fibrin and Syndrome

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these

Topics: Abortion, Habitual; Chorioamnionitis; Chronic Disease; COVID-19; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Placenta; Pregnancy; Pregnancy Outcome; SARS-CoV-2; Syndrome

Clinical and autopsy studies have shown an association between clotting, microembolism, and inhibition of fibrinolysis and respiratory distress after trauma or sepsis. Prophylaxis and treatment with the aim of decreasing the deposition of fibrin in the lungs were associated with a large decrease in the incidence and death rate of this syndrome. Small fibrin degradation products (peptides) are accumulated in the lungs and are only slowly cleared from this organ, especially during states of inhibition of fibrinolysis. These peptides may contribute to the pulmonary damage in several ways. As well as having a direct effect on the endothelium, they act by interfering with other vasoactive substances as bradykinin, histamine, and products of the arachidonic acid cascade. Products of the cyclooxygenase pathway such as thromboxane A2 play a major role in early microembolism, whereas lipoxygenase products seem to be involved in later stages. Pulmonary microembolism thus seems to be one important, but certainly not the only, pathogenetic factor in acute "idiopathic" respiratory failure. Other factors, such as pulmonary contusion, aspiration of gastric contents or blood, or oxygen toxicity, might well be contributory in some cases. Pulmonary microemboli containing fibrin and leukocytes are probably also involved as contributory agents in some cases in the large group of acute respiratory failures due to "known factors."

Topics: Albumins; Animals; Clinical Trials as Topic; Dextrans; Dogs; Fibrin; Fibrinolysis; Hemostasis; Heparin; Humans; Lung; Pulmonary Embolism; Random Allocation; Rats; Respiratory Distress Syndrome; Syndrome; Thrombin; Time Factors

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Cardiopulmonary Bypass; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Infant, Newborn; Kidney Diseases; Myocardial Infarction; Neoplasms; Pregnancy; Pulmonary Embolism; Syndrome; Thrombin; Thrombophlebitis; Thrombosis

This report describes how a finding at the autopsy table led to the observation of a clinical syndrome. A synthesis of autopsy experience, clinical investigations, and experimental and biochemical studies were able to shed light on one factor in the pathogenesis of this syndrome, namely blood coagulation with pulmonary microemboli and release and delayed elimination of peptides from fibrin degradation extravascularly in the lungs. These peptides may both induce increased permeability in the microcirculation and stimulate fibroblast proliferation. Knowledge about the pathogenesis has led to improved prophylaxis and therapy and a reduction of the number of deaths.

Topics: Antifibrinolytic Agents; Autopsy; Blood Coagulation; Capillary Permeability; Cell Division; Embolism, Fat; Fibrin; Fibrin Fibrinogen Degradation Products; Fibroblasts; Humans; Microcirculation; Pulmonary Embolism; Shock; Syndrome

Topics: Animals; Antigen-Antibody Complex; Blood Coagulation Factors; Blood Platelet Disorders; Blood Platelets; Blood Proteins; Cell Membrane; Collagen; Complement System Proteins; Cytoplasmic Granules; Factor VIII; Fibrin; gamma-Globulins; Glycoproteins; Humans; Lectins; Platelet Adhesiveness; Platelet Aggregation; Polylysine; Ristocetin; Syndrome; von Willebrand Factor

Defibrination is a fairly common clinical entity seen in a wide variety of clinical disorders. With an awareness of the likely clinical settings, a high degree of suspicion, and widely available sensitive laboratory tests, the diagnosis is ordinarily easily made. The best therapy is usually that which is directed at the underlying disease rather than at the defibrination syndrome itself. In certain symptomatic cases, heparin and/or replacement therapy is indicated, especially if the underlying disorder cannot be immediately successfully treated. On occasion, antifibrinolytic therapy will be useful, always with due regard to the danger of renal cortical necrosis. Depending on the clinical setting, it may be advisable to give heparin with the antifibrinolytic therapy to minimize that danger.

Topics: Adult; Aged; Antifibrinolytic Agents; Blood Cell Count; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Heparin; Humans; Male; Postoperative Complications; Pregnancy; Prostatic Neoplasms; Sepsis; Syndrome

Topics: Animals; Antifibrinolytic Agents; Autopsy; Blood Coagulation Factors; Dogs; Fibrin; Fibrinolysis; Fibrinolytic Agents; Heart Failure; Humans; Hypoxia; Kidney; Lung; Lymph; Plasminogen Activators; Plasminogen Inactivators; Prostaglandins; Pulmonary Embolism; Pulmonary Veins; Respiration; Respiratory Insufficiency; Syndrome; Thrombin; Wounds and Injuries

Clinical and autopsy studies have shown an association between clotting, microembolism, and inhibition of fibrinolysis and respiratory distress after trauma or sepsis. Prophylaxis and treatment with the aim of decreasing the deposition of fibrin in the lungs were associated with a large decrease in the incidence and death rate of this syndrome. Small fibrin degradation products (peptides) are accumulated in the lungs and are only slowly cleared from this organ, especially during states of inhibition of fibrinolysis. These peptides may contribute to the pulmonary damage in several ways. As well as having a direct effect on the endothelium, they act by interfering with other vasoactive substances as bradykinin, histamine, and products of the arachidonic acid cascade. Products of the cyclooxygenase pathway such as thromboxane A2 play a major role in early microembolism, whereas lipoxygenase products seem to be involved in later stages. Pulmonary microembolism thus seems to be one important, but certainly not the only, pathogenetic factor in acute "idiopathic" respiratory failure. Other factors, such as pulmonary contusion, aspiration of gastric contents or blood, or oxygen toxicity, might well be contributory in some cases. Pulmonary microemboli containing fibrin and leukocytes are probably also involved as contributory agents in some cases in the large group of acute respiratory failures due to "known factors."

