Thrombolytic therapy Flashcards
What process stops bleeding in a blood vessel?
Haemostasis
What type of factors are involved in normal haemostasis?
Extrinsic and intrinsic factors
What is the first step in primary haemostatic plug formation?
Platelets adhere to sub-endothelial regions
What do platelets stimulate to reinforce the platelet aggregate? What happens to the platelet aggregate and fibrin clot as wound healing occurs?
Local activation of plasma coagulation factors
They are degraded
What is the role of the coagulation cascade in haemostasis?
- Each activated factor acts as a catalyst
- Enhances the next reaction
- Results in a large collection of fibrin
- Fibrin forms a plug in the vessel
What must blood do within the vasculature? When must blood clot quickly?
Remain fluid
When exposed to non-endothelial surfaces
What insoluble protein is essential to clot formation? What is the formation of a clot called? Where can a thrombus form?
Fibrin
Thrombosis
Any vessel, artery or vein
What can a venous thrombus develop from? What components attach to a thrombus, increasing its size?
Venous stasis, vessel injury and altered coagulation
Fibrin, platelets and RBCs
What system is activated to restore fluidity when intravascular thrombi occur?
Fibrinolysis
What does a delicate balance prevent in the normal situation?
Thrombosis and haemorrhage
What model describes the primary factors that influence pathologic clot formation?
Virchow’s Triad
What are the three components of Virchow’s Triad?
- Abnormality in blood flow
(AF, left ventricular dysfunction) - Abnormalities of surface in contact with blood
(Vascular injuries, AMI, fracture, chemical irritation) - Abnormalities of clotting components
(Protein C & S deficiency, thrombocytosis)
Where is venous thrombosis mainly found?
Venous circulations
What is venous thrombosis mainly composed of? Where do venous thrombi most often occur? What condition is deep vein thrombosis (DVT) associated with?
Fibrin and erythrocytes
Lower extremities
Venous stasis
What is the most common type of venous thrombosis? Where does arterial thrombosis mainly occur? What conditions can cause arterial thrombosis? What are arterial thrombi primarily composed of?
DVT
Regions of rapid blood flow
Atherosclerosis or arrhythmias
Platelets, fibrin and leukocytes
What class of drug is Heparin?
What class of drug is Aspirin?
What class of drug is Streptokinase?
Anticoagulant
Platelets aggregation inhibitors
Fibrinolytic agents
What are anticoagulants (like UFH, LMWH, warfarin and DOACs) used for?
What are platelet aggregation inhibitors (like aspirin and clopidogrel) used for?
When are fibrinolytic agents (like Streptokinase) notably used?
Treatment and prevention of BOTH venous and arterial thrombi
Prevention of arterial thrombi
During MI
What is the purpose of thrombolytic therapy? What is the role of the fibrinolytic system? What is treatment with fibrinolytic drugs not a substitute for?
Rapid lysis of already formed clots
Restricting clot propagation and fibrin removal
Anticoagulant drugs
What converts plasminogen to plasmin?
Plasminogen activator (t-PA)
What inactivates t-PA in the plasma?
Plasminogen activator inhibitor-1 (PAI-1)
What can activation of the fibrinolytic system with thrombolytic drugs disturb? What does plasmin degrade due to its low substrate specificity?
Regulatory mechanisms and elevate plasmin
Fibrinogen, plasminogen, coagulation factors
What does systemic un-physiological activation of the fibrinolytic system cause?
Consumption of coagulation factors and bleeding
What do thrombolytic drugs cause? What are thrombolytic drugs?
Lysis of clots and reestablish perfusion
Plasminogen activators
What is an ideal fibrinolytic? How do older fibrinolytic (1st gen like Streptokinase) agents differ from newer agents (3rd gen)?
One which can provide clot-selective effects
Older agents are not clot selective, newer have improved fibrin specificity
When are thrombolytics indicated? Why must thrombolysis be accomplished quickly after infarction?
Severe pulmonary embolism, DVT, arterial thromboembolism after MI and acute ischaemic stroke
Clots become more difficult to lyse
What is the impact of recanalization after 6 hours on the infarcted area? What is the impact of using thrombolytic drugs with shorter plasma half-lives?
Diminishing benefit
Greater incidence of rethrombosis
Why is concurrent administration with heparin and antiplatelet drugs advocated? What is a risk of concurrent administration with heparin and antiplatelet drugs?
Reduce reocclusion
Increased risk of bleeding
Where is streptokinase derived from? What is the main effect of systemic streptokinase administration? What are the most common unwanted effects of streptokinase?
β-hemolytic streptococci
Significant lysis of thrombus
Haemorrhage, pyrexia and anaphylaxis (due to immune response)
What type of plasminogen can Urokinase activate? Where is urokinase derived from? Why is urokinase not antigenic?
Circulating and fibrinogen bound
Human cell
It is derived from human cell so has no immune response
What is the principal physiological activator of plasminogen in the blood?
Tissue-type plasminogen activator (t-PA)
What type of binding affinity does t-PA have? How does t-PA activate plasminogen after IV administration?
High binding affinity for fibrin
Fibrin-selective activation
What has Alteplase been shown to be more efficacious than? What is the impact of alteplase on fibrinogenolysis at equi-effective thrombolytic doses?
Streptokinase in establishing coronary reperfusion
Causes less fibrinogenolysis than streptokinase
Why is the rate of re-thrombosis after t-PA greater than after streptokinase? What is the half-life of alteplase? What type of t-PA is reteplase?
Alteplase is rapidly cleared from the blood
5-10 mins
Genetically modified human t-PA
What are the characteristics of reteplase? What is Tenecteplase known as? What are the characteristics of tenecteplase? How is tenecteplase administered?
More potent with rapid onset with short half-life
TNK-tPA
Longer half-life, binds more avidly to fibrin
As IV bolus
What type of complex is Anistreplase? What does Anistreplase cause?
Streptokinase in a noncovalent 1:1 complex with plasminogen
Establishes coronary reperfusion but considerable fibrinogenolysis and is antigenic
What is the principal adverse effect associated with thrombolytic therapy? What should be monitored with laboratory tests when taking Thrombolytics? How does fibrinogenolysis compare between generations of thrombolytics at effective doses?
Bleeding due to fibrinogenolysis
Hypo-fibrinogenemia
Less extensive for second and third generation
What may life-threatening intracranial bleeding necessitate?
Stoppage of therapy and administration of blood
What condition is similar between thrombolytic and anticoagulant drugs?
C/Is
What are some absolute contraindications to thrombolytic drugs?
- Active bleeding
- Cardiopulmonary resuscitation (trauma to thorax possible)
- Intracranial trauma
- Vascular disease
- Cancer
What are some relative contraindications to thrombolytic drugs?
- Uncontrolled hypertension
- Earlier central nervous system surgery
- Any known bleeding risk
How is the degradation of the platelet aggregate and fibrin clot related to wound healing?
A necessary part of the healing process
What was the effect of early streptokinase usage on patient outcomes?
Greater benefits
Why are fibrin-specific factors so beneficial?
Plasmin is responsible for dissolving fibrin clots into soluble FDP but also dissolves fibrinogen into fibrin which negates the effect
Fibrin-specific stops this conversion
Fibrinolytics clinical use and indications
- Acute MI (STEMI)
- DVT
- PE
- Acute ischaemic stroke
- Acute peripheral arterial occlusion
- Occlusion of indwelling catheters
- Intracardiac thrombus formation
