fibrin and Hemorrhagic-Disorders

Acquired factor XIII (FXIII) deficiency, arising from an autoantibody against factor XIII, is a rare bleeding disorder. This autoimmune disorder most commonly occurs in the elderly. Patients who develop such acquired FXIII inhibitors may present with catastrophic bleeding events and are hard to be diagnosed with the normal general coagulation tests. Though the disease is relatively rare, it is known to cause significant mortality. In this article we briefly describe a patient who presented with extensive bleeding and a normal activated partial thromboplastin time and prothrombin time (PT), but had an acquired inhibitor to FXIII; her primary disease was systemic lupus erythematosus (SLE). Also, we will focus on the clinical features, treatment modalities, fibrin structure and epitope identification for acquired factor XIII inhibitor with a review of the literature.

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factor Inhibitors; Epitopes; Factor VIII; Factor XIII Deficiency; Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Autoantigens; Autoimmune Diseases; Biopolymers; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrin; Hemorrhagic Disorders; Humans; Lymphoproliferative Disorders; Male; Middle Aged; Paraproteins; Thrombophilia

Topics: Biomarkers; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Hemorrhagic Disorders; Humans; Immunoenzyme Techniques; Latex Fixation Tests; Nephelometry and Turbidimetry; Polymers; Reference Standards; Specimen Handling; Thrombophilia

The most powerful instrument to establish the presence or absence of a coagulation disorder is the history of the patient. In addition, screening laboratory tests (consisting of the platelet count, bleeding time and global clotting assays, such as the prothrombin time and the activated partial thromboplastin time) may be helpful to support the diagnosis. In two patients, a 21-year-old man and a 10-year-old girl, with a marked history of enhanced bleeding normal screening laboratory tests were found. The male patient had a congenital alpha 2-antiplasmin deficiency and the girl had a homozygous deficiency of factor XIII. Some defects in the coagulation system (such as defects in fibrin network formation and fibrinolysis, but also mild Von Willebrand disease) are indeed not detected by screening laboratory tests. In patients with a strong suspicion of a coagulation disorder such defects should be specifically tested for.

Topics: Adult; alpha-2-Antiplasmin; Antifibrinolytic Agents; Blood Coagulation Tests; Child; Diagnosis, Differential; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Fibrinolysis; Hemorrhagic Disorders; Humans; Male; Medical History Taking; Tranexamic Acid

Topics: Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Thrombosis

Factor XIII (XIII), an enzyme found in plasma (present as a pro-enzyme), platelets and monocytes, is essential for normal haemostasis. It may also have a role to play in the processes of wound healing and tissue repair. Inherited XIII deficiency results in a life-long, severe bleeding diathesis which, if untreated, carries a very high risk of death in early life from intracranial bleeding. XIII is a zymogen requiring thrombin and calcium for activation. In plasma, XIII has two subunits: the 'a' subunit, which is the active enzyme, and the 'b' subunit which is a carrier protein. Activated XIII modifies the structure of clot by covalently crosslinking fibrin through an epsilon (gamma-glutamyl)lysine link. It also crosslinks other proteins, including fibronectin and alpha-2-plasmin inhibitor (alpha-2PI), into the clot through the same link. Clot modified by XIII is physically stronger, relatively more resistant to fibrinolysis and may be a more suitable medium for the ingrowth of fibroblasts. Inheritance of factor XIII is autosomal recessive. The majority of patients with the inherited defect show no XIII activity and absence of 'a' subunit protein in plasma, platelets and monocytes. At the molecular level, the defect is not a major gene rearrangement or deletion, but most likely a single point mutation which may be different in each family. Because of the severity of the bleeding diathesis, prophylaxis is desirable and has been shown to be very effective as the in vivo half-life of plasma XIII is long, and low plasma levels are sufficient for haemostasis. Acquired inhibitors have been reported in only two cases with inherited XIII deficiency. Acquired XIII deficiency has been described in a variety of diseases and bleeding has been controlled by therapy with large doses of XIII in such conditions as Henoch-Schönlein purpura, various forms of colitis, erosive gastritis and some forms of leukaemia. Large dose XIII therapy has also been used in an endeavour to promote wound healing after surgery and bone union in non-healing fractures. The use of XIII in these conditions remains controversial. Very rarely a bleeding diathesis results from the development of a specific inhibitor to XIII arising de novo, often as a complication in the course of a disease or in association with long-term drug therapy. The bleeding diathesis in these patients is difficult to treat.

