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Bob Siegerink - One of the best experts on this subject based on the ideXlab platform.

  • intrinsic Coagulation pathway history of headache and risk of ischemic stroke
    Stroke, 2019
    Co-Authors: Hendrikus J A Van Os, Marieke J H Wermer, Frits R Rosendaal, Jose W P Goversriemslag, Ale Algra, Bob Siegerink
    Abstract:

    Background and Purpose- Hypercoagulable states in migraine patients may play a role in the pathophysiology underlying the association between migraine and ischemic stroke. This study aims to provide more insight into the potential association of headache, ischemic stroke, and the intrinsic Coagulation pathway. Methods- We included patients from the RATIO study (Risk of Arterial Thrombosis in Relation to Oral Contraceptives), a Dutch population-based case-control study including young women (age <50) with ischemic stroke and healthy controls. We defined a headache group based on a questionnaire on headache history. Intrinsic Coagulation Proteins were measured through both antigen levels (FXII, FXI, prekallikrein, HK [high molecular weight kininogen]) and Protein activation, determined by measuring activated Protein complex with C1esterase-inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin-inhibitor (FXIa-AT-INH). We calculated adjusted odds ratios and performed an interaction analysis assessing the increase in stroke risk associated with high levels of intrinsic Coagulation and history of headache. Results- We included 113 ischemic stroke cases and 598 healthy controls. In total, 134 (19%) patients had a history of headache, of whom 38 were cases and 96 controls. The combination of headache and high intrinsic Coagulation Protein levels (all but FXII antigen level and both FXIa-inhibitors) was associated with an increase in ischemic stroke risk higher than was expected based on their individual effects (adjusted odds ratio FXI antigen level alone: 1.7, 95% CI, 1.0-2.9; adjusted odds ratio headache alone: 2.0, 95% CI, 1.1-3.7; combination: 5.2, 95% CI, 2.3-11.6) Conclusions- Headache and high intrinsic Coagulation Protein levels may biologically interact, increasing risk for ischemic stroke.

  • intrinsic Coagulation activation and the risk of arterial thrombosis in young women results from the risk of arterial thrombosis in relation to oral contraceptives ratio case control study
    Circulation, 2010
    Co-Authors: Bob Siegerink, Frits R Rosendaal, Jose W P Goversriemslag, Ten H Cate, Ale Algra
    Abstract:

    Background—Classically, intrinsic Coagulation Proteins are thought to have a minor role in hemostasis. Recently, these Proteins, especially FXII, were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic Coagulation Proteins in young women and the effect of oral contraceptive use on this association. Methods and Results—The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic Coagulation Protein activation was determined by measuring activated Protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were...

  • Intrinsic Coagulation Activation and the Risk of Arterial Thrombosis in Young Women Results From the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Case-Control Study
    Circulation, 2010
    Co-Authors: Bob Siegerink, Frits R Rosendaal, José W. P. Govers-riemslag, H. Ten Cate, Ale Algra
    Abstract:

    BACKGROUND: Classically intrinsic Coagulation Proteins are thought to have a minor role in hemostasis. Recently these Proteins especially FXII were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic Coagulation Proteins in young women and the effect of oral contraceptive use on this association. Methods and Results-The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic Coagulation Protein activation was determined by measuring activated Protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH FXIa-C1-INH Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were calculated with logistic regression. High levels of Protein activation (>90th percentile of controls) showed an increased risk of ischemic stroke: FXIIa-C1-INH (OR 2.1; 95% CI 1.3 to 3.5) FXIa-C1-INH (OR 2.8; 95% CI 1.6 to 4.7) FXIa-AT-INH (OR 2.3; 95% CI 1.4 to 4.0) and Kallikrein-C1 (OR 4.3; 95% CI 2.6 to 7.2). If anything myocardial infarction risk was only increased by Kallikrein-C1-INH (OR 1.5; 95% CI 0.9 to 2.5). Oral contraceptive use further increased the risks. Conclusions-High levels of activated Proteins of the intrinsic Coagulation system are associated with arterial thrombosis whereas the strength of these associations differs for myocardial infarction and ischemic stroke. This contradicts similar analyses among men in the Northwick Park Heart Study. Together with the finding that oral contraceptive use further increases the risks the question of whether the role of intrinsic Coagulation Proteins in the pathogenesis of arterial thrombosis is sex-specific is raised.

Ale Algra - One of the best experts on this subject based on the ideXlab platform.

