Pathophysiology Of Haematological Diseases

Pathophysiology of Haematological Diseases

Haematological diseases encompass a wide range of disorders affecting the blood and its components, including red blood cells, white blood cells, platelets, and plasma. These diseases can significantly impact a patient’s health and quality of life. For pharmacy students, understanding these conditions is crucial for effective patient care and management. This article aims to provide an in-depth overview of various haematological diseases, including iron deficiency anemia, megaloblastic anemia, sickle cell anemia, thalassemia, hereditary and acquired anemias, and hemophilia.

Table of Contents

Iron Deficiency Anemia

Iron deficiency anemia is the most common type of anemia worldwide, resulting from insufficient iron levels in the body. Iron is essential for the production of hemoglobin, the protein in red blood cells that carries oxygen.

Pathophysiology: Iron deficiency can occur due to inadequate dietary intake, increased iron requirements (e.g., during pregnancy), chronic blood loss (e.g., gastrointestinal bleeding), or malabsorption disorders. The lack of iron impairs hemoglobin synthesis, leading to the production of smaller and fewer red blood cells. This results in decreased oxygen-carrying capacity of the blood, causing hypoxia in tissues.

Clinical Manifestations: Patients with iron deficiency anemia may experience a range of symptoms, including fatigue, weakness, pallor, shortness of breath, and dizziness. Severe cases can lead to brittle nails, spoon-shaped nails (koilonychia), and pica (craving for non-nutritive substances like ice, dirt, or starch). Other symptoms may include headaches, cold hands and feet, and chest pain.

Diagnosis: Diagnosis involves a complete blood count (CBC) showing low hemoglobin and hematocrit levels, microcytic and hypochromic red blood cells, and low serum ferritin and iron levels. Additional tests may include total iron-binding capacity (TIBC) and transferrin saturation. A thorough patient history and physical examination are also essential to identify potential causes of iron deficiency.

Treatment and Management: Treatment includes dietary modifications to increase iron intake, such as consuming iron-rich foods like red meat, poultry, fish, legumes, and fortified cereals. Oral iron supplements, such as ferrous sulfate, are commonly prescribed. In cases of severe deficiency or malabsorption, intravenous iron therapy may be necessary. It is also crucial to address underlying causes of iron loss, such as gastrointestinal bleeding or heavy menstrual periods.

Megaloblastic Anemia

Megaloblastic anemia is characterized by the presence of large, abnormal red blood cells due to impaired DNA synthesis. It is commonly caused by deficiencies in vitamin B12 or folate.

Pathophysiology: Vitamin B12 and folate are crucial for DNA synthesis and red blood cell production. Deficiencies can result from poor dietary intake, malabsorption (e.g., pernicious anemia), or increased requirements (e.g., pregnancy). In vitamin B12 deficiency, the lack of intrinsic factor, a protein necessary for vitamin B12 absorption, can lead to pernicious anemia. Folate deficiency can result from inadequate dietary intake, alcoholism, or certain medications.

Clinical Manifestations: Symptoms include fatigue, weakness, pallor, glossitis (inflamed tongue), and neurological symptoms such as numbness, tingling, and cognitive disturbances (in vitamin B12 deficiency). Other symptoms may include diarrhea, weight loss, and a sore mouth or tongue.

Diagnosis : Diagnosis involves a CBC showing macrocytic anemia, elevated mean corpuscular volume (MCV), and low serum levels of vitamin B12 or folate. Additional tests may include serum methylmalonic acid and homocysteine levels, which are elevated in vitamin B12 deficiency. A Schilling test may be performed to diagnose pernicious anemia.

Treatment and Management: Treatment includes supplementation with vitamin B12 or folate, dietary modifications, and addressing underlying causes of deficiency. Vitamin B12 can be administered orally, intramuscularly, or subcutaneously, depending on the severity of the deficiency. Folate supplementation is typically given orally. It is also important to monitor and manage any neurological symptoms associated with vitamin B12 deficiency.

Sickle Cell Anemia

Sickle cell anemia is a genetic disorder characterized by the production of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells.

Pathophysiology : A mutation in the HBB gene causes the production of hemoglobin S, which polymerizes under low oxygen conditions, causing red blood cells to become rigid and sickle-shaped. These cells can obstruct blood flow, leading to vaso-occlusive crises and organ damage. The sickled cells have a shorter lifespan, leading to chronic hemolytic anemia.

