PRN/CIULLA NOTES Flashcards
(133 cards)
1
Q
- activated during coagulation and fibrinolysis
- contains more than 30 circulating blood
- mediate inflamm response
- immune and allergic reactions
- lysing antibody-coated cells
A
Complement system
2
Q
Ag-Ab complexes
- Activates C1
- Cleavages of C3b into C3a and C3b
A
Plasmin
3
Q
Increases vascular permeability
A
C3a
4
Q
- immune adherence of erythrocytes to neutrophils; enhances phagocytosis
A
C3b
5
Q
Kinin system contains four plasma proteins
A
- Factor XII
- Factor XI
- Fletcher (prekallikrein)
- HMWK (Fitzgerald)
6
Q
Kinin system generates this active peptide and proteolytic enzyme
A
- bradykinin
- kallikrein
7
Q
- mediate inflam response
- promote vasodilation
- activator of intrinsic coag
- complement pathways
- involves in chemotaxis and pain sensation
A
Kinin System
8
Q
- keeps blood vessel clear
- important in clot dissolution
- plasminogen activated into plasmin
A
Fibrinolytic System
9
Q
- found in circulation
- glycoprotein produced in the liver
- converted to plasmin by plasminogen activators
A
Plasminogen
10
Q
Plasminogen
-found in plasma (inert)
A
Zymogen
11
Q
- not normally found in circulation
- degrades fibrin clots (fibrinolysis)
- fibrinogen (fibrinogenolysis)
- factors V and VIII
- activates complement system
A
Plasmin
12
Q
Plasminogen Intrinsic Activators
A
- XIIa
- Kallikrein
- HMWK
13
Q
Plasminogen Extrinsic Activators
A
- tissue-type plasminogen activators (t-PA)
- urokinase-type plasminogen activators (u-PA)
14
Q
Plasminogen Exogenous Activators
A
- Therapeutic Agents
- t-PA
- streptokinase
- urokinase
all administered to lyse existing clots
15
Q
REGULATORY PROTEINS OF COAGULATION AND FIBRINOLYSIS
A
- Antithrombin (AT)
- Protein C and S
- Tissue Factor Pathway Inhbitor
- A2- macroglobulin
- a1-antitrypsin
- C1 inhibitor
- A2-antiplasmin
- PAI-1
16
Q
- produced in the liver
- principle of coagulation
- inhibits the serine proteases
- therapeutic heparin substances the action of antithrombin
A
Antithrombin (AT)
17
Q
- Vit K dependent regulatory protein
- Activated when thrombin binds to thrombomodulin on the endothelial cell surface
A
Protein C and S
18
Q
Protein C and S inhibit factors _
A
Factors V and VIII to provide negative feedback on the cascade
19
Q
Inhibits factor Vila-tissue factor complex
A
Tissue Factor Pathway Inhibitor
20
Q
Inhibits thrombin, Xa, kallikrein, and plasmin
A
A2- Macroglobulin
21
Q
a2-macroglobulin inhibits what
A
- thrombin
- Xa
- kallikrein
- plasma
22
Q
Inhibits XIa and inactivates plasmin
A
a1-antitrypsin
23
Q
Inhibits C1 from the complement cascade, and Xlla, XIa,
kallikrein, and plasmin
A
C1 inhibitor
24
Q
Principal inhibitor of fibrinolysis; neutralizes plasmin
A
a2-Antiplasmin
25
- Important inhibitor of fibrinolysis
- Prevents activation of plasminogen by t-PA; released from endothelial cells upon damage
PAI-1 (plasminogen activator inhibitor-1)
26
Thrombotic Disorders
- Primary
- Secondary
27
Primary Thrombotic Disorders
- Deficiency in regulatory proteins
- Decreased activation of the fibrinolytic system
- Genetic mutations
28
Seconday Thrombotic Disorders
- Lupus anticoagulant
- Post-operative status
- Malignancy
- Pregnancy
- Estrogen/oral contraceptives
- Morbid obesity
- Hyperhomocysteinemia
29
- Genetic deficiency occurs about 1:2000 in the general population;
- associated with deep vein thrombosis and pulmonary embolism
- Serine proteases not inhibited; negative feedback to cascade impaired
- Laboratory: Antithrombin activity assay (antigenic testing less common
Antithrombin (AT) deficiency
30
- Vit K dependent regulatory proteins that inactivate factors V and VIII
- Can cause superficial and deep vein thrombosis and/or pulmonary embolism
- Laboratory: Immunologic and functional testing to diagnose
Protein C or Protein S deficiencies
31
- XII, prekallikrein, and HMWK are contact factors in secondary hemostasis, but their most important role is the intrinsic activation of the fibrinolytic system.
