Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

股骨多段闭合骨折病人术前凝血功能的变化

目的 探讨股骨多段闭合骨折病人术前凝血功能的变化。方法 选择创伤股骨多段闭合骨折后当天入院的病人20例,年龄19-45岁,ASA Ⅰ级,为试验组(Ⅰ组);选择健康成年人15人,年龄21-39岁,作为对照组(Ⅱ组);Ⅱ组于清晨空腹采上肢静脉血标本,Ⅰ组病人入院后于骨折的第2天、第6天(手术当天清晨)空腹采上肢静脉血样本,检测血栓弹力图(TEG)指标[R时间、K时间、α角、血栓最大幅度(MA)、血栓硬度(G)]、D-二聚体浓度(D-Di)、血小板计数(PLC)及血小板聚集率(PAgR)的变化。结果 Ⅱ组TEG指标、D-Di、PLC及PAgR均在正常范围。与Ⅱ组比较,Ⅰ组骨折后第2天,K时间缩短(P<0.05),α角、MA、G及D-Di增高(P<0.01);骨折后第6天,R时间缩短(P<0.05),α角、MA、G、D-Di、PLC及PagR增高(P<0.01)。与骨折后第2天比较,Ⅰ组骨折后第6天MA、G、PLT及PAgR增高(P<0.05或0.01)。结论 病人创伤骨折后凝血功能24 h内增强,随时间的延长至术日呈高凝状态,应加强术中管理,并采取相应措施预防术中静脉血栓的发生。     

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.     

Influence of heparin on fibrinogen and D-dimer plasma levels in acute myocardial infarction treated with streptokinase

The purpose of this study was to investigate whether, to whatextent, and through which mechanisms intravenous heparin, administeredbefore and after streptokinase, affects the plasma levels ofD-dimer and fibrinogen in myocardial infarction. Data concerningmortality and incidence of coronary recanalization in patientsreceiving heparin and thrombolytic therapy after acute myocardialinfarction are controversial; furthermore, the mechanisms throughwhich heparin acts in combination with thrombolytic therapyare unclear. Thirty-eight patients with acute myocardial infarctiontreated with streptokinase were considered. Nineteen of themreceived, immediately before the beginning of thrombolytic treatment,a bolus of heparin (100 U. kg¹ intravenously) and, 2 h later,intravenous heparin in doses raising the partial thromboplastintime to 2-2.5 times the normal value (Group 1); the remaining19 did not receive anticoagulant treatment (Group 2). Multipledeterminations of plasma D-dimer and fibrinogen levels wereobtained in all patients before, and in the seven days followingthrombolytic treatment. Six hours after streptokinase, fibrinogendecreased from 304 ± 34 to 61 ± 34 mg. dt¹ inGroup 1 and from 312 ± 29 to 38 ±21 mg. dt¹ inGroup 2 (P<002 versus Group 1). The same difference betweengroups persisted at the 12th and at the 18th hour. D-dimer values,from 0-5 ± 01 \ig. dl¹ in Group 1 and 04 ±01 fig.dt¹ in Group 2, increased at the 1st hour to 37.2 ± 36.5fig. dt¹ and 52.2 ± 39.8 µg. dl¹, respectively.A peak value was reached in both groups at the 6th hour, whichwas followed by a slow decrease. A significant difference betweenthe two groups (P<0.05) was observed at the 1st, 2nd, 4thand 6th hour. An inverse correlation between maximal changesof fibrinogen and of D-dimer was found in both groups (r= 0.89,P<0.001 in Group 1; r=-0.81, P<0.001 in Group 2). The relationship between D-dimer and fibrinogen variations afterstreptokinase and changes induced by heparin, support the hypothesisthat the decrease of fibrinogen, following thrombolysis, isnot only the consequence of its direct degradation, but alsothe result of its transformation by streptokinase into fibrin,fibrin cross-linked (with facilitation of thrombogenic condition)and then into the stable catabolite, D-dimer. These data confirma thrombogenic effect of streptokinase therapy; this tendencycan be limited by prompt use of high doses of heparin.     

Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.     

Relationship of actin filament assembly to clearance of fibrinogen gold, GPIIb-IIIa complexes on spread platelets

Abstract. The present study has evaluated the influence of high concentrations of cytochalasins B and E on the detergent-resistant actin levels in fully spread platelets by PAGE gel electrophoresis, and the effects of the two inhibitors of new actin filament assembly on translocation of fibrinogen gold (Fgn/Au) labelled GPIIb-IIIa receptors on the surface-activated cells. Concentrations of 10^{- 4}m and 10^-5 m cytochalasin B and E reduced detergent-resistant actin in fully spread platelets to levels present in resting discoid platelets in suspension. Despite reduction of actin filaments to levels in resting cells, cytochalasin B did not prevent translocation of Fgn/Au from platelet margins into channels of the open canalicular system (OCS). Similar concentrations of cytochalasin E completely blocked translocation of receptor-ligand complexes and produced a patching phenomenon not observed in previous studies. Rinsing of the spread cells to remove cytochalasin, followed by incubation of the treated platelets in Hank's buffered salt solution (HBSS) restored levels of detergent-resistant actin to those found in untreated, spread platelets. Resting grids of 10 ⁵ m cytochalasin E-treated platelets on drops of HBSS for 15min restored their ability to clear FGN/Au linked to GPIIb-IIIa from exposed surfaces to the OCS, but 10^-4 m cytochalasin E-treated cells remained anergic after incubation on drops of HBSS. Thus a fully assembled cytoplasmic actin filament cytoskeleton does not appear to be essential for translocating receptor-ligand complexes on the platelet surface to the OCS, nor does its presence guarantee that the ability to clear GPIIb-IIIa receptors will be restored.     

Thromboresistant properties of hydrophilic gels

The thromboresistant properties of hydrophilic gels based on copolymers of nitrogen-containing heterocyclic vinyl compounds with vinyl monomers were investigated. The hydrophilic gels were shown to prevent adsorption of fibrinogen, activation of procoagulants, and adhesion of platelets. Hydrogen surfaces possess selective affinity for plasma albumin. The authors consider that the thromboresistant effect of hydrophilic gels is due to the competitive action of plasma albumin. Modification of hydrophilic gels increases their thromboresistant properties.Laboratory of Thromboresistant Materials, Institute of Transplantation of Organs and Tissues, Ministry of Health of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 296–298, March, 1980.     

纤维蛋白原Bβ链基因-1420G/A、-993C/T和-854G/A多态性与冠状动脉粥样硬化性心脏病的关联研究

目的调查健康人和冠状动脉粥样硬化性心脏病(简称冠心病)患者的纤维蛋白原B(fibrino-genB,FGB)β基因-1420G/A、-993C/T和-854G/A的基因多态性频率分布,以及与血浆Fg水平的关系。方法应用等位基因特异性PCR扩增技术和限制性片段长度多态性技术对186例冠心病患者和149名健康对照者进行分析。比浊法测定血浆Fg浓度。结果等位基因频率-1420A在冠心病组为0.33,在对照组为0.26,冠心病组明显比对照组升高,两者比较差异有统计学意义(P<0.05)。等位基因频率-993T和-854A在两组之间无差别。Logistic回归分析显示β-1420G/A与冠心病相关(OR=1.922,P=0.003)。冠心病组血浆Fg水平(3.87±1.75)g/L较健康人组(3.10±0.77)g/L明显升高,且差异有统计学意义(P<0·05)。结论纤维蛋白原Bβ-1420G/A可能与冠心病发病相关联。