CH4 - Hemostasis and Related Disorders Flashcards
1
Q
What is hemostatsis?
A
Damage to the wall is repaired by hemostasis,
2
Q
Hemostasis involves the formation of?
A
a thrombus (clot) at the site of vessel injury
3
Q
Hemostasis stages?
A
primary and secondary.
4
Q
Primary hemostasis?
A
forms a weak platelet plug
5
Q
Primary hemostasis is mediated by?
A
interaction between platelets and the vessel wall
6
Q
Secondary hemostasis?
A
stabilizes the platelet plug
7
Q
Secondary hemostasis is mediated by?
A
the coagulation cascade.
8
Q
What is Step 1 in secondary hemostasis?
A
Transient vasoconstriction of damaged vessel
9
Q
How is Step 1 in secondary hemostasis mediated?
A
by reflex neural stimulation and endothelin release from endothelial cells
10
Q
What is Step 2 in secondary hemostasis?
A
Platelet adhesion to the surface of disrupted vessel
11
Q
In step 2 of secondary hemostasis, how does platelet adhesion occur?
A
Von Willebrand factor (vWF) binds exposed subendothelial collagen,
12
Q
How do platelets bind to vWF?
A
via the GPIb receptor
13
Q
vWF is derived from?
A
the Weibel-Palade bodies of endothelial cells and a-granules of platelets.
14
Q
What is Step 3 in secondary hemostasis?
A
Platelet degranulation
15
Q
In step 3 of secondary hemostasis what does Adhesion induce?
A
shape change in platelets and degranulation with release of multiple mediators
16
Q
What are the mediators released in step 3 of secondary hemostasis?
A
ADP and TXA
17
Q
What is the role of ADP in step 3 of secondary hemostasis?
A
it is released from platelet dense granules; promotes exposure of GPIIb/IIIa receptor on platelets.
18
Q
What is the role of TXA in step 3 of secondary hemostasis?
A
it is synthesized by platelet cyclooxygenase (COX) and released; promotes platelet aggregation
19
Q
What is step 4 in secondary hemostasis?
A
Step 4?Platelet aggregation
20
Q
Where and how do Platelets aggregate in step 4 of secondary hemostasis?
A
at the site of injury via GPIIb/IIIa using fibrinogen (from plasma) as a linking molecule;
21
Q
What does platelet aggregation result in?
A
formation of platelet plug
22
Q
Platelet plug?
A
It is weak; coagulation cascade (secondary hemostasis) stabilizes it.
23
Q
What are disorders of primary hemostasis usually due to?
A
Usually due to abnormalities in platelets;
24
Q
Disorders of primary hemostasis are divided into?
A
quantitative or qualitative disorders
25
What are some Clinical features for disorders of primary hemostasis?
mucosal and skin bleeding.
26
What is the most common overall symptom in mucosal bleeding?
epistaxis
27
What are symptoms of mucosal bleeding?
epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia. Intracranial bleeding occurs with severe thrombocytopenia.
28
What are the symptoms of skin bleeding?
include petechiae (1-2 mm), ecchymoses (> 3 mm), purpura (> 1 cm), and easy bruising;
29
Petechiae are a sign of what?
thrombocytopenia and are not usually seen with qualitative disorders.
30
What are some useful laboratory studies for disorders of primary hemostasis?
platelet count, bleeding time, blood smear, bone marrow biopsy
31
Platelet count
normal 150-400 K/pL; < 50 K/pL leads to symptoms,
32
Bleeding time
normal 2-7 minutes; prolonged with quantitative and qualitative platelet disorders
33
Blood smear
used to assess number and size of platelets
34
Bone marrow biopsy
used to assess megakaryocytes, which produce platelets
35
What is immune thrombocytopenic purpura?
(ITP) is an autoimmune production of IgG against platelet antigens (GPIIb/IIIa)
36
What is the most common cause of thrombocytopenia in children and adults?
immune thrombocytopenic purpura
37
In ITP what results in thrombocytopenia?
Antibody-bound platelets are consumed by splenic macrophages
38
ITP is divided into?
acute and chronic forms
39
Acute form of ITP?
arises in children weeks after a viral infection or immunization;selflimited, usually resolving within weeks of presentation
40
Chronic form of ITP?
arises in adults, usually women of chilbearing age. May be primary or secondary (e.g SLE).