  • intrinsic Coagulation pathway history of headache and risk of ischemic stroke
    Stroke, 2019
    Co-Authors: Hendrikus J A Van Os, Marieke J H Wermer, Frits R Rosendaal, Jose W P Goversriemslag, Ale Algra, Bob Siegerink
    Abstract:

    Background and Purpose- Hypercoagulable states in migraine patients may play a role in the pathophysiology underlying the association between migraine and ischemic stroke. This study aims to provide more insight into the potential association of headache, ischemic stroke, and the intrinsic Coagulation pathway. Methods- We included patients from the RATIO study (Risk of Arterial Thrombosis in Relation to Oral Contraceptives), a Dutch population-based case-control study including young women (age <50) with ischemic stroke and healthy controls. We defined a headache group based on a questionnaire on headache history. Intrinsic Coagulation Proteins were measured through both antigen levels (FXII, FXI, prekallikrein, HK [high molecular weight kininogen]) and Protein activation, determined by measuring activated Protein complex with C1esterase-inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin-inhibitor (FXIa-AT-INH). We calculated adjusted odds ratios and performed an interaction analysis assessing the increase in stroke risk associated with high levels of intrinsic Coagulation and history of headache. Results- We included 113 ischemic stroke cases and 598 healthy controls. In total, 134 (19%) patients had a history of headache, of whom 38 were cases and 96 controls. The combination of headache and high intrinsic Coagulation Protein levels (all but FXII antigen level and both FXIa-inhibitors) was associated with an increase in ischemic stroke risk higher than was expected based on their individual effects (adjusted odds ratio FXI antigen level alone: 1.7, 95% CI, 1.0-2.9; adjusted odds ratio headache alone: 2.0, 95% CI, 1.1-3.7; combination: 5.2, 95% CI, 2.3-11.6) Conclusions- Headache and high intrinsic Coagulation Protein levels may biologically interact, increasing risk for ischemic stroke.

  • intrinsic Coagulation activation and the risk of arterial thrombosis in young women results from the risk of arterial thrombosis in relation to oral contraceptives ratio case control study
    Circulation, 2010
    Co-Authors: Bob Siegerink, Frits R Rosendaal, Jose W P Goversriemslag, Ten H Cate, Ale Algra
    Abstract:

    Background—Classically, intrinsic Coagulation Proteins are thought to have a minor role in hemostasis. Recently, these Proteins, especially FXII, were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic Coagulation Proteins in young women and the effect of oral contraceptive use on this association. Methods and Results—The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic Coagulation Protein activation was determined by measuring activated Protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH, FXIa-C1-INH, Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were...

  • Intrinsic Coagulation Activation and the Risk of Arterial Thrombosis in Young Women Results From the Risk of Arterial Thrombosis in Relation to Oral Contraceptives (RATIO) Case-Control Study
    Circulation, 2010
    Co-Authors: Bob Siegerink, Frits R Rosendaal, José W. P. Govers-riemslag, H. Ten Cate, Ale Algra
    Abstract:

    BACKGROUND: Classically intrinsic Coagulation Proteins are thought to have a minor role in hemostasis. Recently these Proteins especially FXII were implicated as possible key players in the pathogenesis of arterial thrombosis. This study aims to determine the risks of arterial thrombosis conferred by increased activation of intrinsic Coagulation Proteins in young women and the effect of oral contraceptive use on this association. Methods and Results-The Risk of Arterial Thrombosis In relation to Oral contraceptives (RATIO) study is a population-based case-control study including young women (age 18 to 50 years) with myocardial infarction (n=205) and ischemic stroke (n=175) and 638 healthy controls. Intrinsic Coagulation Protein activation was determined by measuring activated Protein-inhibitor complexes. This complex is with C1 esterase inhibitor (FXIIa-C1-INH FXIa-C1-INH Kallikrein-C1-INH) or antitrypsin inhibitor (FXIa-AT-INH). Odds ratios (ORs) and corresponding confidence intervals (95% CIs) were calculated with logistic regression. High levels of Protein activation (>90th percentile of controls) showed an increased risk of ischemic stroke: FXIIa-C1-INH (OR 2.1; 95% CI 1.3 to 3.5) FXIa-C1-INH (OR 2.8; 95% CI 1.6 to 4.7) FXIa-AT-INH (OR 2.3; 95% CI 1.4 to 4.0) and Kallikrein-C1 (OR 4.3; 95% CI 2.6 to 7.2). If anything myocardial infarction risk was only increased by Kallikrein-C1-INH (OR 1.5; 95% CI 0.9 to 2.5). Oral contraceptive use further increased the risks. Conclusions-High levels of activated Proteins of the intrinsic Coagulation system are associated with arterial thrombosis whereas the strength of these associations differs for myocardial infarction and ischemic stroke. This contradicts similar analyses among men in the Northwick Park Heart Study. Together with the finding that oral contraceptive use further increases the risks the question of whether the role of intrinsic Coagulation Proteins in the pathogenesis of arterial thrombosis is sex-specific is raised.