Topics: Amino Acid Sequence; Enzyme Activation; Factor XIII; Factor XIII Deficiency; Fibrin; Hemorrhagic Disorders; Hemostasis; Humans; Molecular Sequence Data; Protein Conformation; Wound Healing

The precipitous increase in the number of structurally defined fibrinogen defects in recent years has resulted from application of high performance liquid chromatography in combination with peptide mapping and sequencing procedures. More recently, application of DNA sequence of polymerase chain reaction products has accelerated the pace of identification of mutations. Highly frequent defects are Arg substitutions, accounting for eight mutation sites substituted by Cys or His and less frequently by Ser. Amino acid substitutions at different positions on all three chains have pointed to possible structures with polymerization-related functions. Also, substitutions yielding consensus sequences resulted in extra glycosylations of the appropriate Asn in four different mutation sites; the impaired polymerization was reported associated with undue bleeding in two of these. Among informative defects have been those of homozygous probands with A alpha 16Arg----His and A alpha 16Arg----Cys in that failure of release of peptide A (but not of B), as shown with A alpha 16Arg----Cys, resulted in markedly delayed polymerization of such fibrin monomers, in general agreement with conclusions reached in studies of normal fibrin. This dysfunction, as well as the slow rate of release of A shown with A alpha 16Arg----His, was associated with clinically significant hemorrhagic diathesis (in the homozygous probands), consistent with the known physiologic importance of peptide A cleavage in normal hemostasis. Also, defects on the A alpha 17-19 sequence resulting in impaired polymerization are consistent with the known role of this segment in polymerization. Of similar interest have been defects within a B beta chain span encoded its exon 2. Two defects resulting in impaired polymerization and thrombin binding were associated with clinical thrombosis commencing in early life, and this lends strong support to other evidence suggesting a role in polymerization and in noncatalytic thrombin binding by this B beta chain segment. Thrombosis associated with A alpha 554Arg----Cys in a heterozygous proband with impaired tPA interaction is unique and may shed light on this poorly understood but important interaction among fibrin, plasminogen, and tPA. A group of different defects within the gamma 275-375 sequence have pointed to a polymerization role, evidenced by delayed gelation and impaired binding of mutant D to normal fibrin E. An unusual example is a 15 residue insertion between gamm

Topics: Afibrinogenemia; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Mutation; Protein Conformation; Protein Processing, Post-Translational; Protein Structure, Tertiary

Topics: Animals; Blood Coagulation; Blood Vessels; Endothelium; Fibrin; Hemorrhagic Disorders; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Thrombocytopenia

Coagulation factor XIII (fibrin stabilizing factor, FSF) is detectable in plasma, platelets, placenta and various tissues. In the activated form FSF has the enzymatic properties of a transglutaminase and is capable of stabilizing fibrin by inducing covalent bondings between fibrin monomers. In patients with congenital factor XIII deficiency or acquired immune inhibitors of fibrin stabilization a severe bleeding tendency is evident. There is not yet enough information available concerning the significance of reduced FSF-activity as cofactor in hemorrhagic diathesis and wound healing disturbances in various disease states. There are some indications from experimental studies that there might be an influence of FSF on tumor growth and metastasis as well as arteriosclerosis. The quantitation of the enzyme by radiological and immunological techniques yield reproducible results. Fibrin in its stabilized or non stabilized form can be discriminated in polyacrylamide gel electrophoresis after reduction of fibrin clots.

Topics: Adult; Blood Coagulation Disorders; Electrophoresis, Polyacrylamide Gel; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Hemorrhagic Disorders; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Hematologic

Topics: Animals; Blood Coagulation; Blood Protein Electrophoresis; Calcium; Enzyme Activation; Factor XII; Factor XIII; Factor XIII Deficiency; Fibrin; Fibrinogen; Fibrinolysin; Half-Life; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Heparin; Humans; Molecular Weight; Rats; Sulfhydryl Compounds; Thrombin

Topics: Abortion, Spontaneous; Blood; Blood Coagulation Tests; Blood Platelets; Cerebral Hemorrhage; Ecchymosis; Factor XIII; Factor XIII Deficiency; Female; Fetal Death; Fibrin; Hematoma; Hemorrhage; Hemorrhagic Disorders; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications, Hematologic; Umbilical Cord

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: Adolescent; Adrenal Glands; Adult; Aged; Blood Coagulation Disorders; Child; Female; Fibrin; Hemorrhagic Disorders; Heparin; Humans; Kidney; Male; Meningitis; Middle Aged; Pneumococcal Infections; Sepsis; Splenectomy; Splenic Diseases; Thrombosis; Waterhouse-Friderichsen Syndrome