Topics: Albumins; Animals; Clinical Trials as Topic; Dextrans; Dogs; Fibrin; Fibrinolysis; Hemostasis; Heparin; Humans; Lung; Pulmonary Embolism; Random Allocation; Rats; Respiratory Distress Syndrome; Syndrome; Thrombin; Time Factors

Toxic anterior segment syndrome (TASS) is an acute, sterile, inflammatory reaction of the anterior segment after intraocular surgeries. We aimed to report an outbreak of TASS which occurred following pterygium surgeries.. A case series.. Four eyes of four patients developed TASS associated with formaldehyde after uneventful primary pterygium surgery with conjunctival autograft. No patients reported pain; all patients demonstrated diffuse corneal edema, epithelial defects, and anterior chamber inflammation without hypopyon, fibrin formation, and vitreous involvement on the first postoperative day. TASS diagnosis was made based on clinical findings. All patients were treated with hourly topical 1% prednisolone acetate (Pred Forte, Allergan, CA), moxifloxacin 0.5% (Vigamox, Alcon, TX), and 0.24% of hyaluronic acid (Artelac complete, Bausch & Lomb). Oral steroid (prednisolone 1 mg/kg) was added on the first week and gradually tapered over weeks. None of the affected corneas improved spontaneously. Best-corrected visual acuity ranged from 20/25000 to 20/200 in the second month after surgery. Keratoplasty was scheduled for all patients.. This is the first study to present TASS cases after pterygium surgery. Clinicians should be aware of TASS that can emerge after an extraocular surgery. In our analysis, since 2% formaldehyde was used by the operating room personnel for cleaning and sterilizing reusable ocular instruments, it was thought that formaldehyde was the most likely cause.

Topics: Anterior Eye Segment; Conjunctiva; Eye Diseases; Fibrin; Formaldehyde; Humans; Hyaluronic Acid; Moxifloxacin; Phacoemulsification; Postoperative Complications; Prednisolone; Pterygium; Syndrome

Dysfibrinogenemia is a rare group of qualitative fibrinogen disorders caused by structural abnormalities in the fibrinogen molecule. The laboratory diagnosis of dysfibrinogenemia is controversial. Fibrinogen Paris V, clinically termed Dusart Syndrome, is a dysfibrinogenemia caused by a single base substitution in the gene coding for the Aα-chain of the fibrinogen molecule.. To diagnose the first Scandinavian family with Fibrinogen Paris V affecting several family members; the proband, a seven-year-old boy with cerebral vein thrombosis.. The diagnosis was established following the ISTH guideline for laboratory testing supplemented with fibrin structure analysis and fibrinogen gene analysis.. Prolonged thrombin time and reduced ratio between the functional and the protein concentration of fibrinogen were observed in four family members who also were characterized by significantly reduced fibrin polymerization (p < 0.001), reduced fibrin fibre diameter (p < 0.001), reduced fibrin mass-length ratio (p < 0.001) and significantly reduced t-PA-induced fibrinolysis of the fibrin clots (p < 0.001) when compared to controls. Fibrinogen gene analysis demonstrated that five of the family members carried the Fibrinogen Paris V mutation. All laboratory tests were normal in the family members carrying the wild type of the fibrinogen gene. Four of the affected patients had suffered from thrombotic episodes. A noticeable feature in the present family was the presence of both venous and arterial thrombosis.. Excellent concordance was observed between the screening and confirmatory tests, fibrin structure analysis and fibrinogen gene analysis. Fibrin structure analysis should be considered in the laboratory algorithm for diagnosis of dysfibrinogenemia.

Topics: Adolescent; Adult; Case-Control Studies; Child; Coagulation Protein Disorders; DNA Mutational Analysis; Female; Fibrin; Fibrinogens, Abnormal; gamma-Glutamyltransferase; Humans; Male; Middle Aged; Pedigree; Protein Multimerization; Scandinavian and Nordic Countries; Syndrome; Thrombin Time; Thrombosis; Young Adult

To report on the histopathologic findings of affected skin in consecutively collected biopsy specimens from 49 patients with erythromelalgia (EM).. Skin biopsy specimens were obtained from the foot arch and analyzed by light microscopy, immunofluorescence microscopy, and electron microscopy.. Oslo University Hospital-Gaustad, University of Oslo, Oslo, Norway.. Thirty-one patients had primary EM, 17 patients had secondary EM, and 1 patient had erythromelalgic syndrome.. Evidence of microvascular abnormalities in skin biopsy specimens.. Light microscopy showed evidence of capillary proliferation in 10 of 31 patients with primary EM and in 1 of 17 patients with secondary EM. The biopsy specimen from the patient with erythromelalgic syndrome showed numerous capillary nests with endothelial cell defects and a slight perivascular inflammatory reaction. Among the 17 secondary EM cases, sparse perivascular lymphocyte infiltrations were observed in the biopsy specimens from 2 patients with chronic myelogenous leukemia and 1 patient with diabetes mellitus. Eleven patients also had signs of vasculopathy based on findings of immunodeposits of C3 and fibrin. Six of 30 patients with primary EM showed endothelial abnormalities on electron microscopy. All 3 investigations showed unremarkable biopsy results in 16 cases.. Histopathologic analysis is not useful as a routine diagnostic tool in EM because no morphological changes are specific to EM. The capillary proliferation and vasculopathy are assumed to be a consequence of intermittent skin hypoxia (vascular hypothesis of pathogenesis). Whether the proliferation is a consequence of EM or a pathogenic factor in the development of the disease is uncertain.

