冠状动脉斑块形态与CD40配体及妊娠相关蛋白酶-A的关系

目的　检测经冠状动脉造影显示为Ⅱ型斑块的冠心病患者血浆中CD4 0配体 (CD4 0L)和妊娠相关蛋白酶 A(PAPP A)水平 ,从临床角度探讨斑块破裂的原因。方法　对 6 8例经冠状动脉造影证实的冠心病患者的冠状动脉斑块形态进行分型。根据斑块形态 ,患者分为 4组 :Ⅰ型病变组 (表面光滑 ,n =1 9) ,Ⅱ型病变组 (表面不规则 ,n =33) ,Ⅲ型病变组 (长段表面不规则 ,n =1 6 ) ,另 2 5例冠状动脉造影正常的患者为对照组。所有患者检测血浆CD4 0L、PAPP A、心肌肌酸激酶 (CK)及肌酸激酶同工酶 (CK MB)。结果　Ⅱ型病变组血浆CD4 0L水平 [(3 2 1± 2 0 8)mg/L]显著高于Ⅰ型病变组[(1 0 3± 0 98)mg/L ,P <0 0 1 ]、Ⅲ型病变组 [(1 2 3± 0 88)mg/L ,P <0 0 5 ]和对照组 [(1 0 1± 0 94 )mg/L ,P <0 0 1 ]。Ⅱ型病变组血浆PAPP A[(1 6 8± 7 2 )mU/L]显著高于Ⅰ型病变组 [(7 3± 4 1 )mU/L ,P <0 0 1 ]、Ⅲ型病变组 [(8 9± 4 9)mU/L ,P <0 0 5 ]和对照组 [(7 1± 4 4)mU/L ,P <0 0 1 ]。Ⅱ型病变组血浆CD4 0L与PAPP A呈显著正相关 (r =0 44 6 ,P <0 0 1 )。结论　冠状动脉造影显示斑块破裂的冠心病患者血浆CD4 0L、PAPP A水平明显升高 ,且CD4 0L与PAPP A呈正相关。提示CD4 0L可能通过上调PAPP A的     

序贯性血液净化治疗重度毒鼠强中毒的研究

目的 :观察序贯性血液净化治疗重度毒鼠强中毒患者的临床疗效和对预后的影响 ,及对毒鼠强的清除作用。　 方法 :18例重度毒鼠强中毒患者入院后 ,除给予常规治疗外 ,同时进行序贯性活性炭血液灌流 (HP)治疗 3～ 5h ,随后立即进行连续性静脉 静脉血液滤过 (CVVH)治疗 2 4～ 36h。观察患者血压、脉搏、血常规及血清酶学变化 ,测定HP治疗前、后血浆中毒鼠强浓度 ,及CVVH治疗 2h、12h滤器前、后血浆及超滤液中毒鼠强浓度。　结果 :患者在中毒 12h内即进行血液净化治疗 (8例 ) ,死亡 1例 ,其余患者痊愈 ;晚期患者在中毒 12h后才进行血液净化治疗 (10例 ) ,2例死亡 ,1例呈去大脑皮层状态 ,1例精神异常。较早治疗患者痊愈率显著高于晚期治疗患者(87 5 %vs 6 0 % ,P <0 0 5 ,χ2 检验 ) ,而痊愈患者平均昏迷时间 5～ 6 0 (2 3 0± 19 9)h ,明显比晚期治疗痊愈患者短[2 0～ 96 (5 9 7± 2 7 7)h ,P <0 0 1,秩和检验 ]。HP治疗后血浆中毒鼠强浓度从 (0 12 4± 0 0 82 )mg/L降至 (0 0 80±0 0 5 5 )mg/L。CVVH治疗 2h及 12h血浆毒鼠强浓度分别为 (0 0 78± 0 0 6 4 )mg/L ,及 (0 0 74± 0 0 5 9)mg/L ,2h及 12h毒鼠强筛选系数分别为 0 839± 0 4 0 9,0 6 86± 0 2 5 3。CVVH治疗 2h 15例患者血浆毒鼠     

