Hematologic Alterations Part 2

Normocytic Anemias

• Characteristics:
  • Normal erythrocyte size and hemoglobin levels, but a decreased number of erythrocytes overall.
• Types:
  • Aplastic anemia
  • Post-hemorrhagic anemia
  • Hemolytic anemia
  • Sickle cell anemia
  • Anemia of chronic diseases (cell size typically normal)

Aplastic Anemia

• Pathophysiology:
  • Bone marrow becomes suppressed, leading to hypocellularity.
  • Bone marrow has increased fat content.
  • Pancytopenia: Deficiency of all three blood cell types (RBCs, WBCs, and platelets).
• Types:
  • Primary acquired: Etiology is unknown.
  • Autoimmune: Cytotoxic T-cells cause bone marrow to fail to produce blood cells.
  • Secondary: Resolves upon removal of the offending agent (e.g., radiation, chemotherapy, certain drugs).
• Clinical Manifestations:
  • Symptoms reflect the most affected cell type and usually progress rapidly.
  • Hypoxemia and Pallor.
  • Weakness.
  • Rapid disease progression leading to death.
  • Infection, indicated by fever.
  • Bleeding.

Posthemorrhagic Anemia

• Cause: Acute blood loss.
• Effects:
  • Internal blood loss: Iron is recovered from destroyed RBCs.
  • External blood loss: Leads to severe iron deficiency, decreasing erythropoiesis.
• Unique Clinical Manifestations:
  • 0. 5 – 1 Liter blood loss: Cardiovascular compensation occurs.
  • Greater than 2 Liters blood loss: Poor cardiovascular compensation that progresses to shock.

Hemolytic Anemia

• Cause: Premature, accelerated destruction of erythrocytes before their normal lifespan of approximately 120 days.
  • Normally, erythropoietin from the kidney stimulates increased erythropoiesis to compensate.
  • In hemolytic anemia, the rate of hemolysis exceeds compensatory erythropoiesis, leading to anemia.
• Types:
  • Congenital Defects
    • Erythrocyte cell membrane defects
    • Hemoglobin synthesis defects (e.g., Sickle cell anemia)
  • Acquired
    • Autoimmune
    • Allogenic: Transfusion reactions due to mismatched RBCs
    • Allergic: Drug-induced
    • Mechanical: Prosthetic cardiac valve causing RBC destruction

Note: There is an image of a Hemolytic anemia blood smear from client with prosthetic heart valve

Hemolytic Anemia - Clinical Manifestations

• Jaundice
  • Heme destruction exceeds the liver’s ability to conjugate and excrete bilirubin.
• Aplastic Crisis
  • No bone marrow production of red blood cells.
• Skeletal Abnormalities
  • In children, expansion of erythroid bone marrow occurs during growth.

Sickle Cell Disease

• Description:
  • Abnormal form of Hemoglobin S within erythrocytes.
  • Autosomal recessive genetic mutation.
• Conditions Causing Sickling:
  • Hypoxemia.
  • Acidosis.
  • Dehydration.
  • Hypovolemia.
  • Hypothermia.
• Reversibility:
  • Sickling can reverse with improved arterial oxygen levels and hydration in some cases.
  • Some red blood cells remain sickled even with full oxygenation, making them vulnerable to hemolysis.

Note: Found in Chapter 30 pp.996-1003

Sickle Cell Disease - Pathophysiology

• Sickle-shaped RBCs:
  • Deliver less oxygen to tissues.
  • Cannot pass through small blood vessels, causing vascular occlusion.
  • Vascular occlusion causes pain.
  • Organ ischemia with possible infarction.
  • In the spleen, hemolysis of sickled cells leads to vascular stasis and infarction, resulting in atrophy and decreased function.

Sickle Cell Disease - Clinical Manifestations

• Usually appears at age 6-12 months.
  • Fetal Hemoglobin is replaced by Hemoglobin S.
• Isolated local manifestations.
  • Any body area with hypoxia.
• Chronic disease with acute exacerbations.
  • Pain.
  • Pallor.
  • Fatigue.
  • Jaundice.
  • Irritability.

