Parenteral anticoagulation (I/V) Amboss Flashcards
Unfractionated heparin (UFH). What drug?
Heparin
What is heparin administration for prophylaxis?
subcutaneous
What is heparin administration for therapeutic?
continuous intravenous infusion (therapeutic administration requires infusion pump)
Heparin monitoring?
aPTT and platelet count
including PLT baseline before treatment is started
Heparin clearance?
Clearance: hepatic (preferred agent for patients with renal insufficiency)
Heparin’s antidote?
Protamine sulfate
Charge of heparin?
negative
protamine sulfate charge?
positive
Why protamine sulfate binds heparin?
positively-charged protein that can neutralize negatively-charged heparin by forming inactive complexes
What drug is preferred for renal insufficiency?
Heparin - because its clearance is hepatic, not renal
What to monitor when use heparin in order to detect HIT?
platelets must be continuously monitored during heparin therapy and a baseline should be established before commencing treatment
Low molecular weight heparin (LMWH) drugs?
enoxaparin, dalteparin, tinzaparin, nadroparin, certoparin
LMWH. Administration?
Subcutaneous
LMWH. Monitoring?
Anti-factor Xa activity can be assessed in specific cases; not generally recommended –>
Only necessary in specific cases, e.g., patients with renal failure, underweight/overweight, as there is a risk of accumulation or underdosing. Anti-factor Xa activity needs to be checked 4 hours after administration (follow-up necessary as drug level is only consistent after several administrations)
LMWH. Clearance?
renal
Why LMWH not suitable in renal insufficiency?
Clearance: renal (contraindicated for patients with renal insufficiency)
LMWH antidote? What scope of reversal?
protamine sulfate (partial reversal –> Protamine antagonizes 50% of the effect of LMWH)
Synthetic heparin. What drug?
fondaparinux
Fondaparinux. Administration?
subcutaneous
Fondaparinux. Monitoring?
Same as heparin:
Not generally recommended;
Anti-factor Xa activity can be assessed in specific cases (Such cases include conditions with increased coagulability (e.g., chronic kidney disease, anemia, thrombocytopenia).
Fondaparinux. Antidote?
Possibly activated prothrombin complex concentrates (aPCC)
Heparinoid (glycosaminoglycan). What drug?
danaparoid
Heparinoid (glycosaminoglycan). All other same with administration and monitoring and antidote as in heparin/fondaparinux.
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Direct thrombin inhibitors. Drugs?
I/v argatroban, bivalirudin, desirudin
p/o dabigatranas
Direct thrombin inhibitors. Monitoring?
not recommended
Direct thrombin inhibitors. Antidote?
Possibly aPCC and/or antifibrinolytics (e.g., tranexamic acid) - if no reversal agent available
Dabigatran: idarucizumab (monoclonal antibody)
Heparin mechanism?
Enhances the activity of antithrombin –> and it leads to decreased action of IIa and Xa. (IT’S INDIRECT INHIBITION!!!!! NES DIRECTLY AFFECT ANTITHROMBIN, NOT IIa and Xa).
Heparin mechanism. Xa inhibition?
antithrombin III potentiation → inhibition of factor Xa → decreased activation of prothrombin → ↓ thrombin→ ↓ fibrinogen activation → ↓ fibrin
Heparin mechanism. IIa inhibition?
Thrombin (factor IIa): UFH binds antithrombin III and thrombin simultaneously at two distinct binding sites → antithrombin III and thrombin held by heparin in close proximity (complex formation) → ↑ thrombin inhibition → ↓ fibrinogen activation → ↓ fibrin
Heparin half life?
SHORT - therefore anticoagulant effect quickly ceases once administration is stopped
LMWH mechanism?
LMWH: binds to antithrombin III → inhibition of factor Xa → decreased conversion of prothrombin → ↓ thrombin
aka PREDOMINANTLY acts on Xa
Fondaparinux mechanism?
Only binds to antithrombin III → selective inhibition of factor Xa
Aka acts only on Xa.
LMWH versus fondaparinux mechanism?
LMWH: PREDOMINANTLY acts on Xa
Fondaparinux: ONLY on Xa
Heparin versus fondaparinux. Bioavailability?
Fondaparinux has better bioavailability than heparin
Heparin versus fondaparinux. Half life?
Fondaparinux has 2-4x longer half time than heparin.
Heparin has short half life –> effec ceases quicly once administration is stopped.
Direct thrombin inhibitors. Mechanism?
Directly inhibit thrombin (freely circulating and in association with clots)
Act independently from antithrombin
!!!!!!!The effect of most parenteral anticoagulants (except for direct thrombin inhibitors) depends on native antithrombin. In patients with antithrombin III deficiency (e.g., due to nephrotic syndrome), this effect is reduced.
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If patient has nephrotic syndrome and reduced ATIII, what effect of parenteral anticoagulants?
effect is reduced
LMWH, fondaparinux
pentasaccharide molecules. what is this anticoagulant?
fondaparinux, ie synthetic heparin
Parenteral anticoagulants. What main side effect?
