path(MESH:Thrombosis)
Thus, by participating in Fenton chemistry, non-transferrin-bound iron (i.e., iron not bound to the physiological iron transport protein, transferrin) causes oxidative damage, cytotoxicity and enhanced endothelial expression of adhesion molecules, thereby enhancing thrombotic risk (Hershko, 2007). PubMed:25307023
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
Therefore, decreased NO bioavailability affects vascular tone, platelet and endothelial function and coagulation, thus increasing thrombotic risk. PubMed:25307023
The abnormal phospholipid membrane asymmetry present in the RBCs of b-thalassaemia and SCD patients, with resultant phosphatidylserine exposure, appears to play a significant role in the aetiology of the observed hypercoagulable state and in the link between haemolysis and thrombosis (Ataga et al, 2007). PubMed:25307023
Because of the large numbers of RBCs present in the blood, even a small fraction of RBCs with phosphatidylserine exposure can result in prothrombotic conditions. PubMed:28458720
However, in the past few decades there has been increasing evidence that RBCs have a variety of active functions in hemostasis and thrombosis that are significant and need to be taken into account in assessing health and disease. PubMed:28458720
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
This common X-linked inherited disorder, characterized by severe intravascular and extravascular haemolysis, is classically triggered by fava bean ingestion or pro-oxidant medications. It causes haemolysis in susceptible individuals and an association with thrombosis was described in multiple case reports (Jewett, 1976; Thompson et al, 2013; Albertsen et al, 2014). PubMed:25307023
More rigid RBCs may be less able to squeeze through the capillaries and they also increase platelet margination described above, both of which increase the susceptibility to thrombosis [18]. PubMed:28458720
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
The RBC-platelet adhesive interaction may be important in pathological conditions associated with a high incidence of thrombosis, such as thalassemia [36] or sickle cell disease [37]. PubMed:28458720
Furthermore, retrospective studies suggest an association between transfusion of older, stored RBCs and thrombosis (Spinella et al, 2009). PubMed:25307023
ADP released from haemolysed RBCs induces CD40LG release from platelets and lymphocytes, thereby contributing to the pro-inflammatory and pro-thrombotic environment (Helms et al, 2013). PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
These ROS then oxidize cell membrane constituents to induce cytotoxicity and promote inflammation and thrombosis. PubMed:25307023
Finally, the cytokines produced through these pathways can then affect endothelial activation, leucocyte recruitment, and ultimately thrombotic risk. PubMed:25307023
The highest prevalence was observed in splenectomized patients. PubMed:25307023
RBC aggregation promotes thrombosis in veins, confirming the pathogenic importance of locally altered blood rheology in the development of venous thrombosis [17]. PubMed:28458720
An increase of fibrinogen concentration can result in greater RBC aggregation, which is associated with a higher incidence of thrombosis. PubMed:28458720
Some diseases, such as diabetes, hypertension, lower limb vein thrombosis, coronary heart disease, can secondarily alter the properties of RBCs, making them stiffer and prothrombotic [24]. PubMed:28458720
More rigid RBCs may be less able to squeeze through the capillaries and they also increase platelet margination described above, both of which increase the susceptibility to thrombosis [18]. PubMed:28458720
Thus the volume fraction of red cells may have a significant impact on hemostasis and thrombosis, with the nature of the effect related to the flow conditions [9]. PubMed:28458720
In addition, reduced NO bioavailability induces platelet activation and aggregation, leading to thrombosis in a mouse model of intravascular haemolysis (Hu et al, 2010). PubMed:25307023
In addition, reduced NO bioavailability induces platelet activation and aggregation, leading to thrombosis in a mouse model of intravascular haemolysis (Hu et al, 2010). PubMed:25307023
When RBCs are damaged by high shear in continuous flow ventricular assist devices, free hemoglobin induces platelet aggregation, contributing to high risk of thrombotic complications [33]. PubMed:28458720
On the other hand, eryptosis is associated with anemia, microcirculatory derangement, and thrombosis [142, 144]. PubMed:29956069
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
The median (and mean—data not shown) free Hb levels preoperatively and at all postoperative time points (immediately and 6 and 12 hr postoperatively) were higher (p50.057) in those who later developed a proven thrombosis (Fig. 3 displays the 12-hr data). PubMed:29603246
Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation. PubMed:29603246
