scholarly journals Platelet Coagulant Activities in Patients with Thrombotic Disorders

1977 ◽  
Author(s):  
P.N. Walsh
Keyword(s):  
Platelet Aggregation ◽  
Intrinsic Factor ◽  
Factor Xa ◽  
Normal Serum ◽  
Alternative Mechanism ◽  
Factor Xii ◽  
Factor X ◽  
Platelet Factor ◽  
Plasma Coagulation ◽  
Normal Platelet

Platelets can initiate intrinsic coagulation by two alternative mechanism, one involving the activation of factor XII by ADP-stimulated platelets (contact product forming activity), and the other involving activation of platelet-associated factor XI by collagen-stimulated platelets (collagen-induced coagulant activity).Subsequently, platelet membrane phospholipo-proteins are made available by which platelets can first promote factor-X activation (intrinsic factor -Xa forming activity) and finally prothrombin activation. Specific assay techniques for each of these platelet coagulant activities have been applied to the study of patients with thrombotic and prethrombotic disorders. We have demonstrated an association between platelet coagulant hyperactivity and the development of post-operative deep vein thrombosis in patients undergoing reconstructive surgery of the hip. In patients with acute primary retinal vein occlusion two- to three-fold elevations of platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation have been observed whereas plasma coagulation and platelet aggregation studies have been normal. In patients with transient cerebral ischemic attacks and normal serum lipids we have found two- to three-fold elevations of platelet coagulant activities concerned with the initiation and early phases of intrinsic coagulation but normal platelet factor 3 activity and normal plasma coagulation and platelet aggregation studies. These studies indicate an association between platelet coagulant hyperactivity and various venous and arterial thrombotic disorders. This association may have important pathogenetic implications.

scholarly journals Different Requirements for Intrinsic Factor-Xa Forming Activity and Platelet Factor 3 Activity and Their Relationship of Platelet Aggregation and Release

1977 ◽  
Author(s):  
P.N. Walsh ◽  
M.S. Lipscomb
Keyword(s):  
Platelet Aggregation ◽  
Intrinsic Factor ◽  
Factor Xa ◽  
Activate Factor ◽  
Factor X ◽  
Membrane Phospholipids ◽  
Platelet Factor ◽  
Washed Platelet ◽  
Coagulant Activity ◽  
Relationship Of

Platelets provide coagulant activity in part by making available membrane phospholipids which promote the reactions of: (1) factors XIa, VIII, IX and calcium to activate factor X (intrinsic factor-Xa forming activity or XaFA); and, (2) factors Xa, V and calcium to activate prothrombin (platelet factor 3 activity or PF3A). We have studied the availability of XaFA and PF3A, platelet aggregation and [14C]-5HT release in washed platelet suspensions, incubated with collagen.XaFA developed rapidly (100% activity at 15-30 sec) well before maximum [14C]-5HT release (2-4 min) and decayed to <10% at 5-10 min.PF3A developed slowly (100% activity after 20 min stirring with collagen) well after maximal aggregation and release. Maximal XaFA availability occurred in unstirred platelet suspensions incubated with collagen and not undergoing aggregation or release, and was not enhanced by stirring, whereas PF3A did not become available unless platelet suspensions were stirred with resultant aggregation and release.PF3A, XaFA, aggregation and release were inhibited by pretreating platelet suspensions with p-chloro-mercuribenzene sulfonate, concanavalin A or a combination of 2-deoxyglucose and antimycin A, whereas pretreatment with indomethacin inhibited aggregation, release and PF3A availability but not XaFA availability. These results indicate that the biochemical determinants of XaFA and PF3A are different.PF3A developed only when aggregation and release occurred whereas XaFA was independent of aggregation and release.

Clinically Mild Thrombasthenia with Normal Platelet Coagulant Activities

1972 ◽  
Vol 28 (03) ◽  
pp. 440-446
Author(s):  
P. N Walsh ◽  
C. R Rizza ◽  
R McLennan
Keyword(s):  
Intrinsic Factor ◽  
Factor Xa ◽  
Platelet Factor ◽  
Present Patient ◽  
Normal Platelet ◽  
Coagulant Activity

