SICKLE CELL DISEASE
Overview:- Red blood cells and sickle cells
Sickle cell anemia is and of a group of inherited disorders known as sickle cell disease. It affects the shape of red blood cells, which carry oxygen to all parts of the body.
Red blood cells are usually round and flexible, so they move easily through blood vessels. In sickle cell anemia, some red blood cells are shaped like sickles or crescent moons. These sickle cells also become rigid and sticky, which can slow or block blood flow.
Signs and symptoms of sickle cell anemia usually appear around 6 months of age. They vary from person to person and may change over time.
SIGNS AND SYMPTOMS CAN INCLUDE:
Anemia: Sickle cells break apart easily and die. Red blood cells usually live for about 120 days before they need to be replaced. But sickle cells typically die in 10 to 20 days, leaving a shortage of red blood cells (anemia). Without enough red blood cells, the body can't get enough oxygen and this causes fatigue.
Episodes of pain: Periodic episodes of extreme pain, called pain crises, are a major symptom of sickle cell anemia. Pain develops when sickle-shaped red blood cells block blood flow through tiny blood vessels to your chest, abdomen and joints.
The pain varies in intensity and can last for a few hours to a few days. Some people have only a few pain crises a year. Others have a dozen or more a year. A severe pain crisis requires a hospital stay.
Some adolescents and adults with sickle cell anemia also have chronic pain, which can result from bone and joint damage, ulcers, and other causes.
Swelling of hands and feet. The swelling is caused by sickle-shaped red blood cells blocking blood circulation in the hands and feet.
Frequent infections: Sickle cells can damage the spleen, increasing vulnerability to infections. Infants and children with sickle cell anemia commonly receive vaccinations and antibiotics to prevent potentially life-threatening infections, such as pneumonia.
Delayed growth or puberty Red blood cells provide the body with the oxygen and nutrients needed for growth. A shortage of healthy red blood cells can slow growth in infants and children and delay puberty in teenagers.
Vision problems. Tiny blood vessels that supply the eyes can become plugged with sickle cells. This can damage the retina — the portion of the eye that processes visual images — and lead to vision problems.
Sickle cell anemia is a form of the inherited blood disorder, sickle cell disease. Sickle cell anemia affects your red blood cells, turning them from round flexible discs into stiff and sticky sickled cells. Sickled cells keep red blood cells from doing their job, which is carrying oxygen throughout your body. Sickled cells also don’t live as long as normal red blood cells. As a result, you don’t have enough healthy red blood cells and you develop anemia, the condition that gives sickle cell anemia its name.
In the past, babies born with sickle cell anemia rarely lived to be adults. Now, thanks to early detection and new treatments, about half of all people who have sickle cell anemia live into their 50s. People who have sickle cell anemia still face potentially life-threatening medical complications. However, healthcare providers have treatments that reduce the risk of complications and ease symptoms when they happen. (Unfortunately, there are many places in the world where people still don’t have access to effective medical treatment for sickle cell anemia.)
PEOPLE AFFECTED BY SICKLE CELL ANEMIA: -
Sickle cell anemia is rare in the United States, affecting about around 100,000 people. It mostly affects people whose ancestry links back to parts of the world where many people have malaria and carry a gene that provides partial protection against anemia. This gene also causes sickle cell anemia. In the United States, sickle cell anemia affects many people who are Black. It may also affect people from southern European, Middle Eastern or Asian Indian ancestry.
AFFECTION OF SICKLE CELL ANEMIA ON PEOPLE: -
Babies born with sickle cell anemia may not have symptoms for several months. When they do, symptoms include extreme tiredness or fussiness from anemia, painfully swollen hands and feet, and jaundice. Babies may also have spleen damage that affects their immune system and increases their risk for bacterial infections. As people with sickle cell anemia grow older, they may develop different and more serious medical problems that happen when organ tissues don’t receive enough oxygen. People with sickle cell anemia are at increased risk for stroke and lung, kidney, spleen and liver damage.
