Coagulation

Front 1

The endothelium is in direct contact with the bloodstream. In normal vessels, the intact endothelium is ___________ and prevents clot formation. When damaged by trauma or infection, the endothelium becomes _______________ and promotes clot formation.

Back 1

The endothelium is in direct contact with the bloodstream. In normal vessels, the intact endothelium is ANTI-THROMBOTIC and prevents clot formation. When damaged by trauma or infection, the endothelium becomes PRO-THROMBOTIC and promotes clot formation.

Front 2

Platelets are circulating, small (___ to____ µm), discoid cells without nuclei that arise from a precursor cell called the megakaryocyte in the bone marrow. They are essentially fragments of the megakaryocyte.

Back 2

Platelets are circulating, small (1.5 to 3 µm), discoid cells without nuclei that arise from a precursor cell called the megakaryocyte in the bone marrow. They are essentially fragments of the megakaryocyte.

Front 3

The fibrinolytic system functions to dissolve, or degrade an existing fibrin clot. This is important because the size of the clot needs to be limited so that the vessel will not be occluded.

Activators of the fibrinolytic system are released from endothelial cells. These activators convert _____________ into _______, which in turn degrades or lyses the fibrin clot.

Back 3

The fibrinolytic system functions to dissolve, or degrade an existing fibrin clot. This is important because the size of the clot needs to be limited so that the vessel will not be occluded.

Activators of the fibrinolytic system are released from endothelial cells. These activators convert PLASMINOGEN into PLASMIN, which in turn degrades or lyses the fibrin clot.

Front 4

Clotting is initiated by disruption or injury to the blood vessel and occurs in two stages:

The first stage or primary hemostasis, is the deposition of _________ at the site of vascular damage. _________ form a plug that stops bleeding within a few minutes.

The next step is secondary hemostasis, which is the reinforcement of the platelet plug with a strong meshwork of ________, resulting in a ________ clot.

At the same time regulatory mechanisms also become activated, which limit clot formation.

Back 4

Clotting is initiated by disruption or injury to the blood vessel and occurs in two stages:

The first stage or primary hemostasis, is the deposition of PLATELETS at the site of vascular damage. PLATELETS form a plug that stops bleeding within a few minutes.

The next step is secondary hemostasis, which is the reinforcement of the platelet plug with a strong meshwork of FIBRIN , resulting in a FIBRIN clot.

At the same time regulatory mechanisms also become activated, which limit clot formation.

Front 5

When the endothelium is damaged, underlying collagen and tissue factor are exposed. von Willebrand factor (vWF) is an adhesive protein produced by ___________ cells. vWF in blood adheres to exposed collagen while simultaneously binding to platelets through the ____________________ receptor complex. This results in adhesion of platelets to the site of vessel injury.

Back 5

When the endothelium is damaged, underlying collagen and tissue factor are exposed. von Willebrand factor (vWF) is an adhesive protein produced by ENDOTHELIAL cells. vWF in blood adheres to exposed collagen while simultaneously binding to platelets through the GLYCOPROTEIN IB(GPIb) receptor complex. This results in adhesion of platelets to the site of vessel injury.

Front 6

Lack of the GPIb receptor complex on platelets results in decreased platelet adhesion at the site of vessel injury and increased bleeding. This platelet disorder is called the ________________.

Back 6

Lack of the GPIb receptor complex on platelets results in decreased platelet adhesion at the site of vessel injury and increased bleeding. This platelet disorder is called the BERNARD-SOULIER DISEASE.

Front 7

Platelet adhesion is followed by platelet activation. Platelets can be activated by a number of different factors including ________, ________, ___and ___________.

Back 7

Platelet adhesion is followed by platelet activation. Platelets can be activated by a number of different factors including COLLAGEN, THROMBIN, ADP and EPINEPHRINE.

Front 8

Activated platelets release procoagulant factors including fibrinogen, factor ___, factor _____, ADP, ATP, serotonin and calcium from storage granules which in turn activate other platelets.

