fibrin and Anemia--Sickle-Cell

Topics: Acute Disease; Anemia, Sickle Cell; Anticoagulants; Bicarbonates; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Glucose; Humans; Plasminogen; Time Factors; Venoms

This is a case report about a 7-year-old male child with sickle cell anemia (S/β

Topics: Acute Chest Syndrome; Anemia, Sickle Cell; Autopsy; Child; Fibrin; Humans; Male; Pulmonary Embolism

Sickle cell disease is a single point mutation disease that is known to alter the coagulation system, leading to hypercoagulable plasma conditions. These hypercoagulable conditions can lead to complications in the vasculature, caused by fibrin clots that form undesirably. There is a need to understand the morphology and structure of fibrin clots from patients with sickle cell disease, as this could lead to further discovery of treatments and life-saving therapies. In this work, a computational imaging analysis method is presented to evaluate fibrin agglomeration in the presence of erythrocytes (RBCs) homozygous for the sickle cell mutation (SS). Numerical algorithms were used to determine agglomeration of fibrin fibers within a matrix with SS RBCs to test the hypothesis that fibrin matrices with the inclusion of SS RBCs possess a more agglomerated structure than native fibrin matrices with AA RBCs. The numerical results showed that fibrin structures with SS RBCs displayed an overall higher degree of agglomeration as compared to native fibrin structures. The computational algorithm was also used to evaluate fibrin fiber overlap (aggregation) and anisotropy (orientation) in normal fibrin matrices compared to fibrin matrices polymerized around SS RBCs; however, there was no statistical difference. Ultrasound measurements of stiffness revealed rigid RBCs in the case of samples derived from homozygous SS blood, and densely evolving matrices, when compared to normal fibrin with the inclusion of AA RBCs. An agglomeration model is suggested to quantify the fibrin aggregation/clustering near RBCs for both normal fibrin matrices and for the altered structures. The results of this work are important in the sense that the understanding of aggregation and morphology in fibrin clots with incorporation of RBCs from persons living with sickle cell anemia may elucidate the complexities of comorbidities and other disease complications.

Topics: Algorithms; Anemia, Sickle Cell; Erythrocyte Aggregation; Erythrocytes; Fibrin; Homozygote; Humans; Imaging, Three-Dimensional; Microscopy, Confocal; Protein Aggregates

Fibrin is an extracellular matrix protein that is responsible for maintaining the structural integrity of blood clots. Much research has been done on fibrin in the past years to include the investigation of synthesis, structure-function, and lysis of clots. However, there is still much unknown about the morphological and structural features of clots that ensue from patients with disease. In this research study, experimental techniques are presented that allow for the examination of morphological differences of abnormal clot structures due to diseased states such as diabetes and sickle cell anemia. Our study focuses on the preparation and evaluation of fibrin clots in order to assess morphological differences using various experimental assays and confocal microscopy. In addition, a method is also described that allows for continuous, real-time calculation of lysis rates in fibrin clots. The techniques described herein are important for researchers and clinicians seeking to elucidate comorbid thrombotic pathologies such as myocardial infarctions, ischemic heart disease, and strokes in patients with diabetes or sickle cell disease.

Topics: Anemia, Sickle Cell; Blood Chemical Analysis; Factor XIIIa; Fibrin; Fibrinogen; Fibrinolysis; Humans; Microscopy, Confocal; Myocardial Infarction; Myocardial Ischemia; Stroke; Thrombin; Thrombosis

Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0·0385 and P = 0·017, respectively), and as expected, were much higher in SSversusAA (P < 0·0001 for both). Thrombin generation in platelet poor plasma was indistinguishable between AA and AS subjects, whereas a paradoxical decrease in endogenous thrombin potential was observed in SS (P ≤ 0·0001). Whole blood tissue factor was elevated in SS compared to AA (P = 0·005), but did not differ between AA and AS. Plasma microparticle tissue factor activity was non-significantly elevated in AS (P = 0·051), but was clearly elevated in SS patients (P = 0·004) when compared to AA controls. Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation.

