Analysis Of The Correlation Between Blood Coagulation State Of Henoch-Schonlein Purpura And Renal Injury During Acute Phase

Objective: Henoch-Schonlein purpura (HSP) is one of the most common vasculitic diseases in childhood. The reported incidence of renal injury ranges from 20-100%. The long-term morbidity of HSP is predominantly associated with renal injury. The prognosis of Henoch-Schonlein purpura (HSP) is mainly determined by the involvement of the kidney, called Henoch-Schonlein purpura nephritis (HSPN), and HSPN probably as a result of immune-mediated endothelial cell damage. But specific diagnostic and prognostic markers have not been established. On the other hand, the pathogentic mechanisms underlying HSP are poorly understood. It has been reported that high coagulation state plays an important role in the development of HSPN. To study the coagulation state in the acute phase of HSP, and the extent of glomrule and tubular involvement in HSP and its relationship to the development of HSPN, and to probe some sensitive index for early diagnosis of renal injury in HSP, we measured three laboratory signs of coagulation and urinary excretion of two glomrule and tubular marker proteins in 36 children with HSP and 10 health controls.Methods: The analysis was performed in 36 patients with HSP admitted in our hospital between January 2006 and November 2006, aged 8.39 +/- 3.11 (SD) years. The patient population consisted of 23 boys and 13 girls.10 healthy, age-matched children served as controls. The diagnosis of HSP was made according to the diagnostic criteria of Practice Pediatrics. All the children were grouped as follows: the control group (G1) consisted of 10 children (aged 4~12 years); the other 36 children (age 3~15 years) with HSP were divided into 2 groups according to clinical symptoms: each containing 18 patients: G2 (with routine urine examination normal), G3 (with hematuria or along with proteinuria, with normal renal function).We determined the levels of plasma and urinary soluble adhesion molecules P-selectin and D-Dimer (D-D), and plasma thrombomodulin (TM), alongside urinary [alpha] 1-microglobulin (α1-MG) and creatinine rate of clearance (Ccr) in patients with HSP and controls respectively. Adhesion molecules were measured in plasma and urine by enzyme-linked immunosorbent assay methods (ELISA). The urinaryα1-MG level was examined by nephelometric immunoassay using a Behring nephelometer analyzer II (Dade Behring). The measurement of 24 hours urinary protein (24h Upro) is performed by immunonephrelometric. All the signs were determined during acute phase. In order to eliminate the effect of urine volume, concentration or dilution, and other factors, we use urinary creatinine to correct the values that we got in the urine.Statistical analysis was performed using one-way ANOVA, the linear regression and correlation. A P value of less than 0.05 was considered as significant.Results:1 It was found that patients with HSP had P-selectin and D-dimer plasma concentrations significantly increased compared with the controls (G1: 9.34+/-3.18ng/ml and 1.01+/-0.31μg/ml; G2: 18.80+/-6.18ng/ml and 1.55+/-0.50μg/ml; vs. G3: 20.70+/-4.52ng/ml and 1.73+/-0.55μg/ml respectively).2 A univariate analysis revealed that plasma TM levels in patients with HSP during the acute phase were significantly higher than those in G2 and controls (G1: 9.68+/-2.14μg/ml; G2:18.30+/-4.63μg/ml; G3: 21.15+/-4.06μg/ml), and the group of G3 is significantly higher than those in G2.Besides that, the level of plasma TM was also positively associated with 24h Upro(r=0.554, P<0.01), and inversely associated with Ccr(r=-0.481, P<0.01).3 It was found that patients with HSPN had P-selectin and D-dimer urinary concentrations significantly increased compared with the controls and G2. (G1: 1.27+/-0.39 ng/ml.cr and 2.33+/-0.71μg/ml.cr; G2: 2.35+/-0.71ng/ml.cr and 4.05+/-1.31μg/ml.cr; vs. G3: 3.06+/-0.80 ng/ml.cr and 7.03+/-1.30μg/ml.cr respectively).4 HSP with urinaryα1-MG levels elevated during the acute phase were significantly higher than those in healthy controls (G1:838.06+/-192.19μg/ml; G2: 1174.81+/-275.73μg/ml; G3: 1241.26+/-263.65μg/ml). And the Ccr levels in patients with HSPN during the acute phase were lower than those in controls and G2 (G1: 89.37+/-14.90 ml/min; G2: 80.40+/-12.87 ml/min; G3: 79.28+/-10.52 ml/min).5 The levels of urinary P-selectin and urinary D-dimer were positively associated with 24h Upro (r=0.569, P<0.01); (r=0.522, P<0.05) andα1-MG (r=0.499, P<0.01); (r=0.398, P<0.01), while inversely associated with Ccr (r=-0.434, P<0.01); (r=-0.294, P<0.05).6 In the linear regression and correlation analysis, increased plasma P-selectin level in parallel to plasma TM (r=0.432, P<0.01) and plasma D-D (r=0.488, P<0.01) levels.Conclusions:1 HSP with plasma TM and P-selectin levels elevated. For plasma soluble TM is derived from damaged endothelium, increased plasma levels of TM in patients with HSP are surrogates of vascular endothelial injury, and soluble P-selectin is defined to be a plasma marker of platelet activation. It is concluded that the endothelial dysfunction and platelet activation may contribute to the developing of HSP.2 The correlation between plasma TM, plasma D-D and plasma P-selectin implying endothelial injury may have some relationship to platelet activation, which may affect mechanism of coagulation and fibrolysis inverse.3 The high concentrations of plasma TM, P-selectin and D-D in patients with HSP, with raised urinary P-selectin and D-D levels in patients with HSPN. As D-D is the specific products of secondary hyperfibrolysis, these findings probably reflect a systemic activation of coagulation in the patients with HSP. When it comes to HSPN, intraglomerular coagulation and fibrinolysis exists in local reactions within inflamed blood vessels, along with the systemic hypercoagulation state, which may exaggerates the renal injury. The haemostatic alterations observed in HSP are important for understanding the pathophysiology of the disease. Plasma TM, urinary P-selectin and D-D may be regarded to be the elevated markers of hypercoagulability with HSP. Clinicians should be aware of these laboratory findings in order to promote the treatment of the disease through anticoagulation and conservation of blood vessel endothelium and so on.4 Plasma TM concentrations, urinary P-selectin and D-D levels were paralleled to 24h Upro andα1-MG, and inversely with the Ccr. This three signs were associated with developing renal involvement, combining with the symptoms and signs. A significant correlation was detected between severity of disease and plasma TM, urinary P-selectin and D-D concentrations, and the increases correlates with severity of the disease. In addition, a relation with disease activity has also been noted and these may be useful markers of disease severity. We therefore sought to define the risk factors of not only development of HSPN, but also development of severe renal injury. The availability of such indexes may have clinical values, because measurement of such a marker can be a non-invasive way of assisting in diagnosis or as an indicator of disease progression.