Sickle Cell Crisis

• Vasoocclusive (thrombotic)
  • Precipitated by physiologic alterations that produce sickling.
  • Vascular occlusion and vasospasm.
• Aplastic
  • Transient cessation of RBC production.
• Sequestration
  • Pooling of blood in the liver and spleen.
• Hyper-hemolytic Anemia
  • Accelerated hemolysis.

Anemia of Chronic Diseases

• Definition
  • Mild to moderate anemia.
  • Normocytic, normochromic.
  • Associated with chronic systemic diseases (cancer, infections, autoimmune disorders).
  • Can be asymptomatic initially, progressing to symptomatic.
  • Can also present as microcytic and hypochromic.

Note: There is an image where part A is a normal blood smear and part B is displaying Microcytic, hypochromic smear

Anemia of Chronic Diseases - Pathophysiology

• Chronic inflammation precipitates anemia of chronic disease.
  • Increased release of cytokines by lymphocytes and macrophages.
  • Decreased erythrocyte life span.
  • Decreased erythropoietin production.
  • Ineffective bone marrow response to erythropoietin.
  • Altered iron metabolism or iron sequestration in macrophages results in iron deficiency.

Polycythemia

• Definition: Overproduction of RBCs.
• Causes:
  • Exogenous Causes: Radiation/drugs.
  • Endogenous Causes:
    • Physiologic compensation.
    • Immune disorders.

Polycythemia - Types

• Relative polycythemia
  • Hemoconcentration of blood due to dehydration.
• Absolute
  • Primary - Polycythemia vera - myeloproliferative
    • Increased RBC
    • Increased WBC
    • Increased Platelets
  • Secondary
    • Increased Erythropoietin secondary to hypoxemia.

Polycythemia - Clinical Manifestations

• Splenomegaly.
• Pain.
• Increased viscosity and thrombocythemia.
• Thrombosis (peripheral and GI organs).
• Plethora (red color of face, hands, feet, ears, mucous membranes).
• Vascular issues.
• Compensation by cardiovascular system.
• Peripheral circulatory alterations.

Alteration in Platelet Function

• Thrombocytopenia is the most common alteration.
  • Platelet count < 150,000 platelets per microliter.
  • Normal platelet count is influenced by age, sex, and ethnicity.
• Causes:
  • Decreased platelet production in bone marrow.
  • Increased breakdown of intravascular platelets.
  • Increased breakdown of extravascular platelets in the spleen or liver.
  • Hypersplenism may sequester platelets and produce lower lab values.
  • Hemodilution when > 10 units of blood are transfused in 24 hours.

Immune Thrombocytopenia Purpura (ITP)

• Most common cause of decreased platelet count after increased platelet destruction.
• Acute:
  • HIV-associated diseases are the most common cause.
  • Childhood - Usually due to viral infection with 1-2 months duration with complete remission but can become chronic.
  • Effect of condition that causes large amount of antigen such as drug allergy or another primary autoimmune disorder.
  • Newborn can have decreased platelets if thrombocytopenia during pregnancy.
• Chronic:
  • Drug therapy (glucocorticoids) is 1st line treatment to decrease immune activity, prevent sequestration, and platelet destruction.
  • IV immunoglobulin is a later option.
  • Splenectomy may be done to eliminate platelet sequestration.
    • Splenectomy leads to a lifelong increased risk of infection

Thrombocytopenia - Lab Data

• With minor trauma or surgery, spontaneous bleeding can occur when platelet count <50,000 per microliter.
• Without trauma, spontaneous bleeding can occur when platelet count <10,000-20,000 per microliter.
• Skin manifestations occur when <10,000 per microliter:
  • Petechiae, ecchymosis, purpura spots.
• Severe spontaneous bleeding can be fatal when involving the central nervous, gastrointestinal, or respiratory system.