Sickle cell anemia is caused by a change in the gene that tells the body to make the iron-rich compound in red blood cells called hemoglobin. Hemoglobin enables red blood cells to carry oxygen from the lungs throughout the body. The hemoglobin associated with sickle cell anemia causes red blood cells to become rigid, sticky and misshapen.
For a child to be affected, both mother and father must carry one copy of the sickle cell gene — also known as sickle cell trait — and pass both copies of the altered form to the child.
If only one parent passes the sickle cell gene to the child, that child will have the sickle cell trait. With one typical hemoglobin gene and one altered form of the gene, people with the sickle cell trait make both typical hemoglobin and sickle cell hemoglobin.
Their blood might contain some sickle cells, but they generally don't have symptoms. They're carriers of the disease, however, which means they can pass the gene to their children.
For a baby to be born with sickle cell anemia, both parents must carry a sickle cell gene. In the United States, sickle cell anemia most commonly affects people of African, Mediterranean and Middle Eastern descent.
Sickle cell anemia can lead to a host of complications, including:
STROKE: Sickle cells can block blood flow to an area of the brain. Signs of stroke include seizures, weakness or numbness of the arms and legs, sudden speech difficulties, and loss of consciousness. If your child has any of these signs and symptoms, seek medical treatment immediately. A stroke can be fatal.
ACUTE CHEST SYNDROME: A lung infection or sickle cells blocking blood vessels in the lungs can cause this life-threatening complication, resulting in chest pain, fever and difficulty breathing. It might require emergency medical treatment.
PULMONARY HYPERTENSION: People with sickle cell anemia can develop high blood pressure in their lungs. This complication usually affects adults. Shortness of breath and fatigue are common symptoms of this condition, which can be fatal.
ORGAN DAMAGE: Sickle cells that block blood flow to organs deprive the affected organs of blood and oxygen. In sickle cell anemia, blood is also chronically low in oxygen. This lack of oxygen-rich blood can damage nerves and organs, including kidneys, liver and spleen, and can be fatal.
Splenic sequestration: A large number of sickle cells can get trapped in the spleen, causing it to enlarge and possibly causing belly pain on the left side of the body. This can be life-threatening. Parents of children with sickle cell anemia should learn to regularly feel their child's spleen for enlargement.
Blindness: Sickle cells can block tiny blood vessels that supply the eyes. Over time, this can lead to blindness.
Leg ulcers: Sickle cell anemia can cause painful open sores on the legs.
Gallstones: The breakdown of red blood cells produces a substance called bilirubin. A high level of bilirubin in the body can lead to gallstones.
Priapism : In this condition, men with sickle cell anemia can have painful, long-lasting erections. Sickle cells can block the blood vessels in the penis, which can lead to impotence over time.
Deep vein thrombosis: Sickling of red cells can cause blood clots, increasing the risk of a clot lodging in a deep vein (deep vein thrombosis) or a lung (pulmonary embolism). Either can cause serious illness or even death.
Pregnancy complications: - Sickle cell anemia can increase the risk of high blood pressure and blood clots during pregnancy. It can also increase the risk of miscarriage, premature birth and having low birth weight babies.
If you carry the sickle cell trait, seeing a genetic counselor before trying to conceive can help you understand your risk of having a child with sickle cell anemia. A genetic counselor can also explain possible treatments, preventive measures and reproductive options.
CAUSES OF SICKLE CELL ANEMIA IN GENERAL: -
People with sickle cell anemia inherit the disease from their biological parents. In sickle cell anemia, the gene that helps make normal red blood cells mutates, or changes. People who inherit the mutated hemoglobin protein gene from both biological parents have sickle cell anemia. People who inherit the mutated gene from one biological parent have the sickle cell trait.
Mutations in SCA:-
Normal red blood cells contain hemoglobin. Hemoglobin is a protein and the main part of red blood cells. When the hemoglobin gene mutates, it creates sickled cells that can’t navigate the network of blood vessels that carry oxygen, nutrients and hormones throughout your body. Here’s why:
Normal hemoglobin is soluble, meaning it dissolves in fluid. Abnormal hemoglobin isn’t as soluble and ends up forming solid clumps in your red blood cells.