Topics: Adult; Aged; Biopsy; Capillaries; Complement C3; Erythromelalgia; Female; Fibrin; Humans; Hypoxia; Male; Microscopy; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Norway; Prospective Studies; Skin; Syndrome

Fat embolization following major trauma is reported to be a quite common event, while the clinical fat embolism syndrome (FES) seems to be a much rarer event. Fat embolism occurs in 2 up to 23% of patients with isolated femoral shaft fractures. This complication appears to be related not only to the fracture, but also to the timing of stabilization. Sometimes it may be impossible to perform histochemical reactions on frozen sections to detect fat emboli thus confirming diagnosis or suspicion of FES. The finding of fibrinogen and platelets around the apparently empty spaces in the blood vessels has been proposed as an evidence for vital reaction due to either a vital cellular reaction or a flotation mechanism, thus supporting an intravital fat embolism. We report a fatal case due to fat embolism syndrome in a young man hospitalized for a right femoral neck fracture, treated with orthopaedic surgery and subjected to an intra-surgery transesophageal echocardiography that revealed embolization of numerous highly echogenic bodies. Four hours after the onset of clinical symptoms the man died from respiratory failure. The autopsy confirmed the clinical diagnosis of fat embolism syndrome. The histological examination revealed a large amount of fat globules in cerebral and pulmonary arteries and in glomerular capillaries, as well as fibrin and platelet deposition confirmed by the positive results by Sudan III staining for lipids and immunohistochemistry with anti-CD61 and anti-fibrinogen antibodies. The quantitative classification of fat embolism was grade 3 of Sevitt's classification or grade 4 of Fineschi's quantification, according to the current quantitative microscopic methods used for grading fat embolism in pulmonary tissue.

Topics: Adult; Antibodies; Blood Platelets; Capillaries; Echocardiography, Transesophageal; Embolism, Fat; Femoral Neck Fractures; Fibrin; Fibrinogen; Forensic Pathology; Humans; Immunohistochemistry; Integrin beta3; Lung; Male; Microscopy, Confocal; Pulmonary Artery; Respiratory Insufficiency; Syndrome

To gain insight into the contribution of platelet-dependent thrombin formation in haemostasis and thrombosis, we investigated under flow conditions the haemostatic functions of platelets from a patient with Scott syndrome. Scott platelets are characterised by a diminished platelet-dependent thrombin generation. Thrombin generation was determined by calibrated automated thrombography and flow-based experiments were performed to reveal collagen-mediated platelet activation and fibrin deposition. Our studies indicate that adherent Scott platelets do not differ from control platelets in the formation of stable platelet aggregates under static and flow conditions. While for adherent control platelets a shape change, e.g. balloon formation, and externalisation of phosphatidylserine (PS) is associated with an increase in intracellular calcium concentration, this is not the case for Scott platelets. The calcium-induced morphological changes in control platelets are accompanied with a diminished recruitment of free flowing platelets. Scott platelets, not showing a calcium-induced shape change, also lost the ability to recruit free flowing platelets. These findings rebut the hypothesis that the mild bleeding tendency of Scott syndrome patients is due to a preserved adhesive activity of patient's platelets. Perfusion of tissue factor (TF)-activated control blood over immobilised collagen results in the formation of fibrin fibers that radiate from platelet aggregates. Although platelet aggregates were also observed after perfusion with TF-activated Scott blood, fibrin deposition was not observed. In conclusion, our findings indicate that platelet adhesion and spreading on a collagen matrix in the absence of fibrin formation is sufficient to sustain haemostasis under non-traumatic conditions.

Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Calcium; Female; Fibrin; Hemorrhage; Humans; Middle Aged; Platelet Aggregation; Regional Blood Flow; Syndrome; Thrombin; Thromboplastin

Human fibrinogen gamma chain variants, termed gamma' chains, contain a unique 20-residue sequence after gamma chain residue 407 that ends at gamma'427, and is designated gamma'(427L). Full-length (FL) gamma'(427L) chains are constituents of a fibrin-dependent thrombin inhibitory system known as antithrombin I, whereas a gamma' chain processed in vivo, termed gamma'(423P), lacks the C-terminal tetrapeptide EDDL, and does not bind thrombin. Together, the gamma'(423P) and gamma'(427L) chains comprise the total plasma fibrinogen gamma' chain content.. Lowered plasma gamma' chain content (i.e. gamma' chain-containing fibrinogen/total fibrinogen ratio) has been shown to correlate with susceptibility to venous thrombosis, thus prompting this study on the total and FL gamma' chain content in 45 subjects with thrombotic microangiopathy (TMA), a disorder characterized by microvascular thrombosis.. We measured by enzyme-linked immunosorbent assay the total gamma' chain-containing fibrinogen/total fibrinogen (Total gamma'-fgn/Total fgn) ratio and the FL gamma' chain-containing fibrinogen/total fibrinogen (FL gamma'-fgn/Total fgn) ratio in these plasmas and in healthy subjects (n = 87).. In healthy subjects, the mean Total gamma'-fgn/Total fgn ratio was 0.127, whereas the FL gamma'-fgn/Total fgn ratio was somewhat lower at 0.099 (P < 0.0001), a difference reflecting the presence of gamma'(423P) chains. In TMA plasmas, both the Total gamma'-fgn and FL gamma'-fgn/Total fgn ratios (0.099 and 0.084, respectively) were lower than those of their healthy subject counterparts (P < 0.0001).. These findings in TMA suggest that reductions in the gamma' chain content indicate reduced antithrombin I activity that may contribute to microvascular thrombosis in TMA.

