Anticoagulants: Direct factor inhibitors

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Anticoagulants: Direct factor inhibitors

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Diagnoses

Anatomy of the coronary circulation
Anatomy clinical correlates: Heart
Coronary artery disease: Pathology review
Anticoagulants: Direct factor inhibitors
Anticoagulants: Heparin
Antiplatelet medications
Thrombolytics
Renal failure: Pathology review
ACE inhibitors, ARBs and direct renin inhibitors
Anatomy of the lungs and tracheobronchial tree
Anatomy clinical correlates: Pleura and lungs
Alveolar surface tension and surfactant
Breathing cycle and regulation
Gas exchange in the lungs, blood and tissues
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Obstructive lung diseases: Pathology review
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy clinical correlates: Other abdominal organs
Bile secretion and enterohepatic circulation
Liver anatomy and physiology
Cirrhosis: Pathology review
Anatomy of the heart
Anatomy of the coronary circulation
Anatomy of the inferior mediastinum
Anatomy of the superior mediastinum
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Cardiac afterload
Cardiac contractility
Cardiac cycle
Cardiac preload
Cardiac work
Cardiovascular system anatomy and physiology
Changes in pressure-volume loops
Frank-Starling relationship
Measuring cardiac output (Fick principle)
Microcirculation and Starling forces
Pressure-volume loops
Stroke volume, ejection fraction, and cardiac output
Heart failure: Pathology review
Anatomy of the coronary circulation
Anatomy clinical correlates: Heart
Cardiovascular system anatomy and physiology
Atherosclerosis and arteriosclerosis: Pathology review
Coronary artery disease: Pathology review
Anatomy of the cerebral cortex
Anatomy of the limbic system
Anatomy clinical correlates: Cerebral hemispheres
Dementia: Pathology review
Mood disorders: Pathology review
Selective serotonin reuptake inhibitors
Serotonin and norepinephrine reuptake inhibitors
Tricyclic antidepressants
Monoamine oxidase inhibitors
Atypical antidepressants
Pancreas histology
Diabetes mellitus: Pathology review
Dyslipidemias: Pathology review
Lipid-lowering medications: Fibrates
Lipid-lowering medications: Statins
Miscellaneous lipid-lowering medications
Enteric nervous system
Esophageal motility
Gastrointestinal system anatomy and physiology
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Hypertension: Pathology review
ACE inhibitors, ARBs and direct renin inhibitors
Adrenergic antagonists: Beta blockers
Calcium channel blockers
Thiazide and thiazide-like diuretics
Anatomy of the thyroid and parathyroid glands
Thyroid and parathyroid gland histology
Endocrine system anatomy and physiology
Thyroid hormones
Hyperthyroidism: Pathology review
Anatomy of the thyroid and parathyroid glands
Thyroid and parathyroid gland histology
Endocrine system anatomy and physiology
Thyroid hormones
Hypothyroidism: Pathology review
Introduction to the skeletal system
Bone remodeling and repair
Bone disorders: Pathology review
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy clinical correlates: Other abdominal organs
Pancreas histology
Pancreatic secretion
Pancreatitis: Pathology review
Anatomy of the diaphragm
Anatomy of the larynx and trachea
Anatomy of the lungs and tracheobronchial tree
Anatomy of the nose and paranasal sinuses
Anatomy of the pleura
Bones and joints of the thoracic wall
Muscles of the thoracic wall
Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Alveolar surface tension and surfactant
Anatomic and physiologic dead space
Breathing cycle and regulation
Gas exchange in the lungs, blood and tissues
Lung volumes and capacities
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Pneumonia: Pathology review
Drug misuse, intoxication and withdrawal: Alcohol: Pathology review
Drug misuse, intoxication and withdrawal: Hallucinogens: Pathology review
Drug misuse, intoxication and withdrawal: Other depressants: Pathology review
Drug misuse, intoxication and withdrawal: Stimulants: Pathology review
Atypical antidepressants
Nasal, oral and pharyngeal diseases: Pathology review
Anatomy of the abdominal viscera: Kidneys, ureters and suprarenal glands
Anatomy of the female urogenital triangle
Anatomy of the male urogenital triangle
Anatomy of the perineum
Anatomy of the urinary organs of the pelvis
Anatomy clinical correlates: Female pelvis and perineum
Anatomy clinical correlates: Male pelvis and perineum
Renal system anatomy and physiology
Urinary tract infections: Pathology review
Anatomy of the lungs and tracheobronchial tree
Fascia, vessels and nerves of the upper limb
Vessels and nerves of the forearm
Vessels and nerves of the gluteal region and posterior thigh
Anatomy clinical correlates: Pleura and lungs
Clot retraction and fibrinolysis
Coagulation (secondary hemostasis)
Platelet plug formation (primary hemostasis)
Deep vein thrombosis and pulmonary embolism: Pathology review
Anticoagulants: Direct factor inhibitors
Anticoagulants: Heparin
Anticoagulants: Warfarin