Back 8

Activated platelets release procoagulant factors including fibrinogen, factor V, factor XIII, ADP, ATP, serotonin and calcium from storage granules which in turn activate other platelets.

Front 9

An important platelet activation route is the cyclooxygenase pathway, which leads to the production of _______________, a potent platelet activator. Aspirin and non-steroidal anti-inflammatory drugs like ibuprofen show platelet inhibitory effects through their inhibition of cyclooxygenase and the formation of _______.

Back 9

An important platelet activation route is the cyclooxygenase pathway, which leads to the production of THROMBOXANE A2 (TxA2), a potent platelet activator. Aspirin and non-steroidal anti-inflammatory drugs like ibuprofen show platelet inhibitory effects through their inhibition of cyclooxygenase and the formation of TxA2.

Front 10

Platelet activation leads to the activation of the ________________ receptor on the platelets.

Back 10

Platelet activation leads to the activation of the GLYCOPROTEIN IIb/IIIa (GP IIb/IIIa) receptor on the platelets.

Front 11

Activated GP IIb/IIIa binds __________. When two activated platelets bind the same ___________ molecule it causes the platelets to stick together or __________. As more and more platelets aggregate, a platelet plug is formed.

Back 11

Activated GP IIb/IIIa binds FIBRINOGEN. When two activated platelets bind the same FIBRINOGEN molecule it causes the platelets to stick together or AGGREGATE. As more and more platelets aggregate, a platelet plug is formed.

Front 12

_____________________ is characterized by deficiency or abnormality of the GP IIb/IIIa receptor. The resulting aggregation defect leads to increased bleeding in affected patients.

Back 12

GLANZMANN'S THROMBASTHENIA is characterized by deficiency or abnormality of the GP IIb/IIIa receptor. The resulting aggregation defect leads to increased bleeding in affected patients.

Front 13

In summary the three steps of primary hemostasis are:

Platelet ________
Platelet ________
Platelet ________

Back 13

In summary the three steps of primary hemostasis are:

Platelet ADHESION
Platelet ACTIVATION
Platelet AGGREGATION

Front 14

While the platelet plug initially stops bleeding, it is ________. Bleeding will begin again unless the platelet plug is stabilized.

Secondary hemostasis is the formation of a gel-like, meshwork of polymerized ________ molecules that stabilizes the platelet plug at the site of vessel injury.

Back 14

While the platelet plug initially stops bleeding, it is UNSTABLE. Bleeding will begin again unless the platelet plug is stabilized.

Secondary hemostasis is the formation of a gel-like, meshwork of polymerized FIBRIN molecules that stabilizes the platelet plug at the site of vessel injury.

Front 15

Fibrin monomer is generated from a soluble molecule, __________ by the proteolytic enzyme ________. Polymerized fibrin forms an insoluble gel or fibrin clot.

Back 15

Fibrin monomer is generated from a soluble molecule, FIBRINOGEN by the proteolytic enzyme THROMBIN. Polymerized fibrin forms an insoluble gel or fibrin clot.

Thrombin generation and fibrin generation, are the ultimate end result of the coagulation cascade.

Front 16

Exposed tissue factor in the damaged vessel wall activates the first coagulation factor in the cascade: F ____.

Back 16

Exposed tissue factor in the damaged vessel wall activates the first coagulation factor in the cascade: F VII.

Front 17

After activation of Factor VII .... FACTOR____, FACTOR ____ and FACTOR _____are sequentially activated. Note that a very small amount of FX can be activated by ______ directly,

Back 17

After activation of Factor VII .... FIX, X and II are sequentially activated. Note that a very small amount of FX can be activated by FVIIa directly,

Front 18

Factor II is also known as ________

Back 18

Factor II is also known as PROTHROMBIN

Front 19

The reaction culminates in the generation of thrombin from prothrombin, which cleaves ___________ (F I) giving rise to _____(F Ia).