- Deficiencies are associated with thrombosis, not hemorrhage.
- All have an autosomal recessive inheritance pattern
Decreased activation of the fibrinolytic system
32
causes a prolonged aPTT; factor XII assay confirms.
Factor XII (Hageman Factor) deficiency
33
causes a prolonged aPTT that shortens in patient plasma incubated with kaolin
Prekallikrein (Fletcher factor) deficiency
34
causes a slightly prolonged aPTT
HMWK (Fitzgerald factor) deficiency
35
characterized by thrombosis due to an inability to generate plasmin
Plasminogen deficiency
36
Deficiency in regulatory proteins
- Antithrombin (AT) deficiency
- Protein C or Protein S deficiencies
37
Decreased activation of the fibrinolytic system
- Thrombosis deficiencies
- all have autosomal recessive
- Factor XII deficiency
- Prekallikrein Factor deficiency
- HMWK deficiency
- Plasminogen deficiency
38
Primary Thrombotic Disorders
Genetic mutations
- Factor V leiden
- Prothrombin gene mutation 20210
- Dysfibrinogenemia
39
- Most common hereditary cause of thrombosis; caused by an amino acid substitution
- Protein C is incapable of inactivating factor V Leiden, causing thrombin generation and subsequent fibrin clot formation.
- Laboratory: PCR-based molecular assay to single-point mutation in the gene for factor V
Factor V Leiden (Activated Protein C Resistance - APCR)
40
- Second most common hereditary cause of thrombosis; caused by an amino acid substitution
-May have slightly elevated prothrombin level
- Laboratory: PCR-based molecular assay
Prothrombin gene mutation 20210
41
- Autosomal-dominant trait; abnormal structure of fibrinogen; caused by gene mutations
- Associated with either bleeding or thrombosis; dependent on the specific gene mutation
Dysfibrinogenemia
42
The body develops autoantibodies against platelet phospholipids; etiology is unknown.
Lupus anticoagulant and anticardiolipin antibodies
43
Thrombotic event starts after tissue factor release during
surgery, activating the extrinsic coagulation (dominant in vivo) pathway.
Post-operative status
44
Risk of malignancy increases because of the release of
thromboplastic substances by neoplastic cells
Malignancy
45
- The placenta is rich in tissue factor, which may enhance thrombosis during pregnancy, especially high-risk patients having caesarian section delivery.
- Factor V and VIII levels increase, contributing to clot formation.
Pregnancy
46
Increase risk of venous thrombosis and renal artery thrombosis
Estrogen/oral contraceptives
47
Results in decreased AT levels and increased PAI-1, causing
thrombosis
Morbid obesity
48
This disorder is linked to atherosclerosis, resulting in arterial and venous thromboembolism. Mechanisms are not fully
understood but may be associated with a reduction in the localized activation of the protein C pathway.
Hyperhomocysteinemia
49
Hemorrhagic Disorders
- Inherited disordees
- Acquired Disorders
- Hemorrhagic Symptoms
- Inherited Intrinsic Pathway Hemorrhagic Disorders
- Acquired Disorders of Coagulation and Fibrinolysis
50
Generally affect only one hemostatic component
(e.g., factor VIII)
Inherited Disorders
51
Involve multiple hemostatic components or pathways
(e.g., warfarin therapy, liver disease)
Acquired Disorders
52
Hemorrhagic Symptoms
Associated with defects in secondary hemostasis; include bleeding into deep tissues, joints, abdominal and other body cavities
53
- Autosomal-dominant trait
- Most common hereditary bleeding disorder; abnormalities in both primary and secondary hemostasis
- Caused by a defect in von Willebrand factor that is needed for platelet adhesion to collagen in primary hemostasis. vWF is also the carrier protein for factor VIII:C in secondary hemostasis.