Topics: Adult; Anemia, Sickle Cell; Antithrombin III; Black or African American; Case-Control Studies; Cell-Derived Microparticles; Cytokines; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Inflammation Mediators; Male; Middle Aged; Peptide Hydrolases; Plasma; Sickle Cell Trait; Thrombin; Thrombophilia; Thromboplastin; Venous Thromboembolism

Topics: Anemia, Sickle Cell; Endothelial Cells; Fibrin; Flow Cytometry; Hemolysis; Hemostasis; Humans; Hypertension, Pulmonary; Inflammation; Models, Biological; Monocytes; Thrombophilia

Complex pertubations of hemostasis occur in sickle cell disease (SCD). Although the procoagulant property of sickle erythrocytes in vitro is tied to exposure of phosphatidylserine (PS), no study has directly linked this PS positivity to in vivo thrombin generation. This study was designed to determine if thrombin generation in SCD correlates with erythrocyte PS, or whether platelets play a significant role. PS was quantified on erythrocytes and platelets from 40 patients with SCD (SS genotype = 25; SC genotype = 15) and 11 controls. Markers of thrombin generation (prothrombin fragment F1.2; thrombin-antithrombin or TAT complexes) and fibrin dissolution (D-dimer; plasmin-antiplasmin or PAP complexes) were also evaluated. Thrombin generation and activation of fibrinolysis occurred with elevations in F1.2, TAT, and D-dimer. Although numbers of both PS-positive erythrocytes and platelets were elevated, there was no correlation between PS-positive platelets and any hemostatic markers. In contrast, correlations were noted between PS-positive erythrocytes and F1.2 (P <.0002), D-dimer (P <.000002), and PAP (P <.01). Correlations between F1.2 and D-dimer (P <.0001) demonstrated that fibrinolysis was secondary to thrombin generation. In patients with the SC genotype, abnormalities in coagulation, although present, were of a lesser magnitude than in SS disease. This study suggests that the sickle erythrocyte is the cell responsible for the thrombophilic state in SCD because associations between erythrocyte PS and thrombin generation were observed. No such relationship with platelet PS was noted. The use of erythrocyte PS as a surrogate marker in trials testing new therapeutic modalities may provide insights into the vascular complications of SCD.

Topics: Adolescent; Adult; alpha-2-Antiplasmin; Anemia, Sickle Cell; Antithrombin III; Biomarkers; Blood Platelets; Child; Child, Preschool; Erythrocytes; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Fibrinolysis; Hemostasis; Humans; Infant; Longitudinal Studies; Peptide Fragments; Peptide Hydrolases; Phosphatidylserines; Prothrombin; Thrombin; Thrombophilia

To characterize the pathophysiology of hyphema clearance, we studied changes in the facility of outflow in experimental hyphema in freshly enucleated rabbit eyes. Hyphemas, with washed normal or sickled red cells (RBCs) (suspended in isotonic phosphate buffer to obtain a hematocrit value comparable to that of whole blood) and occupying 50% to 100% of the anterior chamber volume, caused a marked cell "crowding" in the chamber angle and an increase in the outflow resistance; the facility stabilized at a value 60% lower than the control (p = < 0.001). No significant change in outflow facility was observed in hyphemas of either RBC type occupying 25% of the anterior chamber volume (p = N.S.). Whole blood hyphema occupying 50% of the anterior chamber volume reduced the facility of outflow by 80% of the control mock aqueous value (p = < 0.001); a comparison with 50% hyphema produced by washed RBCs indicated a significant contribution by the plasma (fibrin) component (p = 0.0025) in increasing the resistance to outflow.

Topics: Anemia, Sickle Cell; Animals; Anterior Chamber; Aqueous Humor; Erythrocytes; Fibrin; Humans; Hyphema; Intraocular Pressure; Rabbits

Topics: Adenosine Diphosphate; Anemia, Sickle Cell; Arterial Occlusive Diseases; Bilirubin; Blood; Erythrocytes; Fibrin; Humans; Platelet Adhesiveness; Platelet Aggregation; Veins

Topics: Adolescent; Adult; Anemia, Sickle Cell; Arthritis; Bone and Bones; Child; Child, Preschool; Erythrocytes, Abnormal; Female; Fibrin; Hemoglobin C Disease; Humans; Infarction; Joint Diseases; Male; Middle Aged; Mucins; Necrosis; Osteoporosis; Radiography; Sclerosis; Synovial Fluid; Synovial Membrane; Thalassemia; Uric Acid

Topics: Anemia, Sickle Cell; Animals; Anticoagulants; Coumarins; Fibrin; Heparin; Humans; Male; Priapism; Pulmonary Embolism; Retinal Diseases; Retinal Vessels; Snakes; Thrombosis; Venoms