Children undergoing open heart surgery experience a progressively increasing risk of postoperative infection and thrombosis, increasing need for mechanical ventilation and inotropes, increasing Day 1 through Day 2 peak blood lactate, and decreased nadir mean arterial pressure as the levels of free Hb increase and the levels of haptoglobin decrease. PubMed:29603246
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434
Adult normal levels of preoperative haptoglobin were associated with a substantially and significantly lower incidence of thrombosis than lower levels of haptoglobin (Table 1; row 3). PubMed:29603246
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
More recently, we have described two infants carrying the mutation who manifested with recurrent strokes [8], establishing the concept that primary Cys89Tyr mutation in CD59 leads to a thrombophilic state. PubMed:29929138
In summary, thrombosis is an extremely important prognostic factor both in PNH and in primary Cys89Tyr nonfunctioning CD59. PubMed:29929138
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023
The VWF is prothrombotic and can increase the adhesion of erythrocytes to the endothelium. PubMed:24904418
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
During HUS, endothelial lesions cause a complement dependent activation of immune response and local thrombus formation—attachment of fibrin and platelets to the endothelial lesions and consequently disseminated intravascular coagulation (DIC)—and further mechanical destruction of the red blood cells in the fibrin mesh resulting in hemolysis [82]. PubMed:29956069
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Thrombosis is the prognostic factor with the greatest effect on survival in paroxysmal nocturnal hemoglobinuria (PNH) patients [1, 2]. PubMed:29929138
In summary, thrombosis is an extremely important prognostic factor both in PNH and in primary Cys89Tyr nonfunctioning CD59. PubMed:29929138
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
DIC is characterized by a systemic intravascular coagulation, formation of microvascular thrombi, insufficiently compensated consumption of platelets and coagulation factors, and eventually bleeding tendency [84]. PubMed:29956069
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
Data from several retrospective studies in the preeculizumab era showed that the cause of death was related to thrombosis in 22.2–37.2% of PNH patients. PubMed:29929138
Moreover they have demonstrated that released Hb plays an important role in exacerbating RBC hemolysis, establishing a damaging hemolysis/ oxidative cycle that drives further red cell damage, vascular injury, and thrombosis. PubMed:19276082
Haemolysis, which is observed in multiple diseases, can affect all three components of Virchow’s triad; thus, it is not surprising that there is a link between haemolytic disorders and thrombosis. PubMed:25307023
Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11 PubMed:29603246
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
Thus the volume fraction of red cells may have a significant impact on hemostasis and thrombosis, with the nature of the effect related to the flow conditions [9]. PubMed:28458720
Moreover they have demonstrated that released Hb plays an important role in exacerbating RBC hemolysis, establishing a damaging hemolysis/ oxidative cycle that drives further red cell damage, vascular injury, and thrombosis. PubMed:19276082
Haemolysis, which is observed in multiple diseases, can affect all three components of Virchow’s triad; thus, it is not surprising that there is a link between haemolytic disorders and thrombosis. PubMed:25307023
Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11 PubMed:29603246
Clinical studies have confirmed endothelial dysfunction and vasculopathy in a patient with HO-1 deficiency, and similarly, mice lacking HO-1 have increased vascular injury and thrombotic complications (43, 44). PubMed:19276082
The VWF is prothrombotic and can increase the adhesion of erythrocytes to the endothelium. PubMed:24904418
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
The triad consists of hypercoagulability, blood stasis and endothelial injury/dysfunction, which are useful concepts for understanding thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Thrombosis is the prognostic factor with the greatest effect on survival in paroxysmal nocturnal hemoglobinuria (PNH) patients [1, 2]. PubMed:29929138
In summary, thrombosis is an extremely important prognostic factor both in PNH and in primary Cys89Tyr nonfunctioning CD59. PubMed:29929138
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
This common X-linked inherited disorder, characterized by severe intravascular and extravascular haemolysis, is classically triggered by fava bean ingestion or pro-oxidant medications. It causes haemolysis in susceptible individuals and an association with thrombosis was described in multiple case reports (Jewett, 1976; Thompson et al, 2013; Albertsen et al, 2014). PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
