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Microscopic:
acute pulmonary congestion - alveolar capillaries
engorged with blood; there may be associated alveolar
septal edema &/or focal intraalveolar hemorrhage
chronic pulmonary congestion - the septa are thickened
& fibrotic, & the alveolar spaces may contain numerous
hemosiderin-laden macrophages (heart failure cells)
acute hepatic congestion - the central vein & sinusoids
are distended with blood, central hepatocyte degeneration;
the periportal hepatocytes, better oxygenated because of
their proximity to hepatic arterioles, experience less severe
hypoxia & may only develop fatty change
chronic passive congestion of the liver
Gross: central regions of the hepatic lobules are red-brown &
slightly depressed (owing to a loss of cells) & are
accentuated against the surrounding zones of uncongested
tan liver (nutmeg liver)
Figure 4-13 Virchow triad in thrombosis. Endothelial integrity is the single most important factor. Note
that injury to endothelial cells can affect local blood flow and/or coagulability; abnormal blood flow (stasis
or turbulence) can, in turn, cause endothelial injury. The elements of the triad may act independently or
may combine to cause thrombus formation.
1. Endothelial Injury
The dominant influence; By itself can lead to
thrombosis
Thrombus formation within the cardiac chambers
(e.g., following endocardial injury due to myocardial
infarction), over ulcerated plaques in atherosclerotic
arteries, or at sites of traumatic or inflammatory
vascular injury (vasculitis) is largely due to
endothelial injury.
Physical loss of endothelium will lead to exposure of
subendothelial ECM, adhesion of platelets, release of
tissue factor, & local depletion of PGI2 & PAs.
Any perturbation in the dynamic balance of the pro-
and antithrombotic effects of endothelium can
influence local clotting events
Dysfunctional endothelium may elaborate greater
amounts of procoagulant factors (e.g., platelet
adhesion molecules, tissue factor, PAI) or may
synthesize less anticoagulant effectors (e.g.,
thrombomodulin, PGI2, t-PA).
Significant endothelial dysfunction (in the absence of
endothelial cell loss) may occur due to the
hemodynamic stresses of hypertension, turbulent flow
over scarred valves, or bacterial endotoxins.
Even relatively subtle influences, such as
homocystinuria, hypercholesterolemia, radiation, or
products absorbed from cigarette smoke may initiate
endothelial injury.
2. Alterations in Normal Blood Flow
Primary (Genetic)
Common
Mutation in factor V gene (factor V Leiden)
Mutation in prothrombin gene
Mutation in methyltetrahydrofolate gene
Rare
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Very rare
Fibrinolysis defects
Secondary (Acquired)
High risk for thrombosis
Prolonged bed rest or immobilization
Myocardial infarction
Atrial fibrillation
Tissue damage (surgery, fracture, burns)
Cancer
Prosthetic cardiac valves
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Antiphospholipid antibody syndrome (lupus
anticoagulant syndrome)
Lower risk for thrombosis
Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy)
Oral contraceptive use
Sickle cell anemia
Smoking
Heparin-induced thrombocytopenia syndrome
5% of the population
Occurs when administration of unfractionated heparin
(for purposes of therapeutic anticoagulation) induces
formation of antibodies that bind to molecular
complexes of heparin & platelet factor 4 membrane
protein
This antibody can also bind to similar complexes
present on platelet & endothelial surfaces; the result
is platelet activation, endothelial injury, & a
prothrombotic state.
To reduce this problem, specially manufactured low-
molecular-weight heparin preparationswhich retain
anticoagulant activity but do not interact with
plateletsare used.
Antiphospholipid antibody syndrome
(APAS)
Has protean clinical presentations, including multiple
thromboses
Associated with high titers of circulating antibodies
directed against anionic phospholipids (e.g.,
cardiolipin) or, against plasma protein epitopes that
are unveiled by binding to such phospholipids (e.g.,
prothrombin).
Patients with anticardiolipin antibodies also have a
false-positive serologic test for syphilis because the
antigen in the standard tests is embedded in
cardiolipin. In vitro these antibodies interfere with the
assembly of phospholipid complexes & thus inhibit
coagulation. However, in vivo, the antibodies induce a
hypercoagulable state.
Patients with antiphospholipid antibody syndrome fall
into 2 categories: