Hematology and Oncology

Overview of Hematology and Oncology in Pharmacology

  • Subject: Study of blood and cancer, with focus on hematology.

  • Review physiology related to blood clot formation and medications.

  • Objectives for the week include understanding clotting components, IV products, and brief chemotherapy overview.

Clot Formation (Hemostasis)

Clotting Components

  • Platelets: Circulate in an inactive state until activation.

  • Fibrin: A protein that forms clots, derived from fibrinogen.

  • Hemoglobin (HGB): Protein in red blood cells that binds oxygen for transport.

    • A single red blood cell contains approximately 270 million hemoglobin molecules, compared to populations of major cities.

Activation of Hemoglobin

  • Hemoglobin binds to oxygen in oxygen-rich environments (lungs) and releases it in low oxygen environments (muscle cells).

    • Hem Component: Contains iron that bonds to O2, essential for hemoglobin creation.

    • Anemia: Condition where there's a low hemoglobin count due to insufficient iron or other components.

Mechanism of Clotting (Hemostasis)

  • Baseline State: Bloodstream maintains balance between clotting and bleeding via chemicals like nitric oxide to keep platelets non-sticky.

  • Injury Response:

    1. Vascular Injury: Injury to blood vessel exposes collagen and tissue factors, triggering platelet adhesion.

    2. Platelet Activation:

    • Platelets adhere to collagen via receptors and bind with von Willebrand factor (vWF).

    • Activated platelets change shape to become spiky and sticky, releasing chemicals such as ADP and thromboxane A2.

Clotting Cascade

  • Series of biochemical reactions leading to clot formation.

  • Tissue factor initiates the cascade, activating Factor X, leading to the conversion of prothrombin to thrombin, which then converts fibrinogen to fibrin.

    • Fibrin forms a stabilizing spiderweb mesh that solidifies the clot.

  • Vitamin K: Necessary for synthesizing several clotting factors, including Factor X.

    • Warfarin is a vitamin K antagonist that disrupts clotting processes.

Analogy for Clotting Process

  • Reference to Marvel Universe:

    • Platelets likened to police responding to an explosion (tissue damage).

    • Activated platelets release signals (siren) to recruit more platelets and initiate clotting (Spiderman analogy).

    • Eventually, fibrinogens act like webs to stabilize and form a clot.

Dissolution of Clot (Fibrinolysis)

  • Scabbing process represents clot dissolution, using plasmin to cut fibrin mesh and promote healing.

Review of Clotting Medications

Heparins and Derivatives

  • Unfractionated Heparin (UFH): First generation heparin, used for rapid anticoagulation, only IV.

  • Low Molecular Weight Heparins (LMWH): Examples include Enoxaparin (Lovenox) and Fondaparinux (Arixtra), used for less acute scenarios, mostly subcutaneous.

    • Mechanism: Bind to and activate antithrombin, enhance its activity on Factor Xa, thrombin.

    • Antidote: Protamine sulfate is used to reverse heparin action but is ineffective against LMWHs.

Monitoring and Risks

  • Activated Partial Thromboplastin Time (aPTT): Monitor for unfractionated heparin toxicity to ensure therapeutic levels (usually 60-80 seconds is the target).

  • Hemorrhage Risks: Be vigilant for signs of bleeding, especially in patients on anticoagulation.

  • HIT (Heparin-Induced Thrombocytopenia): Immune response leading to low platelet counts and paradoxical increased clotting risk requires immediate heparin discontinuation and alternative anticoagulant administration.

Vitamin K Antagonists

  • Warfarin (Coumadin): Inhibits vitamin K effects, requires INR monitoring.

    • Therapeutic range: 2-3 for most conditions; higher for prosthetic heart valves.

    • Risks include bleeding, and dietary considerations regarding vitamin K-rich foods must be consistent.

Direct Oral Anticoagulants (DOACs)

  • Direct inhibitors of thrombin (Dabigatran) and Factor Xa (Rivaroxaban, Apixaban).

    • Advantages: No routine monitoring needed, once-daily dosing.

    • Caution: Not suitable for patients with mechanical heart valves or severe renal impairment.

Antiplatelet Medications

  • Used to prevent platelet aggregation in conditions like ST elevation myocardial infarction (STEMI).

  • Major agents: Aspirin, Clopidogrel (Plavix), and others.

    • Dual antiplatelet therapy after stent placement or heart attack should be maintained to prevent reocclusion.

Thrombolytics (Clot Busters)

  • Activators such as Tissue Plasminogen Activator (tPA) should only be used in acute ischemic scenarios, not in bleeding disorders.

    • Caution with blood pressure management to prevent hemorrhagic complications.

IV Products

Erythropoietin (EPO)

  • Stimulates red blood cell production, often used in chronic kidney disease and can elevate blood pressure as a side effect.

Iron Supplementation

  • Iron deficiency treated with Ferrous sulfate orally or under monitored IV conditions (IV iron sucrose).