Clinical conditions

Abdominal quadrants, regions and planes
Anatomy of the abdominal viscera: Blood supply of the foregut, midgut and hindgut
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Innervation of the abdominal viscera
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy of the abdominal viscera: Small intestine
Anatomy of the anterolateral abdominal wall
Anatomy of the diaphragm
Anatomy of the gastrointestinal organs of the pelvis and perineum
Anatomy of the inguinal region
Anatomy of the muscles and nerves of the posterior abdominal wall
Anatomy of the peritoneum and peritoneal cavity
Anatomy of the vessels of the posterior abdominal wall
Anatomy clinical correlates: Anterior and posterior abdominal wall
Anatomy clinical correlates: Inguinal region
Anatomy clinical correlates: Other abdominal organs
Anatomy clinical correlates: Peritoneum and diaphragm
Anatomy clinical correlates: Viscera of the gastrointestinal tract
Appendicitis: Pathology review
Diverticular disease: Pathology review
Gallbladder disorders: Pathology review
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Inflammatory bowel disease: Pathology review
Pancreatitis: Pathology review
Acid-base map and compensatory mechanisms
Buffering and Henderson-Hasselbalch equation
Physiologic pH and buffers
The role of the kidney in acid-base balance
Acid-base disturbances: Pathology review
Anatomy of the abdominal viscera: Kidneys, ureters and suprarenal glands
Kidney histology
Renal system anatomy and physiology
Renal failure: Pathology review
Anatomy of the basal ganglia
Anatomy of the blood supply to the brain
Anatomy of the brainstem
Anatomy of the cerebellum
Anatomy of the cerebral cortex
Anatomy of the cranial meninges and dural venous sinuses
Anatomy of the diencephalon
Anatomy of the limbic system
Anatomy of the ventricular system
Anatomy of the white matter tracts
Anatomy clinical correlates: Anterior blood supply to the brain
Anatomy clinical correlates: Cerebellum and brainstem
Anatomy clinical correlates: Cerebral hemispheres
Anatomy clinical correlates: Posterior blood supply to the brain
Nervous system anatomy and physiology
Amnesia, dissociative disorders and delirium: Pathology review
Central nervous system infections: Pathology review
Cerebral vascular disease: Pathology review
Dementia: Pathology review
Drug misuse, intoxication and withdrawal: Alcohol: Pathology review
Drug misuse, intoxication and withdrawal: Hallucinogens: Pathology review
Drug misuse, intoxication and withdrawal: Other depressants: Pathology review
Drug misuse, intoxication and withdrawal: Stimulants: Pathology review
Mood disorders: Pathology review
Schizophrenia spectrum disorders: Pathology review
Seizures: Pathology review
Traumatic brain injury: Pathology review
Anticonvulsants and anxiolytics: Benzodiazepines
Atypical antipsychotics
Typical antipsychotics
Blood histology
Blood components
Erythropoietin
Extrinsic hemolytic normocytic anemia: Pathology review
Intrinsic hemolytic normocytic anemia: Pathology review
Macrocytic anemia: Pathology review
Microcytic anemia: Pathology review
Non-hemolytic normocytic anemia: Pathology review
Introduction to the central and peripheral nervous systems
Introduction to the muscular system
Introduction to the skeletal system
Introduction to the somatic and autonomic nervous systems
Anatomy of the ascending spinal cord pathways
Anatomy of the descending spinal cord pathways
Anatomy of the muscles and nerves of the posterior abdominal wall
Anatomy of the vertebral canal
Anatomy of the vessels of the posterior abdominal wall
Bones of the vertebral column
Joints of the vertebral column
Muscles of the back
Vessels and nerves of the vertebral column
Anatomy clinical correlates: Anterior and posterior abdominal wall
Anatomy clinical correlates: Bones, joints and muscles of the back
Anatomy clinical correlates: Spinal cord pathways
Anatomy clinical correlates: Vertebral canal
Back pain: Pathology review
Positive and negative predictive value
Sensitivity and specificity
Test precision and accuracy
Type I and type II errors
Anatomy of the breast
Anatomy of the coronary circulation
Anatomy of the heart
Anatomy of the inferior mediastinum