慢性肾功能衰竭患者血浆食欲素A水平的变化

目的 :初步探讨正常人与慢性肾功能衰竭 (CRF)伴代谢性酸中毒 (代酸 )患者血浆食欲素A浓度的测定方法、浓度变化及其意义。　 方法 :正常健康对照组 39例 ,CRF患者 2 6例。采用层析方法将血浆去蛋白化处理及放射免疫分析法测定两组血浆食欲素A水平 ,并比较CRF组代酸纠正前、后血浆食欲素A及血清瘦素浓度的变化。　 结果 :健康组血浆食欲素A浓度为 (6 17± 3 4 8)ng/L ,血清瘦素浓度为 (6 17± 6 13) μg/L。CRF代酸患者血浆食欲素A浓度于纠酸前、后分别为 (10 6± 5 33)ng/L及 (8 17± 4 6 5 )ng/L。纠酸前血浆食欲素A水平较正常对照组显著增高 (P <0 0 0 5 ) ;纠酸后其水平比纠酸前明显下降 (P <0 0 5 ) ,但与正常对照组相比仍明显升高 (P <0 0 5 )。CRF代酸患者 (纠酸前 )血清瘦素浓度为 (18 6± 18 1) μg/L ,明显高于对照组 (P <0 0 1) ;纠酸后其浓度为(32 0± 2 8 2 ) μg/L ,较纠酸前进一步升高 (P <0 0 5 )。　 结论 :CRF患者血浆食欲素A及血清瘦素水平较正常人明显升高且与酸中毒程度呈正相关 ;碱性药物治疗可使CRF患者血浆食欲素A水平明显下降 ,而血清瘦素水平进一步升高。代酸很可能是抑制瘦素合成或分泌 ,促进血浆食欲素A水平升高的重要因素。     

血浆D-二聚体在老年晚期小细胞肺癌患者化疗前后的变化及临床意义

目的探讨老年晚期小细胞肺癌患者经EP方案化疗前后血浆D-二聚体数值的变化及其与化疗疗效的相关性。方法肺癌组选取50例确诊为Ⅲ或Ⅳ期小细胞肺癌患者,所有患者经EP方案(依托泊苷+顺铂)进行化疗。另选取50例本院健康体检者为正常对照组。采用酶联免疫荧光法测定肺癌组患者化疗前后血浆D-二聚体的含量及体检者体检当日的血浆D-二聚体含量。结果晚期小细胞肺癌患者化疗前血浆D-二聚体水平高于正常对照组,P 0. 001;化疗后疗效评估为有效组患者的D-二聚体含量(0. 67±0. 15)mg/L显著低于化疗前(1. 86±0. 13) mg/L,P 0. 001,稳定组D-二聚体含量(1. 72±0. 20) mg/L较化疗前(1. 85±0. 21) mg/L无显著变化,P 0. 05,进展组D-二聚体含量(2. 71±0. 23) mg/L高于化疗前(1. 87±0. 22) mg/L,P 0. 01。结论血浆D-二聚体水平的高低可作为观察老年晚期小细胞肺癌患者化疗疗效的指标之一。     

急性心肌梗死与不稳定型心绞痛患者血栓前体蛋白和肌酸激酶的检测

为了解检测血栓前体蛋白对急性冠状动脉综合征转归的早期诊断价值 ,5 1例临床确诊冠心病患者分为不稳定型心绞痛和急性心肌梗死两组 ,采用酶联免疫吸附法检测各组血浆中血栓前体蛋白含量 ,采用干化学法同步检测患者血清磷酸肌酸激酶及其同工酶。结果发现 ,急性心肌梗死组 2 5例患者血栓前体蛋白均值为 9.9± 3.9mg L ,不稳定型心绞痛组 2 6例患者血栓前体蛋白均值为 2 .6± 1.7mg L ,前者明显升高 ,差别有显著性意义 (P <0 .0 1) ;急性心肌梗死组磷酸肌酸激酶均值为 5 95± 4 32u L ,磷酸肌酸激酶同工酶均值为 10 1± 74u L ,不稳定型心绞痛亚组磷酸肌酸激酶均值为 137± 4 0u L ,磷酸肌酸激酶同工酶均值为 10± 7u L ,前者亦明显升高 ,差别均有显著意义(分别为P <0 .0 5和P <0 .0 1)。结果提示 ,血栓前体蛋白对急性冠状动脉综合征具有早期诊断和鉴别价值     