Back 19

The reaction culminates in the generation of thrombin from prothrombin, which cleaves FIBRINOGEN(F I) giving rise to FIBRIN(F Ia).

Front 20

Fibrin spontaneously polymerizes to form a meshwork, or fibrin clot over the platelet plug. FACTOR _________ crosslinks fibrin, further stabilizing the fibrin clot.

Back 20

Fibrin spontaneously polymerizes to form a meshwork, or fibrin clot over the platelet plug. F XIIIa crosslinks fibrin, further stabilizing the fibrin clot.

Front 21

Other coagulation factors (Factor _____ and Factor _____) serve as co-factors that increase the reaction rate.

In addition, ___________ and _____________ serve as important cofactors for many of the enzymatic reactions.

Back 21

Other coagulation factors (FVa, FVIIIa) serve as co-factors that increase the reaction rate.

In addition, PHOSPHOLIPID and CALCIUM IONS serve as important cofactors for many of the enzymatic reactions.

Front 22

In addition to generating fibrin from fibrinogen, thrombin also serves other important functions that promote clot formation:

Thrombin activates _________.


Thrombin activates FV, FVIII, FXIII, and factor FXI. FXIa in turn activates more molecules of FIX. This leads to an increased rate of clot formation once thrombin is generated.

Back 22

In addition to generating fibrin from fibrinogen, thrombin also serves other important functions that promote clot formation:

Thrombin activates PLATELETS.


Thrombin activates FV, FVIII, FXIII, and factor FXI. FXIa in turn activates more molecules of FIX. This leads to an increased rate of clot formation once thrombin is generated.

Front 23

Both phospholipid and calcium ions are required for several steps in the coagulation cascade. The platelets in the platelet plug provide the phospholipid surface, which binds coagulation factors, bringing them into close physical proximity with each other to achieve the optimal reaction rate. This binding is mediated by _____________.

Back 23

Both phospholipid and calcium ions are required for several steps in the coagulation cascade. The platelets in the platelet plug provide the phospholipid surface, which binds coagulation factors, bringing them into close physical proximity with each other to achieve the optimal reaction rate. This binding is mediated by CALCIUM IONS.

Front 24

In summary, secondary hemostasis can be divided into two stages:

Activation of the coagulation cascade by exposed tissue factor in the wall of a damaged vessel, leading to the formation of _________.


Generation of ________, which polymerizes and forms a gel like meshwork (a fibrin clot) that stabilizes an existing platelet plug, further limiting blood loss at the site of vascular injury.

Not surprisingly, a deficiency of coagulation factors or fibrinogen leads to inadequate secondary hemostasis and increased risk of bleeding.

Back 24

In summary, secondary hemostasis can be divided into two stages:

Activation of the coagulation cascade by exposed tissue factor in the wall of a damaged vessel, leading to the formation of THROMBIN.


Generation of FIBRIN, which polymerizes and forms a gel like meshwork (a fibrin clot) that stabilizes an existing platelet plug, further limiting blood loss at the site of vascular injury.
Not surprisingly, a deficiency of coagulation factors or fibrinogen leads to inadequate secondary hemostasis and increased risk of bleeding.

Front 25

Fibrinolysis is initiated by release of tissue plasminogen activator (tPA) from the ______________________.

Back 25

Fibrinolysis is initiated by release of tissue plasminogen activator (tPA) from the VASCULAR ENDOTHELIUM.

Front 26

Next tPA activates plasminogen to plasmin. Plasmin in turn lyses the __________ producing fibrin degradation products including ___________.

Back 26

Next tPA activates plasminogen to plasmin. Plasmin in turn lyses the FIBRIN producing fibrin degradation products including D-DIMERS.

Front 27

Two proteins regulate the activity of the fibrinolytic system:

______________________which inhibits tPA, thus limiting plasmin generation.


_______________ which inhibits plasmin and limits clot degradation.

Back 27

Two proteins regulate the activity of the fibrinolytic system:

PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1), which inhibits tPA, thus limiting plasmin generation.


