NURS 212: Week 15 - Hematology Part 2

• Sickle cell disease


  Disorders characterized by the presence of an abnormal hemoglobin (Hb S)
• Point mutation


  Change in one nucleotide resulting in a change of one amino acid
• Sickle cell crisis


  1. Deoxygenation and dehydration cause the red cells to solidify and stretch into an elongated sickle shape

  2. Low oxygen levels lead to sickled cells
• Sickle cell disease


  One amino acid (valine) replaces another (glutamic acid) - A point mutation
• Sickle cell disease


  • Autosomal recessive inheritance
  • Both parents carry a recessive allele (Hb S)
  • Normal hemoglobin (HbA)
• Genotypes and Disease Outcomes


  • Sickle cell anemia (HbS and HbS)
  • Sickle cell trait (HbS and HbA) - (a carrier of SCD)
  • Sickle cell thalassemia (HbS and one thalassemia)
  • Sickle cell - hemoglobin C (HbS and either HbC or HgD) -(both C and D are abnormal hemoglobins)
• Sickle Cell Disease is inherited as an autosomal recessive trait.
• If a couple who are not affected has a child with SCD

  The chance that their next child will also have SCD is 25%
• Sickle Cell Anemia is inherited as a recessive trait, two recessive genes required to manifest the disorder
• Genotypes of the parents

  • HbA HbA
  • HbA HbS
  • HbS HbS
  • HbS HbA
• If a couple has a child with SCD

  The chance that their next child will also have SCD is 25%
• Pedigree of a recessive disorder like Sickle Cell Anemia


  • Unaffected female
  • Affected female
  • Affected male
  • Unaffected male
• Sickle Cell Disease


  • Occlusive crisis results in pain
  • Deformed RBC are prone to adhesion and coagulation leading to occlusion of blood vessels and ischemia in the affected limb - PAIN
  • Supplemental O2 helps prevent further sickling and reverts some of the RBCs that have started to sickle back to normal shape
  • Hepatomegaly and splenomegaly can happen if the portal vein (delivers blood to liver and spleen) is restricted by sickled cells occluding the veins
• Sickle Cell Disease


  • ↑ destruction of RBCs
  • ↓ Hct, hematuria (microscopic), ↑ bilirubin in serum leading to jaundice
  • Hydroxyurea (a drug used in SCD to reduce the need for blood transfusions) Increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia
• Thalassemias


  • Autosomal recessive disorders
  • Synthesis of the globin chains of the hemoglobin molecule is slowed or defective
• Thalassemia Genotype Contribution


  • Major: homozygous
  • Minor: heterozygous
• Populations with high prevalence of Thalassemia


  • Greeks
  • Italian
  • Arabs
  • Sephardic Jews
  • Chinese
  • Vietnamese
  • Cambodians
  • Laotians
• Beta Thalassemia


  Beta chains are affected
• Beta-thalassemia minor


  Mild condition
• Beta-thalassemia major (Cooley anemia)


  Life-threatening condition
• Alpha Thalassemia


  • The alpha chains are affected
  • There are 4 genes associated with alpha chains
  • Mutations in 1 or 2 genes usually do not cause health problems (maybe mild anemia)
  • More severe symptoms with Mutations in 3 or all 4 genes
  • Hemoglobin H disease (3 mutations) – Mild to moderate anemia
  • Alpha-thalassemia major (4 mutations) - hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome
• Myeloproliferative red cell disorders


  Thrombocytopenia and Polycythemia
• Polycythemia


  • An increase in the absolute red blood cell (RBC) mass in the body with Increased viscosity and volume of the blood - (with ↑Hgb and↑ Hct)
  • Relative – hemoconcentration of the blood associated with dehydration –RBCs normal, Blood volume is abnormal
  • Absolute – two forms: Primary (polycythemia vera) a stem cell disorder with hyperplastic and neoplastic bone marrow alterations characterized by an abnormal uncontrolled proliferation of RBCs, and Secondary – most common, physiologic response to erythropoietin secretions caused by hypoxia.
• Polycythemia


  • Clinical significance: risk of thrombotic events due to hyperviscosity of the blood. (And potential for progression to leukemia in cases of polycythemia vera)
  • Clinical manifestations result from the increased number of RBCs and hematocrit
  • Abnormal blood flow that increases blood viscosity, creating a hypercoagulable state
  • Tissue injury (ischemia) and infarction with blood vessel blockage
  • Plethora (ruddy, red color of the face, hands, feet, ears, and mucous membranes)
  • Headache, drowsiness, delirium, mania, psychotic depression, chorea, and visual disturbances
  • Will frequently see an enlarged spleen with abdominal pain and discomfort
• Thrombocytopenia


  • Platelet count <150,000/mm3
  • <50,000/mm3: hemorrhage from minor trauma
  • <15,000/mm3: spontaneous bleeding
  • <10,000/mm3: severe bleeding
  • Causes: Decreased platelet production or increased platelet consumption or both
  • Congenital or acquired (secondary to viral infections, drugs, nutritional deficiencies, chronic renal failure, radiation therapy, cancer of the bone marrow)
• Thrombocytopenia


