GGCX ‐related congenital combined vitamin K‐dependent clotting factors deficiency‐1: Description of a fetus with chondrodysplasia punctata

2021 ◽  
Author(s):  
Alix Mathonnet ◽  
Séverine Cunat ◽  
Fabienne Allias ◽  
Sandrine Caillot ◽  
Cyrielle Thonnon ◽  
...  
Keyword(s):  
Vitamin K ◽  
Chondrodysplasia Punctata ◽  
Clotting Factors

scholarly journals Chondrodysplasia Punctata: A Case Report of Fetal Warfarin Syndrome

2017 ◽  
Vol 15 (1) ◽  
pp. 81-84 ◽  
Author(s):  
Swachchhanda Songmen ◽  
Om Biju Panta ◽  
Sharma Paudel ◽  
Ram Kumar Ghimire
Keyword(s):  
Vitamin K ◽  
Heart Valves ◽  
Choanal Atresia ◽  
Prosthetic Heart Valve ◽  
Normal Vaginal Delivery ◽  
Facial Dysmorphism ◽  
Prosthetic Heart Valves ◽  
Chondrodysplasia Punctata ◽  
Clotting Factors ◽  
Nasal Bridge

Chondrodysplasia punctata is abnormal calcification in the cartilage of developing bones and has been seen in association with deranged vitamin K metabolism. Warfarin, an oral anticoagulant acting on vitamin K dependent clotting factors is known to cause chondrodysplasia punctata. Despite the knowledge of the condition the management of patients with prosthetic heart valves might require use of the drug for anticoagulation. Here, we present a case of a fetal warfarin syndrome in a second born child of a 27 year lady under warfarin for prosthetic heart valve. The pregnancy was complicated by polyhydramnios in third trimester and terminated at term by normal vaginal delivery. The baby was well, except for facial dysmorphism in the form of depressed nasal bridge, narrow nares and suspected left choanal atresia. Radiograph revealed stippled ephiphysis of vertebra, femora and humera supporting diagnosis of fetal warfarin syndrome. The baby did not develop any perinatal complication and was discharged home.

Hypercoagulable State in the Watanabe Heritable Hyperlipidemic Rabbit, an Animal Model for the Progression of Atherosclerosis

1989 ◽  
Vol 61 (01) ◽  
pp. 140-143 ◽  
Author(s):  
Yoshitaka Mori ◽  
Hideo Wada ◽  
Yutaka Nagano ◽  
Katsumi Deguch ◽  
Toru Kita ◽  
...  
Keyword(s):  
Vitamin K ◽  
Fibrinogen Level ◽  
Plasma Cholesterol ◽  
Age Groups ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Group A ◽  
Hyperlipidemic Rabbit ◽  
Group B ◽  
Progression Of Atherosclerosis

SummaryBlood coagulation in a strain of rabbits designated as Watanabe heritable hyperlipidemic (WHHL) rabbits was examined. The activities of vitamin K-dependent clotting factors, contact factors and clotting factor VIII (F VIII) and the fibrinogen level were significantly higher in WHHL rabbits than in normolipidemic rabbits (all age groups). Values for vitamin Independent clotting factor were already higher at 2 months of age. Contact factors and fibrinogen levels increased age after 5 to 8 months. F VIII increased between 5 and 8 months and then decreased. At 2 months of age, WHHL rabbits were divided into two groups. Group A was fed standard rabbit chow and group B standard rabbit chow containing 1% probucol. Probucol prevented the progression of atherosclerosis in group B in the absence of a significant reduction in plasma cholesterol level. F VIII and fibrinogen levels were statistically decreased in all rabbits at all ages in group B (P<0.05). These differences in clotting factors between the two groups were most obvious at 8 months (P<0.02).We conclude that vitamin K-dependent clotting factors may increase with hyperlipemia and that increases in F VIII and fibrinogen may be closely related to the progression of throm- boatherosclerosis.