ANTIPLASMIN, which inhibits plasmin and limits clot degradation.

Front 28

As the name implies, antithrombin binds to _________and inactivates it. The antithrombin- thrombin complex is subsequently cleared by the liver.

Back 28

As the name implies, antithrombin binds to THROMBIN and inactivates it. The antithrombin- thrombin complex is subsequently cleared by the liver.

Front 29

Antithrombin activity is potentiated nearly a thousandfold by __________ sulfate, a proteoglycan on the surface of ______________ cells. A similarly structured molecule called ___________ can also potentiate antithrombin. One molecule of heparin can activate many molecules of antithrombin.

Back 29

Antithrombin activity is potentiated nearly a thousandfold by HEPARAN sulfate, a proteoglycan on the surface of ENDOTHELIAL cells. A similarly structured molecule called HEPARIN can also potentiate antithrombin. One molecule of heparin can activate many molecules of antithrombin.

Front 30

T or F: Heparin is often given intravenously or subcutaneously as an anti-thrombotic agent.

Back 30

T: Heparin is often given intravenously or subcutaneously as an anti-thrombotic agent.

Front 31

Antithrombin also inhibits FXIa, Xa and IXa . These complexes are also cleared by the liver.

Because of the important role antithrombin plays in down-regulating clot formation, deficiency of antithrombin is associated with a _________________ tendency.

Back 31

Antithrombin also inhibits FXIa, Xa and IXa . These complexes are also cleared by the liver.

Because of the important role antithrombin plays in down-regulating clot formation, deficiency of antithrombin is associated with a THROMBOTIC tendency.

Front 32

The Protein C system is initiated when thrombin binds to THROMBOMODULIN on the endothelial surface.

Back 32

The Protein C system is initiated when thrombin binds to THROMBOMODULIN on the endothelial surface.

Front 33

What is thrombomodulin?

Back 33

Thrombomodulin is an integral membrane protein expressed on the surface of endothelial cells.

It functions as a cofactor in the thrombin-induced activation of protein C in the anticoagulant pathway by forming a 1:1 stoichiometric complex with thrombin. This raises the speed of protein C activation thousandfold. Thrombomodulin-bound thrombin has no procoagulant effect.

Front 34

This thrombin-thrombomodulin complex activates Protein C. With the help of its cofactor Protein ____, activated Protein C (APC) degrades F Va and F VIIIa, which are major cofactors in the clotting cascade. This slows down the rate of thrombin generation and fibrin formation. Thus, the Protein C system acts as the brake on the coagulation system.

Back 34

This thrombin-thrombomodulin complex activates Protein C. With the help of its cofactor Protein S, activated Protein C (APC) degrades F Va and F VIIIa, which are major cofactors in the clotting cascade. This slows down the rate of thrombin generation and fibrin formation. Thus, the Protein C system acts as the brake on the coagulation system.

Front 35

Deficiency of either Protein S or Protein C is associated with an increased risk of _________ thrombosis.

Back 35

Deficiency of either Protein S or Protein C is associated with an increased risk of VENOUSthrombosis.

Front 36

Similarly, mutations of F V can render the protein resistant to the action of activated Protein C. This disorder, __________ mutation, or _________________, is one of the most common thrombotic abnormalities

Back 36

Similarly, mutations of F V can render the protein resistant to the action of activated Protein C. This disorder, F V LEIDEN mutation, or ACTIVATED PROTEIN C RESISTANCE, is one of the most common thrombotic abnormalities

Front 37

WRITE OUT!

