vitamin-k-semiquinone-radical and Factor-VII-Deficiency

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency.. We performed a literature search and included all articles published between 1980 and August 2015.. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

Topics: Factor VII Deficiency; Factor VIIa; Female; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Infections; Male; Neoplasms; Prognosis; Vitamin K

Congenital bleeding disorders of the vitamin K-dependent coagulation factors represent only about 15-20% of all congenital bleeding disorders. However, they played an important role of the history of blood coagulation. Prothrombin was the first entity dealt with. Subsequently, in the late 1940s or early 1950s, the discovery of factor IX allowed the separation of hemophilia into two groups, A and B. In the 1950s, the discovery of factors VII and X allowed the formulation of a logic and plausible explanation for the clotting mechanism. The subsequent discovery of vitamin K-dependent proteins with an inhibitory effect on blood coagulation has further enhanced the importance of the vitamin K-dependent clotting factors. Recently, the study of families with multiple defects of the prothrombin complex has spurred the interest in vitamin K metabolism and the gamma-carboxylation system. The relevance of these studies had also an important role in the understanding the mechanism of action of other noncoagulation-related proteins. The vitamin K-dependent clotting factors represent a homeostatic mechanism at the basis of the hypercoagulability (thrombosis)-hypocoagulability (hemorrhagic) system, namely, to a mechanism that is vital for survival. The different bleeding condition will be dealt with separately, namely, prothrombin or Factor II, Factor VII, Factor IX (hemophilia B), and Factor X deficiencies. An additional heading deals with the combined defect of the prothrombin complex, namely, combined deficiency of Factor II, Factor VII, Factor IX, and Factor X. Since, sometimes, a hemorrhagic role has been attributed to Protein Z deficiency, another vitamin K-dependent protein, this defect will also be dealt with, even though briefly. Each deficiency has been approached in a global manner, namely, with adequate reference to history, background, prevalence, classification, hereditary pattern, biochemistry and function, molecular biology, clinical picture, updated laboratory diagnosis, prognosis, and therapy. Particular emphasis has been placed on the significance of cases with "true" deficiency [cross-reacting material (CRM negative)] and cases with abnormalities (CRM positive). The genetic, clinical, and laboratory implications of these two forms have been extensively discussed in every instance. The importance of a multiple, combined diagnostic approach that has to include whenever possible clotting, chromogenic, immunological, and molecular biology studies has bee

Topics: Blood Coagulation Disorders; Blood Proteins; Factor VII Deficiency; Factor X Deficiency; Hemophilia B; Humans; Hypoprothrombinemias; Prognosis; Vitamin K

Topics: Afibrinogenemia; Antigens; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Sedimentation; Blood Transfusion; Factor VII Deficiency; Factor XIII Deficiency; Fibrinogen; Hemophilia A; Hemophilia B; Humans; Vitamin K; von Willebrand Diseases

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Factor V Deficiency; Factor VII Deficiency; Factor VIII; Fibrinogen; Freezing; Hemophilia A; Hemophilia B; Hemorrhage; Hemostasis; Humans; Hypoprothrombinemias; Plasma; Plasma Volume; Prothrombin; Prothrombin Time; Thromboplastin; Vitamin K

A hereditary deficiency in coagulation factor VII (FVII) may affect the international normalized ratio (INR) value. However, FVII deficiency is occasionally associated with a tendency to bleed spontaneously. We hypothesized that perioperative substitution with coagulation factor concentrates might not be indicated in most patients.. In this retrospective data analysis, we included all patients with hereditary heterozygous FVII deficiency who underwent surgical procedures at the University Hospital Basel between December 2010 and November 2015. In addition, by searching the literature, we identified publications reporting patients with FVII deficiency undergoing surgical procedures without perioperative substitution.. We identified 22 patients undergoing 46 surgical procedures, resulting in a prevalence of 1:1500-2000. Coagulation factor concentrates were administered during the perioperative period in 15 procedures (33 %), whereas in the other 31 procedures (66 %), FVII deficiency was not substituted. No postoperative bleeding or thromboembolic events were reported. In addition, we found no differences in pre- and postoperative hemoglobin and coagulation parameters, with the exception of an improved postoperative INR value in the substituted group. In the literature review, we identified five publications, including 125 patients with FVII deficiency, undergoing 213 surgical procedures with no perioperative substitution.. Preoperative substitution using coagulation factor concentrates does not seem to be mandatory in patients with an FVII level ≥15 %. For decision-making on preoperative substitution, patient history of an increased tendency to bleed may be more important than the FVII level or increased INR value.

