Updated: 3/2/2019

Anticoagulants

Topic
Review Topic
0
0
Questions
7
0
0
Evidence
4
0
0
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 factor
      • 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 theurapeutic 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
      • prosthetic valves (requiring an INR of 2.5-3.5) 
      • atrial arrhythmias
  • Toxicity
    • transient hypercoagulability
      • transient protein C deficiency when beginning warfarin treatment
        • due to short half life of protein C
      • can lead to skin necrosis and dermal vascular thrombosis
        • pain, bullae formation, and skin necrosis following initiation of warfarin likely has warfarin-induced skin necrosis
        • often occurs in women who have protein C deficiency
        • treatment includes administration of vitamin K, protein C concentrate and discontinuation of warfarin 
      • give heparin as you begin warfarin treatment
    • bleeding
      •  retroperitoneal hematoma - back/abdominal pain and hemodynamic compromise 
        • CT scan to identify and guide treatment 
    • teratogenic
      • bone dysmorphogenesis
      • not used in pregnancy
    • drug interactions
      • P450 metabolism 
        • inducers → ↓ PT
          • increase in P450 degrades more warfarin and levels fall
          • carbamazepine, barbiturates, rifampin
        • inhibitors → ↑ PT
          • decrease in P450 degrades less warfarin and levels rise
          • macrolides, cimetidine, imidazoles
      • ASA, sulfonamides, 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, bivalirudin
  • Mechanism
    • direct inihibtors of thrombin (IIa)
  • Clinical use
    • alternative to heparin
      • e.g. during HIT
    • unstable angina during percutaneous transluminal coronary angioplasty
Factor Xa Inhibitors
  • Mechanism
    • factor Xa inhibitor
  • Clinical use
    • anticoagulation requiring single daily dosing - ideal for a simple medication regimen 
 

Please rate topic.

Average 4.0 of 5 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
Questions (7)
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
Calculator

Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK

(M2.HE.93) A 65-year-old male presents to the emergency department with a 2-day onset of right-lower quadrant and right flank pain. He also states that over this period of time he has felt dizzy, light-headed, and short of breath. He denies any recent trauma or potential inciting event. His vital signs are as follows: T 37.1 C, HR 118, BP 74/46, RR 18, SpO2 96%. Physical examination is significant for an irregularly irregular heart rhythm as well as bruising over the right flank. The patient's medical history is significant for atrial fibrillation, hypertension, and hyperlipidemia. His medication list includes atorvastatin, losartan, and coumadin. IV fluids are administered in the emergency department, resulting in an increase in blood pressure to 100/60 and decrease in heart rate to 98. Which of the following would be most useful to confirm this patient's diagnosis and guide future management? Review Topic

QID: 104635
1

Ultrasound of the right flank

0%

(0/20)

2

Radiographs of the abdomen and pelvis

0%

(0/20)

3

Magnetic resonance angiography

35%

(7/20)

4

MRI abdomen/pelvis

0%

(0/20)

5

CT abdomen/pelvis

60%

(12/20)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 5

(M2.HE.4686) A 65-year-old veteran with a history of hypertension, diabetes, and end-stage renal disease presents with nausea, vomiting, and abdominal pain. The patient was found to have a small bowel obstruction on CT imaging. He is managed conservatively with a nasogastric tube placed for decompression. After several days in the hospital, the patient’s symptoms are gradually improving. Today, he complains of left leg swelling. On physical exam, the patient has a swollen left lower extremity with calf tenderness on forced dorsiflexion of the ankle. An ultrasound confirms a deep vein thrombus. An unfractionated heparin drip is started. What should be monitored to adjust heparin dosing? Review Topic

QID: 107401
1

Prothrombin time

0%

(0/2)

2

Activated partial thromboplastin time

100%

(2/2)

3

Internationalized Normal Ratio (INR)

0%

(0/2)

4

Creatinine level

0%

(0/2)

5

Liver transaminase levels

0%

(0/2)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 2
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
ARTICLES (5)
POSTS (1)
N Engl J Med. 2003 Jul 10;349(2):146-53. [PMID]12853587[/PMID]
Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.
  • Heme
  • - Anticoagulants
Lee AY
Topic COMMENTS (13)
Private Note