Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula / 中国天然药物

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group (M), QFOL-treated group (Q) and the control group (C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins (DEPs) were identified (15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B (FpB) and heparin cofactor II (HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the FpB level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.

Label-free quantitative proteomics reveals fibrinopeptide B and heparin cofactor II as potential serum biomarkers in respiratory syncytial virus-infected mice treated with Qingfei oral liquid formula / 中国天然药物

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections. Qingfei oral liquid (QFOL), a traditional Chinese medicine, is widely used in clinical treatment for RSV-induced pneumonia. The present study was designed to reveal the potential targets and mechanism of action for QFOL by exploring its influence on the host cellular network following RSV infection. We investigated the serum proteomic changes and potential biomarkers in an RSV-infected mouse pneumonia model treated with QFOL. Eighteen BALB/c mice were randomly divided into three groups: RSV pneumonia model group (M), QFOL-treated group (Q) and the control group (C). Serum proteomes were analyzed and compared using a label-free quantitative LC-MS/MS approach. A total of 172 protein groups, 1009 proteins, and 1073 unique peptides were successfully identified. 51 differentially expressed proteins (DEPs) were identified (15 DEPs when M/C and 43 DEPs when Q/M; 7 DEPs in common). Classification and interaction network showed that these proteins participated in various biological processes including immune response, blood coagulation, complement activation, and so forth. Particularly, fibrinopeptide B (FpB) and heparin cofactor II (HCII) were evaluated as important nodes in the interaction network, which was closely involved in coagulation and inflammation. Further, the FpB level was increased in Group M but decreased in Group Q, while the HCII level exhibited the opposite trend. These findings not only indicated FpB and HCII as potential biomarkers and targets of QFOL in the treatment of RSV pneumonia, but also suggested a regulatory role of QFOL in the RSV-induced disturbance of coagulation and inflammation-coagulation interactions.

Plasma heparin cofactor II activity correlates with the incidence of in-stent restenosis after the intervention of arteriosclerosis obliterans in lower extremity / 中南大学学报(医学版)

OBJECTIVE@#To explore the relationship between activity of plasma heparin cofactor II (HC II) and the incidence of in-stent restenosis aft er the intervention of arteriosclerosis obliterans in lower extremity.@*METHODS@#A total of 62 patients with arteriosclerosis obliterans in lower extremity underwent femoropopliteal stent implantation. They were divided into 2 groups: A high HC II activity group (≥100%, n=40) and a low HC II activity group (<100%, n=22). All patients filled in follow up tables and conducted body examination. Possible risk factors resulting in restenosis were collected. Patients were followed up for 6 months after femoropopliteal stent implantation.@*RESULTS@#Baseline clinical characteristics were not significantly different between the 2 groups. The degree and incidence of angiographic restenosis at the end of the 6th month after the implantation in the high HC II activity group were all significantly lower than those in the low HC II activity group (P<0.05). Multivariate analysis demonstrated that high plasma HC II activity was an independent factor in reducing the incidence of angiographic restenosis (OR=0.982, P=0.048, 95%CI, 0.966, 0.998).@*CONCLUSION@#High plasma HC II activity is an independent factor in reducing the degree of in-stent restenosis. The lower the plasma HC II activity, the severer the degree of in-stent restenosis.

Inherited Thrombophilia

Inherited thrombophilia has been an area of intense clinical research since the description of deficiency of antithrombin III [1965], protein C [1981] and protein S [1985]. It is now possible to identify the inherited thrombophila in about 50% of cases of venous thrombosis. Certain components of inherited thrombophilia have a major impact on anticoagulant therapy, so basic knowledge about them is necessary in every medical speciality