Red blood cells need to be flexible to squeeze and slide their way through narrow blood vessels. Red blood cells carrying abnormal solid hemoglobin can’t do that. Instead, blood cells with abnormal hemoglobin end up blocking blood vessels and blood flow.
Normal red blood cells live about 120 days. Sickled cells self-destruct within 10 to 20 days. Normally, your bone marrow makes enough red blood cells to replace dying cells. When cells die earlier than usual, your bone marrow becomes like a factory struggling to match supply with demand. When the bone marrow factory can’t keep up, you don’t have enough red blood cells.
SIGNS AND SYMPTOMS OF SICKLE CELL ANEMIA:- symptoms typically start when babies are 5 to 6 months old. As they grow older, most people with sickle cell anemia have increased risk for developing new medical conditions. Some of these conditions are life-threatening. But by learning about conditions and symptoms, people with sickle cell anemia can seek help at the first sign of trouble so healthcare providers can treat the condition.
VASO-INCLUSIVE CRISIS (VOC):-
Healthcare providers may call this condition acute pain crisis. VOC, or acute pain crises, is the most common reason why people with sickle cell anemia go to the emergency room or need to spend time in the hospital.
Sudden intense pain.
Pain can be sharp or stabbing.
VOC may affect any part of your body, but typically affects your abdomen, lower back, arms and legs.
Living with VOC is one of the more difficult aspects of having sickle cell anemia. Among other symptoms and complications, people who have sickle cell anemia may feel depressed or anxious because they’re dealing with certain stigmas associated with the condition.
Healthcare providers sometimes call VOC the invisible illness because people who are having a pain crisis many times don’t have symptoms other than sudden excruciating pain that’s only eased with opioid painkillers.
Studies show sickle cell anemia carries a stigma linked to people’s need for opioid painkillers to manage VOC. Other studies show people who are members of racial minorities receive less pain medication and have to wait longer for pain medication than people who are white. Combined, these stigmas are a one-two-punch, as sickle cell anemia commonly affects people who are Black or Hispanic.
ACUTE CHEST SYNDROME (ACS): -
Acute chest syndrome is the most common complication of sickle cell anemia. It’s also the most common cause of death and the second most common cause of hospital admission. It happens when sickled cells clump and clog blood vessels in your lungs. Symptoms include:
- Sudden chest pain.
- Trouble breathing.
People who have sickle cell anemia may have mild, moderate or severe forms of anemia. Symptoms include:
Having skin color that’s more pale than usual.
Fatigue: This is feeling too tired to manage daily activities.
Trouble breathing: In addition to these symptoms, babies with anemia may be unusually fussy or irritable. Children may not grow as fast as other children their age or may enter puberty later than children their age.
Stroke: - Anyone who has sickle cell anemia is at risk for stroke, including babies. Approximately 11% of people with sickle cell anemia have strokes by age 20, and 24% have strokes by age 45. Here is information on stroke symptoms:
- Severe headache.
- Sudden weakness on one side of your or your child’s body.
- Change in alertness.
- Trouble speaking.
- Trouble seeing.
- Trouble walking.
- Splenetic sequestration
This happens when sickled cells become stuck in your spleen, forcing your spleen to get larger. Splenic sequestration often causes acute anemia. Symptoms include:
Pain in your upper left belly (abdomen).
Sometimes, children’s enlarged spleens are visible or can be felt through their skin.
People with sickle cell anemia have an increased risk for infections caused by Streptococcus pneumoniae, Haemophilus influenzae and non-Typhi Salmonella species. Symptoms include:
- Trouble breathing.
- Pain in bones.
About 35% of all people who are assigned male at birth (AMAB) who have sickle cell anemia develop priapism, or painful erections, that last four hours or more.
Leg ulcers: - About 2% of people with sickle cell anemia develop leg ulcers, usually after age 10. Leg ulcers are more common in people AMAB and people age 65 and older. Symptoms are painful sores that don’t heal. People often develop these sores on their ankles.