Rodger L. Bick - One of the best experts on this subject based on the ideXlab platform.

  • recurrent miscarriage syndrome and infertility due to blood Coagulation Protein platelet defects a review and update
    Clinical and Applied Thrombosis-Hemostasis, 2005
    Co-Authors: Rodger L. Bick, Debra Hoppensteadt
    Abstract:

    Three-hundred fifty-one women were referred for thrombosis and hemostasis evaluation after suffering recurrent miscarriages. All patients were referred by a high-risk obstetrician or reproductive medicine specialist after anatomic, hormonal or chromosomal defects had been ruled out. These patients were assessed over a three year period. The mean patient age at referral was 34 years and the mean number of miscarriages was 2.9 (2-9). All patients underwent a thorough evaluation for thrombophilia and, when indicated, a hemorrhagic disorder. Of the 351 patients, 29 (8%) had no defect. Of the remaining 322 patients, 7 (2%) had a bleeding disorder: 3 with platelet dysfunction, 1 with Factor XIII deficiency, 3 with von Willebrand's and 3 with Osler-Weber-Rendu. The remainder of the patients had a thrombophilia as follows: 195 (60%) had antiphospholipid syndrome, 64 (20%) had Sticky Platelet Syndrome, 38 (12%) had MTHFR mutation, 23 (7.1%) had PAI-1 polymorphism, 12 (3.7%) had Protein S deficiency, 12 (3.7%) had Factor V Leiden, 3 (1%), had AT deficiency, 3 (1%) had Heparin-Cofactor II deficiency, 3 (1%) had TPA deficiency, and 6 (2%) had Protein C deficiency. There were a total of 364 defects found in the 312 patients harboring thrombophilia; thus, several harbored two and a few harbored three separate defects. All patients with thrombophilia were treated with preconception ASA at 81 mg/day with the immediate post-conception addition of heparin or LMW heparin (Dalteparin). Both ASA and heparin/LMW heparin were used to term. The first 120 patients were treated with unfractionated heparin at 5,000 U every 24 hours, subcutaneously and the last 192 have been treated with Dalteparin at 5,000 U/day subcutaneously. The patients with MTHFR were also treated with folate at 5 mg/day + pyridoxine at 50 mg/day. All patients were carefully monitored with CBC and platelet counts, anti-Xa levels, frequent ultrasounds and physical exams. Only 2 of the thrombophilia patients suffered another miscarriage; all others had a normal term delivery. There were no pregnancy-related thromboses, no delivery complications and no episodes of post-partum thrombosis. The only bleeding consisted of 1-4 cm bruises at injection sites. No episodes of thrombocytopenia (HIT) were noted. In our experience, thrombophilia is a common cause of recurrent miscarriage and all patients with no anatomical, hormonal or chromosomal defect should be evaluated for thrombophilia or a bleeding disorder. The success rate of normal term delivery in these 312 patients was 94% using ASA + heparin or Dalteparin. In addition, side effects of therapy were minimal.

  • RECURRENT MISCARRIAGE SYNDROME AND INFERTILITY CAUSED BY BLOOD Coagulation Protein OR PLATELET DEFECTS
    Hematology oncology clinics of North America, 2000
    Co-Authors: Rodger L. Bick
    Abstract:

    Recurrent miscarriage syndrome (RMS) is a common obstetrical problem affecting more than 500, 000 women per year 7 ; infertility, although less well defined in the population, is also a common clinical problem. Recurrent miscarriage, based on the available literature and the author's experience, is generally caused by certain well-defined defects: about 7% results from chromosomal abnormalities, about 10% is caused by anatomical abnormalities, about 15% seems to result from hormonal abnormalities (progesterone, estrogens, diabetes, or thyroid disease), about 6% cannot be explained, and the remainder, about 55% to 62%, are caused by blood Coagulation Protein or platelet defects. 7 The approximate prevalence of causes of RMS and infertility are summarized in Figure 1. 7 In contrast, about 90% of first-time miscarriages are caused by a chromosomal defect and as many as 25% of first-time pregnancies may end in miscarriage. 7

Patrick J. Skelly - One of the best experts on this subject based on the ideXlab platform.