SummaryThe results of assaying platelet coagulant activities in a patient with clinically mild thrombasthenia are compared with those previously reported in 4 patients with clinically severe and 2 patients with moderately severe thrombasthenia. Contact product forming activity and platelet factor 3 activity were normal in the present patient, and decreased in the more severely affected patients. Intrinsic factor-Xa forming activity was normal or supranormal in all patients. Collagen-induced coagulant activity was present in mildly and moderately affected patients and absent in severely affected patients. The present patient would appear to possess both alternative mechanisms by which platelets can initiate intrinsic clotting, compared to the moderately affected patients who lack one and the severely affected patients who lack both pathways. Although the present patient’s platelets failed to aggregate in response to ADP they responded normally to ADP in the assay for contact product forming activity.

scholarly journals Platelet Function and Pyrophosphates in Osteogenesis Imperfecta

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 500-509 ◽  
Author(s):  
William E. Hathaway ◽  
Clive C. Solomons ◽  
John E. Ott
Keyword(s):  
Platelet Aggregation ◽  
Osteogenesis Imperfecta ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Platelet Rich Plasma ◽  
Elevated Serum ◽  
Normal Serum ◽  
Platelet Factor ◽  
Normal Platelet

Abstract Platelet function and serum pyrophosphate (PPi) levels were measured in 15 osteogenesis imperfecta (OI) patients and their parents. The bleeding time was abnormal in five of the subjects. Platelet adhesion to glass was occasionally abnormal (9 of 30 subjects). Platelet factor 3 (PF3) release was impaired in all patients except one and in one or both parents. Platelet aggregation to ADP was abnormal in most of the subjects. Aggregation to collagen was also frequently defective. Thrombin-induced platelet aggregation was always normal. Serum PPi levels were elevated in 62.5% of the subjects. The increased level of PPi was occasionally related to the defect in release of PF3; however, addition of PPi to normal platelet-rich plasma (PRP) did not alter the PF3 release or ADP aggregation. Thrombin-clotted PRP contributed to the elevated PPi but no more in the subjects than in the controls. Presumed carriers of the gene for OI may have defective platelet function and elevated serum PPi, even though no obvious signs of the disease are apparent.

Essential Athrombia

1975 ◽  
Vol 33 (02) ◽  
pp. 278-285 ◽  
Author(s):  
Şeref Inceman ◽  
Yücel Tangün
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Aggregation Response ◽  
Platelet Disorder ◽  
Fibrinogen Content

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”

Platelet Coagulant Activities and Retinal Vein Thrombosis

1977 ◽  
Vol 38 (02) ◽  
pp. 0399-0406 ◽  
Author(s):  
Peter N. Walsh ◽  
Richard E. Goldberg ◽  
Richard L. Tax ◽  
Larry E. Magargal
Keyword(s):  
Platelet Aggregation ◽  
Venous Thrombosis ◽  
Retinal Vein Occlusion ◽  
Serotonin Release ◽  
Platelet Factor ◽  
Trigger Mechanism ◽  
Local Conditions ◽  
Plasma Coagulation ◽  
Vein Thrombosis ◽  
Vein Occlusion

SummaryTo determine whether platelets play a role in the pathogenesis of retinal vein occlusion (RVO), platelets and coagulation were evaluated in 28 patients with RVO. Platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation were 2–4 fold increased in 9 patients with acute primary RVO but not in patients with acute secondary (10 patients) or chronic (9 patients) RVO. Platelet factor 3 activity, platelet aggregation, serotonin release by platelets and plasma coagulation were normal in all patients. Platelets may provide a trigger mechanism for venous thrombosis in the eye when local conditions permit.

Spectrophotometric Determination of Factor Xa Generation in Factor IX Concentrates

1977 ◽  
Vol 37 (03) ◽  
pp. 535-540 ◽  
Author(s):  
D. S Pepper ◽  
D Banhegyi ◽  
Ann Howie
Keyword(s):  
Intrinsic Factor ◽  
Factor Xa ◽  
Factor Ix ◽  
Factor V ◽  
Factor X ◽  
Generation Times ◽  
Incubation Periods ◽  
Multiple Sample ◽  
Recording Spectrophotometer