Topics: ADAM Proteins; ADAMTS13 Protein; Adult; Aged; Aged, 80 and over; Anemia, Hemolytic; Black or African American; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinogen; Haplotypes; Humans; Linear Models; Male; Microcirculation; Middle Aged; Polymorphism, Genetic; Purpura, Thrombotic Thrombocytopenic; Reference Values; Syndrome; Thrombosis; White People

To present clinical findings of a cluster of cases of toxic anterior segment syndrome (TASS) after uneventful phacoemulsification cataract surgery.. Department of Ophthalmology, Akdeniz University, Antalya, Turkey.. Six eyes of 6 patients developed TASS after uneventful phacoemulsification cataract surgery with implantation of a 3-piece acrylic IOL performed by 2 ophthalmologists on the same day. Clinical findings included corneal edema, Descemet's membrane folds, anterior chamber reaction, fibrin formation, and irregular, dilated, and unreactive pupils.. Glutaraldehyde 2% solution was used inadvertently by the operating room staff who cleaned and sterilized reusable ocular instruments before autoclaving. None of the affected corneas improved. Additional surgical procedures were required and included penetrating keratoplasty, trabeculectomy, and glaucoma tube implantation.. Glutaraldehyde in concentrations generally used for cold sterilization is highly toxic to the corneal endothelium. The operating room staff involved in sterilizing instruments should be well educated about and careful to follow the protocols to properly clean and sterilize reusable ocular instruments.

Topics: Aged; Anterior Eye Segment; Corneal Edema; Descemet Membrane; Disease Outbreaks; Disinfectants; Drug Hypersensitivity; Female; Fibrin; Glutaral; Humans; Lens Implantation, Intraocular; Male; Middle Aged; Phacoemulsification; Pupil Disorders; Syndrome; Turkey

The purpose of the study was to determine the level of thrombus precursor protein (TrP) in patients with acute coronary syndrome (ACS). Twenty-six patients with ACS and anginal pain experienced during 2 to 12 hours (7.2 +/- 1.3 hours), admitted to cardiological intensive care unit, were enrolled in the study. Five ml of blood were sampled from a cubital vein of all the patients during the phase of the most intensive pain. TrP blood levels were measured with ELISA, Enzyme-Linked Immunoadsorbent Assay. The control group consisted of 29 healthy volunteers and 22 patients with stable exertional stenocardia. A significant increase in TpR (7.2 +/- 1.45 mcg/ml) was noted in the ACS patients as early as during the first 6 hours, vs. the healthy controls (1.01 +/- 0.12 mcg/ml) and the patients with stable stenocardia (1.21 +/- 0.06 mcg/ml), p < 0.01. A high level of TrP in the ACS patients could be noted earlier than a diagnostically significant increase in creatine phosphokinase level. No direct correlation was observed between the TrP level and the dynamics of such indices of the procoagulatory hemocoagulation chain as fibrinogen, prothrombin index, and active partial thromboplastin time. The results of the study demonstrate that the measurement of TrP level is highly informative when the intensity of intravascular blood coagulation in ACS patients is to be evaluated, which can be used to clarify indications to anticoagulation therapy. The enzyme immune method of TrP detection in the plasma of ACS patients can be recommended for clinical application.

Topics: Acute Disease; Biomarkers; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Severity of Illness Index; Syndrome

We report two cases of atypical defibrination syndromes in patients with respectively acute monoblastic leukemia (chronic myeloid leukemia initially) and acute lymphoblastic leukemia. Hemostasis studies show low fibrinogen level, elevated D-dimers, decreased alpha 2 antiplasmin and factor V, normal antithrombin III values. Plasminogen is below the normal range in one patient. Soluble complexes, which are an important argument for diagnosis of intravascular coagulation disease, are not detected in both patients. Primary or secondary hyperfibrinolysis seems also excluded since euglobulin clot lysis time was normal. Enzymatic proteolysis of fibrinogen (or fibrin) by the blast cells has been reported by some authors; this mechanism could account for the hemostasis abnormalities observed in these two patients.

Topics: Adult; alpha-2-Antiplasmin; Antithrombin III; Diagnosis, Differential; Disseminated Intravascular Coagulation; Factor V Deficiency; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Leukemia, Monocytic, Acute; Male; Neoplastic Stem Cells; Plasminogen; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Syndrome

In two young patients with an elevated temperature, a girl aged 6 months and a boy aged 10 months, purpura and oedema were noticed on the face, ears, arms and legs. On one occasion the boy lost blood anally. A histopathological examination revealed leucocytoclastic vasculitis with fibrin deposits. The diagnosis was 'acute haemorrhagic oedema of infancy' (AHOI), a relatively unknown variant of palpable purpura due to leucocytoclastic vasculitis affecting infants and young children (up to two years of age). AHOI is characterised clinically by marked oedema and fever as well as large palpable purpuric and ecchymotic skin lesions in a target-like pattern mainly on the face, ears and extremities. The skin lesions heal spontaneously within one to three weeks and internal organs are rarely affected. This is in contrast to Henoch-Schönlein purpura, which was observed in a 5-year old boy suffering from similar skin lesions on the legs as well as painful joints, in whom IgA deposits were found in the vasculitis. Henoch-Schönlein purpura is clinically characterised by palpable purpura on the extensor surfaces of the legs and on the buttocks, whereas in AHOI larger purpura and ecchymoses are found on the face, ankles and wrists, with far more extensive oedema. There are also histological differences: in AHOI there is more extensive vasculitis with fibrin deposits and IgA deposits are seen in a minority of cases. Awareness of this relatively unknown form of leucocytoclastic vasculitis will assist in making an early diagnosis possible, thereby avoiding unnecessary treatment and concern.

