thromboplastin and Hemorrhagic-Disorders

Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed.

Topics: Annexin A2; Anticoagulants; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Blood Coagulation Disorders; Blood Coagulation Tests; Carboxypeptidase B2; Disseminated Intravascular Coagulation; Fibrinolysis; Forecasting; Granulocyte Precursor Cells; Hemorrhagic Disorders; Humans; Leukemia, Promyelocytic, Acute; Oxides; Recombinant Proteins; Risk Factors; S100 Proteins; Thrombomodulin; Thrombophilia; Thromboplastin; Tretinoin; Urokinase-Type Plasminogen Activator

Tissue factor (TF) is the cellular receptor and cofactor for blood coagulation factor VII (FVII). Exposure of flowing blood to cells that express TF leads to the initiation of blood coagulation. A recent study of mice expressing low levels of TF has demonstrated the importance of TF and FVII in maintaining adequate haemostasis within the heart. In addition, the study indicates that the heart is subject to a succession of minor bleeds most probably as a result of repetitive minor mechanical injury to the blood vessels.

Topics: Animals; Blood Coagulation; Endomyocardial Fibrosis; Factor VII; Gene Expression; Heart; Hemorrhagic Disorders; Hemosiderin; Hemostasis; Mice; Myocardial Contraction; Thromboplastin

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Factors; Catalysis; Enzyme Activation; Factor XII; Fibroblasts; Hemorrhagic Disorders; Humans; Lipoproteins; Phospholipids; Surface Properties; Thromboplastin

Topics: Aminocaproates; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Proteins; Hemophilia A; Hemorrhagic Disorders; Humans; Plasminogen; Thromboplastin

Topics: Abruptio Placentae; Adrenal Glands; Aminocaproates; Animals; Basement Membrane; Biopsy; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Brain; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Hemorrhage; Hemorrhagic Disorders; Heparin; Humans; Hypertension, Malignant; Kidney Cortex Necrosis; Kidney Failure, Chronic; Kidney Glomerulus; Liver; Maternal Mortality; Microscopy, Electron; Myocardium; Placental Extracts; Pre-Eclampsia; Pregnancy; Rabbits; Shwartzman Phenomenon; Thromboplastin; Thrombosis

Topics: Antithrombins; Blood Coagulation; Fibrinolysis; Hemorrhagic Disorders; Hemostasis; Heparin Antagonists; Humans; Leukemia; Leukocytes; Thromboplastin

Topics: Anticoagulants; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Diagnosis, Differential; Fibrin; Fibrinogen; Hemorrhage; Hemorrhagic Disorders; Humans; Prothrombin; Prothrombin Time; Thromboplastin; Vascular Resistance

Topics: Anticoagulants; Female; Fetal Death; Fibrinolysis; Hemorrhagic Disorders; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Cell Membrane Permeability; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Thrombocythemia, Essential; Thrombocytopenia; Thromboplastin

Topics: Animals; Blood Coagulation; Blood Platelets; Erythrocytes; Fibrinolysis; Hemorrhagic Disorders; Humans; Thromboplastin

Topics: Blood Coagulation Disorders; Hemorrhagic Disorders; Hemostasis; Humans; Mutation; Thromboplastin

Very premature infants are at high risk of bleeding complications; however, few data exist on ranges for standard coagulation tests.. The primary objective of this study was to measure standard plasma coagulation tests and thrombin generation in very premature infants compared with term infants. The secondary objective was to evaluate whether an association existed between coagulation indices and intraventricular hemorrhage (IVH).. Cord and peripheral blood of neonates < 30 weeks gestational age (GA) was drawn at birth, on days 1 and 3 and fortnightly until 30 weeks corrected gestational age. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and coagulation factor levels were measured and tissue factor-stimulated thrombin generation was characterized. Control plasma was obtained from cord blood of term neonates.. One hundred and sixteen infants were recruited. Median (range) GA was 27.7 (23.7-29.9) weeks and mean (SD) birth weight was 1020 (255) g. Median (5th-95th percentile) day 1 PT, APTT and fibrinogen were 17.5 (12.7-26.6) s, 78.7 (48.7-134.3) s and 1.4 (0.72-3.8) g L(-1) , respectively. No difference in endogenous thrombin potential between preterm and term plasma was observed, where samples were available. Levels of coagulation factors II, VII, IX and X, protein C, protein S and antithrombin were reduced in preterm compared with term plasma. Day 1 APTT and PT were not associated with IVH.. In the largest cross-sectional study to date of very preterm infants, typical ranges for standard coagulation tests were determined. Despite long clotting times, thrombin generation was observed to be similar in very preterm and term infants.

