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Hemostasis > Secondary Hemostasis and Fibrinolysis > Flashcards

Secondary Hemostasis and Fibrinolysis Flashcards

1
Q

Factor I Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Fibrinogen

Pathway: Common

Group: Fibrinogen

Function/role: Substrate (only acted on by the enzyme without furthering the cascade)

Site of production: liver

Monitored with what test: PT, PTT, TT, Fibrinogen Assay

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2
Q

Factor II Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Prothrombin

Pathway: Common

Group: Prothrombin

Function/role: Serine protease (Converts inert factors (zymogens) into active forms)

Site of production: Liver

Monitored with what test: PT, PTT

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3
Q

Factor III Alternate names, pathway, function/role, site of production

A

Alternate names: Tissue Factor

Pathway: Extrinsic

Function/role: Cofactor (extrinsic Xase)

Site of production: Tissue (nonvascular)

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4
Q

Factor V Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Proacelerin

Pathway: Common

Group: Fibrinogen

Function/role: Cofactor (prothrombinase complex)

Site of production: Liver

Monitored with what test: PT, PTT

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5
Q

Factor VII Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: proconvertin

Pathway: Extrinsic

Group: Prothrombin

Function/role: Serine Protease

Site of production: Liver

Monitored with what test: PT

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6
Q

Factor VIII Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: antihemophilic factor

Pathway: Intrinsic

Group: Fibrinogen

Function/role: Cofactor (intrinsic Xase)

Site of production: liver

Monitored with what test: PTT

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7
Q

Factor IX Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Christmas factor

Pathway: Intrinsic

Group: Prothrombin

Function/role: Serine protease

Site of production: Liver

Monitored with what test: PTT

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8
Q

Factor X Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Stuart factor

Pathway: Common

Group: Prothrombin

Function/role: Serine protease

Site of production: Liver

Monitored with what test: PT, PTT

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9
Q

Factor XI Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: plasma thromboplastin antecedent

Pathway: Intrinsic

Group:Contact

Function/role: Serine protease, contact factor

Site of production: Liver

Monitored with what test: PTT

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10
Q

Factor XII Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: Hageman factor

Pathway: Intrinsic

Group: Contact

Function/role: Serine protease (Converts inert factors (zymogens) into active forms), contact factor

Site of production: Liver

Monitored with what test: PTT

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11
Q

Factor XIII Alternate names, pathway, group, function/role, site of production, monitored by what test

A

Alternate names: stabilizing factor

Pathway: Common

Group: Fibrinogen

Function/role: Transglutaminase—forms stable X-linked covalent bonds on fibrin

Site of production: BM monos, macs, and megakaryocytes

Monitored with what test: Urease

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12
Q

PK Alternate names, pathway, group, function/role, monitored by what test

A

Alternate names: Prekallikrein. Fletcher factor

Pathway: intrinsic

Group: contact

Function/role: Cofactor; contact factor

Monitored with what test: PT

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13
Q

HMWK Alternate names, pathway, group, function/role, monitored by what test

A

Alternate names: High Molecular Weight Kiminogen, Fitzgerald factor

Pathway: Intrinsic

Group: contact

Function/role: Platelet adhesion; stabilize FVIII; contact factor; serine protease complexed with HK

Monitored with what test: PTT

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14
Q

Which factors are Vitamin K dependent. Describe why these factors are Vitamin K dependent.

A

Facilitates y-carboxylation of the factors (II, VII, IX, X, PC, PS) which leads to an extra group being added to the y-carbon. Ca+2 binds to this site; induces conformational charge that allows the factor to bind to phospholipids Acarboxy proteins: Vitamin K dependent factors produced by the absence of vitamin K

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15
Q

Describe or diagram the coagulation cascade. Order the reactions from activation of the extrinsic and intrinsic pathways to fibrin formation and discuss each reaction/component.

A
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16
Q

Discuss the conversion of fibrinogen to a stabilized fibrin polymer.

A

Step 1
• Thrombin cleaves Fibrinopeptides A (α) and B(β) from the central E domain of the fibrinogen molecule
• Result: Fibrin Monomer (unstable)

Step 2
• Fibrin monomers spontaneously polymerize
• Result: unstable Fibrin Polymers (Note: Fibrin polymers are the endpoint for the PT and PTT test)

Step 3
• Factor XIIIa forms covalent bond between adjacent D-domains
• Result: Stable (stronger) fibrin

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17
Q

What is the proper specimen for most coagulation tests and the ratio of anticoagulant to blood in the container? What happens if the proper ratio is not obtained?