  • The blood fluke Schistosoma mansoni cleaves the Coagulation Protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin.
    Parasites & vectors, 2018
    Co-Authors: Qiang Wang, Akram A. Da’dara, Patrick J. Skelly
    Abstract:

    Schistosomes are blood dwelling parasitic worms that cause the debilitating disease schistosomiasis. Here we examined the influence of the parasites on their external environment by monitoring the impact of adult Schistosoma mansoni worms on the murine plasma proteome in vitro and, in particular, on how the worms affect the blood Coagulation Protein high molecular weight kininogen (HK). Following the incubation of adult schistosomes in murine plasma, two-dimensional differential in-gel electrophoresis (2D-DIGE) was conducted to look for changes in the plasma proteome compared with control plasma. A major change to the blood Protein kininogen (HK) was observed, and the interaction of Schistosoma mansoni parasite with this Protein alone was then investigated by western blot analysis and activity assays. Finally, the generation of bradykinin from HK was monitored using a bradykinin detection kit. The most striking change to the plasma proteome concerned HK; while the full-length Protein was more abundant in control plasma, carboxyl-terminal truncated forms were more abundant in plasma that contained schistosomes. Incubating parasites in buffer with pure HK followed by Western blot analysis confirmed that human HK is degraded by the worms. The resulting digestion pattern differed from that brought about by kallikrein, a host serine protease that normally acts on HK to release the vasodilator bradykinin. We found that live schistosomes, while digesting HK, do not generate bradykinin nor do they cleave a chromogenic kallikrein substrate. Since the cleavage of HK by the worms is not impeded by the serine protease inhibitor PMSF but is blocked by the cysteine protease inhibitor E64c, we hypothesize that schistosome tegumental cysteine proteases are responsible for HK cleavage. Since proteomic and biochemical studies have revealed that the schistosome tegument contains two cysteine proteases belonging to the calpain family (SmCalp1 and SmCalp2) we conclude that these are likely responsible for the HK cleavage reported here. Schistosome cleavage of HK should help impede blood clotting and inflammation around the worms in vivo and so promote their ease of movement within the vasculature of their hosts.

  • The blood fluke Schistosoma mansoni cleaves the Coagulation Protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin
    BMC, 2018
    Co-Authors: Qiang Wang, Akram A. Da’dara, Patrick J. Skelly
    Abstract:

    Abstract Background Schistosomes are blood dwelling parasitic worms that cause the debilitating disease schistosomiasis. Here we examined the influence of the parasites on their external environment by monitoring the impact of adult Schistosoma mansoni worms on the murine plasma proteome in vitro and, in particular, on how the worms affect the blood Coagulation Protein high molecular weight kininogen (HK). Methods Following the incubation of adult schistosomes in murine plasma, two-dimensional differential in-gel electrophoresis (2D-DIGE) was conducted to look for changes in the plasma proteome compared with control plasma. A major change to the blood Protein kininogen (HK) was observed, and the interaction of Schistosoma mansoni parasite with this Protein alone was then investigated by western blot analysis and activity assays. Finally, the generation of bradykinin from HK was monitored using a bradykinin detection kit. Results The most striking change to the plasma proteome concerned HK; while the full-length Protein was more abundant in control plasma, carboxyl-terminal truncated forms were more abundant in plasma that contained schistosomes. Incubating parasites in buffer with pure HK followed by Western blot analysis confirmed that human HK is degraded by the worms. The resulting digestion pattern differed from that brought about by kallikrein, a host serine protease that normally acts on HK to release the vasodilator bradykinin. We found that live schistosomes, while digesting HK, do not generate bradykinin nor do they cleave a chromogenic kallikrein substrate. Since the cleavage of HK by the worms is not impeded by the serine protease inhibitor PMSF but is blocked by the cysteine protease inhibitor E64c, we hypothesize that schistosome tegumental cysteine proteases are responsible for HK cleavage. Conclusions Since proteomic and biochemical studies have revealed that the schistosome tegument contains two cysteine proteases belonging to the calpain family (SmCalp1 and SmCalp2) we conclude that these are likely responsible for the HK cleavage reported here. Schistosome cleavage of HK should help impede blood clotting and inflammation around the worms in vivo and so promote their ease of movement within the vasculature of their hosts

Qiang Wang - One of the best experts on this subject based on the ideXlab platform.