过敏性支气管哮喘儿童正常T淋巴细胞表达和分泌的活性调节蛋白基因启动子-28位基因多态性研究

目的　探讨中国儿童正常T淋巴细胞表达和分泌的活性调节蛋白 (RANTES)基因启动子 - 2 8位基因多态性对儿童过敏性哮喘的影响。方法　采用聚合酶链反应 限制性片段长度多态性(PCR RFLP)方法 ,对 10 0例过敏性哮喘儿童 (A组 )的RANTES基因进行多态性分析 ,用化学发光法检测患者血浆总IgE浓度 ,用酶联免疫吸附试验 (ELISA)检测血浆中RANTES浓度 ,用全自动血细胞计数仪进行嗜酸粒细胞计数 ;并与 90名健康儿童 (B组 )进行比较。结果　 (1)RANTES启动子 - 2 8位存在C/G 2种等位基因 ,A组和B组G等位基因频率分别为 19 5 %、10 6 % ,两组间G等位基因频率比较差异有显著性 (P <0 0 5 ) ;(2 )基因型CC、CG、GG的哮喘儿童血浆RANTES浓度分别为 (2 89± 199)ng/L、(5 15± 119)ng/L、(10 71± 138)ng/L ,3种基因型间比较差异有显著性 (P <0 0 1) ;(3)A组血浆总IgE浓度 (以lgIgE表示 )分别为 2 4 5± 0 12、2 77± 0 0 7、3 16± 0 0 9,组间 3种浓度比较差异无显著性 (P >0 0 5 ) ;(4)A组外周血嗜酸粒细胞计数分别为 (2 9± 1 4 )× 10 8/L、(6 4± 0 8)× 10 8/L、(9 9± 2 3)×10 8/L ,组间细胞计数比较差异有显著性 (P <0 0 1)。结论　RANTES启动子 - 2 8C/G基因多态性与儿童过敏性哮喘易感性相关 ,     

快速测定血浆B型钠尿肽鉴别老年人呼吸困难病因的临床观察

目的　评估快速B型钠尿肽 (BNP)测定在老年人呼吸困难诊断及充血性心力衰竭(CHF)近期预后判断的意义。　方法　根据最后诊断将 2 92例老年呼吸困难患者分为 4组 :CHF组( 14 6例 )、肺病组 ( 75例 )、CHF 肺病组 ( 5 2例 )和非CHF 非肺病组 ( 19例 ) ,采用干式快速免疫荧光法定量测定全部患者的血浆BNP浓度。　结果　CHF组BNP水平为 ( 736± 381)ng/L ;肺病组为 ( 6 2± 37)ng/L ;CHF 肺病组为 ( 5 14± 32 7)ng/L ;非CHF 非肺病组为 ( 6 1± 2 9)ng/L。肺病组的BNP水平与非CHF 非肺病组差异无显著性 (P >0 0 5 ) ,其余各组间差异有显著性 (P <0 0 1)。心功能Ⅱ～Ⅳ级〔纽约心脏学会 (NYHA)分级〕的BNP水平分别为 ( 374± 2 2 1)ng/L、( 6 34± 336 )ng/L、( 96 4± 32 1)ng/L ,组间差异有显著性 (P <0 0 1)。BNP值等于 110ng/L为界值时预测CHF的准确性最强。经短期观察发现 ,CHF组 14 6例中有 2 1例发生心血管事件 ,其BNP水平显著高于无心血管事件患者〔( 110 9± 4 31)ng/L和 ( 6 73± 336 )ng/L ,P <0 0 1)〕。　 结论　快速测定血浆BNP有助于鉴别老年人呼吸困难病因 ,是一种判断CHF预后的客观性指标     

