HAEMATOLOGY

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HAEMATOLOGY

• Week 7 Lecture Outline

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BLOOD CLOTTING DISORDERS, ANTICLOTTING AND
THROMBOLYTIC DRUGS

• 1. Normal hemostasis
• 2. Clotting disorders
• 3. Anticlotting
• thrombolytic drugs
• 4. Drug interactions

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BLOOD CELL DISORDERS

• 1. Disorders of white blood cells
• 2. Disorders of red blood cells
• 3. Anaemia

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HAEMATOLOGY

• Normal blood
• Blood cell production
• Functions
• Disorders

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NORMAL HEMOSTASIS

• Mechanisms of Hemostasis
• vessel spasm (constriction)
• platelet plug (250 000/ml, aggregation)
• coagulation (clot, more stable, fibrin clotting
  pathway - cascade)
• clot retraction (joining)
• clot resolution (fibrinolysis, plasmin)

• Balance between clot formation and lysis
• Prevent loss of blood from damaged vessels -
  clots at sites of injury
• Clots form also within blood vessels - hypoxia -
  infarction
• MI/stroke and hypercoagulable states

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CLOTTING DISORDERS

• Venous thrombosis - develop where blood flow is
  slow
• atherosclerosis, DM, smoking, cholesterol vs
• immobility, DVTs, CHF, oral contraceptives,
  pregnancy, malignancy

• Arterial thromboses - platelets adhere to wall
• HYPER-COAGULABILITY STATES
• increased platelet function vs increased clotting
  activity, xs coagulation

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BLEEDING DISORDERS

• impairment of blood coagulation associated with
  defects in platelets, coagulation factors and
  vascular integrity
• decrease in platelets (thrombocytopenia)
• decrease in platelet production (cancer)

• drug-induced -quinine
• idiopathic - thrombocytopenic purpura
• impaired platelet function - ASA
• impaired synthesis of factors V, VII, IX, XI,
  XII, vit K
• hereditary-hemophilia (factor VIII /A, IX/B,
  XI/C)
• vascular disorders

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ANTICLOTTING DRUGS - anticoagulants

• Heparin
• suppression of fibrin formation by promoting
  inactivation of clotting factors
• Warfarin
• antagonist of vitamin K, blocking synthesis of
  factors VII, IX, X
• Compare and contrast source, chemistry, kinetics
  - time course, indications, use in pregnancy,
  monitoring, reversal of overdose

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THROMBOLYTIC DRUGS

• Promote the conversion of plasminogen to plasmin
  which degrades fibrin clots, fibrinogen and other
  clotting factors
• Streptokinase, Alteplase (tPA/recombinant DNA
  technology), Urokinase
• Acute MI, DVT, massive PE
• Preparations, administration (w/in 4-6 hr),
  adverse effects (bleeding, allergic reaction,
  fever, reversal with aminocaproic acid)

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ANTIPLATELET DRUGS

• inhibit platelet aggregation by inactivating
  cyclo-oxygenase, enzyme responsible for
  thromboxane A2 synthesis which promotes platelet
  aggregation
• aspirin, sulfinpyrazone, dipyridamole
• reduce incidence of MI in patients with unstable
  angina and reduce occurrence of TIAs in patients
  with atherosclerosis

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DRUG INTERACTIONS

• Drugs that increase the effects of warfarin
• Drugs that promote bleeding
• Drugs that decrease the effects of warfarin
• warfarin vs heparin
• warfarin vs ASA and NSAIDs
• warfarin vs barbiturates, and many others

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DISORDERS OF WBCs

• 1. Neutropenia - decrease in neutrophils
• 2. Infectious mononucleosis - EBV
• 3. Leukemias - immature neoplastic cells
• acute vs chronic
• 4. Lymphomas - malignant neoplasms of lymphoid
  tissue (Hodgkins vs non-H)
• 5. Multiple myeloma - plasma cell cancer of
  osseous tissue
• 6. AIDS

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DISORDERS OF RBCs

• Red cell destruction
• Anaemia
• blood loss, haemolytic, hereditary disorders,
  deficiency types, bone marrow depression, chronic
  disease --- transfusion therapy
• Polycythemia - high total RBC mass
• Hyperbilirubinemia - increased bilirubin
• RBCs and Aging - decline of haemoglobin

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ANAEMIA

• IRON-DECIENCY ANEMIA
• body stores, absorption, dietary requirement and
  sources, metabolic function
• pathophysiology - increased demand
• symptoms - listlessness, fatigue, paleness
• diagnosis - hypochromic or microcytic RBC
• oral and parenteral iron

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ANAEMIA

• FOLIC ACID DEFICIENCY
• DNA synthesis
• poor diet, malabsortion
• megaloblastic anaemia, leukopenia,
  thrombocytopenia, kidney and GIT damage
• need to properly diagnose

• VITAMIN B12 DEFICIENCY (cyanocobalamins)
• DNA synthesis
• impaired absorption (intrinsic factor)
• megaloblastic anaemia and injury to the NS,