47 Flashcards
intro
heparin: heterogenous mucopolysaccarides (GAG + pentasaccharides)
- physiologically made by mast cells, pneumocytes, liver cells
heparin derivatives
UFH:
- large molecules
- longer GAG chain
- bind antithrombin 3, factor 10 and thrombin (F2) + other intrinsic factors
- heparin has similar effects as antithrombin 3
LMWH:
- fragments of UFH
- shorter GAG chain
- ONLY bind antithrombin 3 and F10, some partially bind F2
Pentasaccharides:
- no protein structure
- 5 monosaccharide units
mechanism of action
antithrombin 3 inhibits clotting factors
- bind AT3 –> inhibit clotting factors 2a + 10a, 9a, 11a, 12a (2,9,10,11,12)
- inhibition of AT3 –> inhibit F10 –> inhibit prothrombin activation –> inhibit thrombin –> inhibit fibrin
indications
prevention + treatment
VTE (venous thromboembolism)
unfractionated heparin
complete intrinsic and common pathway
- adults: aPTT test
- children: anti-Xa activity
pharmacokinetics of heparin
large molecule –> poor distribution through membranes
- does not cross placenta
- does not appear in breast milk
side effects of heparin
bleeding: protamine sulfate (1mg to each 100IU heparin)
thrombocytopenia: HIT2
osteoporosis (longer than 6m treatment)
contraindications: allergy, thrombocytopenia, active bleeding, risk of bleeding, renal/liver failure
LMWH
dalteparine, enoxaparine, nadroparine, bemiparine
aFX + F2 (partly)
advantages:
- longer half-life (1x daily)
- no necessity of excessive lab monitoring
- anti-Xa assay
- very safe
- low risk of overdosing
semisynthetic pentasaccharides
fondaparinux
- no protein structure
- no cross-reactivity
- very selective against aFX
- long half-life (>12h) 1x daily
- no HIT
clinical use:
- DVT (during surgery)
- Venous thromboembolism
- HIT-2
disadvantage:
- protamine sulphate ineffeciency
HIT-2
ACTIVATORY IgG antibodies against antigen which heparin-bounded on platelet F4
- bond signal thrombocyte elimination by immune system
- excessive aggregation of thrombocytes –> severe thrombosis
