1. Thalassemia
    • Autosomal recessive inherited disease
    • Two forms: minor and major
    • Two types: alpha and beta
  2. Thalassemia minor
    • defective gene inherited from only one parent
    • affected person becomes a carrier with no symptoms
  3. Thalassemia major
    • defect gene inherited from both parents
    • abnormal form of hemoglobin results in excessive destruction of RBCs and anemia
  4. Alpha thalassemia
    • occurs when gene(s) related to alpha globin proteins are missing or mutated
    • ~14% African Americans are silent carriers
  5. Beta thalassemia
    • occurs when gene defects affect production of beta globin protein
    • ~10-15% Mediterranean and SE Asian descent have
  6. Diagnosis of thalassemia
    • found in early childhood - present with symptoms of severe anemia
    • physical exam shows enlarged spleen
    • blood sample shows small, abnormally shaped RBCs; anemia
    • Electrophoresis reveals abnormal forms of hemoglobin
  7. Treatment of thalassemia
    • blood transfusion
    • folate supplements
  8. Polycythemia vera
    • abnormal increase in # of blood cells (primarily RBC) produced by bone marrow
    • cause unknown, may be linked to abnormalities of chromosomes 8, 9, 13 & 20
    • two types; relative and absolute
    • most commonly seen in men 40-65
  9. Relative polycythemia vera
    • increase in RBC mass due to loss of plasma volume w/out corresponding decrease in RBC
    • due to dehydration or excessive use of diuretics
  10. Absolute polycythemia vera
    increase in mass of RBC, WBC and platelets in the absence of recognizable physical stimulus
  11. Signs/symptoms of polycythmia vera
    • neurological; dizziness, headaches, visual disturbances, itching/pain in fingers and toes
    • hypertension
    • tromboembolism
  12. Treatments of polycythemia vera
    all aimed at decreasing thickness of blood - phlebotomy, chemotherapy, pain meds, histamine 1 receptor antagonists (H1)
  13. Hemostasis
    the arrest of bleeding from an injured blood vessl requiring the combined activity of vascular responses, platelets and clotting factors
  14. Vascular responses to hemostasis
    • vasoconstriction
    • compression of wounded blood vessl
  15. Platelet reponses to hemostasis
    • platelets adhere to damaged tissue to form aggregates
    • mobilize clotting factors
  16. Clotting factors in hemostasis
    • interact to produce thrombin which fibrinogen to fibrin for strengthening the clot
    • (I don't think that "fibrinogen" is a verb. That sentence makes no sense)
    • something here is formed in the liver
    • Vitamin K is required to synthesize prothrombin and thrombin
  17. Thrombocytopenia
    • insufficient platelet levels associated with abnormal bleeding
    • results from one of three conditions; reduced platelet production, platelet trapping in spleen, increased platelet destruction
  18. Reduced platelet production
    • impaired platelet production in bone marrow
    • causes include diseases (leukemia, anemia), viral infections (HIV) or toxic chemicals (chemo drugs, heavy alcohol consumption)
  19. Platelet trapping in spleen
    enlarged spleen may harbor too many platelets leading to decreased platelet numbers in circulation
  20. Increased platelet destruction
    conditions; pregnancy, idiopathic thrombocytopenia purpura (ITP - immune system identifies platelets as a threat and forms antibodies), autoimmune (lupus, RA), bacteremia (bacteria in the blood), thromboti thrombocytopenic purpura (TTP - small blood clots suddenly form throughout body destroying large numbers of platelets), hemolytic uremic syndrome (associated with E. coli; causes sharp drop in platelets, destroys RBC, impairs kidney functions), certain medications (trigger immune system to destroy platelets)
  21. Diagnosis of thrombocytopenia
    • microscopic exam of blood
    • bone marrow biopsy
    • physical exam
  22. Treatment of thrombocytopenia
    • determine, then treat underlying cause (ya think?)