    • Monitor hemoglobin, hematocrit, and ferritin levels for effectiveness.

Blood Products

  • Types of Products:

    • PRBC’s (Packed Red Blood Cells): For severe anemia (<7 HGB).

    • Must be matched for type (ABO and Rh).

    • Platelets: For very low counts and administered quickly without type and cross-matching.

    • Fresh Frozen Plasma (FFP): Contains clotting factors, needs to be thawed and administered swiftly.

    • Cryoprecipitate: Concerns specific factors and used based on significant clotting factor deficiencies.

Blood Transfusion Reactions

  • Recognize signs of acute hemolytic reactions, febrile reactions, transfusion-associated circulatory overload (TACO), and sepsis.

  • Monitor vital signs and manage IV lines accordingly during transfusion processes.

Chemotherapy Overview

  • Cytotoxic Chemo: Rapidly dividing cancerous cells are targeted but healthy cells are also affected, leading to side effects such as nausea, hair loss, and myelosuppression (hemorrhage risk).

  • Examples: Methotrexate and Mercaptopurine, which interrupt DNA synthesis.

  • Hormonal Therapies: Tamoxifen as an estrogen receptor blocker reduces estrogen-driven tumor growth; associated risks include increased endometrial cancer risk and thromboembolic events.

These notes are designed to give a comprehensive understanding of hematology oncology within pharmacology, capturing all relevant details from the lecture. Please study thoroughly to grasp all mechanisms, risks, and medications discussed.

Adverse Effects

  • Unfractionated Heparin (UFH): Bleeding, thrombocytopenia, osteoporosis (long-term use).

  • Low Molecular Weight Heparins (LMWH): Similar to UFH, with less risk of HIT but still potential for bleeding.

  • Warfarin (Coumadin): Major risks include excessive bleeding, skin necrosis, and teratogenic effects.

  • Direct Oral Anticoagulants (DOACs): Risk of bleeding, especially gastrointestinal; less risk of drug-drug interactions compared to warfarin.

  • Antiplatelet Medications: Risks include bleeding and gastrointestinal upset.

  • Thrombolytics (tPA): Major risk of bleeding, especially hemorrhagic stroke.

Drug-Drug Interactions

  • Unfractionated Heparin: Increased bleeding risk with other anticoagulants, NSAIDs, and some antibiotics.

  • LMWH: Similar interactions as UFH; caution with other anticoagulants.

  • Warfarin: Interacts with many medications (e.g., antibiotics can increase INR; NSAIDs can increase bleeding risk).

  • DOACs: Should be used cautiously with strong CYP3A4 and P-glycoprotein inhibitors.

  • Antiplatelet Medications: Increased bleeding risk with anticoagulants and NSAIDs.

  • Thrombolytics: Must avoid concomitant use with anticoagulants.

Generic Names

  • Unfractionated Heparin: Heparin sodium.

  • Low Molecular Weight Heparins: Enoxaparin (Lovenox), Fondaparinux (Arixtra).

  • Warfarin: Warfarin sodium.

  • DOACs: Dabigatran (Pradaxa), Rivaroxaban (Xarelto), Apixaban (Eliquis).

  • Antiplatelet Medications: Aspirin, Clopidogrel (Plavix).

  • Thrombolytics: Alteplase (tPA).

Contraindications

  • Unfractionated Heparin: Active bleeding, severe thrombocytopenia, hypersensitivity to heparin.

  • LMWH: Similar to UFH; caution in renal impairment.

  • Warfarin: Active bleeding, pregnancy (unless for specific conditions), severe liver disease.

  • DOACs: Active bleeding, severe renal impairment, mechanical prosthetic heart valves.

  • Antiplatelet Medications: Active bleeding, severe thrombocytopenia.

  • Thrombolytics: Active bleeding, history of hemorrhagic stroke, recent surgery.

Priority Nurse Assessments

  • Unfractionated Heparin: Monitor aPTT and signs of bleeding.

  • LMWH: Monitor for signs of thrombocytopenia and bleeding; check anti-Xa levels as indicated.

  • Warfarin: Monitor INR; assess dietary vitamin K intake.

  • DOACs: Monitor renal function; assess signs of bleeding.

  • Antiplatelet Medications: Monitor for signs of bleeding and cardiac symptoms.

  • Thrombolytics: Monitor vital signs and assess for signs of bleeding and neurological changes.

Mechanisms

  • Unfractionated Heparin: Binds to antithrombin III, inhibiting thrombin and factor Xa.

  • LMWH: Similar to UFH but with higher specificity for factor Xa.

  • Warfarin: Inhibits vitamin K epoxide reductase, preventing synthesis of vitamin K-dependent clotting factors.

  • DOACs: Directly inhibit thrombin or factor Xa, providing anticoagulation without the need for monitoring.

  • Antiplatelet Medications: Inhibit platelet aggregation via different mechanisms (e.g., aspirin inhibits COX-1).

  • Thrombolytics: Converts plasminogen to plasmin, breaking down fibrin in clots.