Inhibiting factor XIa to prevent thromboembolism

2021 ◽  
Author(s):  
Gregory B. Lim
Keyword(s):  
Inhibiting Factor ◽  
Factor Xia

The Activation of Human Factor IX

1975 ◽  
Vol 33 (03) ◽  
pp. 553-563 ◽  
Author(s):  
B Østerud ◽  
K Laake ◽  
H Prydz
Keyword(s):  
Molecular Weight ◽  
Sodium Dodecyl ◽  
Apparent Molecular Weight ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Human Factor Ix ◽  
Factor Xia ◽  
Tissue Thromboplastin ◽  
Native Factor

SummaryThe activation of factor IX purified from human plasma has been studied. Factor XIa and kallikrein separately activated factor IX to factor IXa. In both cases factor IX a had an apparent molecular weight of about 42–45000 in sodium dodecyl sul-phate-polyacrylamide disc gel electrophoresis compared with a molecular weight of about 70000 for the native factor IX. The activation by XIa required Ca2+-ions whereas Ca2+-ions did not influence the activation by kallikrein. A mixture of tissue thromboplastin and factor VII or RusselPs-viper venom alone did not activate factor IX. Trypsin activated and plasmin inactivated factor IX.

Amidolytic Detection of Prothrombin Activation Products after SDS-Gel Electrophoresis

1989 ◽  
Vol 61 (03) ◽  
pp. 386-391 ◽  
Author(s):  
Guido Tans ◽  
Truus Janssen-Claessen ◽  
Jan Rosing
Keyword(s):  
Gel Electrophoresis ◽  
Activated Protein C ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Product Formation ◽  
Chromogenic Substrate ◽  
Nitrocellulose Membrane ◽  
Activation Products ◽  
Factor Xia ◽  
Prothrombin Activation

SummaryIn this paper we report a method via which enzymatically active products formed during prothrombin activation can be detected by simple photographic means after SDS-gel electrophoresis, blotting onto a nitrocellulose membrane and visualization with the chromogenic substrate, S2238. After amidolytic detection the same nitrocellulose membrane can also be used for immunologic detection of prothrombin activation products, thus allowing a complete description of product formation during prothrombin activation.The detection limit of the so-called “amidoblot” is approximately 3 ng thrombin per gel sample which is comparable to the sensitivity of immunoblotting.It is further shown that the amidoblot technique can also be applied to other coagulation factors for which a suitable chromogenic substrate is available (factor XIIa, kallikrein, factor XIa, factor Xa, plasmin and activated protein C).

Inactivation of Factor XIa in Vivo: Studies in Chimpanzees and in Humans

1996 ◽  
Vol 76 (04) ◽  
pp. 549-555 ◽  
Author(s):  
Walter A Wuillemin ◽  
C Erik Hack ◽  
Wim K Bleeker ◽  
Bart J Biemond ◽  
Marcel Levi ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Life Time ◽  
In Vivo Studies ◽  
Clinical Samples ◽  
Plasma Samples ◽  
C1 Inhibitor ◽  
Elimination Kinetics ◽  
Factor Xia ◽  
Best Parameter

SummaryC1-inhibitor (C1Inh), antithrombin III (ATIII), α1-antitrypsin (a1AT), and α2-antiplasmin (a2AP) are known inhibitors of factor XIa (FXIa). However, their precise contribution to FXIa inactivation in vivo is not known. We investigated FXIa inactivation in chimpanzees and assessed the contribution of these inhibitors to FXIa inactivation in patients with presumed FXI activation.Chimpanzees were infused with FXIa and the various FXIa-FXIa inhibitor complexes formed were measured. Most of FXIa was complexed to C1Inh (68%), followed by a2AP (13%), a1AT (10%), and ATIII (9%). Analysis of the plasma elimination kinetics revealed a half-life time of clearance (t1/2) for the FXIa-FXIa inhibitor complexes of 95 to 104 min, except for FXIa-a1AT, which had a t1/2 of 349 min. Due to this long t1/2, FXIa-a1AT complexes were predicted to show the highest levels in plasma samples from patients with activation of FXI. This was indeed shown in patients with disseminated intravascular coagulation, recent myocardial infarction or unstable angina pectoris. We conclude from this study that in vivo C1Inh is the predominant inhibitor of FXIa, but that FXIa-a1 AT complexes due to their relatively long t1/2 may be the best parameter to assess FXI activation in clinical samples.

