Use of a non-depleting anti-CD4 antibody to modulate the immune response to coagulation factors VIII and IX

2002 ◽  
Vol 118 (3) ◽  
pp. 839-842 ◽  
Author(s):  
Nina Salooja ◽  
Geoffrey Kemball-Cook ◽  
Edward G. D. Tuddenham ◽  
Julian Dyson
Keyword(s):  
Immune Response ◽  
Coagulation Factors ◽  
Viii And Ix

Recombinant factor VIIa

2005 ◽  
Vol 93 (06) ◽  
pp. 1027-1035 ◽  
Author(s):  
Marco Zaffanello ◽  
Dino Veneri ◽  
Massimo Franchini
Keyword(s):  
Recombinant Factor Viia ◽  
Factor Viia ◽  
Current Knowledge ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Viii And Ix ◽  
Bleeding Episodes ◽  
Uncontrolled Bleeding

SummaryRecombinant activated factor VII (rFVIIa, Novo Seven®) has been successfully used to treat bleeding episodes in patients with antibodies against coagulation factors VIII and IX. In recent years, rFVIIa has also been employed for the management of uncontrolled bleeding in a number of congenital and acquired haemos- tatic abnormalities. Based on a literature search, this review examines the current knowledge on therapy with rFVIIa, from the now well-standardized uses to the newer and less well-characterised clinical applications.

Ham-Wasserman Lecture

Hematology ◽  
2002 ◽  
Vol 2002 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Pier M. Mannucci
Keyword(s):  
Large Scale ◽  
Coagulation Factors ◽  
Gene Replacement ◽  
Infectious Complications ◽  
Inherited Disorders ◽  
Secondary Tumors ◽  
Human Immunodeficiency Viruses ◽  
First Millennium ◽  
Viii And Ix ◽  
Bloodborne Infections

Abstract Known since the beginning of the first millennium, the hemophilias are among the most frequent inherited disorders of blood coagulation and definitely the most severe. In the 1970s, with the availability of concentrated preparations of the deficient coagulation factors VIII and IX and with the large-scale adoption of home treatment, hemophilia care became one of the most gratifying examples of successful secondary prevention of a chronic disease. Unfortunately, in the early 1980s it was recognized that factor concentrates prepared from plasma pooled from thousands of donors transmitted the hepatitis and the human immunodeficiency viruses. The scientific community reacted promptly to the devastation brought about by hepatitis and AIDS. The last 15 years of the second millennium have witnessed the development of methods that, when applied during concentrate manufacturing, inactivate viruses escaping the screening procedures. The adoption of these measures has reduced dramatically the risk of transmission of bloodborne infections. The production of recombinant factors and their availability for patients’ treatment epitomize progress in hemophilia care through DNA technology. Methods based on the polymerase chain reaction (PCR) have unraveled an array of gene lesions associated with hemophilia, permitting improved secondary control of the disease through carrier detection in women from affected families and prenatal termination of their affected male infants. This article will review the aforementioned areas of progress and discuss unresolved problems (such as treatment of patients with antibodies, the risk of new infectious complications, and the issue of secondary tumors). Hopes and expectations for further improvement in the third millennium and particularly the prospects of hemophilia cure though gene replacement therapy will also be mentioned.

THE EFFECT OF THE VENOM OF THE ORIENTAL HORNET ON COAGULATION FACTORS

1987 ◽  
Author(s):  
A Kornberg ◽  
S Kaufman ◽  
L Silber ◽  
J Ishay
Keyword(s):  
Human Plasma ◽  
Degradation Products ◽  
Anticoagulant Activity ◽  
Coagulation Factors ◽  
Plasma Fibrinogen ◽  
Thrombin Time ◽  
Clotting Factors ◽  
Viii And Ix