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Component Transfusion; Cerebral Ventricles; Cross-Sectional Studies; Female; Fetal Blood; Fibrinogen; Gestational Age; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Intensive Care, Neonatal; Intracranial Hemorrhages; Male; Partial Thromboplastin Time; Prospective Studies; Prothrombin Time; Recombinant Proteins; Reference Standards; Thrombin; Thromboplastin; Vitamin K

Bleeding upon major surgery or severe trauma is treated by transfusion with crystalloids, colloids, or plasma. This treatment, however, can lead to dilutional coagulopathy and impaired hemostasis. We investigated the suitability of two integrative coagulation tests to measure the hemostatic activity of diluted plasma.. Plasma from healthy donors was diluted in vitro with saline or colloid (venofundin or gelofusin). Coagulant activity in response to tissue factor was monitored by calibrated automated thrombin (CAT) generation and rotational thromboelastography (TEG), detecting formation of elastic fibrin clots. Plasma from patients receiving fluid infusion during coronary artery bypass grafting (CABG) was analyzed with the same assays.. Optimal activity of CAT and TEG assays required the presence of 10 pmol per L tissue factor and 4 micromol per L phospholipid vesicles or 100 x 10(9) platelets (PLTs) per L. Strikingly, thrombin generation and clot formation became impaired at a higher extent of dilution with PLTs present (< or =40% plasma) than with phospholipid vesicles present (< or =60% plasma). Colloids aggravated the dilution effect on clot formation, but FFP antagonized the dilution effect on thrombin and clot formation. In contrast, fibrinogen and Factor (F)XIII only restored the impaired clot formation. In plasma samples from patients undergoing CABG, CAT and TEG assay variables were altered to an extent corresponding with the volume of fluid infusion.. Thrombin generation and clot formation are reduced at a plasma dilution of more than 40 percent. In either process, PLTs can partly compensate for the dilution effect. In vitro dilution with colloids impaired fibrin clot elasticity compared to saline.

Topics: Anticoagulants; Blood Coagulation; Blood Platelets; Colloids; Coronary Artery Bypass; Crystalloid Solutions; Gelatin; Hemorrhagic Disorders; Heparin; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Osmolar Concentration; Plasma; Plasma Substitutes; Protamines; Recombinant Proteins; Succinates; Thrombelastography; Thrombin; Thromboplastin

In a patient who presented with a severe coagulation deficiency in plasma contrasting with a very mild hemorrhagic diathesis a homozygous Arg67His mutation was identified in the prothrombin gene. Wild-type (factor IIa [FIIa]-WT) and mutant Arg67His thrombin (FIIa-MT67) had similar amidolytic activity. By contrast, the k(cat)/K(m) value of fibrinopeptide A hydrolysis by FIIa-WT and FIIa-MT67 was equal to 2.1 x 10(7) M(-1)s(-1) and 9 x 10(5) M(-1)s(-1). Decreased activation of protein C (PC) correlated with the 33-fold decreased binding affinity for thrombomodulin (TM; K(d) = 65.3 nM vs 2.1 nM, in FIIa-MT67 and in FIIa-WT, respectively). In contrast, hydrolysis of PC in the absence of TM was normal. The Arg67His mutation had a dramatic effect on the cleavage of protease-activated G protein-coupled receptor 1 (PAR-1) 38-60 peptide (k(cat/)K(m) = 4 x 10(7) M(-1)s(-1) to 1.2 x 10(6) M(-1)s(-1)). FIIa-MT67 showed a weaker platelet activating capacity, attributed to a defective PAR-1 interaction, whereas the interaction with glycoprotein Ib was normal. A drastic decrease (up to 500-fold) of the second-order rate constant pertaining to heparin cofactor II (HCII) interaction, especially in the presence of dermatan sulfate, was found for the FIIa-MT67 compared with FIIa-WT, suggesting a severe impairment of thrombin inhibition by HCII in vivo. Finally, the Arg67His mutation was associated with a 5-fold decrease of prothrombin activation by the factor Xa-factor Va complex, perhaps through impairment of the prothrombin-factor Va interaction. These experiments show that the Arg67His substitution affects drastically both the procoagulant and the anticoagulant functions of thrombin as well as its inhibition by HCII. The mild hemorrhagic phenotype might be explained by abnormalities that ultimately counterbalance each other.

Topics: Arginine; Blood Coagulation Disorders; Cell Line; Consanguinity; Factor Va; Factor Xa; Female; Fibrinopeptide A; Hemorrhagic Disorders; Heparin Cofactor II; Histidine; Homozygote; Humans; Hydrolysis; Infant; Mutagenesis, Site-Directed; Mutation; Protein C; Prothrombin; Receptor, PAR-1; Receptors, Thrombin; Thrombin; Thrombomodulin; Thromboplastin; Transfection

