Thrombosis Flashcards
1
Q
What is the inappropriate formation of platelet or fibrin clots obstructing blood vessels called?
A
Thrombosis
2
Q
What is the loss of blood supply due to thrombosis called?
A
Ischemia
3
Q
What is the term for tissue death caused by thrombosis?
A
Necrosis
4
Q
What is the predisposition to thrombosis due to congenital or acquired disorders called?
A
Thrombophilia
5
Q
What is the term for reduced or halted blood flow?
A
Stasis.
6
Q
What is an abnormality in platelet function categorized as in thrombosis etiology?
A
Coagulation system abnormality.
7
Q
What is the role of leukocyte activation molecules in thrombosis etiology?
A
They contribute to coagulation system abnormalities.
8
Q
What aspect of blood vessels is considered in coagulation system abnormalities?
A
Blood vessel wall integrity.
9
Q
What type of inflammation can contribute to thrombophilia?
A
Chronic or acute inflammation.
10
Q
What is released that promotes thrombosis in thrombophilia?
A
Prothrombotic mediators.
11
Q
What habits and conditions affect hemostasis and contribute to thrombosis risk?
A
Acquired thrombosis risk factors.
12
Q
What type of diseases increase thrombosis risk through various mechanisms?
A
Systemic diseases.
13
Q
What are examples of conditions that contribute to the risk factors for thrombosis?
A
Immobilization, lipid metabolism imbalance, HRT, surgeries, smoking, inflammation, and central venous catheter.
14
Q
What are examples of systemic disease that contribute to the risk factors for thrombosis?
A
Antiphospholipid syndrome, myeloproliferative neoplasms, hepatic diseases, cancer, leukemia, etc.
15
Q
What condition is indicated by thrombosis in young adults, unusual sites, recurrent thrombotic events, or a family history of thrombosis?
A
Congenital thrombophilia.
16
Q
What genetic mutation affecting coagulation is a common cause of congenital thrombophilia?
A
Factor V Leiden mutation.
17
Q
What mutation in the prothrombin gene is associated with an increased risk of thrombosis?
A
Prothrombin G20210A mutation.
18
Q
What protein deficiencies contribute to congenital thrombophilia?
A
Protein C, Protein S, and Antithrombin deficiencies.
19
Q
What genetic assays are available for detecting congenital thrombophilia?
A
Antithrombin activity assay, Protein C and Protein S activity assays, Activated Protein C resistance and Factor V Leiden mutation assays, Prothrombin G20210A mutation assay, Dysfibrinogenemia and fibrinolysis tests.
20
Q
What is the most common inherited thrombophilia?
A
Factor V Leiden mutation.
21
Q
What is the second most common inherited thrombophilia?
A
Prothrombin G20210A mutation.
22
Q
This is a concept wherein thrombosis often results from multiple risk factors converging?
A
Double Hit Hypothesis
23
Q
What does the Double Hit Hypothesis imply about single genetic defects in thrombosis?
A
Single genetic defects are not enough to cause thrombosis
24
Q
What are immunoglobulins that bind to protein-phospholipid complexes?
A
Antiphospholipid antibodies.
25
What are the types of antiphospholipid antibodies?
Lupus anticoagulant, anticardiolipin antibodies, anti-beta-2 glycoprotein I antibodies.
26
What condition is associated with transient ischemic attacks, strokes, coronary and peripheral artery disease, venous and arterial thrombosis, and pregnancy complications?
Antiphospholipid syndrome.
27
What methods are used to detect lupus anticoagulant?
Clot-based assays such as dilute Russell viper venom time and partial thromboplastin time.
28
What tests are used to detect anticardiolipin antibodies and anti-beta-2 glycoprotein I antibodies?
Immunoassays
29
What are the key assays used to detect lupus anticoagulant?
Dilute Russell viper venom time
Silica-based partial thromboplastin time.
30
What older assays were used for lupus anticoagulant detection?
Kaolin clotting time and dilute thromboplastin time.
31
What is the four-step algorithm for lupus anticoagulant testing?
Prolonged clot time, mixing study, correction with phospholipids, and exclusion of other coagulopathies.
32
What is the coating used in the microplate for the anticardiolipin antibody immunoassay?
Cardiolipin-beta-2 glycoprotein I complex.
33
What detection method is used in the anticardiolipin antibody immunoassay?
Enzyme-labeled anti-human immunoglobulin G, immunoglobulin M, or immunoglobulin A.
34
In what units are the results of the anticardiolipin antibody immunoassay reported?
GPL, MPL, or APL units.
35
What is used when routine assays for Lupus Anticoagulant, Anticardiolipin, and Beta-2 Glycoprotein I are negative?
Antiphosphatidylserine Immunoassay
36
What does the Antiphosphatidylserine Immunoassay detect?
Antibodies specific to phosphatidylserine
37
What can lead to increased thrombin production?
Activated Protein C (APC) resistance
38
What does the APC-protein S complex hydrolyze?
Factors 5a and 8a
39
What mutation resists hydrolysis, leading to thrombosis?