急性心肌梗死患者血浆Ⅲ型前胶原氨基末端肽与左室重构及心功能关系的研究

目的　观察急性心肌梗死 (AMI)患者胶原代谢与早期左室重构的相互关系。方法　AMI患者 48例 ,根据二维超声心动图分为重构组与非重构组。应用放免法测定血浆Ш型前胶原氨基末端肽 (PⅢNP)含量 ,并与左室结构及舒缩功能参数做相关分析。结果　两组基线PⅢNP含量相似 ,AMI后患者第 4周、第 12周血浆PШNP含量分别为 (9 2 3± 3 13 ) μg/L、(6 3 3± 2 41) μg/L与第 2天 (5 2 2± 1 19) μg/L及正常对照组 (5 2 1± 1 18) μg/L比较明显升高 (P均 <0 0 1)。重构组第 4周、第 12周血浆PⅢNP含量均明显高于同时间点非重构组含量 (12 73±3 2 3 ) μg/L对 (6 53± 2 61) μg/L ;(6 49± 3 11) μg/L对 (5 49± 2 93 ) μg/L(P均 <0 0 1)。第 4周、第 12周血浆PⅢNP含量与LVESVI有良好的正相关 (r =0 40 5;r =0 513 ,P均 <0 0 1) ,与VE/VA有良好负相关 (r =-0 3 86;r=-0 3 57,P 均 <0 0 1) ,与EF有明显负相关 (r=-0 42 6;r=-0 3 4 6,P 均 <0 0 1)。结论　AMI后早期左室重构过程与心肌胶原代谢增强有关 ,血浆PⅢNP含量可作为反映重构过程的有效指标     

氧化型低密度脂蛋白自身抗体与冠心病的关系

目的研究血清氧化型低密度脂蛋白自身抗体(oxLDL-Ab)、C-反应蛋白(CRP)、血浆纤维蛋白原(FIB)、血小板平均体积(MPV)与冠心病的关系。方法分别测定冠心病组71例、正常对照组66例的血清oxLDL-Ab、CRP、血浆FIB和MPV。结果oxLDL-Ab:冠心病组ox-LDL-IgG(23·3±5·5)U/L,对照组oxLDL-IgG(16·7±5·2)U/L,P<0·001;冠心病组oxLDL-IgM(5·0±2·1)U/L,对照组oxLDL-IgM(1·9±1·3)U/L,P<0·001;CRP:冠心病组(16·5±2·9)mg/L,对照组(3·6±1·4)mg/L,P<0·05;FIB:冠心病组(4·0±0·9)g/L,对照组(2·8±0·3)g/L,P<0·01;MPV:冠心病组(10·3±2·0)×10-15L,对照组(7·8±1·4)×10-15L,P<0·01。结论oxLDL-Ab、CRP、FIB浓度升高和MPV增大是冠心病的重要危险因素。     

冠心病及冠心病等危症患者血浆脂联素、氮端脑利钠肽前体的测定及相关性研究

目的 探讨测定血浆脂联素(adiponectin,APN)与氮端脑利钠肽前体(N-terminal pro brain natriuretic peptide,NT-proBNP)浓度在反映动脉粥样硬化范围和冠状动脉狭窄程度的临床意义.方法 将符合入选标准的140例患者根据检查结果 分为4组:冠状动脉性心脏病(冠心病)合并等危症组(39例)、单纯冠心病组(42例),冠心病等危症组(24例)以及对照组(35例).采用定量的酶联免疫测定法(ELISA法)测定血浆APN浓度,采用RocheElecsys 1010自动分析仪测定血浆NT-proBNP浓度,所得结果 进行统计学分析.结果 冠心病等危症组、冠心病组和冠心病合并等危症组与对照组比较,血浆APN浓度依次逐步降低,差异有统计学意义[(9.34±0.58)mg/L, (6.59±0.15)mg/L, (3.01±0.22)mg/L比(13.51±0.93)mg/L;F=3.625,P<0.05).冠心病等危症组、冠心病组和冠心病合并等危症组与对照组比较,血浆NT-proBNP浓度显著升高,差异有统计学意义[(331.93±106.76)pg/mL, (320.82±78.85)pg/mL,(438.58±106.01)pg/mL比(65.60±12.03)pg/mL;F=74.082,P<0.01).直线相关分析显示,血浆APN浓度与血浆NT-proBNP浓度负相关(r=-0.217,P=0.01);Gensini积分与血浆APN浓度呈负相关(r=-0.522,P<0.001),与血浆NT-proBNP浓度呈正相关(r=0.257,P=0.002).结论 同时测定血浆APN浓度和血浆NT-proBNP浓度有助于更好地预测动脉粥样硬化的范围和反映冠状动脉狭窄的程度.     

