Expression of Platelet Membrane Glycoprotein Ib/Ⅸ/Ⅴ Complex,a Receptor of Thrombin,in Patients with Hemorrhagic Thrombopathy

To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.     

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on the expression of platelet membrane glycoprotein I b/IX/V complex in patients with chronic renal failure

ABSTRACT Objective： To investigate the effect of Xiaoyu Zhixue Tablet （消瘀止血片, XYZXT） on the expression of platelet membrane glycoprotein （GP） Ⅰ b/Ⅸ/Ⅴ complex and GP Ⅰ b α in patients with chronic renal failure （CRF） in early metaphase. Methods： Fifty-one patients with CRF in early metaphase （treated group） were treated with XYZXT, 3 months as the course of treatment for 2 courses. The previous therapies remained unchanged. Flow cytometry was used to assess the expression of platelet GP Ⅰb/Ⅸ/Ⅴ complex and GP Ⅰb α in patients with CRF, and turbidity method was used to determine the platelet maximum aggregation rate （MAR）, meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group （31 healthy subjects）. Results： Compared with the normal control group, expressions of GP Ⅰ b/Ⅸ/Ⅴ complex and GPⅠb α, and platelet MAR in CRF patients were significantly lower （P=0.007,P=0.001,P=0.009） before the treatment; after the treatment with XYZXT, the above indexes in CRF patients were remarkably increased （P=0.033,P=0.026, P=0.045）, but still lower than those in the normal control group, however, it was not statistically significant. Conclusion： （1） The expression of GP Ⅰ b/Ⅸ/Ⅴ complex in CRF patients of early metaphase was decreased, which lead to platelet aggregation dysfunction. This might be one of the reasons for the hemorrhagic trend in CRF. （2） XYZXT was able to upgrade expressions of GP Ⅰb/Ⅸ/Ⅴ complex and GPⅠb α in CRF patients, improve platelet function and clown-regulate platelet activation in patients with CRF.     

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on Expression of Platelet Membrane Glycoproteins in Patients with Hemorrhagic Thrombopathy

Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrornbopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n = 50) treated with adrenosin, vitamins C, K and P, both for 6 months.The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GP Ⅱ b, GPⅢ a and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89.8% in TCM group and 54.0% in the WM group (X2 =45.83, P＜0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (X2 = 62.06, P＜0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GP Ⅲ a and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P＞0.05) and higher than those in the WM group (P＜0.05).Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰ b/Ⅸ, GP Ⅱ b/Ⅲ a complexes, GP Ⅰ b, GPⅢ a and P-selectin at the level of receptor protein.     

Association of the Platelet Membrane Glycoprotein Ⅰ a C807T Gene Polymorphism with Aspirin Resistance

To explore the correlation between the C807T polymorphism of platelet membrane gly- coprotein Ⅰa (GPⅠa) gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin (100 mg/d) for 7 days. Platelet aggregation function was detected using adenosine diphosphate (ADP) and arachidonic acid (AA) before and after the administration of aspi- rin. Then the subjects were divided into three groups according to the results of platelet aggregation function: an aspirin resistant (AR) group, an aspirin semi-responder (ASR) group and an aspi- rin-sensitive (AS) group. Platelet GPⅠa gene 807CT polymorphism was examined by means of po- lymerase chain reaction-sequence specific primers (PCR-SSP). The results showed that T allelic fre- quency in AR group and ASR group were higher that of AS group (P<0.005), and the prevalence of genotypes (TT TC) of these two groups was significantly higher than that in AS group (P<0.05). Platelet GPⅠa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression (OR=3.76, 95% CI: 2.87–9.58). The results suggest that inherited platelet GPⅠa variations may have an important impact on aspirin resistance and the presence of GPⅠa T allele may be a marker of genetic susceptibility to aspirin resistance.     