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; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Coumarins; Drug Therapy; Fibrin; Hemorrhagic Disorders; Hemostasis; Heparin; Humans

Topics: Adult; Clinical Trials as Topic; Dentistry, Operative; Fibrin; Hemorrhagic Disorders; Humans; Mouth Mucosa; Oroantral Fistula; Surgery, Oral; Tissue Adhesives; Tooth Extraction

Simultaneous evaluation of coagulation and fibrinolysis facilitates an overall understanding of normal and pathological haemostasis. We established an assay for assessing clot formation and fibrinolysis simultaneously using clot waveform analysis by the trigger of a mixture of activated partial thromboplastin time reagent and an optimized concentration of tissue-type plasminogen activator (0·63 μg/ml) to examine the temporal reactions in a short monitoring time (<500 s). The interplay between clot formation and fibrinolysis was confirmed by analysing the effects of argatroban, tranexamic acid and thrombomodulin. Fibrinogen levels positively correlated with coagulation and fibrinolytic potential and initial fibrin clot formation was independent of plasminogen concentration. Plasminogen activator inhibitor-1-deficient (-def) and α2-antiplasmin-def plasmas demonstrated different characteristic hyper-fibrinolytic patterns. For the specificity of individual clotting factor-def plasmas, factor (F)VIII-def and FIX-def plasmas in particular demonstrated shortened fibrinolysis lag-times (FLT) and enhanced endogenous fibrinolysis potential in addition to decreased maximum coagulation velocity, possibly reflecting the fragile formation of fibrin clots. Tranexamic acid depressed fibrinolysis to a similar extent in FVIII-def and FIX-def plasmas. We concluded that the clot-fibrinolysis waveform analysis technique could sensitively monitor both sides of fibrin clot formation and fibrinolysis, and could provide an easy-to-use assay to help clarify the underlying pathogenesis of bleeding disorders in routine clinical practice.

Topics: Arginine; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Hemorrhagic Disorders; Humans; Kinetics; Pipecolic Acids; Sulfonamides; Thrombomodulin; Tranexamic Acid

Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Hemorrhagic Disorders; Humans; Thrombosis

Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1 have been implicated in the pathogenesis of pleural injury. However, their role in the control of pleural organization has been unclear. We found that a C57Bl/6j mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural organization resulting in pleural rind formation (14 d). In transgenic mice overexpressing human PAI-1, intrapleural fibrin deposition was increased, but visceral pleural thickness, lung volumes, and compliance were comparable to wild type. CBB injury in PAI-1(-/-) mice significantly increased visceral pleural thickness (P < 0.001), elastance (P < 0.05), and total lung resistance (P < 0.05), while decreasing lung compliance (P < 0.01) and lung volumes (P < 0.05). Collagen, α-smooth muscle actin, and tissue factor were increased in the thickened visceral pleura of PAI-1(-/-) mice. Colocalization of α-smooth muscle actin and calretinin within pleural mesothelial cells was increased in CBB-injured PAI-1(-/-) mice. Thrombin, factor Xa, plasmin, and urokinase induced mesothelial-mesenchymal transition, tissue factor expression, and activity in primary human pleural mesothelial cells. In PAI-1(-/-) mice, D-dimer and thrombin-antithrombin complex concentrations were increased in pleural lavage fluids. The results demonstrate that PAI-1 regulates CBB-induced pleural injury severity via unrestricted fibrinolysis and cross-talk with coagulation proteases. Whereas overexpression of PAI-1 augments intrapleural fibrin deposition, PAI-1 deficiency promotes profibrogenic alterations of the mesothelium that exacerbate pleural organization and lung restriction.

Topics: Animals; Bleomycin; Blood Coagulation; Epithelium; Fibrin; Hemorrhagic Disorders; Humans; Lung; Lung Injury; Mice; Mice, Inbred C57BL; Mice, Knockout; Plasminogen Activator Inhibitor 1; Pleura; Soot; Thrombin

Fibrinogen—a 340-kDa glycoprotein—plays a crucial role in blood coagulation, platelet aggregation, wound healing, and other physiological processes. A mutation in fibrinogen may lead to congenital dysfibrinogenemia,a rare disease characterized by the functional deficiency of fibrinogen. About 580 cases of abnormal fibrinogens have been reported worldwide; thereof 335 cases in the fibrinogen Aa chain[1]. To our knowledge, only five cases of abnormal fibrinogens with two mutations [2–6] and one case of two different mutations in the same family [7] have been described earlier. A 52-year-old female was examined for bleeding. Routine hemostasis screening resulted in a diagnosis of dysfibrinogenemia. Functional testing revealed prolonged fibrin polymerization, prolonged lysis of the clot, abnormal fibrin morphology,and fibrinopeptides release. Genetic analysis showed two heterozygous nonsense mutations—previously described mutation AaGly13Glu and a novel mutation Aa Ser314Cys. The mutation Aa Gly13-Glu was found in her brother and niece, but there was no evidence in either of the mutation Aa Ser314Cys. While mutation Aa Gly13Glu is responsible for abnormal fibrinopeptide release and prolonged thrombin time, the novel mutation Aa Ser314Cys seems to affect fibrin morphology and fibrinolysis.