Topics: Acute Disease; Child, Preschool; Diagnosis, Differential; Ecchymosis; Edema; Female; Fever; Fibrin; Humans; IgA Vasculitis; Immunoglobulin A; Infant; Male; Purpura; Skin; Syndrome; Vasculitis, Leukocytoclastic, Cutaneous

Systemic sclerosis (SSc) is a disease characterized by progressive microvascular occlusion and fibrosis resulting in irreversible organ damage, the pathogenesis of which is felt to be of vascular origin. To gain a comprehensive view of the coagulation/fibrinolytic balance in SSc, a number of haemostatic and fibrinolytic variables were measured in 26 SSc patients (11 limited, 15 diffuse) and in 22 control subjects. Of the coagulation activation markers, the mean plasma level of prothrombin fragment 1 + 2 (F1 + 2), but not of thrombin-antithrombin complexes (TAT), was higher in SSc patients than in controls (P < 0.001). Plasma levels of fibrin split product D-dimer (DD), fibrinogen (FNG) and von Willebrand factor (vWF) were higher amongst patients than controls (P < 0.001). vWF and FNG levels were positively correlated (P < 0.001). Mean levels of DD and vWF were more elevated in patients with diffuse than limited disease (P = 0.001 and P = 0.04, respectively). On the fibrinolytic side, defective tissue plasminogen activator (tPA) release (venous occlusion test, stimulated level < basal level) was noted in 46% (12/26) of SSc patients, but only in 4% (1/22) of controls. Patients had higher mean levels of tPA inhibitor (PAI) than controls (P < 0.001), levels being more elevated amongst patients with diffuse than limited disease (P = 0.01). An abnormally high lipoprotein (a) [Lp(a)] level was found in 9% (2/20) of control subjects, but in 30% (8/26) of SSc patients (P = 0.04) where it clustered with fibrinolytic defects. Altogether, these data suggest that patients with SSc are in a hypercoagulable state characterized by elevated plasma levels of FNG and vWF, by a dual hypofibrinolytic pattern (defective tPA release and elevated PAI), and by increased thrombin generation with enhanced fibrin formation. Higher levels of vWF, DD and PAI in patients with diffuse disease are consistent with more extensive (micro)vascular involvement, although no causal relationship can be inferred. The lack of a parallel increase of TAT with F1 + 2, in the presence of normal levels of antithrombin III (ATIII), indirectly suggests an impairment of the heparan sulphate-ATIII system which would favour thrombin generation. Since thrombin may act as a mitogen for fibroblasts, may upregulate vWF, PAI and endothelin production by endothelial cells, and may promote fibrin deposition on the vessel wall leading to worsening of microvascular occlusions, limitation of thrombin generation, besi

Topics: Adult; Antithrombin III; Blood Coagulation; Endothelins; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Lipoprotein(a); Male; Middle Aged; Prothrombin; Scleroderma, Systemic; Syndrome; Thrombin; Tissue Plasminogen Activator; von Willebrand Factor

To evaluate the role of disseminated intravascular coagulation (DIC) and to determine the influence of antithrombin, protein C, and plasminogen activator inhibitor 1 on multiple organ dysfunction syndrome (MODS) and outcome in patients with systemic inflammatory response syndrome (SIRS), we made a prospective cohort study. The study subjects consisted of thirty-five patients who exhibited two or more of the conditions of SIRS for more than three consecutive days. They were classified into subgroups of survivors (n = 13) and nonsurvivors (n = 22). The global coagulation and fibrinolytic markers, antithrombin, protein C, and plasminogen activator inhibitor 1 were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, and 5th days. The results of these measurements, demographic data, criteria of severity, incidence of MODS were compared between the subgroups. For prediction of patient's death, a receiver operating characteristic (ROC) curve analysis was made. DIC was frequently associated with SIRS patients (29/35, 82.9%). A significant decrease in the DIC score was found in the survivors (p = 0.0001). None of them suffered from DIC on the 5th day. In the nonsurvivors, low levels of protein C and antithrombin and markedly high values of plasminogen activator inhibitor 1 continued up to the 5th day, no improvement of the DIC was observed during the study period and the number of the dysfunctioning organs were significantly higher than in the survivors. Plasminogen activator inhibitor 1 on the 5th day had prognostic value for the prediction of death on the SIRS patients. In conclusion, DIC occurs commonly in patients with SIRS and may be the main determinant for the outcome of these patients. Changes in antithrombin, protein C, and plasminogen activator inhibitor 1 are one of the aggravating factors of MODS. Furthermore, plasminogen activator inhibitor 1 is a good predictor of death in these patients.

Topics: Adult; Aged; Anticoagulants; APACHE; Biomarkers; Combined Modality Therapy; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Humans; Japan; Male; Middle Aged; Plasma; Plasminogen Activator Inhibitor 1; Platelet Count; Prospective Studies; ROC Curve; Sepsis; Survivors; Syndrome; Systemic Inflammatory Response Syndrome; Treatment Outcome

The activity of several proteins involved in fibrinolysis and the morphological changes in the blood vessel walls of pigs infected with highly virulent (Malawi'83) and moderately virulent (Dominican Republic '78-DR'78) ASF virus isolates were determined. Pigs infected with the Malawi'83 virus developed an increased fibrinolytic activity due to high plasma levels of tissue-plasminogen activator (t-PA) of 71.3 +/- 22.8 IU/ml (mean +/- SD), which correlated well with an increased activation of interstitial capillary endothelial cells and high levels of 1150 +/- 73.6 nM of fibrin monomer in the circulation. Animals infected with DR'78 virus, in contrast, showed an inhibition of fibrinolysis in the late stages of disease with almost a 5-fold increase of plasminogen activator inhibitor (PAI) activity of 196.0 AU/ml. These results suggest that activation of the fibrinolytic system in pigs infected with the Malawi'83 virus is probably due to increased formation and deposition of fibrin in the circulation, contributing to an increased bleeding tendency and higher mortality. On the contrary, animals infected with DR'78 virus developed an inhibition of fibrinolysis and thus a reduction in bleeding.

