Thrombosis, Embolism and Infarction Flashcards
what is thrombosis
pathologic formation of intravascular blood clot
where can thrombi occur
in veins or arteries
most commonly thrombi are found in and originate from
deep veins of lower extremities (leg)
characteristics of thrombi
- Lines of Zahn (alternating layers of platelets, fibrin and red blood cells)
- attached to vessel walls
what is Virchow’s Triad of formation
- Endothelial damage
- Alterations in normal blood flow
- Hypercoagulability
Normally, thrombosis is prevented bc
- Intact endothelium limits exposure to subendothelial collagen and tissue factor
- Endothelial cells produce prostacyclin and nitric oxide- inhibit vasodilation and platelet aggregation
- Endothelial cells produce substances which inhibit thrombin and coagulation factors
- Secrete tissue plasminogen activator
- Secrete thrombomodulin
endothelial damage can be defined as
any disturbance in dynamic balance of endothelium can lead to thrombosis
physical loss of endothelium leads to
- exposure of subendithelial ECM
- aggregation of platelets
- release of TF
- local depletion of prostaglandins and plasminogen activators
how does endothelial cell dysfunction disturb balance
convert procoagulant factors to anticoagulant effectors
name 3 causes of endothelial cell damage
- atherosclerosis
- increased homocysteine levels
- vasculitis
normal blood flow is
laminar - platelets flow centrally in vessel lumen, separated from endothelium by slower moving plasma
what can cause alteration in blood flow
- turbulence
2. stasis
what is turbulence
countercurrents and pockets of stasis contribute to arterial and cardiac thrombi
what is stasis
contributes to venous thrombi (slow moving blood)
ulcerated atherosclerotic plaques cause
turbulence and exposure to ECM
aneurysms cause
local stasis
myocardial infarctions cause
stasis and flow abnormalities
mitral valve stenosis cause
left atrial dilation
arterial fibrillation and stasis
hyperviscosity causes
- polycythemia
2. sickle cell anemia
what is polycythemia
small vessel stasis and increased resistance to blood flow
what is sickle cell anemia
vascular occlusion
other clinical settings for thrombosis
- arterial aneurysms in myocardial infarction
- immobilization (causes DVT)
- trauma, surgery, burns associated with reduced physical activity
- cardiac failure
- malignancies associated with tumour-associated tissue thromboplastic release (called migratory trombophlebitis)
hypercoagulability/thrombophilia due to increased
procoagulation or defective anticoagulation
inherited forms of hypercoagulability/thrombophilia
- patients present with deep venous thrombosis at young age
- usually veins of leg are involved
name 4 inherited hypergoaulable diseases
- Factor V Mutation/Leiden mutation
- Prothrombin 20210A
- Protein C/S deficiency
- Antithrombin III deficiency
Factor V Leiden has a mutated form of factor
V therefore lack cleave site for deactivation by protein C and S
Factor V Mutation presents in –% of Caucasians
2-15%
Factor V mutation is one of the most common reasons for inherited
hypercoagulation
do homozygous and heterozygous pts have an increase risk of thrombosis with a factor V mutation
homozygous
what happens in pts with heterozygous genes for factor V mutation
propensity for thrombosis with other acquired risk factors:
- pregnancy
- prolonged best rest
- long airplane flights
prothrombin 20210A is what type of mutation
point mutation in prothrombin - increased gene expression
prothrombin 20210A increases
thrombin increases chance of thrombosis
Protein C/S deficiency decreases
negative feedback on coagulation cascade
describe Warfarin skin necrosis
Protein C/S deficiency causes skin thrombosis at onset of warfrin therapy (normally, warfarin causes temporary deficiency of protein C and S in normal individuals)
the drug warfarin is given to patients with
thrombosis
what is heparin
an anticoagulant
mechanism of action of heparin
- given to patients to prevent thrombosis
- acts by binding and activating antithrombin III
what happens to patients with antithrombin III deficiency
heparin is unable to find to antithrombin III and anticoagulation is not achieved
pts with antithrombin III deficiency is given —- insntead
Coumadin
Name 2 acquired hypercoaulable states
- Heparin induced thrombocytopenia
2. antiphospholipid antibody syndrome/ lupus anticoagulant syndrome
when does heparin induced thrombocytopenia occur
following administration of unfractionated heparin
what happens in heparin induced thrombocytopenia
induces antibodies which recognize complexes of heparin and platelet factor 4 on the surface of platelets
heparin induced thrombocytopenia can lead to
thrombocytopenia
prothrombotic state
what is used instead of unfractionated heparin
newer low molecular weight fractionated heparins - less incidence of HIT
see slide 25
see slide 25
clinical presentation of Antiphopholipid Antibody Syndrome/ Lupus Anticoagulant syndrome
- recurrent thrombosis
- repeated miscarriages
- cardiac valve vegetations
- thromboytopenia
- pulmonary embolism
- bowel infarction
- renovascular hypertension
mechanism of antiphospholipid antibody syndrome/ lupus anticoagulant syndrome
- auto-antibodies induce a hypercoaguable state mediated by binding to epitopes on prothrombin
- activating platelets and endothelial injury
primary form of antiphospholipid antibody syndrome/ lupus anticoagulant syndrome
no autoimmune disorders associated with certain drugs/infections
secondary form of antiphospholipid antibody syndrome/ lupus anticoagulant syndrome
associated with lupus
aggressive form of antiphospholipid antibody syndrome/ lupus anticoagulant syndrome causes
widespread small vessel thrombi and multiorgan failure
antiphospholipid antibody syndrome/ lupus anticoagulant syndrome causes a false positive for
serologic test fr syphillis
what are the types of thrombi
- mural - occur on endocardium; not occlusive
- arterial
- venous