  • The blood fluke Schistosoma mansoni cleaves the Coagulation Protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin.
    Parasites & vectors, 2018
    Co-Authors: Qiang Wang, Akram A. Da’dara, Patrick J. Skelly
    Abstract:

    Schistosomes are blood dwelling parasitic worms that cause the debilitating disease schistosomiasis. Here we examined the influence of the parasites on their external environment by monitoring the impact of adult Schistosoma mansoni worms on the murine plasma proteome in vitro and, in particular, on how the worms affect the blood Coagulation Protein high molecular weight kininogen (HK). Following the incubation of adult schistosomes in murine plasma, two-dimensional differential in-gel electrophoresis (2D-DIGE) was conducted to look for changes in the plasma proteome compared with control plasma. A major change to the blood Protein kininogen (HK) was observed, and the interaction of Schistosoma mansoni parasite with this Protein alone was then investigated by western blot analysis and activity assays. Finally, the generation of bradykinin from HK was monitored using a bradykinin detection kit. The most striking change to the plasma proteome concerned HK; while the full-length Protein was more abundant in control plasma, carboxyl-terminal truncated forms were more abundant in plasma that contained schistosomes. Incubating parasites in buffer with pure HK followed by Western blot analysis confirmed that human HK is degraded by the worms. The resulting digestion pattern differed from that brought about by kallikrein, a host serine protease that normally acts on HK to release the vasodilator bradykinin. We found that live schistosomes, while digesting HK, do not generate bradykinin nor do they cleave a chromogenic kallikrein substrate. Since the cleavage of HK by the worms is not impeded by the serine protease inhibitor PMSF but is blocked by the cysteine protease inhibitor E64c, we hypothesize that schistosome tegumental cysteine proteases are responsible for HK cleavage. Since proteomic and biochemical studies have revealed that the schistosome tegument contains two cysteine proteases belonging to the calpain family (SmCalp1 and SmCalp2) we conclude that these are likely responsible for the HK cleavage reported here. Schistosome cleavage of HK should help impede blood clotting and inflammation around the worms in vivo and so promote their ease of movement within the vasculature of their hosts.

  • The blood fluke Schistosoma mansoni cleaves the Coagulation Protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin
    BMC, 2018
    Co-Authors: Qiang Wang, Akram A. Da’dara, Patrick J. Skelly
    Abstract:

    Abstract Background Schistosomes are blood dwelling parasitic worms that cause the debilitating disease schistosomiasis. Here we examined the influence of the parasites on their external environment by monitoring the impact of adult Schistosoma mansoni worms on the murine plasma proteome in vitro and, in particular, on how the worms affect the blood Coagulation Protein high molecular weight kininogen (HK). Methods Following the incubation of adult schistosomes in murine plasma, two-dimensional differential in-gel electrophoresis (2D-DIGE) was conducted to look for changes in the plasma proteome compared with control plasma. A major change to the blood Protein kininogen (HK) was observed, and the interaction of Schistosoma mansoni parasite with this Protein alone was then investigated by western blot analysis and activity assays. Finally, the generation of bradykinin from HK was monitored using a bradykinin detection kit. Results The most striking change to the plasma proteome concerned HK; while the full-length Protein was more abundant in control plasma, carboxyl-terminal truncated forms were more abundant in plasma that contained schistosomes. Incubating parasites in buffer with pure HK followed by Western blot analysis confirmed that human HK is degraded by the worms. The resulting digestion pattern differed from that brought about by kallikrein, a host serine protease that normally acts on HK to release the vasodilator bradykinin. We found that live schistosomes, while digesting HK, do not generate bradykinin nor do they cleave a chromogenic kallikrein substrate. Since the cleavage of HK by the worms is not impeded by the serine protease inhibitor PMSF but is blocked by the cysteine protease inhibitor E64c, we hypothesize that schistosome tegumental cysteine proteases are responsible for HK cleavage. Conclusions Since proteomic and biochemical studies have revealed that the schistosome tegument contains two cysteine proteases belonging to the calpain family (SmCalp1 and SmCalp2) we conclude that these are likely responsible for the HK cleavage reported here. Schistosome cleavage of HK should help impede blood clotting and inflammation around the worms in vivo and so promote their ease of movement within the vasculature of their hosts

  • Additional file 1: of The blood fluke Schistosoma mansoni cleaves the Coagulation Protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin
    2018
    Co-Authors: Qiang Wang, Akram A. Da’dara, Patrick Skelly
    Abstract:

    Table S1. Sequences of peptides identified by mass spectrometry from Protein spots 1–4 (as shown in Fig. 1a). Spots 1 and 2 are from plasma sample obtained in the absence of parasites (green) and spots 3 and 4 are from plasma sample that contained adult schistosomes (red), as described in methods. An “x” indicates that the peptide was found in the indicated Protein spot. The amino acid start and end positions of each peptide within the murine high molecular weight kininogen (accession designation: KNG1_MOUSE) sequence are given. (PDF 418 kb