41
What is the risk involved in chronic ITP?
May cause short-lived thrombocytopenia in offspring since antiplatelet IgG can cross the placenta.
42
laboratory findings for ITP include
decreased platelet count, often < 50 K/pL, Normal PT/FTT, Coagulation factors are not affected. increased megakaryocytes on bone marrow biopsy
43
What is the Initial treatment for ITP?
corticosteroids.
44
How will children and adults respond to the initial treatment for ITP?
Children respond well; adults may show early response, but often relapse.
45
In addition to corticosteroids what else is used in the treatment of ITP?
IVIG is used to raise the platelet count in symptomatic bleeding, but its effect is short-lived,
46
What is a permenant solution for patients with ITP?
Splenectomy eliminates the primary source of antibody and the site of platelet destruction (performed in refractory cases).
47
What is microangiopathic hemolytic anemia?
Pathologic formation of plateletmicrothrombin small vessels
48
How are plateletmicrothrombin formed and what is the result?
Platelets are consumed in the formation of microthrombi sheering the RBCs as they cross microthrombi, resulting in hemolytic anemiawith schistocytes
49
What is microangiopathic hemolytic anemia seen in?
thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
50
What is TTP due to?
decreased ADAMTS13 which is an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation.
51
How does TTP lead to microangiopathic hemolytic anemia?
1. Large, uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi.
52
Decreased ADAMTS13 is usually due what?
an acquired autoantibody;
53
TTP is most commonly seen in?
adult females
54
HUS is due to?
Hemolytic uremic syndrome is due to endothelial damage by drugs or infection.
55
HUS is classically seen in?
children with E coli G157;H7 dysentery, which results from exposure to undercooked beef
56
How is E Coli related to microangiopathic hemolytic anemia?
E coli verotoxin damages endothelial cells resulting in platelet microthrombi
57
The clinical findings for HUS and TTP include
Skin and mucosal bleeding, Microangiopathic hemolytic anemia, Fever, Renal insufficiency, CNS abnormalities
58
Renal insufficiency is more common in HUS or TTP?
HUS ? thrombi involve vessels of the kidney
59
CNS abnormalities are more common in HUS or TTP?
TTP ? Thrombi involve vessels of the CNS
60
Laboratory findings for microangiopathic hemolytic anemia include?
Thrombocytopenia with increased bleeding time Normal PT/PTT (coagulation cascade is not activated), anemia with schistocytes, increased megakaryocytes on bone marrow biopsy
61
Treatment for microangiopathic hemolytic anemia?
involves plasmapheresis and corticosteroids, particularly in TTP.
62
What are the qualitative platelet disorders?
bernard-soulier, Glanzmann thrombasthenia, asprin, uremia
63
Bernard-Soulier syndrome
is due to a genetic GPIb deficiency; platelet adhesion is impaired.
64
In Bernard-Soulier what lab test are you interested in?
Blood smear which shows mild thrombocytopenia with enlarged platelets.
65
Glanzmann thrombasthenia is due to?
a genetic GPIIb/IIIa deficiency; platelet aggregation is impaired.
66
Aspirin and microangiopathic hemolytic anemia?
it irreversibly inactivates cyclooxygenase; lack of TXA, impairs aggregation.
67
Uremia and microangiopathic hemolytic anemia
disrupts platelet function; both adhesion and aggregation are impaired.
68
What does secondary hemostasis do?
Stabilizes the weak platelet plug via the coagulation cascade
69
In secondary hemostasis the coagulation cascade generates?
thrombin, which converts fibrinogen in the platelet plug to fibrin.
70
In secondary hemostasis what happens to fibrin?
It is cross-linked, yielding a stable platelet-fibrin thrombus.
71
Where are the factors of the coagulation cascade produced?
In the liver in an inactive state.
72
What does activation of the factors of the coagulation cascade require?
exposure to an activating substance, Phospholipid surface of platelets, calcium
73
What are the activating substances involved in the activation of the factors of the coagulation cascade?
Tissue thromboplastin activates factor VII (extrinsic pathway). Subendothelial collagen activates factor XII (intrinsic pathway).
