Vazquez-Mellado Alberto, Pequeño-Luévano Myrna, Cantu-Rodriguez Olga Graciela, Villarreal-Martínez Laura, Jaime-Pérez José Carlos, Gomez-De-Leon Andres, De La Garza-Salazar Fernando, Gonzalez-Llano Oscar, Colunga-Pedraza Perla, Sotomayor-Duque Guillermo, Gomez-Almaguer David
a Haematology Department, Hospital Universitario Jose Eleuterio Gonzalez , Autonomous University of Nuevo Leon , Monterrey , Mexico.
Hematology. 2016 Jun;21(5):311-6. doi: 10.1080/10245332.2015.1133008. Epub 2016 Feb 24.
Thrombotic thrombocytopenic purpura (TTP) is characterized by a reduction in the von Willebrand cleavage protein ADAMTS-13, mainly as a consequence of autoimmunity. Plasma exchange (PEx) is standard, achieving complete remission (CR) in 77-83% of cases, but rates are variable depending on ADAMTS-13 activity and relapse is frequent in patients with <10%. Thus, an effective front-line immunosuppressive treatment is needed.
We administered PEx daily until CR and rituximab 100 mg/dose/week for 4 consecutive weeks to 10 patients with a first TTP episode and 1 relapsed patient (8 females (72%) and 3 males (28%)). Median age was 34 years (15-46) and laboratory parameters at diagnosis were as follows: platelets 11 × 10(9)/l (range 7-27.4 × 10(9)/l), lactate dehydrogenase 1822 U/l (range 705-8220 U/l, normal 70-180 U/l), and haemoglobin 6 g/dl (range 4.2-11.8 g/dl). ADAMTS-13 activity was determined in eight patients and was <10% in all. ADAMTS-13 autoantibody titre was determined in seven patients and was >15 units/ml in all (ref: negative <12, undetermined 12-15, positive >15 units/ml); Shiga toxin was negative in all patients. The median number of PEx until CR was 7 (range 4-12); prednisone 1 mg/kg was administered to six patients.
The median follow-up was 22 months (range 4-49) and the estimated 2-year relapse-free survival was 89%; one HIV+ patient relapsed at 8 months follow-up. No complications related to PEx or rituximab were reported.
Our study suggests that low-dose rituximab and PEx are effective as front-line treatment for acute TTP; however, a prospective trial is needed to demonstrate whether low-dose rituximab is as effective as the conventional dose.
血栓性血小板减少性紫癜（TTP）的特征是血管性血友病因子裂解蛋白酶ADAMTS - 13减少，主要是自身免疫的结果。血浆置换（PEx）是标准治疗方法，77 - 83%的病例可实现完全缓解（CR），但缓解率因ADAMTS - 13活性而异，ADAMTS - 13活性<10%的患者复发频繁。因此，需要一种有效的一线免疫抑制治疗方法。
我们对10例首次发作的TTP患者和1例复发患者（8名女性（72%）和3名男性（28%））每日进行血浆置换直至达到完全缓解，并连续4周每周给予100mg剂量的利妥昔单抗。中位年龄为34岁（15 - 46岁），诊断时的实验室参数如下：血小板11×10⁹/L（范围7 - 27.4×10⁹/L），乳酸脱氢酶1822U/L（范围705 - 8220U/L，正常70 - 180U/L），血红蛋白6g/dl（范围4.2 - 11.8g/dl）。对8例患者测定了ADAMTS - 13活性，所有患者均<10%。对7例患者测定了ADAMTS - 13自身抗体滴度，所有患者均>15单位/ml（参考值：阴性<12，未确定12 - 15，阳性>15单位/ml）；所有患者的志贺毒素均为阴性。达到完全缓解所需的血浆置换中位数为7次（范围4 - 12次）；6例患者给予1mg/kg的泼尼松。
中位随访时间为22个月（范围4 - 49个月），估计2年无复发生存率为89%；1例HIV阳性患者在随访8个月时复发。未报告与血浆置换或利妥昔单抗相关的并发症。
我们的研究表明，低剂量利妥昔单抗和血浆置换作为急性TTP的一线治疗是有效的；然而，需要进行前瞻性试验来证明低剂量利妥昔单抗是否与传统剂量一样有效。