von Willebrand disease
54
- Clinical: Mild to moderate bleeding dependent of vWF and VIII:C levels menorrhagia common symptom in women
von Willebrand disease
55
Von Willebrand Disease Laboratory
- Decreased vWF:RCo, vWF:Ag, and VIII:C; abnormal platelet aggregation with ristocetin
- variable aPTT (often prolonged because of decreased VIILC), - prolonged bleeding time
56
von Willebrand Disease Treatment
- Factor VIII concentrates
- DDAVP (deamino-D-arginine-vasopressin) used to raise plasma levels of vWF and VIII:C
57
- Sex-linked disorder transmitted on the X chromosome by carrier women to their sons
- Accounts for 80% of the hemophilias; second most common hereditary
bleeding disorder
- from spontaneous mutations.
- Clinical: Bleeding symptoms are proportional to the degree of the factor deficiency. Spontaneous bleeding occurs often and is especially bad in joint regions (hemarthrosis).
Factor VIII:C (hemophilia A, classic hemophilia) deficiency
58
Factor VIII :C (hemophilia A, classic hemophilia) deficiency laboratory
- prolonged aPTT only
Factor VIII: C assay to confirm
59
Treatment for Factor VIII :C (hemophilia A, classic hemophilia) deficiency
- Cryoprecipitate and Factor VIII concentrates in mild cases
- DDAVP used to stimulate the release of VIII:C and VWF from stored reserves
60
- Sex-linked recessive trait
- Accounts for 20% of the hemophilias; third most common hereditary bleeding disorder
Factor IX (Hemophilia B, Christmas disease) deficiency
61
Bleeding symptoms are similar to those seen in hemophilia A
Factor IX (hemophilia B, Christmas disease) deficiency
62
Factor IX (hemophilia B, Christmas disease) deficiency laboratory
- prolonged aPTT only
- factor IX assay to confirm
63
Factor IX (hemophilia B, christmas disease) deficiency treatment
- FFP or Factor IX concentrates
64
- Mainly seen in the Ashkenazi Jewish population
- Characterized by clinical bleeding that is asymptomatic until surgery or trauma
Factory XI (hemophilia C) deficiency
65
Factory XI (hemophilia C) deficiency laboratory
- proloned aPTT only
- Factor IX assay to confirm
66
Inherited Extrinsic and Common Pathway Hemorrhagic Disorders
- Factor VII (stable factor) deficiency
- Factor X (Stuart Prower) deficiency
- Factor V (Owren disease, labile factor) deficiency
- Factor II (prothrombin) deficiency
- Factor I (fibrinogen) deficiency
- Factor XIII (fibrin-stabilizing factor) deficiency
I, II, V, VII, X, XIII
67
-,Autosomal-recessive trait
- Clinical: Soft tissue bleeding
- Laboratory: Prolonged PT only
Factor VII (stable factor) deficiency
68
- Autosomal-recessive trait
- Clinical: Soft tissue bleeding and chronic bruising
- Laboratory: Prolonged PT and aPTT
Factor X (Stuart- Prower) deficiency
69
- Autosomal-recessive trait
- Clinical: Mild to moderate bleeding symptoms
- Laboratory: Prolonged PT and aPTT
Factor V (Owren disease, labile factor) deficiency
70
- Autosomal-recessive trait
- Clinical: Mild bleeding symptoms
- Laboratory: Prolonged PT and aPTT
Factor II (prothrombin) deficiency
71
- Autosomal-recessive trait; results from the following inherited disorders\
- Afibrinogenemia
- Hypofibrinogenemia
- Clinical: Spontaneous bleeding of mucosa, intestines, and intracranial sites
- Laboratory: Prolonged bleeding time (fibrinogen bridges do not form; platelet aggregation defect), decreased fibrinogen concentration, and prolonged PT, aPTT, and thrombin time
Factor I (fibrinogen) deficiency
72
- Autosomal-recessive trait
- Clinical: Spontaneous bleeding, delayed wound healing, and unusual scar formation; increased incidence of spontaneous abortion
- Laboratory: 5.0 M urea test abnormal, PT and aPTT = Normal, enzymatic and immunologic studies can be done
Factor XIII (fibrin-stabilizing factor) deficiency
73
Acquired Disorders of Coagulation and Fibrinolysis
- Hepatic disease
- Vitamin K deficiency
- DIC with secondary with fibrinolysis
- Primary fibrinogenolysis
74
- The liver is the major site of hemostatic protein synthesis.