Exposure of blood to tissue factor (TF) activates the extrinsic (TF:FVIIa) and intrinsic (FVIIIa:FIXa) pathways of coagulation. In this study, we found that mice expressing low levels of human TF ( approximately 1% of wild-type levels) in an mTF(-/-) background had significantly shorter lifespans than wild-type mice, in part, because of spontaneous fatal hemorrhages. All low-TF mice exhibited a selective heart defect that consisted of hemosiderin deposition and fibrosis. Direct intracardiac measurement demonstrated a 30% reduction (P < 0.001) in left ventricular function in 8-month-old low-TF mice compared with age-matched wild-type mice. Mice expressing low levels of murine FVII ( approximately 1% of wild-type levels) exhibited a similar pattern of hemosiderin deposition and fibrosis in their hearts. In contrast, FIX(-/-) mice, a model of hemophilia B, had normal hearts. Cardiac fibrosis in low-TF and low-FVII mice appears to be caused by hemorrhage from cardiac vessels due to impaired hemostasis. We propose that TF expression by cardiac myocytes provides a secondary hemostatic barrier to protect the heart from hemorrhage.

Topics: Animals; Endomyocardial Fibrosis; Factor VII; Fibrinogen; Gene Expression; Genetic Predisposition to Disease; Hemophilia B; Hemorrhagic Disorders; Hemosiderin; Hemostasis; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Models, Biological; Muscle, Skeletal; Myocardium; Organ Specificity; Protein Structure, Tertiary; Recombinant Fusion Proteins; Thromboplastin; Ventricular Dysfunction, Left

Factor VII (FVII) requires the cleavage of an internal peptide bond and the association with tissue factor (TF) to attain its fully active FVIIa conformation. This event alone leaves FVIIa in a zymogen-like state of relatively low specific activity. The TF-induced allosteric enhancement of FVIIa's activity contributes to the procoagulant activity of the complex. We have characterized two naturally occurring mutations (S363I - W364C) on FVII gene. Both homozygous patients for each mutation have a normal FVII: Ag level associated to an undetectable FVII coagulant activity. The patient carrying the allele 364C had a more severe hemorrhagic diathesis than the S363I mutant. To understand the mechanism of these deficiency, in vitro expression analysis with further biochemical characterization of recombinant proteins of both mutants FVII-363I, FVII-364C and wild type (WTFVII) FVII constructs were done. The results recapitulated the patients' plasma data with normal Ag level and no detectable coagulant activity. The D-F-Pip-R-pNA and CH(3)SO(2)-D-CHA-A-But-R chromogenic substrates were used to evaluate the amidolytic activity of WT and mutant FVII in presence and absence of recombinant tissue factor (rTF). Binding of FVII to rTF by a solid phase binding assay was done using recombinant human rTF. The results of amidolytic assays showed that rTF enhances 28 fold the value of the specificity of constant (kcat/K(m)) in WT but no activity was detectable in either mutant constructs under any condition. The equilibrium dissociation constant of rTF-FVIIa interaction showed Kd equal to 4.4 +/- 0.2nM, 4.9 +/- 0.5nM and 6 +/- 0.9 of WT, 363I and 364C FVII forms, respectively. The K(d) values of the non activated forms were equal to 24.7 +/- 3.3, 24.4 +/- 3.1 and 20.6 +/- 4nM, respectively. These data demonstrate that, compared to the WT form, FVII-363I and FVII-364C have no significant affinity change for TF and that the detrimental effect of these two mutations is attributable to the loss of an efficient catalytic machinery in the FVII molecule causing a severe deficiency of coagulant activities.

Topics: Adult; Catalysis; Chromogenic Compounds; Factor VII; Factor VII Deficiency; Factor X; Hemorrhagic Disorders; Homozygote; Humans; Kinetics; Male; Point Mutation; Protein Binding; Thromboplastin

Monocyte tissue factor expression was evaluated in 67 patients with hepatosplenic Schistosomiasis. They were classified as Child A (n = 15), Child B (n = 15), Child C (n = 12) and Bleeders (n = 10), in addition to 15 healthy controls. Mononuclear cells were cultured in vitro with and without lipopolysaccharide (LPS) to assess monocyte tissue factor (TF) antigen (Ag) and activity (Act) in cell lysate, in addition to measurement of prothrombin fragment 1 + 2 (F1 + 2) as a marker of in vivo thrombin generation. A significant increase in monocyte TF Ag and TF Act was noted in all stages of the disease compared with the control group, with marked accentuation during an acute attack of variceal bleeding. This enhanced monocyte expression was noted before the addition of LPS and became more obvious with addition of LPS. An increasing level of F1 + 2 was similarly noted. These findings constitute further evidence for an existing prothrombotic state in hepatosplenic Schistosomiasis, and also that monocytes are closely implicated in the haemostatic diathesis characterizing the disease.

Topics: Adult; Case-Control Studies; Hemorrhagic Disorders; Humans; Lipopolysaccharides; Liver Diseases; Monocytes; Peptide Fragments; Prothrombin; Schistosomiasis; Severity of Illness Index; Splenic Diseases; Thrombophilia; Thromboplastin

Topics: Blood Coagulation; Enzyme Activation; Factor IX; Factor XI Deficiency; Factor XII Deficiency; Hemorrhagic Disorders; Kininogens; Plasma; Prekallikrein; Thrombin; Thromboplastin; Thrombosis

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u-PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.