Mutations which Introduce Free Cysteine Residues in the Gla-Domain of Vitamin K Dependent Proteins Result in the Formation of Complexes with α1-Microglobulin

1996 ◽  
Vol 75 (01) ◽  
pp. 070-075 ◽  
Author(s):  
E G C Wojcik ◽  
P Simioni ◽  
M v d Berg ◽  
A Girolami ◽  
R M Bertina
Keyword(s):  
Vitamin K ◽  
Protein C ◽  
Cysteine Residue ◽  
Factor Ix ◽  
Disulphide Bond ◽  
Clotting Factors ◽  
High Molecular Weight Complex ◽  
Low Concentrations ◽  
Gla Domain ◽  
Formation Of Complexes

SummaryWe have previously described a genetic factor IX variant (Cys18→Arg) for which we demonstrated that it had formed a heterodimer with armicroglobulin through formation of a disulphide bond with the remaining free cysteine residue of the disrupted disulphide bond in the Gla-domain of factor IX. Recently, we observed a similar high molecular weight complex for a genetic protein C variant (Arg-1→Cys). Both the factor IX and the protein C variants have a defect in the calcium induced conformation. In this study we show that the aminoterminus of this protein C variant is prolonged with one amino acid, cysteine. This protein C variant, as well as protein C variants with Arg9→Cys and Ser12→Cys mutations which also carry a free cysteine residue, are shown to be present in plasma as a complex with α1-microglobulin. A prothrombin variant with a Tyr44→Cys mutation, had not formed such a complex. Furthermore, complexes between normal vitamin K-dependent clotting factors and α1-microglobulin were shown to be present in plasma at low concentrations. The data suggest that the presence of an unpaired cysteine residue in the propeptide or the N-terminal half of the Gla-domain has strongly promoted the formation of a complex with α1-microglobulin in the variants.

Kinetic Aspects of the Interaction of Blood-Clotting Enzymes

1968 ◽  
Vol 20 (01/02) ◽  
pp. 078-087 ◽  
Author(s):  
H. C Hemker ◽  
A. D Muller
Keyword(s):  
Vitamin K ◽  
Blood Clotting ◽  
Experimental Results ◽  
Factor X ◽  
Clotting Factors ◽  
Vitamin K Deficiency ◽  
K Deficiency

SummaryPIVKA, the circulating anticoagulant protein found in vitamin K deficiency can, on kinetical grounds, be recognized as an analogue of factor X. The existence of analogues of other vitamin K-dependent clotting factors cannot be ruled out, but need not be assumed to explain the experimental results.

The Reaction of Thiol Compounds with the Vitamin-K Dependent Clotting Factors

1969 ◽  
Vol 21 (03) ◽  
pp. 573-579 ◽  
Author(s):  
P Fantl
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Anaerobic Conditions ◽  
Clotting Factors ◽  
Thiol Compounds ◽  
Aerobic Conditions ◽  
One Stage ◽  
Factor Ii ◽  
Ph Dependent ◽  
The One

SummaryTreatment of human and dog oxalated plasma with 0.2 to 1.0 × 10−1 M 2.3-dithiopropanol (BAL) or dithiothreitol (DTT) at 2–4° C for 30 min results in the reduction of the vitamin-K dependent clotting factors II, VII, IX and X to the respective-SH derivatives. The reaction is pH dependent. Under aerobic conditions the delayed one stage prothrombin time can be partly reversed. Under anaerobic conditions a gradual prolongation of the one stage prothrombin time occurs without reversal.In very diluted plasma treated with the dithiols, prothrombin can be converted into thrombin if serum as source of active factors VII and X is added. In contrast SH factors VII, IX and X are inactive in the specific tests. Reoxidation to active factors II, VII, IX and X takes place during adsorption and elution of the SH derivatives. The experiments have indicated that not only factor II but also factors VII, IX and X have active-S-S-centres.

Increased Activity of Vitamin K-Dependent Clotting Factors in Human Hyperlipoproteinaemia – Association with Cholesterol and Triglyceride Levels

1977 ◽  
Vol 38 (02) ◽  
pp. 0465-0474 ◽  
Author(s):  
M Constantino ◽  
C Merskey ◽  
D. J Kudzma ◽  
M. B Zucker
Keyword(s):  
Vitamin K ◽  
Plasma Lipids ◽  
Coagulation Factors ◽  
Clotting Factor ◽  
Factor X ◽  
Clotting Factors ◽  
Blood Coagulation Factors ◽  
Cholesterol Levels ◽  
Type V ◽  
Increased Activity

SummaryLevels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.

scholarly journals Vitamin K-dependent protein S is similar to rat androgen-binding protein