Pulmonary hypertension (PH):- About 6% to 11% of people with sickle cell anemia develop pulmonary hypertension (PH). Symptoms include:
- Racing pulse
- Fainting (passing out) or dizziness.
- Feeling short of breath during exercise or activity and difficulty breathing when at rest.
- Chronic kidney disease
- About 30% of people with sickle cell anemia have chronic kidney disease.
- A need to pee (urinate) more often.
- Loss of appetite.
- Swollen hands, feet and ankles.
- Shortness of breath.
- Blood in pee (hematuria) or pee that looks foamy.
- Puffy eyes.
- Dry and itchy skin (pruritus).
- Trouble concentrating.
- Trouble sleeping.
- Nausea or vomiting.
- Muscle cramps.
- High blood pressure (hypertension).
- Skin color that’s noticeably darker than usual.
- Detached retina
- Sickled cells can cause detached retinas by blocking blood vessels in your retinas.
- Common symptoms include:
- Seeing flashes of light.
- Seeing many floaters — flecks, threads, dark spots and squiggly lines that drift across your vision. (Seeing a few here and there is normal and not cause for alarm.)
- Darkening of your peripheral vision (side vision).
- Darkening or shadows covering part of your vision.
- Darkening or shadow covering part of your vision.
VASO-OCCLUSION: - Vaso-occlusion, or blood vessel occlusion, leading to ischemia is the predominant pathophysiology responsible for acute systemic painful vaso-occlusive crisis (VOC) and the requirement for emergency medical care by SCD patients. Intravital imaging studies done in transgenic humanized SCD mice and in vitro flow chamber studies done with SCD human blood over the past decade have contributed to the current understanding of vaso-occlusion as the interplay among impaired blood rheology, increased adhesiveness of erythrocytes with inflammatory cells and vascular endothelium, and hemostatic activation. The blood rheology is dictated by the hematocrit, plasma viscosity, and erythrocyte deformability. The increased plasma viscosity, which occurs as a result of chronic hemolysis and reduced sickle erythrocyte deformability due to Hb polymerization and dehydration, contributes to impaired flow of blood through capillaries and postcapillary venules of tissues with high oxygen demand. Poorly deformable sickle erythrocytes may become mechanically sequestered in the microcirculation to promote transient vaso-occlusion. Importantly, sickling-dependent damage of erythrocyte membranes also promotes exposure of adhesion molecules and binding motifs not normally expressed on erythrocytes, such as phosphatidyl serine (PS), basal cell adhesion molecule-1/Lutheran (B-CAM-1/Lu), integrin-associated protein (IAP), and intercellular-adhesion-molecule-4 (ICAM-4). As a result of chronic anemia, the bone marrow undergoes stress reticulocytosis and releases immature erythrocytes or reticulocytes, which are decorated with adhesion molecules such as α4β1 integrin (VLA-4) and CD36. Recent studies performed in SCD mice have also established a major role for adhesive interactions of erythrocytes and reticulocytes with inflammatory and endothelial cells in promoting vaso-occlusion in SCD.
Endothelial dysfunction and sterile inflammation (discussed below), which are hallmarks of SCD, may contribute to upregulation of selectins (P- and E-), vascular-cell-adhesion-molecule-1 (VCAM-1), ICAM-1, and major leukocyte chemoattractants such as KC (in mice) or interleukin-8 (IL-8) (in humans) on endothelial cells. The inflammatory milieu in SCD may also promote activation of neutrophils, monocytes, and platelets, leading to their increased adhesion to each other and to activated endothelium. Indeed, SCD patients are known to have elevated levels of neutrophils, monocytes and platelets at baseline, and elevated levels of circulating neutrophil-platelet and monocyte-platelet aggregates in SCD human blood correlate with disease severity. Also, thrombocytopenia is a major predictor of progression of VOC in SCD patients to the potentially lethal lung injury known as acute chest syndrome (ACS), suggesting a role for platelet sequestration at sites of vaso-occlusion. These clinical findings supported a role for inflammatory cells in vaso-occlusion and served as the impetus for several in vivo studies in transgenic SCD mice that led to the development of the current multicellular paradigm of vaso-occlusion.
