fibrin and Anemia

The multiple roles of red blood cells (RBCs) are often neglected as contributors in hemostasis and thrombosis. Proactive opportunities to increase RBC numbers, either acutely or subacutely in the case of iron deficiency, are critical as RBCs are the cellular elements that initiate hemostasis together with platelets and stabilize fibrin and clot structure. RBCs also possess several functional properties to assist hemostasis: releasing platelet agonists, promoting shear force-induced von Willebrand factor unfolding, procoagulant capacity, and binding to fibrin. Additionally, blood clot contraction is important to compress RBCs to form a tightly packed array of polyhedrocytes, making an impermeable seal for hemostasis. All these functions are important for patients having intrinsically poor capacity to cease bleeds (ie, hemostatic disorders) but, conversely, can also play a role in thrombosis if these RBC-mediated reactions overshoot. One acquired example of bleeding with anemia is in patients treated with anticoagulants and/or antithrombotic medication because upon initiation of these drugs, baseline anemia doubles the risk of bleeding complications and mortality. Also, anemia is a risk factor for reoccurring gastrointestinal and urogenital bleeds, pregnancy, and delivery complications. This review summarizes the clinically relevant properties and profiles of RBCs at various steps of platelet adhesion, aggregation, thrombin generation, and fibrin formation, including both structural and functional elements. Regarding patient blood management guidelines, they support minimizing transfusions, but this approach does not deal with severe inherited and acquired bleeding disorders where a poor hemostatic propensity is exacerbated by limited RBC availability, for which future guidance will be needed.

Topics: Anemia; Blood Platelets; Erythrocytes; Fibrin; Hemorrhage; Hemostasis; Humans; Thrombosis

Patient blood management strategies for total hip and knee arthroplasty are controversial. They range from pre-operative haemoglobin optimisation to intra- and post-operative interventions. The aim of this study was to assess the various treatment modalities with respect to blood loss, haemoglobin levels and blood transfusions.. The analysis was based on the principles of a systematic review. The literature was searched in PubMed for the period from 2004 to November 2014. The articles were reviewed with respect to blood loss, post-operative haemoglobin drop, blood transfusions and length of hospital stay. The papers were evidence-graded. Non-randomised clinical studies and papers not concerning total hip or knee arthroplasty were excluded as were studies lacking a control group. Subanalyses were performed for tranexamic acid, tourniquet and fibrin use.. A total of 49 studies were found eligible which is equivalent to a total of 4,752 patients. Tranexamic acid administered either orally, topically, intravenously or in combination decreased blood loss, increased the post-operative haemoglobin level, decreased the number of patients receiving blood transfusions and minimised the length of stay. A similar result was found for fibrin spray in total hip arthroplasty. However, for total knee arthroplasty, the outcome was blurred. Tourniquet use was uniformly not significant in the measured parameters.. Tranexamic acid is useful in managing anaemia and blood loss. Fibrin sealant also has this potential, but is not more potent than tranexamic acid. Tourniquet use is not advantageous.

Topics: Adult; Anemia; Antifibrinolytic Agents; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Blood Loss, Surgical; Blood Transfusion; Female; Fibrin; Hemoglobins; Humans; Length of Stay; Male; Postoperative Period; Tourniquets; Tranexamic Acid

