3. Thrombosis and Embolism Flashcards
- Embolism - fragment of blood clot breaks off and travels throughout the ____
- Systemic - derived from ____ emboli
- Pulmonary - the major silent killers, comes from ____ (undetected until the thrombotic event)
- Fat/marrow - less common, but seen in fat embolism syndrome - crushing of ____ and deep fractures - marrow spilling into blood stream
vasculature
artrial
DVT
legs
- Denuted epithelium > expose ECM > collagen/vWF > recruits platelets > adhere, activated and aggregate > for the primary platelet plug > stabilized through intiiation of coag cascade > activated by ____, TF turns on factors in ext pathway > form a complex on platelet surface > allows to cleave ____ to thrombin > thrombin cleaves fibrinogen bt platelets > forms fibrin, and stablized with ____
- Want to dissolve fibrin mesh > ____ phase > clot organizes and dissolves > prevents propagation of clot
- If clot were to propagate > beginning thrombus formation; it serves as a ____ of additional platelets/RBCs/WBCs
- Prevent propagation with ____ and ____ > become important in thrombosis formation
TF prothrombin F13 fibrinolytic catcher PTA thrombomodulin
• Hemostasis- a series
of regulated processes that maintain blood in a ____, ____ STATE in normal vessel while rapidly forming a LOCALIZED HEMOSTATIC PLUG, at the site of vascular injury.
• Thrombosis- a
series of ____ processes contributes to the formation of a clotted mass within the uninterrupted vascular system.
* Clotted mass - not localized \_\_\_\_ plug * In thrombosis, favor pro-agg processes over anti-agg processes * In bleeding disorders, favor anti-coag or pro-coag
fluid
clot-free
dysregulated
hemostatic
Virchow’s Triad
• Describes the inter-relationship between the 3-primary abnormalities that lead to thrombus formation
• 3 conditions that lead to thrombosis: ○ \_\_\_\_ injury leads to abnormal \_\_\_\_ and \_\_\_\_ § "Wash" away protective effects of endo layers § Physical change in vasculature leading to abnormal BF § Endo has both pro and anti-thrombotic properties, so its injured, you will see an increase in \_\_\_\_ ○ Abnormal BF leads to endothelial and hypercoagulability § Turbulence - ocean hitting rocks on the beach § \_\_\_\_ - little to no circulation § Coagulation factors are in the blood, so this affects \_\_\_\_ ○ Hypercoagulability
endothelial BF hypercoagulability coagulation stasis hypercoagulability
Endothelial Injury
• Particularly important for thrombus formation in heart or ____ circulation
– WHY? – because normal high flow impedes clotting by preventing platelet adhesion and dilution of coagulation factors.
• Causative Factors – Hemodynamic disruptions (\_\_\_\_) – Turbulent blood flow (for example in regions of \_\_\_\_) – Bacterial \_\_\_\_ – Hyperlipidemia (for example: areas of \_\_\_\_ plaques) – \_\_\_\_ smoke – \_\_\_\_ injury
• Hypertension - increase pressure on endothelium > alters expression of endothelial \_\_\_\_ > pro-agg genes are hyper-expressed • Turbulent BF - scarring, plaque formation • Bacterial endotoxins - bacteria release \_\_\_\_ > injure endo • Hyperlipidemia - plaque is highly \_\_\_\_, highly reactive lipid that sits in lumen > these plaques can ulcerate > lipid expose, recruiting platelets leading to thrombus formation ○ Physically, the plaques occlude part of lumen • Cig - \_\_\_\_ environment • Radiation - \_\_\_\_
arterial hypertension scarring endotoxins ulcerated cigarette radiation
genes ROS oxidated oxidative scarring
Endothelium: pro and anti-thrombotic properties
Endothelial injury causes changes in the dynamic balance of pro and anti- thrombotic activities.
