A very potent factor V inhibitor interferes with the levels of all coagulation factors and causes a fatal hemorrhagic syndrome

SummaryTwenty-one cardiothoracic surgical patients have been treated with fibrin as a topical hemostatic/sealing agent, prepared from bovine fibrinogen clotted with bovine thrombin. Serum samples have been collected before treatment with fibrin and postoperatively between 1 and 9 days, 3 and 12 weeks, and 6 and 8 months. The titers of anti-bovine fibrinogen antibodies, measured by ELISA specific for immunoglobulins IgG or IgM, increased to maximal values after about 8 or 6 weeks, respectively. After 8 months, IgG titers were on average 20-fold lower than the mean maximal value, while IgM titers returned to the normal range. IgG was the predominant anti-bovine fibrinogen immunoglobulin as documented by ELISA, affinity chromatography and electrophoresis. Anti-bovine fibrinogen antibodies present in patients reacted readily with bovine fibrinogen, but did not cross-react with human fibrinogen as measured by ELISA or by immunoelectrophoresis. A significant amount of antibodies against bovine thrombin and factor V has been found, many cross-reacting with the human counterparts. No hemorrhagic or thrombotic complications, or clinically significant allergic reactions, occurred in any patient, in spite of antibody presence against some bovine and human coagulation factors. The treatment of patients with bovine fibrin, without induction of immunologic response against human fibrinogen, appeared to be an effective topical hemostatic/sealing measure.

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Changes Occurring During Coagulation in Glass. I. Normal Human Blood

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654484 ◽

1960 ◽

Vol 4 (01) ◽

pp. 001-016

Author(s):

Jessica H. Lewis ◽

Paul Didisheim ◽

John H. Ferguson ◽

Kenichi Hattori

Keyword(s):

Coagulation Factors ◽

Factor Ix ◽

Factor Vii ◽

Sodium Oxalate ◽

Factor V ◽

Rapid Rise ◽

Rapid Fall ◽

Glass Tubes ◽

Normal Human ◽

The Individual

SummaryNormal whole blood was allowed to stand in glass tubes at 37° C, and the clotting process stopped at various intervals by the addition of sodium oxalate. During the first 15 minutes a marked acceleration of clotting activity was found. Study of the individual coagulation factors showed the following changes: a sustained and rapid fall in platelet count, a sustained and rapid rise in PTC (factor IX), a steady fall in fibrinogen, a more gradual fall in AHF (factor VIII), a rapid rise and subsequent fall in proaccelerin (factor V) activity, a somewhat lesser and slower rise and fall in proconvertin (factor VII) activity, and a slow fall in prothrombin concentration. No changes were noted in Hageman factor or PTA activities.

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Coagulation Findings in Rats with Experimental Hypersplenism and Their Changes after Splenectomy and after Administration of Adrenaline

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654190 ◽

1970 ◽

Vol 23 (03) ◽

pp. 593-600

Author(s):

P Pudlák ◽

I Farská ◽

V Brabec ◽

V Pospíšilová

Keyword(s):

Factor Viii ◽

Normal Control ◽

Normal Values ◽

Coagulation Factors ◽

Factor Vii ◽

Factor V ◽

Thrombin Time ◽

Factor Ii ◽

Recalcification Time

Summary1. The following coagulation changes were found in rats with experimental hypersplenism: a mild prolongation of the recalcification time, shortened times in Quick’s test, a lowered activity in plasma thrombin time and shortened times in the partial thromboplastin test. Concentrations of factor II, V, VII (+X), VIII and X did not differ from those of normal control rats.2. The administration of adrenaline to hypersplenic rats induced the correction of the partial thromboplastin test, Quick’s test and plasma thrombin time to normal values. Concentrations of coagulation factors were not significantly changed. An increase was found in factor V.3. Splenectomy performed in hypersplenic rats was followed by a shortened recalcification time, a prolongation of the partial thromboplastin test and of the test with partial thromboplastin and kaolin. A prolongation was also observed in Quick’s test. Complete correction of plasma thrombin time was not observed. The concentration of factor VII increased.4. The administration of adrenaline to splenectomized rats with experimental hypersplenism did not induce any significant changes with the exception of a corrected plasma thrombin time and a decreased concentration of factor VIII.5. A different reaction of factor VIII to adrenaline in normal and hypersplenic rats is pointed out.

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Cryo-EM structures of human coagulation factors V and Va

Blood ◽

10.1182/blood.2021010684 ◽

2021 ◽

Author(s):

Eliza A Ruben ◽

Michael J Rau ◽

James Fitzpatrick ◽

Enrico Di Cera

Keyword(s):