Topics: Adolescent; Adult; Aged; Aprotinin; Blood Coagulation; Cell Differentiation; Cysteine Endopeptidases; Female; Fibrinolysis; Gene Expression Regulation, Leukemic; Hemorrhagic Disorders; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Pancreatic Elastase; Thromboplastin; Tissue Plasminogen Activator; Tretinoin; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

High doses of aprotinin have been shown to reduce blood loss and blood transfusion requirements in patients undergoing open heart surgery and recent studies in animals have shown that aprotinin was able to reduce bleeding associated with rt-PA administration. Our study was designed to demonstrate an effect of aprotinin (Iniprol) on the prolongation of the bleeding time associated with the treatment with a potent analogue of ticlopidine: clopidogrel. Bleeding time was determined in rats by transection of the tip of the tail. 2 hours after a single oral administration, clopidogrel (5 mg/kg, p.o.), induced a 4-fold increase in the bleeding time. Aprotinin administered as a bolus iv injection followed by continuous infusion strongly reduced bleeding time prolongation associated with clopidogrel treatment. This effect was dose-related and reached a maximum (congruent to 50% inhibition--P < 0.001) at and above the total dose of 40 U Ph Eur/kg (80,000 KIU/kg). After administration of a total dose of 60 U Ph Eur/kg (120,000 KIU/kg), aprotinin modified neither the antiaggregating effect of clopidogrel nor its antithrombotic activity, as determined in various experimental models. For this reason, aprotinin might constitute a useful antagonist of the haemorrhagic risk associated with interventional therapy under treatment with ticlopidine or clopidogrel.

Topics: Animals; Aprotinin; Arteriovenous Shunt, Surgical; Bleeding Time; Clopidogrel; Constriction; Hemorrhagic Disorders; Hemostasis; Rats; Rats, Sprague-Dawley; Thromboplastin; Thrombosis; Ticlopidine

Pathological inhibitors of the coagulation which are recognized by characteristic laboratory findings may cause an increased inclination to haemorrhage, may be clinically mute or also may effect an increased inclination to thrombosis (lupus inhibitors). It is reported on patients with rare coagulation inhibitors, a pathologic antithrombin with normal reptilase time and an antithromboplastin with protracted effect, in which thromboses appeared. The occurrence of thromboses in these patients up to now does not allow the assumption of an effect of these inhibitor substances furthering thrombosis, but only the statement that despite coagulation-analytically recognizable inhibition effects the development of a thrombosis is not prevented. A prophylactic factor substitution in operative interventions is not indicated.

Topics: Adult; Antithrombins; Female; Hemorrhagic Disorders; Humans; Male; Thrombin Time; Thrombophlebitis; Thromboplastin; Thrombosis

Ten individuals from three unrelated families suffered from an usual inherited haemorrhagic disorder. The defect was associated with reduced prothrombin conversion as shown by a grossly abnormal prothrombin consumption index. All known plasma coagulation factors were present in adequate concentrations but in the two families tested the results were consistent with a defect of the interaction between plasma and platelets or phospholipid. Some of the affected family members exhibited a mild bleeding tendency characterized by post-operative or post-partum haemorrhage but none suffered spontaneous bleeding. In therapeutic trials in one of the patients both plasma and platelet transfusions were needed in order to correct the abnormality. This finding together with in vitro and other in vivo studies indicated that the abnormality is associated with an inhibitor of the interaction between plasma and phospholipid during blood coagulation. The results suggest the possibility of an abnormality of the gamma-carboxyglutamic acid residues of one or more vitamin K dependent coagulation factors but immunological and electrophoretic studies have so far failed to detect this. The findings underline the importance of a test of prothrombin conversion in screening procedures for an otherwise unexplained bleeding disorder.

Topics: Adolescent; Adult; Factor X; Female; Hemorrhagic Disorders; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Pedigree; Prothrombin; Prothrombin Time; Thromboplastin; Whole Blood Coagulation Time

We studied a coagulation abnormality present in 12 members of five kindreds who bruised easily and bled excessively after minor trauma. Their activated partial thromboplastin times were between 32 and 39 seconds (normal, 22.8 to 28.8 seconds). Prothrombin times, thrombin times, platelet-function tests and the levels of factors XII, XI, IX, VIII, prekallikrein and high-molecular-weight kininogen were normal. Within these kindreds inheritance of prolonged partial thromboplastin times followed an autosomal and probably dominant pattern. The prolonged thromboplastin times were corrected by normal plasma and by normal plasma adsorbed with celite, but there was no mutual correction between plasmas of the patients. These subjects shared a common defect in the intrinsic pathway of coagulation that we designate by the proband's surname, Passovoy.