A 
Sodium Citrate (binds Calcium)
9:1 ratio blood to anticoagulant. An underfilled tube would result in too much anticoagulant and would falsely prolong hemostasis test results such as the PT and PTT. An overfilled tube would result in not enough anticoagulant and would falsely decrease hemostasis test result.
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18
Q

Fibrinogen Group

A

Acted on by thrombin
Unstable—lose activity when stored
Absent in serum—consumed during clotting
Members: Factor I (Fibrinogen), Factor V, Factor XIII, Factor VIII

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19
Q

Contact Group

A

Initial activation of intrinsic pathway
Stable and present in serum after clotting
Members: Factor XI, Factor XII, PK, HK

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20
Q

Prothrombin Group

A

Vitamin K Dependent (needs to bind Ca+2)
Have GLA-domain
Area where vitamin K dependent carboxylation occurs
Stable in stored plasma and serum
Members: Facter II, Factor VII, Factor IX, Factor X, Protein C and S

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21
Q

Prothrombin Time (PT)

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: 1) Screen for extrinsic or common pathway factor/inhibitor deficiencies
2) Monitor oral anticoagulant therapy

Principle: Measure the time from activation of the extrinsic pathway to fibrin formation

Reagents Involved: 1) Tissue thromboplastin (rabbit brain with Ca)

Normal Reference Interval: 10-13 seconds

Significance of Abnormal Results: Decreased: not clinically significant
Increased: Extrinsic of common pathway factor deficiency or inhibitor, or taking oral anticoagulants

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22
Q

Fibrinogen Assay

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: To quantitatively measure the amount of fibrinogen present

Principle: TT is inversely proportionally to the fibrinogen concentration. Establish a standard curve and use the patient’s thrombin time result to plug into the curve and determine the concentration of fibrinogen

Reagents Involved: Thrombin Reagent

Normal Reference Interval: 200-400 mg/dL

Significance of Abnormal Results: Increased: usually not clinically significant
Decreased: fibrinogen deficiency, fibrin inhibitors

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23
Q

Thrombin Time

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: 1) Evaluates the conversion of fibrinogen to fibrin 2) Screens for heparin

Principle: Add excess thrombin reagent to sample, measure the time it takes until clot forms

Reagents Involved: Thrombin Reagent

Normal Reference Interval: 10-22 seconds

Significance of Abnormal Results: Decreased: not clinically significant
Increased: deficiency of fibrinogen; presence of heparin, FDPs or plasmin

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24
Q

Reptilase Time

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: 1) Evaluate the conversion of Fibrinogen to Fibrin 2) Screens for heparin (in conjunction with thrombin time)

Principle: Same as the thrombin time, except initiated with a different reagent (this reagent is not affected by the presence of heparin)

Reagents Involved: Reptilase (found in venom of Bothrops atrox snake)

Normal Reference Interval: 16-22 seconds
Significance of Results: increase = deficiency of fibrinogen

25
Q

D-Dimer Assay

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: To detect D-dimer fragments formed during fibrinolysis

Principle: A latex with antibodies specific for the D-dimer fragment is used

Reagents Involved: Latex coated with anti-d-dimer monoclonal antibodies

Normal Reference Interval: <250ng/mL

Significance of Results: Increased conditions with increased fibrinolysis such as DVT or DIC

26
Q

5M Urea

Purpose

Principle

Reagents Involved

Normal Reference Interval

Significance of Abnormal Results

A

Purpose: To screen for deficiencies in Factor XIII

Principle: Unstable fibrin is soluble in 5M urea after 24 hours

Reagents Involved: 5M urea

Normal Reference Interval: Clot present in 24 hours

Significance of Results: Clot disappears between 0-24 hours = Factor XIII deficiency

27
Q

Compare and Contrast Fibrin Degradation Products (FDPs) and D-dimers. Discuss their structure, the lab test(s) used to measure them, and the clinical application for the tests.

A

FSP are degradation products of fibrin and fibrinogen (Fragments X, Y, D, and E). Increases indicate increased fibrinolytic activity

FDP is a latex screening test that doesn’t distinguish between fibrin degradation products and fibrinogen degradation products

D-Dimers are fibrin degradation products that contain “D” fragments that have been covalently bonded to one another by factor XIII

28
Q

Discuss the different functionalities of thrombin

A

Procoagulant Functions:
• Converts Fibrinogen and fibrin
• Activates Factor XIII to XIIIa
• Positive feedback for cofactors V, VIII, IX

Anticoagulant Functions
• Involved with activation of Protein C (inhibitor of fibrin formation)
• Stimulates endothelial cells to release