Bleeding disorders can be broadly classified as shown below:

1. Defects of the platelet plug:

A. Platelet Defects
I.Quantitative Defects
II. Qualitative Defects
III. von Willebrand factor (vWF) Defects
Deficiency of vWF
Abnormal vWF function or structure

2. Defects of the fibrin clot:

A. Coagulation factor deficiencies:
I. Acquired - often deficiency of multiple factors
II. Inherited - often deficiency of a single factor
B. Inhibitors to coagulation factors:
I. Drugs
II. Acquired antibodies

Back 37

Bleeding disorders can be broadly classified as shown below:

1. Defects of the platelet plug:

A. Platelet Defects
I.Quantitative Defects
II. Qualitative Defects
III. von Willebrand factor (vWF) Defects
Deficiency of vWF
Abnormal vWF function or structure

2. Defects of the fibrin clot:

A. Coagulation factor deficiencies:
I. Acquired - often deficiency of multiple factors
II. Inherited - often deficiency of a single factor
B. Inhibitors to coagulation factors:
I. Drugs
II. Acquired antibodies

Front 38

If the bleeding is mostly pinpoint or of the oozing type, and involves mostly mucous membranes (bleeding of the nose, oral cavity, or heavy periods), then a _________ plug defect is more likely. A _________ clot defect is more likely if there is history of bleeding into the soft tissue or joint spaces, and the bruise is larger.

Back 38

If the bleeding is mostly pinpoint or of the oozing type, and involves mostly mucous membranes (bleeding of the nose, oral cavity, or heavy periods), then a PLATELET plug defect is more likely. A FIBRIN clot defect is more likely if there is history of bleeding into the soft tissue or joint spaces, and the bruise is larger.

Front 39

Thrombocytopenia is usually clinically silent until the count is less than 50,000/µL. (Normal >________/µL) Excessive bleeding may occur with trauma or surgery. Spontaneous bleeding can occur when the count is <10,000/µL.

Back 39

Thrombocytopenia is usually clinically silent until the count is less than 50,000/µL. (Normal >150,000/µL) Excessive bleeding may occur with trauma or surgery. Spontaneous bleeding can occur when the count is <10,000/µL.

Front 40

Thrombocytopenia can be caused by:
1. Decreased production due to __________failure
2. Increased consumption due to bleeding and clot formation
3. Increased destruction, usually _______ mediated
4. Sequestration by an enlarged ________

Back 40

Thrombocytopenia can be caused by:
1. Decreased production due to bone marrow failure
2. Increased consumption due to bleeding and clot formation
3. Increased destruction, usually immune mediated
4. Sequestration by an enlarged SPLEEN

Front 41

Acquired platelet qualitative defects are very common - usually caused by drug therapy. The most frequent offender is ________, which irreversibly inhibits platelet function. Many other drugs have also been implicated in causing transient platelet qualitative defects, including ibuprofen and other non-steroidal anti-inflammatory drugs, and anti-platelet agents such as _________(Plavix) and __________(Ticlid).

Back 41

Acquired platelet qualitative defects are very common - usually caused by drug therapy. The most frequent offender is ASPIRIN, which irreversibly inhibits platelet function. Many other drugs have also been implicated in causing transient platelet qualitative defects, including ibuprofen and other non-steroidal anti-inflammatory drugs, and anti-platelet agents such as CLOPIDOGREL(Plavix) and TICLOPIDINE(Ticlid).

Front 42

Overall, the incidence of congenital qualitative platelet is extremely low. The underlying causes include absence of crucial ___________ proteins, lack of ___________ response or __________________defects. The diagnosis often requires complex platelet function assays, aggregation studies, electron microscopy and other highly specialized tests.

Back 42

Overall, the incidence of congenital qualitative platelet is extremely low. The underlying causes include absence of crucial RECEPTOR PROTEINS, lack of ACTIVATION response or STORAGE GRANULE defects. The diagnosis often requires complex platelet function assays, aggregation studies, electron microscopy and other highly specialized tests.

Front 43

vWF is important in both primary and secondary clot formation. It mediates the adhesion of platelets to injured vessel wall. It also serves as a carrier protein for ___________ and stabilizes ___________. Without vWF, ___________is rapidly cleared by the ________after synthesis.

When vWF is decreased, there is decreased platelet adhesion and platelet plug formation, as well as decreased _________activity level.