Anti-thrombotic
Factors that normally inhibit thrombosis
- Fibrinolytic
- Anti-coagulants; heparin, anti-thrombin, thrombomodulin
- Anti-platelet aggregatory, PGI2, ADPase NO
- Normal endothelium - anti-____
- Activate fibrinolysis - ____
- All of these are released by endothelium; if scarred, inflamed, covered by plaque > shifted balance from anti to pro-thrombotic state
thrombotic
TPA
Endothelium: pro and anti-thrombotic properties
Endothelial injury causes changes in the dynamic balance of pro and anti- thrombotic activities.
Pro-thrombotic
Factors that normally activate clot formation in response to injury
- ____ and vWF exposed
- Activation of ____ cascade
- secrete inhibitor sof ____
- In damaged endothelium > exposed collagen/ECM > platelets adhere, activated and promote thrombosis
- ____ plaque is a breeding ground for platelet aggregation and adhesion
ECM
coagulation
plasminogen activator (PAIs)
ulcerated thrombotic
Alterations in Blood Flow
Turbulence-Causes endothelial injury and contributes to formation of counter currents and local pockets of ____ (as in veins)
Turbulence and stasis
Promotes endothelial activation through flow induced changes in ____ expression
Brings platelets into contact with endothelium.
Prevents ____ of clotting factors by fresh blood
____ inflow of clotting inhibitors
* Normal blood flow = \_\_\_\_ flow * Turbulence - altered BF > counter currents and pockets of slow BF * Both turbulence and stasis is sensed by endothelium, and activates the endothelium > changes gene expression > increasing pro-agg compounds
stasis gene dilution retards laminar
Blood flow may be altered by: - \_\_\_\_, create turbulence exposes ECM • \_\_\_\_- local stasis - non-contractile \_\_\_\_ • Hyper-\_\_\_\_syndrome • \_\_\_\_ cell anemia
• UAP - acts as a catcher of \_\_\_\_, fibrin - bumps within lumen that increase turbulent flow • Red - highest rate of flow; blue is lowest rate of flow** • The first three are all structural changes (UAP, A and NCM) • BF altered at level of blood itself: ○ HVS - blood is \_\_\_\_, and it flows more slowly (phenotypically similar to \_\_\_\_) ○ SCA - looks identical to activated platelet with \_\_\_\_, thereby altering BF
ulcerated atherosclerotic plaques aneurysms myocardium viscosity sickle
platelets
thicker
pseudopodia
Hyper-coagulability ( a.k.a. thrombophilia)
Any alteration in the coagulation pathway that predisposes to thrombosis
Genetic (primary)
•Factor V mutations (____ mutation), 2- 15% of ____ carry this mutation. Factor V cannot be inactivated by Protein-____
•Mutations in ____, Protein C or Protein ____
•Increased pro-thrombin due to ____ mutations
•Homocystenemia •Fibrinolytic defects (very rare)
* Not as defining of a factor as altered BF or endothelial injury * F5 sits on platelet surface and holds pro-thrombin to close prox to F10, now cannot turn off thrombin synthesis - \_\_\_\_ * Homocystenemia - \_\_\_\_ residues bind to fibrin and keep it from breaking down * FD - genetic mutations in factors involved in breaking down \_\_\_\_ mesh; not very common bc they're \_\_\_\_ in utero
leiden caucasians C anti-thrombin III S promoter thrombophiliac cysteine fibrin lethal
Hyper-coagulability (a.k.a. thrombophilia)
Acquired (secondary) HIGH risk for thrombosis •Auto-immune: \_\_\_\_ antibody syndrome or \_\_\_\_ induced thrombocytopenia •Cancer •Prolonged \_\_\_\_ rest or immobilization •Disseminated intravascular coagulation •\_\_\_\_ •Atrial fibrillation •Tissue injury: i.e fracture.
