PDF(1626 KB)
PDF(1626 KB)
PDF(1626 KB)
3岁男孩反复血小板减少伴溶血性贫血
Recurrent thrombocytopenia with hemolytic anemia in a boy aged 3 years
患儿男，3岁8个月，反复血小板减少伴溶血性贫血3年余，体检无肝脾、淋巴结肿大，无手指畸形。实验室结果示直接抗人球蛋白试验阴性，凝血功能正常，胆红素、乳酸脱氢酶及网织红细胞升高，完善血管性血友病因子裂解酶（von Willebrand factor-cleaving protease，ADAMTS13）活性检测示极度缺乏，ADAMTS13活性抑制性抗体阴性，二代测序发现ADAMTS13基因存在复合杂合突变，最终确诊为先天性血栓性血小板减少性紫癜。该病易误诊为Evans综合征，临床诊断较困难，该患儿自出生时即起病，但历时3年才得以确诊，因此，当患儿出生时有黄疸、反复血小板减少伴溶血性贫血、直接抗人球蛋白试验阴性时，需警惕先天性血栓性血小板减少性紫癜，尽快完善ADAMTS13活性及抑制性抗体检测来协助诊断、指导治疗，必要时完善基因检测以确诊。
A boy, aged 3 years and 8 months, had recurrent thrombocytopenia with hemolytic anemia for more than 3 years. The physical examination showed no enlargement of the liver, spleen, and lymph nodes or finger deformities. Laboratory results showed a negative result of the direct antiglobulin test, normal coagulation function, and increases in bilirubin, lactate dehydrogenase and reticulocytes. The results of von Willebrand factor-cleaving protease ADAMTS13 activity assay showed extreme deficiency, and antibody assay showed negative ADAMTS13 inhibitory autoantibodies. Next-generation sequence showed compound heterozygous mutation in the ADAMTS13 gene. The boy was diagnosed with congenital thrombotic thrombocytopenic purpura. This disease may be easily misdiagnosed as Evans syndrome and is difficult to diagnose in clinical practice. The child had developed the disease since birth, but it took 3 years to make a confirmed diagnosis. Therefore, congenital thrombotic thrombocytopenic purpura should be considered for children with jaundice at birth, recurrent thrombocytopenia with hemolytic anemia, and negative results of the direct antiglobulin test. The detection of ADAMTS13 activity and ADAMTS13 inhibitory autoantibodies should be performed as soon as possible for a definite diagnosis, and gene detection should be performed to make a confirmed diagnosis when necessary.
先天性血栓性血小板减少性紫癜 / 血管性血友病因子裂解酶 / 血小板减少 / 溶血性贫血 / 儿童
Congenital thrombotic thrombocytopenic purpura / von Willebrand factor-cleaving protease / Thrombocytopenia / Hemolytic anemia / Child
[1] Jaime-Pérez JC, Aguilar-Calderón PE, Salazar-Cavazos L, et al. Evans syndrome:clinical perspectives, biological insights and treatment modalities[J]. J Blood Med, 2018, 9:171-184.
[2] Mariotte E, Azoulay E, Galicier L, et al. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocyto-penic purpura):a cross-sectional analysis of the French national registry for thrombotic microangiopathy[J]. Lancet Haematol, 2016, 3(5):e237-e245.
[3] Joly BS, Stepanian A, Leblanc T, et al. Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency:a cohort study of the French national registry for thrombotic microangiopathy[J]. Lancet Haematol, 2016, 3(11):e537-e546.
[4] Carmi O, Berla M, Shoenfeld Y, et al. Diagnosis and management of catastrophic antiphospholipid syndrome[J]. Expert Rev Hematol, 2017, 10(4):365-374.
[5] 中华医学会血液学分会血栓与止血学组. 弥散性血管内凝血诊断中国专家共识(2017年版)[J]. 中华血液学杂志, 2017, 38(5):361-363.
[6] 张沛, 匡仟卉柠, 高春林, 等. 儿童典型溶血尿毒综合征36例临床分析[J]. 中华实用儿科临床杂志, 2020, 35(5):360-364.
[7] Joly BS, Zheng XL, Veyradier A. Understanding thrombotic microangiopathies in children[J]. Intensive Care Med, 2018, 44(9):1536-1538.
[8] Rashid A, Mushtaq N, Mansoori H. Congenital thrombotic thrombocytopenic purpura with a novel ADAMTS13 gene mutation[J]. Cureus, 2020, 12(12):e12053.
[9] Krogh AS, Waage A, Quist-Paulsen P. Congenital thrombotic thrombocytopenic purpura[J]. Tidsskr Nor Laegeforen, 2016, 136(17):1452-1457.
[10] Joly BS, Coppo P, Veyradier A. Pediatric thrombotic thrombocytopenic purpura[J]. Eur J Haematol, 2018, 101(4):425-434.
[11] Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants:a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)[J]. Genet Med, 2020, 22(2):245-257.
[12] Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura[J]. J Thromb Haemost, 2020, 18(10):2486-2495.
[13] Moschcowitz E. Hyaline thrombosis of terminal arterioles and capillaries:a hitherto undescribed disease[J]. Proc NY Pathol Soc, 1924, 24:4-21.
[14] Lotta LA, Wu HM, Mackie IJ, et al. Residual plasmatic activity of ADAMTS13 is correlated with phenotype severity in congenital thrombotic thrombocytopenic purpura[J]. Blood, 2012, 120(2):440-448.
[15] Levy GG, Nichols WC, Lian EC, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura[J]. Nature, 2001, 413(6855):488-494.
[16] Scully M. Hereditary thrombotic thrombocytopenic purpura[J]. Haematologica, 2019, 104(10):1916-1918.
[17] van Dorland HA, Taleghani MM, Sakai K, et al. The international hereditary thrombotic thrombocytopenic purpura registry:key findings at enrollment until 2017[J]. Haematologica, 2019, 104(10):2107-2115.
[18] Matsumoto M, Kokame K, Soejima K, et al. Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome[J]. Blood, 2004, 103(4):1305-1310.
[19] Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura[J]. Blood, 2017, 129(21):2836-2846.
[20] Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura[J]. N Engl J Med, 2019, 380(4):335-346.
[21] Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocy-topenic purpura:pathogenesis, diagnosis and potential novel therapeutics[J]. J Thromb Haemost, 2017, 15(10):1889-1900.
[22] Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura[J]. J Thromb Haemost, 2020, 18(10):2496-2502.
[23] Coppo P, Cuker A, George JN. Thrombotic thrombocytopenic purpura:toward targeted therapy and precision medicine[J]. Res Pract Thromb Haemost, 2019, 3(1):26-37.
[24] Adili R, Holinstat M. Formation and resolution of pial microvascular thrombosis in a mouse model of thrombotic thrombocytopenic purpura[J]. Arterioscler Thromb Vasc Biol, 2019, 39(9):1817-1830.
[25] Kopi? A, Benamara K, Piskernik C, et al. Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura[J]. J Thromb Haemost, 2016, 14(7):1410-1419.
[26] Scully M, Knöbl P, Kentouche K, et al. Recombinant ADAMTS-13:first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura[J]. Blood, 2017, 130(19):2055-2063.
[27] 王夕妍, 杨仁池. 血栓性血小板减少性紫癜治疗新进展[J]. 中华血液学杂志, 2019, 40(12):1055-1059.