Back 43

vWF is important in both primary and secondary clot formation. It mediates the adhesion of platelets to injured vessel wall. It also serves as a carrier protein for FVIII and stabilizes FVIII. Without vWF, FVIII is rapidly cleared by the LIVER after synthesis.

When vWF is decreased, there is decreased platelet adhesion and platelet plug formation, as well as decreased FVIII activity level.

Front 44

There are 3 major types of von Willebrand's Disease. Type ____is by far the most common type. The various types of vWD are characterized by:

Type1: decreased vWF level

Type 2: vWF with abnormal function and/or multimer composition; vWF level is normal or decreased. Several subtypes exist.

Type 3: complete absence of vWF

Back 44

There are 3 major types of von Willebrand's Disease. Type 1 is by far the most common type. The various types of vWD are characterized by:

Type1: decreased vWF level

Type 2: vWF with abnormal function and/or multimer composition; vWF level is normal or decreased. Several subtypes exist.

Type 3: complete absence of vWF

Front 45

Type 1 and most subtypes of Type 2 are due to mutation of one of the two alleles for the vWF gene, thus they are inherited in an ________________ manner. Type 3 is due to mutation of BOTH alleles, thus there is complete absence of vWF and it is an ________________ disease.

Back 45

Type 1 and most subtypes of Type 2 are due to mutation of one of the two alleles for the vWF gene, thus they are inherited in an AUTOSOMAL DOMINANT manner. Type 3 is due to mutation of BOTH alleles, thus there is complete absence of vWF and it is an AUTOSOMAL RECESSIVE disease.

Front 46

vWF antigen test: measures the concentration of _____________ in the plasma

Back 46

vWF antigen test: measures the concentration of vWF PROTEIN in the plasma

Front 47

vWF R:Co (ristocetin cofactor assay): A functional assay measuring the ability of vWF to cause ___________________ in the presence of ristocetin.

Back 47

vWF R:Co (ristocetin cofactor assay): A functional assay measuring the ability of vWF to cause PLATELET CLUMPING in the presence of ristocetin.

Front 48

vWF multimer analysis by gel electrophoresis: examines the composition of vWF multimers. An abnormal pattern is often seen in various forms of Type ____ vWD.

Back 48

vWF multimer analysis by gel electrophoresis: examines the composition of vWF multimers. An abnormal pattern is often seen in various forms of Type 2 vWD.

Front 49

Factor VIII level: It is decreased markedly in type ____, decreased and proportional to the degree of decrease of vWF antigen in type _____. In type 2, there is less correlation between VWF:Ag levels and FVIII levels depending on whether the structurally abnormal vWF is able to bind FVIII.

Back 49

Factor VIII level: It is decreased markedly in type 3, decreased and proportional to the degree of decrease of vWF antigen in type 1. In type 2, there is less correlation between VWF:Ag levels and FVIII levels depending on whether the structurally abnormal vWF is able to bind FVIII.

Front 50

Etiology of Multiple Factor Deficiencies:

Vitamin ____ deficiency or _______ therapy. (More details later)

________ dysfunction: Most coagulation factors are synthesized by the liver. Synthesis is markedly decreased with severe liver disease.

Increased ___________ due to ongoing or recent thrombosis, such as in disseminated intravascular coagulation(DIC), which can consume various coagulation factors, leading to multiple factor deficiency.

Back 50

Etiology of Multiple Factor Deficiencies:

Vitamin K deficiency or WARFARIN therapy. (More details later)

LIVER dysfunction: Most coagulation factors are synthesized by the liver. Synthesis is markedly decreased with severe liver disease.

Increased CONSUMPTION due to ongoing or recent thrombosis, such as in disseminated intravascular coagulation(DIC), which can consume various coagulation factors, leading to multiple factor deficiency.

Front 51

Etiology of Single Factor Deficiencies: These are usually hereditary due to genetic mutations. Most common are Hemophilia A (F _______ deficiency) and Hemophilia B (F __________ deficiency).