Anatomy of the lungs and tracheobronchial tree
Anatomy of the pleura
Anatomy of the superior mediastinum
Bones and joints of the thoracic wall
Muscles of the thoracic wall
Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Breast
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Cardiovascular system anatomy and physiology
Respiratory system anatomy and physiology
Aortic dissections and aneurysms: Pathology review
Coronary artery disease: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Pleural effusion, pneumothorax, hemothorax and atelectasis: Pathology review
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Gastrointestinal system anatomy and physiology
Enteric nervous system
Colorectal polyps and cancer: Pathology review
Diverticular disease: Pathology review
Laxatives and cathartics
Anatomy of the diaphragm
Anatomy of the larynx and trachea
Anatomy of the lungs and tracheobronchial tree
Anatomy of the nose and paranasal sinuses
Anatomy of the pleura
Bones and joints of the thoracic wall
Muscles of the thoracic wall
Vessels and nerves of the thoracic wall
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Lung cancer and mesothelioma: Pathology review
Nasal, oral and pharyngeal diseases: Pathology review
Obstructive lung diseases: Pathology review
Pneumonia: Pathology review
Restrictive lung diseases: Pathology review
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Bile secretion and enterohepatic circulation
Enteric nervous system
Gastrointestinal system anatomy and physiology
Inflammatory bowel disease: Pathology review
Malabsorption syndromes: Pathology review
Bacillus cereus (Food poisoning)
Campylobacter jejuni
Clostridium difficile (Pseudomembranous colitis)
Clostridium perfringens
Escherichia coli
Norovirus
Salmonella (non-typhoidal)
Shigella
Staphylococcus aureus
Vibrio cholerae (Cholera)
Yersinia enterocolitica
Anatomy of the heart
Anatomy of the lungs and tracheobronchial tree
Anatomy of the pleura
Anatomy clinical correlates: Heart
Anatomy clinical correlates: Mediastinum
Anatomy clinical correlates: Pleura and lungs
Anatomy clinical correlates: Thoracic wall
Alveolar surface tension and surfactant
Anatomic and physiologic dead space
Breathing cycle and regulation
Diffusion-limited and perfusion-limited gas exchange
Gas exchange in the lungs, blood and tissues
Pulmonary shunts
Regulation of pulmonary blood flow
Respiratory system anatomy and physiology
Ventilation
Ventilation-perfusion ratios and V/Q mismatch
Zones of pulmonary blood flow
Cardiac afterload
Cardiac contractility
Cardiac cycle
Cardiac preload
Cardiac work
Frank-Starling relationship
Measuring cardiac output (Fick principle)
Pressure-volume loops
Stroke volume, ejection fraction, and cardiac output
Acid-base map and compensatory mechanisms
Buffering and Henderson-Hasselbalch equation
Physiologic pH and buffers
The role of the kidney in acid-base balance
Apnea, hypoventilation and pulmonary hypertension: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
Heart failure: Pathology review
Lung cancer and mesothelioma: Pathology review
Obstructive lung diseases: Pathology review
Pleural effusion, pneumothorax, hemothorax and atelectasis: Pathology review
Pneumonia: Pathology review
Restrictive lung diseases: Pathology review
Tuberculosis: Pathology review
Introduction to the cardiovascular system
Introduction to the lymphatic system
Microcirculation and Starling forces
Cirrhosis: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
Heart failure: Pathology review
Hypothyroidism: Pathology review
Nephrotic syndromes: Pathology review
Renal failure: Pathology review
Antidiuretic hormone
Phosphate, calcium and magnesium homeostasis
Potassium homeostasis
Renin-angiotensin-aldosterone system
Sodium homeostasis
Diabetes insipidus and SIADH: Pathology review
Electrolyte disturbances: Pathology review
Parathyroid disorders and calcium imbalance: Pathology review
Anxiety disorders, phobias and stress-related disorders: Pathology Review
Apnea, hypoventilation and pulmonary hypertension: Pathology review
Mood disorders: Pathology review
Psychological sleep disorders: Pathology review
Adrenergic antagonists: Beta blockers
Anticonvulsants and anxiolytics: Barbiturates