Topics: Adult; Afibrinogenemia; Blood Protein Electrophoresis; Child; Codon, Nonsense; Female; Fibrin; Fibrinogens, Abnormal; Fibrinopeptide A; Hemorrhagic Disorders; Heterozygote; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Point Mutation; Protein Processing, Post-Translational

Topics: Antithrombins; Benzimidazoles; Blood Coagulation; Blood Coagulation Factors; Dabigatran; Drug Evaluation, Preclinical; Drug Monitoring; Factor VIIa; Fibrin; Hemorrhagic Disorders; Humans; In Vitro Techniques; Point-of-Care Systems; Pyridines; Recombinant Proteins; Thrombelastography; Thrombin; Whole Blood Coagulation Time

Endotoxemia caused by bacterial lipopolysaccharides (LPS) deleteriously affects many aspects of hemostasis. Much of this effect is well characterized as being secondary to the LPS-mediated inflammatory response, but direct effects of LPS on coagulation factors may also contribute to disregulation of the hemostatic process. Spectrophotometric assays were used to investigate the effects of LPS from different bacteria on thrombin and plasmin activities. We found that enzymatic activity of purified thrombin, but not plasmin, decreases in the presence of endotoxin. LPS-mediated inhibition of thrombin activity can be reversed by plasma gelsolin and recombinant endotoxin-neutralizing protein. Preincubation of thrombin with LPS before platelet activation results in inhibition of aggregation and secretion. Additionally, a decrease of elastic shear moduli of fibrin gels was observed when their formation was induced with thrombin preincubated with LPS or when LPS was present in fibrinogen solutions during fibrin gel formation. When added to platelet-rich plasma, after activation with collagen, LPS-inhibited thrombin activity. LPS-mediated inhibition of thrombin activity may contribute to the hemostasis dysfunctions observed during endotoxemia.

Topics: Calcium; Collagen; Endotoxemia; Escherichia coli; Fibrin; Gels; Gelsolin; Hemorrhagic Disorders; Humans; Klebsiella pneumoniae; Lipopolysaccharides; Platelet Aggregation; Pseudomonas aeruginosa; Recombinant Proteins; Salmonella enteritidis; Shear Strength; Species Specificity; Thrombin

We describe a 56-year-old patient with multiple myeloma and very high paraprotein concentration (IgG kappa). Coagulation studies showed unclottable thrombin and reptilase times caused by impaired fibrin polymerization presumably due to the paraproteinemia. There was no obvious bleeding tendency. The differential diagnosis of thrombin time prolongation includes inhibition of the added thrombin by exogenous heparin, hirudin or seldom by endogenous heparin-like anticoagulants or by acquired (bovine) thrombin antibodies, qualitative fibrinogen disorders (congenital and acquired dysfibrinogenemia), quantitative fibrinogen disorders (severe hypo- and afibrinogenemia) and delayed fibrin polymerization due to fibrin/fibrinogen degradation products, paraproteins and antibodies against fibrin(ogen). In multiple myeloma, thrombin time prolongation may seldom be due to endogenous heparin-like anticoagulants or antibodies to thrombin and more frequently to impaired fibrin polymerization by paraproteins. Simultaneous reptilase time prolongation as present in this case hints to this latter possibility.

Topics: Diagnosis, Differential; Fibrin; Hemorrhagic Disorders; Humans; Immunoglobulin kappa-Chains; Male; Middle Aged; Multiple Myeloma; Thrombin Time

Ten thousand & thirty seven autopsies performed from the year 1982 to 1992 were studied retrospectively, to find out the number of deaths due to bleeding diathesis. Eighty-seven (0.87%) patients died due to bleeding diathesis, out of which haemolytic uraemic syndrome (HUS) was seen in 9 cases (10.34%), disseminated intravascular coagulation (DIC) in 67 cases (77.01%) & 11 cases were grouped as miscellaneous. Martius scarlet blue stain was carried out to demonstrate fibrin & depending on the number of thrombi in the glomerulus & blood vessels, the lesions were graded as mild, moderate or severe. Kidney was the most common organ involved in all groups of bleeding diathesis. In DIC kidney & lung involvement was almost equal.