Topics: Adult; Aged; Factor VII; Factor VII Deficiency; Female; Heterozygote; Humans; International Normalized Ratio; Male; Middle Aged; Perioperative Care; Postoperative Complications; Postoperative Hemorrhage; Prevalence; Retrospective Studies; Thromboembolism; Vitamin K

Combined deficiency of the vitamin K-dependent clotting factors (VKCFD) is a rare bleeding disorder involving defective gamma-carboxylation of coagulation factors II , VII, IX and X as well as natural anticoagulants protein C and protein S. The disease is characterized by a cluster of different, often life threatening, bleeding symptoms occurring both spontaneously and in a surgical setting. In the present paper we describe two different treatment modalities to be used both in a programmed surgical procedure and in an emergency scenario. As this disease is a natural model that resembles oral anticoagulation, our experience discloses a possible rationale in the use of recombinant activated FVII for warfarin reversal.

Topics: Adult; Biopsy; Blood Coagulation Disorders, Inherited; Blood Coagulation Tests; Blood Loss, Surgical; Factor VII; Factor VII Deficiency; Factor VIIa; Female; Gastroscopy; Hemostasis, Surgical; Homozygote; Humans; Mixed Function Oxygenases; Recombinant Proteins; Tooth Extraction; Vitamin K; Vitamin K Epoxide Reductases

Topics: Aminocaproic Acid; Blood Transfusion; Deamino Arginine Vasopressin; Edema; Factor VII Deficiency; Factor VIIa; Hemostatics; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Postoperative Hemorrhage; Recombinant Proteins; Shock; Tooth Extraction; Vitamin K

Topics: Acetaminophen; Acetylcysteine; Factor IX; Factor VII Deficiency; Humans; International Normalized Ratio; Liver Function Tests; Poisoning; Prothrombin Time; Time Factors; Vitamin K

Four factor deficiency is variably associated with mild to fatal bleeding. We describe a 3-month-old boy, born of consanguineous parents, who presented with a right subdural haematoma and a clotting screen showing a prothrombin time (PT) > 100 s, an activated partial thromboplastin time (aPTT) > 150 s, a fibrinogen of 0.4 g/l, and fibrinogen degradation products < 1 microg/ml. He was given 300 U of factor IX concentrate (containing factors II and X) and 1 mg of vitamin K intravenously. Forty-five minutes later, clotting tests showed a PT of 24 s, an aPTT of 31 s and a fibrinogen of 2.6 g/l. The patient was found to be deficient in all the vitamin K-dependent factors: factors II, VII, IX and X, protein C and protein S. A 14-base deletion was found in intron 1 (bases 1056-1069) of the gamma-carboxylase gene. The patient and his elder sister were homozygous for this deletion, whereas both parents were heterozygous. The deletion destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. Our results suggest that this element may be involved in the regulation of gamma-carboxylase expression. Expression studies are being completed so that this region can be definitively ascribed as a cis-acting element involved in gene regulation.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Carbon-Carbon Ligases; Consanguinity; Factor VII Deficiency; Factor X Deficiency; Female; Hematoma, Subdural; Hemophilia B; Humans; Hypoprothrombinemias; Infant; Introns; Male; Protein C Deficiency; Protein Processing, Post-Translational; Protein S Deficiency; Sequence Deletion; Thrombophilia; Vitamin K