Ultrasensitive Fluorogenic Substrates for Serine Proteases

1997 ◽  
Vol 78 (04) ◽  
pp. 1193-1201 ◽  
Author(s):  
Saulius Butenas ◽  
Maria E DiLorenzo ◽  
Kenneth G Mann
Keyword(s):  
Serine Proteases ◽  
Factor Viia ◽  
Activated Protein C ◽  
Factor Xa ◽  
High Specificity ◽  
High Rate ◽  
Fluorogenic Substrates ◽  
Type Plasminogen Activator ◽  
Factor Xia ◽  
Coagulation And Fibrinolysis

SummarySelective, sensitive assays for the quantitation of serine proteases involved in coagulation and fibrinolysis have been developed employing fluorogenic substrates containing a 6-amino-1-naphthalenesulfonamide leaving group (PNS-substrates). Over one hundred substrates were evaluated for hydrolysis by the serine proteases of blood coagulation and fibrinolysis, and substrate structure-efficiency correlations were examined. PNS-substrates which contain Lys in the P1 position are specific for Lys-plasmin and are either not hydrolyzed or hydrolyzed at a relatively low rate by factor Xa, thrombin, or urokinase-type plasminogen activator (uPA). These substrates allow quantitation of Lys-plasmin at concentrations as low as 1 pM. Eighteen of over 90 substrates tested for factor XIa are hydrolyzed by this enzyme at a relatively high rate reaching a kcat value of 170 s-1 and allowing quantitation of factor XIa at 10 fM. Eighteen of almost 90 PNS-substrates tested display high specificity for thrombin, some exceeding that for factor Xa by > 10,000-fold and > 100-fold for activated protein C (APC). Seven of these substrates have a over 100 s-1 and three of them have a KM below 1 μM. They allow the quantitation of thrombin at concentrations as low as 20 fM. For APC, uPA and the factor Vila/tissue factor complex, quantitation is feasible at 1 pM concentration. For factor Xa and factor VIIa the limits are 0.4 pM and 40 pM respectively. The PNS-substrates presented in this study may be employed for the development of direct and sensitive serine protease assays.

Acquired Factor XI Inhibitors in Two Patients with Hereditary Factor XI Deficiency

1984 ◽  
Vol 51 (03) ◽  
pp. 371-375 ◽  
Author(s):  
Kangathevy Morgan ◽  
Sandra Schiffman ◽  
Donald Feinstein
Keyword(s):  
Protein A ◽  
Lambda Light Chain ◽  
Factor Xi ◽  
Spontaneous Bleeding ◽  
Factor Xi Deficiency ◽  
Hereditary Factor ◽  
Coagulation Mechanism ◽  
Factor Xia ◽  
Polyclonal Igg ◽  
Glass Surfaces

SummaryTwo patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients’ plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients’ plasmas adsorbed to Protein A- Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.

FAKTOR PENDUKUNG DAN PENGHAMBAT DALAM PROSES PERUBAHAN ORGANISASI PADA POLITEKNIK KESEHATAN KEMENKES PALANGKA RAYA

2017 ◽  
Vol 13 (2) ◽  
pp. 119-128
Author(s):  
Nang Randu Utama
Keyword(s):  
Mental Model ◽  
Teaching And Learning ◽  
Learning Technology ◽  
Teaching Aids ◽  
Inhibiting Factors ◽  
Inhibiting Factor ◽  
Management Perspective ◽  
The Republic ◽  
Technical Guidance