- cardiac
arterial and cardiac thrombi develop at sites of
turbulence or endothelial injury
venous thrombi develop at sites of
stasis
arterial and venous thrombi can both propagate towards
heart - can detach and become emboli
DVT occur in what veins
- popliteal
- femoral
- iliac
LE DVTs associated with
stasis and hypercoagulable states
predisposing factors of DVT
immobilization, congestive heart failure, pregnancy, tumors
DVTs can emobolize to
lungs and cause pulmonary infarction
pulmonary infarction are asymptomatic in –% cases
50% (develop collateral channels)
arterial thrombi may send fragments (emboli) in
systemic circulation
which organs are more prone to emboli
organs that get more % of cardiac output
ex. brain, kidneys, spleen
what is disseminated intravascular coagulation (DIC)
-fibrin thrombi in small vessels that cause circulatory insufficiency
DIC is a consumptove coagulopathy, meaning
there is reduced platelets, fibrinogen, F-VIII and other consumable clotting factors
in what patient type is DIC seen in
- obstetric complications
- advanced malignancy
- shock
DIC is caused by
widespread activation of thrombin
what organs are affected by DIC
brain, heart, kidneys
DIC is initially
thrombotic, then bleeding (after clotting factors used up)
what is an embolus
intravascular mass carried away by blood stream to a site remote from its origin
emboli may consist of
- blood clots (thromboembolism- most common),
- atherosclerotic plaques (cholesterol clefts seen)
- gas / air
- amniotic fluid
- fat
- bone marrow fragments
- microorganisms
- tumor cells
pulmonary embolism due to
thromboemboli
name 4 sources of pulmonary thrombi
- Deep saphenous veins
- Periprostatic venous plexus
- Uterine venous plexus
- Right atrium
risk factors for pulmonary embolism
- immobility due to recent surgery, injury or obesity
- hereditary states eg. factor V leiden
- oral contracepties
- neoplasms
complications of pulmonary embolism
- sudden death (saddle embolus)
- pulmonary infarct
- pulmonary hypertenstion
pulmonary infarct
occlusion of large or medium artery obstructed in compromised lung (eg. pneumonia, congestive heart disease)
pulmonary hypertension
> 60% obstruction by thrombus and with chronic emboli, increases work of R ventricle
systemic thromboembolism usually — emboli
arterial
systemic thromboembolism cause
infarction and gangrene
80% of systemic thromboembolism arise from — heart
left heart
paradoxical emobli
-emboli gaining access to systemic circulation through heart defects
how does air embolisms form
air enters venous circulation
how does air embolisms form
air enters venous circulation
air enters venous circulation through
- neck wounds
- thoracocentesis
- puncture of major veins during surgical procedures
- hemodialysis
air enters venous circulation through
- neck wounds
- thoracocentesis
- puncture of major veins during surgical procedures
- hemodialysis
gas bubbles within circulation can coalesce to form
frothy masses obstructing blood flow
gas bubbles within circulation can coalesce to form
frothy masses obstructing blood flow
decompression sickness affects
deep sea scuba divers
decompression sickness affects
deep sea scuba divers
how do you treat acute decompression sickness
placing individual in high pressure chamber
how do you treat acute decompression sickness
placing individual in high pressure chamber
mechanisms of fat embolism
mechanical obstruction of circulation and endothelial damage caused by fatty acids release from embolizing fat globules
what is caissons disease
chronic form of decompression sickness
-persistence of gas emboli in skeletal system causing ischemic necrosis of bone
clinical symptoms of amniotic emboli
severe dyspnea cyanosis hypotensive shock seizures coma
most common risk factors for fat embolism
long bone fracture after accidents or orthopedic procedures
clinical consequences of fat embolism
- respiratory failure (tachypnea, dyspnea, tachcardia, petechie)
- neurologic findings (delirium, coma)
when do clinical symptoms of fat embolism appear
1-3 days after injury
mechanisms of fat embolism
mechanical obstruction of circulation and endothelial damage caused by fatty acids release from embolizing fat globules
amniotic fluid emboli
amniotic fluid enters venous circulation through torn veins in pts having difficult labor or immediate postpartum period
clinical symptoms of amniotic emboli
severe dyspnea cyanosis hypotensive shock seizures coma
infarct
localized area of dead cells within an organ
white infarcts occur in
arterial occlusions in solid organs with end-arterial circulation (heart, spleen, kidney)
which is more damaging: hypoxia or ischemia
ischemia - bc decreased oxygen, nutrients and decreased removal of toxic metabolites
causes on infarcts
- obstruction of vessel
2. hyptension
septic infarctions
an infarct is converted into an abscess by superimposed infection
red (hemorrhagic) infarcts seen with
- venous occlusions (ovary)
- loose tissue (lung)
- dual circulations (lung and small intestine) - blood flows form an unobstructed parallel supply into a necrotic zone
- sluggish venous outflow
- blood flow re-established to site of previous arterial occlusion and necrosis (e.g., following angioplasty of an arterial obstruction)
white (anemic) infarcts occur in organs with – blood supply
single (ie. heart, spleen)
white infarcts occur in
arterial occlusions in solid organs with end-arterial circulation (heart, spleen, kidney)
most infarcts morphologically show
ischemic coagulative necrosis
Brain and CNS show what type of infarct
liquefactive necrosis
septic infarctions
an infarct is converted into an abscess by superimposed infection
— blood supply helps against infarction
alternate (ex. liver, lung)
— arterial vascular obstruction causes infarction
end (ex. spleen)
— developing occlusions less likely to cause infarction
slow
neurons have irreversible damage in – minutes
3-4
myocardial cells damage in – minutes
20-30