The extract from the venom sac of Vespa orientalis (VSE) inactivates exogenous and endogenous thromboplastin (Joshua and Ishay, Toxicon, 13:11-20,1975). The prolongation of both prothrombin time (PT) and recalcification time suggests inactivation of other factors. The aim of the present study is to investigate the effect of VSE on clotting factors. A lyophilized VSE with protein concentration of 5 mg/ml was used. Studies were performed in vitro with human plasma and in vivo in cats. Routine methods were employed for the assay of PT, activated tissue thromboplastin (APTT), thrombin time (TT), fibrinogen degradation products (FDP), fibrinogen and factors V,VII,VIII,IX,X. Human plasma was incubated with various concentrations of VSE (0,1,5,10,50,100 μg/ml) for 60 min and for various incubation times (0,5,15,30,+ 60,90,120 min) with 50 μg/ml VSE (n=8). 1 μg/ml VSE prolonged PT from 13.5 to 16 sec (p<0.05) and APTT from 62 to 180 sec. PT was maximal (17.7 sec) with 10 μg/ml and APTT (442 sec) with 50 μg/ml VSE. Factors V,VII,X decreased gradually from 94-105% to 11%,11% and 29% with 100 μg/ml VSE and VIII and IX to 1% even with 1 μg/ml VSE. After 5 min with constant concentration of VSE (50 μg/ml) PT was 14.9 sec (normal 13 sec) and APTT 165 sec (normal 54 sec). Both were maximal (17.5 and 298 sec) after 60 min. Factors VII and X decreased to 13% and 32% and VIII and IX to >1% after 60 min of incubation. Injection of 5 mg/kg VSE to cats (n=6-8) resulted in prolongation of PT from 9.4 to 11.2 sec and of APTT from 19.5 to 63 sec after 5 min. Both were maximal after 90 min (12.3 and 127 sec). Factors V,VII and X decreased from 100% to 7.6%, 13% and 37% and VIII and IX to 1% after 10 min. In all experiments TT and plasma fibrinogen were not affected and FDP were normal. Heating of VSE for 5 min at 80°C abolished completely the anticoagulant activity but dialysis for 24 hr at 4°C had no effect on it. The activity was eluted on Sephadex-25 both in void and post void volumes. The results show that VSE has a potent anticoagulant activity against various factors. Factors VIII and IX are markedly decreased. The effect on V, VII and X is moderate. Plasma fibrinogen is not affected. The nature and clinical significance of the anticoagulant activity merit further investigation.

Therapeutic levels of human factor VIII and IX using HIV-1–based lentiviral vectors in mouse liver

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1173-1176 ◽  
Author(s):  
Frank Park ◽  
Kazuo Ohashi ◽  
Mark A. Kay
Keyword(s):  
Fold Increase ◽  
Lentiviral Vectors ◽  
Coagulation Factors ◽  
Human Factor Viii ◽  
Immunodeficiency Virus ◽  
Viii And Ix ◽  
Immunocompetent Mice ◽  
Dose Dependent ◽  
Hiv 1

Lentiviral vectors have the potential to play an important role in hemophilia gene therapy. The present study used human immunodeficiency virus (HIV)-based lentiviral vectors containing an EF1 enhancer/promoter driving human factors VIII (hFVIII) or IX (hFIX) complementary DNA expression for portal vein injection into C57Bl/6 mice. Increasing doses of hFIX-expressing lentivirus resulted in a dose-dependent, sustained increase in serum hFIX levels up to approximately 50-60 ng/mL. Partial hepatectomy resulted in a 4- to 6-fold increase (P < 0.005) in serum hFIX of up to 350 ng/mL compared with the nonhepatectomized counterparts. The expression of plasma hFVIII reached 30 ng/mL (15% of normal) but was transient as the plasma levels fell concomitant with the formation of anti-hFVIII antibodies. However, hFVIII levels were persistent in immunodeficient C57Bl/6 scid mice, suggesting humoral immunity-limited gene expression in immunocompetent mice. This study demonstrates that lentiviral vectors can produce therapeutic levels of coagulation factors in vivo, which can be enhanced with hepatocellular proliferation.

