Blood Coagulation Flashcards
What is thrombosis?
The formation of an unwanted clot within blood vessels or the heart.
What is a thrombus?
A clot that adheres to a vessel wall.
What is an embolus?
A clot that floats within the blood.
Why are thrombi and emboli dangerous?
They may occlude blood vessels.
What are the steps required for clot formation?
Platelet activation and aggregation, formation of thrombin, production of fibrin, when cross-linked, stabilizes the clot.
How do platelets respond to vascular trauma?
By adhesion to the injury site, release of intracellular granules, and aggregation of the platelets.
What initiates the coagulation cascade leading to fibrin formation?
Factors released from injured tissue and platelets.
How is thrombin formed?
From prothrombin (factor II) by factor Xa.
What does thrombin catalyze?
The conversion of fibrinogen to fibrin.
What stabilizes the clot?
Cross-linking of fibrin strands.
What do endothelial cells maintain to prevent pathological thrombosis?
A nonthrombogenic lining in blood vessels.
How does the maintenance of transmural negative electrical charge help in preventing thrombosis?
It prevents the adhesion of circulating platelets.
What activates the fibrinolytic pathway?
The release of plasminogen activators.
What degrades coagulation factors in the prevention of thrombosis?
The activation of protein C.
What do Heparin-like proteoglycans do in preventing thrombosis?
Inhibit coagulation.
What is the role of prostacyclin (PGI2) in thrombosis prevention?
It is a potent inhibitor of platelet aggregation.
Name three categories of drugs that affect blood coagulation.
Platelet inhibitors, anticoagulants, thrombolytics.
List the platelet inhibitors.
Aspirin, ticlopidine, clopidogrel, abciximab, dipyridamole, eptifibatide.
Name the anticoagulants.
Heparin,
Low molecular weight heparin: Enoxaparin, tinzaparin.
Bivalirudin, Lepirudin: Not available in Jordan.
dalteparin, rivaroxaban.
Warfarin.
Dabigatran.
Apixaban.
Name the thrombolytics.
Alteplase, streptokinase, urokinase.
Name the drugs used in the treatment of bleeding.
Aminocaproic acid, protamine sulfate, vitamin K, tranexamic acid, aprotinin.
When should antiplatelet therapy be initiated after an infarction or stroke to obtain significant benefit?
Within 2 hours.
Why are antiplatelet drugs administered as adjuncts to thrombolytic therapy along with anticoagulants like heparin?
To maintain perfusion and limit the size of myocardial infarction.
What do platelet aggregation inhibitors target to interfere with platelet aggregation signals?
Inhibit COX-1, block GPIIb/IIIa, or ADP, or increase cAMP.
What is the goal of therapy with aspirin?
To selectively inhibit the synthesis of platelet thromboxane A2 by irreversibly inhibiting cyclooxygenase enzyme, thereby inhibiting platelet aggregation.
What does a small dose of aspirin inhibit?
Thromboxane synthesis in platelets (TXA2) but not prostacyclin (PGI2) synthesis in endothelium.
What is the dosage range for low-dose aspirin therapy?
81 to 325 mg per day.
What is the mechanism of action of aspirin?
Selective inhibition of COX-1 in low dose.
List the therapeutic uses of aspirin.
Prophylactic treatment of transient cerebral ischemia, reducing the incidence of recurrent myocardial infarction, decreasing mortality in post-myocardial infarction, and preventing coronary thrombosis in patients with unstable angina.
What are the adverse effects of aspirin?
Bleeding and gastrointestinal ulceration.
How do ticlopidine and clopidogrel inhibit platelet activation?
By blocking specific receptors for adenosine diphosphate (ADP) on the platelet membrane and inhibiting glycoprotein (GP IIb/IIIa) receptors.
What are the therapeutic uses of ticlopidine and clopidogrel?
Alternative prophylactic therapy to aspirin in secondary prevention of stroke, myocardial infarction, and unstable angina.
What is the most serious side effect of ticlopidine?
Neutropenia.
What other side effects are associated with ticlopidine?
Thrombocytopenia and aplastic anemia.
How is clopidogrel activated and what can diminish its action?
Clopidogrel is a prodrug activated by CYP450; hepatic enzyme inhibitors (e.g., omeprazole) can diminish its action.
What is abciximab and why is its use limited?
A murine monoclonal antibody against GP IIb/IIIa; its use is limited because it is expensive.
What is eptifibatide and how is it administered?
A GP IIb/IIIa blocker, available only IV because oral is too toxic.
How does dipyridamole inhibit platelet aggregation?
By inhibiting phosphodiesterase, which increases cAMP in platelets.
How is dipyridamole taken and what are its primary uses?
Taken orally; primary prophylaxis in patients with prosthetic heart valves (in combination with warfarin) and as prophylactic therapy to treat angina pectoris (in combination with aspirin).