Back 51

Etiology of Single Factor Deficiencies: These are usually hereditary due to genetic mutations. Most common are Hemophilia A (F VIII deficiency) and Hemophilia B (F IX deficiency).

Front 52

The synthesis of ____, _____, ____, ____, Protein ___and Protein ____require the presence of vitamin K, which catalyzes the post-translational gamma carboxylation of glutamic acid residues on those proteins. The gamma-carboxyl group added allows these coagulation factors to bind to __________ surface with the help of _______ ions. Thus, vitamin K deficiency results in multiple factor deficiency.

Back 52

The synthesis of FII, FVII, FIX, FX, Protein C and Protein S require the presence of vitamin K, which catalyzes the post-translational gamma carboxylation of glutamic acid residues on those proteins. The gamma-carboxyl group added allows these coagulation factors to bind to PHOSPHOLIPID surface with the help of CALCIUM ions. Thus, vitamin K deficiency results in multiple factor deficiency.

Front 53

The sources of Vitamin K include green leafy vegetables in the diet and synthesis by _________________. Deficiency can be caused by dietary imbalance or recent ________ therapy. Newborns often have a ___________ vitamin K deficiency. In the U.S., most infants are given a vitamin K shot at birth.

Back 53

The sources of Vitamin K include green leafy vegetables in the diet and synthesis by NORMAL GUT BACTERIAL FLORA. Deficiency can be caused by dietary imbalance or recent ANTIBIOTIC therapy. Newborns often have a PHYSIOLOGIC vitamin K deficiency. In the U.S., most infants are given a vitamin K shot at birth.

Front 54

Vitamin K functions only in the _________ form. Warfarin blocks the reduction of vitamin K and interferes with the formation of ______________ groups on FII, FVII, FIX, FX, protein C and protein S. The result is lower activity levels of these proteins in blood, slowing the rate of clot formation. This results in a reduced risk of thrombosis, but increased risk of bleeding. For this reason warfarin therapy must be monitored closely, usually with the _______________ .

Back 54

Vitamin K functions only in the REDUCED form. Warfarin blocks the reduction of vitamin K and interferes with the formation of GAMMA-CARBOXYL groups on FII, FVII, FIX, FX, protein C and protein S. The result is lower activity levels of these proteins in blood, slowing the rate of clot formation. This results in a reduced risk of thrombosis, but increased risk of bleeding. For this reason warfarin therapy must be monitored closely, usually with the PROTHROMBIN TIME(PT) ASSAY.

Front 55

It takes ___________ hours for the warfarin to fully affect coagulation factor levels and the same length of time for factor levels to recover once the warfarin therapy is stopped.

Back 55

It takes 24 to 48 hours for the warfarin to fully affect coagulation factor levels and the same length of time for factor levels to recover once the warfarin therapy is stopped.

Front 56

Both the gene for FVIII and FIX are located on the X chromosome, therefore hemophilia A and B are _______________ disorders.

Back 56

Both the gene for FVIII and FIX are located on the X chromosome, therefore hemophilia A and B are X-LINKED RECESSIVE disorders.

Front 57

FVIII inhibitors are primarily IgG auto-antibodies that are directed against FVIII. These inhibitors occur in 10-15% of patients with hemophilia ____ . Their immune systems react as if the FVIII given as treatment was a foreign protein and develop antibodies against it.

Factor VIII inhibitors can also occur occasionally in non-hemophiliacs, mostly in ______________________.

Back 57

FVIII inhibitors are primarily IgG auto-antibodies that are directed against FVIII. These inhibitors occur in 10-15% of patients with hemophilia A. Their immune systems react as if the FVIII given as treatment was a foreign protein and develop antibodies against it.

Factor VIII inhibitors can also occur occasionally in non-hemophiliacs, mostly in PREGNANT or POSTPARTUM WOMEN and OLDER ADULTS.

Front 58

Most of the coagulation tests performed require whole blood collected in a ______ top (contains _______ anticoagulant) test tube that is plastic or silicone coated. A _______ tube cannot be used because its _________ charged surface will activate the coagulation cascade prematurely.