SummaryPrevious work from this department, concerned with testing the potential thrombogenicity of therapeutic factor IX concentrates, demonstrated that following recalcification of factor IX concentrates thrombin was generated within 3-30 minutes of incubation (Sas et al. 1975). The test developed (known as the TGt 50 test) is a two-stage assay and was thus found to be time consuming, tedious and tended to become inaccurate with long incubation periods and a large number of samples. A semiautomatic version of the test is reported in which the synthetic peptide Bz-ILE-GLU-GLY-ARG-pNA (S-2222) is added to recalcified, diluted factor IX concentrate in the micro-cuvette of a multiple sample recording spectrophotometer. Information can be obtained on (a) the amount of Xa (if any) present prior to recalcification (b) the initial amount of Xa formed and (c) the time taken to activate all factor X to Xa. Direct graphical interpretation shows a number of qualitative differences between commercial preparations, but by either of the criteria (b) or (c) above, it is possible to place the different products into “activated” and “non activated” groups such that both the Xa generation times and TGt 50 tests identify the same two groups of products. This agreement also indicates that the TGt 50 test is independent of the intrinsic factor V levels in the various concentrates.

Activation of Human Coagulation Factor VIII by Activated Factor X, the Common Product of the Intrinsic and the Extrinsic Pathway of Blood Coagulation

1982 ◽  
Vol 47 (02) ◽  
pp. 096-100 ◽  
Author(s):  
K Mertens ◽  
R M Bertina
Keyword(s):  
Factor Viii ◽  
Human Factor ◽  
Intrinsic Factor ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Factor X ◽  
Extrinsic Factor ◽  
Extrinsic Pathway ◽  
Factor Ixa ◽  
The Common

SummaryThe intrinsic activation of human factor X has been studied in a system consisting of purified factors and in plasma. In both these systems factor Xa stimulated the activation of factor X by factor IXa plus factor VIII This is due to the activation of factor VIII by factor Xa. When this factor Xa is formed via the extrinsic pathway, the extrinsic factor X activator functions as a stimulator of the intrinsic factor X activator.

Platelet Coagulant Activities and Clinical Severity in Haemophilia

1973 ◽  
Vol 29 (03) ◽  
pp. 722-729 ◽  
Author(s):  
Peter N. Walshi ◽  
S. G Rainsford ◽  
Rosemary Biggs
Keyword(s):  
Factor Viii ◽  
Intrinsic Factor ◽  
Factor Xa ◽  
Clinical Severity ◽  
Platelet Factor ◽  
Early Stages ◽  
Coagulant Activity ◽  
Severe Group

SummaryAssays for platelet coagulant activities concerned with the initiation and progress of intrinsic coagulation were done pair-wise in two groups of 16 haemophiliacs without detectable factor VIII. The patients in the ‘severe’ group had experienced 7.9-22.8 (mean 13.7) spontaneous haemorrhages per 100 days during an average of 431 days of observation, whereas those in the ‘mild’ group had bled 0-5.5 (mean 3.2) times per 100 days during an average of 282 days of observation. Contact product forming activity, collagen-induced coagulant activity and intrinsic factor-Xa forming activity were decreased in the severely-affected group and increased in the mildly affected group, whereas there was no great difference in platelet factor 3 activity between the two groups. Variations of platelet coagulant activities concerned with the initiation and early stages of intrinsic coagulation may influence clinical severity in haemophilia.

Regulation of Factor VIIIa in the Intrinsic Factor Xase

1999 ◽  
Vol 82 (08) ◽  
pp. 193-200 ◽  
Author(s):  
Philip Fay
Keyword(s):  
Factor Viii ◽  
Intrinsic Factor ◽  
Factor Xa ◽  
Clinical Importance ◽  
Factor X ◽  
Subunit Dissociation ◽  
Protein Factor ◽  
Catalytic Rate Constant ◽  
Factor Ixa ◽  
Factor Viiia

IntroductionHemophilia A, the most common of the severe, inherited bleeding disorders, results from a deficiency or defect in the plasma protein factor VIII. The activated form of the protein serves as an essential cofactor for factor IXa in the conversion of factor X to factor Xa. This surface-bound complex of enzyme and cofactor is referred to as the intrinsic factor Xase. Factor VIIIa dramatically increases the catalytic rate constant for substrate conversion by an unclear mechanism. The activity and stability of the factor Xase appears to be regulated by the integrity of the cofactor. Factor VIIIa possesses a labile structure, and subunit dissociation results in the decay of Xase activity. Furthermore, factor VIIIa is a substrate for proteolytic inactivation by several enzymes, including factor IXa, the enzyme for which it serves as a cofactor. Although interest in the structure, function, and metabolism of factor VIII is commensurate with its biochemical and clinical importance, the molecular basis for its role in coagulation and the regulation of function through complex intramolecular and intermolecular interactions remain poorly understood.

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