The use of replacement FVII is critical to the successful treatment of life-threatening bleeds in newborns and infants with severe FVII deficiency (<1%). However, the clinical efficacy, optimum dosage and pharmacologic recovery of rFVIIa in such children has not been studied systematically. This report is a case of an infant with severe FVII deficiency (FVII:C at 0%) and massive intracranial haemorrhage in which successful use of rFVIIa (NovoSeven) was carefully monitored. The drug was administered by intravenous bolus through a central line every 4 h at each of three dose levels: 15 microg kg-1, 22 microg kg-1 and 30 microg kg-1. FVII:C was >100% between 30 and 180 min after each infusion with mean trough levels above 25% for all three dose levels. There was no evidence of hyper-coagulation as indicated by measurements of the platelet count, D-dimer, plasma protamine paracoagulant and fibrinogen levels in spite of high FVII:C concentration. In this infant, rFVIIa was well-tolerated, maintained effective haemostasis with good clinical outcome, and produced consistent therapeutic mean trough levels above 25% FVII:C even at 15 microg kg-1 every 4 h.

Topics: Antigens; Blood Coagulation Tests; Factor VII; Factor VII Deficiency; Factor VIIa; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hematoma; Hemostasis; Hispanic or Latino; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intracranial Hemorrhages; Male; Platelet Count; Protamines; Prothrombin; Recombinant Proteins; Vitamin K

Abnormal bleeding following routine orchectomy of a 5-month-old mixed breed was determined to be due to factor VII deficiency. Although pedigree information was unavailable, failure to respond to vitamin K therapy and the absence of a plasma coagulation inhibitor suggested that the factor VII deficiency was likely inherited rather than acquired.

Topics: Animals; Blood Coagulation Factors; Dog Diseases; Dogs; Factor VII Deficiency; Male; Orchiectomy; Vitamin K

Factor VII deficiency is characterized by epistaxis, bruising, hemarthrosis, menorrhagia, gastrointestinal bleeding, hematuria, and intracranial hemorrhage during infancy. Causes of acquired factor VII deficiency include liver disease, Vitamin K deficiency, and warfarin administration. Congenital factor VII deficiency is an autosomal recessive disorder, with the homozygotes having a severe deficiency and the heterozygotes a moderate deficiency of factor VII. Orthopedic, gynecological, cardiothoracic, and abdominal surgical procedures have been successfully performed in patients with factor VII deficiency both with and without factor VII replacement. We present two patients with moderate and moderately severe factor VII deficiency who successfully underwent intracranial procedures using plasma during the perioperative period for factor VII replacement. One patient successfully underwent stereotactic placement of mesial temporal lobe depth electrodes and subdural strip electrodes followed by anterior temporal lobectomy for medically refractory seizures. The second patient successfully underwent craniotomy for an olfactory groove meningioma. No bleeding complications were encountered with any of the three intracranial procedures performed. These cases represent the first reported cases of successful intracranial procedures in patients with factor VII deficiency, other than shunting procedures performed for intraventricular hemorrhage during infancy.

Topics: Adult; Aged; Blood Transfusion; Brain; Brain Neoplasms; Craniotomy; Electrodes, Implanted; Factor VII Deficiency; Female; Humans; Male; Meningioma; Neurosurgery; Psychosurgery; Seizures; Stereotaxic Techniques; Temporal Lobe; Vitamin K

Hereditary combined deficiency of vitamin K-dependent factors is a rare entity. We report a 7-year-old girl of Arab origin with hereditary deficiency of the procoagulants factors II, VII, IX and X and the natural anticoagulants proteins C and S. The patient is the tenth offspring of a consanguinous marriage and presented at 6 weeks with spontaneous intracerebral haemorrhage. Symptoms improved following plasma infusion. A sibling died at 5 d from uncontrollable umbilical bleeding. Blood coagulation work-up at 6 years showed: factor II:C (activity) 12 U/dl, factor II:Ag (antigen) 40 U/dl; factor VII:C 12 U/dl; factor IX:C 36 U/dl, factor IX:Ag 57 U/dl; factor X:C 17 U/dl, factor X:Ag 54 U/dl; protein C activity 43 U/dl; protein C:Ag 45 U/dl; protein S:Ag 34 U/dl; levels of factors V:C and VIII:C were normal. Assays of coagulation factors in the parents and five of the siblings were within the normal range. Following acute infection and dilantin therapy procoagulant activity levels were reduced further and were partially increased after vitamin K infusion. Crossed immunoelectrophoresis of prothrombin in the presence of calcium lactate revealed a population of des-carboxyprothrombin. Serum vitamin K epoxide levels were undetectable. The data suggest that the defect in our patient stems from abnormal carboxylation of the vitamin K-dependent proteins and that the mode of inheritance is autosomal recessive.