Increased plasma levels of tissue factor pathway inhibitor-activated factor X complex in patients with disseminated intravascular coagulation

Plasma levels of tissue factor pathway inhibitor (TFPI)-activated factor Xa (FXa) complex were measured in patients with disseminated intravascular coagulation (DIC), pre-DIC, and DIC. Plasma levels of plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were significantly higher in patients with DIC than in those with pre-DIC or non-DIC; the levels of these hemostatic markers were significantly higher in patients with pre-DIC than in those with non-DIC. Plasma levels of thrombin-antithrombin complex (TAT) were significantly higher in patients with DIC or pre-DIC than in those with non-DIC. Plasma levels of tissue factor (TF), total TFPI, free TFPI, and TFPI-Xa complex were significantly higher in patients with DIC than in those with non-DIC. Plasma levels of TFPI-Xa complex were significantly increased in patients with pre-DIC as compared to those with non-DIC; however, plasma free TFPI levels were significantly decreased in patients with pre-DIC as compared to those with non-DIC. These findings suggest that free TFPI might be consumed in the pre-DIC state, thereby confirming the activation of the extrinsic pathway. Plasma levels of TFPI-Xa complex were significantly correlated with TF, free TFPI, and total TFPI. Increased plasma TFPI-Xa complex levels might be useful for the diagnosis of DIC or pre-DIC, particularly that occurring by activation of the extrinsic pathway of blood coagulation.     

Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation

Plasma-soluble fibrin monomer (SFM) level in patients with disseminated intravascular coagulation (DIC) was significantly higher than the level in patients with pre-DIC or in non-DIC patients, and the level in patients with pre-DIC was significantly higher than that in non-DIC patients. There was no significant difference in plasma SFM levels among various diseases underlying DIC. Plasma SFM level in patients with good outcome was significantly decreased after treatment for DIC. The sensitivity of fibrin degradation products and platelet number was high for DIC, but not for pre-DIC. The sensitivity of thrombin-antithrombin III complex, plasmin-plasmin inhibitor complex, and SFM was high for both DIC and pre-DIC. The specificity of these markers was also high. Receiver operating characteristic analysis suggests that plasma SFM level could be the most useful marker for the diagnosis of both DIC and pre-DIC. © 1996 Wiley-Liss, Inc.     

Hemostatic molecular markers before the onset of disseminated intravascular coagulation

We retrospectively measured various hemostatic markers in 240 patients with disseminated intravascular coagulation (DIC) before the onset of DIC and in 110 non-DIC patients, and examined their usefulness for the diagnosis of pre-DIC. Changes in prothrombin time ratio and fibrinogen levels were not significant before the onset of DIC. The plasma levels of fibrinogen and fibrin degradation products before the onset of DIC were increased and the platelet count was gradually reduced in nonleukemic patients; these changes were already significant in the non-DIC state. The plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were increased before the onset of DIC. In leukemic patients, the plasma levels of sFM on day 5, those of TAT on day 3, and D-dimer on day 1, were significantly increased before the onset of DIC. The levels of most hemostatic markers 7 days before the onset of DIC were not different from those observed in the non-DIC state. In nonleukemic patients, only D-dimer, sFM, and TAT levels were significantly increased 7 days before the onset of DIC compared with values in the non-DIC state. The positive rate of hemostatic markers for the diagnosis of DIC, TAT, and PPIC were high during the pre-DIC and non-DIC groups. The plasma levels of sFM and D-dimer were low in non-DIC and increased gradually during the pre-DIC state. These findings suggest that hemostatic molecular markers such as sFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC, although their cutoff values were different among various diseases.     