Relationship between Platelet Activation Related Factors and Polymorphism of Related Genes in Patients with Coronary Heart Disease of Blood-stasis Syndrome

Objective： To comparatively study the expressive conditions of platelet activation related factors （GPⅠb, GPⅡb-Ⅲa and GMP-140） in healthy subjects and patients with coronary heart disease （CHD） of blood-stasis （BS） or non-blood-stasis （non-BS） syndrome, and to analyze the relationship between the activities of various glycoproteins and the polymorphism of genes. Methods： With case control design adopted, patients with the CHD （40 of BS, 37 of non-BS） and 39 healthy subjects for control, all fitting to the inclusion criteria, were selected in this study. The number of affected coronary branches was recorded by the contrast examination. The mean fluorescence intensity （MFI） of GPⅠb, GPⅡb-Ⅲa, and GMP-140 （CD42b, CD61, CD62p） in patients and healthy persons was measured with flow cytometry, the polymorphism of HPA-3 gene was detected by Taqman probe technique and that of HPA-2 gene was determined by gene sequencing. Results： MFI of CD61 and CD62p was higher in the CHD patients than in the healthy control, which was also higher in patients of BS syndrome than in patients of non-BS syndrome （P〈0.05）; MFI of CD42b was lower in the CHD patients than in the healthy control （P〈0.05）, but showing insignificant difference between BS and non-BS syndrome （P〉0.05）; at the same time, no significant difference of all the above-mentioned three MFI could be found in patients with various numbers of affected coronary branches, neither in patients with different genotypes at GPⅡb HPA-3 and GPⅠb HPA-2 polymorphism loci （P〉0.05）. Conclusion： （1） The activities of GP Ⅱ b-Ⅲa and GMP-140 were obviously increased in the genesis and developing process of CHD and CHD of BS syndrome, and so they could be taken as one of the objective indexes for microscopic diagnosis of BS syndrome. （2） The level of GPⅠb was lower in CHD patients than in healthy persons, but it was not a sensitive indicator for BS syndrome of CHD. （3） Levels of GP Ⅱb-Ⅲa, GPⅠb a     

Effects of salivae miltiorrhizae liguspyragine hydrochloride and glucose injection (参芎葡萄糖注射液) on the levels of main platelet thrombin receptors in chronic haemodialysis patients

Objective:To investigate the effects of Salvia Miltiorrhiza Liguspyragine Hydrochloride and Glucose Injection(参芎葡萄糖注射液,SLGI) on the expression of platelet membrane receptors proteinase-activated receptor-1(PAR1) and proteinase-activated receptor-4(PAR4) in end-stage renal disease(ESRD) patients on chronic haemodialysis(HD).Methods:Eighty-six ESRD patients on HD(treated group) were treated with SLGI,7 days as one therapeutic course,for two successive courses.The previous therapies were unchanged.Flow cytometry was used to assess the expression of platelet PAR1 and PAR4 in the patients,and turbidity method was used to determine the platelet maximum aggregation rate(MAR).Meanwhile,renal function was measured.The final data were compared with those before treatment and with those in the normal control group(54 healthy subjects).Results:Compared with the normal control group,the expressions of PAR1 and PAR4 and platelet MAR in ESRD patients on HD was significantly higher before treatment(P=0.001,P=0.006, and P=0.008);after treatment with SLGI,the above indices in patients were remarkably decreased(P=0.036 and P=0.046),except PAR4(P=0.067),but still higher than those in the normal control group,however,it was not statistically significant.Conclusions:(1) The overexpression of PAR1 and PAR4 might lead to increased platelet aggregation and this could be one of the reasons for the thrombotic events in ESRD patients on HD.(2) SLGI was able to down-regulate the expression of PAR1 in ESRD patients on HD,improve platelet function,and regulate platelet activation.     

The Effect of Paroxetine on Depressive Symptom with Somatic Disease and Change of Platelet 5-HT Concentration

To date,about1 1 .3 % of adults in the worldsuffered from depressive disorder each year.And 1 /4— 1 /3 of patients in general hospitals had accompa-nied depression.It was proved that depressed pa-tients showed lower basal values of platelet5 - HTconcentration and reduced 5 - HT uptake in compari-son to healthy subjects.According to the latest re-port the change of platelet5 - HT was used as an indi-cator of cumulative peripheral 5 - HT uptake blockadeproduced by selective serotonin reuptak…     

Optimal low dosage of acetylsalicylic acid (ASA) for the prevention and treatment of ischemic cerebrovascular disease in geriatric patients.

A series of 108 geriatric patients with ischemic cerebrovascular disease were treated with low dose aspirin (acetylsalicylic acid, ASA). Daily doses of 100 mg, 50 mg and 25 mg were administered to three groups of 36 patients. Changes in platelet aggregation responses were dynamically observed in 64 (22 normal subjects, 42 patients). Monitoring of 22 normal subjects revealed inhibition of platelet aggregation at a dose of 300 mg or 100 mg which could last as long as 7 days. This suggests that 100 mg or less could be clinically effective. Satisfactory inhibitory effects on platelet aggregation were observed in all three groups, with 14 patients in each group given daily doses of 100 mg, 50 mg and 25 mg during four weeks' observation. The most effective inhibition was obtained in the 50 mg group. Therefore, the authors recommend 50 mg/d as the optimal dosage for low dose aspirin therapy in geriatric patients.