Pulmonary vascular inflammatory disorders may involve all components of the pulmonary vasculature, including capillaries. The principal histopathologic features of pulmonary capillaritis include capillary wall necrosis with infiltration by neutrophils, interstitial erythrocytes, and/or hemosiderin, and interalveolar septal capillary occlusion by fibrin thrombi. Immune complex deposition is variably present. Patients often present clinically with diffuse alveolar hemorrhage, which is characterized by dyspnea and hemoptysis; diffuse, bilateral, alveolar infiltrates on chest radiograph; and anemia. Pulmonary capillaritis has been reported with variable frequency and severity as a manifestation of Wegener's granulomatosis, microscopic polyarteritis, systemic lupus erythematosus, Goodpasture's syndrome, idiopathic pulmonary renal syndrome, Behçet's syndrome, Henoch-Schönlein purpura, IgA nephropathy, antiphospholipid syndrome, progressive systemic sclerosis, and diphenylhydantoin use. In addition to history, physical examination, and routine laboratory studies, certain ancillary laboratory tests, such as antineutrophil cytoplasmic antibodies, antinuclear antibodies, and antiglomerular basement membrane antibodies, may help diagnose an underlying disease. Diagnosis of pulmonary capillaritis can be made by fiberoptic bronchoscopy with transbronchial biopsy, but thoracoscopic biopsy is often employed. Since many disorders can result in pulmonary capillaritis with diffuse alveolar hemorrhage, it is crucial for clinicians and pathologists to work together when attempting to identify an underlying disease. Therapy depends on the disorder that gave rise to the pulmonary capillaritis and usually includes corticosteroids and cyclophosphamide or azathioprine. Since most diseases that result in pulmonary capillaritis are treated with immunosuppression, infection must be excluded aggressively.

Topics: Anemia; Bronchoscopy; Capillaries; Diagnosis, Differential; Dyspnea; Erythrocytes; Fibrin; Hemoptysis; Hemorrhage; Hemosiderin; Humans; Immunosuppressive Agents; Lung; Lung Diseases; Necrosis; Neutrophils; Pulmonary Alveoli; Pulmonary Embolism; Thoracoscopy; Vasculitis

Topics: Adrenal Glands; Aldosterone; Anemia; Biopsy, Needle; Cholinesterases; Erythropoietin; Fibrin; Graft Rejection; Humans; Hyperparathyroidism; Hypertension; Juxtaglomerular Apparatus; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Polycythemia; Proteinuria; Radioisotope Renography; Renin; Transplantation, Homologous; Ultrasonography

Topics: Anemia; Animals; Ascorbic Acid; Biomechanical Phenomena; Cicatrix; Collagen; Denervation; Fibrin; Fibroblasts; Glucocorticoids; Glycoproteins; Glycosaminoglycans; Granulation Tissue; Guinea Pigs; Histamine; Humans; Lathyrism; Microbial Collagenase; Oxygen; Rabbits; Rats; Species Specificity; Stress, Physiological; Time Factors; Wound Healing; Wounds and Injuries

Echis carinatus is the most important cause of morbidity and mortality from snake bite in Nigeria and in many other parts of the world. Forty-six patients with systemic poisoning by this snake were given echis antivenom made either by the South African Institute for Medical Research (S.A.I.M.R.) or by Behringwerke (North and West African polyvalent antivenom). A simple test of blood coagulability was used to assess whether an adequate neutralizing dose of antivenom had been given. An average of 15.2 ml S.A.I.M.R. antivenom restored normal coagulability permanently in all 23 patients in one group, but in the other group receiving an average dose of 37.9 ml Behringwerke antivenom normal clotting resulted in only 18 out of 23 patients. Local tissue swelling was similar in both groups, but local necrosis occurred in three patients treated with Behringwerke antivenom and in none given S.A.I.M.R. antivenom.

Topics: Acute Disease; Anemia; Antivenins; Blood Coagulation; Cerebral Hemorrhage; Codeine; Epinephrine; Fibrin; Fibrinogen; Hematocrit; Histamine H1 Antagonists; Humans; Hydrocortisone; Nigeria; Prednisone; Shock; Snake Bites; Snake Venoms

At the final stages of blood coagulation, fibrinogen is processed into insoluble fibrin by thrombin resulting in fibril-like structure formation. Via further cross-linking reactions between the fibrin gamma subunit by the catalytic action of blood transglutaminase (Factor XIII), this molecule gains further physical stability. Meanwhile, since fibrinogen is expressed in various cells and tissues, this molecule can exhibit other functions apart from its role in blood coagulation. To create a system studying on aberrant coagulation and investigate the physiological functions, using a model fish medaka (Oryzias latipes), we established gene-deficient mutants of fibrinogen gamma subunit protein in parallel with its biochemical analysis, such as tissue distribution pattern and substrate properties. By genetic deletion via genome editing, two distinct mutants displayed retardation of blood coagulation. The mutants showed lower hematocrit with aberrant erythrocyte maturation, which indicates that fibrin deficiency caused severe anemia, and also appeared as a model for investigation of the fibrin function.