Buffered citrate maintains the pH of the specimen near the physiologic pH, and also prevents clotting of the specimen in the specimen tube prior to analysis by binding to ________ ions, which are required for many steps of the coagulation cascade. Always mix the citrate buffer and blood immediately after drawing the specimen.

Back 58

Most of the coagulation tests performed require whole blood collected in a BLUE top (contains CITRATE anticoagulant) test tube that is plastic or silicone coated. A GLASS tube cannot be used because its NEGATIVELY charged surface will activate the coagulation cascade prematurely.

Buffered citrate maintains the pH of the specimen near the physiologic pH, and also prevents clotting of the specimen in the specimen tube prior to analysis by binding to calcium ions, which are required for many steps of the coagulation cascade. Always mix the citrate buffer and blood immediately after drawing the specimen.

Front 59

Hemolyzed specimens, whether due to a traumatic blood draw or real intravascular hemolysis in the patient, are unacceptable. Both the mechanical trauma associated with a bad draw and the free red cell membranes can activate the coagulation cascade _____________.

As explained before, half-filled tubes should not be accepted because the excess ________________ will interfere with clot based coagulation tests.

Back 59

Hemolyzed specimens, whether due to a traumatic blood draw or real intravascular hemolysis in the patient, are unacceptable. Both the mechanical trauma associated with a bad draw and the free red cell membranes can activate the coagulation cascade PREMATURELY.

As explained before, half-filled tubes should not be accepted because the excess CITRATE BUFFER will interfere with clot based coagulation tests.

Front 60

There are two main causes of prolongation of TT:

1.
2.

Less common causes include:
Fibrinogen with abnormal function
Antibodies that inhibit thrombin
Inhibition of thrombin due to increased fibrin degradation products, such as D-dimer

Back 60

There are two main causes of prolongation of TT:

1. Heparin contamination
2. Low fibrinogen level
Less common causes include:
Fibrinogen with abnormal function
Antibodies that inhibit thrombin
Inhibition of thrombin due to increased fibrin degradation products, such as D-dimer

Front 61

Prolongation of PT or aPTT could be due to factor deficiency or an inhibitor. _________________ is often done to distinguish the two possibilities.

Back 61

Prolongation of PT or aPTT could be due to factor deficiency or an inhibitor. A 1:1 MIXING STUDY is often done to distinguish the two possibilities.

Front 62

In this assay, the patient plasma is mixed at a 1:1 ratio with normal pooled plasma. If the patient plasma is deficient in coagulation factor(s), then the normal plasma should provide enough coagulation factors to ________ the prolongation of clotting time. Factor deficiency can be confirmed by measuring individual factor levels.

If an inhibitor is the cause of the prolongation, the inhibitor will inhibit coagulation factor from both the patient's and the normal pool plasma. Thus, the prolongation will _______.

Back 62

In this assay, the patient plasma is mixed at a 1:1 ratio with normal pooled plasma. If the patient plasma is deficient in coagulation factor(s), then the normal plasma should provide enough coagulation factors to CORRECT the prolongation of clotting time. Factor deficiency can be confirmed by measuring individual factor levels.

If an inhibitor is the cause of the prolongation, the inhibitor will inhibit coagulation factor from both the patient's and the normal pool plasma. Thus, the prolongation will PERSIST.

Front 63

In addition, the aPTT is often repeated after the 1:1 mix has been incubated for one or two hours at 37ºC. This is done to detect a _________________, which characteristically shows further prolongation of the aPTT upon incubation of the 1:1 mix. It is important for labs to recognize _________________, because they are associated with severe bleeding tendencies.

Back 63

In addition, the aPTT is often repeated after the 1:1 mix has been incubated for one or two hours at 37C. This is done to detect a FVIII INHIBITOR which characteristically shows further prolongation of the aPTT upon incubation of the 1:1 mix. It is important for labs to recognize FVIII INHIBITORS, because they are associated with severe bleeding tendencies.