scholarly journals The use of combined hormonal contraception in the context of the COVID-19 pandemic

2021 ◽  
pp. 186-196
Author(s):  
A. T. Uruymagova ◽  
V. N. Prilepskaya ◽  
E. A. Mezhevitinova ◽  
M. T. Poghosyan
Keyword(s):  
Immune Response ◽  
High Risk ◽  
Severe Disease ◽  
Hormonal Contraception ◽  
Coagulation Factors ◽  
Thromboembolic Complications ◽  
Global Pandemic ◽  
Combined Hormonal Contraception ◽  
Prolonged Immobilization ◽  
Arteries And Veins

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared the cause of a global pandemic in early 2020. Patients with COVID-19 are at high risk for thrombotic occlusions of the arteries and veins. There are many ways that explain the high risk of thrombosis in COVID-19, they are conditionally divided into two main categories: mechanisms in which the renin-angiotensinaldosterone system is involved and mechanisms that affect the regulation of the immune response. It is assumed that the uncomplicated course of the disease is characterized by endothelial dysfunction, but if the process progresses with a pronounced immune response, plasma coagulation factors may also be involved, which significantly increases the risks of thromboembolic complications. The use of combined hormonal contraception (CHC) in the current conditions raises a number of concerns. According to some researchers, disorders of the hemostasis system observed in patients with COVID-19 may worsen while taking CHC and increase the risk of thromboembolic complications, which is especially important in severe disease with prolonged immobilization. However, with the use of CHC, the increase in thrombotic risks is explained primarily by changes in the plasma component of the hemostasis sys tem. At first glance, the recommendations to stop hormone therapy with confirmed COVID-19 seem logical, but they are based only on the procoagulant activity of estrogens, and not on real evidence. In patients with COVID-19, the increase in coagulation is associ ated with massive damage to the vascular endothelium (the so-called «external» coagulation pathway) and the immune response, and not with a primary increase in the level of coagulation factors per se. At the same time, stopping the intake of estrogens deprives the patient of their important protective effect. Thus, it became necessary to develop clinical guidelines for the management of women using contraception in the context of the COVID-19 pandemic.

The Global Need and Availability of Plasma Coagulation Factors VIII and IX in Hemophilia Context: A Global Health Estimate Reporting

2021 ◽  
Author(s):  
Elisângela César dos Santos Anjos ◽  
Fabiano Romanholo Ferreira ◽  
Paulo Henrique de Souza Bermejo ◽  
Marina Figueiredo Moreira ◽  
David Nadler Prata
Keyword(s):  
Global Health ◽  
Coagulation Factors ◽  
Plasma Coagulation ◽  
Viii And Ix

Acquired coagulopathy and complement system pathology in chronic hepatic disorders.

2021 ◽  
Author(s):  
Е.Ю. Коновалова ◽  
М.В. Преснякова
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Complement System ◽  
Clinical Picture ◽  
Coagulation Factors ◽  
Innate Immune ◽  
Complement System Proteins ◽  
Hepatic Diseases ◽  
System Components

Комплемент и коагуляция являются эволюционно связанными протеолитическими гуморальными системами, которые имеют решающее значение для осуществления врожденного иммунного ответа на повреждение и инфекцию, ограничения кровотечения и патологического тромбообразования. Печень играет центральную роль в функционировании системы гемостаза и комплемента: она синтезирует большинство факторов свертывания и их ингибиторов, а также протеины системы комплимента. При хронических заболеваниях печени нарушения системы гемостаза протекают по типу коагулопатий, выраженность которых будет определять клиническую картину основного заболевания. В обзоре представлены данные о роли сосудисто-тромбоцитарного, коагуляционного, антикоагулянтного и фибринолитического звеньев системы гемостаза и компонентов системы комплемента в патогенезе хронических заболеваний печени. Complement and coagulation are evolutionarily related proteolytic humoral systems that are crucial for the innate immune response to injury and infection, for limiting hemorrhage and pathological thrombosis. The liver plays a central role in the functioning of hemostasis and complement system. It synthesizes most coagulation factors and their inhibitors, as well as complement system proteins. In chronic hepatic diseases, hemostasis disorders proceed as coagulopathies, and their severity determine the clinical picture of basic disease. This review presents data about the role of vascular-platelet, coagulant, anticoagulant and fibrinolytic links of hemostasis and complement system components in the pathogenesis of chronic hepatic diseases.