What is the main disadvantage of dipyridamole?
Headache.
What is an advantage of dipyridamole compared to other platelet inhibitors?
No excess risk of bleeding.
What are the two types of heparin used clinically?
Standard heparin and low-molecular-weight heparin (LMWH).
How is LMWH derived?
From standard heparin.
What is the advantage of LMWH over standard heparin?
Greater bioavailability and longer-lasting effect.
Why is LMWH more effective than standard heparin?
It is more effective in preventing and treating venous thromboembolism.
How is LMWH administered?
Subcutaneous administration (e.g., dalteparin, enoxaparin).
What is a monitoring advantage of LMWH over standard heparin?
LMWH requires less monitoring.
How does heparin work?
Binds to antithrombin III, inducing conformational changes that accelerate the interaction of antithrombin III with coagulation factors; also catalyzes the inhibition of thrombin by heparin cofactor II and factor Xa.
What are the therapeutic uses of heparin?
Deep vein thrombosis, pulmonary embolism, myocardial infarction, and treating pregnant women with venous thromboembolism.
How must heparin be administered?
Parenterally, either subcutaneously or intravenously.
Why is intramuscular heparin contraindicated?
Because of hematoma formation.
How quickly does maximal anticoagulant effect occur after IV heparin injection?
Within minutes.
How is heparin prescribed?
On a unit basis rather than a milligram basis.
What does heparin inhibit?
Both in-vitro and in-vivo clotting of blood.
What are the adverse effects of heparin?
Bleeding and thrombocytopenia.
In which conditions is heparin contraindicated?
Bleeding, recent surgery, liver disease, renal disease, severe hypertension, and thrombocytopenia.
What is the mechanism of action of warfarin?
Warfarin is a vitamin K antagonist that induces hypocoagulability by forming structurally incomplete clotting factors.
What are the therapeutic uses of warfarin?
Treatment of venous thrombosis and pulmonary emboli.
What is the main adverse effect of warfarin?
Bleeding.
How is warfarin administered?
Orally.
How does warfarin differ from heparin in terms of hypocoagulability?
Warfarin induces hypocoagulability only in-vivo, unlike heparin.
In which conditions is warfarin contraindicated?
Pregnancy, gastrointestinal ulceration, thrombocytopenia, hepatic or renal disease, recent surgery, and severe hypertension.
What is the purpose of thrombolytic therapy?
Rapid lysis of already formed clots.
How is fibrinolysis initiated?
By activation of the proenzyme plasminogen into plasmin.
What does plasmin do in fibrinolysis?
Catalyzes the degradation of fibrin.
What initiates the conversion of plasminogen to plasmin?
Plasminogen activators, tissue-type plasminogen activator, and single chain urokinase type plasminogen activator.
How do older first-generation thrombolytic drugs compare to newer drugs?
They are not selective.
What is alteplase (tPA) and its generation?
A second-generation tissue-type plasminogen activator.
What are the therapeutic uses of alteplase?
Treatment of myocardial infarction, pulmonary embolism, and acute ischemic stroke.
Why is alteplase superior to streptokinase and urokinase?
It is more effective in dissolving older clots.
When should alteplase be administered for an ischemic stroke?
Within 3 hours of the ischemic stroke.
What are the adverse effects of alteplase?
Bleeding, including gastrointestinal and cerebral hemorrhages.
What are the therapeutic uses of streptokinase?
Acute pulmonary embolism, venous and arterial thrombosis, and acute myocardial infarction.
What are the adverse effects of streptokinase?
Bleeding and hypersensitivity.
What are the therapeutic uses of urokinase?
Severe pulmonary emboli and deep vein thrombosis.
What is the main adverse effect of urokinase?
Bleeding.
Name two third-generation thrombolytic drugs.
Reteplase and tenecteplase.
What is anistreplase?
A preformed complex of streptokinase and plasminogen, and it’s a prodrug.
In which conditions are thrombolytic drugs contraindicated?
Pregnancy, metastatic cancers, and history of cerebrovascular accidents.
What are the therapeutic uses of aminocaproic acid and tranexamic acid?
To treat bleeding and overcome the effect of alteplase, streptokinase, and urokinase.
What is the adverse effect of aminocaproic acid and tranexamic acid?
Intravenous thrombosis.
What is the therapeutic use of protamine sulfate?
To treat bleeding and reverse the effect of heparin.
What are the adverse effects of protamine sulfate?
Bradycardia, hypotension, and flushing.
What is the therapeutic use of vitamin K?
To treat bleeding and overcome the effect of warfarin.
How long does the response to vitamin K take?
24 hours (time required to synthesize new coagulation factors).
What is the therapeutic use of sodium bicarbonate?
To treat aspirin toxicity by increasing renal elimination of aspirin.
What is the therapeutic use of aprotinin?
Inhibits streptokinase bleeding.