Topics: Adolescent; Adult; Blood Coagulation Factors; Blood Coagulation Tests; Child; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Pedigree; Thromboplastin

Topics: Adolescent; Adult; Blood Coagulation Tests; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Thromboplastin

A moderate bleeding diathesis transmitted as an autosomal dominant was found in five members of four generations of the same family. The affected patients had prolonged partial thromboplastin-times and normal levels of all the known clotting-factors. The haemorrhagic diathesis was attributed to a deficiency of a hitherto unrecognised coagulation factor--i.e., the Passovoy facto.

Topics: Adult; Aluminum Hydroxide; Blood Coagulation Factors; Blood Coagulation Tests; Child; Deficiency Diseases; Female; Hemorrhagic Disorders; Hemostasis; Humans; Infant, Newborn; Male; Middle Aged; Pedigree; Thromboplastin

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

The role of disseminated intravascular clotting (DIC) in the pathogenesis of the bleeding diathesis kwashiorkor was investigated in 22 patients. According to the severity of the clinical and haematological findings, two grades of DIC were observed. A severe grade of DIC was shown in 6 cases (5 fatal) presenting with thrombocytopenia, hypofibinogenaemia, and multiple coagulation defects, and with abnormally prolonged partial thromboplastin,prothombin, and thrombin times]. A second goups of 16 patients (7 fatal) showed a less severe grade of DIC manifested by thrombocytopenia, low fibringoen level, and a clotting factor defect shown by rpolonged prothrombin and thrombin times.

Topics: Blood Cell Count; Blood Platelets; Child, Preschool; Dehydration; Disseminated Intravascular Coagulation; Female; Fibrinogen; Hemorrhagic Disorders; Humans; Infant; Kwashiorkor; Male; Prothrombin Time; Thrombin; Thromboplastin

A new case of facultative hemorrhagic diathesis is described in a 19 year old female and the coagulatory anomaly examined. The experiments show that the coagulatory disturbance should be ascribed to a defective aggregation of fibrin monomers associated with hypofibrinogenemia. Some of its characteristics are the markedly prolonged thrombin-, reptilase-time as well prolonged prothrombin and partial thromboplastin time. The plasma fibrinogen concentration measured by the immunologic method is reduced. The streptokinase induced digestion of fibrinogen Giessen II plasma occurred at a slower rate than normal plasma with persistence of the large fibrinogen degradation products. Fibrinogen Giessen II appears to be a congenital hypodysfibrinogenemia with abnormality of fibrinogen resulting in delayed coagulation and a retarded fibrinogenolysis rate.

Topics: Adult; Afibrinogenemia; Batroxobin; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Streptokinase; Thrombin; Thromboplastin

Topics: Biopsy, Needle; Blood Coagulation Disorders; Hemorrhagic Disorders; Hepatitis; Humans; Hypoprothrombinemias; Infant; Infusions, Parenteral; Iron; Liver Function Tests; Malabsorption Syndromes; Male; Prothrombin Time; Thromboplastin; Vitamin K; Vitamin K Deficiency

Topics: Blood Coagulation Tests; Bone Marrow; Bone Marrow Cells; Bone Marrow Examination; Daunorubicin; Disseminated Intravascular Coagulation; Fibrinogen; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Heparin; History, 20th Century; Humans; Leukemia, Myeloid, Acute; Thromboplastin

Topics: Aged; Blood Coagulation Tests; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrinolysis; Hemorrhagic Disorders; Heparin; Humans; Male; Methods; Protamines; Thrombin; Thromboplastin

Topics: Adult; Blood Coagulation Tests; Factor IX; Factor VII; Factor VII Deficiency; Factor X; Female; Hemorrhagic Disorders; Heterozygote; Homozygote; Humans; Male; Prothrombin; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Proteins; Blood Sedimentation; Factor IX; Factor V; Factor VIII; Factor X; Factor XIII; Female; Fibrinogen; Hemorrhagic Disorders; Heterozygote; Humans; Infant; Infant, Newborn; Male; Prothrombin; Thrombelastography; Thrombin; Thromboplastin

Topics: Aneurysm; Cerebral Arterial Diseases; Creatinine; Dextrans; Factor VIII; Fibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Kidney Diseases, Cystic; Male; Middle Aged; Platelet Adhesiveness; Prothrombin Time; Thrombin; Thromboplastin

Topics: Adolescent; Adult; Blood Coagulation Disorders; Female; Fibrinolysis; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Male; Middle Aged; Thromboplastin

Topics: Blood; Female; Hemorrhagic Disorders; Humans; Infant, Newborn; Labor, Obstetric; Postpartum Period; Pregnancy; Thromboplastin; Umbilical Cord

Topics: Aged; Anticoagulants; Antithrombins; Blood Coagulation Disorders; Factor VIII; Female; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Humans; Male; Middle Aged; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin

Topics: Afibrinogenemia; Aged; Blood Coagulation Tests; Blood Platelets; Blood Protein Disorders; Factor VIII; Female; Fibrin; Hemorrhagic Disorders; Humans; Immunoglobulin G; Japan; Male; Middle Aged; Multiple Myeloma; Thromboplastin; Waldenstrom Macroglobulinemia

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Fibrinogen; Hemorrhagic Disorders; Hemostasis; Humans; Liver Diseases; Prothrombin Time; Thrombin; Thrombocytopenia; Thromboplastin

Topics: Administration, Oral; Adult; Blood Coagulation Tests; Dicumarol; Factor IX; Factor VII; Factor X; Factor XI; Female; Hemorrhagic Disorders; Humans; Malingering; Middle Aged; Substance-Related Disorders; Thromboplastin

Topics: Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Blood Protein Disorders; Blood Protein Electrophoresis; Hemorrhagic Disorders; Hemostasis; Humans; Immunodiffusion; Immunoglobulin G; Immunoglobulin M; Leukemia, Lymphoid; Multiple Myeloma; Platelet Adhesiveness; Thromboplastin; Waldenstrom Macroglobulinemia

Topics: Adenoidectomy; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Factor IX; Factor VIII; Factor XI; Factor XI Deficiency; Female; Fibrinogen; Hemorrhagic Disorders; Humans; Middle Aged; Postoperative Complications; Thromboplastin; Tonsillectomy

Topics: Adenine Nucleotides; Adult; Blood Coagulation Tests; Blood Platelets; Clot Retraction; Collagen; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Platelet Adhesiveness; Respiratory Distress Syndrome, Newborn; Thrombelastography; Thrombin; Thromboplastin

Topics: Adult; Blood Coagulation Tests; Diagnostic Errors; Female; Hematology; Hemorrhagic Disorders; Humans; Pre-Eclampsia; Pregnancy; Prothrombin Time; Thromboplastin

Topics: Acute Kidney Injury; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Coronary Disease; Female; Heart Arrest; Hemorrhagic Disorders; Humans; Hyaline Membrane Disease; Infant, Newborn; Ischemia; Kidney Transplantation; Male; Obstetric Labor Complications; Pregnancy; Shock, Septic; Shwartzman Phenomenon; Thrombocytopenia; Thromboembolism; Thromboplastin; Toxemia; Wounds and Injuries

Topics: Abortion, Septic; Blood Coagulation Disorders; Embolism, Amniotic Fluid; Female; Fetal Death; Fibrinolysis; Gelatin; Hemorrhagic Disorders; Humans; Hydrogen-Ion Concentration; Placenta; Placenta Diseases; Plasma Substitutes; Pregnancy; Pregnancy Complications; Pulmonary Embolism; Shock, Hemorrhagic; Shock, Septic; Streptokinase; Thrombophlebitis; Thromboplastin; Thrombosis

Topics: Blood Coagulation Tests; Child; Female; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Male; Methods; Thrombelastography; Thromboplastin

Topics: Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Hemorrhagic Disorders; Humans; Kidney Failure, Chronic; Kidney Transplantation; Thromboplastin; Transplantation, Homologous; Uremia

Topics: Adult; Blood Circulation Time; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Breast Neoplasms; Carcinoma; Factor XI; Factor XI Deficiency; Female; Hemorrhage; Hemorrhagic Disorders; Humans; Mastectomy; Methods; Microscopy, Phase-Contrast; Plasma Substitutes; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Tests; Factor XI Deficiency; Female; Hemorrhagic Disorders; Humans; Male; Thromboplastin

Topics: Abruptio Placentae; Adult; Aprotinin; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Factor V; Factor VIII; Female; Fibrinogen; Glass; Hemorrhage; Hemorrhagic Disorders; Humans; In Vitro Techniques; Middle Aged; Plasminogen; Postoperative Complications; Pregnancy; Prothrombin; Thrombin; Thromboplastin; Time Factors

Topics: Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Factor IX; Factor VIII; Hemorrhagic Disorders; Humans; Prothrombin Time; 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 Coagulation Disorders; Child; Diagnosis, Differential; Factor VIII; Factor XIII; Hemorrhagic Disorders; Humans; Male; Thromboplastin

Topics: Adolescent; Blood Coagulation Tests; Blood Platelets; Child; Factor XI Deficiency; Factor XII; Female; Hemorrhagic Disorders; Humans; Male; Middle Aged; Thromboplastin

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Electroconvulsive Therapy; Factor VIII; Fibrinolysis; Hemorrhagic Disorders; Humans; Male; Thromboplastin

Topics: Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Protein Disorders; Calcium; Collagen; Connective Tissue; Fibrin; Fibrinogen; gamma-Globulins; Hemorrhagic Disorders; Humans; Male; Multiple Myeloma; Nitrogen Mustard Compounds; Plasmapheresis; Prothrombin Time; Thromboplastin; Tryptophan