1987 ◽  
Vol 243 (1) ◽  
pp. 293-296 ◽  
Author(s):  
M E Baker ◽  
F S French ◽  
D R Joseph
Keyword(s):  
Vitamin K ◽  
Binding Protein ◽  
Protein A ◽  
Serine Proteinase ◽  
Protein S ◽  
Clotting Factors ◽  
The Family ◽  
Androgen Binding Protein ◽  
Dependent Protein ◽  
Androgen Binding

Vitamin K-dependent protein S belongs to the family of clotting factors (e.g. Factors IX and X, and protein C). Unlike the other clotting factors, the C-terminal half (residues 250-634) of protein S is not a serine proteinase. In fact, the function of residues 250-634 of protein S is unknown. By using computer programs designed to detect evolutionary relationships between proteins, we find that this part of protein S is similar to rat androgen-binding protein, a protein produced and secreted by testicular Sertoli cells. The homology between protein S and androgen-binding protein suggests new approaches for elucidating their functions.

scholarly journals Vitamin K-Dependent Coagulation Factors That May be Responsible for Both Bleeding and Thrombosis (FII, FVII, and FIX)

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 42S-47S ◽  
Author(s):  
Antonio Girolami ◽  
Silvia Ferrari ◽  
Elisabetta Cosi ◽  
Claudia Santarossa ◽  
Maria Luigia Randi
Keyword(s):  
Venous Thrombosis ◽  
Vitamin K ◽  
Protein C ◽  
Protein S ◽  
Coagulation Factors ◽  
Bleeding Tendency ◽  
Clotting Factors ◽  
Protein Z ◽  
Clinical Observations

Vitamin K-dependent clotting factors are commonly divided into prohemorrhagic (FII, FVII, FIX, and FX) and antithrombotic (protein C and protein S). Furthermore, another protein (protein Z) does not seem strictly correlated with blood clotting. As a consequence of this assumption, vitamin K-dependent defects were considered as hemorrhagic or thrombotic disorders. Recent clinical observations, and especially, recent advances in molecular biology investigations, have demonstrated that this was incorrect. In 2009, it was demonstrated that the mutation Arg338Leu in exon 8 of FIX was associated with the appearance of a thrombophilic state and venous thrombosis. The defect was characterized by a 10-fold increased activity in FIX activity, while FIX antigen was only slightly increased (FIX Padua). On the other hand, it was noted on clinical grounds that the thrombosis, mainly venous, was present in about 2% to 3% of patients with FVII deficiency. It was subsequently demonstrated that 2 mutations in FVII, namely, Arg304Gln and Ala294Val, were particularly affected. Both these mutations are type 2 defects, namely, they show low activity but normal or near-normal FVII antigen. More recently, in 2011-2012, it was noted that prothrombin defects due to mutations of Arg596 to Leu, Gln, or Trp in exon 15 cause the appearance of a dysprothrombinemia that shows no bleeding tendency but instead a prothrombotic state with venous thrombosis. On the contrary, no abnormality of protein C or protein S has been shown to be associated with bleeding rather than with thrombosis. These studies have considerably widened the spectrum and significance of blood coagulation studies.

Familial Warfarin Resistance

1983 ◽  
Vol 17 (4) ◽  
pp. 281-283 ◽  
Author(s):  
Robert J. Holt ◽  
César O. Freytes
Keyword(s):  
Venous Thrombosis ◽  
Vitamin K ◽  
Genetic Basis ◽  
Clotting Factors ◽  
First Report ◽  
Documented Case ◽  
Coumarin Anticoagulant ◽  
Familial Type ◽  
Warfarin Resistance ◽  
Hepatic Synthesis

Warfarin, a coumarin anticoagulant, acts by interfering with the hepatic synthesis of the vitamin-K-dependent clotting factors. It is used clinically in the treatment or prophylaxis of venous thrombosis and embolisms. Resistance to the effects of the coumarin and indanedione anticoagulants has been reported in rats and man, but its incidence has been defined as extremely rare. Resistance has been described as relative, acquired, or hereditary. The first well-documented case was also the first report to identify a genetic basis for this resistance. Since that time, there has been only one other study that strengthened the evidence for a hereditary transmission, and only a few other reports have suggested hereditary influence as a reason for coumarin resistance. In this report, a patient who presented with a familial-type warfarin resistance is described. A discussion of previous reports and possible mechanisms for nonfamilial warfarin resistance is also included.

Sign in / Sign up

Export Citation Format

Share Document