Plasma Thromboplastin Component Research Articles

Molecular mechanism of microRNA125 regulating human coagulation factor IX gene with nonsense mutation

目的构建人凝血因子Ⅸ小基因（Mini-hF9）及无义突变体，检测其mRNA表达水平，分析microRNA125对无义突变的F9基因表达调控的分子机制。方法利用PCR定点突变技术构建若干无义突变的人Mini-hF9并转染哺乳动物细胞HEK293T等，同时转染miR-125模拟物，通过实时荧光定量PCR (q-PCR）检测Mini-hF9基因mRNA表达水平。结果成功构建了Mini-hF9并在细胞中正确剪接。成功构建了无义突变体M1 (nt 34 G>T in Exon 7）、M2（nt 52 G>T in Exon 7）和M3 (nt 85 G>T in Exon 7）。M1和M2突变体中Mini-hF9基因mRNA表达水平分别为野生型的14.1%（t=15.464，P=0.004）和22.4%（t=15.755，P=0.004），通过放线菌酮处理实验证实这是由于无义介导的mRNA降解（nonsense-mediated mRNA decay, NMD）所致。分别转染miR-125a模拟物和miR-125b模拟物后，M1突变体中Mini-hF9基因mRNA水平分别升高到1.70倍（t=−4.883，P=0.039）和2.40倍（t=−17.537，P=0.003），M2突变体Mini-hF9mRNA水平分别升高到2.02倍（t=−19.264，P=0.003）和2.07倍（t=−9.158，P=0.012）。结论无义突变发生的位置是触发NMD途径的一个关键因素；microRNA125能够通过抑制NMD途径提高无义突变的凝血因子Ⅸ的mRNA水平。

COAGULATION PROFILE AND PLATELET PARAMETERS OF THE ARABIAN SAND GAZELLE (GAZELLA SUBGUTTUROSA MARICA): COMPARISON WITH HUMANS AND CAMELS

During March 2009, we evaluated the hemostatic profile and platelet indices of 18 Arabian sand gazelles (Gazella subgutturosa marica) and compared the results with those from humans and camels (Camelus dromedarius). Gazelles and camels had shorter activated partial thromboplastin times, lower proconvertin and higher antihemophilic factor coagulation activity, and plasma fibrinogen levels than humans. Prothrombin time was longer in sand gazelles and shorter in camels than it was in humans. Plasma thromboplastin component, Stuart factor, and plasma thromboplastin antecedent were similar in gazelles, humans, and camels, whereas the platelet count of the sand gazelle was significantly higher than it was for camels and humans.

The partial thromboplastin time: defining an era in coagulation

The partial thromboplastin time: defining an era in coagulation

Oscar Ratnoff: his contributions to the golden era of coagulation research.

Oscar Ratnoff: his contributions to the golden era of coagulation research.

Home Transfusions of Hemophiliacs

We have had three years' experience with a home transfusion program for hemophiliacs. The group consisted of 36 patients, of which 32 had antihemophilic factor deficiency and 4 had plasma thromboplastin component deficiency. There were minimal technical problems and no serious transfusion reactions. Although there was an increase in the number of reported hemorrhages, there was a concomitant decrease in the number of hospital admissions. Of importance is the fact that there was a decrease in the number of severe orthopedic problems and days lost from school or work. Of equal importance was the psychological impact of home transfusion on patients and their families. This included a sense of self-reliance, an increase in mobility, and freedom from fear. The authors conclude that, until a prophylactic regimen is feasible, home transfusion is the treatment of choice for hemophilia.

Intracranial Suppurative Disease

To Editor.— The paper on Intracranial Suppurative Disease (218: 1542, 1971) would lead one to believe that something new had been developed to obviate intracranial surgery for brain abscess. It should be pointed out that a focal intracranial lesion is not necessarily surgical lesion. The fact that carotid angiograms were normal in six cases initially bears this out. However, in cases 3 and 7, when carotid angiography disclosed a mass lesion, surgery was carried out in conventional manner. In case 1, it is stated that the strongest deterrent to craniotomy was fear of hemorrhage. I could see no indication for craniotomy with normal angiogram and sonoencephalogram. Competent hematologists assure me that plasma thromboplastin component deficiency can be controlled readily by administration of factor IX at time of surgery. In short, this article emphasizes a dogma taught me as a resident: ... in central nervous system sepsis mass