Topics: Anemia; Animals; Factor XIII; Fibrin; Fibrinogen; Oryzias; Thrombin; Transglutaminases

The relationships among the hemostatic markers, the development of deep vein thrombosis (DVT) and the withdrawal of fondaparinux due to a reduction in the hemoglobin levels were examined.. Two-hundred twenty-one Japanese patients who underwent major orthopedic surgery and were treated with 1.5mg of fondaparinux instead of 2.5mg of fondaparinux were studied. Forty-seven of 221 patients discontinued fondaparinux treatment (withdrawal group) and 37 patients developed DVT.. The age, frequency of total knee arthroplasty (TKA), withdrawal of fondaparinux, reduction of hemoglobin and the plasma levels of soluble fibrin (SF), D-dimer and fibrinogen and fibrin degradation product (FDP) on day 1 after the operation were significantly higher in the patients with DVT. Elevated SF, D-dimer or FDP levels were associated with the risk for DVT. The age, frequency of TKA or DVT, anti-Xa activity and the creatinine, FDP and D-dimer levels were significantly higher in the withdrawal group. An anti-Xa level >0.33 mg/l and an elevated D-dimer or FDP level were associated with the risk of withdrawal.. The age and SF levels, TKA and withdrawal of fondaparinux were related to the risk of DVT, and the anti-Xa activity, creatinine level and DVT were related to the risk of withdrawal of fondaparinux due to a reduction in hemoglobin.

Topics: Age Factors; Aged; Aged, 80 and over; Anemia; Anticoagulants; Arthroplasty, Replacement, Knee; Biomarkers; Factor Xa; Factor Xa Inhibitors; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fondaparinux; Hemoglobins; Humans; Male; Middle Aged; Polysaccharides; Risk Factors; Venous Thrombosis

Scleroderma renal crisis (SRC) can lead to end-stage renal disease (ESRD) and subsequent need for dialysis and/or renal transplantation. We review all reported cases of renal transplantations in scleroderma patients from PubMed search, present UNOS data on transplant outcomes, and identify predictors for allograft SRC. Of the five cases with recurrent SRC, all developed ESRD within a year of onset of native kidney SRC, whereas none of those who developed ESRD more than 1-2 years after the onset of SRC developed recurrence. Anemia preceded allograft SRC in two cases, pericardial effusion in one, and skin tightening in two others. UNOS data (October 1987-July 2004) documented 260 transplants performed for the renal diagnosis of scleroderma, with a 5-year graft survival rate of 56.7%. The risk for allograft SRC recurrence appears to correlate with early native renal function loss following the onset of SRC. Recurrent SRC in the allograft may be heralded by multiple clinical markers known to be predictive of severe scleroderma, including progression of diffuse skin thickening, new-onset anemia and cardiac complications.

Topics: Anemia; Arterioles; Autoimmune Diseases; Disease Progression; Edema; Female; Fibrin; Graft Rejection; Graft Survival; Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Kidney Tubules; Leukocytes, Mononuclear; Lymphocytes; Middle Aged; Pericardial Effusion; PubMed; Recurrence; Renal Dialysis; Risk Factors; Scleroderma, Systemic; Skin; Thrombosis; Time Factors; Transplantation, Homologous

An 80-years-old man was admitted to our clinic because of upper gastrointestinal bleeding with tarry stool for 3 days after taking non steroidal antiinflammatory drugs (NSAID) for back pain. The history was otherwise unremarkable.. Laboratory results showed anaemia. Initial endoscopy revealed acute bleeding from an elevated ulcer in the pars inferior of the duodenum. The bleeding was successfully treated by epinephrine and fibrin injection. Biopsies showed inflammatory changes without presence of malignant cells. In the CT scan of the abdomen there was a mass near the ligament of Treitz of 6.3 cm in diameter adjacent to the duodenum.. The abdominal tumor was not suitable for ultrasound-guided biopsy. Therefore, laparotomy and surgical resection of the tumor were performed. Histology showed a gastrointestinal stromal tumor (GIST) with infiltration of the muscle layer of the duodenal wall with one small local metastasis. No lymph node metastases were present. The tumor was surgically completely removed and the regular follow-up examinations have fo far shown no evidence for tumor recurrence or metastases.. In upper gastrointestinal bleeding from unusual sites, GIST has to be considered as an underlying disease even if endoscopic biopsies are negative for neoplastic changes.

