Updated: 12/27/2018

Anticoagulants

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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
 

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Questions (10)
Lab Values
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/L
Female: 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/mL
Female: 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/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative 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/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 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/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 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/min
Female: 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 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 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
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(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

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(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

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(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

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PREFERRED RESPONSE 5
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