Topics: Blood Coagulation Disorders; Child; Factor VII Deficiency; Factor X Deficiency; Female; Glycoproteins; Hemophilia B; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Pedigree; Protein C Deficiency; Protein S; Vitamin K; Vitamin K 1

A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX, and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitamin-antagonist-related rodenticides. The cats did not have evidence of hepatic disease, gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in normalization of clotting factor concentrations. However, when treatment was discontinued in 2 cats, prothrombin and activated partial thromboplastin values became prolonged again, although the cats did not have clinical signs of a bleeding disorder.

Topics: Animals; Blood Coagulation Disorders; Breeding; Cat Diseases; Cats; Factor VII Deficiency; Factor X Deficiency; Female; Hemophilia B; Hypoprothrombinemias; Male; Partial Thromboplastin Time; Pedigree; Prothrombin; Prothrombin Time; Vitamin K; Vitamin K Deficiency

Human coagulation factor VII is a trace plasma protein belonging to the vitamin K-dependent factors. Two specific and sensitive immunoradiometric assays for factor VII were developed using immunopurified rabbit antibodies against the Ca(II)-independent and Ca(II)-dependent conformation of factor VII. Both assays were insensitive to the activation state of factor VII. The distribution of factor VII antigen was studied in 40 healthy individuals and the antigen level in normal plasma was calculated to be 0.52-0.62 micrograms/ml. The two assays were used in a comparative study of factor VII procoagulant activity and factor VII antigen in patients treated with oral anticoagulants.

Topics: Animals; Antibodies; Anticoagulants; Calcium; Epitopes; Factor VII; Factor VII Deficiency; Factor VIIa; Humans; Protein Conformation; Rabbits; Radioimmunoassay; Reference Values; Vitamin K

Combined deficiency of coagulant activity of the vitamin K-dependent factors was found in a 14-year-old boy suffering from severe hemorrhages. Immunoassays revealed the presence of acarboxyprothrombin. The bleedings could be controlled, but the coagulation defects persisted during more than 2 years' follow-up and could not be corrected by oral or parenteral vitamin K. No intoxication or underlying disease was found. The abnormality was considered a congenital disorder of the carboxylation of prothrombin.

Topics: Adolescent; Blood Coagulation Factors; Factor VII Deficiency; Factor X Deficiency; Follow-Up Studies; Hemophilia B; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Male; Protein Processing, Post-Translational; Prothrombin; Vitamin K

A new chromogenic method has been developed and rigorously standardized for the estimation of factor VII in defibrinated diluted plasma. This method employs a mixture of CaCl2-rabbit brain thromboplastin as activator, diluted factor VII deficient plasma as source of factor X and the chromogenic substrate S2222 for the measurement of factor Xa. The chromogenic method was insensitive to cold- and kaolin-induced activation of factor VII, this in contrast to the one-stage clotting assay. Results obtained with the chromogenic method revealed good correlation with the clotting method in 33 normal subjects, in 42 patients on oral anticoagulant therapy and in five patients with severe congenital factor VII deficiency. A good correlation was also obtained with 'Thrombotest'. Comparative estimation of factor VII and of factor VII cross-reacting material in supernatants of BaCl2 adsorbed plasma of coumarin treated patients revealed that the chromogenic method does not measure decarboxy factor VII. Detailed investigations revealed a half life for decarboxy factor VII of 2.1 +/- 0.6 h.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Barium; Cold Temperature; Factor VII; Factor VII Deficiency; Factor X; Female; Humans; Male; Methods; Vitamin K

Topics: Administration, Oral; Animals; Anticoagulants; Biomarkers; Blood Coagulation Disorders; Blood Proteins; Cattle; Cold Temperature; Factor VII; Factor VII Deficiency; Factor X; Factor X Deficiency; Humans; Hypoprothrombinemias; Kaolin; Protein Precursors; Prothrombin; Prothrombin Time; Rabbits; Thromboplastin; Vitamin K

Prolonged thromboplastin time but normal partial thromboplastin time in coagulation analysis lead to the diagnosis of factor VII-deficiency. The different forms of congenital and acquired factor VII-deficiency and the appropriate therapies are discussed, especially with regard to the recently available factor VII preparation.