Multiple haemolytic disorders and therapeutic interventions produce substantial intravascular haemolysis. Examples include PNH, SCD, thalassaemias, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis and stomatocytosis, pyruvate kinase deficiency, autoimmune haemolytic anaemia, microangiopathies, acute haemolytic transfusion reactions, mechanical circulatory support [e.g., left ventricular assist device (LVAD)/extracorporeal membrane oxygenation (ECMO)], RBC transfusions and infusions of RBC substitutes. These disorders, therapies and procedures are also associated with an increased risk of thrombosis. PubMed:25307023
The highest prevalence was observed in splenectomized patients. PubMed:25307023
DIC is characterized by a systemic intravascular coagulation, formation of microvascular thrombi, insufficiently compensated consumption of platelets and coagulation factors, and eventually bleeding tendency [84]. PubMed:29956069
Although haemolysis and thrombosis are hallmarks of the thrombo microangiopathies, such as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome (TTP/HUS), it is difficult to isolate the causative role of haemolysis in the pathophysiology of thrombosis in these complex disorders. PubMed:25307023
Furthermore, retrospective studies suggest an association between transfusion of older, stored RBCs and thrombosis (Spinella et al, 2009). PubMed:25307023
In addition, reduced NO bioavailability induces platelet activation and aggregation, leading to thrombosis in a mouse model of intravascular haemolysis (Hu et al, 2010). PubMed:25307023
In addition, reduced NO bioavailability induces platelet activation and aggregation, leading to thrombosis in a mouse model of intravascular haemolysis (Hu et al, 2010). PubMed:25307023
ADP released from haemolysed RBCs induces CD40LG release from platelets and lymphocytes, thereby contributing to the pro-inflammatory and pro-thrombotic environment (Helms et al, 2013). PubMed:25307023
However, in the past few decades there has been increasing evidence that RBCs have a variety of active functions in hemostasis and thrombosis that are significant and need to be taken into account in assessing health and disease. PubMed:28458720
On the other hand, an abnormally high hematocrit is associated with thrombosis, and patients with polycythemia vera or taking erythropoietin are more susceptible to thrombosis and thromboembolism [4, 5]. PubMed:28458720
Some diseases, such as diabetes, hypertension, lower limb vein thrombosis, coronary heart disease, can secondarily alter the properties of RBCs, making them stiffer and prothrombotic [24]. PubMed:28458720
Because of the large numbers of RBCs present in the blood, even a small fraction of RBCs with phosphatidylserine exposure can result in prothrombotic conditions. PubMed:28458720
The ability of cells to generate MPs in vivo is an important regulatory mechanism of physiologic reactions, a means for intercellular communications and a pathogenic component in many diseases that impact hemostasis and thrombosis [50, 51]. PubMed:28458720
An increase of fibrinogen concentration can result in greater RBC aggregation, which is associated with a higher incidence of thrombosis. PubMed:28458720
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
The median (and mean—data not shown) free Hb levels preoperatively and at all postoperative time points (immediately and 6 and 12 hr postoperatively) were higher (p50.057) in those who later developed a proven thrombosis (Fig. 3 displays the 12-hr data). PubMed:29603246
Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation. PubMed:29603246
Children undergoing open heart surgery experience a progressively increasing risk of postoperative infection and thrombosis, increasing need for mechanical ventilation and inotropes, increasing Day 1 through Day 2 peak blood lactate, and decreased nadir mean arterial pressure as the levels of free Hb increase and the levels of haptoglobin decrease. PubMed:29603246
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434
There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246
Adult normal levels of preoperative haptoglobin were associated with a substantially and significantly lower incidence of thrombosis than lower levels of haptoglobin (Table 1; row 3). PubMed:29603246
Data from several retrospective studies in the preeculizumab era showed that the cause of death was related to thrombosis in 22.2–37.2% of PNH patients. PubMed:29929138
More recently, we have described two infants carrying the mutation who manifested with recurrent strokes [8], establishing the concept that primary Cys89Tyr mutation in CD59 leads to a thrombophilic state. PubMed:29929138
In summary, thrombosis is an extremely important prognostic factor both in PNH and in primary Cys89Tyr nonfunctioning CD59. PubMed:29929138
On the other hand, eryptosis is associated with anemia, microcirculatory derangement, and thrombosis [142, 144]. PubMed:29956069
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.