74
Where does the Calcium involved in the activation of the factors of the coagulation cascade come from?
derived from platelet dense granules
75
Disorders of secondary hemostasis are usually due to?
factor abnormalities
76
What are the clinical features of disorders of secondary hemostasis?
they include deep tissue bleeding into muscles and joints (hemarthrosis) and rebleeding after surgical procedures (e.g circumcision and wisdom tooth extraction).
77
Laboratory studies for Disorders of secondary hemostasis include?
PT (prothrombin time) and PTT (partial thromboplastin time)
78
Prothrombin time (PT)
measures extrinsic (factor VII) and common (factors II, V, X, and fibrinogen) pathways of the coagulation cascade
79
Extrinsic pathway of the coagulation cascade
factor VII
80
Common pathway of the coagulation cascade
factors II, V, X, and fibrinogen
81
Partial thromboplastin time (PTT) measures
intrinsic (factors XII, XI, IX, VIII) and common (factors II, V, X, and fibrinogen) pathways of the coagulation cascade
82
What is involved in Hemophilia A?
Genetic factor VIII (FVIII) deficiency, X-linked recessive (predominantly affects males)
83
Does Hemophilia A require a family history of it?
Can arise from a new mutation (de novo) without any family history
84
Hemphilia A presents with?
deep tissue, joint, and postsurgical bleeding
85
Clinical severity of hemophilia A depends on?
the degree of deficiency
86
Laboratory findings of hemophilia A include
1. increased PTT; normal PT 2. decreased FVIII 3. Normal platelet count and bleeding time
87
What does treatment of hemophilia A involve?
recombinant FVIII.
88
What is christmas disease?
Hemophilia B - Genetic factor IX deficiency, Resembles hemophilia A, except FIX levels are decreased instead of FVIII
89
What is coagulation factor inhibitor?
Acquired antibody against a coagulation factor resulting in impaired factor function; anti-FVIII is most common,
90
Clinical and lab findings for hemophilia B?
its similar to hemophilia A, PTT does not correct upon mixing normal plasma with patient's plasma (mixing study) due to inhibitor; PTT does correct in hemophilia A.
91
How can you tell the difference between hemophilia A and B?
mixing study
92
von Willebrand Disease
Genetic vWF deficiency
93
What is the most common inherited coagulation disorder?
von Willebrand disease
94
Does von Willebrand Disease result in qualitative or quantitative disorders?
Multiple subtypes exist, causing quantitative and qualitative defects;
95
What is the most common type of von Willebrand Disease?
is autosomal dominant with decreased vWF levels
96
von Willebrand Disease presents with?
mild mucosal and skin bleeding; low vWF impairs platelet adhesion.
97
Laboratory findings for von Willebrand Disease include
1. increased bleeding time 2. increased PTT: normal PT ? Decreased FVIII half-life (vWF normally stabilizes FVIII); 3. Abnormal ristocetin test
98
What is usually not seen with von Willebrand Disease that is unusual
deep tissue, joint, and postsurgical bleeding are usually not seen.
99
Why is there an Abnormal ristocetin test in von Willebrand disease
Ristocetin induces platelet aggregation by causing vWF to bind platelet GPIb; lack ofvWF ?> impaired aggregation ?> abnormal test.
100
What is the treatment for von willebrand disease?
desmopressin (ADH analog), which increases vWF release from Weibel-Palade bodies of endothelial cells
101
How does vitamin K deficiency relate to hemostasis?
Disrupts function of multiple coagulation factors
102
What is involved in Vitamin K activation?
Vitamin K is activated by epoxide reductase in the liver
103
What does Activated vitamin K do?
it gamma carboxvlates factors II, VII, IX, X, and proteins C and S; gamma carboxylation is necessary for factor function.
104
Vitamin K deficiency occurs in?
1. Newborns 2. Long-term antibiotic therapy 3. Malabsorption
105
Why is there vitamin K deficiency in newborns?
its due to lack of GI colonization by bacteria that normally synthesize vitamin K; vitamin K injection is given prophylactic ally to all newborns at birth to prevent hemorrhagic disease of the newborn
106
How does Long-term antibiotic therapy elad to Vitamin K deficiency?
disrupts vitamin K-producing bacteria in the GI tract
107
How does Malabsorption lead to Vitamin K deficincy?
leads to deficiency of fat-soluble vitamins, including vitamin K
108
What are some other causes of secondary hemostasis?
liver failure, large volume transfusion,
109
How does liver failure lead to secondary hemostasis?
decreased production of coagulation factors and decreased activation of vitamin K by epoxide reductase;
110
How is the effect of liver failure on coagulation followed?
followed using PT.