Anticonvulsants and anxiolytics: Benzodiazepines
Antihistamines for allergies
Nonbenzodiazepine anticonvulsants
Opioid agonists, mixed agonist-antagonists and partial agonists
Tricyclic antidepressants
Cytokines
Inflammation
Anatomy of the abdominal viscera: Blood supply of the foregut, midgut and hindgut
Anatomy of the abdominal viscera: Esophagus and stomach
Anatomy of the abdominal viscera: Large intestine
Anatomy of the abdominal viscera: Small intestine
Anatomy of the gastrointestinal organs of the pelvis and perineum
Anatomy of the vessels of the posterior abdominal wall
Anatomy clinical correlates: Viscera of the gastrointestinal tract
Gastrointestinal bleeding: Pathology review
Anatomy of the blood supply to the brain
Anatomy of the cranial base
Anatomy of the cranial meninges and dural venous sinuses
Anatomy of the nose and paranasal sinuses
Anatomy of the suboccipital region
Anatomy of the temporomandibular joint and muscles of mastication
Anatomy of the trigeminal nerve (CN V)
Bones of the cranium
Bones of the neck
Deep structures of the neck: Prevertebral muscles
Muscles of the face and scalp
Nerves and vessels of the face and scalp
Superficial structures of the neck: Cervical plexus
Anatomy clinical correlates: Bones, fascia and muscles of the neck
Anatomy clinical correlates: Skull, face and scalp
Anatomy clinical correlates: Temporal regions, oral cavity and nose
Anatomy clinical correlates: Trigeminal nerve (CN V)
Anatomy clinical correlates: Vessels, nerves and lymphatics of the neck
Headaches: Pathology review
Anatomy of the abdominal viscera: Liver, biliary ducts and gallbladder
Anatomy of the abdominal viscera: Pancreas and spleen
Anatomy clinical correlates: Other abdominal organs
Gallbladder histology
Liver histology
Bile secretion and enterohepatic circulation
Liver anatomy and physiology
Pancreatic secretion
Jaundice: Pathology review
Anatomy of the elbow joint
Anatomy of the glenohumeral joint
Anatomy of the hip joint
Anatomy of the knee joint
Anatomy of the radioulnar joints
Anatomy of the sternoclavicular and acromioclavicular joints
Anatomy of the tibiofibular joints
Joints of the ankle and foot
Joints of the wrist and hand
Anatomy clinical correlates: Arm, elbow and forearm
Anatomy clinical correlates: Clavicle and shoulder
Anatomy clinical correlates: Knee
Anatomy clinical correlates: Leg and ankle
Anatomy clinical correlates: Wrist and hand
Gout and pseudogout: Pathology review
Rheumatoid arthritis and osteoarthritis: Pathology review
Seronegative and septic arthritis: Pathology review
Anatomy of the knee joint
Anatomy clinical correlates: Knee
Rheumatoid arthritis and osteoarthritis: Pathology review
Seronegative and septic arthritis: Pathology review
Candida
Clostridium difficile (Pseudomembranous colitis)
Enterobacter
Enterococcus
Escherichia coli
Proteus mirabilis
Pseudomonas aeruginosa
Staphylococcus aureus
Bacterial and viral skin infections: Pathology review
Skin histology
Skin anatomy and physiology
Acneiform skin disorders: Pathology review
Papulosquamous and inflammatory skin disorders: Pathology review
Pigmentation skin disorders: Pathology review
Skin cancer: Pathology review
Vesiculobullous and desquamating skin disorders: Pathology review
Anatomy of the heart
Anatomy of the vagus nerve (CN X)
Aortic dissections and aneurysms: Pathology review
Cardiomyopathies: Pathology review
Coronary artery disease: Pathology review
Heart blocks: Pathology review
Supraventricular arrhythmias: Pathology review
Valvular heart disease: Pathology review
Ventricular arrhythmias: Pathology review
Hunger and satiety
Anxiety disorders, phobias and stress-related disorders: Pathology Review
Breast cancer: Pathology review
Colorectal polyps and cancer: Pathology review
Dementia: Pathology review
Diabetes mellitus: Pathology review
GERD, peptic ulcers, gastritis, and stomach cancer: Pathology review
Heart failure: Pathology review
HIV and AIDS: Pathology review
Hyperthyroidism: Pathology review
Inflammatory bowel disease: Pathology review
Jaundice: Pathology review
Lung cancer and mesothelioma: Pathology review
Malabsorption syndromes: Pathology review
Mood disorders: Pathology review
Tuberculosis: Pathology review

