DISORDERS OF FIBRINOLYTIC SYSTEM and THROMBOTIC DISORDERS Flashcards
it comprises an inactive proenzyme, plasminogen, which can be converted to the active enzyme, plasmin, which in turn degrades fibrin into soluble fibrin degradation products.
fibrinolytic system
excessive amounts of plasminogen activators from damaged cells/malignant cells
primary fibrinolysis
secondary fibrinolysis is can be caused by
DIC; uncontrolled, inappropriate formation of fibrin within the blood vessels
example:
infection
neoplasm
snake bite
HTR
the disorder of fibrinolytic system can impair the breakdown of fibrin resulting in a build-up of fibrin thus resulting to __
thrombosis
Plasminogen Deficiency
what are its subclassification
plasminogen deficiency type 1
plasminogen deficiency type II
subclassification of plasminogen deficiency which is the True plasminogen deficiency (hypoplasminogenemia)
plasminogen deficiency type 1
subclassification of plasminogen deficiency wherein there’s Proportionate decrease in both level of plasminogen and its activity
plasminogen deficiency type I
cause of plasminogen deficiency type I
congenital plasminogen deficiency is caused by MUTATIONS in the PLG gene
this gene provides instructions for making a protein called plasminogen
PLG gene
dx for plasminogen deficiency 1
genetic testing
research studies
other name for plasminogen deficiency type I
hypoplasminogenemia
plasminogen deficiency, type I
subclassification of plasminogen deficiency wherein the level of immunoreactive plg is normal whereas the specific functional activity is markedly reduced because of abnormalities in the variant plg molecule
plasminogen deficiency type II
refers to an increased tendency to develop thrombi or emboli
thrombosis
thrombosis is sometimes called as ____
hypercoagulable state
thrombosis is a multifaceted disorder resulting from abnormalities in blood flow, such as
stasis
abnormalities in the coagulation system
plt function
leukocyte activation molecules
blood vessel wall
predisposition to thrombosis
thrombophilia
abnormality of blood coagulation that increases the risk of thrombosis
thrombophilia
thrombophilia, it may be due to ____
physical, biological, and chemical events
thrombophilia, it may be due to physical, biological, and chemical events such as :
acute or chronic inflammation
inappropriate or uncontrolled plt activation
uncontrolled triggering of the plasma coagulation system
inadequate control of coagulation-impaired fibrinolysis
classification of thrombosis
venus and arterial thrombosis
what are the venous thrombosis
deep vein thrombosis
portal vein thrombosis
renal vein thrombosis
jugular vein thrombosis
budd chiari syndrome
paget-schroetter disease
cerebral venous sinus thrombosis
formation of blood clot within a deep bein
deep vein thrombosis
affects the superficial leg veins from the iliac, poplietal, and femoral veins of the upper leg and calves
deep vein thrombosis
signs of deep vein thrombosis
swelling, pain, and redness in the affected area especially the entire legs
form of venous thrombosis affecting the hepatic portal vein which can lead to portal hypertension and reduction of supply to the liber
portal vein thrombosis
obstruction of the renal vein by a thrombus
renal vein thrombosis
jugular vein thrombosis may occur during __
infection, malignancy, or infusion of the intravenous drug`
conditions associated with jugular vein thrombosis
systemic sepsis, pulmonary embolism, papilledema
this is the form of thrombosis present abdominal pain, hepatomegaly and ascites
budd-chiari syndrome
there is a blockage of the inferior vena cava by a thrombus
budd-chiari sundrome
conditions that usually occurs after exercise
paget schroetter disease
there is an obstruction of the upper extremity vein by a thrombus
paget schroetter disease
rare form of thrombosis which result from a blockage of the diural venous sinuses by a thrombus
cerebral venous sinus thrombosis
cerebral venous sinus thrombosis has the same symptoms of ___
stroke, headache, and abnormal vision
it is the formation of accumulation of thrombi within an artery known as
atherosclerotic plaque
arterial thrombosis is also known as
atherothrombosis
it causes infarction to different organs in the body
arterial thrombosis
arterial thrombosis is common to _____% patient not receiving anticoagulant therapy
ex, MI or stroke
5%
suspected when thrombotic events occur in young adults and their unusual sites (mesentery, renal, or axillary veins )
genetic or congenital thrombosis
it involved the alteration of guanine to adenine at the base of the 20210 of the 3` untranslated region of prothrombin gene
prothrombin 20210 mutation
prothrombin 20210 mutation is found in __ % with clotting disorder
10%
second most common inherited thrombophilic tendency in patients with family history of DVT
prothrombin 20210 mutation
associated with higher levels of prothrombin, averaging to 130%
prothrombin 20210 mutation
prothrombin 20210 mutation is linked to other clotting events such as
coronary artery disease
venous clots
etc
hyperhomocysteinuria
deficient in 3 enzymes
methionine synthase
cystathionine-B-synthase
5, 10 methyltetrahydrofolate reductase
increased level of homocysteine
hyperhomocysteinemia
may predispose to arterial thrombosis and venous thromboembolism
hypercysteinuria
May be due to deficiency in enzymes that will
hydrolyze homocysteine in several end products
Hyperhomocysteinuria
Plasma homocysteine levels are ≥10 fold in
homozygous cystathionine-ß-synthase deficiency.