Protein C ◽

Activated Protein C ◽

Factor Xa ◽

Coagulation Factor ◽

Coagulation Factors ◽

Proteolytic Processing ◽

Coagulation Cascade ◽

Factor V ◽

Prothrombinase Complex ◽

A2 Domain

Coagulation factor V is the precursor of factor Va that, together with factor Xa, Ca2+ and phospholipids, defines the prothrombinase complex and activates prothrombin in the penultimate step of the coagulation cascade. Here we present cryo-EM structures of human factors V and Va at atomic (3.3 Å) and near-atomic (4.4 Å) resolution, respectively. The structure of fV reveals the entire A1-A2-B-A3-C1-C2 assembly but with a surprisingly disordered B domain. The C1 and C2 domains provide a platform for interaction with phospholipid membranes and support the A1 and A3 domains, with the A2 domain sitting on top of them. The B domain is highly dynamic and visible only for short segments connecting to the A2 and A3 domains. The A2 domain reveals all sites of proteolytic processing by thrombin and activated protein C, a partially buried epitope for binding factor Xa and fully exposed epitopes for binding activated protein C and prothrombin. Removal of the B domain and activation to fVa exposes the sites of cleavage by activated protein C at R306 and R506 and produces increased disorder in the A1-A2-A3-C1-C2 assembly, especially in the C-terminal acidic portion of the A2 domain responsible for prothrombin binding. Ordering of this region and full exposure of the factor Xa epitope emerge as a necessary step for the assembly of the prothrombin-prothrombinase complex. These structures offer molecular context for the function of factors V and Va and pioneer the analysis of coagulation factors by cryo-EM.

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Coagulation factors synthesis by the liver, with special reference to Factor VIII and Factor V

Haemostatic Failure in Liver Disease ◽

10.1007/978-94-009-6006-0_2 ◽

1984 ◽

pp. 5-23 ◽

Cited By ~ 1

Author(s):

J. C. Giddings

Keyword(s):

Factor Viii ◽

Special Reference ◽

Coagulation Factors ◽

Factor V

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TWO CASES OF NEONATAL PURPURA FULMINANS HOMOZYGOUS FOR PROTEIN C DEFICIENCY IN A CHINESE FAMILY

10.1055/s-0038-1644308 ◽

1987 ◽

Author(s):

M C SHEN ◽

S H CHEN ◽

K S LIN

Keyword(s):

Vitamin K ◽

Protein C ◽

Newborn Infants ◽

Purpura Fulminans ◽

Coagulation Factors ◽

Chinese Family ◽

Factor V ◽

Autosomal Dominant Disorder ◽

Protein C Deficiency ◽

Venous Thromboembolic

Protein C (PC) deficiency associated with hereditary venous thromboembolic disease was first reported in 1981 and is inherited as an autosomal dominant disorder. The prevalence of heterozygous PC deficiency is estimated to be 1 to 4% in venous thrombotic diseases. The homozygous PC deficiency is even rare, and has been reported in only about 10 families througout the world. It usually presents in newborn infants as purpura fulminans or severe thrombotic disease. We herein report two newborn brothers in a Chinese family, who manifested with purpura fulminans soon after birth and died at age of 21 days and 27 days respectively. Vitamin K was administered to the second baby after birth. Both parents are not consanguineous and there were no family histories of thromboembolism on paternal and maternal sides. Blood sample was not available for specific studies in the first baby. PC antigen level by electroimmunoassay was <6% in the second baby and 49% and 60% respectively in their mother and father. Antithrombin III activity by amidolytic method was 49% in the second baby, and 90% and 97% respectively in their mother and father. Vitamin K-dependent coagulation factors and factor V were within the expected range for a newborn. Factor VIII and fibrinogen level were notably decreased. Autopsy findings of the two newborns demonstrated the similar pictures characterized by fibrin thrombi in blood vessels causing extensive hemorrhagic infarts of skin, lung, liver, kidneys, testis, urinary bladder, esophagus and brain. Our Data indicate that neonatal purpura fulminans can be familial and caused by severe homozygous PC deficiency.

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FACTOR II ACTIVATING ACTIVITY IN EXTRACTS OF TUMORAL NECROSIS FROM TWO MURINE BREAST ADENOCARCINOMAS

10.1055/s-0038-1643206 ◽

1987 ◽

Author(s):

A Blanco ◽

R Bonfil ◽

O Bustoabad ◽

M Lazzari

Keyword(s):

Coagulation Factors ◽

Factor Vii ◽

Factor V ◽

Factor X ◽

Extrinsic Pathway ◽

Factor Ii ◽

Metastatic Capacity ◽

Plasma Recalcification Time ◽

Recalcification Time ◽

Breast Adenocarcinomas

Increased deposition and lysis of fibrin, associated with malignant tissue, has led to look for activators of both the coagulation and fibrinolytic systems produced by tumor cells. We report the evidences of a procoagblant activity (PA) in the extracts of intratumoral necrosis from two experimental breast adenocarcinomas in murine model (BALB/c). The tumors have different metastatic capacity (MC). M3 without MC and MM3 with high MC.The addition of the extracts to: 1- Normal Plasma, 2- Deficient substrates in coagulation factors, 3- Purified, fibrinogen (I), showed: 1- Shortening of the plasma recalcification time (PRT) and APTT, without ;modification on prothrombin time (PT), 2- Reduction of the PRT on deficient substrates in factors: VIII; VII; VII and X; V; V, VII and X; without modification on II deficient substrate, 3- No PA on I. Table:C: Control, s: seconds, m: minutes. The PA was not affected by heparin. The results suggest that the PA is independent of the presence of either factor VIII or factor VII (intrinsic or extrinsic pathway respectively), as well as presence of either factor V or factor X. Any effect was observed either on factor II deficient substrate or on I, so, there was no evidence of thrombin activity The PA could be act directly on factor II, suggesting that fibrin formation could be induced by a “non-classical” activation pathway. No significant differences (p>0.5) in PA were observed between both tumoral necrosis extracts. The necrotic area in M3 (37%) is bigger than in MM3 (18%). So, much more PA could be present in MM3 and this could play a role in the MC of this tumor.