111
How does Large-volume transfusion lead to secondary hemostasis?
it dilutes coagulation factors, resulting in a relative deficiency
112
What is Heparin induced thrombocytopenia?
Platelet destruction that arises secondary to heparin therapy
113
How does Heparin induced thrombocytopenia lead to thrombosis?
Fragments of destroyed platelets may activate remaining platelets, leading to thrombosis
114
What is disseminated intravascular coagulation?
Pathologic activation of the coagulation cascade
115
What does disseminated intravascular coagulation result in?
1. Widespread microthrombi result in ischemia and infarction, 2. Consumption of platelets and factors results in bleeding, especially from IV sites and mucosal surfaces (bleeding from body orifices).
116
Is disseminated intravascular coagulation usually primary or secondary?
Almost always secondary to another disease process
117
What are some situations that may result in disseminated intravascular coagulation?
Obstetric complications, sepsis, adenocarcinoma, Acute promyelocytic leukemia, Rattlesnake bite
118
Obstetric complications and disseminated intravascular coagulation
Tissue thromboplastin in the amniotic fluid activates coagulation
119
Sepsis and disseminated intravascular coagulation
(especially with E. coli or Neisseria meningitidis) ? Endotoxins from the bacterial wall and cytokines (e.g TNF and IL-1) induce endothelial cells to make tissue factor.
120
Adenocarcinoma and disseminated intravascular coagulation
Mucin activates coagulation.
121
Acute promyelocytic leukemia and disseminated intravascular coagulation
Primary granules activate coagulation.
122
Rattlesnake bite and and disseminated intravascular coagulation
Venom activates coagulation
123
Laboratory findings for disseminated intravascular coagulation include?
decreased platelet count, increased PT/PTT, decreased fibrinogen, Microangiopathic hemolytic anemia, Elevated fibrin split products, particularly D-dimer
124
What is the best screening test for DIC?
Elevated D-dimer
125
D dimer is derived from?
splitting of cross-linked fibrin; D-dimer is not produced from splitting of fibrinogen.
126
Treatment of DIC involves?
addressing the underlying cause and transfusing blood products and cryoprecipitate (comains coagulation factors), as necessary.
127
What does normal fibrinolysis do?
Normal fibrinolysis removes thrombus after damaged vessel heals
128
Tissue plasminogen activator (tPA)
converts plasminogen to plasmin
129
Plasmin
cleaves fibrin and serum fibrinogen, destroys coagulation factors, and blocks platelet aggregation.
130
a2-antiplasmin
inactivates plasmin.
131
What are the disorders of fibrinolysis due to? What does this result in?
plasmin overactivity resulting in excessive cleavage of serum fibrinogen.
132
What are some examples of disorders of fibrinolysis?
radical prostatectomy, cirrohsis of the liver
133
How does radical prostatectomy lead to a disorder of fibrinolysis?
Release of urokinase activates plasmin
134
How does cirrhosis of the liver lead to a disorder of fibrinolysis?
reduced production of a2-antiplasmin
135
How does disorders of fibrinolysis present?
with increased bleeding (resembles DIC)
136
Laboratory findings for disorders of fibrinolysis include
Increased PT/PTT, increased bleeding time with normal platelet count, Increased fibrinogen split products without D-dimers
137
Why is there increased fibrinogen split products without D-dimers in disorders of fibrinolysis?
Serum fibrinogen is lysed; however, D-dimers are not formed because fibrin thrombi are absent
138
Why is there increased bleeding time with disorders of fibrinolysis?
Plasmin blocks platelet aggregation
139
Why is there increased PT/PTT with disorders of fibrinolysis?
Plasmin destroys coagulation factors.
140
What is the treatment for disorders of fibrinolysis?
it is aminocaproic acid, which blocks activation of plasminogen.
141
What is thrombosis?
