Path: Hemodynamics 2 Flashcards
________ is inappropriate formation of blood clot in a blood vessel, usually occlusive.
Thrombosis
There are three predisposing factors to thrombosis:
referred to as Virchow’s triad by elderly pathologists
(1) Endothelial injury, (2) Abnormal blood flow, and (3) Hypercoagulability.
__________ is the most important factor predisposing to thrombosis.
Endothelial injury
The hemodynamic stress of hypertension or toxicity of hypercholesterolemia or products absorbed from smoking can create these pro-thrombotic events:
increase endothelial procoagulant factors or decrease their anticoagulant factors enough to cause thrombosis
T/F: Abnormal blood flow, either turbulence or stasis, and turbulent blood flow over ulcerated atherosclerotic plaques does NOT predispose to thrombosis.
False. They do predispose one to thrombosis.
T/F: thrombosis is more common in veins and more serious in arteries.
True
Thrombosis due to endothelial injury is mediated by:
endothelial cell activation or dysfunction
T/F: Activated or dysfunctional (messed up) endothelial cells express more thrombomodulin, tissue factor protein inhibitor and other anti-coagulant factors.
False. Less of each
Describe the effect of activated or dysfunctional endothelial cells on secretion of plasminogen activator inhibitors and up/down regulation of expression of t-PA.
Activated or dysfunctional endothelial cells also secrete plasminogen activator inhibitors and downregulate the expression of tissue plasminogen activator (t-PA).
Does the presence of plasminogen activator inhibitors and the downregulation of t-PA cause clotting? Explain.
No, but it is more likely to fail to stop a clot from occluding the entire vessel when platelets clot out of control.
Stasis promotes thrombosis by allowing platelets to spend more time sitting on ________ .
Endothelial cells
Normal blood flow is laminar and the platelets (and other cells) are concentrated in the central, more rapidly flowing bloodstream, while there is a peripheral layer of _______, moving more slowly, spending more time in contact with the blood vessel lining.
plasma
Describe the cellular presentation of polycythemia vera.
abnormally large number of erythrocytes, an autonomous proliferation of erythroid line bone marrow cells
Describe the condition Waldenstrom macroglobulinemia as it relates to viscosity and Ab load in the plasma.
abnormally thick hyperviscuous plasma loaded with excess IgM. Due to an autonomous proliferation of B lymphocytes making IgM.
How does turbulent blood flow promote thrombosis?
By activating, sometimes even injuring endothelial cells, and by creating countercurrents (eddies) creating local pockets of stasis.
What is the medical, super-sciency YAY! term for a hypercoagulable state?
thrombophilia
Hypercoagulable states can be congenital. List 6.
Factor V Leiden mutation Prothrombin gene mutation Methyl-tetra-hydro-folate reductase gene mutation Anti-thrombin 3 deficiency Protein C deficiency Protein S deficiency
Hypercoagulable states can be caused by acquired circumstances such as surgery or trauma. Name 5 other potential causes.
Cancer Bed-ridden state DIC Heparine-induced thrombocytopenia Antiphospholipid syndrome
_____________ is the most common inherited hypercoagulable state (5% of whites).
Factor V Leiden mutation
Describe the elevated risk (e.g. two-fold…) of venous thrombosis associated with Factor V Leiden mutation for heterozygotes and homozygotes.
Heterozygotes have a 5-fold higher risk of venous thrombosis and homozygotes have a 50-fold increased risk
In Factor V Leiden mutation, mutation in clotting factor V makes it resistant to activated __________, resulting in the loss of an important clot-limiting counter-regulatory mechanism.
protein C (activated form of which plays an important role in regulating anticoagulation) -Proteolytically inactivating proteins Factor Va and Factor VIIIa
_____________ is the second most common inherited hypercoagulable state (2% of whites) and it confers a 3-fold increased risk of venous thrombosis.
Prothrombin G20210A mutation
T/F: many pts with heterozygous mutations for hypercoagulable states or mutations causing less hypercoagulability live a normal lifespan without suffering venous thrombosis, and others get a deep venous thrombosis (typically in a leg) only when their congenital hypercoagulability is combined with an acquired hypercoagulability.
True
Patients under the age of ____ , who present with thrombosis, should be worked up for inherited hypercoagulability.
50
Why are patients hypercoagulable post-surgery?
surgery cuts blood vessels. Clotting factors inevitably spread beyond surgical site and can initiate clotting at other locations in the body.
Why does cancer, especially malignant tumors that outgrow their blood supplies, cause a hypercoagulable state?
This is partly due to the inflammatory response to malignant tumors.
Also, very often malignant tumors outgrow their blood supply and have some necrosis, which releases highly thrombogenic necrotic debris into the general circulation.
Malignant tumors frequently compress veins or invade them, partially or completely obstructing blood flow in them, creating turbulent flow or stasis, either of which predisposes to thrombosis. Malignant glandular tumors that produce mucin, which gets into the bloodstream, are particularly likely to cause thrombosis, because mucin is thrombogenic.
Describe migratory thrombophlebitis.
Metastatic cancers can cause simultaneous venous thrombi and inflammation to pop up at one subcutaneous site after another. This is called migratory thrombophlebitis
What makes antiphospholipid antibody syndrome life-threatening?
causes arterial thrombosis
Describe the laboratory findings in the serum of pts with antiphospholipid antibody syndrome.
These patients have autoantibodies against phospholipids (actually against plasma protein antigens unveiled by binding to phospholipids).