Topics: Child; Factor VII; Factor VII Deficiency; Female; Humans; Intestinal Absorption; Male; Nutritional Physiological Phenomena; Vitamin K

Topics: Blood Coagulation Factors; Chromatography, DEAE-Cellulose; Edetic Acid; Factor IX; Factor VII; Factor VII Deficiency; Factor X; Factor X Deficiency; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Hypoprothrombinemias; Infant, Newborn; Prothrombin; Vitamin K

Topics: Acute Disease; Adolescent; Adult; Factor V Deficiency; Factor VII Deficiency; Factor X Deficiency; Humans; Hypoprothrombinemias; Middle Aged; Muscle Spasticity; Paraplegia; Quadriplegia; Spinal Cord Injuries; Vitamin K

Topics: Blood Coagulation Tests; Coumarins; Factor VII Deficiency; Factor X Deficiency; Humans; Hypoprothrombinemias; Plasma; Thromboplastin; Vitamin K

Topics: Alanine Transaminase; Animals; Animals, Newborn; Blood Coagulation; Blood Coagulation Disorders; Cats; Depression, Chemical; Dose-Response Relationship, Drug; Drug Interactions; Factor V Deficiency; Factor VII; Factor VII Deficiency; Female; Folic Acid; Hemophilia A; Hypoprothrombinemias; Liver; Maternal-Fetal Exchange; Phenobarbital; Phenytoin; Pregnancy; Primidone; Rats; Vitamin K

Topics: Adult; Blood Coagulation Tests; Blood Transfusion; Diagnosis, Differential; Factor VII; Factor VII Deficiency; Female; Hemophilia A; Humans; Male; Middle Aged; Prothrombin Time; Tooth Extraction; Vitamin K

Topics: Blood Coagulation Tests; Factor VII; Factor VII Deficiency; Factor X; Heterozygote; Homozygote; Humans; Hypoprothrombinemias; Infant; Male; Pedigree; Vitamin K

Topics: Animals; Factor IX; Factor VII; Factor VII Deficiency; Factor X; Hemophilia B; Hypoprothrombinemias; In Vitro Techniques; Liver; Perfusion; Prothrombin; Rats; Vitamin K

Topics: Adult; Blood Coagulation Tests; Factor VII; Factor VII Deficiency; Female; Humans; Stanozolol; Uterine Hemorrhage; Vitamin K

Topics: Animals; Cattle; Dicumarol; Dogs; Factor VII Deficiency; Factor XI Deficiency; Fibrin; Hemophilia A; Hemophilia B; In Vitro Techniques; Prothrombin; Snakes; Thrombin; Thromboplastin; Time Factors; Tissue Extracts; Venoms; Vitamin K

Topics: Blood Coagulation Tests; Factor IX; Factor VII Deficiency; Female; Humans; Infant; Prothrombin; Purpura; Thromboplastin; Vitamin K

Topics: Factor VII; Factor VII Deficiency; Factor X; Humans; Hypoprothrombinemias; Liver Diseases; Prothrombin; Vitamin K

Topics: Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Blood Platelet Disorders; Factor VII Deficiency; Female; Humans; Hypoprothrombinemias; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Thrombocytopenia; Vitamin K

Topics: Antifibrinolytic Agents; Factor VII Deficiency; Humans; Hypoprothrombinemias; Infant; Purpura; Vitamin K

Topics: Child; Child, Preschool; Factor VII Deficiency; Female; Genes, Recessive; Heterozygote; Homozygote; Humans; Male; Pedigree; Vitamin K