Topics: Afibrinogenemia; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Calcium; Female; Hemorrhagic Disorders; Hemostasis; Humans; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Serotonin; Thromboplastin

Topics: Abortion, Missed; Abruptio Placentae; Adolescent; Adult; Aprotinin; Blood Coagulation Tests; Female; Hematoma; Hemorrhagic Disorders; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thromboplastin; Uterine Hemorrhage

Topics: Adenine Nucleotides; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Citrates; Densitometry; Factor XII; Freezing; Hemorrhagic Disorders; Humans; Silicones; Thrombin; Thromboplastin; von Willebrand Diseases

Topics: Adult; Blood Coagulation Tests; Diagnosis, Differential; Factor XI; Factor XI Deficiency; Factor XII; Hemorrhagic Disorders; Humans; Male; Prothrombin Time; Thromboplastin

Topics: Anticoagulants; Blood Coagulation Tests; Drug Therapy; Hemorrhagic Disorders; Humans; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Tests; Factor XI; Factor XI Deficiency; Hemorrhage; Hemorrhagic Disorders; Humans; Postoperative Complications; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Tests; Blood Donors; Blood Platelets; Blood Preservation; Blood Transfusion; Fibrinogen; Hemorrhagic Disorders; Heparin; Humans; In Vitro Techniques; Refrigeration; Thromboplastin

Topics: Arteriosclerosis; Hemorrhagic Disorders; Heparin; Lipoproteins; Myocardial Infarction; Oxalates; Thromboplastin

Topics: Blood Chemical Analysis; Blood Coagulation Factors; Factor XI; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Thromboplastin

Topics: Anemia; Exchange Transfusion, Whole Blood; Factor VII Deficiency; Factor VIII; Hemophilia B; Hemorrhagic Disorders; Humans; Hyperbilirubinemia; Hypoprothrombinemias; Infant; Infant, Newborn; Infant, Newborn, Diseases; Prednisone; Scalp; Skull Fractures; Thromboplastin; Vitamin K 1

Topics: Anticoagulants; Blood; Geriatrics; Hemorrhagic Disorders; Polycythemia; Pulmonary Heart Disease; Syndrome; Thromboplastin

Topics: Autoimmune Diseases; Female; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Pregnancy; Pregnancy Complications, Hematologic; 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: Abruptio Placentae; Afibrinogenemia; Aminocaproates; Aminocaproic Acid; Blood Coagulation Tests; Blood Transfusion; Calcium; Dexamethasone; Drug Therapy; Female; Fetal Death; Fibrinogen; Fibrinolysin; Hemorrhagic Disorders; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thromboplastin; Tolonium Chloride; Uterine Hemorrhage

Topics: Blood Coagulation Tests; Hematologic Tests; Hemorrhagic Disorders; Humans; Plasma; Thromboplastin

Topics: Anticoagulants; Enzyme Inhibitors; Hemorrhagic Disorders; Heparin; Humans; Thromboplastin

Topics: Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Sex Chromosome Disorders; Thrombocytopenia; Thromboplastin

Topics: Blood Coagulation; Blood Coagulation Tests; Factor VII Deficiency; Factor VIII; Hemophilia B; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin Time; Thromboplastin

Topics: Blood Coagulation Tests; Genetic Diseases, X-Linked; Hemorrhagic Disorders; Humans; Leukemia; Leukemia, Hairy Cell; Lymphatic Diseases; Metabolism; Severe Combined Immunodeficiency; Thrombocytopenia; Thromboplastin

Topics: Adolescent; Aminocaproates; Aminocaproic Acid; Child; Chromatography; Factor IX; Factor VIII; Fibrinolysin; Fibrinolysis; Hemophilia A; Hemorrhagic Disorders; Humans; Thromboplastin

Topics: Hemorrhagic Disorders; Humans; Thromboplastin

Topics: Hemorrhagic Disorders; Thromboplastin

Topics: Diagnosis, Differential; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Syndrome; Thromboplastin

Topics: Hemorrhage; Hemorrhagic Disorders; Humans; Partial Thromboplastin Time; Thromboplastin

Topics: Blood Coagulation Tests; Blood Platelets; Hematologic Diseases; Hemorrhagic Disorders; Humans; Platelet Function Tests; Thromboplastin

Topics: Hemorrhagic Disorders; Humans; Minority Groups; Racial Groups; Thromboplastin

Topics: Blood Platelets; Glycine max; Hemorrhagic Disorders; Humans; Phospholipids; Thromboplastin

Topics: Glycine max; Hemophilia A; Hemorrhagic Disorders; Hemostatics; Phospholipids; Prothrombin; Thromboplastin

Topics: Blood Platelets; Hematologic Diseases; Hemorrhagic Disorders; Thromboplastin

