Anticoagulant, Antiplatelet, and Thrombolytic Therapy Flashcards
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