Topics: Autopsy; Disseminated Intravascular Coagulation; Female; Fibrin; Hemolytic-Uremic Syndrome; Hemorrhagic Disorders; Humans; Kidney; Lung; Male; Necrosis; Retrospective Studies; Staining and Labeling; Thrombosis

A congenitally abnormal fibrinogen was isolated from the blood of a young woman with a severe bleeding diathesis. Coagulation tests showed a prolonged Thrombin and Reptilase time partially corrected by Ca2+. Polymerization of thrombin induced preformed fibrin monomers was severely impaired. Thrombin caused the release of fibrinopeptides with normal retention times on HPLC. However, the rate of release was abnormally slow and the total amount of fibrinopeptide A (FpA) released reached only approximately 50% of the theoretical maximum. The rate and quantity of FpA release was normal when Reptilase was used. Transmission Electron Microscopy (TEM) of Thrombin induced clots showed an altered clot structure characterized by a reduced mean fiber diameter. The mother has a polymerization defect similar to the propositus, her fibrinopeptide release is unaffected however. The father has a minor fibrinopeptide release defect suggesting the presence of two populations of fibrinogen. This study supports the idea that the fibrinogen isolated from the propositus has two defects inherited as separate genetic traits. This fibrinogen has been named Fibrinogen Guarenas I.

Topics: Adolescent; Afibrinogenemia; Biopolymers; Female; Fibrin; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Hemorrhagic Disorders; Humans; Kinetics; Male; Metrorrhagia; Microscopy, Electron; Thrombin; Thrombin Time

Topics: Adolescent; Adult; Aged; Aprotinin; Drug Combinations; Face; Factor XIII; Female; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Hemorrhagic Disorders; Humans; Male; Maxilla; Middle Aged; Thrombin; Tissue Adhesives

alpha 2-Antiplasmin (alpha 2-AP) is a major fibrinolysis inhibitor, whose complete, congenital absence has been found to be associated with a distinct hemorrhagic diathesis. We studied a 15-yr-old male with a hemorrhagic diathesis after trauma from early childhood on. This bleeding tendency was associated with a minimal alpha 2-AP level recorded functionally in the immediate plasmin inhibition test: less than or equal to 4% of normal. However, a normal plasma concentration of alpha 2-AP antigen (83%) was found. His sister (5 yr old) showed similar results (2 and 92%). In their family, eight heterozygotes could be identified by half-normal activity results and normal antigen concentrations. The inheritance pattern is autosomal recessive. On analysis, the alpha 2-AP of the propositus was homogeneous in all respects tested, suggesting a homozygous defect. We designated the abnormal alpha 2-AP as alpha 2-AP Enschede. alpha 2-AP Enschede showed the following characteristics: (a) complete immunological identity with normal alpha 2-AP; (b) normal molecular weight (sodium dodecyl sulfate-polyacrylamide gel electrophoresis); (c) normal alpha-electrophoretic mobility; (d) presence in plasma of both molecular forms excluding an excessive conversion to the less reactive non-plasminogen-binding form; (e) quantitatively normal binding to lys-plasminogen and to immobilized plasminogen kringle 1-3; and (f) normal Factor XIII-mediated binding to fibrin. Functional abnormalities were found in: (i) no inhibition of amidolytic activities of plasmin and trypsin, even on prolonged incubation; (ii) no formation of plasmin-antiplasmin complexes in plasma with plasmin added in excess; and (iii) no inhibition of fibrinolysis by fibrin-bound alpha 2-AP. In the heterozygotes, the presence of abnormal alpha 2-AP did not interfere with several functions of the residual normal alpha 2-AP. One-dimensional peptide mapping showed an abnormal pattern of papain digestion. We conclude that in this family, abnormal antiplasmin molecules, defective in plasmin inhibition but with normal plasminogen-binding properties, have been inherited. The residual plasminogen-binding properties do not protect against a hemorrhagic diathesis.

Topics: Adolescent; alpha-2-Antiplasmin; Fibrin; Fibrinolysin; Fibrinolysis; Hemorrhagic Disorders; Humans; Immunodiffusion; Immunoelectrophoresis, Two-Dimensional; Male; Mutation; Papain; Pedigree; Plasminogen

A patient with an acquired inhibitor to factor XIII is reported. The patient's plasma produced a profound inhibition of factor XIII activity in normal plasma measured by a dansylcadaverine casein assay and stimulated a very abnormal pattern of fibrin cross-linking, not normally seen with factor XIII. Partial characterisation of the inhibitor suggests that it is heat stable and not an immunoglobulin.