    • preventative measures
    • platelet transfusions
  23. Coagulation defects
    • coagulation is a complex process involving different plasma proteins or factors to control bleeding
    • involves forming a blood clot (thrombus) to prevent further blood loss from damanged tissues, blood vessels and/or organs
    • coagulation factors are synthesized by the liver and require Vitamin K for normal activity
  24. Factors involved in coagulation
    • Factor II (prothrombin)
    • Factor VII
    • Factor IX
    • Factor X
  25. Hereditary bleeding disorders
    inherited X-linked recessive diseases most often affecting males
  26. Hemophilia A
    • inherited; caused by deficiency in blood clotting factor VIII
    • mild to moderate symptoms - bleeding does not occur unless there is localized trauma (dental procedure, surgery)
    • severe - spontaneous bleeding may occur several times per month during childhood (GI bleeding, bleeding into joints); chronic bleeding and inflammation causes joint fibrosis, intracranial hemorrhage can lead to death
  27. Treatment of hemophilia A
    • replace missing clotting factor VIII
    • use of synthetic hormone desmopressin in mild cases
    • blood transfusion
    • genetically engineered clotting factor VIII
  28. von Willebrand disease
    • caused by deficiency in two blood clotting proteins - von Willebrand factor and blood clotting factor VIII
    • most common hereditary bleeding disorder, most cases are mild
    • usually diagnosed in adulthood
    • affects both men and women
    • bleeding may occur after surgery or tooth extraction
    • asprin and other NSAIDs may worsen condition
    • bleeding may decrease during pregnancy
  29. Diagnosis of von Willebrand disease
    • prolonged bleeding time
    • platelet aggregation test (count may be normal)
    • ristocetin cofactor test (von Willebrand factor level is reduced)
    • symptoms may develop suddenly (excessive or uncontrollable bleeding following surgery or childbirth at site of intravenous injection) or slowly (clots in veins are more common than bleeding, as in people with cancer
  30. Treatment of von Willebrand disease
    • lifestyle changes to minimize trauma
    • synthetic hormone desamino-8-arginine vasopressin
    • antihemophilic factor alphanate
    • blood plasma or clotting factor VIII
  31. Disseminated intravascular coagulation (DIC)
    • inherited; condition where small blood clots develop throughout the bloodstream, blocking small vessels
    • increased clotting depleted platelets and clotting factors needed to control bleeding, causing excessive bleeding
    • occurs in different disorders; sepsis, vascular endothelial injury, shock, obstetrical complications, neoplasms
  32. Pathogensis of DIC
    • involves release of thrombin into systemic circulation
    • systemic coagulation occurs
    • suppression of normal physiological anticoagulation processes
    • extensive clotting produces diffuse tissue damage, organ damage, consumptive coagulopathy (extensive bleeding due to depleted platelets and clotting factors)
  33. Diagnosis of von Willebrand disease
    blood tests (decreased platelet numbers, prolonged clotting time)
  34. Treatment of von Willebrand disease
    • ID and treat underlying cause (obstetrical cause, infection, cancer)
    • supportive medications (platelet transfusions, coagulation inhibitors, intravenous anticoagulants)
  35. Neutropenia
    • WBC - abnormally low number of neutrophils in blood
    • increases risk for bacterial and fungal infections
    • complication of medication that suppress cellular functions within bone marrow such as chemo, radiation therapy and immunosuppressant therapy
  36. Causes of neutropenia
    • bacterial infections
    • viral infections
    • allergic disorders
    • medications
    • autoimmune disorders
    • spleen disorders
    • cancer
    • toxins
  37. Treatment of neutopenia
    • colony-stimulating growth factors to stimulate production of WBC
    • corticosteroids may help if the neutropenia is caused by an autoimmune reaction
    • antithymocyte globulin to suppress activity of the immune system in disorders such as aplastic anemia
    • removal of enlarged spleen may cure the neutropenia resulting from hypersplenism
  38. Idiopathic hypereosinophilic syndrome
    • WBC - characterized by peripheral blood eosinophilia causing organ system dysfunction
    • directly related to eosinophilia in absence of parasitic, allergic or other causes of eosinophilia
    • occurs predominantly in men 20-50
    • organ dysfunction can develop - can be any organ but usually heart, lungs, spleen, skin, nervous system
    • cardiac involvement often causes morbidity and mortality
  39. Eosinophilic-myalgia syndrome
    • recognized in 1989 in NM in 3 patients who had an illness with a unique array of symptoms such as peripheral blood eosinophilia and myalgia
    • multi-organ disease characterized by elevated circulating eosinophils
    • associated with ingestion of OTC supplements containing L-tryptophan
    • symptoms may rand from self-limited myalgias and fatigue to potentially fatal illness characterized by skin changes, nervous system abnormalities and pulmonary arterial hypertension
Card Set
pharma II blood diseases pt 2