Clinical Manifestations: Patients may experience episodes of severe pain, known as vaso-occlusive crises, which can affect various parts of the body, including the chest, abdomen, and joints. Other symptoms include anemia, jaundice, and complications such as stroke, acute chest syndrome, and organ damage. Chronic complications may include leg ulcers, gallstones, and delayed growth and development in children.

Diagnosis : Diagnosis involves a CBC showing anemia, sickle-shaped cells on a peripheral blood smear, and hemoglobin electrophoresis confirming the presence of hemoglobin S. Newborn screening programs can detect sickle cell disease early, allowing for prompt intervention and management.

Treatment and Management: Management includes pain relief, hydroxyurea therapy to reduce sickling episodes, blood transfusions, and bone marrow transplant in severe cases. Pain management may involve the use of nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and other analgesics. Hydroxyurea increases the production of fetal hemoglobin, which reduces the tendency of red blood cells to sickle. Regular blood transfusions can help prevent complications such as stroke. Bone marrow or stem cell transplant offers a potential cure but is associated with significant risks.

Thalassemia

Thalassemia is a group of inherited blood disorders characterized by reduced or absent production of one of the globin chains of hemoglobin.

Pathophysiology : Mutations in the genes encoding the alpha or beta globin chains result in imbalanced globin chain production, leading to ineffective erythropoiesis and hemolysis. Alpha thalassemia results from deletions or mutations in the alpha globin genes, while beta thalassemia results from mutations in the beta globin genes. The severity of the disease depends on the number and type of mutations.

Clinical Manifestations: Symptoms range from mild anemia to severe transfusion-dependent anemia, growth retardation, and complications such as iron overload and bone deformities. Patients with severe thalassemia may experience fatigue, weakness, pallor, jaundice, and hepatosplenomegaly. Chronic transfusions can lead to iron overload, causing damage to the heart, liver, and endocrine organs.

Diagnosis : Diagnosis involves a CBC showing microcytic anemia, hemoglobin electrophoresis, and genetic testing to identify specific mutations. Prenatal testing and genetic counseling are important for families with a history of thalassemia.

Treatment and Management: Management includes regular blood transfusions, iron chelation therapy to prevent iron overload, and bone marrow transplant in severe cases. Blood transfusions help maintain adequate hemoglobin levels and prevent complications such as growth retardation and bone deformities. Iron chelation therapy, using agents such as deferoxamine, deferasirox, or deferiprone, is essential to prevent iron overload from repeated transfusions. Bone marrow or stem cell transplant offers a potential cure but is associated with significant risks and requires a suitable donor.

Hereditary and Acquired Anemias

Hereditary anemias include conditions such as hereditary spherocytosis and glucose-6-phosphate dehydrogenase (G6PD) deficiency, while acquired anemias include aplastic anemia and anemia of chronic disease.

Hereditary Anemias

Pathophysiology: Genetic mutations affecting red blood cell membrane proteins or enzymes. Hereditary spherocytosis is caused by mutations in genes encoding proteins involved in the red blood cell membrane structure, leading to spherical-shaped cells that are prone to hemolysis. G6PD deficiency results from mutations in the G6PD gene, leading to reduced enzyme activity and increased susceptibility to oxidative stress.

Clinical Manifestations: Symptoms vary but may include anemia, jaundice, and splenomegaly. Patients with hereditary spherocytosis may experience hemolytic anemia, jaundice, and splenomegaly. G6PD deficiency can cause episodic hemolytic anemia triggered by infections, certain medications, or foods (e.g., fava beans).

Diagnosis: CBC, peripheral blood smear, and specific tests for enzyme activity or genetic mutations. Hereditary spherocytosis is diagnosed by the presence of spherocytes on a peripheral blood smear and increased osmotic fragility. G6PD deficiency is diagnosed by measuring G6PD enzyme activity in red blood cells.

Treatment and Management: Supportive care, splenectomy in severe cases, and avoidance of triggers (e.g., certain medications in G6PD deficiency). Patients with hereditary spherocytosis may benefit from folic acid supplementation and splenectomy to reduce hemolysis. G6PD deficiency management involves avoiding known triggers and providing supportive care during hemolytic episodes.