Bleeding, drug interactions
Parenteral anticoagulants.
UFH and LMWH. What side effect?
Allergic reactions
Heparin-induced thrombocytopenia: risk of type 2 HIT LMWH:UFH ≈ 1:10
Osteoporosis
Drug interactions (e.g., ASA, tetracycline)
UFH and LMWH. Why is adverse osteoporosis?
Dose-dependent; therefore, switch to oral anticoagulants for long-term therapy. Osteoporosis is most likely related to increased osteoclastic activity, but decreased production of calcitriol is another potential cause
Parenteral anticoagulants. What main side effect?
Fondaparinux?
Occasionally low platelet count
Parenteral anticoagulants. What main side effect?
Heparinoid (glycosaminoglycan)
Asthma exacerbation (rarely)
Parenteral anticoagulants. What main side effect?
Direct thrombin inhibitors
Allergic reactions, fever
!!!!!Heparin treatment requires regular monitoring of the platelet count, especially for UFH, even before starting treatment.
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Thrombocitopenia in anticoagulants?
Treatment with heparin, especially UFH, can cause thrombocytopenia.
Thrombocytopenia may be immune-mediated heparin-induced thrombocytopenia (formerly known as type 2 HIT) or non-immune heparin associated thrombocytopenia (formerly known as type 1 HIT):
Immune HIT. type?
Type 2 HIT
Non-Immune HIT. type?
type 1 HIT
Indications.
LOW-dose heparin?
DVT prophylaxis for prolonged bedrest, peri- and postoperative state, immobility
Indications.
HIGH-dose heparin?
Immediate anticoagulation effect for:
- Atrial fibrillation
- DVT, acute arterial thrombosis, PE
- Acute coronary syndrome, MI
- Mechanical heart valve replacement
- VTE prophylaxis for patients with hemodialysis, heart-lung machine, etc.
Indications.
Low molecular weight heparin?
Prophylaxis of DVT in orthopedic and abdominal surgery, prolonged immobility
Treatment of DVT
Acute coronary syndrome
Indications.
Direct thrombin inhibitors?
AF, VTE, Type 2 HIT
What anticoagulants have highest risk for HIT?
unfractionated heparin
Which type of HIT has worse prognosis?
type 2 HIT has a worse prognosis than type 1 HIT
What is BAD HIT?
Use direct thrombin inhibitors (Bivalirudin, Argatroban, Dabigatran) to treat the BAD HIT (heparin induced thrombocytopenia)
Contraindication for parenteral anticoagulants?
Recent stroke
Uncontrolled hypertension
Active bleeding
HIT (except for direct thrombin inhibitors which can be used for anticoagulation in HIT)
HIT. What anticoagulants can be used?
direct thrombin inhibitors
Pregnancy and anticoagulations. Mechanism of hypercoagulability?
Physiological hypercoagulability (e.g., due to increased levels of clotting factors) leads to increased risk of thrombosis.
What anticoagulants can be used in pregnancy?
UFH and LMWH
Which anticoagulant has fewer side effects in comparison to other?
LMWH has fewer side effects.
Patients with decreased renal function. Which cannot be used and why?
In severe renal failure: accumulation of LMWH → increased bleeding risk → adjust dose or switch to UFH
Heparin Low-dose dosing frequency?
Low dose: subcutaneous administration every 8–12 hrs
Heparin High-dose dosing frequency?
High dose: intravenous administration with bolus and continuous application via infusion pump
LMWH dosing?
Dosage depends on specific drug used, indication, body weight, and kidney function; adjust to body weight and decreased kidney function.
Effect of LMWH lasts for about ………
Effect of LMWH lasts for about 12 hours
LMWH.
Monitoring of anti-factor Xa is only necessary in patients with decreased kidney function (and significant over- or underweight); anti-factor Xa activity is measured 4 hrs after administration
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Severe bleeding is more common in heparin or LMWH?
Heparin
HIT is more common in heparin of LMWH?
Type 2 HIT is about 10-fold more common
What to monitor if heparin is used therapeutically?
If used therapeutically, PTT levels have to be monitored frequently (target range: 1.5–2.5-fold prolongation)
In what CcCl is contraindicated LMWH?
Contraindicated if renal function is poor (CrCl < 30mL/min)
LMWH - No full antagonist available (only partial that binds 50proc)
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When to use heparin?
Emergencies and renal failure
Patient has renal failure, what anticoagulant is used?
Heparin - for patients with advanced renal failure (e.g., in patients with severe renal insufficiency (CrCl < 30mL/min) or the elderly)
LMWH - contraindicated in <30ml/min
LMWH use?
DVT prophylaxis, outpatient care (longer half-life → fewer injections)
Generally preferred to UFH (fewer side effects, easier handling) as long as there are no contraindications