Tissue Plasminogen Activator

Nitric Oxide and Prostacyclin

29
Q

Antithrombin

A

Inactivates the serine proteases—thus inhibiting the coagulation cascade

30
Q

Heparin Cofactor II

A

Inhibits thrombin only
Most effective in extravascular locations
Actions accelerated by heparin and dermatan sulfate

31
Q

Protein C & S

A

They work together as major inhibitors of blood coag, vitamin K dependent made by liver
Protein C—can only bind to free protein S—inhibits Va, VIIIa
Protein S—cofactor for the protein C pathway, two different types (bound and free)
• Bound to complement C4b binding protein, PC effects are low

32
Q

Tissue Factor Pathway Inhibitor

A

An inhibitor of the extrinsic pathway. Binds to Factor Xa and neutralizes it, resulting in a conformation change that promotes binding of the Factor Xa/TFPI complex with the Factor VIIa/TF complex—resulting in its inhibition

33
Q

Factor X deficiency
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Mild to severe bleeding

Pathophysiology: Inherited deficiency

lab results
PT, PTT: Increased
Factor X assay: decreased
Russell’s Viper Venom — Abnormal

34
Q

Factor VII deficiency
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Mild to severe bleeding

Pathophysiology: inherited deficiency

lab results
PT: Increased
Factor VII: Decreased

35
Q

Factor XIII deficiency
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Umbilical cord bleeding shortly after birth
Excess bleeding after circumcision
Spontaneous intracranial bleeding

Pathophysiology: inherited deficiency

lab results:
PT, PTT, TT, Fibrinogen: Normal

36
Q

Factor XII, HK, or PK deficiency
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: No bleeding symptoms

Pathophysiology: Inherited deficiency

lab results:
PTT: Increased
Factor XII, PK assay, HK assay: depend on deficiency

37
Q

Hemophillia A
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Severe bleeding common, Hemarthrosis. Deep and Delayed bleeding

Pathophysiology: Deficiency in Factor VIII
X linked Recessive

lab results:
Bleeding time, platelet count, platelet aggregation, PT, TT: Normal
PTT: Increased
Mixing Studies: correction
Factor VIII: Decreased

38
Q

Hemophillia B
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Severe bleeding common, Hemarthrosis, Deep and Delayed bleeding

Pathophysiology: Deficiency in Factor IX
X linked Recessive

Lab results:
PT, TT, Fibrinogen: Normal
PTT: increased
Mixing studies: Corrected

39
Q

Factor XI deficiency
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Bleeding possible in 50% of cases

Pathophysiology: Inherited deficiency

Lab results:
PTT: increased

40
Q

Factor Assay
Purpose, principle, reagents, result significance

A

Purpose: To quantitatively measure coagulation factors

Principle: Modification of the PT or PTT. Specific factor deficient plasma is mixed with patient plasma. If the pt is deficient in the same factor it will be prolonged, if not deficient in the factor it will be normal

Reagents Involved: Substrate plasms
Reagents of PT and PTT

Significance of Results: Prolonged — patient is deficient in that factor being analyzed

41
Q

Mixing Studies
Purpose, principle, reagents, result significance

A

Purpose: Differentiate between a true factor deficiency and a factor inhibitor

Principles: Patient plasma is mixed in a 1:1 ratio with normal reagent plasma. A PT/PTT test is then performed on this mixture. If the patient is deficient in a coag factor, the normal plasma present will supply enough to the deficient factor to “correct” the PT/PTT result. If the patient has a circulating inhibitor, then the correction will not occur

Reagents: Normal Reagent plasma

Significance of Results: Correction = factor deficiency

42
Q

Bethesda Titers
Purpose, principle, reagents, result significance

A

Purpose: Determine amount of a specific coagulation inhibitor

Principle: Equal volumes of normal pooled plasma and patient plasma are mixed,and a factor assary is ran, results are interpreted from a Bethesda chart

Reagents: Normal pooled plasma and factor assay reagents

Significance of results: Compare to Bethesda chart standard curve

43
Q

Describe treatment options for the following conditions:
Hemophilia A

A

cryoprecipitate or factor VIII concentrates; DDAVP possible

44
Q

Describe treatment options for the following conditions:
Hemophilia B

A

FFP; Factor IX concentrate

45
Q

Afibrinogenemia
Clinical manifestation, pathophysiology, lab results

A

Clinical Manifestation: Can be severe; may have spans without bleeding

Pathophysiology: Inherited deficiency of Factor I

Lab Results:
PT, PTT, TT: Prolonged
Fibrinogen: low, less than 5 mg/dL

46
Q

Hypofibrinogenimia
Clinical manifestation, pathophysiology, lab results

A

Clinical manifestation: Often asymptomatic; may have excess bleeding after trauma