true or false
true
inherited cause of hyperhomocysteinuria
low levels of an enzymes necessary for the
conversion of homocysteine to cysteine which increase the risk of
a clotting event.
acquired event of hyperhomocysteinuria
advance age and diet
factor V leiden mutation is also called as
activated protein C resistance
factor V Leiden Mutation or
Activated Protein C Resistance
is identified on what year
1993
factor V Leiden Mutation or
Activated Protein C Resistance
it was identified in 1993 as the tope leading cause of
blood blots among white population
The most common genetic risk of factor for
blood clots.
Factor V Leiden Mutation or
Activated Protein C Resistance
The mutation happens in Factor V protein,
which is known as the
Leiden protein
Factor V Leiden Mutation or
Activated Protein C Resistance
The mutated plasma protein is resistant to
regulation by _____that is why
clotting is uncontrolled
activated protein C
posses only the Leiden
protein and an 80-fold increased risk of clotting qdisorder compared to the general unaffected
population
Factor V Leiden homozygotes
are believed to
produced about 50% of Leiden protein and have 5-7 fold increased risk of clotting disorder compared to the
general population
Factor V Leiden heterozygotes
OTHER FACTOR V MUTATION:
Factor V Cambridge mutation
Factor V Hongkong mutation
Elevated levels of other clotting factors as a prociagulant can
also be associated with increased risk of
thrombosis
list the mentioned clotting factors
- Factor VIII
- Factor IX
- Factor XI
- Factor I
- vWF
A serine protease inhibitor (serpin) that
neutralizes thrombin, Factor Ixa, Xa, Xia & XIIa.
ANTITHROMBIN
ANTITHROMBIN
Its activity is enhanced by
unfractionated heparin, LMW heparin, and systemic entasaccharide
First of the plasma coagulation control protein
to be identified and first assayed in the
laboratory
ANTITHROMBIN
Acquired antithrombin deficiency
- Liver disease
- Nephrotic syndrome
- Prolonged heparin therapy
- Oral contraceptives
- DIC (AT is rapidly consumed)
Congenital antithrombin deficiency
Defect in heparin binding sites causing
severe clotting tendencies that usually
presents in early stage of life
2 types of antithrombin deficiency
type I and II AT deficiency
this type of AT deficiency refers to the genetic alteration usually
leads to drastic decrease levels in AT
Type I AT deficiency
this type of AT deficiency refers to the genetic alteration leads to
abnormal function of the plasma protein.
type II AT deficiency
type of protein C deficiency wherein there’s low protein C levels
and activity.
Type I Protein C deficiency
type of protein C deficiency wherein there’s ow protein C
activity due to genetic alteration of protein C
sequence resulting to abnormal functioning.
Type II Protein C deficiency
this protein C deficiency appears in newborn infants.
Homozygous Protein C Deficiency
Homozygous Protein C Deficiency
can cause what type of purpura
purpura fulminans in children
caused by rapid drop in protein C and factor VII resulting to temporary super clotting state in the extremities
warfarin induced skin necrosis
can also cause neonatal purpura fulminans which is
clinically indistinguishable from Protein C deficiency.
protein S deficiency
a type of protein S deficiency wherein there’s a proportional
decrease in the level and activity of Protein S
type I protein S deficiency
a type of protein S deficiency wherein the levels of the free and bound forms are normal, but there is an abnormal function due to genetic alteration in the gene sequence
type II protein S deficiency
a type of protein S deficiency wherein there’s a normal level to total protein S but with clinically significant decrease in free protein S levels
type III protein S deficiency
Deficiency leads to increased thombi formation
due to low/deficient activity to inhibit thrombin
Heparin Cofactor II Deficiency
type of heparin cofactor II deficiency where in there’s a decreased in both levels and
functional capacity
type I (quantitative)
type of heparin cofactor II deficiency where in there’s a decreased in functional
capacity but with normal levels of heparin
cofactor II.
type II (qualitative)
Small thrombomodulin fragments circulates in
soluble form in plasma of healthy individuals.
thrombomodulin Deficiency
thrombomodulin Deficiency
increased levels are seen in patients with ___
venous and arterial clotting conditions and
DIC