Epidemiological evidence indicates that VOC is frequently initiated by an inflammatory or environmental stimulus, including infection, hypoxia, dehydration, acidosis, or other unidentified factors. Inspired by this clinical evidence, in vivo studies have been primarily conducted by challenging SCD mice with an inflammatory stimulus such as TNFα , heme, Hb , hypoxia, epinephrine , or lipopolysaccharide (LPS) to trigger vaso-occlusion. Importantly, these in vivo studies suggest that the cellular and molecular mechanisms of vaso-occlusion are also dictated by the type of organ or vascular bed. Using intravital imaging, Frenette and coworkers found that vaso-occlusion in the cremaster muscle microcirculation of TNFα-challenged SCD mice occurred primarily in postcapillary venules. Cremaster vaso-occlusion was initiated by P-/E-selectin-dependent neutrophil rolling followed by CD11a-CD18 (LFA-1) and CD11b-CD18 (Mac-1) β2-integrin-mediated firm arrest, E-selectin-dependent clustering of Mac-1 on arrested neutrophils, and capture of sickle erythrocytes by adhered neutrophils through binding of Mac-1 clusters to an unknown ligand on erythrocytes. Inhibition or deletion of endothelial E-selectin , neutrophil Mac-1, CXCR2 receptor for endothelial-expressed chemokine KC (CXCL-1), or reduction in circulating neutrophil counts using hydroxyurea attenuated vaso-occlusion in the cremaster microcirculation of SCD mice. These studies suggested a role for erythrocyte–neutrophil–endothelium adhesion in promoting vaso-occlusion in the systemic microcirculation. However, recent evidence also supports a role for platelet–neutrophil–endothelium adhesion in promoting systemic vaso-occlusion. Platelet nucleation on arrested neutrophils leading to platelet–neutrophil aggregation was also shown to promote vaso-occlusion in the cremaster microcirculation of TNFα-challenged SCD mice, which was mediated by P-selectin and Mac-1 on activated platelets and neutrophils, respectively. P-selectin upregulation and Mac-1 activation on platelets and neutrophils, respectively, was shown to be dependent on phosphorylation of serine/threonine kinase AKT2, as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2)-mediated reactive oxygen species (ROS) production.
DIAGNOSIS OF SCA: -
Healthcare providers diagnose sickle cell anemia by taking blood samples. They may use a technique called hemoglobin electrophoresis or high-performance liquid chromatography. This test identifies and measures different types of hemoglobin in red blood cells, including the abnormal hemoglobin that causes sickle cell anemia. (Starting in 2007, all babies born in the United States have sickle cell anemia tests right after they’re born. Early diagnosis and treatment are why fewer babies and young children born in the United States die of sickle cell anemia.)
CHANCES THAT MY CHILD WILL BE BORN WITH SICKLE CELL ANEMIA: -
That depends on whether you and/or your partner inherited sickle cell anemia or have sickle cell trait. Sickle cell trait isn’t a disease. People with sickle cell trait have a mixture of normal and abnormal hemoglobin in their red blood cells. They have enough normal hemoglobin in their red blood cells to prevent the cells from sickling. However, they do have an increased risk of having children with sickle cell anemia.
If you and your partner both have sickle cell trait, your child has a 25% chance of being born with sickle cell anemia. If only one of you has sickle cell trait, your child won’t be born with sickle cell anemia, but there’s a 50% chance that your child will be born with sickle cell trait. Studies estimated about 1 to 3 million people in the United States carry sickle cell trait, including about 8% to 10% of people who are Black.
PRENATAL SCREENING: - Healthcare providers can diagnose sickle cell anemia before your baby is born. They do this by taking a sample of the biological mother’s amniotic fluid or tissue from the biological mother’s placenta. Then, they examine the samples for signs of the sickle hemoglobin gene that causes the condition.