  • Causes: Most common forms result from increased platelet consumption
  • Heparin-induced, idiopathic (immune), thrombotic, and disseminated intravascular coagulation (DIC)
  • Individuals who have thrombocytopenia are at increased risk for venous or arterial thrombosis because a prothrombotic state is caused by antibody binding to platelets that cause activation, aggregation and consumption
  • Venous thrombi is more common
• Immune (idiopathic) thrombocytopenic purpura (ITP)


  • The chronic form has IgG autoantibody that targets platelet glycoproteins
  • Antibody-coated platelets are sequestered and removed from the circulation
  • An acute form of ITP often develops after a viral infection and is one of the most common childhood bleeding disorders
• Heparin-induced thrombocytopenia (HIT)


  • ~4% of patients develop HIT (if using unfractionated heparin)
  • Incidence is lower if you use low-molecular weight heparin
  • Adverse drug reaction caused by IgG antibodies against heparin-platelet factor 4 complex
  • ↓ of 50% of platelets seen in 90% of patients
  • Decreased counts begin day 5 – 10 after administration
• Thrombocytopenia: Manifestations


  • Decreased platelet counts
  • Minor bleeding problems: Petechia and purpura
  • Bleeding from mucosal sites (epistaxis, hematuria, menorrhagia, bleeding gums)
  • Intracranial bleeds or internal bleeding is rare
• Petechia, Purpura and Eccyhmoses


  • Petechia: a small (<3 mm) red or purple spot caused by bleeding into the skin
  • Ecchymoses
  • Purpura: (>3 mm) bleeds - a rash of purple spots on the skin caused by internal bleeding from small blood vessels
  • These bleeds in the skin do not blanch when pressed
• von Willebrand Disease


  • von Willebrand factor is necessary for stabilization of factor VIII in circulation and for normal adherence of platelets to damaged vessels. (von Willebrand factor and factor VIII circulate in blood as a complex)
  • Decreased or absent levels of von Willebrand factor leads to bleeding
  • Epistaxis, mucosal bleeding, echymoses, GI bleeding, and menorrhagia are common (hemarthrosis is rare)
  • Inherited as an autosomal dominant disorder
  • Both men and women affected
• Vitamin K deficiency


  • Vit K deficiency will increase bleeding
  • Vit K is a fat soluble vitamin that is required for the complete synthesis and function of coagulation proteins (factors II, VII, IX, X) and coagulation inhibitors (protein C and protein S)
  • Vit K obtained from food (liver, cheese, butter, egg yolks, and green, leafy vegetables) and synthesized in the gut by intestinal flora and stored in the liver
  • Absorption depends on bile acids and adequate mucosal function in the intestines
• Vitamin K Deficiency


  • Newborns – may be related to liver-immaturity and the lack of vit K synthesis in the intestine until the gut is colonized with the necessary flora
  • Liver dysfunction can lead to deficient clotting factors as well as insufficient vit K
  • Coumadin-type drugs are vit K antagonists that inhibit the normal activity of vit K in the synthesis of clotting factors
• Disseminated Intravascular Clotting (DIC)


  • Acquired syndrome (complication) in which clotting and bleeding occur simultaneously
  • Widespread clotting in small vessels lead to blood vessel occlusion and tissues ischemia and consumption of clotting factors and platelets which may lead to hemorrhage
• Predisposing conditions that can initiate DIC

  • Acute: Shock: hemorrhagic, cardiogenic, anaphylactic
  • Septicemia
  • Hemolysis: d/t mismatched blood transfusions or acute hemolysis from infections
  • Obstetric: abruptio placentae, amniotic fluid embolism, septic abortion
  • Cancers
  • Crush – tissue injury
  • Burns, trauma, heatstroke, snakebites
• DIC


  1. Stimulus activates clotting cascade

  2. Intravascular thrombin is produced

  3. Catalyzes fibrinogen to fibrin and platelet aggregation

  4. Widespread fibrin and platelet deposition in capillaries and arterioles

  5. Causing thrombosis

  6. This excessive clotting activates fibrinolytic system

  7. Breaks down clot to from fibrin split products or fibrin degradation products (FDP)

  8. FDP is anticoagulant and inhibit clotting

  9. Accumulation of FDP and consumption of clotting factors results in inability to form stable clots

  10. Causes bleeding
• DIC Clinical Manifestations


  • Clinical course varies from acute, severe process that may be life threatening to chronic condition with lab abnormalities
  • Symptoms relate to bleeding or thrombosis:
  • Bleeding: petechiae, purpura or hemorrhage (leading to cardiovascular shock)
  • Bleeding from any orifice and any puncture
  • Thrombosis: ischemia and necrosis from thrombosis to organs like kidneys, heart, lungs and brain
• •Symptoms relate to bleeding or thrombosis:

  –Bleeding: petechiae, purpura or hemorrhage (leading to cardiovascular shock)

  •Bleeding from any orifice and any puncture

  –Thrombosis: ischemia and necrosis from thrombosis to organs like kidneys, heart, lungs and brain
• The spleen also stores platelets and produces antibodies that fight infection.
• The spleen filters blood to remove old or damaged red cells, bacteria, and other foreign particles.