HEMODYNAMICS LECTURE 2: Hemostasis & thrombosis Flashcards
What is the purpose of endothelial cells in hemostasis?
Express anticoagulant or procoagulant factors to regulate clotting
Where do platelets originate?
Megakaryocytes in bone marrow
What are the two pathways of the coagulation cascade?
Intrinsic and extrinsic
How is the intrinsic pathway activated?
Contact with collagen
How is the extrinsic pathway activated?
Contact with tissue factor (thromboplastin) following tissue injury
Where do the intrinsic and extrinsic pathways converge?
Factor Xa
What is the key event of the common coagulation cascade?
The conversion of fibrinogen to fibrin
What converts fibrinogen into fibrin?
Thrombin
What are 2 vital cofactors in the coagulation cascade?
Calcium and vitamin K
What is PT, and what does it measure?
Prothrombin time, measures clotting time in extrinsic and common pathways
How is the PT test done?
Add tissue factor, phospholipids, and Ca++ to citrated plasma
What is aPTT, and what does it measure?
Activated partial thromboplastin time, measures clotting time in intrinsic and common pathways
How is the aPTT test done?
Add negative charge, phospholipids, and Ca++ to plasma
What is TT, and what does it measure?
Thrombin time, measures function and level of fibrinogen in blood
How is the TT test done?
Add thrombin to plasma
Which clotting time is usually the fastest?
PT
Which clotting time is usually the slowest?
aPTT
What is a normal platelet count?
150000-450000 plt/mcL
What is a low platelet count called?
Thrombocytopenia
What is a high platelet count called?
Thrombocytosis
What are the three components of virchow’s triad?
- Endothelial injury
- Abnormal blood flow
- Hypercoagulability
How does endothelial injury lead to thrombosis?
Loss of endothelial cells or imbalance of pro-and anti-coagulation factors can lead to abnormal blood flow or hypercoagulability
How does abnormal blood flow lead to thrombosis?
Turbulence or stasis can lead to endothelial injury or hypercoagulability
What are two kinds of hypercoagulability?
Primary (genetic)
Secondary (acquired through e.g. OCP, pregnancy, HRT, cancer, aging, smoking, obesity)
What are thrombi composed of?
Platelets, RBCs, WBCs, fibrin
What is the term for the alternating bands of light platelets and fibrin with darker red blood cells?
Lines of Zahn
Why are arterial thrombi most commonly found in the aorta and its major branches?
High pressure and turbulence
What is an example of endothelial damage in large arteries that can lead to thrombosis?
Ruptured atherosclerotic plaque
What is an example of abnormal blood flow in large arteries that can lead to thrombosis?
Aneurysm
What is an example of hypercoagulability in large arteries that can lead to thrombosis?
Polycythemia
Where do venous thrombi normally develop?
In the deep veins of the legs in the sinuses above valves
What are two main causes of venous thrombi?
- Reduced venous return
- Hypercoagulability
Why are 50% of DVTs asymptomatic?
Because collateral vessels form
Why does DVT cause PE?
Because the lungs contain the first microvasculature the embolism will encounter
What are 4 things that may happen to a thrombus?
- Dissolution
- Propagation
- Embolization
- Organization and recanalization
What is organization and recanalization of the thrombus?
Invasion by connective tissue and blood vessel formation through the thrombus
What 3 classes of drugs are used to treat or prevent thrombus?
- Anticoagulants
- Antiplatelets
- Thrombolytics
Which group of drugs block the liver enzyme required for vitamin K activation?
Coumarins (e.g. warfarin)
Which drug activates antithrombin to block thrombin from converting fibrinogen into fibrin?
Heparin
Which group of drugs either inhibit thrombin or factor Xa?
Direct oral anticoagulants (DOACs)
What are 2 examples of antiplatelet drugs?
Aspirin, thromboxane inhibitors
What are 2 examples of thrombolytic drugs?
Streptokinase, tissue plasminogen activator (tPA)
What are 3 risks of thrombosis treatment?
- Bleeding
- Vascular calcification due to vitamin K inactivation
- Embolization
What is the term for a sudden, insidious onset of widespread fibrin thrombi in the
microcirculation?
Disseminated intravascular coagulation (DIC)
Why does DIC cause uncontrolled bleeding?
It uses up all the platelets and clotting factors
What are 4 treatments for pulmonary embolism?
- Prevention, e.g. anticoagulants
- Inferior vena cava filter
- Thrombolytics
- Embolectomy
What kind of embolism may occur after skeletal or soft tissue injuries (e.g. CPR) and burns?
Fat or marrow embolism
What kind of embolism may occur due to surgical incision, intravascular catheters, laparoscopic procedures, chest wall injuries, or scuba diving?
Air embolism
What causes amniotic fluid embolism?
Amniotic fluid containing fetal epithelial cells and lanugo enters maternal circulation through open uterine and cervical veins
What will happen to an infarct if it is not fatal?
Scar tissue formation
Why are infarcts mostly caused by arterial thrombosis?
Because when a vein is occluded then the body is able to divert the blood to collateral vessels
Name 2 ways to classify infarcts
- Colour
- Presence of infection
What kind of infarcts occur in organs rich in blood supply?
Hemorrhagic (red) infarcts
Name 2 examples of organs that hemorrhagic infarcts occur
Lungs, small intestine
Explain the mechanism of hemorrhagic infarcts
Affected loose necrotic tissue fills with blood from surrounding blood vessels
What kind of infarcts occur in solid organs with end-arterial circulation?
Anemic (pale) infarcts
Name 3 examples of organs that may be affected by anemic infarcts
Heart, spleen, kidney
Explain the mechanism of anemic infarcts
The only artery supplying the organ with blood is occluded. Blood cannot accumulate from surrounding vessels as the organ tissue is dense/solid
Why do brain infarcts typically result in liquefactive necrosis?
Because neurons contain proteolytic enzymes that are released upon cell death
What are 4 factors the affect the development of an infarct?
- Nature of blood supply (single or dual)
- Rate of occlusion development
- Cells’ vulnerability to hypoxia
- Patient’s SpO2
