Anticoagulant, Antiplatelet, and Thrombolytic Therapy Flashcards
(25 cards)
1
Q
Formation of Platelet Plug
A
- Platelets interact with collagen on surface of damaged blood vessel
- Platelets adhere to site of vessel injury initiating platelet activation and aggregation
- Aggregation: fibrinogen bridges form between glycoprotein IIb/IIIa (GP IIb/IIIa) receptors (activated by collagen, thrombin, PAF, ADP, TXA2) on adjacent platelets
- Aggregated platelets constitute the ‘plug’ which temporarily stops bleeding but is unstable
2
Q
Coagulation
A
- Coagulation: production of fibrin, a protein meshwork that reinforces the platelet plug
- Fibrin produced via 2 pathways: intrinsic and extrinsic systems
–> Intrinsic (aka contact activation pathway):
all necessary clotting factors present in vasculature
–> Extrinsic (aka tissue factor pathway):
requires tissue factor (complex of several compounds present in vascular subendothelium)
–> paths converge at factor Xa, both systems are required for optimal fibrin production - Factor VII, IX, X, and prothrombin need Vitamin K synthesis
3
Q
Controls for Hemostasis
A
- Controls protect against widespread coagulation
- With healing of injured vessel, need mechanism to remove clot
Antithrombin: protein which forms a complex with clotting factors to inactivate them
Plasmin: enzyme formed from precursor plasminogen, digests fibrin meshwork of clot, facilitating clot removal (body’s own thrombolytic)
4
Q
Arterial Thrombosis
A
- Platelets adhere to artery wall due to wall damage or rupture of atherosclerotic plaque
- Platelet aggregation occludes artery and initiates coagulation cascade
- Platelet plug becomes reinforced with fibrin
- Get localized tissue injury due to lack of perfusion –> stroke, acute MI, peripheral vascular disease
5
Q
Venous Thromboembolism (VTE)
A
- Develop at sites with slow blood flow
- Stagnation of blood initiates coagulation cascade –> fibrin production traps RBCs and platelets forming a thrombus
- Part of thrombus may break off to form embolus –> travels within vasculature to cause clot at distant site (e.g. clot in pulmonary artery = pulmonary embolism)
- Clinical outcome: injury secondary to embolization at a site distant from original thrombus
- S&S: pain/tenderness (calf), swelling of ankle/foot, redness, warmth
6
Q
Pulmonary Embolism (PE)
A
- Symptoms: unexplained shortness of breath, rapid breathing, chest pain (may be worse upon deep breath), rapid heart rate, light headedness or passing out
7
Q
Virchow’s Triad
A
- factors that contribute to thrombosis
- Hypercoaguable state: malignancy, pregnancy, birth control, trauma, IBD, nephrotic syndrome, sepsis
- Vascular Wall Injury: trauma/surgery, venepuncture, heart valve disease, atherosclerosis, indwelling catheters
- Circulatory stasis: atrial fibrillation, LV dysfunction, immobility, venous insufficiency, venous obstruction
- Endocarditis
8
Q
Risk for VTE
A
Strong risk
- Prolonged hospitalization
- Surgery (especially orthopaedic or cancer-related)
- Prolonged immobility (e.g. bed-ridden)
Moderate risk
- Increasing age (esp. 60+)
- Personal or family history of VTE
- Cancer/chemotherapy
- Estrogen-based medication (e.g. oral contraceptives, hormone replacement therapy)
Other
- Obesity, smoking, pregnancy or post-partum
9
Q
Risk for Bleeding
A
Major risk factors: Current uncontrolled bleeding or recent bleed Severe hypertension Severe thrombocytopenia Bleeding disorders (e.g. hemophilia) Recent trauma Intracranial hemorrhage Patients undergoing lumbar puncture (or recent LP), regional anesthesia (epidural), surgery of eye, brain or spinal cord Abnormal liver function Anatomical lesion (neoplasm, CNS lesion)
10
Q
Drug Therapy
A
Aimed at
- Thrombosis prevention in at risk patients: VTE/arterial thrombus (stroke, MI) prophylaxis
- Thrombosis treatment (aka “therapeutic anticoagulation”) –> DVT and PE/ ischemic stroke, MI
- Dose depends on indication
11
Q
VTE Prophylaxis
A
- VTE is the most common preventable cause of hospital death
- Most patients have at least 1 VTE risk factor
- Strong evidence for routine use of VTE prophylaxis for most hospitalized patients –> contraindications: active bleeding or very high bleeding risk in which case mechanical prophylaxis (e.g. compression stockings) should be used
- VTE prophylaxis is the number one ranked patient safety practice for hospitals
12
Q
Contraindications to Therapy
A
Current uncontrolled bleeding or recent bleed Severe hypertension Severe thrombocytopenia Bleeding disorders (e.g. hemophilia) Recent trauma Intracranial hemorrhage Patients undergoing lumbar puncture (or recent LP), regional anesthesia (epidural), surgery of eye, brain or spinal cord Abnormal liver function Anatomical lesion (neoplasm, CNS lesion)
13
Q
Signs and Symptoms of Bleeding
A
Hemodynamic effects (decrease BP, increase HR)
Bruises, petechiae, hematomas
Blood in stool, melena
Cloudy or discoloured urine