     

Safety,pharmacokinetic and pharmacodynamic studies of batifiban injection following single- and multiple-dose administration to healthy Chinese subjects

Batifiban, a synthetic cyclic peptide, is a potent platelet glycoprotein GPⅡb/Ⅲa antagonist which may be useful in the treatment and prevention of acute coronary syndromes. The pharmacokinetics and pharmacodymanic （inhibition of platelet aggregation） effects, and tolerability of batifiban were investigated in healthy subjects following single bolus injection with doses of 55, 110, or 220 μg/kg, or multiple doses of an bolus followed intravenous infusion for 24 h （180 μg/kg plus 2.0 μg/minokg, and 220 μg/kg plus 2.5μg/minokg） in this phase I clinical trial. Plasma levels of batifiban and areas under the curve were found to be proportional to doses. Batifiban was rapidly eliminated with a half-life of approximately 2.5 h. Significant differences were noted for plasma levels of batifiban and areas under the curve between males and females. No significant differences in the terminal half-life were found between males and females. Batifiban reversibly inhibited ex vivo platelet aggregation in a dose- and concentration-dependent manner, consistent with its mechanism as a GPⅡ b/Ⅲa antagonist. Single and multiple intravenous doses of batifiban were found to be safe and well tolerated in healthy subjects. These results support a bolus injection plus intravenous infusion regimen of batifiban for the treatment and prevention of acute coronary syndromes.     

Pharmacokinetic and pharmacodynamic properties of batifiban coadministered with antithrombin agents in Chinese healthy volunteers

The combined use of batifiban, a synthetic platelet GP II b/IIIa receptor antagonist, and an- tithrombin agents is an attractive option for the treatment of patients with non-ST-segment elevation （NSTE） acute coronary syndrome （ACS） and those scheduled for percutaneous coronary intervention. To observe whether antithrombin agents affect the pharmacokinetic and pharmacodynamic properties of batifiban in combination therapy and optimize clinical administration dosage of batifiban, an open-label and parallel study was conducted. Thirty healthy subjects were randomly divided into three groups, which were sequentially treated with batifiban alone, or oral coadministration of clopidogrel, aspirin and UFH, or batifiban coadministered with these antithrombin agents. Blood samples were collected at pre-specified time points. The evaluation index included the inhibition of platelet aggregation and pharmacokinetic parameters. The pharmacokinetic parameters of batifiban and batifiban coadministered with antithrombin agents showed no significant differences. The mean inhibition rate of platelet aggre- gation （%） suggested that neither batifiban alone nor antithrombin agents alone could provide such po- tent inhibition rate （〉80%） to obtain the best clinical efficacy, but they had a synergistic effect on plate- let inhibition. No serious adverse effects were observed. The results in these healthy subjects suggest that batifiban coadministrated with antithrombin agents could achieve optimum clinical treatment effect for patients with NSTE ACS, and also those scheduled for percutaneous coronary intervention.     

The Expression of TNF-α and ICAM-1 in Lesions of Lichen Planus and Its Implication

In order to investigate the role of TNF-α and ICAM-1 in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of TNF-α and ICAM-1 in skin le- sions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-α and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins (both P<0.05). Meanwhile, there was a obvious correlation between the in- crease of TNF-α and that of ICAM-1 in lichen planus. The expression of TNF-α and ICAM-1 might play an important role in the development of lichen planus.     

Effects of glycoprotein Ⅱb/Ⅲa antagonists and chloride channel blockers on platelet cytoplasmic free calcium

Platelet activation plays an important role in thrombosis. Platelet glycoprotein Ⅱ b/Ⅲ a （ GPⅡ b/Ⅲ a ） is the receptor of fibrinogen. Platelet cross-linking with fibrinogen through GP Ⅱ b/Ⅲ a is the process of thrombosis. Ca^2＋ is an important intracellular second messenger in platelet activation. It has been reported that GP Ⅱ b/Ⅲ a receptors were involved in the calcium influx of activated platelet, and GP Ⅱ b/Ⅲ a receptor had characteristics of calcium channel or an adjacent calcium channel.     