Acquired Anemias

Pathophysiology: Result from external factors such as autoimmune destruction of bone marrow (aplastic anemia) or chronic inflammation (anemia of chronic disease). Aplastic anemia is characterized by pancytopenia and hypocellular bone marrow, often resulting from autoimmune destruction of hematopoietic stem cells. Anemia of chronic disease is associated with chronic infections, inflammatory diseases, or malignancies, leading to impaired iron utilization and reduced erythropoiesis.

Clinical Manifestations: Symptoms include fatigue, pallor, and susceptibility to infections. Patients with aplastic anemia may present with symptoms of anemia (fatigue, pallor), thrombocytopenia (easy bruising, bleeding), and leukopenia (recurrent infections). Anemia of chronic disease typically presents with mild to moderate anemia, often without specific symptoms, but may include fatigue and weakness.

Diagnosis: CBC, bone marrow biopsy, and tests for underlying conditions. Aplastic anemia is diagnosed by a CBC showing pancytopenia and a bone marrow biopsy revealing hypocellularity. Anemia of chronic disease is diagnosed based on a CBC showing normocytic or microcytic anemia, low serum iron, low transferrin saturation, and elevated ferritin levels, along with the presence of a chronic inflammatory or infectious condition.

Treatment and Management: Immunosuppressive therapy, treatment of underlying conditions, and supportive care. Aplastic anemia treatment may include immunosuppressive therapy (e.g., antithymocyte globulin, cyclosporine), hematopoietic stem cell transplant, and supportive care (e.g., blood transfusions, antibiotics). Management of anemia of chronic disease focuses on treating the underlying condition and may include erythropoiesis-stimulating agents in certain cases.

Hemophilia

Hemophilia is a genetic bleeding disorder caused by deficiencies in clotting factors VIII (Hemophilia A) or IX (Hemophilia B).

Pathophysiology: Mutations in the F8 or F9 genes result in deficient or dysfunctional clotting factors, leading to impaired blood clotting and prolonged bleeding. Hemophilia A is more common than Hemophilia B and is caused by a deficiency in factor VIII, while Hemophilia B is caused by a deficiency in factor IX. Both conditions are inherited in an X-linked recessive pattern, primarily affecting males.

Clinical Manifestations: Patients may experience spontaneous bleeding, prolonged bleeding after injuries, and joint damage due to recurrent hemarthrosis. Common sites of bleeding include joints (hemarthrosis), muscles, gastrointestinal tract, and brain. Recurrent joint bleeding can lead to chronic arthropathy and disability. Severe cases may present with life-threatening bleeding episodes.

Diagnosis: Diagnosis involves measuring clotting factor levels, genetic testing, and family history. A prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time (PT) suggests a deficiency in intrinsic pathway factors. Specific assays for factor VIII and IX levels confirm the diagnosis. Genetic testing can identify mutations in the F8 or F9 genes.

Treatment and Management: Management includes replacement therapy with clotting factor concentrates, preventive measures to avoid bleeding, and emerging gene therapy approaches. Replacement therapy involves intravenous administration of recombinant or plasma-derived factor VIII or IX concentrates. Prophylactic treatment aims to maintain clotting factor levels above a certain threshold to prevent spontaneous bleeding. Patients are advised to avoid activities that increase the risk of bleeding and to use protective gear during sports. Gene therapy, which involves introducing a functional copy of the defective gene, is an emerging treatment option with the potential for long-term correction of the clotting factor deficiency.

Case studies

Iron Deficiency Anemia

Case Study: A 35-year-old woman presents to the clinic with complaints of fatigue, weakness, and shortness of breath on exertion. She also reports heavy menstrual periods for the past six months. On physical examination, she appears pale and has brittle nails. Laboratory tests reveal a hemoglobin level of 9 g/dL, mean corpuscular volume (MCV) of 70 fL, and serum ferritin of 8 ng/mL.

Discussion: This patient has iron deficiency anemia likely due to chronic blood loss from heavy menstrual periods. Treatment includes oral iron supplements and dietary modifications to increase iron intake. It is also important to address the underlying cause of heavy menstrual bleeding, which may involve referral to a gynecologist.