Topics: Acute Disease; African Swine Fever; African Swine Fever Virus; Animals; Edema; Fibrin; Fibrinolysis; Hemorrhage; Kidney; Liver; Plasminogen Inactivators; Swine; Syndrome; Thrombosis; Tissue Plasminogen Activator; Virulence

Fibrinogen Dusart is a congenital dysfibrinogenemia (A-alpha 554 Arginine-->Cysteine) associated with severe thrombotic disorder, high incidence of thrombotic embolism, and abnormal fibrin polymerization. This thrombotic disorder was attributed to an abnormal clot thrombolysis with reduced plasminogen binding to fibrin and defective plasminogen activation by tissue plasminogen activator. The purpose of this work was to assess whether clot architecture could be involved in the thromboresistance of the fibrin Dusart and the high incidence of embolism. An important change in Dusart fibrin clot structure was identified with dramatic decrease of gel porosity (Ks), fiber diameters (d), and fiber mass-length ratios (mu) derived from permeation analysis. In addition, rigidity of the Dusart clot was found to be greatly increased compared with normal fibrin. We provide evidence that both thrombolysis resistance and abnormal rigidity of the fibrin Dusart are related to this abnormal architecture, which impairs the access of fibrinolytic enzymes to the fibrin and which is responsible for a brittle clot that breaks easily, resulting in a high incidence of embolism. Indeed, when restoring a normal clot structure by adding dextran 40 (30 mg/mL) before coagulation, clot thrombolysis and clot rigidity recovered normal values. This effect was found to be dose-dependent. We conclude that clot architecture is crucial for the propensity of blood clot to be degraded and that abnormal clot structure can be highly thrombogenic in vivo. The alpha-C domains of fibrinogen are determinant in fibrin clot structure.

Topics: Dextrans; Fibrin; Fibrinogens, Abnormal; Fibrinolysis; Humans; Microscopy, Electron; Syndrome

Patients with the hypereosinophilic syndrome (HES) are at increased risk of thrombosis and have signs of fibrin deposition in the myocardial cavity; the pathogenesis of these complications is still unknown. We have studied a 51-year-old man affected by HES with heart, lung, skin, and gastrointestinal involvement. Routine laboratory parameters of the hemostatic system were normal with the exception of blood fibrinolytic activity. The latter was evaluated by both diluted blood clot lysis time and euglobulin lytic activity on fibrin plates before and after 10 min venous occlusion. The fibrinolytic activity measured on four occasions during a 3-month period, was impaired both in basal conditions and following venous occlusion. Platelet studies on two different occasions before and during therapy showed spontaneous platelet aggregation, lowered threshold concentrations of various aggregating agents, reduced platelet regeneration time and increased plasma beta-thromboglobulin concentration. The patient's polymorphonuclear cells (more than 75% eosinophils) were devoid of any procoagulant activity (PCA). Instead, patient's mononuclear cells studied before therapy generated significantly higher PCA on stimulation by endotoxin than cells from control subjects. The procoagulant response to endotoxin decreased markedly during therapy. The observed abnormalities could, at least partially, contribute to fibrin deposition in HES.

Topics: beta-Thromboglobulin; Blood Coagulation Factors; Blood Coagulation Tests; Eosinophilia; Fibrin; Fibrinolysis; Heart Failure; Humans; Male; Middle Aged; Platelet Aggregation; Syndrome

A transitory deposit of a fibrin-like material in the anterior chamber following extracapsular cataract extraction and intraocular lens (IOL) implantation is described. In two studies, one retrospective of 352 operations and one prospective of 189 operations, the fibrinoid reaction was observed in 17% and 11% of the eyes, respectively. The reaction appeared in the early postoperative period in an otherwise quiet eye and the signs varied from a few threads in the pupil area to a dense pupillary membrane in front of the IOL. The deposit disappeared one day to three weeks postoperatively, usually without any remnants. The majority of eyes with the fibrinoid reaction had received a posterior chamber IOL. A strong association with the exfoliation syndrome was found and an increased vascular permeability is suggested as a probable cause of the reaction.

Topics: Aged; Anterior Eye Segment; Cataract Extraction; Eye Diseases; Female; Fibrin; Humans; Lenses, Intraocular; Prospective Studies; Retrospective Studies; Syndrome

The loin pain hematuria syndrome has been characterized as a constellation of severe recurrent flank pain and hematuria, occurring predominantly in young women. We studied a 17-year-old woman who had recurrent right flank pain, gross hematuria, and fever, without evidence of urinary tract infection. Her physical exam was remarkable for right costovertebral angle tenderness and a normal BP. Her urinalysis showed blood and protein but her creatinine clearance and 24-hour urinary calcium excretion were normal. A kidney biopsy was remarkable for arteriolar subintimal fibrous thickening and fibrin deposition, but no glomerulonephritis. Her peripheral hemostasis evaluation was normal except for circulating platelet aggregates and elevated fibrinopeptide A levels. On two occasions, her serum was unable to normally support prostacyclin (PGI2) production by cultured human umbilical endothelial cells, as measured by radioimmunoassay (RIA) of its stable metabolite 6-keto-PGF alpha. Blood samples from the right renal vein and inferior vena cava revealed a selective elevation of fibrinopeptide A in the right renal venous effluent. The presence of circulating platelet aggregates and elevated levels of fibrinopeptide A (a cleavage product of fibrin) suggests that platelet activation and fibrin deposition may play a role in the pathogenesis of this disorder. The inability of her serum to normally support the production of the potent antiplatelet and antithrombotic substance, PGI2, could represent a primary renovascular endothelial cell defect.