- can result in decreased synthesis of coagulation or regulatory proteins; it also causes impaired clearance of activated hemostatic components.
- Laboratory: Prolonged PT, aPTT, bleeding time, and possibly decreased platelet counts because of hypersplenism, alcohol toxicity, and disseminated intravascular coagulation (DIG)
Hepatic diseasw
75
- Needed for liver synthesis of functional factors II, VII, IX,
and X.
- Produced by normal intestinal flora.
- Deficiencies in this can result from oral antibiotics, vitamin K antagonists (warfarin), or decreased absorption resulting from obstructive jaundice
- Breast-fed babies are more prone because breast milk is sterile, which allows no bacterial intestinal colonization to occur.
- Laboratory: Prolonged PT (VII, X, II) and prolonged aPTT (IX, X, II)
Vitamin K
76
Predisposing condition triggers systemic clotting; leads to systemic fibrinolysis and bleeding
DIC with secondary fibrinolysis
77
Predisposing condition triggers systemic clotting; leads to systemic fibrinolysis and bleeding
DIC with secondary fibrinolysis
78
- Triggering events include gram-negative septicemia, acute promyelocytic leukemia (FAB M3), obstetrical complications, massive tissue damage.
- Fibrinogen group factors (I, V, VIII, XIII) and platelets are consumed in clotting.
DIC with secondary fibrinolysis
79
DIC with secondary fibrinolysis laboratory
Prolonged: PT, aPTT, thrombin time
Decreased: Platelet count, antithrombin, finrinogen
Abnormal: Fibrin and Fibrinogen degradation products (D-dimer and FDP)
80
A systemic thrombotic event causes multiple organ failure;
systemic lysis ultimately leads to severe hemorrhage.
DIC with secondary fibrinolysis
81
Treatment for DIC with secondary fibrinolysis
- FFP
- platelet transfusions
- antithrombin concentrates
- heparin to stop systemic clotting
82
Plasminogen is inappropriately activated to plasmin in the absence of clot formation. Plasmin circulates free in plasma and destroys factors I, V, and VIII.
- Caused by certain malignancies (e.g., prostate cancer) or massive tissue damage that causes release of plasminogen activators
Primary fibrinogenolysis
83
Primary fibrinogenolysis laboratory
Prolonged: PT, aPTT, thrombin time
Low: Fibrinogen conc (plasmin degrades fibrinogen, V, and VIII)
Normal: Platelet count, RBC morph, antithrombin conc
Present: Fibrinogen degredation products (abnormal FDP test)
Absent: Fibrin degradation products (normal D-di er; no clot formation)
84
Hemorrhagic symptoms occur that may resemble DIG.
Primary fibrinogenolysis
85
Treatment for primary fibrinogenolysis
Epsilon aminocaproic acid (EACA) is used to turn off
inappropriate systemic lysis.
86
Coagulation Testing
Nontraumatic Venipuncture
A. Nontraumatic Venipuncture: It is essential that trauma be avoided because it may introduce tissue thromboplastin that would activate coagulation
87
Coagulation testing
Order of draw
It is important that proper order of draw be followed. Collect
tube for coagulation testing before any tubes containing heparin, EDTA, sodium fluoride, or clot-promoting additives
88
Coagulation Testing
Uses
Plastic- or Silicone-Coated Glass Tubes: Plain glass tubes will activate the intrinsic pathway, including the activation of the contact factors prekallikrein, XI, and XII.
89
Coagulation Testing
Ratio of Blood to anticoagulant
9:1 to 3.2% sodium anticoagulant
excess citrate = falsely long coag times
90
Coagulation Test
Specimen Processing
- process ASAP
- within 4 hrs aPTT; 24 hrs PT
- Centri = platelet poor plasma and remove plasma from cells, can freeze plasma at -20 C
91
Coagulation Test
Temperature
37 C
labile factors breakdown at >37 C
factors VII and CI = activated at cold temp
92
- Screening test for factors XII, XI, prekallikrein, HMWK, IX, VIII, X, V, II, and I (intrinsic/common pathways)
- Monitors unfractionated heparin therapy
Activated Partial Thromboplastin Time (APTT)
93
APTT reagents
- Platelet phospholipid substitute with an activator (kaolin, celite, silica, or ellagic acid)
- Calcium choride
94
APTT principle
phospholipid/activator reagent to citrated platelet-poor plasma and incubate to allow for contact factor activation. Add calcium chloride; measure the time required for clot formation.
