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What are the three important dysfunctions of blood commonly treated with various agents?
What is the normal platelet count per microliter of blood?
150,000-450,000
What is the process by which blood forms clots?
Coagulation or clotting
Platelets are also known as thrombocytes.
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Prothrombin is present in blood plasma that is converted into active thrombin by a clotting factor known as factor _.
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What is the role of Adenosine diphosphate (ADP) in platelet activation?
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What is the function of Thromboxane A2 in the context of platelets?
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How do Clopidogrel and Aspirin act as antiplatelets?
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What is the mechanism of action of Tranexamic acid?
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Name two Glycoprotein IIb/IIIa receptor antagonists and explain their mechanism of action.
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Study Notes
Hematology System
- The hematology system includes three main components: erythrocytes (RBCs), leukocytes (WBCs), thrombocytes (platelets), and plasma.
Platelets
- Platelets are responsible for stopping bleeding by forming a clot.
- Normal platelet count is 1,50,000-4,50,000 per microliter of blood.
- Coagulation or clotting is the process by which blood forms clots.
- Clotting factors and anticoagulants are made in the liver.
Thrombosis
- Thrombosis is the formation or presence of a blood clot in a blood vessel.
- The vessel may be any vein or artery, such as in a deep vein thrombosis or a coronary artery thrombosis.
- The clot itself is termed a thrombus.
Prothrombin
- Prothrombin is a protein produced by the liver.
- Prothrombin is converted into active thrombin by a clotting factor known as factor X or prothrombinase during coagulation.
- Thrombin is an enzyme that causes the clotting of blood by converting fibrinogen to fibrin.
Stages of Blood Clotting
- Stage 1: Formation of prothrombin activator.
- Stage 2: Conversion of prothrombin into thrombin.
- Stage 3: Conversion of fibrinogen into fibrin.
Anticoagulants
- Anticoagulants are substances that prevent coagulation of blood.
- Types of anticoagulants:
- Anticoagulants used to prevent blood clotting inside the body (in vivo).
- Anticoagulants used to prevent clotting of blood that is collected from the body (in vitro).
- Anticoagulants used to prevent blood clotting both in vivo and in vitro.
- Examples of anticoagulants: Heparin, Warfarin, Rivaroxaban.
Heparin
- Heparin is a naturally produced anticoagulant in the body.
- Mechanism of action: prevents blood clotting by its antithrombin activity.
- Heparin is enhancing the activity of the endogenous inhibitor "antithrombin" by 1000 x.
Heparin Pharmacokinetics
- Absorption and Distribution: Heparin is unable to cross membranes, including those of the GI tract, and must be given by injection (IV or subQ).
- Metabolism and Excretion: Heparin undergoes hepatic metabolism and is excreted through the renal route.
- Half-life: short (about 1.5 hours), but increased in patients with hepatic or renal disease.
Antidote for Heparin
- Protamine sulfate is the antidote for heparin overdose.
- Dosage of protamine: 1 mg of protamine inactivates 100 units of heparin.
Rivaroxaban
- Rivaroxaban is an oral anticoagulant indicated for prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery.
- Mechanism of action: Rivaroxaban inhibits both free Factor Xa and Factor Xa bound in the prothrombinase complex.
- Adverse effects: thrombocytopenia, retroperitoneal hemorrhage, hypersensitivity, cerebral hemorrhage.
Vitamin K
- Newborns are prone to vitamin K deficiency due to:
- Limited transport of vitamin K across the placental barrier.
- Immature prothrombin synthesis in the liver.
- Sterile gut, lacking bacteria necessary for vitamin K synthesis.
- Newborn infants receive a single dose of vitamin K at birth to prevent bleeding disorders.
Warfarin
- Warfarin is an anticoagulant used to prevent clots.
- Mechanism of action: Warfarin inhibits the vitamin K-dependent synthesis of clotting factors II, VII, IX, and X.
- Side effects: severe bleeding, including heavier than normal menstrual bleeding, hematuria, black or bloody stool, blood in vomiting, blood in sputum.
Fibrinolytics
- Fibrinolytics are substances that break down blood clots.
- Examples: Alteplase, Reteplase, Anistreplase, Streptokinase, Urokinase.
- Mechanism of action: Fibrinolytics activate plasminogen to produce plasmin, which breaks down fibrin.
Antiplatelets
- Antiplatelets are a group of medicines that stop blood cells (platelets) from sticking together and forming a blood clot.
- Examples: Aspirin, Clopidogrel, Prasugrel.
- Mechanism of action: Antiplatelets inhibit the activation of platelets by blocking the production of thromboxane A2 or by inhibiting the ADP receptor.
Tranexamic acid
- Tranexamic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin.
- Indications: used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, and nose bleeds (epistaxis).
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