Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor IX is the zymogen of the serine protease factor IXa involved in blood coagulation. In addition to a catalytic domain homologous to the chymotrypsin family, it has Ca2+, phospholipid, and factor VIIIa binding regions needed for full biologic activity. We isolated a nonfunctional factor IX protein designated factor IXEagle Rock (IXER) from a patient with hemophilia B. The variant protein is indistinguishable from normal factor IX (IXN) in its migration on sodium dodecyl sulfate-gel electrophoresis, isoelectric point in urea, carbohydrate content and distribution, number of gamma-carboxyglutamic acid residues, and beta-OH aspartic acid content, and in its binding to an anti-IXN monoclonal antibody which has been shown previously to inhibit the interaction of factor VIIIa with factor IXaN. Further, IXER is cleaved to yield a factor IXa-like molecule by factor XIa/Ca2+ at a rate similar to that observed for IXN. However, in contrast to IXaN, IXaER does not bind to antithrombin-III (specific inhibitor of IXaN) and does not catalyze the activation of factor X (substrate) to factor Xa. To identify the mutation in IXER, all eight exons of IXN and IXER gene were amplified by the polymerase chain reaction technique and cloned. A single point mutation (G----T) which results in the replacement of Val for Gly363 in the catalytic domain of IXER was identified. Gly363 in factor IXa corresponds to the universally conserved Gly193 in the active site sequence of the chymotrypsin serine protease family. X-ray crystallographic data in the literature demonstrate a critical role of this Gly in stabilizing the active conformation of chymotrypsin/trypsin in two major ways: 1) in the formation of the substrate binding site; and 2) in the development of the oxyanion hole. Our computer structural data support a concept that the Gly363----Val change prevents the development of the active site conformation in factor IXa such that the substrate binding site and the oxyanion hole are not formed in the mutated enzyme.
 ...
PMID:Experimental and theoretical evidence supporting the role of Gly363 in blood coagulation factor IXa (Gly193 in chymotrypsin) for proper activation of the proenzyme. 230 34

The association between coagulation abnormalities and pregnancy outcome was investigated in a case-control study conducted at Lady Hardings Medical College and Associated Hospitals in New Delhi, India, in 1991-92. Enrolled were 30 neonates born to mothers with pregnancy-induced hypertension (PIH) and 30 infants of normotensive mothers. Compared with control infants, infants of mothers with PIH had significantly elevated levels of prothrombin time (PT), partial thromboplastin time with kaolin (PTTK), thrombin time (TT), and fibrinogen and fibrinogen degradation products (FDP) and significantly reduced platelet counts and fibrinogen. PTTK and TT were significantly higher in neonates born to mothers with hypertension of more than 1 month's duration, but the difference in PT, fibrinogen, and platelet count was not significant. Also observed was a significant correlation between decreasing gestational age and derangement in all coagulation parameters and between decreasing birth weight and an increase in FDP level. The incidence of disseminated intravascular coagulation was higher in preterm than term neonates. 43.3% of neonates required admission to the neonatal intensive care unit and the perinatal mortality rate was 3.3%.
 ...
PMID:Correlation of coagulation abnormalities with clinical outcome in neonates of mothers with pregnancy induced hypertension. 983 64

A prominent evidence of inherited bleeding disorder in newborn males is excessive post-circumcision bleeding. Male circumcision in Nigeria is the rule rather than the exception. Male siblings of some of the Nigerian haemophiliacs consequently died from severe post-circumcision bleeding. The aim was to determine the incidence of inherited factor VIIIc (FVIIIc) deficiencies in live male infants undergoing circumcision in South West, Nigeria. The study population was 244 male infants drawn from University College Hospital and Our Lady of Apostles Catholic Hospital, Oluyoro, Ibadan. Pre-circumcision prothrombin time, activated partial thromboplastin time and FVIIIc levels were determined. Clinical features of inherited bleeding disorder particularly family history of bleeding diathesis, history of cephalhaematoma and bleeding from the umbilical stump in neonatal life were determined with the aid of a questionnaire. Only one of the mothers (0.4%) gave a family history of bleeding disorder. A history of excessive bleeding from the umbilical stump post delivery was obtained in three (2%) of the patients. Five (2%) other subjects had cephalhaematoma post delivery. Two of the subjects (0.8%) had prolonged activated partial thromboplastin time. The factor VIIIc level was between 31% and 49% in 16.1%, while 1.6% of the neonates had levels between 20% and 26%. This study detected four of the 244 (1.64%) neonates with FVIIIc deficiency, suggestive of either mild haemophilia or von Willebrand's disease. A larger study (including family studies) will be required, so as to arrive at the exact incidence of both haemophilia A and vWD in live male infants in Nigeria.
 ...
PMID:Incidence of factor FVIIIC deficiency in live male infants undergoing circumcision in South West, Nigeria. 1788 Apr 45

Blast is one of the major causes of injury and death in recent armed conflicts. With increased use of improvised explosive devices in Iraq and Afghanistan, more than 71% of combat casualties are caused by explosions. Blast injuries can range from primary (caused by shock wave) to quaternary injuries (e.g., burns), and such injuries can result in an acute coagulopathy denoted by a hypocoagulable state. It is not clear if this coagulopathy observed in victims of explosion is caused by local or general effect of the primary blast injury itself. In this study, 13 pigs were subjected to severe isolated open-field blast injury and we measured indices of coagulation impairment during the first hour after injury: ROTEM, prothrombin time, activated partial thromboplastin time, coagulation factors, thrombin generation potential, platelet count, platelet activation, platelet function, and procoagulant microparticle formation. After 1 h, the mortality was 33%. No coagulation dysfunction was observed in the survivors in this period. This study presented a highly reproducible and consistent isolated blast injury in large mammals with comprehensive coagulation testing. The data suggest that isolated primary blast injury is not responsible for acute coagulopathy of trauma in victims of explosion but seems to lead to an early hypercoagulable state.
...
PMID:Comprehensive evaluation of coagulation in swine subjected to isolated primary blast injury. 2564 12