95
APTT ref range
23-35 sec
96
Prolonged aPTT can indicate:
- Factor deficiencies in the intrinsic/common pathways; factor activity less than 25-30% will prolong
- Acquired circulating inhibitor: Heparin, lupus inhibitor, or antibody to a specific factor
97
Sources of error for aPTT
- Improper sample collection, preparation, and inherent patient problems
- Falsely long aPTT: Blood collection tube not full, large clot in tube, heparin contamination from line draw, hematocrit >55.0%, and lipemia/icterus only if optical method us
- Falsely short aPTT: Hemolysis, small clot in tube, and plasma containing platelets (not platelet poor)
- Incorrect reagent preparation: Incorrect dilution, water impurities, or improper storage
- Instrumentation: Problems with temperature, light source, bubbles in sample
98
- Screening test for factors VII, X, V, II, and I (extrinsic/common pathways)
- Monitors anticoagulation therapy by vitamin K antagonists
(warfarin/coumarin)
Prothrombin Time (PT)
99
PT reagents
Thromboplastin source (tissue factor/TF) with calcium chloride
100
Principle of PT
Add thromboplastin reagent containing calcium chloride to citrated platelet-poor plasma; measure the time required for clot formation.
101
PT ref range
10-14 sec
102
Used to monitor warfarin/coumarin therapy
INR
103
Prolonged PT can indicate
factor deficiencies in the extrinsic/common pathways; factor activity less than 25-30% or warfarin therapy will prolong
the PT
104
Sources of error on PT
Improper sample collection, improper preparation, and inherent patient problems
1) Falsely long PT: Same as for aPTT
2) Falsely short PT: Small clot in tube
Reagent preparation and instrumentation problems are the same as for aPTT.
105
performed when the PT or aPTT is prolonged to differentiate a factor deficiency from a circulating inhibitor. Patient plasma is mixed with normal pooled plasma and test(s) is(are) repeated.
Mixing study
106
Mixing studies shortening of the time
Shortening of the time into the reference range (correction) indicates a factor deficiency (hereditary, or acquired causes such as warfarin therapy or liver disease).
107
Partial or no correction Mixing Study
Partial or no correction indicates a circulating inhibitor (heparin, lupus inhibitor, VIII inhibitor, IX inhibitor).
108
quantitative test for fibrinogen. Thrombin reagent is, added to diluted citrated patient plasma. Thrombin clotting time obtained is read using a standard curve and is inversely proportional to fibrinogen,concentration.
Fibrinogen level
109
qualitative/quantitative test for fibrinogen. Thrombin
reagent is added to undiluted patient plasma and result is reported in seconds. Presence of heparin, degradation products, or low fibrinogen level will prolong the result.
Thrombin time
110
used to confirm a suspected factor deficiency, as suggested
by a mixing study that shows correction. Test measures the ability of patient plasma to correct the PT or aPTT result obtained with plasma known to be factor deficient (compared to known standards). The factor activity percent is reported
Factor assays
111
The unstable clot that forms in factor XIII deficiency dissolves in 5.0 M urea; a factor XHIa-stabilized clot remains intact
in 5.0 M urea for at least 24 hours.
5.0 M urea clot solubility test
112
a sensitive test that uses snake venom as the reagent to activate factor X in the cascade. If the lupus inhibitor is
present, the venom is neutralized, and the test is prolonged.
Dilute Russell viper venom test
113
- Whole blood is placed in a glass tube containing activator. Determine time it takes the clot to form; blood is kept at 37°C during testing.
- Point-of-care test performed at a clinic, cardiac catheterization laboratory, or surgical suite.
- Most often used to monitor high-dose heparin therapy during coronary artery bypass surgery
Activated clotting time (ACT)
114
Evaluation Tests for the Fibrinolytic System
- Fibrinogen Degredation Products
- D-Dimee Assay
115
Latex particles are coated with antibody against fibrinogen and are mixed with patient serum. Macroscopic agglutination indicates degradation products. This is a nonspecific test that will be abnormal when either fibrin degradation products or fibrinogen degradation products are present (DIG and primary fibrinogenolysis).