Transcript

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Anticoagulant medications help to prevent thrombi, or blood clots from forming. These medications work by interfering with the normal function of proteins called clotting factors in a chemical process called the coagulation cascade, or secondary hemostasis where hemo refers to blood, and stasis means to halt or stop. While the most common anticoagulants like warfarin and heparin act on multiple coagulation factors, in this video we’re gonna focus on anticoagulants that work on a single coagulation factor; either thrombin or activated factor X.

Now, before we discuss heparin in detail we need to talk about the coagulation cascade which is where heparin exerts its effect. The coagulation cascade starts via two pathways --the extrinsic and intrinsic pathways. The intrinsic pathway starts when circulating factor XII comes into contact with the surface of activated platelets or collagen. Activated factor XII, then activates factor XI, which activates factor IX which activates factor X. Factor X starts the common pathway where it activates factor II, or thrombin, which activates factor I that builds the fibrin mesh. When factor II gets activated it also activates 4 other factors: V, VIII, IX, and XIII. Factor V gets activated and acts as a cofactor for X, factor VIII acts as a cofactor for factor IX, and factor XIII helps factor I, or fibrin, form crosslinks. In the extrinsic pathway, exposed tissue factor activates factor VII, which activates factor X and starts the common pathway.

Now, the most common point of clot regulation is when a coagulation factor called thrombin is produced. Thrombin, or activated factor II, is a very important clotting factor, because it has multiple pro-coagulative functions. Think of thrombin as the accelerator on a car--the pedal that takes secondary hemostasis from 20 miles per hour to 100 miles per hour! First, thrombin binds to receptors on platelets causing them to get activated. Activated platelets change their shape to form tentacle-like arms that allow them to stick to other platelets. Second, thrombin activates two cofactors; factor V used in the common pathway, and factor VIII used in the intrinsic pathway. Third, thrombin proteolytically cleaves fibrinogen or factor I, into fibrin or factor Ia which binds with other fibrin proteins to form a fibrin mesh. And finally, thrombin proteolytically cleaves stabilizing factor or factor XIII into factor XIIIa. Factor XIIIa combines with a calcium ion cofactor to form cross links between the fibrin chains, further reinforcing the fibrin mesh.

The direct thrombin inhibitors and the direct factor Xa inhibitors inhibit the coagulation cascade by binding to their corresponding coagulation factors after they’ve been activated. The direct thrombin inhibitors can bind to thrombin that’s in the circulation and those already attached to a forming clot. Factor Xa inhibitors have the same function on Xa, however, it has an overall greater effect on anticoagulation since it’s higher up in the coagulation cascade, so each molecule of the medication can prevent multiple thrombins from being activated by a factor Xa. Now, in terms of laboratory parameters, direct thrombin inhibitors prolong thrombin time, and have less effect on prothrombin time, or PT, which assesses the extrinsic and common coagulation pathways, and partial thromboplastin time, or aPTT, that assesses the intrinsic and common coagulation pathways. Direct factor Xa inhibitors prolong both PT and aPTT, but have no effect on thrombin time. However, both classes of direct factor inhibitors do not require routine monitoring.

Now, let's discuss each class of medications in more detail starting with the direct thrombin inhibitors like bivalirudin, lepirudin, and argatroban, which are given intravenously, desirudin, which is given subcutaneously, and dabigatran, which is given peroral. This class of medications was initially isolated from the saliva of leeches due to its anticoagulant effect. Although they are not as frequently used as heparin, they can be a 2nd line medication in people with a history of deep vein thrombosis to prevent pulmonary embolism, or atrial fibrillation to prevent strokes. Direct thrombin inhibitors are especially useful when heparin causes an adverse reaction called HIT, or heparin induced thrombocytopenia. HIT occurs when some people produce antibodies, which bind to heparin bound to a protein on the surface of platelets called platelet factor 4. The complex antibody-heparin-platelet factor 4 leads to platelet activation and aggregation, hence thrombosis. There is also destruction of platelets by cells of the spleen called macrophages, resulting in a low platelet count. These medications are also used in combination with antiplatelet agents like aspirin and clopidogrel to prevent clot formation in patients undergoing coronary artery surgery.

Sources

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