Heparin cofactor II (HCII) activity and antigen assay and their significance in thrombotic diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the plasma HCII activity and antigen level variations and their relationship with arterial and deep venous thrombotic diseases.</p><p><b>METHODS</b>Seventy-five patients with brain infarction (BI), 50 myocardial infarction (MI), 36 deep venous thromboembolic disease (DVT) and 50 healthy controls were entered in this study. Plasma HCII activity was measured with chromogenic substrate method and the HCII antigen level by Western blotting assay. Plasma antithrombin (AT) activity was detected for the HCII deficiency individuals with DVT using chromogenic substrate method.</p><p><b>RESULTS</b>There was no significant difference in the mean plasma HCII activity and antigen levels between BI group [(99.97 +/- 21.14)% and 0.96 +/- 0.24], MI group [(98.18 +/- 29.35)% and 0.95 +/- 0.20] and healthy controls [(96.80 +/- 20.11)% and 0.93 +/- 0.19]. The plasma HCII activity and antigen concentrations in patients with DVT [(89.57 +/- 17.12)% and 0.87 +/- 10.18] tended to be decreased as compared with healthy controls, but they were not significant. No significant difference was found for the prevalence of HCII deficiency between patient groups and control group. The HCII deficiency individuals with DVT had normal AT activity and fibrinogen concentration.</p><p><b>CONCLUSIONS</b>Plasma HCII deficiency may not be the risk factor for arterial thrombosis in the Han population of Hunan Chinese. It is needed to further confirm if decreased plasma HCII is correlated with venous thrombosis.</p>

Coagulopathies and Ischemic Stroke

The etiology of ischemic stroke remains undetermined in nearly 40% of patients despite extensive evaluations. Coagulopathies associated with cerebrovascular ischemia may be familial or acquired and account for 4% of all strokes. The four important naturally occurring circulation proteins that inhibit coagulation are protein C, protein S, antithrombin III, and heparin cofactor II. A carefully balanced interaction between these proteins and normal vascular endothelial cells comprise a major barrier inhibiting thrombosis. The true deficiencies of these proteins are usually inherited although many conditions such as DIC, malignancy, malnutrition, infection, and neutropenia can be associated with acquired deficiencies. Although some data suggest an association between arterial strokes and the deficiency of these proteins in young adults, cerebral venous thrombosis and venous infarcts gave been reported far more commonly with deficiencies of any of these proteins. The understanding of the molecular events underlying coagulation has improved in recent years. This has led to development of specific assays that can identify genetic abnormalities which can cause coagulopathies. Although the technology has improved the fundamental approach to the patient has not changed. A primary care physician requires a basic knowledge of the principles of blood coagulation so as to treat patients with simple problems and refer patients with more unusual or complex disorders on to the specialist. The recognition that hypercoagulable states are sometimes found in ischemic stroke patients has led to testing for these rare conditions. Coagulopathies related to protein C, protein S, or antithrombin III deficiencies, activated protein C resistance, prothrombin gene mutation, anticardiolipin antibodies, or lupus anticoagulant can be evaluated with various coagulation testing strategies.

Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

Dermatan sulfates and heparin, similar to the mammalian glycosaminoglycans, but with differences in the degree and position of sulfation were previously isolated from the body of the ascidian Styela plicata and Ascidia nigra. These differences produce profound effects on their anticoagulant properties. S. plicata dermatan sulfate composed by 2-O-sulfatedalpha-L-iduronic acid and 4-O-sulfated N-acetyl-beta-D-galactosamine residues is a potent anticoagulant due to a high heparin cofactor II activity. Surprisingly, it has a lower potency to prevent thrombus formation on an experimental model and a lower bleeding effect in rats than the mammalian dermatan sulfate. In contrast, A. nigra dermatan sulfate, also enriched in 2-O-sulfated alpha-L-iduronic acid, but in this case sulfated at O-6 of the N-acetyl-beta-D-galactosamine units, has no in vitro or in vivo anticoagulant activity, does not prevent thrombus formation but shows a bleeding effect similar to the mammalian glycosaminoglycan. Ascidian heparin, composed by 2-O-sulfated alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (75 percent) and alpha-L-iduronic acid, N- and 6-O-sulfated glucosamine (25 percent) disaccharide units has an anticoagulant activity 10 times lower than the mammalian heparin, is about 20 times less potent in the inhibition of thrombin by antithrombin, but has the same heparin cofactor II activity as mammalian heparin

Trombocitopenia inducida por heparina en Argentina. ¿Una entidad de tratamiento diferente que en el resto del mundo? / Heparin induced thrombocytopenia. ¿A different treatment in Argentine?

La trombocitopenia inducida por heparina de tipo II tiene un orígen inmunológico y se caracteriza por el descenso de las cifras plaquetarias, generalmente después del 5§ día de exposición a la droga y una paradójica y severa tendencia trombofílica adquirida. El cuadro se resuelve sólo con la suspensión de la administración de heparina. Requiere un alto índice de sospecha pues las manifestaciones clínicas del mismo pueden estar enmascaradas por el proceso original que resultó en la indicación de heparina en forma profiláctica o terapéutica. El artículo resume las manifestaciones clínicas y los estudios de laboratorio confirmatorios. Se enfatiza en el tratamiento la particular situación de carencia que padece esta entidad en nuestro país, ya que no se cuenta con la provisión regular de los tres agentes terapéuticos de eficacia reconocida: hirudina, danaparoid o argatroban.