Fibrin Degredation Products (FDPs)
116
Latex particles are coated with antibody against D-dimer.
Highly specific measurement for fibrin degradation products; does not detect fibrinogen degradation products. Abnormal result indicates a clot has formed, been stabilized by factor XHIa, and is being lysed by plasmin (abnormal in DIC,
but normal in primary fibrinogenolysis).
D-Dimer Assay
117
Anticoagulant Therapies
- Unfractioned Heparin Therapy
- Warfarin (Coumadin/Coumarin) Therapy
118
Treatment of choice to prevent extension of existing clots due to acute thrombotic events (e.g., venous and arterial thrombosis, pulmonary embolism, thrombophlebitis, acute myocardial infarction)
Unfractioned Heparin Therapy
119
Therapy involves a bolus of heparin, followed by continuous infusion. Antithrombin must be present with levels of 40-60% of normal for heparin to work.
Unfractioned Heparin Therapy
120
The antithrombin/heparin complex inhibits serine proteases, including Xlla, XIa, IXa, Xa, Ha, and kallikrein. Inhibition is immediate
Unfractioned Heparin Therapy
121
It inhibits the conversion of fibrinogen to fibrin, platelet aggregation, and activation of factor XIII.
Unfractioned Heparin Therapy (UHT)
122
Heparin activity can be immediately reversed by administration of
protamine sulfate (UHT)
123
Monitor with aPTT; therapeutic range is approximately 1.5-2 times patient's baseline aPTT value prior to treatment. Dosage is adjusted accordingly.
Unfractioned Heparin Therapy
124
Daily platelet counts should be performed on heparinized patients to monitor for heparin-induced thrombocytopenia (HIT). If detected, heparin therapy is immediately halted and different anticoagulant therapies are considered.
Unfractioned Heparin Therapy
125
- This oral anticoagulant is prescribed on an outpatient basis to prevent extension of existing clots and recurrence of thrombotic events, and prophylactically it is often prescribed postsurgery to prevent thrombosis
- Vitamin K antagonist
Warfarin (Coumadin®/Coumarin) Therapy
126
Inhibits liver synthesis of functional prothrombin group factors II, VII, IX, and X. Factor VII is affected first (short half-life) and to the greatest extent.
Warfarin (Coumadin/Coumarin) Therapy
127
Overlap with heparin therapy is common, because full anticoagulant action of this is not achieved for 4-5 days.
- often used for up to 6 months or longer
Warfarin (Coumadin/Coumarin) Therapy
128
Monitor with PT and INR; INR therapeutic range is 2.0-3.0 for most conditions. If INR is higher with serious bleeding, vitamin K can be administered to reverse affects.
Warfarin (Coumadin/Coumarin) Therapy
129
Other Medications Used in Hemostasis
- Low molecular weight heparin
- Direct thrombin inhibitor
- fibrinolytic therapy
- antiplatelet medications
130
- enoxaparin sodium
- subcutaneous injection, requires antithrombin to work
- Fixed dose response reduces the need for laboratory monitoring.
- Lower risk of heparin-induced thrombocytopenia (HIT)
- It is mainly an anti-Xa inhibitor; anti-IIa response is reduced.
- If monitoring is needed, perform anti-Xa assay.
Low molecular weight heparin
131
- argatroban, lepirudin, bivalirudin
- inactivates thrombin only; does not require presence of antithrombin to work
- Used in place of unfractionated or low-molecular-weight heparin when HIT suspected
- These medications will prolong the PT, aPTT, and thrombin time.
Direct thrombin inhibitor
132
Tissue plasminogen activator, streptokinase or
urokinase, can be used to lyse existing clots and reestablish vascular perfusion.
- These medications convert plasminogen to plasmin.
- Plasmin destroys the fibrin clot, factors I, V, and VIII.
- Affected tests include PT, aPTT, thrombin time, fibrinogen,
FDP, and D-dimer (also bleeding time because of low fibrinogen).
Fibrinolytic therapy
133
aspirin, Plavix®, ticlopidine, and nonsteroidal
anti-inflammatory drugs/NSAIDS) may be used in conjunction with other anticoagulant therapies to prevent recurrence of thrombotic events
Antiplatelet medications
