thromboplastin and Blood-Platelet-Disorders

The molecular mechanisms responsible for the hemostatic efficacy of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) in platelet-related bleeding disorders remain unclear. The general concept is that rFVIIa locally enhances thrombin generation at the site of injury, where tissue factor (TF) has become exposed. However, a growing amount of evidence shows that rFVIIa is also able to exert its activity in a manner independent of TF. Using an in vitro flow model, we recently showed that TF-independent thrombin generation is responsible for increased platelet deposition onto injured vessels following rFVIIa administration. Furthermore, it has been shown that rFVIIa can restore platelet aggregation in Glanzmann's thrombasthenia (GT) patients via TF-independent thrombin generation. However, the mechanism behind TF-independent thrombin generation remains to be elucidated. It is postulated that, in vivo, both the TF-dependent and TF-independent thrombin generation induced by rFVIIa contribute to the control of hemorrhage in patients with platelet-related bleeding disorders and, perhaps, other causes of hemorrhagic diatheses.

Topics: Blood Coagulation; Blood Platelet Disorders; Factor VIIa; Hemophilia A; Hemostasis; Humans; Platelet Activation; Recombinant Proteins; Thromboplastin

Platelets play a central role in haemostasis. Not only are they involved in aggregatory and agglutination responses but they are also implicated in the clotting system. The conversion of prothrombin to thrombin, in the presence of coagulation factors Va, Xa and calcium ions, is termed prothrombinase activity. For optimal expression of this process a negatively charged phospholipid surface is required. Platelets can provide such an environment, by exposing negatively charged phospholipids at their external plasma membrane, by a 'flip-flop' process whereby negatively charged phospholipids, predominantly phosphatidylserine, move from the inner plasma membrane leaflet to the outer leaflet upon the activation of platelets by certain agonists. Such agonists include collagen and thrombin and the amount of prothrombinase activity expressed is well correlated with the propensity of the agonist to activate platelet calcium-dependent protease, calpain. This enzyme is then thought to act upon platelet cytoskeletal components, thus breaking the restraining action of the cytoskeleton upon the platelet plasma membrane and facilitating 'flip-flop'. The platelet plasma membrane is therefore a dynamic surface capable of catalytic functions in coagulation systems. Recent research has high-lighted abnormalities in platelet prothrombinase expression in certain disease states. These include Bernard-Soulier syndrome, essential thrombocythaemia and conditions where the lupus anticoagulant may be present.

Topics: Blood Platelet Disorders; Blood Platelets; Cell Membrane; Factor V; Factor X; Factor Xa; Humans; Phospholipids; Platelet Activation; Thromboplastin

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Child; Factor X; Factor XII; Female; Fibrinolysin; Fibrinolysis; Hemostasis; Humans; Lipoproteins; Male; Prothrombin Time; Purpura, Thrombocytopenic; Thrombin; Thromboplastin; Thrombosis; von Willebrand Diseases

Topics: Blood Coagulation Factors; Blood Platelet Disorders; Disseminated Intravascular Coagulation; Factor IX; Factor V; Factor VII; Factor VIII; Factor X; Factor XII; Factor XIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolytic Agents; Heparin; Humans; Plasminogen; Prothrombin; Thrombin; Thromboplastin