Avaliaçäo da atividade da antitrombina-III na Doença Hipertensiva Específica da Gravidez (DHEG) / Antithrombin-III activity in preeclampsia

A antitrombina-III (AT-III) constitui um anticoagulante natural sintetizado no fígado capaz de inibir a trombina (fator IIa), os fatores Xa, IXa, XIa, XIIa, VIIa ligado ao fator tissular, a calicreína e a plasmina. A afinidade da AT-III pela trombina é aumentada, em cerca de 1000 vezes, na presença de heparina ou de sulfato de heparan. A Doença Hipertensiva Específica da Gravidez (DHEG), na sua forma pura, catacteriza-se pelo aparecimento em grávida normotensa, após a vigésima semana de gestaçäo, da tríade sintomática: hipertensäo, proteinúria e edema. A DHEG é uma doença incurável, exceto pela interrupçäo da gravidez e pode evoluir para quadros ainda mais complexos como eclâmpsia, síndrome HELLP (hemolysis, elevated liver enzyme, low platelets) ou CID (coagulaçäo intravascular disseminada). O objetivo desse trabalho foi avaliar a atividade plasmática da AT-III com o agravamento da doença. Admitindo-se uma coagulopatia de consumo na DHEG, como sugere a literatura, era de se esperar níveis reduzidos de AT-III. Estudos recentes têm sugerido que outro anticoagulante natural, o co-fator II da heparina (HC II), possui uma importância maior na neutralizaçäo da trombina durante a gestaçäo , o que explicaria a ausência de alteraçäo da atividade da AT-III na DHEG, encontrada neste trabalho. Considerando esse resultado e os relatos da literatura, é possível inferir que a diferenca entre gestantes saudáveis e apresentando DHEG seja mais pronunciada para o HC II que para a AT-III. Estudos posteriores com a avaliaçäo simultânea de ambos anticoagulantes, ao longo da gravidez, tornam-se necessários para elucidar a questäo

Cofactor II de la heparina (HCII), un inhibidor de trombina cuyo rol fisiologico no esta completamente esclarecido / Heparin cofactor II, a thrombin inhibitor with a still unclarified physiologic role

El Cofactor II de la Heparina (HCII) es una proteína perteneciente al sistema de coagulación que inhibe específicamente trombina, processo que es potenciado por acción de los glicosaminoglicanos dermatán sulfato y heparina. Hasta el momento las deficiencias congénitas de HCII encontradas en forma aislada no están asociadas con eventos trombóticos, sí desarollan eventos trombóticos cuando están asociadas a otros factores predisponentes. Se observó disminución en los niveles de HCII en hepatopatías, coagulación intravascular diseminada, en anemia drepanocítica, encontrándose niveles elevados en embarazo a término y por el uso de contraceptivos orales. En el laboratorio realizamos el dosaje del HCII en la población normal de la ciudad de Buenos Aires, en diversas patologías como sepsis, quemados , anticoagulados con dicumarínicos y con heparina, diabéticos, hiperhomocisteinemia, observándose valores disminuidos principalmente en sepsis y pacientes diabéticos. El HCII es una glicoproteína que participa en la inhibición de trombina pero cuyo rol fisiológico no está completamente esclarecido. Es probable que el HCII inhiba trombina en el espacio extravascular, y está relacionado con la regulación de procesos inflamatorios y de reparación tisular.

Antithrombin III, heparin cofactor II and histidine-rich glycoprotein in patients with pulmonary embolism

In seventy-two patients hospitalized for clinical suspicion of pulmonary embolism [PE], level of antithrombin III [AT III], heparin cofactor II [HC II] and histidine-rich glycoprotein [HRGP] were determined. Forty-four patients were positive for PE and twenty-nine received standard heparin. HC II and HRGP did not show any statistically significant variation between patients who were positive or negative for PE. Moreover, presence or absence of heparin therapy in these patients did not modify the level of these two proteins. In contrast, AT III showed a statistically significant reduction in PE than non-PE. Since AT III is one of the most powerful inhibitors against serine protease enzymes of coagulation cascade, it is possible that low levels in patients with PE could be considered as the expression of consumption to prevent further thrombus formation