Clinical study of the ascending aorta wall motion by velocity vector imaging in patients with primary hypertension

We studied the wall motion characteristics of the ascending aorta by velocity vector imaging （VVI） in primary hypertension patients. The ascending aortas both in 30 patients with primary hypertension and 30 normal controls were examined by Acuson sequoia 512 equiped with VVI. The maximum velocity （Vs, Ve） of every point on the anterior wall of ascending aorta both in systole and diastole was measured. The aortic diameter was wider in the hypertension patients than that in the healthy subjects （P〈0.05）. The movement amplitude of the anterior wall of the ascending aorta in long axis view in the hypertension patients was lower than that in the healthy subjects （P〈0.05）. The motion and time to peak in systole of each point of the ascending aorta in the healthy subjects had no significant difference （P〉0.05）. The velocity curves of the anterior wall of ascending aorta both in the hypertension and healthy subjects were regular, and the curve in systole was named S wave and that in diastole named E wave. The velocity of S wave and E wave was slower in the hypertension patients than that in the healthy subjects （P〈0.05）. The time to peak of S wave on the anterior wall of ascending aorta in systole was shorter in the hypertension patients than in the healthy subjects （P〈0.05）. VVI could be used to accurately and directly observe the movement character of the ascending aorta walls, which would help us understand the elasticity of great arteries in patients with hypertension.     

Effect of polymorphism and type Ⅱ diabetes on aspirin resistance in patients with unstable coronary artery disease

Background Aspirin is widely used in the secondary prevention of coronary artery diseases, including myocardial infarction, stroke, and vascular related deaths. However, the antiplatelet effect of aspirin appears to be variable and aspirin resistance (AR) is currently still controversial for Chinese patients. The aim of this study was to describe the prevalence of AR, and identify possible risk factors associated with a lack of response to aspirin treatments in patients with unstable coronary artery disease.Methods Platelet function tests with arachidonic acid (ARA) and urinary 11-dehydro-thromboxane B2 (11-DH-TXB2) concentrations were performed in 262 patients with unstable coronary artery disease who had not been taking aspirin before admission. ARA induced platelet aggregation and 11-DH-TXB2 were detected to evaluate the functional and biochemical responses to aspirin before and on days 1, 4, and 10 after aspirin administration. Six-month follow-up was completed in patients who developed AR to evaluate the effect of aspirin in a long-term treatment. GP1 Bα (C1018T), PI(A1/A2), P2Y1(A1622G), TBXA2R (T924C) were also detected to evaluate the influence of genetic variant on aspirin responsiveness.Results A total of 8.8% of patients were indentified as AR at the first day after aspirin treatment. The level of urine 11-DH-TXB2 in the AR group was higher compared to non-AR group (P ＜0.05). There was no relationship between ARA induced platelet aggregation and urinary 11-DH-TXB2 levels (r=0.038, P=0.412). The results of DNA sequencing showed that TBXA2R-924TT homozygotes had a significantly high rate of AR. Logistic regression demonstrated that diabetes was an independent risk factor of AR.Conclusions In the beginning period of administration, aspirin was not a sufficient factor that inhibits platelet aggregation. TBXA2R-g24T allele was involved in AR. Diabetes was an independent risk factor of AR.     

Different Expressions of Protein Kinase C-α,βⅠ and βⅡ in Glomeruli of Diabetic Nephropathy Patients

In current study, the expressions of protein kinase C （PKC）-α, βⅠ and βⅡ as well as their correlation to the expression of transforming growth factor-βⅠ （TGF-βⅠ） and vascular endothelial growth factor （VEGF） were investigated in glomeruli of normal renal tissues taken from human kidney tumors and kidney tissues from patients with diabetic nephropathy （DN）. The accumulation of glomerular extracelluar matrix （ECM） was determined by PAS staining, the expressions of PKC-α, PKC-βⅠ, PKC-βⅡ, TGF-βⅠ and VEGF were measured by semi-quantitative immunohistochemistry. Our results showed that in glomeruli of normal renal tissues, PKC-α and βⅡ had a strong expression whereas the expression of PKC-βⅠ was weak; in glomeruli of DN patients, the expressions of PKC-α, PKC-βⅠ, VEGF and TGF-βⅠ and the accumulation of ECM increased significantly, but the expression of PKC-βⅡ decreased markedly. Meanwhile, the expressions of PKC-α and βⅠ had a positive correlation to the expressions of VEGF and TGF-βⅠ respectively, whereas PKC-βⅡ showed no correlation to VEGF and TGF-βⅠ. It is concluded that the expressions of PKC-α, βⅠ and βⅡ in glomeruli of normal subjects and DN patients are different. PKC-α seems to play a critical role in human DN by up-regulating VEGF expression, whereas PKC-βⅠ is relatively important for the up-regulation of TGF-βⅠ and the accumulation of ECM under diabetic conditions.     