Topics: Anticoagulants; Hemorrhagic Disorders; Immunoglobulins; Thromboplastin

Topics: Factor VII; Hemorrhagic Disorders; Thromboplastin

Topics: Hemophilia A; Hemorrhagic Disorders; Humans; Medical Records; Medicine; Plasma; Sex Chromosome Disorders; Thromboplastin

Topics: Annexin A5; Hemorrhagic Disorders; Humans; Spondylitis; Spondylitis, Ankylosing; Thromboplastin

Topics: Blood Platelets; Factor V Deficiency; Hemophilia A; Hemorrhagic Disorders; Humans; Medical Records; Medicine; Thromboplastin

Topics: Anticoagulants; Arthritis; Arthritis, Rheumatoid; Hemorrhagic Disorders; Medical Records; Thromboplastin

Topics: Hemorrhagic Disorders; Thromboplastin

Topics: Blood Coagulation; Hemorrhagic Disorders; Humans; Plasma; Prothrombin; Thromboplastin

Topics: Blood Platelets; Hemorrhagic Disorders; Thromboplastin

Topics: Aged; Blood Coagulation Disorders; Factor XI Deficiency; Hemophilia A; Hemorrhagic Disorders; Humans; Medical Records; Medicine; Thromboplastin

Topics: Anticoagulants; Arthritis; Arthritis, Rheumatoid; Blood Coagulation; Hemorrhagic Disorders; Humans; Thromboplastin

Topics: Hemorrhagic Disorders; Humans; Myocardial Infarction; Pulmonary Embolism; Thromboplastin; Thrombosis

Topics: Clinical Laboratory Techniques; Hematologic Diseases; Hemorrhagic Disorders; Thromboplastin

Topics: Blood Coagulation Disorders; Hemorrhage; Hemorrhagic Disorders; Plasma; Thromboplastin

Topics: Hematologic Diseases; Hemorrhagic Disorders; Thromboplastin

Topics: Blood Coagulation Disorders; Hemorrhagic Disorders; Thromboplastin

Topics: Afibrinogenemia; Amniotic Fluid; Factor Xa; Female; Fibrinogen; Hemorrhage; Hemorrhagic Disorders; Humans; Labor, Obstetric; Pregnancy; Thromboplastin; Work

Topics: Gynecology; Hemorrhagic Disorders; Thromboplastin

Topics: Hematologic Agents; Hemorrhagic Disorders; Thromboplastin

Topics: Blood Coagulation; Hemorrhagic Disorders; Thromboplastin

Topics: Blood Platelets; Hemorrhagic Disorders; Humans; Racial Groups; Thromboplastin

Topics: Blood Coagulation Disorders; Hemophilia A; Hemophilia B; Hemorrhage; Hemorrhagic Disorders; Medicine; Thromboplastin

Topics: Blood Platelets; Hemorrhagic Disorders; Humans; Thromboplastin

Topics: Hemorrhagic Disorders; Thromboplastin

Topics: Factor XI Deficiency; Hemorrhage; Hemorrhagic Disorders; Thromboplastin

Topics: Anticoagulants; Blood Coagulation; Hemorrhagic Disorders; Humans; Immunoglobulins; Thromboplastin

Topics: Diagnosis, Differential; Hemophilia B; Hemorrhagic Disorders; Thromboplastin

Topics: Factor IX; Hemorrhagic Disorders; In Vitro Techniques; Plasma; Thromboplastin; Vascular Diseases

Topics: Factor IX; Factor VIII; Hemorrhagic Disorders; Plasma; Serum; Serum Globulins; Syndrome; Thromboplastin

Topics: Child; Diagnosis, Differential; Hemorrhagic Disorders; Humans; Infant; Syndrome; Thromboplastin

Topics: Globulins; Hemophilia A; Hemorrhagic Disorders; Plasma; Thromboplastin

Topics: Factor IX; Hemophilia A; Hemophilia B; Hemorrhagic Disorders; Medicine; Sex Chromosome Disorders; Thromboplastin

Topics: Diagnosis, Differential; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Infant; Infant, Newborn; Prothrombin; Thromboplastin

Topics: Hemophilia A; Hemorrhagic Disorders; Medicine; Plasma; Thromboplastin

Topics: Blood; Factor XI; Hemophilia A; Hemorrhagic Disorders; Humans; Medicine; Sex Chromosome Disorders; Thromboplastin

Topics: Diagnosis, Differential; Hematologic Diseases; Hemophilia A; Hemophilia B; Hemorrhagic Disorders; Medicine; Thromboplastin

Topics: Factor Xa; Hemorrhagic Disorders; Thromboplastin

Topics: Cell Differentiation; Hemorrhagic Disorders; Thromboplastin

Topics: Blood Coagulation; Hemorrhagic Disorders; Thromboplastin

Topics: Child; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Thromboplastin

Topics: Hemorrhage; Hemorrhagic Disorders; Humans; Prothrombin; Serum; Thromboplastin