Overview Anticoagulants decrease the formation of fibrin clots heparin warfarin (coumadin) bivalirudin Heparin Mechanism catalyzes the binding of antithrombin III to multiple clotting factors inactivates several factors IIa (thrombin) Xa IXa XIa XIIa Clinical use immediate anticoagulation pulmonary embolism acute coronary syndrome stroke MI DVT DIC during pregnancy does not cross placenta Toxicity bleeding osteoporosis heparin-induced thrombocytopenia (HIT) heparin binds to platelet factor IV antibodies bind to and activate platelets leads to hypercoagulable state and thrombocytopenia hypersensitivity Pharmacology IV delivery only for therapeutic anticoagulation short half-life (2h) large, water-soluble polysaccharide low-molecular-weight heparins (e.g. enoxaparin) have advantages of longer half-lives (2-4x) less thrombocytopenia enhanced activity against factor Xa administered subcutaneously without laboratory (PTT) monitoring not easily reversible Monitoring partial thromboplastin time (PTT) Antagonist protamine sulfate positively charged to bind negatively charged heparin Warfarin (Coumadin) Mechanism ↓ hepatic synthesis of vitamin K-dependent clotting factors prevents the reduction of vitamin K, a necessary step in the synthesis of clotting factors vitamin K epoxide reductase is inhibited γ-carboxylation of clotting factors cannot occur affected clotting factors include II VII IX X protein C protein S no effect on clotting factors already present affects the extrinsic pathway Clinical use chronic anticoagulation DVT prophylaxis post-STEMI heart valve damage atrial arrhythmias Toxicity transient hypercoagulability transient protein C deficiency when beginning warfarin treatment due to short half life of protein C coagulation factors have relatively long half lives can lead to skin necrosis and dermal vascular thrombosis give heparin as you begin warfarin treatment bleeding teratogenic bone dysmorphogenesis not used in pregnancy drug interactions P450 metabolism inducers → ↓ PT increase in P450 degrades more warfarin and levels fall mnemonics Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs Chronic Alcohol St. John’s wort Phenytoin Phenobarbital Nevirapine Rifampin Griseofulvin Carbamazepine inhibitors → ↑ PT decrease in P450 degrades less warfarin and levels rise mnemonics AAA RACKS In GQ Magazine Acute Alcohol Abuse Ritonavir Amiodarone Cimetidine/Ciprofloxacin Ketoconazole Sulfonamides Isoniazid Grapefruit juice Quinidine Macrolides ASA, sulfonamides, and phenytoin displace warfarin from plasma proteins, leading to increased free fraction → ↑ PT cholestyramine ↓ oral absorption due to low pKa Pharmacology oral long half life (>30 hr) small, lipid-soluble Monitoring prothrombin time (PT) INR (tested PT / reference PT)^(calibration value) Antagonist vitamin K (slow onset) fresh frozen plasma (fast onset) Lepirudin and Bivalirudin Mechanism direct inhibtors of thrombin (IIa) Clinical use alternative to heparin during heparin-induced thrombocytopenia unstable angina during percutaneous transluminal coronary angioplasty Factor Xa Inhibitors (Apixaban and Rivaroxaban) Mechanism competitive inhibitor of factor Xa Clinical use treatment and prophylaxis for deep venous thrombosis and pulmonary embolism stroke prophylaxis for patients with atrial fibrillation
QUESTIONS 1 of 10 1 2 3 4 5 6 7 8 9 10 Previous Next Lab Values Blood Hematologic Cerebrospinal Sweat, Urine, and BMI Blood, Plasma, Serum Reference Range ALT 8-20 U/L Amylase, serum 25-125 U/L AST 8-20 U/L Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL Calcium, serum (Ca2+) 8.4-10.2 mg/dL Cholesterol, serum Rec: < 200 mg/dL Cortisol, serum 0800 h: 5-23 μg/dL //1600 h: 3-15 μg/dL 2000 h: ≤ 50% of 0800 h Creatine kinase, serum Male: 25-90 U/LFemale: 10-70 U/L Creatinine, serum 0.6-1.2 mg/dL Electrolytes, serum Sodium (Na+) 136-145 mEq/L Chloride (Cl-) 95-105 mEq/L Potassium (K+) 3.5-5.0 mEq/L Bicarbonate (HCO3-) 22-28 mEq/L Magnesium (Mg2+) 1.5-2.0 mEq/L Estriol, total, serum (in pregnancy) 24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL 28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL Ferritin, serum Male: 15-200 ng/mLFemale: 12-150 ng/mL Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL Female: premenopause: 4-30 mIU/mL midcycle peak: 10-90 mIU/mL postmenopause: 40-250 pH 7.35-7.45 PCO2 33-45 mmHg PO2 75-105 mmHg Glucose, serum Fasting: 70-110 mg/dL2-h postprandial:<120 mg/dL Growth hormone - arginine stimulation Fasting: <5 ng/mLProvocative stimuli: > 7ng/mL Immunoglobulins, serum