Inhibition of Extrinsic Pathway Inhibitor Shortens the Coagulation Time of Normal Plasma and of Hemophilia Plasma

1991 ◽  
Vol 66 (04) ◽  
pp. 464-467 ◽  
Author(s):  
Ole Nordfang ◽  
Sanne Valentin ◽  
Thomas C Beck ◽  
Ulla Hedner
Keyword(s):  
Coagulation Factors ◽  
Inhibitory Antibody ◽  
Extrinsic Pathway ◽  
Coagulation Time ◽  
Plasma Analysis ◽  
Normal Plasma ◽  
Low Concentrations ◽  
Viii And Ix ◽  
Dependent Pathway ◽  
Individual Donor

SummaryAn increasing amount of evidence suggests that coagulation factors VIII and IX play a role not only in the intrinsic but also in the extrinsic pathway of coagulation. In this context the influence of the Extrinsic Pathway Inhibitor (EPI) on the coagulation time of hemophilia plasma lacking FVIII or FIX has been investigated. The coagulation time was measured in a dilute thromboplastin assay. Addition of recombinant EPI (rEPI) prolonged the coagulation time of normal plasma while the addition of an inhibitory antibody against EPI shortened the coagulation time. At low concentrations of thromboplastin the coagulation time of hemophilia plasma was prolonged and at all dilutions of thromboplastin, addition of anti-EPI IgG normalized the coagulation time of a hemophilia plasma. Analysis of 10 individual donor plasma samples and 8 individual hemophilia samples showed that addition of anti-EPI IgG shortened the coagulation time more in hemophilia plasma than in normal plasma. This illustrates the importance of a powerful extrinsic FVII dependent pathway to achieve hemostasis in the case of FVIII or FIX deficiency (hemophilia A and B).

Efleet of Endotoxin on the Activity of Coagulation Factors VII, VIII and IX Produced during Organ Perfusion

1974 ◽  
Vol 32 (02/03) ◽  
pp. 528-537
Author(s):  
W Jean Dodds ◽  
Stein A. Evensen
Keyword(s):  
Factor Viii ◽  
Actinomycin D ◽  
Platelet Rich Plasma ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Protein Synthesis Inhibitors ◽  
Factor Viii Activity ◽  
Coagulation Activity ◽  
Viii And Ix ◽  
Initial Perfusion

SummaryThe effect of bacterial endotoxin on the production of factor VII, VIII and IX activities in isolated rabbit livers, spleens and kidneys was investigated. The organs were perfused for 4 hours with fluid devoid of coagulation activity and containing either endotoxin or glucose-saline diluent. A series of parallel experiments included an initial hour of perfusion to ensure removal of tissue-stored coagulation activity, and perfusion with platelet-rich plasma and protein synthesis inhibitors. Endotoxin increased factor VII production in all organs but especially in livers not subjected to the initial perfusion; this effect was abolished by actinomycin D and puromycin. Endotoxin had little effect on hepatic factor VIII and IX activities but it inhibited production of both factors in the kidney and of factor VIII in the spleen. Initial perfusion prevented this inhibition of splenic factor VIII activity. These data suggest that endotoxin increases factor VII synthesis and causes consumption of factors VIII and IX in perfused kidneys and, to a lesser extent, spleens. Also, initial perfusion appears to prevent the subsequent consumption of splenic factor VIII by endotoxin. This response may involve activation of some tissue-bound or stored factor(s) or may be due to removal of an inhibitor substance.

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