Effect of resveratrol on platelet aggregation in vivo and in vitro

Objective Low or moderate consumption of red wine has a greater benefit than the consumpti on of other beverages in the prevention of atherosclerosis and coronary heart di sease and this is increasingly attributed to the polyphenol compounds in red win e, such as resveratrol. In the present study, we investigated the effect of res veratrol on platelet aggregation in vitro and in vivo. Methods Platelet aggregation in rabbits and normal subjects was measured using Born’s me thod. Results Resveratrol, at 10-1000 μmol/L, significantly inhibited platelet aggregation i n vitro induced by collagen, thrombin, and ADP in healthy subjects. The inhibit ory effect was concentration- dependent. Hypercholesterolemia induced by high- cholesterol diet enhanced ADP- induced platelet aggregation. Resveratrol 4 mg ·kg(-1)·d(-1)inhibited ADP- induced platelet aggregation in vivo de spite no changes in serum lipid levels. Conclusions Resveratrol inhibits platelet aggregation both in vitro and in vivo. This may b e one of the mechanisms by which resveratrol prevents atherosclerosis.     

脉血康胶囊对PCI术后急性冠脉综合症患者长期预后的改善作用

Objective:To study the changes of adenosine diphosphate(ADP)-induced platelet aggregation rate,and evaluate the effects of Maixuekang Capsule(脉血康胶囊,MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention(PCI).Methods:A total of 236 patients with acute coronary syndrome,who received successful PCI,were randomly assigned to a trial group(116 cases) and a control group(120 cases) according to random numbers;treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms.In the trial group,the patients were treated with MKC combined with routine medication,and in the control group the patients were treated with routine medication.The therapeutic course for the two groups was 12 months and the follow-up was 12 months.The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein(hs-CRP) were determined before PCI,12 h and 30 days after PCI.In the meantime,the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up.Results:Compared with before PCI,the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI(P0.05).They were significantly reduced after 30-day-treatment of MKC,showing statistical differences when compared with those in the control group(P0.05).During the 12-month follow-up,the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group(6.9%vs.12.5%,P0.01).Conclusions:ADP-induced platelet aggregation function was significantly elevated after PCI.MKC improved the prognosis of patients with acute coronary syndrome,possibly through inhibiting the platelet aggregation,fighting against inflammation,and protecting the vascular endothelial function.     

Effect of sublingual immunotherapy on level of cytokines in PBMCs of patients with allergic asthma

This study examined the possible mechanism of sublingual immunotherapy(SLIT) in the treatment of allergic asthma.Forty asthma patients allergic to dust mite were enrolled.They received SLIT with dermatophagoides farinae(Der.f) drops for one year.Thirty healthy subjects served as controls.The levels of IL-4 and IFN-γ of peripheral blood mononuclear cells(PBMCs) were determined in allergic asthma patients before and after the SLIT as well as the healthy subjects.The results showed that the level of IL-4 was substantially increased and that of IFN-γ remarkably decreased in the patients before the SLIT as compared with those in the healthy subjects(P<0.05).After the SLIT,the level of IL-4 was significantly reduced and that of IFN-γ elevated in these allergic asthma patients.It was concluded that sublingual immunotherapy is effective for patients with allergic asthma.And it may work by regulating the balance of Th1/Th2 through changing the expression of IL-4 and IFN-γ in PBMCs.     

Epidemic hemorrhagic fever. The mechanism of coagulation and fibrinolysis.

To understand the mechanism of hemorrhage, coagulation and fibrinolysis in epidemic hemorrhagic fever (EHF), thrombin time (TT), prothrombin time (PT), fibrinogen (FIG), the platelet count (PLAT), plasminogen (PLG), antithrombin-III (AT-III), fibrin-fibrinogen degraded products (FDP) and platelet functions of aggregation and release were studied dynamically with advanced methods in 134 EHF patients. TT and PT were prolonged, FIG, AT-III and PLG were decreased and FDP was increased. Besides, the decrease of PLAT, the platelet functions of aggregation and release were below the normal level. The results showed that the balance of blood coagulation and fibrinolysis was lost from the early stage of the disease.