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Feiba Immuno: A Preparation with Factor Eight Inhibitor Bypassing Activity

10.1055/s-0039-1682501 ◽

1977 ◽

Author(s):

F. Elsinger

Keyword(s):

Factor Viii ◽

Factor Xa ◽

Coagulation Factors ◽

Active Principle ◽

Factor Viii Inhibitor ◽

Factor V ◽

In Vitro Experiments ◽

Factor X ◽

Viii Inhibitor

FEIBA IMMUNO is a preparation in which a new activity is generated capable of bypassing factor VIII. The preparation which is used to treat patients with inhibitors (especially inhibitors to factor VIII) is standardized in FEIBA units, i.e. in terms of its in vitro capacity to shorten the activated PTT of a factor VIII inhibitor plasma.It could be concluded from different in vitro experiments that none of the classic’ activated coagulation factors is responsible for the factor VIII bypassing reaction; FEIB-activity seems to be correlated to a new complex of coagulation factors.To get an answer to the question which coagulation factors are essential for FEIB-activity, we tried to generate this activity from different deficient plasmas; from these experiments the following conclusions could be drawn:, the presence of at least factors VII, IX, and X is essential for the generation of the molecular species responsible for factor VIII as well as factor X bypassing activity, but factor V is not bypassed. This activity is not factor Xa itself. Factors VIII and V are not necessary for the generation of this active principle, but factor V is finally needed for its bypassing action.

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ANTICOAGULANT EFFECT OF INCUBATED FIBRINOGEN

Canadian Journal of Biochemistry and Physiology ◽

10.1139/y58-029 ◽

1958 ◽

Vol 36 (1) ◽

pp. 249-259 ◽

Cited By ~ 3

Author(s):

D. C. Triantaphyllopoulos

Keyword(s):

Ammonium Sulphate ◽

Coagulation Factors ◽

The Other ◽

Anticoagulant Effect ◽

Factor Vii ◽

Factor V ◽

Thrombin Time ◽

Fresh Plasma ◽

Native Plasma ◽

Ammonium Sulphate Saturation

Sterile fibrinogen rendered non-clottable by incubation was mixed with fresh plasma and the thrombin time determined. An appreciable prolongation was observed. The incubated fibrinogen was then fractionally precipitated with ammonium sulphate. The material precipitated between 25 and 50% ammonium sulphate saturation, when added to freshly drawn but still unclotted blood, or native plasma, prevented its coagulation. This action could be reversed by an approximately fivefold dilution with distilled water and addition of calcium chloride and thrombin, thus excluding fibrinolysis as the cause of the anticoagulant effect. Determinations of the respective coagulation factors showed that no decrease occurred in prothrombin, factor VII, plasma thromboplastin component, and fibrinogen. On the other hand a statistically significant decrease in factor V was observed when calcium was present.

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Parahaemophilia: A Rare Case Report

Journal of Bangladesh College of Physicians and Surgeons ◽

10.3329/jbcps.v38i4.48985 ◽

2020 ◽

Vol 38 (4) ◽

pp. 205-208

Author(s):

Mohammed Nuruzzaman Bhuiyan ◽

Susane Giti ◽

Arif Ahmed Khan ◽

Md Moshiur Rahman ◽

Md Anwarul Karim

Keyword(s):

Rare Case ◽

Bleeding Time ◽

Armed Forces ◽

Coagulation Factors ◽

Activated Partial Thromboplastin Time ◽

Factor V ◽

Thrombin Time ◽

Normal Range ◽

Rare Case Report ◽

Mucosal Bleeding

Parahaemophilia or Owren’s diseaseis a rare haemorrhagic disorder occurs due to congenital and frequently familial deficiency of Factor V.It is characterized by epistaxis, bruising, mucosal bleeding, soft tissue bleeding and haemarthrosis. We report a case of 6 year old female patient with overlapping features with other haemorrhagic disorder. With the complaints of recurrent episodic per rectal bleeding, patient was evaluated at different hospitals in Chattagram and was diagnosed as a case of Haemophilia B and treated accordingly. As her condition was not improved expectedly, she was referred to Armed Forces Institute of Pathology (AFIP) for further evaluation. The lab tests showed prolongation of prothrombin time (PT) and activated partial thromboplastin time (APTT), with normal bleeding time (BT) and thrombin time (TT). Coagulation factors assay revealed a significant decrease of factor V, 1% of normal range. Other coagulation factors are normal. She was treated with FFP and recovered four weeks after treatment. J Bangladesh Coll Phys Surg 2020; 38(4): 205-208

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