IgA 76-390 mg/dL IgE 0-380 IU/mL IgG 650-1500 mg/dL IgM 40-345 mg/dL Iron 50-170 μg/dL Lactate dehydrogenase, serum 45-90 U/L Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL Female: follicular phase: 5-30 mIU/mL midcycle: 75-150 mIU/mL postmenopause 30-200 mIU/mL Osmolality, serum 275-295 mOsmol/kd H2O Parathyroid hormone, serume, N-terminal 230-630 pg/mL Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L Phosphorus (inorganic), serum 3.0-4.5 mg/dL Prolactin, serum (hPRL) < 20 ng/mL Proteins, serum Total (recumbent) 6.0-7.8 g/dL Albumin 3.5-5.5 g/dL Globulin 2.3-3.5 g/dL Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h Thyroxine (T4), serum 5-12 μg/dL Triglycerides, serum 35-160 mg/dL Triiodothyronine (T3), serum (RIA) 115-190 ng/dL Triiodothyronine (T3) resin uptake 25%-35% Urea nitrogen, serum 7-18 mg/dL Uric acid, serum 3.0-8.2 mg/dL Hematologic Reference Range Bleeding time 2-7 minutes Erythrocyte count Male: 4.3-5.9 million/mm3Female: 3.5-5.5 million mm3 Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/hFemale: 0-20 mm/h Hematocrit Male: 41%-53%Female: 36%-46% Hemoglobin A1c ≤ 6 % Hemoglobin, blood Male: 13.5-17.5 g/dLFemale: 12.0-16.0 g/dL Hemoglobin, plasma 1-4 mg/dL Leukocyte count and differential Leukocyte count 4,500-11,000/mm3 Segmented neutrophils 54%-62% Bands 3%-5% Eosinophils 1%-3% Basophils 0%-0.75% Lymphocytes 25%-33% Monocytes 3%-7% Mean corpuscular hemoglobin 25.4-34.6 pg/cell Mean corpuscular hemoglobin concentration 31%-36% Hb/cell Mean corpuscular volume 80-100 μm3 Partial thromboplastin time (activated) 25-40 seconds Platelet count 150,000-400,000/mm3 Prothrombin time 11-15 seconds Reticulocyte count 0.5%-1.5% of red cells Thrombin time < 2 seconds deviation from control Volume Plasma Male: 25-43 mL/kgFemale: 28-45 mL/kg Red cell Male: 20-36 mL/kgFemale: 19-31 mL/kg Cerebrospinal Fluid Reference Range Cell count 0-5/mm3 Chloride 118-132 mEq/L Gamma globulin 3%-12% total proteins Glucose 40-70 mg/dL Pressure 70-180 mm H2O Proteins, total < 40 mg/dL Sweat Reference Range Chloride 0-35 mmol/L Urine Calcium 100-300 mg/24 h Chloride Varies with intake Creatinine clearance Male: 97-137 mL/minFemale: 88-128 mL/min Estriol, total (in pregnancy) 30 wks 6-18 mg/24 h 35 wks 9-28 mg/24 h 40 wks 13-42 mg/24 h 17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 hFemale: 2.0-8.0 mg/24 h 17-Ketosteroids, total Male: 8-20 mg/24 hFemale: 6-15 mg/24 h Osmolality 50-1400 mOsmol/kg H2O Oxalate 8-40 μg/mL Potassium Varies with diet Proteins, total < 150 mg/24 h Sodium Varies with diet Uric acid Varies with diet Body Mass Index (BMI) Adult: 19-25 kg/m2 Calculator ( ) xy AC 7 8 9 ÷ 4 5 6 × 1 2 3 - 0 . = + Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.28) A 66-year-old male with a history of deep venous thrombosis is admitted to the hospital with shortness of breath and pleuritic chest pain. He is treated with an anticoagulant, but he develops significant hematochezia. His BP is now 105/60 and HR is 117; both were within normal limits on admission. The effects of the anticoagulant are virtually completely reversed with the administration of protamine. Which of the following was the anticoagulant most likely administered to this patient? Review Topic QID: 101338 1 Warfarin 10% (2/20) 2 Enoxaparin 0% (0/20) 3 Heparin 90% (18/20) 4 Bivalirudin 0% (0/20) 5 Dabigatran 0% (0/20) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 3 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.18) A 58-year-old Caucasian male with a history of peripheral vascular disease is admitted to the hospital with a painful, pulseless foot. He is prescribed antiplatelet and anticoagulant drugs. Which of the following matches a drug with its correct characteristic? Review Topic QID: 100534 1 Warfarin: directly inhibits thrombin 5% (7/148) 2 Heparin: activates antithrombin 3 58% (86/148) 3 Aspirin: reversibly inhibits COX-1 9% (13/148) 4 Clopidogrel: antagonizes ADP receptors on endothelial cells 26% (38/148) 5 Prasugrel: reduced risk of bleeding compared to other drugs in its class 2% (3/148) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK (M1.HE.60) A 48-year-old woman is admitted to the hospital and requires anticoagulation. She is administered a drug that binds tightly to antithrombin III. Which of the following drugs was administered? Review Topic QID: 101370 1 Aspirin 2% (2/99) 2 Warfarin 12% (12/99) 3 Dabigatran 16% (16/99) 4 Rivaroxaban 5% (5/99) 5 Enoxaparin 65% (64/99) M1 Select Answer to see Preferred Response PREFERRED RESPONSE 5