Recombinant FVIIa (rFVIIa) has been shown to improve hemostasis in patients with thrombocytopenia and to prevent or control bleeding episodes in patients with inherited deficiencies of major PLT glycoproteins, but the mechanism of action is not well understood.. Effects of rFVIIa on hemostasis were explored with an in vitro perfusion technique. Blood samples, from healthy donors or from patients with congenital defects of PLT glycoprotein IIb-IIIa (GPIIb-IIIa), were anticoagulated with low-molecular-weight heparin. Experimental thrombocytopenia (<6000 PLTs/microL) was induced by a filtration procedure. rFVIIa was added to blood samples at therapeutic concentrations. A severe GPIIb-IIIa impairment was also induced by exposure of normal blood samples to a specific antibody. Perfusion studies were performed through annular chambers containing damaged vascular segments. The presence of fibrin and PLTs on the perfused subendothelium was morphometrically quantified.. Under conditions of experimental thrombocytopenia, addition of rFVIIa enhanced fibrin formation in a dose-dependent manner (p < 0.05). Improvements in local fibrin generation and partial restoration of PLT interactions were also observed after incubation of blood from patients with Glanzmann's thrombasthenia with rFVIIa at 5 microg per mL (180 microg/kg). Similar improvements were observed in blood samples incubated with antibodies to GPIIb-IIIa. rFVIIa in whole normal blood also enhanced fibrin formation but PLT deposition was unaffected. Evaluation of prothrombin fragments 1 and 2 in the perfusates confirmed that rFVIIa increased thrombin generation in all cases.. Our data indicate that rFVIIa promotes a procoagulant activity at sites of vascular damage. This mechanism could explain the beneficial hemostatic effect of rFVIIa in patients with thrombocytopenia or with Glanzmann's thrombasthenia.

Topics: Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Factor VIIa; Fibrin; Hemostasis; Humans; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Prothrombin; Recombinant Proteins; Thrombasthenia; Thrombocytopenia; Thromboplastin

Studies were performed on a patient with a longstanding bleeding disorder whose major defects were impaired platelet prothrombinase activity in the absence of added factor Va, and a platelet factor V value that was either decreased or at the lower limit of normal when assayed on multiple occasions. In contrast, plasma factor V values were consistently normal. Unlike Scott Syndrome, in which platelet prothrombinase activity is decreased in both the presence and absence of added factor V, her platelets appeared to utilize added factor Va normally in supporting the generation of prothrombinase activity. These findings suggest an intrinsic defect in platelet factor V as the basis of her platelet prothrombinase defect. This defect appears to be different than that described in the Quebec platelet disorder (factor V Quebec). Immunoblot analyses of washed platelet lysates demonstrated a pattern of variably sized factor V molecules that was entirely similar to that observed in normal platelets, and both the heavy and light chains of her factor V after thrombin cleavage were of the same size as that observed in normal platelets. In addition, her platelet multimerin was normal and immunoblot analysis excluded the type of generalized granular protein defect and pathological proteolysis that has been suggested to explain the factor V defect in the Quebec platelet disorder. The findings in this patient thus suggest a new type of platelet factor V defect as the basis for the impaired capacity of her activated platelets to support prothrombinase generation. The findings further support an important role for platelet factor V in hemostasis.

Topics: Blood Coagulation Factors; Blood Platelet Disorders; Calcimycin; Dose-Response Relationship, Drug; Factor Va; Female; Hemorrhage; Humans; Kinetics; Thrombin; Thromboplastin

Topics: Binding Sites; Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Collagen; Factor X; Humans; Membrane Lipids; Phosphatidylserines; Phospholipases A; Phospholipids; Platelet Aggregation; Thrombin; Thromboplastin

Prothrombinase activities of platelets have been measured in diluted platelet-rich plasma using a chromogenic substrate assay and purified coagulation factors. No abnormalities in prothrombinase activities were found for platelets from patients with storage pool disease (dense-body deficiency), grey platelet syndrome, and Glanzmann's thrombasthenia. It is concluded that neither release of dense bodies and alpha-granules nor aggregation of platelets are essential prerequisites for exposure of a procoagulant surface. Platelets from patients with Bernard-Soulier syndrome, however, have approximately 10-fold higher prothrombinase activities in the non-stimulated form than normal non-stimulated platelets. The increased procoagulant activity cannot be completely ascribed to an increase in platelet size. It is suggested that the increased prothrombinase activity reflects an increased exposure of phosphatidylserine at the outer surface of non-stimulated Bernard-Soulier platelets, earlier described by Perret et al (1983).