Double-Blind Studies on the Use of Steroids in the Treatment of Acute Hemarthrosis in Patients with Hemophilia

Two double-blind studies showed the clinical effectiveness of a five-day course of corticosteroid treatment of acute hemarthrosis in boys with hemophilia. When antihemophilic factor or plasma thromboplastin component was given repeatedly until return of joint function was judged complete, significantly less replacement therapy of this type was needed if corticosteroids were added to the regimen. When replacement therapy was limited to a single dose of 25 units of antihemophilic factor per kilogram 89 per cent of patients in the corticosteroid group responded favorably, whereas 34 per cent of those in the control group needed additional replacement for complete return of joint function. Immobilization and splinting were not used in the treatment of the joint. These measures tend to weaken the surrounding muscle structure and thereby increase the amount of physical therapy and time needed before ambulation and complete return of function are possible.

The separation of clotting factors: II (Prothrombin) and IX (Plasma thromboplastin component) by isoelectric focusing

1. 1.|Isoelectric focusing was used in an attempt to separate bovine clotting Factors II, VII, IX and X. Factors II and IX were recovered and separated. Poor recovery of Factors VII and X was obtained. These factors did not focus sharply at any particular pH. 2. 2.|Although immunologic studies revealed that the purification of Factors II and IX was incomplete, their separation as achieved by isoelectric focusing was of high enough resolution to allow studies on some of their characteristics. 3. 3.|Factor II was unreactive to 25% sodium citrate or to brain thromboplastin in the absence of serum. Factor IX was recovered in its inactive form. The isoelectric point of Factor II varied between pH 4.6 and 4.9, and that of Factor IX between 4.1 and 4.5. 4. 4.|Further modifications of the techniques used should achieve improved separation and recovery of clotting factors.

Neuropathy induced by hemorrhage.

NEUROPATHY produced by hemorrhage is an infrequently diagnosed and poorly understood condition which has a distinct clinical constellation of signs and symptoms permitting early recognition and treatment before paralysis occurs. It is the purpose of this paper to present three illustrative cases and to discuss the pathogenesis and treatment. Hemorrhage in or around one or more peripheral nerves may be associated with mild or severe pain of acute or subacute onset in the distribution of the involved nerve, followed by motor weakness, atrophy, sensory loss, and loss of the appropriate reflexes. Complete recovery occurs if the hemorrhage is stopped but may be delayed for many months. Conditions Associated With Hemorrhage-Induced Neuropathy Bleeding Disorders.— Any congenital, acquired, or iatrogenic hemorrhagic disorder may cause hemorrhage into or around a peripheral nerve. This condition has been reported with plasma thromboplastin component and antihemophilic globulin 1-5 deficiency, as well as with heparin,

Excision of a pseudocyst of the hand in a hemophiliac (PTC-deficiency). Use of a plasma thromboplastin component concentrate.

A pseudocyst was successfully excised from the hand of a plasma thromboplastin component (IX) deficient patient. The coagulation defect was controlled by infusions of IX-rich plasma fraction.

Hemophilia polymorphism--the genetic plot thickens.

Hemophilia was recognized as a profound bleeding disorder transmitted as a sex-linked recessive trait in the nineteenth century. By the turn of the century it was clear that the fault lay with the blood and not the blood vessels. By the late 1930's, it was established that the hemophilic patient lacked a plasma activity (antihemophilic globulin, AHG, or factor VIII) needed to generate a prothrombin activator. The early 1950's held a surprise: whereas about 85 per cent of hemophilic patients lacked factor VIII activity, about 15 per cent lacked a different activity (plasma thromboplastin component, PTC, or factor IX) needed . . .