Topics: Adolescent; Epoprostenol; Female; Fibrin; Hematuria; Humans; Kidney; Pain; Platelet Aggregation; Syndrome

Activation of plasminogen by tissue-type plasminogen activator (tpA) is potentiated by fibrin. We have demonstrated the role of fibrin polymerization in the potentiating effect of tpA-induced fibrinolysis. Therefore a pathogenic mechanism of thrombotic disorder may be related to an abnormal fibrin polymerization: the abnormal clot being less accessible to fibrinolysis than normal one. This defective lysis may be due to a defective enhancement by the abnormal fibrin of plasminogen activation by tpA, as demonstrated for fibrinogen Dusard, a congenital dysfibrinogenemia associated with a very severe thrombotic disorder. In some other cases, a decrease in the availability of the plasmin cleavage sites in fibrin clot may be involved. On the contrary, some antithrombotic drugs such as pentosane polysulfate in modifying clot structure allow a better degradation of fibrin clot by fibrinolytic enzymes. It is speculated that this enhanced fibrinolysis could explain, almost in part, the antithrombotic action of these drugs.

Topics: Blood Coagulation; Fibrin; Fibrinolysis; Humans; Pedigree; Pentosan Sulfuric Polyester; Syndrome; Thrombin; Thrombosis

Topics: Aged; Aged, 80 and over; Blood Platelet Disorders; Female; Fibrin; Heparin; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Count; Retrospective Studies; Syndrome; Thrombocytopenia

Topics: Blood Coagulation; Eosinophilia; Fibrin; Humans; Male; Middle Aged; Monocytes; Syndrome

Congenital dysfibrinogenaemia is described in three members of a family presenting with recurrent thrombosis and in two other young members not yet affected. An abnormality in the polymerization of fibrin monomers was noted. In addition, the pathological fibrin clots were found to be less sensitive to degradation by a post venous occlusion euglobulin solution than normal fibrin. After fibrin clot incubation with lys-plasminogen at different concentrations, the biological activity of plasminogen in patient fibrin clot on S 2251 after SK-addition, was less than that observed with normal fibrin. It is speculated that defective in vivo thrombolysis might explain the recurrent thrombosis observed in this family. This finding represents a new concept in understanding thromboembolic diseases.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Male; Pedigree; Syndrome; Thromboembolism

Occlusion of the microcirculatory bed vessels with various kinds of microthrombi: fibrin, erythrocytic, leukocytic, and thrombocytic is pathognomonic for the morphological picture of the disseminated intravascular blood coagulation syndrome. Fibrin is the mandatory component of all kinds of microthrombi. The term "fibrinembolism" does not reflect all the complexity of the morphological manifestations of the process. In the group of fibrin thrombi, true fibrin, hyalin, globular thrombi as well as separate strands and filaments of fibrin are distinguished. True fibrin thrombi occur in the venous part of the microcirculatory bed and represent rounded formations of tightly interwoven fibrin filaments. Hyalin thrombi are dense homogeneous formations ultrastructurally different from true fibrin ones by the degree of polymerization (they are particularly characteristic of renal glomerular capillaries). Globular thrombi consist of erythrocytes coated with fibrin and occur in shock. Individual strands and filaments of fibrin are not thrombi but possibly represent a certain stage in the formation of fibrin thrombi; they occur in sinusoids of the liver and spleen. It is for these formation that the term "fibrin-embolism" is most suitable.

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Histocytochemistry; Humans; Microcirculation; Syndrome; Thrombosis

Two hundred eighty consecutive vitrectomies in diabetic patients were studied retrospectively. In 15 eyes, interlacing fibrin-like strands appeared on the surface of the retina and behind the iris plane from two to 14 days postoperatively. One or two days later, a gelatinous mass formed in the center of the vitreous activity, leading to the development of tractional retinal detachment and rubeosis iridis with neovascular glaucoma. Large doses of systemic and topical corticosteroids reversed the fulminating course of this complication in six of 15 eyes. The combination of lens surgery or scleral buckling procedure with vitrectomy, and the presence of retinal detachment preoperatively seemed to predispose to this complication. It is possible that multiple surgical procedures performed during the same operation cause an increase in vascular permeability resulting in the formation of a gelatinous, fibrin-like material in the diabetic eye.

Topics: Adult; Aged; Diabetic Retinopathy; Eye Diseases; Female; Fibrin; Glaucoma; Humans; Intraocular Pressure; Iris Diseases; Male; Middle Aged; Postoperative Complications; Retinal Detachment; Retrospective Studies; Syndrome; Vitreous Body

Patients with ischaemic heart disease of severe forms with congested insufficiency of the circulation have chronic latent disseminated intravascular blood coagulation, which is confirmed by the increased level of soluble fibrin, products of breakdown of fibrinogen-fibrin, decreased activity of antithrombin III, marked sludging of erythrocytes at the microcirculatory level. A high degree of the correlation between the content of soluble fibrin and the marked sludge-phenomenon was found. Thromboembolic complications arising in this group of patients were accompanied by marked progress of the disorders found, which permitted one to isolate a limited as the the number of parameters coagulogram for the diagnosis of acute intravascular thrombosis in the patients with ischaemic heart diseases with congested insufficiency of the circulation. The important role of a preserved plasmin system for the prognosis in patients with congested insufficiency of the circulation with thromboembolic complications is shown.

