Heparin Anticoagulants I Flashcards
Heparin Chemistry
Strongly acidic mucopolysaccharide
Repeating units of suflated glucuronic acid and sulfated glucosamine
Heterogenous weighted compounds
Found in mast cells
Actions of Heparin
Inhibits factor Xa and IIa (thrombin)
Inhibits XIIa and VIa as well
At high concentrations inhibits the aggregation of platelets
INDIRECTLY inhibits VIIa via TFPI
Heparin MoA
Binds ATIII and causes conformational change in ATIII
ATIII inhibits Xa, IXa, XIa, XIIa, IIa, and VIIa
More Actions of Heparin
Plasma clearing: heparin causes vessels to release lipase to break down chylomicrons in plasma
Binds to vascular lining to neutralize the positive charge
Causes release of Tissue Factor Pathway Inhibitor (TFPI)
Heparin Monitoring
Via APTT
Therapeutic range is when APTT is 2-2.5 x baseline
Metabolism
25% excreted in urine
Metabolized in liver
Duration of action
Rapid onset
Half life: 1-3 hours
Endogenous modulators of heparin
AT (main co-factor)
Heparin cofactor II (second co-factor)
Tissue Factor Pathway Inhibitor
Platelet factor 4 (platelet neutralizing protein)
Side Effects of Heparin
Hemorhagic complications
Heparin induced thrombocytopenia (antiheparin/PF4 antibodies)
Osteoporosis
Alopecia
Clinical Use of Heparin
Therapeutic/surgical/prophylactic anticoagulation
Unstable angina and ACS
Adjunct therapy with thrombolytic drugs
Thrombotic and ischemic stroke
Protamine Sulfate
Basic protein, heparin antagonist
Causes hypotension and bradycardia
Low Molecular weight Heparins
Outpatient settings: prophylaxis/treatment of DVT, management of ACS
Higher bioavailability than heparin
Longer duration of action
less bleeding
Antithrombin-Concentrates (AT)
Tx of acquired or congenital AT deficiency
Tx of DIC in sepsis
Hirudin
From leeches
Direct thrombin inhibitor
Used in patients who are heparin compromised
Can sometime still form antibodies though
Argatroban
Synthetic anti-thrombin agent
Special usage in HIT
Inhibits thrombin, no coagulation factors.
Requires no cofactors