Pathologic formation of an intravascular blood clot (thrombus), Can occur in an artery or vein,
142
What is the most common location for thrombosis?
it is the deep veins (DVT) of the leg below the knee
143
What is thrombosis characterized by?
lines of Zahn and attachment to vessel wall
144
What are the lines of Zahn?
alternating layers of platelets/fibrin and RBCs
145
What distinguishes thrombus from a postmortem clot?
lines of Zahn and attachment to vessel wall
146
What are three major risk factors for thrombosis?
disruption in blood flow, endothelial cell damage, and hypercoagulable state (Virchow triad)
147
What is normal blood flow?
blood flow is normally continuous and laminar; keeps platelets and factors dispersed and inactivated
148
What happens to blood flow that causes an increase in the risk for thrombosis?
Stasis and turbulence of blood flow increases risk for thrombosis
149
What are some examples of disruption of normal blood flow?
Immobilization?increased risk for deep venous thrombosis 2. Cardiac wall dysfunction (e.g arrhythmia or myocardial infarction) 3. Aneurysm
150
How does endothelial cell damage increase the risk for thrombosis?
Endothelial damage disrupts the protective function of endothelial cells, increasing the risk for thrombosis
151
How do endothelial cells prevent thrombosis?
1. Block exposure to subendothelial collagen and underlying tissue factor 2. Produce prostacyclin (PGI2) and NO, 3. Secrete heparin-like molecules, 4. Secrete tissue plasminogen activator (tPA) 5. Secrete thrombomodulin
152
How does endothelial cells use the secretion of tPA to prevent thrombosis?
converts plasminogen to plasmin, which (1) cleaves fibrin and serum fibrinogen, (2) destroys coagulation factors, and (3) blocks platelet aggregation
153
How does the secretion of thrombomodulin from endothelial cells prevent thrombosis?
redirects thrombin to activate protein C, which inactivates factors V and VIII
154
How do endothelial cells use the secretion of heparin-like molecules to prevent thrombosis?
augment antithrombin III (ATIII) which inactivates thrombin and coagulation factors
155
How does endothelial cells use the production of prostacyclin (PGI2) and NO to prevent thrombosis?
vasodilation and inhibition of platelet aggregation
156
What are the causes of endothelial cell damage?
atherosclerosis, vasculitis, and high levels of homocysteine
157
Vitamin B12 and folate deficiency result in?
mildly elevated homocysteine levels, increasing the risk for thrombosis.
158
What does folic acid circulate as?
methyl-THF (tetrahydrofolate, THF) in the serum,
159
How does THF participate in the synthesis of DNA precursors?
Methyl is transferred to cobalamin (vitamin B12) which transfers methyl to homocysteine resulting in methionine
160
What does a lack of vitamin B12 or folate lead to?
decreased conversion of homocysteine to methionine resulting in buildup of homocysteine
161
Cystathionine beta synthase (CBS) deficiency results in what?
high homocysteine levels with homocystinuria,
162
What does CBS do?
CBS converts homocysteine to cystathionine
163
CBS deficiency leads to?
homocysteine buildup
164
CBS deficiency is characterized by?
vessel thrombosis, mental retardation, lens dislocation, and long slender fingers
165
what is a hypercoagulabe state due to?
excessive procoagulant proteins or defective anticoagulant proteins; may be inherited or acquired
166
What is the classic presentation for a hypercoagulable state?
recurrent DVTs or DVT at a young age, usually occurs in the deep veins of the leg; other sites include hepatic and cerebral veins
167
What are some causes of a hypercoagulable state?
protein C and S deficiency, factor V Liden deficiency, prothrombin 20210A, ATIII deficiency, oral contraceptives
168
protein C or S deficiency
(autosomal dominant) decreases negative feedback on the coagulation cascade (hypercoagulable state)
169
Proteins C and S normally do what?
inactivate factors V and VIII
170
Protein C and S deficiency increases the risk for what?
warfarin skin necrosis
171
What does the initial stage of warfarin therapy result in?
a temporary deficiency of proteins C and S (due to shorter half-life) relative to factors II, VII, IX, and X
172
In preexisting C or S deficiency, what danger does the initial stage of warfarin therapy present?
a severe deficiency is seen at the onset of warfarin therapy increasing the risk for thrombosis, especially in the skin
173
What is Factor V Leiden?
a mutated form of factor V that lacks the cleavage site for deactivation by proteins C and S
174
What is the most common inherited cause of hypercoagulable state?