Topics: Acetates; Blood Coagulation Disorders; Blood Coagulation Tests; Electrophoresis, Polyacrylamide Gel; Factor XIII; Female; Fibrin; Hemorrhagic Disorders; Humans; Urea

A prospective study of 76 preoperative patients with aortic aneurysms was undertaken to determine the true incidence of associated disseminated intravascular coagulation (DIC). Although 39% of the patients showed a notable elevation of the fibrin split products level, only three had thrombocytopenia and a clinical bleeding diathesis, as well. Thus, clinically overt DIC occurred preoperatively in only 4% of the patients. All three patients had extensive aneurysms that involved the thoracoabdominal aorta. Preoperative fibrinogen levels in this series tended to be high-normal or elevated and were not good indicators of underlying excessive fibrinolysis. Hemostatic abnormalities, such as ecchymoses and petechiae, may be the key to the clinical diagnosis of DIC in preoperative patients with aortic aneurysms.

Topics: Aged; Aorta, Abdominal; Aorta, Thoracic; Aortic Aneurysm; Blood Platelet Disorders; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Prospective Studies

341 cases of surgery on patients with difficulties in hemostasis are reported. Therapy was the use of fibrine fixation technique, a simple and riskless method. Tooth extractions and other surgical interventions oin anticoagulated patients may be performed without interruption of the anticoagulant therapy, also patients with hemorrhages and other complications need not be expected, if the material is properly handled.

Topics: Fibrin; Gingivectomy; Gingivoplasty; Hemorrhagic Disorders; Hemostasis, Surgical; Humans; Oral Hemorrhage; Tooth Extraction

Topics: Dental Care; Fibrin; Hemorrhagic Disorders; Hemostasis, Surgical; Hemostatics; Humans; Oral Hemorrhage; Tissue Adhesives

Two new families of congenital dysfibrinogenemia originating from French Canada are reported. The dysfibrinogenemia in the first family is characterized by an abnormal aggregation of the fibrin monomers; the defect in the second family is due to a faulty release of fibrinopeptides during the proteolytic phase of the thrombin-fibrinogen reaction.

Topics: Blood Coagulation Disorders; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Male

Topics: Amyloidosis; Arthritis, Juvenile; Blood Platelets; Child; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans

Topics: Fibrin; Hemorrhagic Disorders; Humans; Paraproteinemias; Polymers

When injury of a major vessel can be ruled out as the cause of bleeding after tonsillectomy, a discrete disturbance of hemostasis must be considered. These are mainly slight thrombopathies or a pathologically increased fibrinolysis, which were not detected by routine tests and the past history. In former times severe bleeding disorders were a strict contra-indication for tonsillectomy. Under the supposition of an exact coagulogram and the substitution of highly purified factor concentrates the risk of severe post-tonsillectomy hemorrhages in such patients today is nearly the same as in patients with a normal hemostase.

Topics: Antifibrinolytic Agents; Blood Coagulation Factors; Blood Platelet Disorders; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Postoperative Complications; Tissue Adhesives; Tonsillectomy

Topics: Fibrin; Hemorrhagic Disorders; Humans; Male; Microscopy, Electron; Middle Aged; Waldenstrom Macroglobulinemia

Topics: Adolescent; Adult; Blood Platelets; Blood Transfusion; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hematuria; Hemolytic-Uremic Syndrome; Hemorrhagic Disorders; Heparin; Humans; Male; Melena; Middle Aged; Neurologic Manifestations; Prednisolone; Pregnancy; Pregnancy Complications, Hematologic; Thrombocytopenia

Topics: Blood Coagulation Factors; Collagen; Disseminated Intravascular Coagulation; Fibrin; Hemorrhagic Disorders; Hemostasis; Humans; Microcirculation; Mononuclear Phagocyte System; Platelet Adhesiveness; Polymers; Thrombin

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: Adult; Anti-Glomerular Basement Membrane Disease; Blood Coagulation Disorders; Female; Ferritins; Fibrin; Glomerulonephritis; Hemorrhagic Disorders; Humans

Topics: Abdomen; Antibodies; Blood Coagulation Tests; Blood Protein Disorders; Chromatography; Cold Temperature; Diagnosis, Differential; Ecchymosis; Electrophoresis; Factor XIII; Female; Fibrin; Fibrinogen; Hematuria; Hemorrhagic Disorders; Humans; Immunoglobulin G; Isoniazid; Middle Aged; Pain; Sarcoidosis

Topics: Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Hysterectomy; Molecular Conformation; Plasma; Prothrombin Time; Thrombin

An abnormal fibrinogen (fibrinogen Cleveland II) was detected in the plasma of a 23-yr-old white man with a mild bleeding diathesis. The one-stage prothrombin time, thrombin time, and Reptilase time were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the proband's plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH(2)-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.

