petechiae	3	Immunoglobulin; methylprednisolone	7 days
2	Parikh O, et al.^[7]	2006	56	1	10 hours	Petechiae	2	Immunoglobulin	7 days
3	Jara Sanchez C. et al.^[8]	2008	37	1	1 day	Petechiae	3	Gamma globulin; glucocorticoids; SDP transfusion	4 days
3	Jara Sanchez C. et al.^[8]	2008	37	2	3 days	Petechiae	12	Splenectomy; glucocorticoids	7 days
4	Drudi F, et al.^[9]	2010	NR	1	19 days	Petechiae	7	Immunoglobulin; dexamethasone; SDP transfusion	Death?
5	Mantzourani M, et al.^[10]	2010	56	1	3 days	Nose bleeding and petechiae	5	Immunoglobulin	5 days
				2	3 days	NR	28	NR	10 days
				3	3 days	NR	128	NR	N/A
6	Pino MS, et al.^[11]	2012	70	1	1 day	Petechiae and ecchymosis	0	Immunoglobulin; methylprednisolone; SDP transfusion	6 days
7	Zeng RC, et al.^[12]	2010	57	2	5 days	Tiredness	28	Ethamsylate?	7 days
				3	4 days	None	19	Ethamsylate; rhTPO	9 days
				4	4 days	None	39	rhTPO	8 days
				5	1 day	Tiredness and dental bleeding	20	Ethamsylate	8 days
				6	N/A	None	Normal	N/A	N/A
				7	3 days	Dental bleeding	60	Ethamsylate	8 days
				8	1 day	Dental bleeding	39	Ethamsylate	10 days
8	Miarons M, et al. ^[13]	2015	70	4	NR	None	39	Prednisone	4 weeks
9	Luo Q, et al.^[14]	2016	39	1	10 days	Petechiae	3	SDP transfusion; ethamsylate; IL-11	5 days
9	Luo Q, et al.^[14]	2016	39	2	7 hours	Petechiae	9	Gamma globulin; SDP transfusion; ethamsylate; IL-11	4 days
10	Current case	2019	29	1	21 days	None	74	Observation	N/A
10	Current case	2019	29	2	6 hours	Uterine bleeding	3	Oxytocin; SDP transfusion; dexamethasone; IL-11; rhTPO	11 days

[1]	刘超, 陈晓燕, 吴文齐, 竺晓凡. KDSR基因的纯合子突变可能导致1例患儿的角化异常和血小板减少[J]. Chinese Medical Sciences Journal, 2020, 35(3): 278-282.
[2]	黄河, 林颖, 姚荣欣, 何牧卿, 林晓骥. 静脉丙种球蛋白联合血小板输注、利伐沙班治疗肝素诱导的危重血小板减少症1例[J]. Chinese Medical Sciences Journal, 2019, 34(1): 60-64.

优先出版

当期目次

过刊浏览

虚拟专题

作者中心

评阅者中心