Blood

• Hemostasis: Prevents excessive bleeding and propagation of clotting beyond the site of injury
• Phases of hemostasis:

  • Vascular phase: brings about vasoconstriction to reduce blood flow
  • Reflex sympathetic activity releases Norepinephrine & epinephrine, activating alpha-1 receptor to constrict blood vessels
  • Platelet phase: induces platelet aggregation through Thromboxane A2 and ADP
  • Coagulation phase: produces clotting factors through extrinsic and intrinsic pathways to promote coagulation
  • Fibrinolysis phase: degrades fibrin and fibrinogen to prevent clot propagation
• Hemostasis disorders:

  • Vascular disorders: sympathetic activity not intact, leading to vessel constriction issues
  • Platelet disorders: Thrombocytopenia (persistent decrease in platelets) due to reduced production or increased destruction, abnormal pooling in spleen; Thrombocytosis (abnormal increase in platelets)
  • Coagulation disorders: Impaired coagulation due to Factor VIII deficiency (hemophilia A), Factor IX deficiency (Christmas disease/hemophilia B), Vit K deficiency (hypoprothrombinemia)
• Vitamin K:

  • Physiological role: activates liver receptor to promote production of clotting factors
  • Causes of deficiency: inadequate intake, reduced absorption due to obstructive jaundice or chronic intestinal disorder, reduced utilization due to liver issues or drug-induced factors
• Fibrinolysis inhibitors:

  • Increased fibrinolysis: treated with aminocaproic acid
  • Reduced fibrinolysis: treated with plasmin or plasminogen activator
• Treatment of bleeding disorders:

  • Objectives: promoting platelet aggregation, promoting coagulation, inhibiting fibrinolysis
  • Classes of drugs: Platelet aggregation promoters (ADP), Coagulants (Vitamin K), Fibrinolytic inhibitors (Aminocaproic acid, Tranexamic acid)
• Treatment of coagulopathy:

  • Objectives: inhibiting platelet aggregation, inhibiting coagulation, promoting fibrinolysis
  • Classes of drugs: Platelet aggregation inhibitors (COX inhibitors, ADP inhibitors, Phosphodiesterase inhibitors), Fibrinolytics (streptokinase, urokinase), Anticoagulants (Heparin, Warfarin)
• Heparin:

  • Found in mast cells of liver, lungs, and intestinal mucosa
  • Acts by activating plasma antithrombin III to decrease thrombin and factors IXa, Xa, Xia, XIIa
  • Antagonized by protamine sulfate
• Oral anticoagulants (Vitamin K Antagonists):

  • Inhibit Vitamin K epoxide and reductase to decrease factor II, VII, IX, X
  • Effective only in vivo, slow onset of action
• Anticoagulants are effective only in vivo, not in vitro because there is no liver in vitro
• Anticoagulants have a slow onset of about 2-3 days because they only affect the newly synthesized factors; the already present factors will keep working until they expire
• Anticoagulants are bound to plasma proteins (95%)
• Anticoagulants cross the placental barrier and are secreted in milk
• All anticoagulants cross because they are lipid-soluble, so they are not given during pregnancy and lactation
• Anticoagulants are metabolized in the liver and excreted in urine since they are lipid-soluble
• Uses of anticoagulants include:

  • Open heart surgery (heparin)
  • Deep venous thrombosis (heparin, warfarin)
  • Pulmonary embolism (heparin, warfarin)
  • Arterial embolism (heparin, warfarin)
  • Disseminated intravenous coagulation due to exhausted clotting factors (heparin)
  • Acute myocardial infarction (warfarin)
  • Cerebrovascular disease; i.e. stroke (warfarin)
• Adverse drug reactions of anticoagulants include bleeding, thrombocytopenia (heparin), and allergy
• Contraindications for anticoagulants:

  • Hemorrhage
  • Ulcers of GIT
  • Recent stroke
  • Threatened abortion
  • Hypertension
  • Allergy
  • Pregnancy (warfarin)
  • Lactation (warfarin)
• Drug interactions that increase the effect of anticoagulants include antibacterials, paraffin, phenylbutazone, cimetidine, and aspirin
• Drug interactions that reduce the effect of anticoagulants include cholestyramine, aluminum hydroxide gel, barbiturates, and estrogen
• Causes of anemia:

  • Blood loss (hemorrhage anemia)
  • Increase rate of RBC destruction (hemolytic anemia)
  • Decrease rate of RBC production
• Types of anemia:

  • Aplastic anemia due to bone marrow depression
  • Iron deficiency anemia (microcytic-hypochromic anemia)
  • Vitamin deficiency anemia (megaloblastic or macrocytic-hyperchromic anemia)
• Iron deficiency anemia:

  • Daily iron requirements are 0.5 – 1.0 mg for adult male
  • Causes include nutritional deficiency, chronic blood loss, and chronic nose bleeding
• Treatment of iron deficiency anemia includes adequate food intake, correction of the cause, and iron supplementation
• Iron preparation:

  • Oral forms include inorganic (ferrous sulfate) and organic iron (ferrous gluconate, fumerate, succinate, glutamate)
  • Parenteral forms include organic iron only (iron dextran, dextriferrin, iron sorbitol)
• Iron toxicities:

  • Oral preparations can cause irritation of the GIT resulting in mucosal damage, gastric discomfort, nausea/vomiting, and diarrhea
  • Parenteral preparations can lead to flushing, nausea, vomiting, and allergy
• Vitamin B-12:

  • Obtained from animal products
  • Daily requirements are 2-5 micrograms
  • Functions include DNA synthesis and nerve integrity
• Causes of Vitamin B-12 deficiency:

  • Inadequate food intake
  • Malabsorption due to gastric gland atrophy or tapeworm infestation
  • Depletion of hepatic stores due to absence of transcobalamin II
• Folic acid:

  • Obtained from liver and green plants
  • Daily requirement is 50-100 micrograms
  • Physiological function is the synthesis of DNA
• Causes of folic acid deficiency:

  • Less dietary intake
  • Malabsorption due to intestinal disorder
  • Impaired utilization due to liver damage or drug-induced inhibition