Podcast
Questions and Answers
Sickle cell disease is a single base change from GAG to ______.
Sickle cell disease is a single base change from GAG to ______.
GTG
Approximately ______ million people are affected by sickle cell disease worldwide.
Approximately ______ million people are affected by sickle cell disease worldwide.
3
Sickle cell disease is inherited in an ______ manner.
Sickle cell disease is inherited in an ______ manner.
autosomal recessive
Hemoglobin S has the unique property of ______ when it releases oxygen.
Hemoglobin S has the unique property of ______ when it releases oxygen.
Signup and view all the answers
The amino acid substitution in sickle cell disease is from glutamic acid to ______.
The amino acid substitution in sickle cell disease is from glutamic acid to ______.
Signup and view all the answers
Hemoglobin S forms long, rigid fibers which ______ the red blood cells.
Hemoglobin S forms long, rigid fibers which ______ the red blood cells.
Signup and view all the answers
Sickle cell disease is a significant global health ______.
Sickle cell disease is a significant global health ______.
Signup and view all the answers
Hypercoagulable state is associated with increased levels of ______ in the blood.
Hypercoagulable state is associated with increased levels of ______ in the blood.
Signup and view all the answers
The exposure of ______ on the surface of RBCs provides a docking site for coagulation complexes.
The exposure of ______ on the surface of RBCs provides a docking site for coagulation complexes.
Signup and view all the answers
The gene responsible for sickle cell disease is located on chromosome ______.
The gene responsible for sickle cell disease is located on chromosome ______.
Signup and view all the answers
Abnormal expression of ______ on circulating endothelial cells is noted during pain episodes.
Abnormal expression of ______ on circulating endothelial cells is noted during pain episodes.
Signup and view all the answers
Thrombin-Antithrombin complexes are one of the ______ of coagulation that increase in a hypercoagulable state.
Thrombin-Antithrombin complexes are one of the ______ of coagulation that increase in a hypercoagulable state.
Signup and view all the answers
In cases of sickle cell disease, targeting ______ may have therapeutic benefits.
In cases of sickle cell disease, targeting ______ may have therapeutic benefits.
Signup and view all the answers
In sickle cell disease, a self perpetuating vicious cycle leads to acute complications such as ______.
In sickle cell disease, a self perpetuating vicious cycle leads to acute complications such as ______.
Signup and view all the answers
One of the painful acute symptoms in sickle cell disease is vaso-occlusive ______.
One of the painful acute symptoms in sickle cell disease is vaso-occlusive ______.
Signup and view all the answers
Acute chest syndrome is characterized by respiratory signs including ______.
Acute chest syndrome is characterized by respiratory signs including ______.
Signup and view all the answers
Chronic complications of sickle cell disease can include chronic ______.
Chronic complications of sickle cell disease can include chronic ______.
Signup and view all the answers
Common sites for painful crises in sickle cell disease include joints and ______.
Common sites for painful crises in sickle cell disease include joints and ______.
Signup and view all the answers
The leading cause of hospitalization in sickle cell disease is vaso-occlusive ______.
The leading cause of hospitalization in sickle cell disease is vaso-occlusive ______.
Signup and view all the answers
In sickle cell disease, the presence of a new pulmonary infiltrate can indicate ______.
In sickle cell disease, the presence of a new pulmonary infiltrate can indicate ______.
Signup and view all the answers
Organ damages in sickle cell disease may lead to multiple ______.
Organ damages in sickle cell disease may lead to multiple ______.
Signup and view all the answers
Pharmacological approaches target PS in Townes sickle mice aged ______ weeks.
Pharmacological approaches target PS in Townes sickle mice aged ______ weeks.
Signup and view all the answers
The heme injection creates a ______ crisis model.
The heme injection creates a ______ crisis model.
Signup and view all the answers
Two groups in the study are SCD control and SCD ______.
Two groups in the study are SCD control and SCD ______.
Signup and view all the answers
The treatment involved intravenous ______ at 10mg/kg.
The treatment involved intravenous ______ at 10mg/kg.
Signup and view all the answers
The study showed that PS003biv decreased vaso-occlusion in both the liver and the ______.
The study showed that PS003biv decreased vaso-occlusion in both the liver and the ______.
Signup and view all the answers
Light sheet microscopy was used for ______ of RBCs.