Diagnosis of disseminated intravascular coagulation by hemostatic molecular markers

In the present study, the positive rate of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), and D-dimer for the diagnosis of disseminated intravascular coagulation (DIC) was evaluated. The study comprised 307 patients with DIC, 123 with pre-DIC, and 121 with non-DIC. Plasma levels of TAT, PPIC, sFM, and D-dimer were significantly higher in DIC and pre-DIC patients than in non-DIC patients. In DIC patients, the positive rate of sFM was high and that of D-dimer was low; the positive rate of PPIC was higher in patients with hematopoietic malignancy than in those without this disease. In pre-DIC patients, the positive rate of all markers was low (<0.16), and the positive rate of PPIC was relatively high. In non-DIC patients, the positive rate of all hemostatic markers was low (<0.16), that of sFM being the lowest. Scoring the positive rate of TAT, PPIC, and sFM disclosed the following results: 72% of DIC patients had three or more points, 17.6% of pre-DIC patients had three or more points, and almost all (96.6%) non-DIC patients had two or less points. Scoring the positive rate of TAT, PPIC, and D-dimer disclosed the following results: 52.9% of DIC patients and 27.4% of pre-DIC patients had three or more points and almost all (96.7%) non-DIC patients had 2 or less points. These data suggest that the combination of TAT, PPIC, and sFM is useful for making the diagnosis of DIC.     

Increased truncated form of plasma tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation

To evaluate that the relationship between the truncated form of tissue factor pathway inhibitor (TFPI) and the stage of disseminated intravascular coagulation (DIC), we measured the plasma levels of tissue factor (TF) antigen and the intact and truncated forms of TFPI antigens in 41 patients with DIC, 12 with pre-DIC, and 20 with non-DIC. The plasma TF and total TFPI antigen levels were significantly higher in patients with DIC than in non-DIC patients. Plasma levels of intact TFPI antigen in the pre-DIC groups were significantly lower than in the non-DIC and DIC groups. The truncated form of TFPI antigen levels in DIC patients were significantly increased compared with those in non-DIC and pre-DIC patients. The fact that the intact form of TFPI was decreased in pre-DIC patients compared with that in non-DIC patients, suggests that it is consumed in the pre-DIC state and that hypercoagulability occurs in pre-DIC patients. The increased level of the truncated form of TFPI in DIC patients may be attributed to proteolysis of the intact form of TFPI in these patients. The increased level of the truncated form of TFPI may be a useful index for the diagnosis of DIC. Am. J. Hematol. 60:94–98, 1999. © 1999 Wiley-Liss, Inc.     

Hemostatic study before onset of disseminated intravascular coagulation

Early diagnosis is necessary for the treatment of disseminated intravascular coagulation (DIC), but criteria for the stage preceding the diagnosis of DIC (pre-DIC) have not yet been established. To clarify hemostatic abnormalities that occur before the onset of DIC, we performed hemostatic studies in 117 patients within at least a week before the onset of DIC (pre-DIC), in 237 patients with DIC, and in 50 patients without DIC or pre-DIC (non-DIC). Levels of FDP, PT, and fibrinogen, and platelet counts were significantly abnormal after the onset of DIC, but not before. Thrombin-antithrombin III complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), and FDP-D-dimer levels were significantly higher before the onset of DIC compared to the non-DIC patients. Hemostatic abnormalities were observed within a week before the onset of DIC. Monitoring the plasma levels of TAT, PIC, and FDP-D-dimer might be useful for the diagnosis of a pre-DIC condition.     

Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.     

Plasma level of tumor necrosis factor in disseminated intravascular coagulation

The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascular coagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC.     

Monoclonal antibody specific for tissue factor pathway inhibitor-factor Xa complex: its characterization and application to plasmas from patients with disseminated intravascular coagulation and pre-disseminated intravascular coagulation.