Tests of Blood Coagulation and Hemostasis

Previous articles in this series have dealt with the prothrombin time (PT) and the coagulation time (CT).^1,2For many years these were the only tests available for the detection of clotting disorders. With the development of the thromboplastin generation test (TGT) and the partial thromboplastin time (PTT^3,4), clinically important clotting defects which previously went undetected now can be identified. The TGT and PTT are not substitutes for the PT; they are sensitive to different clotting factors. However, the use of the TGT and PTT has largely done away with the usefulness of the Lee-White test. Even when the CT is made more sensitive by the use of tubes coated with silicone, the test remains less sensitive to mild clotting disorders than the TGT or PTT (unpublished data). In addition, for the detection of clinically significant deficiencies of factor VIII (antihemophilic factor) or IX (plasma thromboplastin component), the PTT

Effect of plasma transfusions on the prothrombin time and clotting factors in liver disease.

PATIENTS with liver disease have multiple coagulation defects. Although excessive fibrinolysis, thrombocytopenia, and deficiencies of factors IX (plasma thromboplastin component) and XI (plasma thromboplastin antecedent) may be present in these patients, the most consistent abnormality is a prolonged prothrombin time.1 2 3 This abnormal prothrombin time is usually due to combined deficiencies of factors II (prothrombin), V (proaccelerin), VII (proconvertin) and X (Stuart factor). Treatment for the correction of abnormal clotting mechanisms in patients with severe liver disease is limited. Epsilon aminocaproic acid, steroids and heparin are of value only in occasional patients who exhibit excessive fibrinolysis or disseminated intravascular coagulation.4 , 5 Improvement . . .

Tests of Blood Coagulation and Hemostasis

Probably the most widely used of all clotting tests, Quick's prothrombin time (PT)¹is perhaps the least well understood. Despite its name, we now know that the PT is relatively insensitive to prothrombin (factor II). The test measures the rate of conversion of prothrombin to thrombin in the presence of a tissue extract (thromboplastin) and calcium ions, followed by the polymerization of fibrinogen by thrombin to fibrin. The PT is influenced by the concentrations of four clotting factors besides prothrombin: I (fibrinogen), V (labile factor), VII (stable factor), and X (Stuart-Prower factor). In addition, heparin prolongs the PT, a point frequently overlooked in managing patients treated with anticoagulants. However, the sensitivity of the PT to many factors is the very reason that it is so useful clinically. In patients receiving anticoagulants orally, deficiencies develop in four clotting factors: prothrombin, VII, IX (plasma thromboplastin component), and X. Factor VII decreases

Evidence for a New Plasma Thromboplastin Factor I. Case Report, Coagulation Studies and Physicochemical Properties

Abstract Studies of defective plasma thromboplastin formation in four siblings indicated a defect which was different from any of the known coagulation factor deficiency states. Although none of the children had any history of hemorrhagic tendencies, a prolonged whole blood clotting time in an 11-year-old girl led to the findings of a markedly prolonged partial thromboplastin time (PTT), abnormal thromboplastin generation test (TGT), and a normal prothrombin time in the patient and in three of her ten siblings. The abnormal PTT and TGT were corrected by aluminum hydroxide adsorbed fresh plasma and by serum. Using the kaolin-PTT system, equal mixtures of plasma from the patients and normal plasma produced a normal time. In addition, plasmas deficient in plasma thromboplastin antecedent (PTA), Hageman factor (HF), antihemophilic factor (AHF), or plasma thromboplastin component (PTC) corrected the abnormality. Physical and chemical properties of plasma correcting the defect in vitro indicated that the defect is closely related to that found in PTA and HF deficient plasma.

A Clinical Evaluation of Plasma Thromboplastin Antecedent (PTA) Deficiency

Article1 May 1965A Clinical Evaluation of Plasma Thromboplastin Antecedent (PTA) DeficiencyFRED G. CONRAD, WILLIAM L. BRENEMAN, DOROTHY B. GRISHAM, B.S.FRED G. CONRADSearch for more papers by this author, WILLIAM L. BRENEMANSearch for more papers by this author, DOROTHY B. GRISHAM, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-885 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince Rosenthal, Dreskin, and Rosenthal (1) first described plasma thromboplastin antecedent (PTA) deficiency 10 years ago, investigators from numerous hematology centers have emphasized the infrequent occurrence of this defect. Reports of the relative rate of occurrence of patients deficient in antihemophilic factor (AHF) and plasma thromboplastin component (PTC) are remarkably stable at a 4 to 1 ratio in this country and throughout the world (2-4). The reports of relative occurrence of PTA show marked variations from less than 1% to 18% of the total thromboplastinogen disorders (5-8).Contrary to the usually reported low incidence, our studies indicate that PTA deficiency...