Factor V Leiden mutation (FV R506Q)
40
What is APC resistance tested using?
Detect the presence of Factor V Leiden.
41
What is mixed with patient plasma in the APC resistance test?
Factor V-depleted plasma.
42
What is the APC resistance ratio?
Less than 1.8.
43
What is compared in the APC resistance test?
Clotting times with and without Activated Protein C (APC).
44
A mutation that leads to elevated prothrombin levels, increasing thrombotic risk.
Prothrombin G20210A mutation.
45
What genetic change occurs in the Prothrombin G20210A mutation?
Guanine to adenine substitution at position 20210.
46
By how much do prothrombin levels increase in individuals with the Prothrombin G20210A mutation?
130%.
47
What is the thrombosis risk for heterozygotes with the Prothrombin G20210A mutation?
2 to 3 times higher than normal.
48
A significant thrombophilia risk factor that can be congenital or acquired.
Antithrombin deficiency.
49
What type of enzyme inhibitor is antithrombin?
Serine protease inhibitor.
50
What conditions can lead to acquired antithrombin deficiency?
Liver disease, nephrotic syndrome, heparin therapy, disseminated intravascular coagulation.
51
What are the two types of congenital antithrombin deficiency?
Type I: Reduced production, Type II: Nonfunctional molecules.
52
What is the reference range for adult plasma antithrombin levels?
78%–126%.
53
What is the reference range for antithrombin antigen levels?
22–39 mg/dL.
54
This is an assay for antithrombin deficiency that detects both quantitative and qualitative deficiencies?
Chromogenic Antithrombin Activity Assay
55
A test that measures the concentration of antithrombin using a latex microparticle immunoassay.
Antithrombin antigen assay.
56
What type of antithrombin deficiency does the antithrombin antigen assay detect?
Quantitative (Type I) deficiency.
57
What therapy can mask mild antithrombin deficiency?
Coumadin therapy.
58
Why should antithrombin testing be avoided after thrombotic events?
Because results may be inaccurate.
59
A condition where prolonged heparin therapy causes heparin resistance due to antithrombin consumption.
Heparin resistance.
60
Why does heparin become ineffective in certain patients?
Heparin requires antithrombin to function.
61
What test is necessary to confirm antithrombin deficiency?
Antithrombin assay.
62
What is the treatment for antithrombin deficiency?
Antithrombin concentrate (Thrombate III).
63
A process where thrombin binds to thrombomodulin, shifting from a procoagulant to an anticoagulant.
Protein C control pathway.
64
What is the function of activated Protein C in coagulation?
It hydrolyzes coagulation factors Va and VIIIa, reducing clot formation.
65
What is the role of Protein S in the Protein C control pathway?
It stabilizes the activated Protein C complex for effective anticoagulation.
66
What complex hydrolyzes coagulation factors Va and VIIIa?
Activated Protein C-Protein S complex.
67
In what forms does Protein S exist?
Free or bound to C4b-binding protein.
68
Which form of Protein S can act as an activated Protein C cofactor?
Free Protein S.
69
A deficiency that leads to recurrent venous thrombosis and pulmonary embolism.
Protein C or Protein S deficiency.
70
What condition increases the risk of deep vein thrombosis and stroke, particularly in younger patients?
Protein C or Protein S deficiency.
71
How much does the risk of thrombosis increase in individuals with heterozygous Protein C or Protein S deficiency?
1.6 to 11.5-fold.
72
What fatal condition occurs in neonates with homozygous Protein C deficiency?
Neonatal purpura fulminans.
73
What is the reference range for Protein C and Protein S?
65–140%.
74
What Protein C and Protein S levels indicate deficiency?
30–65% in heterozygotes, less than 65% in deficiency states.
75
In which conditions is Protein C and Protein S activity decreased?
Pregnancy, liver/renal disease, disseminated intravascular coagulation, and warfarin therapy.
76
What test detects Protein S activity by prolonging clot time in the presence of activated Protein C?
Clot-based functional assays.
77
What test measures total and free Protein S to detect both quantitative and qualitative deficiencies?
Immunoassays.
78
What are examples of arterial thrombotic diseases?
Peripheral vascular occlusion, myocardial infarction, and cerebrovascular ischemia.
79
What is the main cause of arterial thrombotic diseases?
Atherosclerotic plaque formation.
80
What are the traditional predictors of arterial thrombosis?
Elevated total cholesterol, low-density lipoprotein cholesterol, and increased total cholesterol to high-density lipoprotein cholesterol ratio.
81
This is a marker of thrombosis?
Homocysteine
82
An acute-phase reactant produced by the liver in response to inflammation.
C-reactive protein.
83
A C-reactive protein level greater than 1.5 mg/L indicates this condition and its associated risks.
Atherosclerosis
Risk of MI or Stroke
84
A byproduct of methionine metabolism.
Plasma homocysteine.
85
Vitamins essential for the regulation of homocysteine levels.
Vitamin B6, Vitamin B12, and folate.
86
Enzyme deficiencies that increase homocysteine levels.
Cystathionine beta-synthase and methionine synthase deficiencies.