Factor V Leiden
175
What is Prothrombin 20210A?
it is an inherited point mutation in prothrombin that results in increased gene expression,
176
Increased prothrombin (prothrombin 20210A) results in what?
increased thrombin, promoting thrombus formation.
177
What does ATIII deficiency result in?
decreases the protective effect of heparin-like molecules produced by the endothelium, increasing the risk for thrombus
178
What do heparin-like molecules normally do?
activate ATIII, which inactivates thrombin and coagulation factors
179
What happens in ATIII deficiency?
PTT does not rise with standard heparin dosing.
180
Pharmacologic heparin works by doing what?
binding and activating ATIII
181
High doses of heparin in someone with ATIII deficiency results in what?
activate limited ATIII; Coumadin is then given to maintain an anticoagulated state.
182
How are oral contraceptives associated with a hypercoagulable state?
Estrogen induces increased production of coagulation factors, thereby increasing the risk for thrombosis
183
What is an embolism?
Intravascular mass that travels and occludes downstream vessels; symptoms depend on the vessel involved
184
What is a thromboembolus due to?
a thrombus that dislodges;
185
What is the most common type of embolus?
thromboembolus (>95%)
186
Atherosclerotic embolus is due what?
to an atherosclerotic plaque that dislodges.
187
Atherosclerotic embolus is characterized by what?
the presence of cholesterol clefts in the embolus
188
Fat embolus is associated with what?
bone fractures, particularly long bones, and soft tissue trauma
189
When does a fat embolus develop?
while fracture is still present or shortly after repair
190
What is fat embolus characterized by?
dyspnea (fat, often with bone marrow elements, is seen in pulmonary vessels and petechiae on the skin overlying the chest
191
Gas embolus is classically seen in what?
decompression sickness.
192
Decompression sickness
Nitrogen gas precipitates out of blood due to rapid ascent by a diver (gas embolus)
193
What does gas embolus presents with?
joint and muscle pain (bends) and respiratory symptoms (chokes)
194
Caisson disease
Chronic form of gas embolus that is characterized by multifocal ischemic necrosis of bone
195
Gas embolus and laproscopic surgery?
may also occur during laparoscopic surgery (air is pumped into the abdomen)
196
Amniotic fluid embolus
enters maternal circulation during labor or delivery
197
How does amniotic fluid embolus present?
with shortness of breath, neurologic symptoms, and DIC (due to the thrombogenic nature of amniotic fluid)
198
How is amniotic fluid embolus characterized?
by squamous cells and keratin debris, from fetal skin, in the embolus
199
pulmonary embolism is usually due to?
thromboembolus;
200
What is the most common source of thromboembolus?
deep venous thrombus (DVT) of the lower extremity usually involving the femoral, iliac, or popliteal veins
201
Pulmonary embolism is most often clinically silent because?
the lung has a dual blood supply via pulmonary and bronchial arteries and the embolus is usually small (self-resolves)
202
When does pulmonary infarction occur?
if a large- or medium-sized artery is obstructed in patients with pre-existing cardiopulmonary compromise; only 10% of PEs cause infarction
203
How does pulmonary infarction present?
with shortness of breath, hemoptysis, pleuritic chest pain, and pleural effusion
204
In pulmonary infarction what does the V/Q lung scan show?
a mismatch; perfusion is abnormal.
205
In pulmonary infarction what does the spiral CT show?
a vascular filling defect in the lung
206
What is useful in determining DVT?
lower extremity Doppler ultrasound is useful to detect DVT
207
In pulmonary infarction what happens the the D-dimer
it is elevated
208
In pulmonary infarction what does gross examination reveal?
a hemorrhagic, wedge-shaped infarct
209
In pulmonary infarction sudden death occurs with?
a large saddle embolus that blocks both left and right pulmonary arteries or with significant occlusion of a large pulmonary artery
210
In pulmonary infarction sudden death with a large saddle embolus, death is due to?
electromechanical dissociation
211
Pulmonary hypertension may arise with what?
chronic emboli that are reorganized over time.
212
Systemic embolism is usually due to?
thromboembolus
213
Where does systemic embolism most commonly arise?
in the left heart and travels down systemic circulation to occlude flow to organs, most commonly lower extremities