LOW risk for thrombosis •\_\_\_\_ •Cardiomyopathy •\_\_\_\_ •Hepatic dysfunction •\_\_\_\_ states (pregnancy and post-partum) •Smoking
• Autoimmune - generate antibody to self > these abs recognize epitopes on endo or platelet and cause aggregation ○ Heparin-induced - \_\_\_\_, not fractionated properly • Why leads to thrombocytopenia (8-12 days is half-life of platelet) - do not have the capacity to generate a lot of platelets • High levels of estrogen stimulate \_\_\_\_ factors ○ Becomes a problem if the person has a \_\_\_\_ mutation that is previously unknown > sever problems
anti-phospholipid heparin bed myocardial infarction oral contraceptives sickle cell anemia hyper-estrogenic
impure
pro-coagg
genetic
Disseminated Intravascular Coagulation
Pathological Activation of clotting in response to septicemia, cancer, obstetric, amniotic fluid retention. Initial thrombotic disorder may become a bleeding catastrophe
Features
Widespread thrombi in ____
During coagulation phase; micro-thrombi consume platelets and coagulation factors (____). During fibrinolysis phase they release factors that inhibit normal ____ formation- thus contributing to excessive bleeding
• Secondary consequence that isn't a disease • Amniotic fluid or BM, here it's a bacterial \_\_\_\_ > causes a thrombotic event > microcirculature (extremities) > given heparin to dissolve what's in microcirculation, so it gives your body back it's normal co-agg factors ○ Baby - a lot of bleeding - given heparin > thrombi formed in microcirculation (toes, fingers) > consuming platelets and co-agg factors > consumption coagulopathy > these regions are getting the co-agg > do not have enough \_\_\_\_ co-agg factors in your BS; if you're bleeding out, you cannot form a normal plug • Here, bacterial infection > bruising, cannot respond to simple cut
microcirculation
consumption coagulopathy
endotoxin
circualting
General features and types of thrombi
General features
- Can develop anywhere in ____
- Size and shape depend on site of ____
- ____ attached to the underlying vascular surface
- Both arterial an venous thrombi propagate towards the ____
- Propagating portion often poorly attached and prone to fragment and emboli
Types:
•Arterial-grow ____ from point of attachment
•Venous-grow in direction of ____
•Mural- thrombi that grow in the ____ chambers or ____ lumen
vasculature origin focally heart retrograde blood flow heart aortic
Arterial (white) Thrombi
•Usually begin at site of turbulence or endothelial injury; often superimposed on ____ plaque
•Frequently ____
•Consist of meshwork of platelets, fibrin fewer red cells and degenerating leukocytes
•Most common sites in DECREASING order of frequency
•____ artery
•____ artery
•____ artery
• In artery > BF is quicker > won't capture as many \_\_\_\_ > white thrombi • Have a \_\_\_\_ appearance (fibrin-RBC-fibrin-RBC-etc.) • L: thrombus is attached to the injured point in the endothelial surface ○ Mag: alternating series of RBC-fibrin-RBC-etc. > striated > lines of \_\_\_\_; will not see this in venous thrombi
ruptured occlusive coronary cerebral femoral
RBC
striated
Zahn
Venous (red) Thrombi
•Most often ____
•The thrombus forms a long cast of the lumen, has a point of attachment
•Form in sluggish venous circulation thus contain more ____ cells
•Prone to develop in areas of stasis
•Most occur in superficial or deep veins of ____
•Thrombi in ____ veins of legs cause local congestion, swelling or pain •Thrombi in ____ veins - embolize
Common pre-disposing factors to DVT:
____ rest, immobilization (____ rides), injury trauma, ____
• Venous thrombi or red thrombi are mostly occlusive. Like the arterial, it forms a long cast of the lumen and a point of attachment. Most commonly in the \_\_\_\_ veins of the leg. So if they are in the superficial vein, often you have associated with that area of occlusion where these thrombi are: edema, pain, swelling, and deep vein thrombosis. They are often deep and vein thrombosis is not diagnosed or seen \_\_\_\_ unless there is an embolic event such as a pulmonary embolism. Individuals who already have clotting problems or more prone to thrombosis are also more prone to deep vain thrombosis and they are predisposed to these lack of mobility, bed rest, long airplane rides, injury, trauma, burns. • Venous thrombi is deep red, no lines of \_\_\_\_ ○ Richer in RBC
occlusive red legs superficial deep
bed
airplane
burns
superficial
clinically
Zahn