SICKLE CELL HEMOGLOBINOPATHIES COMPLICATING PREGNANCY: -
-Sickle cell hemoglobinopathies are hereditary disorders. It is caused by a point mutation in the β globin gene on chromosome II. This results in substitution of valine for glutamic acid at position 6 of the β-chain of normal hemoglobin. Gene mutation—when homozygous the individual has sickle cell anemia (Hb-SS). She has a small quantity of fetal hemoglobin (HbF) but no HbA. Heterozygous individual for sickle cell hemoglobin has sickle cell trait (HbAS). Such an individual has about 55–60% of HbA and 35–40% of HbS. Sickle cells have a life span of 5–10 days compared to normal RBCs of 120 days. The prevalence rate of sickle cell hemoglobinopathies is highest in Africa and ranges from 20% to 50%. HbC is produced when there is substitution of lysine for glutamic acid at the sixth postion of the globin-chain. HbC is less soluble than HbA and can cause hemolytic anemia. Management of these women with HbC is same as that of with women with HbSS. During crises these patients become profoundly thrombocytopenic and there is fall in hematocrit value.
Sickle cell-β-thalassemia-is observed when one β chain gene carries the sickle cell mutation and the other gene is deleted. Pregnancy outcome is similar to sickle cell anemia. Sickle cell trait: Hb-S comprises 30–40% of the total hemoglobin, the rest being Hb–A, Hb–A2 and Hb–F. If the husband is a carrier, there is 25% chance that the infant will be homozygous sickle cell disease and 50%—sickle cell trait. As such, preconceptional counseling should be done to know whether the husband also carries the trait or not. There is no special problem so far as reproductive performance is concerned. The patient will require iron supplementation. As the concentration of Hb–S is low, crisis is rare but can occur in extreme hypoxia. Hematuria and urinary infection are quite common. Sickle cell disease: Homozygous sickle cell disease (Hb–SS) is transmitted equally by males and females. Partner must be tested. Termination of pregnancy is an option if a fetus is diagnosed to have major hemoglobinopathy on prenatal diagnosis by CVS.
Pathophysiology: Red cells with HbS in oxygenated state behave normally but in the deoxygenated state it aggregates, polymerizes and distort the red cells to sickle. These sickle shaped cells block the microcirculation due to their rigid structure. This sickling phenomenon is precipitated by infection, acidosis, dehydration, hypoxia and cooling. The cells have got shorter life span and are more fragile. Increased destruction leads to hemolysis, anemia and jaundice.
(a) Refractory hypochromic anemia
(b) Identification by sickling test
(c) Persistent reticulocytosis (10–20%) (d) High fasting serum iron level
(e) Identification of the type of hemoglobinopathies by electrophoresis.
Effects on pregnancy: There is increased incidence of miscarriage (25%), prematurity, IUGR and fetal loss. Perinatal mortality is high. Incidence of preeclampsia, postpartum hemorrhage and infection is increased. Increased maternal morbidity is due to infection (UTIs), cerebrovascular accident and sickle cell crisis. Maternal death is increased up to 25% due to pulmonary infarction, acute chest syndrome, congestive heart failure and embolism. Effects on the disease:There is chance of sickle cell crisis which usually occurs in the last trimester. Two types are met —(1) hemolytic crisis and (2) painful crisis. Hemolytic crisis: It is due to hemolysis with rapidly developing anemia along with jaundice. There is associated leukocytosis and fever.
Painful (vaso-occlusive) crisis: It is due to vascular occlusion of the various organs by capillary thrombosis resulting in infarction. Organs commonly affected due to vaso-occlusion and infarction are: bones (osteonecrosis), kidney (renal medulla), hepatosplenomegaly, lung (infarction) and heart (failure), neurologic (seizures, stroke) and super added infections are high.
HOMOEOPATHIC MEDICINES FOR MANAGING SICKLE CELL HAEMOGLOBINOPATHIS: -
- There are many Homoeopathic remedies which may include: -
- Pulsatilla _nigricans
- Chininum sulph
- Natrum Mur
- Chininum Arsenicum
- Ferrum met