Headache, faintness (suggests cerebral bleed)
Lumbar or pelvic pain (suggests adrenal or ovarian hemorrhage)
14
Q
Unfractioned Herparin (UFH)
A
- Mixture of long polysaccharide chains with many negatively charged groups
- Mechanism of action: increases antithrombin activity to neutralize thrombin and factor Xa (also IX, XI, XII) and suppress fibrin formation
- Does not lyse existing clots, but stop clot progression (allows body’s own thrombolytic system to remove clot)
15
Q
Pharmacoinetics of UFH
A
- Absorption and distribution: very large, highly polar molecule - no oral absorption, does not cross membranes or placenta
- Non-specific protein binding –> high interpatient variability in levels/activity
- Onset immediate with IV (slower with SC)
- Short half life (~ 1.5 hr) –> short duration (hours)
- Renal or hepatic disease –> decreased metabolism and excretion –> prolonged duration of action
- Safe in pregnancy
16
Q
Therapeutic Uses of UFH
A
- IV catheter lock flush (smallest dose)
- Thrombosis prevention (small-moderate dose)–> VTE prophylaxis, prevention of coagulation with devices of extracorporeal circulation (e.g. dialyzers)
- Thrombosis treatment (highest dose) –> DVT, PE, stroke, MI (adjunct to thrombolytic therapy), disseminated intravascular coagulation (DIC)
17
Q
UFH Side Effects: Bleeding
A
- Hemorrhage (~10%) biggest concern
- Risk minimization: assess for risk factors, monitor and titrate dosing as per nomogram/ anticoagulation guidelines, caution if using with antiplatelet drugs, monitor for signs and symptoms of bleeding (especially with treatment doses)
- Management of bleeding: stop UFH, FFP (fresh frozen plasma), protamine IV (rarely used)
18
Q
UFH Side Effects: Spinal/Epidural Hematoma
A
- Patients undergoing spinal puncture or epidural anesthesia at high risk
- Bleeding into spinal cord –> pressure can lead to paralysis
- Risk factors: epidural catheter; concurrent use of other anticoagulants or antiplatelet drugs; history of traumatic spinal puncture, spinal deformity, injury or surgery
- Monitor neurologic status
- Hold heparin for epidural manipulation
19
Q
UFH Side Effects: Heparin-Induced Thrombocytopenia (HIT)
A
- Immune-mediated reaction – formation of an antibody-heparin-protein complex that binds to platelets –> platelet activation, aggregation
- Leads to large drop in platelet count and 30 x higher risk of thrombosis
- Incidence ~ 0.5 – 3%, mortality up to 50%
- Develops 5-14 days after starting therapy (or immediately if previous heparin exposure)
- Blood test(s) confirm diagnosis
20
Q
Management of HIT
A
- Close monitoring of platelet count and for signs of thrombosis
- If HIT suspected: D/C heparin, must anticoagulate with alternative non-heparin drug, avoid LMWH, platelet transfusions, send blood sample for definitive diagnosis (HIT assay)
- If history of HIT –> not an absolute contraindication to using heparin again in future (needs careful assessment of risk/benefit)
21
Q
UFH: Other Side Effects
A
Hypersensitivity Reactions
- Product is an animal extract (contain antigens)
- May be chills, fever, urticaria
- Anaphylaxis rare
22
Q
UFH: Drug Interaction
A
- Antiplatelet drugs increase bleeding risk –> ASA, GP IIb/IIIa inhibitors, ADP receptor antagonists
- BUT…. these are often combined judiciously, based on careful evaluation of clotting vs. bleeding risk factors
23
Q
UFH: Monitoring
A
- Hemogloblin, platelet count, signs and symptoms of bleeding
- High interpatient variability so individualized dosing needed for therapeutic anticoagulation –> Goal: optimize dosing to prevent thrombosis and avoid bleeding
- For IV infusion –> monitor aPTT levels and adjust infusion rate using local laboratory “nomogram”
- Activated Partial Thromboplastin Time (aPTT)
- -> Measures activity of intrinsic clotting system and factors in the final common pathway
- -> Reagent added to test tube with blood sample, time to clot is measured in seconds
- -> Therapeutic anticoagulation range = 1.5 – 2 times control
- Anti-Xa (not usually) –>Measures ability of UFH to inhibit factor Xa in the reagent
24
Q
UFH: Dosing and Administration
A
- Dosed in units not mg
- Do not give IM (risk of hematoma)
- Treatment (therapeutic anticoagulation):
- -> Weight-based IV bolus dose then continuous IV infusion with rate titration per aPTT nomogram
- -> May overlap with warfarin therapy
- Prophylaxis: low dose SC injection - i.e. 5000 units SC BID-TID –> no monitoring (no effect on aPTT at low SC doses)
- IV catheter lock flush
25
UFH: A High Alert Medication
- High risk for serious medication error
- Many different products, concentrations
- Check product and calculations carefully
- -> IV infusion: 25,000 units per 250 mL IV bag
- -> SC injection: 5,000 units per 0.5 mL vial or pre-filled syringes
- -> Catheter lock flush: 300 units per 3 mL pre-filled syringe
- Independent double-check for UFH IV infusion pump settings