This study aims to obtain a description of the supporting and inhibiting factors in the process of organizational change of education based on management perspective that occurs in the scope of higher health education of the Ministry of Health of the Republic of Indonesia. This study used a qualitative approach by conducting case study at Palangka Raya Health Polytechnic. The research results are as follows: (a) Supporting factor that must be there is the existence of a manual or technical guidance in organizing the organization; (b) Whereas the inhibiting factor is the old habits, the mindset, the mental model is still inhibiting from the organizers and members of the organization; (c) The inhibiting factor is the existence of selfishness of each highly visible party; (d) Inhibitors may also occur if there are still "little kings" and selfishness from each of the former institutions; (e) Other issues that support in this process of change are in terms of facilities and infrastructure, namely the availability of buildings and land; (f) Another inhibiting factor is that in terms of educational qualifications, there are departments that do not meet, for example in the midwifery department there are still many average teachers with Diploma IV education background and non-linear education; (g) Inhibiting factors may also occur if the reason of seniority is always carried around; (h) The inhibiting factor is lack of human resources in using modern health equipment, including the use of teaching aids in accordance with the progress of science and teaching and learning technology.   Penelitian ini bertujuan untuk memperolah gambaran mengenai faktor pendukung dan penghambat dalam proses perubahan organisasi pendidikan yang ditinjau dari perspektif manajemen yang terjadi di lingkup organisasi pendidikan tinggi kesehatan Kementerian Kesehatan Republik Indonesia. Penelitian ini menggunakan pendekatan kualitatif dengan melakukan studi kasus pada institusi Politeknik Kesehatan Kemenkes Palangka Raya. Hasil penelitian adalah sebagai berikut: (a) Faktor pendukung yang harus ada yaitu adanya buku pedoman atau petunjuk teknis dalam penyelenggaraan organisasi; (b) Sedangkan yang menjadi faktor penghambat itu adalah kebiasaan lama, mindset-nya, mental model-nya masih bersifat menghambat dari para pengelola dan anggota organisasi; (c) Faktor penghambat yaitu adanya keegoisan masing-masing pihak yang sangat tampak; (d) Penghambat juga dapat terjadi apabila masih ada “raja-raja kecil” dan keegoisan dari masing-masing institusi yang dulu; (e) Perihal lain yang mendukung dalam proses perubahan ini adalah dari sisi sarana dan prasarana, yaitu tersedianya gedung dan tanah; (f) Faktor penghambat lain yaitu dari sisi kualifikasi pendidikan ternyata ada jurusan yang tidak memenuhi, misalnya di jurusan kebidanan masih banyak rata-rata tenaga pengajar dengan latar pendidikan Diploma IV dan pendidikannya tidak linear; (g) Faktor penghambat juga dapat terjadi apabila alasan senioritas selalu dibawa-bawa; (h) Faktor penghambat yaitu masih kurang kesiapan sumber daya manusia dalam menggunakan alat-alat kesehatan modern termasuk penggunaan alat bantu belajar mengajar yang sesuai dengan kemajuan ilmu pengetahuan dan teknologi pengajaran dan pembelajaran.

Kualitas Pelayanan Surat Izin Mengemudi (SIM) Pada Kantor Satuan Lalu Lintas Polres Karimun

2019 ◽  
Vol 2 (2) ◽  
pp. 246
Author(s):  
Ade Sarmini
Keyword(s):  
Service Quality ◽  
Human Resources ◽  
Public Service ◽  
Research Method ◽  
Consumer Trust ◽  
Population Mobility ◽  
Descriptive Research ◽  
Road Users ◽  
Inhibiting Factor

<em><span lang="EN-SG">Along with increasing population mobility and increasing road users the need to have a SIM is increasing every day. Where the administration of traffic and services, such as SIM, STNKB and BPKB are oriented to the principle of quick and easy without ignoring the identification and extension of the letter. This research uses descriptive research method. Descriptive research is intended to explore and clarify phenomena or social realities. From the results of the study showed that the implementation of public service quality in making SIMs at the Karimun Regional Police Traffic Unit Office was seen from the aspect of physical facilities (tangible), reliability (responsiveness), responsiveness, assurance and empathy were running pretty good. Especially relating to the ability and reliability to provide trusted services, the ability to help and provide services quickly and appropriately, as well as being responsive to consumer desires, abilities and friendliness and employee courtesy in assuring consumer trust and firm but attentive attitudes of employees towards consumers . Although it is indeed an inhibiting factor for SIM services such as human resources, the level of awareness and facilities and infrastructure are still found in the service of making SIMs at the Karimun Regional Traffic Unit Office</span></em>

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