Pathophysiology: Inherited deficiency of Factor I

Lab result:
Platelet count, bleeding time, platelet aggregation test, PT, PTT: Normal
TT: Increased
Fibrinogen: 20-100mg/dL (low)

47
Q

Describe treatment options for the following conditions:
Factor I Deficiency

A

Cryoprecipitate; each blood type has different amounts of vWF: Type O have least, Type B has the most

48
Q

Intrinsic Pathway
Factors involved, triggers/activators, endpoint, tests to monitor

A

Increase Pathway: PK, HK, MF, XII, XI, IX, VIII

Trigger: Autoactivation of contact factors

Endpoint: activation of common pathway

Test to monitor: PTT

49
Q

Extrinsic Pathway
Factors involved, triggers/activators, endpoint, tests to monitor

A

Factors involved: TF, VII

Triggers: Tissue damage that releases TF

Endpoint: Activation of common pathway

Test to monitor: PT

50
Q

Common pathway
Factors involved, triggers/activators, endpoint, tests to monitor

A

Factors involved: X, V, II, I

Triggers: Intrinsic and extrinsic Xase complexes

Endpoint: fibrin formation

Tests to monitor: PTT, PT

51
Q

List and describe specific clinical symptoms associated with bleeding disorders related to:

Platelet or Vascular Problems

A

Petechiae (small pinpoint bruises)

52
Q

List and describe specific clinical symptoms associated with bleeding disorders related to:

Coagulation Factor Problems

A

Hemarthrosis (joint bleeding); delayed bleeding; deep bleeding

53
Q

Discuss inhibitors of single factors and therapy for low and high responders

A

Each coag factor has an inhibitor. The most common single inhibitors are VIII and IX. The inhibitors are autoantibodies specific for a factor. Low responders can be treated with large amounts of factor concentrates. High responders are difficult to treat. Recombinant F-VIIa show promise as a means of activating Factor X and bypassing the intrinsic pathway

54
Q

Patient 1: Increased, Decreased or Normal?
Bleeding Time - 5 minutes (1-10 min)
Platelet Count - 220,000/uL (150,000 - 450,000)
aPTT - 30 seconds (25 - 36 sec)
PT - 17 seconds (10 - 13 sec)
Mixing Studies - Corrected
D-dimer - normal

A

BLEEDING TIME NORMAL
PLATELET COUNT NORMAL
PTT NORMAL
PT ABNORMAL

POSSIBLE DIAGNOSIS: EXTRINSIC PATHWAY FACTOR DEFICIENCY

55
Q

Patient 2:
Bleeding Time - 3 minutes (1 - 10min)
Platelet Count - 310,000/uL (150,000 - 450,000)
aPTT - 82 seconds (25 - 36 sec)
PT - 27 seconds (10 - 13 sec)
Fibrinogen Assay - 289 mg/dL (200 - 400 mg/dL)
Mixing Studies - corrected
D-dimer - normal

A

BLEEDING TIME NORMAL
PLATELET COUNT NORMAL
PTT ABNORMAL
PT ABNORMAL
FIBRINOGEN ASSAY NORMAL

POSSIBLE DIAGNOSIS: COMMON PATHWAY FACTOR DEFICIENCY

56
Q

Patient 3

Bleeding Time - >15 minutes (1 - 10 min)
Platelet Count - 220,000/uL (150,000 - 450,000)
aPTT - 47 seconds (25 - 36 sec)
PT - 11 seconds (10 - 13 sec)
D-dimer - normal
Platelet Aggregation Studies - abnormal with ristocetin

A

BLEEDING TIME: ABNORMAL
PLATELET COUNT: NORMAL
PTT: ABNORMAL
PT: NORMAL

DIAGNOSIS: VON WILLEBRAND FACTOR DEFICIENCY

57
Q

Patient 4

Bleeding Time - 8 minutes (1 - 10 min)
Platelet Count - 285,000/uL (150,000 - 450,000)
aPTT - 30 seconds (25 - 36 sec)
PT - 11 seconds (10 - 13 sec)
D-dimer - abnormal (elevated)

A

BLEEDING TIME NORMAL
PLATELET COUNT NORMAL
PTT NORMAL
PT NORMAL
POSSIBLE DIAGNOSIS: INCREASED FIBROLYSIS

58
Q

Patient 5:
Platelet Count -302,000/uL (150,000 - 450,000)
aPTT - 64 seconds (25 - 36 sec)
PT - 12 seconds (10 - 13 sec)
D-dimer - normal
Mixing Studies - not corrected

A

PLATELET COUNT NORMAL
PTT INCREASED
PT NORMAL

INTRINSIC PATHWAY INHIBITOR

Hemostasis (3 decks)

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