Light sheet microscopy was used for ______ of RBCs.
Signup and view all the answers
Results indicated that PS003biv decreased ______ and coagulation activation.
Results indicated that PS003biv decreased ______ and coagulation activation.
Signup and view all the answers
The model for heme was used to provoke vaso-occlusion in SCD ______ state.
The model for heme was used to provoke vaso-occlusion in SCD ______ state.
Signup and view all the answers
Inhibition of factor Xa decreased plasma TAT levels and plasma IL-6 along with lowering numbers of ______ in the lungs.
Inhibition of factor Xa decreased plasma TAT levels and plasma IL-6 along with lowering numbers of ______ in the lungs.
Signup and view all the answers
Sickle mice treated with FII ASO showed significantly improved ______ compared to those administered control ASO.
Sickle mice treated with FII ASO showed significantly improved ______ compared to those administered control ASO.
Signup and view all the answers
Thrombin is both a central protease in hemostasis and a key modifier of ______ processes.
Thrombin is both a central protease in hemostasis and a key modifier of ______ processes.
Signup and view all the answers
In FIIlox/- sickle mice, there was a reduction in ______, which includes neutrophils and monocytes.
In FIIlox/- sickle mice, there was a reduction in ______, which includes neutrophils and monocytes.
Signup and view all the answers
The sickle cells induced an increase in ______ within the lungs.
The sickle cells induced an increase in ______ within the lungs.
Signup and view all the answers
Significant improvement was noted in SCD-associated end-organ damage, including nephropathy and ______ hypertension.
Significant improvement was noted in SCD-associated end-organ damage, including nephropathy and ______ hypertension.
Signup and view all the answers
Vascular congestion was pronounced in HbS/FIIWT mice but remarkably reduced in HbS/FIIlox/−mice due to ______ treatment.
Vascular congestion was pronounced in HbS/FIIWT mice but remarkably reduced in HbS/FIIlox/−mice due to ______ treatment.
Signup and view all the answers
Sickle cell disease patients may benefit from treatments such as hydroxyurea and ______.
Sickle cell disease patients may benefit from treatments such as hydroxyurea and ______.
Signup and view all the answers
Anti-thrombin plays a crucial role in the regulation of ______ in the coagulation cascade.
Anti-thrombin plays a crucial role in the regulation of ______ in the coagulation cascade.
Signup and view all the answers
Inhibition of the synthesis of the pro-thrombin was achieved by using ______.
Inhibition of the synthesis of the pro-thrombin was achieved by using ______.
Signup and view all the answers
Activation of coagulation in sickle cell mice is ______ dependent.
Activation of coagulation in sickle cell mice is ______ dependent.
Signup and view all the answers
Inhibition of TF has no effect on ______ or red blood cell maturation in sickle cell mice.
Inhibition of TF has no effect on ______ or red blood cell maturation in sickle cell mice.
Signup and view all the answers
In mouse models of SCD, inhibition of TF reduces inflammation and ______ cell activation.
In mouse models of SCD, inhibition of TF reduces inflammation and ______ cell activation.
Signup and view all the answers
Infiltration of ______ in the lungs and livers is increased in Berkeley sickle mice compared to WT controls.
Infiltration of ______ in the lungs and livers is increased in Berkeley sickle mice compared to WT controls.
Signup and view all the answers
Levels of ______ were increased in the lungs and livers of BERK mice.
Levels of ______ were increased in the lungs and livers of BERK mice.
Signup and view all the answers
Blocking TF attenuates neutrophil ______ into the lungs of BERK mice.
Blocking TF attenuates neutrophil ______ into the lungs of BERK mice.
Signup and view all the answers
In sickle cell mice, TF plays an important role in activation of ______ and inflammation.
In sickle cell mice, TF plays an important role in activation of ______ and inflammation.
Signup and view all the answers
The study used ______ antibodies to assess the effects of inhibiting TF.
The study used ______ antibodies to assess the effects of inhibiting TF.
Signup and view all the answers
Sickle cell disease leads to increased ______ cell activation in affected mice.
Sickle cell disease leads to increased ______ cell activation in affected mice.
Signup and view all the answers
Control mice were treated with ______ IgG for comparison in the experiments.
Control mice were treated with ______ IgG for comparison in the experiments.
Signup and view all the answers
Study Notes
Sickle Cell Disease Overview
- Sickle cell disease (SCD) is a global health problem, affecting approximately 3 million people worldwide.