Topics: Bernard-Soulier Syndrome; Blood Platelet Disorders; Blood Platelets; Humans; Platelet Storage Pool Deficiency; Thrombasthenia; Thromboplastin

Topics: Adenosine Diphosphate; Adolescent; Adult; Aged; Arachidonic Acids; Bleeding Time; Blood Platelet Disorders; Child; Child, Preschool; Female; Fibrinogen; Humans; Male; Metabolism, Inborn Errors; Middle Aged; Pedigree; Platelet Aggregation; Thromboplastin

Topics: Animals; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Survival; Humans; Infant, Newborn; Lipid Metabolism; Nucleotides; Oxygen Consumption; Platelet Adhesiveness; Platelet Aggregation; Thrombin; Thromboplastin

Hémorrhagic manifestations are relatively common in dysproteinemias (7 à 15% in myeloma, 36% in macroglobulinemia) but they are not often related to a qualitative platelet defect. In the present work we have studied the influence of some monoclonal immunoglobulins on the function of isolated normal platelets. The results show that platelet aggregations to collagen and ADP are impaired in presence of high concentration of paraproteins (about 50 gm/l). The molecular size of the protein is also important. This is in agreement with most studies and support the hypothesis that paraproteins interfere with platelet activity.

Topics: Blood Platelet Disorders; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Multiple Myeloma; Paraproteinemias; Platelet Adhesiveness; Platelet Aggregation; Surface Properties; Thromboplastin; Waldenstrom Macroglobulinemia

Congenital release thrombocytopathy must be included in the differential diagnosis of bleeding diatheses in women. A review of the coagulation profiles of 7 patients with congenital release thrombocytopathy suggests that more sophisticated platelet aggregation studies must be performed when routine screening procedures fail to determine the cause of a clinically suspected bleeding disorder. Establishing the diagnosis helps to avoid the use of medications which cause an acquired platelet dysfunction, and contributes to adequate prophylaxis against surgical and obstetric hemorrhage.

Topics: Adenosine Diphosphate; Adult; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Collagen; Epinephrine; Female; Humans; Middle Aged; Parity; Platelet Aggregation; Platelet Factor 3; Pregnancy; Prothrombin Time; Retrospective Studies; Thrombin; Thromboplastin

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Diagnosis, Differential; Hemorrhagic Disorders; Humans; Thromboplastin

A 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 MUM) although a small wave of primary aggregation was obtained by very large ADP concentrations (25-50 muM). 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. Release 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."

Topics: Adenosine Diphosphate; Blood Cell Count; Blood Platelet Disorders; Blood Platelets; Child; Clot Retraction; Epinephrine; Female; Humans; Nephelometry and Turbidimetry; Platelet Aggregation; Ristocetin; Thrombin; Thromboplastin

Topics: Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Dog Diseases; Dogs; Female; Prothrombin Time; Thromboplastin

Topics: Adult; Blood Cell Count; Blood Platelet Disorders; Blood Platelets; Child; Child, Preschool; Clot Retraction; Female; Humans; Male; Middle Aged; Neoplasms; Prothrombin Time; Thrombocytopenia; Thrombocytosis; Thromboplastin

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Child; Collagen; Epinephrine; Glass; Humans; Male; Phospholipids; Platelet Adhesiveness; Prothrombin; Thromboplastin; Venoms

Topics: Aged; Blood Coagulation Tests; Blood Platelet Disorders; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Gastrointestinal Hemorrhage; Heparin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Prothrombin Time; Thromboplastin

Topics: Adenosine Diphosphate; Aged; Biological Assay; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Collagen; Colorimetry; Epinephrine; Female; Fibrinogen; Folic Acid; Humans; Lacticaseibacillus casei; Male; Middle Aged; Platelet Adhesiveness; Prothrombin Time; Radioisotope Dilution Technique; Schilling Test; Thromboplastin; Thrombosis; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Humans; Mass Screening; Methods; Prothrombin Time; Thrombin; Thromboplastin

