阵发性睡眠性血红蛋白尿症、自身免疫性溶血性贫血与遗传性球形红细胞增多症溶血特征比较

Comparison of hemolytic characteristics among paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia and hereditary spherocytosis

目的确定在阵发性睡眠性血红蛋白尿症（PNH）、自身免疫性溶血性贫血（AIHA）与遗传性球形红细胞增多症（HS）鉴别诊断中有重要参考价值的溶血特征。方法比较1998年1月至2017年4月108例经典型PNH患者、127例AIHA患者与172例HS患者的临床表现和溶血特征。结果①网织红细胞比例（Ret％）：PNH患者Ret％[6．70％（0．14％～22．82％）]明显低于AIHA患者114．00％（0．10％～55．95％），z=7．101，P〈0．001l和HS患者11．83％（0．60％-57．39％），z=8．477，P〈0．001]。轻度贫血时，PNH与AIHA患者Ret％水平差异无统计学意义，AIHA患者Ret％水平低于HS患者17．63％（1．87％～29．20％）对11．20％（3．31％-22．44％），z=-2．165，P=0．030]。中、重度贫血时，PNH患者Ret％水平均显著低于AIHA和／-IS患者。②总胆红素（TBIL）：HS患者TBIL水平为79．3（11．2～244．0）μmol／L，显著高于AIHA患者[57．6（7．6～265．0）gmol／L]与PNH患者[26．2（4．6～217．7）gmol／L]（z值分别为5．469、-2．165，P值均〈0．001）；HS患者TBIL超过4倍正常值上限比例（64．1％）明显高于AIHA患者（37．7％，Х^2=19．896，P〈0．001）和PNH患者（4．6％，P〈0．001）。③LDH：PNH患者LDH水平为1500（216～5144）U／L，显著高于AIHA患者[487（29—35]6）U／L]与HS患者[252（132～663）U／L]（z值分别为-9．556、-11．518，P值均〈0．001）；79．1％的PNH患者LDH水平〉1000U／L，明显高于AIHA患者（13．0％，r=93．748，P〈0．001）和HS患者（0，P〈0．001）。④脾大：43．5％的PNH患者脾大，中、重度脾大者占16．0％；而98．6％的AIHA患者和100．0％的HS患者脾大（P〈0．001），中、重度脾大者分别占63，0％（P〈0．001）和90．4％（P〈0．001）。⑤胆囊结石：43．1％的HS患者合并胆囊结石，明显高于AIHA患者（10．5％，P〈0．001）与PNH患者（2．9％，P〈0．001）。结论综合评估Ret0／0、TBIL、LDH水平、脾大及胆囊结石这五项溶血特征，可以清晰地倾向性判断PNH、AIHA和HS，并为下一步进行特异性实验室检查确诊提供可靠的诊断思路。这种综合评估简单、实用、有效，具有重要的临床意义。

Objective To determine the valuable hemolytic characteristics in differential diagnosis of paroxysmal nocturnal hemoglobinuria （PNH）, autoimmtme hemolytic anemia （AIHA） and hereditary spherocytosis （HS）. Method The clinical and hemolytic characteristics of 108 PNH patients, 127 AIHA patients and 172 HS patients diagnosed from January 1998 to April 2017 were compared. Results ①Reticulocyte percentage （Ret%） of PNH patients E6.70% （0.14%-22.82%）] was significantly lower than that of AIHA E 14.00%（0.10%-55.95%）, P 〈 0.0011 and HS patients [ 11.83%（0.60%-57.39%）, P 〈 0.001 ]. The Ret% in PNH patients were significantly lower than those in AIHA and HS patients at the same levels of anemia, except for in mild anemia between PNH and AIHA patients. However, when comparing the Ret% between AIHA and HS patients, there was significant difference only in mild anemia 7.63%（1.87%-29.20%）% vs 11.20%（3.31%-22.44%）, z = -2.165, P = 0.0301. ②The level of TBIL in HS patients was significantly higher than that in AIHA and PNH patients [79.3 （11.2-244.0） μmol/L vs 57.6 （7.6-265.0） μmol/L, z = 5.469, P 〈 0.001 ; 79.3（11.2-244.0） μmol/L vs 26.2（4.6-217.7）μmol/L, z = -2.165, P〈 0.0011, and the proportion of HS patients with TBIL more than 4 times the upper limit of normal （ULN） （64.1%） was significantly higher than that of AIHA （37.7%, Х^2= 19.896, P〈0.001） and PNH patients （4.6%, P 〈 0.001）. ③The LDH level of PNH patients was significantly higher than that of AIHA and HS [ 1 500 （216-5 144） U/L vs 487 （29-3 516） U/L, z = -9.556, P 〈 0.001; 1 500 （216-5 144） U/L vs 252 （132-663） U/L, z =- 11.518, P 〈 0.001], and the proportion of PNH patients with LDH more than 1 000 U/L （79.1%） was significantly higher than that of AIHA patients （13.0%, 2; = 93.748, P 〈 0.001） and HS patients （0, P〈 0.001）. ④Splenomegaly occurred in 43.5% of PNH patients, including 16.0% with severe splenomegaly. In contrast, the occurrence of splenomegaly was 98.6% in AIHA patients and 100.0% in HS patients （P 〈 0.001）, and 63.0% of AIHA patients （P 〈 0.001） and 90.4% of HS patients （P 〈 0.001） were with severe splenomegaly. ⑤Yhe prevalence of cholelithiasis in HS patients was up to 43.1%, significantly higher than that in AIHA patients （10.5%, P 〈 0.001） and PNH patients （2.9%, P〈 0.001）. Conclusion The comprehensive assessment of the five hemolytic characteristics is simplified, practical and efficient, with great clinical significance, providing specific indicators for differential diagnosis and efficient approach for making further work-up.