Christmas Disease and Myocardial Infarction

THE PURPOSE of this report is to describe the unusual circumstance of a patient with congenital factor IX or plasma thromboplastin component (PTC) deficiency (Christmas disease) who had clinical evidence of continued hypocoagulability throughout his lifetime but, nevertheless, spontaneously developed a myocardial infarction when he reached the sixth decade. In addition, a second and fatal coronary occlusion occurred 11 years later while being treated in the hospital for uncontrolled bleeding and at the point where plasma replacement had completely ameliorated the hemorrhage. These observations are of interest because they have bearing on the general concept of blood coagulability as it affects the genesis of occlusive coronary artery disease. Report of a Case A 67-year-old white man was admitted to the Graduate Hospital of the University of Pennsylvania in November 1962 because of oral bleeding of three days' duration. The blood loss, estimated to be one pint, occurred in the

VITAMIN K-INDUCED PROTHROMBIN FORMATION: CORRECTION.

I am indebted to M. J. Smith of the Massachusetts General Hospital for pointing out to me that plasma thromboplastin antecedent (factor XI) is not a vitamin K-dependent clotting protein. In a recent paper [Science 145, 926 (1964)], I had listed it along with plasma thromboplastin component (factor IX), proconvertin (factor VII), and prothrombin as clotting proteins under probable genetic control by vitamin K in the mammal. Instead of PTA, I should have listed Stuart's factor (X), which appears now to be well established as a vitamin K-dependent clotting factor. ROBERT E. OLSON Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Correlation of the oxygendissociation curves of adult and fetal hemoglobin solutions with the H + ion concentration gradients of adult and fetal red blood cells

children has any history of hemorrhagic tendencies, a prolonged whole-blood clotting time in an l l -year-old girl led to the findings of a markedIy prolonged partial thromboplastin time ( P T T ) , abnormal thromboplastin generation test (TGT) , and a normal prothrombin time (PT) in the patient and in 3 of her 10 siblings. The abnormal PTT and T G T were corrected by aluminum hydroxide adsorbed fresh plasma and by serum. Using the kaot in-PTT system, equal mixtures of plasma from the patients and normal plasma produced a normal time. In addition, plasmas deficient in plasma thromboplastin antecedent (PTA) , Hageman factor (HF) , antihemophilic factor (AHF) , or plasma thromboplastin component (PTC) corrected the abnormality. Specific assays of the patients' plasmas (confirmed by two other coagulation laboratories) for fibrinogen (I) , prothrombin ( I I ) , proaccelerin (V), AHF (VI I I ) , PTC ( IX) , Stuart factor (X) , PTA (XI ) , HF ( X I I ) , and anticoagulant activity were all within normal limits. Physical and chemical properties of plasma correcting the defect in vitro ( temperature and storage stability, glass activation, chemical adsorption, and chemical fraetionation) indicate that the defeet is closely related to that found in PTAand HF-deficient plasma. These findings suggest the existence of a previously undeseribed coagulation factor which is similar to the known glass contact factors, PTA and HF.

NEUROPATHY IN HEMOPHILIA.

INTRA-ARTICULAR and intramuscular hemorrhages are well recognized as frequent causes for disability in patients with hemophilia. Another less common cause for impaired motility of an extremity in a hemophiliac is involvement of a peripheral nerve by hemorrhage. The purposes of this communication are to report the incidence and nature of the peripheral nerve lesions observed in 206 patients with hemophilia; to review the pertinent literature; and to discuss briefly the pathogenesis, management, and prognosis of this somewhat neglected complication of hemophilia. <h3>Materials and Methods</h3> The 206 hemophiliacs were all admitted to the Mount Sinai Hospital, New York. The criteria employed for the diagnosis of hemophilia have been presented elsewhere.¹Deficiency of factor IX (plasma thromboplastin component) was demonstrated in 17 patients and of plasma thromboplastin antecedent (factor XI) in 6. The remainder were deficient in factor VIII (antihemophilic factor) or were hospitalized at a time when facilities for determining