Topics: Aged; Antithrombin III; Coronary Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heart Failure; Humans; Male; Middle Aged; Syndrome; Thromboembolism

Rats experimentally infected with Trypanosoma brucei rhodesiense developed a syndrome characterized by anemia, splenomegaly, and glomerulonephritis. Serologic evaluation revealed that the syndrome was accompanied by the presence of 3 autoantibodies--cold-active hemagglutinin, immunoconglutinin, and antibody to fibrinogen/fibrin products. Fluorescein isothiocyanate conjugated antibody tests showed the presence of fixed complement and fibrinogen on both trypanosomes and erythrocytes. All infected rats died by the ninth day of the infection with 5 animals showing signs of pulmonary involvement and shock. From these observations it is suggested that autoantigens, autoantibodies, and complement may have been causal in this syndrome.

Topics: Anemia; Animals; Antigen-Antibody Reactions; Autoantibodies; Complement Fixation Tests; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glomerulonephritis; Hemagglutinins; Kidney; Male; Rats; Spleen; Splenomegaly; Syndrome; Trypanosomiasis, African

Topics: Adult; Afibrinogenemia; Fibrin; Humans; Injections, Intravenous; Kaolin; Male; Syndrome

Circulating anticoagulants are unusual in drug-induced syndromes. We evaluated the prolonged thrombin time of plasma from a patient with a procainamide-induced syndrome. This defect was shown to be due to a circulating anticoagulant that was not of fibrin or fibrinogen origin and that prolonged thrombin and reptilase clotting times of plasma. Subclinical doses of heparin sodium induced hemorrhagic manifestations in this patient. Following cessation of heparin therapy, the circulating anticoagulant persisted but the bleeding tendency abated. All clinical and laboratory manifestations of this syndrome abated gradually following cessation of procainamide therapy.

Topics: Aged; Batroxobin; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Fibrin; Fibrinogen; Humans; Male; Procainamide; Syndrome; Thrombin

Kidney biopsies from ten children with recurrent macroscopic haematuria, showed mesangial deposition of IgG, IgA and complement. Eight of these ten biopsies also showed disposition of properdin, a basic euglobulin intimately involved in the alternate pathway of complement activation. Serum haemolytic complement activity was normal in the eight patients tested. Incubation of the serum at 4 degrees C for 24 dours did not result in any change in complement activity. Theses data suggest that the mesangial inflammatory process in these patients may be medicated in part by the alternate pathway of complement activation and that the mechanism is activated locally.

Topics: Adolescent; Beta-Globulins; Child; Child, Preschool; Complement System Proteins; Female; Fibrin; Hematuria; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Kidney; Kidney Glomerulus; Male; Properdin; Recurrence; Syndrome

Topics: Adult; Bone and Bones; Central Nervous System; Female; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Placenta; Polyhydramnios; Pregnancy; Respiratory Distress Syndrome, Newborn; Subarachnoid Hemorrhage; Syndrome

Topics: Angiomatosis; Argon; Autopsy; Basement Membrane; Erythrocytes; Fibrin; Fluorescein Angiography; Humans; Laser Therapy; Lasers; Leukocytes; Lipid Metabolism; Macrophages; Male; Microscopy, Electron; Middle Aged; Regional Blood Flow; Retina; Retinal Artery; Retinal Pigments; Retinal Vessels; Syndrome; Thrombosis; Time Factors

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Diagnosis, Differential; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinolysis; Humans; Infant; Male; Syndrome

Topics: Blood Proteins; Complement System Proteins; Dengue; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Hemorrhagic Fevers, Viral; Humans; Shock; Syndrome; Thailand; Thrombocytopenia; Transferrin

Topics: Acute Disease; Adult; Aged; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Ecchymosis; Ethanol; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Mucous Membrane; Protamines; Prothrombin Time; Syndrome; Thrombocytopenia

Topics: Adult; Aged; Aneurysm; Aortic Aneurysm; Arteriosclerosis; Blood Cell Count; Blood Coagulation; Blood Platelets; Buttocks; Cell Survival; Chromium Radioisotopes; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Hemangioma; Humans; Iodine Radioisotopes; Middle Aged; Purpura, Thrombocytopenic; Skin Neoplasms; Syndrome; Thrombosis

Topics: Animals; Dog Diseases; Dogs; Fibrin; Intervertebral Disc Displacement; Ischemia; Necrosis; Spinal Cord; Syndrome

Topics: Adolescent; Azathioprine; Biopsy; Child; Child, Preschool; Female; Fibrin; Glomerulonephritis; Humans; Immunoglobulin G; Infant; Kidney Glomerulus; Male; Microscopy, Fluorescence; Nephrotic Syndrome; Prednisone; Proteinuria; Purpura; Skin; Syndrome

Topics: Fibrin; Fibrinolysis; Humans; Male; Prostatic Neoplasms; Syndrome

Topics: Fibrin; Humans; Myocardial Infarction; Syndrome

Topics: Coagulants; Fibrin; Fibrinogen; Humans; Purpura; Purpura, Thrombocytopenic; Syndrome; Thrombocytopenia

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

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

Topics: Fibrin; Fibrinolysis; Hemorrhage; Humans; Male; Neoplasms; Prostatic Neoplasms; Syndrome

Topics: Female; Fibrin; Hemorrhage; Humans; Menorrhagia; Metrorrhagia; Pregnancy; Syndrome; Thrombosis; Uterine Hemorrhage; Uterus

Topics: Fibrin; Fibrinolysis; Hemorrhage; Humans; Leukemia; Leukemia, Myeloid; Syndrome

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