Topics: Aged; Aged, 80 and over; Anemia; Biopsy; Duodenal Neoplasms; Endoscopy, Digestive System; Epinephrine; Fibrin; Gastrointestinal Hemorrhage; Humans; Immunohistochemistry; Male; Stromal Cells; Tomography, X-Ray Computed; Treatment Outcome

Maternal anemia and low birth weight (LBW) may complicate malaria in pregnancy, and placental monocyte infiltrates have been associated with LBW, and anecdotally with anemia. We examined placental pathology from 357 Malawian women. Intervillous monocyte infiltrates were frequent in placental malaria and were not seen in uninfected placentas. Histology was grouped according to a 5-point scale. Dense monocyte infiltrates and presence of intramonocytic malaria pigment were associated with anemia and LBW. Of factors associated with LBW and/or anemia in univariate analysis, gravidity (P = 0.002), number of antenatal clinic (ANC) visits (P < 0.001), malaria pigment in fibrin (P = 0.03), and monocyte malaria pigment (P = 0.0001) remained associated with lower birth weight by multivariate analysis. Associated with maternal anemia were HIV infection (P < 0.0001), intervillous monocyte numbers (P < 0.0001), number of ANC visits (P = 0.002), and recent febrile symptoms (P = 0.0001). Pigment-containing placental monocytes are associated with anemia and LBW due to malaria, and may have a causative role in their development.

Topics: Adolescent; Adult; Anemia; Animals; Birth Weight; Female; Fibrin; Hemoglobins; Humans; Infant, Low Birth Weight; Infant, Newborn; Malaria, Falciparum; Middle Aged; Monocytes; Pigments, Biological; Placenta; Pregnancy; Pregnancy Complications, Parasitic; Pregnancy Outcome; Prospective Studies; Risk Factors

Although the importance of injury with consequent activation of endothelium is well-recognized in diseases affecting the glomerular endothelial cell (GEN), research on GEN injury in vivo has been hampered by the lack of adequate animal models. Here we report the establishment and characterization of a new GEN injury model in rats. This model was induced by selective renal artery perfusion with anti-GEN IgG and resulted in the severe acute renal failure with marked platelet deposition and development of a thrombotic microangiopathy involving glomeruli. Peritubular capillary endothelial cells were also damaged that was associated with severe tubular necrosis. Although the glomerular changes were severe, half of the glomeruli recovered by day 10, while interstitial changes remained throughout our observation time course. Proliferation of GEN was observed during the recovery phase. An increased expression of endothelial nitric oxide synthase in GEN was also observed, and may be an adaptive mechanism to counteract the thrombosis and ischemia. This model should be useful to investigate the pathophysiology of renal microvascular diseases and the mechanisms of GEN injury, activation and recovery in vivo.

Topics: Acute Kidney Injury; Anemia; Animals; Blood Urea Nitrogen; Collagen; Complement System Proteins; Disease Models, Animal; Endothelial Growth Factors; Endothelium, Vascular; Fibrin; Kidney; Kidney Glomerulus; Laminin; Lymphokines; Macrophages; Male; Nitric Oxide Synthase; Proteinuria; Rats; Rats, Wistar; Thrombocytopenia; Time Factors; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Rats infected with Trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. Anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. Depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable immune complexes were observed. Terminally, consumption of immunologic factors coincided with accelerated partial thromboplastin times. At death, convulsions and hemoptysis with labored breathing suggested that the animals died of respiratory failure and that disseminated intravascular coagulation may have occurred. It is suggested that microthrombiosis might have resulted from the immunologic interaction of complex-coated blood cells with immunoconglutinin and contributed to the terminal disease signs.