- It's one of the most common genetic diseases.
- Newborn cases of sickle cell anemia in 2015 were distributed heavily in specific geographic areas (a map showing distribution is included in the presentation).
Sickle Cell Disease Definition
- A single base change (GAG to GTG) in the beta chain of human haemoglobin.
- This change results in the amino acid valine substituting glutamic acid, leading to the formation of hemoglobin S (HbS).
- HbS has the unique property of polymerizing upon oxygen delivery, forming long rigid fibers that distort red blood cells, causing sickling.
Sickle Cell Disease Pathophysiology
- A self-perpetuating vicious cycle leads to acute and chronic complications.
- Acute complications include vaso-occlusive crises, acute chest syndrome, stroke, thromboembolic events, and infections.
- Chronic complications include chronic anemia, spleen damage, and multi-organ damage.
- Key elements in the pathophysiology are: hemolysis, HbS polymerization, sickling, vaso-occlusion, and sterile inflammation.
Major Acute Symptoms
- Vaso-occlusive Painful Crisis: Sudden, throbbing pain following vaso-occlusion, affecting joints, extremities, and lower back; a leading cause of hospitalization.
- Acute Chest Syndrome: Presence of new pulmonary infiltrate, leading to chest pain, fever, dyspnea, and cough. Leading cause of death.
- Stroke: Blood vessel blockage or burst in the brain; a main cause of morbidity and mortality, leading to transient ischemic attacks (TIAs).
Sickle Cell Disease: Symptoms
- Almost every organ in the body can be affected due to microvessel involvement.
- The disease reduces life expectancy by about 30 years.
- The disease causes a poor quality of life.
Sickle Cell Disease Treatments
- Hematopoietic stem cell transplantation: A curative treatment involving bone marrow replacement with healthy stem cells.
- Hydroxurea: A supportive treatment that prevents oxidative damage to red blood cells (RBCs) and decreases endothelial cell adhesion.
- L-glutamine: A supportive treatment that prevents oxidative damage to RBCs.
- Voxelotor: A supportive treatment that helps with hemoglobin-oxygen affinity and inhibits HbS polymerization.
- Crizanlizumab: A supportive treatment that inhibits endothelial cell, platelet, and RBC interactions.
- Blood transfusion: A supportive treatment to help with anemia and stroke prevention.
Hypercoagulable State
- SCD patients show a hypercoagulable state, characterized by increased coagulation factors, reduced natural anticoagulants, and endothelial changes.
- Biomarkers include: Thrombin-antithrombin complexes, prothrombin fragment 1+2, D-dimer, and exposure of phosphatidylserine.
- Expression of tissue factor (TF) is increased during pain episodes.
Hypercoagulable State: Clinical Data
- Thromboembolic events (pulmonary embolism and deep vein thrombosis) in SCD patients are relatively common (up to 25%).
- High recurrence, but also high bleeding risk.
Coagulation in SCD Pathophysiology
- Coagulation in SCD is triggered by TF-exposing cells and red blood cells.
- Activation of coagulation increases inflammation and endothelial cell activation, forming a vicious cycle known as thromboinflammation.
- Inhibition of TF reduces inflammation and endothelial cell activation in mouse models.
Targeting Protein S in Sickle Cell Disease
- Protein S deficiency is frequent in SCD patients.
- It's associated with resistance to activated protein C.
- Rationale: The rationale behind targeting protein S is to reduce ongoing activation of coagulation, accelerated clearance of RBCs, and the role of protein S in the clearance of phosphatidylserine-exposing cells.
- PROSICK Study: A study investigating the role and potential pharmacological approach of targeting protein S in SCD.
PROSICK: Role of Protein S in SCD
- Role of PS deficiency in a mouse model of SCD (HbSS mice).
- Protein S in the pathogenesis of SCD in humans (cellular and ex-vivo approaches).
- Pharmacological approaches targeting PS, showing a potential positive effect on vaso-occlusion in the liver and lungs.
- Decreased hemolysis and coagulation activation in mice with PS003biv compared to controls in tests.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on sickle cell disease, including its genetic basis, transmission patterns, and implications on health. This quiz covers key facts about hemoglobin S, its effects on red blood cells, and related health issues. Perfect for biology students and health professionals alike!