Tissue factor pathway inhibitor (TFPI), a Kunitz-type protease inhibitor with three tandem inhibitory domains (K1, K2 and K3), inhibits the initial reactions of the extrinsic blood coagulation pathway through its K1 and K2 domains. We prepared and characterized a monoclonal antibody (Mab8-1) against TFPI-factor Xa (TFPI-Xa) complex. The reactivities of Mab8-1 toward TFPI-Xa complex, TFPI without C-terminal (TFPI-C)-Xa complex, K1K2-Xa complex and K2K3-Xa complex were examined using a surface plasmon resonance analysis (Biacore). The Biacore system allowed a quantitative analysis of antibody-antigen interaction, in real time, from which the association and dissociation rate constants could readily be obtained. The bindings of Mab8-1 to TFPI-Xa complex, TFPI-C-Xa complex and K2K3-Xa complex were each concentration-dependent. However, no binding of Mab8-1 to the K1K2-Xa complex was observed. The binding of Mab8-1 to TFPI or Xa was also not observed. These results suggested that the epitope for Mab8-1 was exposed in the K3 domain of TFPI, which was generated by the conformational change after the formation of TFPI-Xa complex. We then developed an enzyme-linked immunosorbent assay method specific for TFPI-Xa complex using Mab8-1, and we used this assay to measure plasma levels of TFPI-Xa. The normal range assessed from analyses of plasma from 30 normal healthy volunteers was 17.7-66.7 with a mean of 35.5 +/- 11.7 pmol/l. In order to asses the clinical implication of TFPI-Xa complex in the plasma of patients with thrombotic disorders, plasma concentrations were measured in 37 patients with disseminated intravascular coagulation (DIC) caused by a variety of underlying diseases. The TFPI-Xa antigen levels were significantly higher in the patients with DIC (51.9 +/- 21.6 pmol/l) and the 36 patients with pre-DIC (55.1 +/- 20.2 pmol/l) than in the 137 non-DIC patients (37.9 +/- 13.1 pmol/l). In the patients with DIC or pre-DIC, there was no significant correlation between TFPI-Xa complex and the elevated levels of thrombin-antithrombin complex, plasmin-alpha2 plasmin inhibitor complex, D-dimer, soluble fibrin monomer, soluble thrombomodulin or tissue factor. These data indicate that the plasma level of TFPI-Xa seems to be a novel independent molecular marker of DIC and pre-DIC.     

Measurement of thrombus precursor protein in septic patients with disseminated intravascular coagulation and liver disease

BACKGROUND AND OBJECTIVES: Disseminated intravascular coagulation (DIC) is a syndrome characterized by systemic intravascular activation of coagulation leading to the widespread deposition of fibrin in the circulation. Therefore, the determination of soluble fibrin is crucial for the diagnosis of DIC. Thrombus precursor protein (TpP) levels can be determined as a measure of soluble polymers, which are the immediate precursors of insoluble fibrin. In this study, the potential diagnostic usefulness of this TpP test was investigated in septic patients with DIC and liver diseases. DESIGN AND METHODS: TpP analysis was performed on 155 plasma samples from 95 septic patients, including 72 patients without liver disease and 23 patients with liver diseases, and on 42 plasma samples from normal healthy subjects. The study population was subdivided according to three phases of DIC described as compensated, decompensated and full-blown DIC. Plasma TpP level was determined using a new assay, the TpPTM (American Biogenetic Sciences, USA), which is based on an ELISA method. RESULTS. Septic patients with decompensated (16.1 9.1 mg/mL) or full- blown (20.9 12.4 mg/mL) phases of DIC had significantly higher TpP levels than those with the compensated (5.6 6.2 mg/mL) phase of DIC or healthy controls (2.9 1.6 mg/mL). In septic patients with liver disease, a significant difference was found between the TpP levels of patients with full- blown DIC (21.6 10.6 mg/mL) and those of patients with the decompensated phase (13.4 6.5 mg/mL). Plasma TpP levels correlated significantly with other DIC parameters including platelet count, fibrinogen, antithrombin and TAT, and correlated weakly with D-dimer. INTERPRETATION AND CONCLUSIONS: Our findings indicate that septic patients who developed decompensated or full-blown DIC or organ dysfunction have significantly higher plasma levels of TpP, and suggest the potential usefulness of the TpP assay as an aid to the diagnosis of DIC in cases of sepsis and liver disease complicated by sepsis.