87
A genetic mutation linked to elevated homocysteine but not an independent thrombosis risk factor.
Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.
88
This helps blood clot and activates platelets. No standardized tests at the moment?
Fibrinogen
89
This is a type of LDL, competes ith plasminogen, slows clot breakdown, and higher in African Americans but more in Caucasians?
Lipoprotein A
90
A condition characterized by generalized activation of hemostasis due to systemic disease.
Disseminated
91
A rapidly progressing, uncompensated form of Disseminated Intravascular Coagulation with severe deficiencies in hemostasis components.
Acute Disseminated Intravascular Coagulation.
92
A slowly developing form of Disseminated Intravascular Coagulation that is often compensated and associated with chronic diseases.
Chronic Disseminated Intravascular Coagulation.
93
What is the primary culprit in the pathophysiology of Disseminated Intravascular Coagulation?
Circulating thrombin.
94
What is the sequence of events leading to Disseminated Intravascular Coagulation?
Thrombin activates platelets and coagulation proteins → Formation of fibrin microthrombi → Consumption of coagulation factors, proteins, and platelets → Activation of fibrinolysis and release of toxic, inflammatory mediators.
95
The presence of schistocytes in a blood film suggests this condition.
Disseminated Intravascular Coagulation.
96
A laboratory finding characterized by a decreased platelet count.
Thrombocytopenia.
97
A biomarker elevated above 10,000 ng/mL in Disseminated Intravascular Coagulation.
D-dimer.
98
The primary goal in the treatment of Disseminated Intravascular Coagulation.
Treat the underlying disorder (surgery, antibiotics).
99
A pharmacological treatment used for clotting control in Disseminated Intravascular Coagulation but carries a risk of bleeding.
Unfractionated heparin.
100
A laboratory method used to monitor heparin therapy in Disseminated Intravascular Coagulation.
Anti-factor Xa assays.
101
A contraindicated therapy in Disseminated Intravascular Coagulation except in cases of systemic fibrinolysis.
Antifibrinolytic therapy.
102
What occurs when a blood clot forms in a vein or artery?
Thrombosis
103
What is elevated during active clot formation and breakdown and is a traditional marker for thrombosis?
D-dimer
104
What are the newer markers for thrombotic activity in conditions like disseminated intravascular coagulation, trauma, and septicemia?
Thrombin-Antithrombin Complex (TAT)
Prothrombin Fragment F1.2 (PF 1.2)
105
What is produced when antithrombin neutralizes thrombin?
Thrombin-Antithrombin Complex (TAT)
106
What is the half-life of Thrombin-Antithrombin Complex (TAT)?
3 minutes
107
What enhances the reaction of Thrombin-Antithrombin Complex (TAT)?
Heparin
108
What is released during the conversion of prothrombin to thrombin?
What is elevated in venous thromboembolism and is a sensitive marker for thrombosis?
Prothrombin Fragment F1.2 (PF 1.2)
109
What is the half-life of Prothrombin Fragment F1.2 (PF 1.2)?
90 minutes
110
The required anticoagulant for blood collection in Thrombin-Antithrombin Complex and Prothrombin Fragment 1.2 assays.
3.2% sodium citrate (Light-Blue)
111
The reason for quick processing of plasma samples in Thrombin-Antithrombin Complex and Prothrombin Fragment 1.2 assays.
To prevent false elevation of markers due to in vitro activation.
112
The correct handling procedure for plasma samples in Thrombin-Antithrombin Complex and Prothrombin Fragment 1.2 assays.
Plasma should be centrifuged and separated immediately, then frozen until analysis.
113
What is an adverse immune response to heparin therapy causing thrombocytopenia and serious thrombotic events?
Heparin-Induced Thrombocytopenia (HIT)
114
What is the mechanism behind Heparin-Induced Thrombocytopenia (HIT)?
Formation of IgG antibodies against heparin-platelet factor 4 (PF4) complexes
115
What is the mortality rate associated with Heparin-Induced Thrombocytopenia (HIT)?
20%
116
Thrombotic HIT that is benign thrombocytopenia occurring in 30% of patients within 1-3 days, limited and non-thrombotic?
HIT Type 1
117
Thrombotic HIT occurring after 5 days of heparin use or earlier if previously exposed, with a decrease in platelet count exceeding 40%.
HIT Type 2
118
What is the 4Ts approach for diagnosing Heparin-Induced Thrombocytopenia (HIT)?
Thrombocytopenia, Timing of platelet count fall, Thrombosis, Other causes
119
What is a technically demanding functional assay for diagnosing HIT with 50% sensitivity?
Platelet Aggregometry
120
What functional assay for HIT has higher sensitivity compared to Platelet Aggregometry?
Washed Platelet Lumiaggregometry
121
What is the reference method for diagnosing HIT that requires a radionuclide license?
14C-Serotonin Release Assay (SRA)
122
What are the tests for monitoring direct thrombin inhibitors?
Partial Thromboplastin Time (PTT), Activated Clotting Time (ACT), Ecarin Clotting Time, Plasma-diluted Thrombin Time (HEMOCLOT Thrombin)