Topics: Agglutinins; Anemia; Animals; Antigen-Antibody Complex; Autoantibodies; Blood Coagulation Disorders; Complement System Proteins; Fibrin; Fibrinogen; Rats; Thrombocytopenia; Trypanosomiasis, African

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: Acute Kidney Injury; Anemia; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Kidney Diseases; Kidney Failure, Chronic; Peritoneal Dialysis; Polycythemia; Renal Dialysis

Topics: Acute Kidney Injury; Anemia; Basement Membrane; Blood Coagulation Disorders; Capillaries; Epithelial Cells; Fibrin; Fluorescent Antibody Technique; Glomerulonephritis; Hematuria; Histocytochemistry; Humans; Immunoglobulins; Kidney; Kidney Glomerulus; Kidney Tubules; Microscopy, Electron; Prognosis; Proteinuria; Statistics as Topic

Topics: Anemia; Animals; Blood Platelets; Disease Models, Animal; Erythrocytes, Abnormal; Fibrin; Hemangioma; Mice; Microscopy, Electron, Scanning; Neoplasm Transplantation; Neoplasms, Experimental; Purpura, Thrombocytopenic; Skin; Skin Neoplasms; Transplantation, Homologous

Topics: Anemia; Calcium; Cobalt; Female; Fibrin; Histocytochemistry; Humans; Iron; Lipid Metabolism; Organ Size; Placenta; Polysaccharides; Pregnancy; Pregnancy Complications, Hematologic; Time Factors

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: Anemia; Anemia, Hypochromic; Biomedical Research; Blood Chemical Analysis; Collagen Diseases; Enzyme Inhibitors; Fibrin; Hemophilia A; Hepatitis; Hepatitis A; Jaundice; Jaundice, Obstructive; Leukemia; Liver Cirrhosis; Multiple Myeloma; Nephritis; Nephrotic Syndrome; Physiology; Purpura; Thrombin; Uremia

Dogs with sustained anemia plus hypoproteinemia due to bleeding and a continuing low protein or protein-free diet containing abundant iron have been used in the present work to test food proteins and supplements as to their See PDF for Structure capacity to produce new hemoglobin and plasma proteins. The reserve stores of blood protein-producing materials are thus largely depleted in such animals and sustained levels of 6 to 8 gm. per cent hemoglobin and 4 to 5 gm. per cent plasma protein can be maintained for considerable periods of time. The stimulus of double depletion drives the body to use all protein building materials with the utmost conservation. This represents a severe biological test for food and body proteins and its assay value must have significance. Measured by this biological test in these experiments, casein stands well up among the best food proteins. The ratio of plasma protein to hemoglobin is about 40 to 50 per cent, which emphasizes the fact that these dogs produce on most diets about 2 gm. hemoglobin to 1 gm. plasma protein. The reason for this preference for hemoglobin production is obscure. The mass of circulating hemoglobin is greater even in this degree of anemia and the life cycle of hemoglobin is much longer than that of the plasma protein. Egg protein, egg albumin, and lactalbumin all favor the production of more plasma protein and less hemoglobin as compared with casein. The plasma protein to hemoglobin ratio is increased, sometimes above 100 per cent. Supplements to the above proteins of casein digests or several amino acids may return the response toward that which is standard for casein. Histidine as a supplement to egg protein increases the total blood protein output and brings the ratio of plasma protein to hemoglobin toward that of casein. Beef muscle goes to the other extreme and favors new hemoglobin production up to 4 gm. hemoglobin to 1 gm. plasma protein-a ratio of 25 per cent. The total amounts of new blood proteins are high. Lactalbumin as compared with casein shows a lower total blood protein output and a plasma protein to hemoglobin ratio of 70 to 90 per cent. Amino acid supplements are less effective. See PDF for Structure Fibrin is a good food protein in these experiments-much like casein. When fed over these 5 week periods it causes a sustained increase in blood fibrinogen. Folic acid in the doses given has no effect on the expected response to various diets. Peanut flour is a very poor diet for the product

Topics: Amino Acids; Anemia; Animals; Blood Proteins; Caseins; Cattle; Diet; Dietary Supplements; Dogs; Fibrin; Hypoproteinemia; Iron; Lactalbumin; Proteins; Swine; Viscera