Megaloblastic Anemia

Case Study: A 60-year-old man presents with fatigue, pallor, and numbness in his hands and feet. He has a history of chronic gastritis and has been taking proton pump inhibitors for several years. Laboratory tests show a hemoglobin level of 10 g/dL, MCV of 110 fL, and low serum vitamin B12 levels. Further tests reveal elevated methylmalonic acid and homocysteine levels.

Discussion: This patient has megaloblastic anemia due to vitamin B12 deficiency, likely secondary to malabsorption caused by chronic gastritis and long-term use of proton pump inhibitors. Treatment includes intramuscular vitamin B12 injections followed by oral supplementation. Monitoring and managing neurological symptoms are also important.

Sickle Cell Anemia

Case Study: A 10-year-old boy with known sickle cell anemia presents to the emergency department with severe pain in his legs and abdomen. He has a history of frequent pain crises and has been hospitalized multiple times. On examination, he is in distress and has tenderness over his legs and abdomen. Laboratory tests show a hemoglobin level of 7 g/dL and elevated reticulocyte count.

Discussion: This patient is experiencing a vaso-occlusive crisis, a common complication of sickle cell anemia. Management includes pain relief with opioids, hydration, and oxygen therapy. Hydroxyurea therapy may be considered to reduce the frequency of pain crises. Regular follow-up and preventive care are essential to manage complications and improve quality of life.

Thalassemia

Case Study: A 5-year-old girl of Mediterranean descent presents with fatigue, pallor, and poor growth. Her parents report that she has been receiving blood transfusions every few weeks since infancy. Laboratory tests reveal a hemoglobin level of 6 g/dL, MCV of 60 fL, and elevated serum ferritin levels. Hemoglobin electrophoresis shows an abnormal pattern consistent with beta-thalassemia major.

Discussion: This patient has beta-thalassemia major, a severe form of thalassemia requiring regular blood transfusions. Management includes regular transfusions to maintain adequate hemoglobin levels and iron chelation therapy to prevent iron overload. Genetic counseling and consideration of bone marrow transplant as a potential cure are also important aspects of care.

Hereditary and Acquired Anemias

Hereditary Spherocytosis Case Study: A 15-year-old boy presents with jaundice, fatigue, and splenomegaly. He has a family history of anemia and jaundice. Laboratory tests show a hemoglobin level of 10 g/dL, MCV of 85 fL, and increased reticulocyte count. A peripheral blood smear reveals spherocytes, and an osmotic fragility test is positive.

Discussion: This patient has hereditary spherocytosis, a genetic disorder affecting red blood cell membrane proteins. Management includes folic acid supplementation and monitoring for complications such as gallstones. In severe cases, splenectomy may be considered to reduce hemolysis and improve symptoms.

Aplastic Anemia

Case Study: A 25-year-old woman presents with fatigue, easy bruising, and recurrent infections. Laboratory tests show pancytopenia with a hemoglobin level of 8 g/dL, white blood cell count of 2,000/µL, and platelet count of 50,000/µL. A bone marrow biopsy reveals hypocellular marrow with decreased hematopoietic cells.

Discussion: This patient has aplastic anemia, likely due to autoimmune destruction of hematopoietic stem cells. Treatment includes immunosuppressive therapy with antithymocyte globulin and cyclosporine, as well as supportive care with blood transfusions and antibiotics. Hematopoietic stem cell transplant may be considered for eligible patients.

Hemophilia

Case Study: A 7-year-old boy presents with recurrent joint swelling and pain, particularly in his knees and elbows. He has a family history of bleeding disorders. Laboratory tests show a prolonged activated partial thromboplastin time (aPTT) and low factor VIII levels, confirming a diagnosis of Hemophilia A.

Discussion: This patient has Hemophilia A, a genetic bleeding disorder. Management includes regular replacement therapy with factor VIII concentrates to prevent bleeding episodes and joint damage. Education on avoiding activities that increase the risk of bleeding and the use of protective gear during sports is also important. Emerging gene therapy approaches offer potential long-term solutions.

Conclusion

Understanding haematological diseases is essential for pharmacy students to provide effective patient care. Early diagnosis and appropriate management can significantly improve patient outcomes. Future advancements in treatment, such as gene therapy, hold promise for better management of these conditions. Pharmacy students should stay informed about the latest research and developments in haematology to provide the best care for their patients.