Topics: Adenine Nucleotides; Amines; Aspirin; Blood Platelet Disorders; Blood Platelets; Carbon Isotopes; Cell Membrane; Cerebral Hemorrhage; Collagen; Contusions; Ecchymosis; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Secretions; Platelet Adhesiveness; Serotonin; Thromboplastin; Vitamin K Deficiency Bleeding

Topics: Animals; Aorta, Thoracic; Autoradiography; Blood Coagulation; Blood Platelet Disorders; Cell Nucleus; Cyanosis; DNA; DNA Repair; Endothelium; Endotoxins; Factor XII; Ischemia; Isotope Labeling; Kidney; Male; Polymers; Rats; Shwartzman Phenomenon; Thromboplastin

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Dicumarol; Factor VII; Glycine max; Hemorrhage; Hemostatics; Humans; Pedigree; Phospholipids; Plasma; Prothrombin; Prothrombin Time; Rabbits; Thrombocytopenia; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Hemoglobinometry; Hemophilia A; Hemophilia B; Hemorrhage; Humans; Male; Prothrombin Time; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombotic Thrombocytopenic; Rheumatic Diseases; Telangiectasia, Hereditary Hemorrhagic; Thromboplastin; von Willebrand Diseases

Topics: Adenosine Diphosphate; Adult; Blood Coagulation; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Clot Retraction; Collagen; Factor X; Female; Humans; Pedigree; Platelet Adhesiveness; Thromboplastin

Topics: Animals; Blood Cell Count; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Disseminated Intravascular Coagulation; Factor V; Factor VII; Female; Fibrin; Fibrinogen; Hematocrit; Injections, Intravenous; Male; Rabbits; Thrombin; Thromboplastin

Topics: Animals; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Fibrinogen; Fibrinolysin; Fibrinolysis; Injections, Intravenous; Lichens; Platelet Adhesiveness; Prothrombin Time; Pulmonary Artery; Pulmonary Embolism; Pulmonary Veins; Rabbits; Spores; Thromboplastin

Topics: Blood Platelet Disorders; Blood Preservation; Freezing; Hemorrhage; Humans; Male; Military Medicine; Prothrombin Time; Thromboplastin; Transfusion Reaction

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Hemostasis; Humans; Methods; Thrombelastography; Thrombocytopenia; Thromboplastin

Topics: Aspirin; Blood Cell Count; Blood Platelet Disorders; Blood Platelets; Factor XII; Female; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal-Fetal Exchange; Pregnancy; Prothrombin Time; Thromboplastin

Topics: Blood Cell Count; Blood Coagulation; Blood Platelet Disorders; Female; Fibrinogen; Fibrinolysis; Humans; Infant, Newborn; Infant, Premature; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Thromboplastin

Topics: Adenine Nucleotides; Adenosine Diphosphate; Blood Coagulation Factors; Blood Platelet Disorders; Humans; Kaolin; Myeloproliferative Disorders; Thromboplastin

Topics: Aminocaproates; Aprotinin; Blood Platelet Disorders; Blood Platelets; Fibrinolysis; Hemorrhage; Humans; In Vitro Techniques; Male; Postoperative Complications; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Prothrombin Time; Thromboplastin

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adult; Aspirin; Blood Coagulation; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cell Aggregation; Child; Clot Retraction; Connective Tissue; Epinephrine; Female; Genes, Dominant; Humans; In Vitro Techniques; Kaolin; Lipids; Male; Middle Aged; Pedigree; Platelet Adhesiveness; Temperature; Thromboplastin

Topics: Adenine Nucleotides; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Citric Acid Cycle; Erythrocytes; Female; Glycogen; Humans; Lipoproteins; Microscopy, Electron; Platelet Adhesiveness; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Adenine Nucleotides; Blood Platelet Disorders; Cell Membrane; Immunoglobulin G; Phospholipids; Pyruvate Kinase; Surface Properties; Thromboplastin

Topics: Anticoagulants; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Factor IX; Factor VII; Factor X; Fibrinogen; Hemostasis; Heparin; Humans; Prothrombin; Thrombelastography; Thrombin; Thromboplastin; Thrombosis; Vitamin K