Topics: Adult; Animals; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Hydrogen-Ion Concentration; Immunoelectrophoresis; Male; Microscopy, Electron; Pedigree; Peptide Hydrolases; Peptides; Prothrombin Time; Snakes; Thrombin; Time Factors; Venoms

Topics: Adolescent; Adult; Child; Female; Fibrin; Hemorrhagic Disorders; Hepatitis; Humans; Male; Middle Aged

Topics: Animals; Blood Protein Electrophoresis; Cobalt; Electrophoresis, Polyacrylamide Gel; Factor XIII; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Male; Methods; Molecular Conformation; Molecular Weight; Rabbits

Topics: Afibrinogenemia; Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Hemorrhagic Disorders; Humans; Methods; Prothrombin Time; Time Factors

Topics: Acute Disease; Disseminated Intravascular Coagulation; Fibrin; Hemorrhagic Disorders; Humans; Liver Diseases; Prothrombin Time

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: Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Child; Diagnosis, Differential; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinolysis; Hemorrhagic Disorders; Heparin; Hepatitis; Humans; Infections; Pediatrics; Uremia

Topics: Abortion, Septic; Adolescent; Adult; Anticoagulants; Antithrombins; Blood; Blood Coagulation Disorders; Blood Coagulation Factors; Child; Disseminated Intravascular Coagulation; Encephalitis; Encephalitis Viruses; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Liver; Male; Necrosis; Pituitary Gland; Pregnancy; Prostatic Neoplasms; Prothrombin; Sepsis; Shock, Septic; Spleen; Streptokinase

Topics: Aminocaproates; Animals; Antifibrinolytic Agents; Aprotinin; Cattle; Fibrin; Fibrinolysis; Fibrinolytic Agents; Hemorrhagic Disorders; Humans; In Vitro Techniques; Insecta; Venezuela

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anticoagulants; Arthritis, Rheumatoid; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cardiovascular Diseases; Cattle; Child; Child, Preschool; Dogs; Electrophoresis; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Male; Menstruation; Methods; Middle Aged; Neoplasms; Plasminogen; Pregnancy; Rabbits; Sex Factors; Thromboembolism; Thrombosis; Uremia

Topics: Autopsy; Blood Cell Count; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Blood Preservation; Extracorporeal Circulation; Fibrin; Fibrinolysin; Hemorrhagic Disorders; Heparin; Humans; Kidney; Lung; Methods; Plasminogen; Plastics; Postoperative Complications; Silicon; Thrombosis; Time Factors

Topics: Acute Kidney Injury; Esophagus; Extracorporeal Circulation; Fibrin; Fibrinolysis; Hemorrhage; Hemorrhagic Disorders; Humans; Kidney; Lung; Pleura; Pneumonectomy; Postoperative Complications; Splenectomy; Thrombosis

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: Adolescent; Afibrinogenemia; Blood Coagulation Disorders; Bone Marrow Cells; Cardiac Tamponade; Factor V Deficiency; Factor VIII; Fibrin; Hemorrhagic Disorders; Humans; Leukemia, Myeloid, Acute; Male; Pericarditis; Pericardium; Staining and Labeling

Topics: Adult; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Neuraminic Acids; Thrombin

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Factor XIII; Fibrin; Fibrinolysin; Genetics, Medical; Hemorrhagic Disorders; Humans; Immunoelectrophoresis; Male; Siblings

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Cerebral Hemorrhage; Child; Diagnosis; Enzymes; Factor XIII; Fibrin; Genetics, Medical; Hemarthrosis; Hematoma; Hematoma, Subdural; Hemorrhagic Disorders; Humans; Knee Joint

Topics: Child; Erythroblastosis, Fetal; Factor XIII; Fibrin; Hematologic Diseases; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Premature

Topics: Blood Transfusion; Child; Factor XIII; Fibrin; Genetics, Medical; Hemorrhagic Disorders; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases

Topics: Adult; Blood Coagulation; Female; Fibrin; Hemorrhagic Disorders; Humans; Metabolism, Inborn Errors; Plasma

Topics: Alpha-Globulins; Anemia; Biological Assay; Biomedical Research; Blood Coagulation; Blood Coagulation Factors; Calcium; Collagen Diseases; Cysteine; Factor XIII; Fibrin; Hemorrhagic Disorders; Humans; Leukemia; Liver; Liver Diseases; Lymphoma; Neoplasms; Pathology; Serum Globulins; Sulfhydryl Compounds; Thrombin

Topics: Anesthesia; Blood Protein Disorders; Coagulants; Fibrin; Fibrinogen; Hemorrhagic Disorders; Hemostatics; Humans; Postoperative Complications

Topics: Antibodies; Deoxyribonuclease I; Drug Therapy; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemorrhagic Disorders; Niacin; Physiology; Plasminogen; Pyrogens; Streptodornase and Streptokinase; Streptokinase; Thrombolytic Therapy; Thrombosis; Toxicology

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Plasma; Polymerization; Thrombolytic Therapy

Topics: Blood Coagulation Disorders; Electrons; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Microscopy; Microscopy, Electron; Thrombolytic Therapy

Topics: Connective Tissue; Factor XIII; Fibrin; Fibroblasts; Hemorrhagic Disorders; Humans; In Vitro Techniques; Wound Healing

Topics: Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhagic Disorders; Humans; Plasma; Proteolysis; Thrombolytic Therapy

Topics: Embolism; Embolism, Fat; Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Postpartum Hemorrhage; Postpartum Period; Pulmonary Embolism

Topics: Blood Coagulation; Blood Coagulation Disorders; Factor XIII; Fibrin; Hemorrhagic Disorders; Humans; Vascular Diseases

Topics: Blood Coagulation; Blood Coagulation Disorders; Fibrin; Hemorrhagic Disorders; Humans

A bleeding disorder occurring during labour and affecting mother and foetus is described. All stages of coagulation were normal until the reaction fibrinogen-->fibrin. Either there was some abnormality present in the fibrinogen molecule, or there was an "anticoagulant" acting at this stage. The abnormality was reversible by protamine sulphate and toluidine blue, but in other respects did not resemble hyperheparinaemia. Reversibility of a clotting defect by protamine or toluidine blue is not sufficient evidence on which to make a diagnosis of hyperheparinaemia. Demonstration of a prolonged clotting time occurring in late pregnancy does not necessarily justify the diagnosis of "afibrinogenaemia."

Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Hemorrhagic Disorders; Humans; Pregnancy

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Humans; Vascular Diseases

Topics: Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Labor, Obstetric; Pregnancy

Topics: Blood Transfusion; Fibrin; Hemophilia A; Hemorrhagic Disorders; Humans; Hypoprothrombinemias; Prothrombin; Syndrome; Thrombocytopenia

Topics: Coagulants; Extracellular Space; Fibrin; Fibrinogen; Hemorrhagic Disorders; Hemostatics; Humans

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Humans

Topics: Afibrinogenemia; Delivery, Obstetric; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Hemorrhagic Disorders; Humans; Pregnancy

Topics: Amniotic Fluid; Fibrin; Hemorrhage; Hemorrhagic Disorders; Obstetric Labor Complications

Topics: Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Placenta; Pregnancy

Topics: Abortion, Induced; Female; Fetus; Fibrin; Hemorrhagic Disorders; Humans; Pregnancy; Stillbirth; Syndrome

Topics: Fibrin; Hemorrhagic Disorders; Humans

Topics: Blood Coagulation; Blood Coagulation Disorders; Embolism; Female; Fibrin; Hemorrhagic Disorders; Heparin; Humans; Infant, Newborn; Meconium; Placenta; Pregnancy; Shock

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Humans; Male; Neoplasms; Prostatic Neoplasms

Topics: Fibrin; Hemorrhagic Disorders; Humans

Topics: Blood Coagulation; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans

Topics: Female; Fibrin; Hemorrhage; Hemorrhagic Disorders; Humans; Obstetric Labor Complications; Obstetrics; Pregnancy

Topics: Fibrin; Fibrinolysin; Hemorrhagic Disorders; Plasma

Topics: Fibrin; Hemorrhagic Disorders

Topics: Fibrin; Fibrinolysis; Hemorrhage; Hemorrhagic Disorders; Humans; Syndrome; Thrombolytic Therapy

Topics: Afibrinogenemia; Fibrin; Fibrinolysis; Hemorrhagic Disorders

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Hepatophyta; Liver Diseases

Topics: Afibrinogenemia; Blood Coagulation; Fibrin; Hemorrhagic Disorders

Topics: Blood Coagulation Disorders; Fibrin; Hemorrhagic Disorders; Humans; Polycythemia Vera

Topics: Blood; Disease Susceptibility; Fibrin; Hemorrhagic Disorders; Humans