Topics: Adenine Nucleotides; Aged; Blood Coagulation Factors; Blood Platelet Disorders; Bone Marrow Diseases; Carbon Isotopes; Cell Aggregation; Collagen; Epinephrine; Female; Hematocrit; Hemorrhage; Humans; Male; Microscopy, Electron; Middle Aged; Myeloproliferative Disorders; Phosphates; Serotonin; Sodium; Thromboplastin

Topics: Adolescent; Adult; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Child; Female; Glycogen Storage Disease; Glycogen Storage Disease Type I; Humans; Infant; Male; Thromboplastin

A family with congenital thrombocytopenia is described through four generations where the mode of inheritance appears to be an autosomal dominant. Spontaneous bruising of varying severity, menorrhagia, and profuse bleeding at operation necessitating transfusion were predominant in the history. Platelet function tests were performed on the various patients. Platelet aggregation by adenosine diphosphate (ADP) was found to be defective, though liberation of platelet factor III and platelet thromboplastic function were found to be normal when corrected for deficient numbers.

Topics: Adult; Blood Coagulation Tests; Blood Platelet Disorders; Female; Genes, Dominant; Hemorrhagic Disorders; Humans; Male; Menorrhagia; Thrombocytopenia; Thromboplastin

Topics: Adult; Blood Cell Count; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Cholesterol; Erythrocyte Count; Female; Hematocrit; Hemoglobinometry; Humans; Lipids; Male; Middle Aged; Phospholipids; Polycythemia Vera; Thromboplastin

Topics: Biological Assay; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelet Disorders; Female; Fibrin; Humans; Immunoelectrophoresis; Male; Neoplasms; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Humans; Thromboembolism; Thrombophlebitis; Thromboplastin; Thrombosis

Topics: Anemia, Macrocytic; Blood Platelet Disorders; Blood Platelets; Chromatography, Paper; Female; Humans; In Vitro Techniques; Ovarian Diseases; Phospholipids; Polycythemia Vera; Primary Myelofibrosis; Prothrombin; Thrombin; Thromboplastin; Uremia

Topics: Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Factor VIII; Gastrointestinal Hemorrhage; Hemophilia A; Humans; Male; Thromboplastin; von Willebrand Diseases

Topics: Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Humans; In Vitro Techniques; Medical Laboratory Science; Thromboplastin

Topics: Adrenal Cortex Hormones; Anticoagulants; Arteriosclerosis; Blood Platelet Disorders; Coronary Disease; Fats; Female; Humans; Intracranial Embolism; Intracranial Embolism and Thrombosis; Neoplasms; Pharmacology; Postoperative Complications; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Thrombophilia; Thromboplastin; Thrombosis

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Classification; Fibrin; Genetics, Medical; Hemophilia A; Humans; Purpura; Surgery, Oral; Thrombin; Thromboplastin

Topics: Blood Coagulation Tests; Blood Platelet Disorders; Blood Transfusion; Factor VIII; Genetics, Medical; Hemophilia A; Hot Temperature; Humans; Hydrogen-Ion Concentration; Refrigeration; Thromboplastin; von Willebrand Diseases

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adolescent; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Platelets; Child; Factor IX; Factor VIII; Humans; Kaolin; Serotonin; Thrombasthenia; Thromboplastin

Topics: Blood Platelet Disorders; Blood Platelets; Busulfan; Hemorrhagic Disorders; Humans; Phospholipids; Research; Thrombocythemia, Essential; Thrombocytosis; Thromboplastin; Uracil

Topics: Blood Platelet Disorders; Dicumarol; Drug Therapy; Factor V Deficiency; Factor VII Deficiency; Factor VIII; Factor XII; Hemophilia A; Hemophilia B; Hemorrhagic Disorders; Heparin; Humans; Hypoprothrombinemias; Prothrombin; Prothrombin Time; Serum Globulins; Thrombocytopenia; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Diagnosis, Differential; Humans; Thromboplastin