Transcript HealthyQuest Presentation

Thrombophilia
Failure of the Inherent Anticoagulation
Defense System
Mervyn A. Sahud, M.D., A.B.I.M.-Hem.
Medical Director, Coagulation, Quest Diagnostics Nichols Institute
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
2
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
3
Deep Vein Thrombosis —
A Leg Up on Blood Clots
4
Valve Cusp Thrombus
(Autopsy Specimen)
5
Thrombophilia
DVT
only
• 2 million Americans
affected with DVT
each year
DVT
&
PE
• 600,000 of these
develop pulmonary
embolism (PE)
Die
from
PE
• 60,000 of those with
DVT and PE die
each year
DVT, deep vein thrombosis.
Rosendall FR. Lancet. 1999:353:1167-1173.
Anderson FA Jr, et al. Arch Intern Med. 1991;151:933-938.
6
Thrombophilia
• 5% - 8% of population affected by genetic
defects leading to thrombosis predisposition
• 25% suffer chronic swelling, skin ulceration,
and impaired mobility secondary to “venous
hypertension”
7
DVT…What’s New?
• 50% (soon to be 100%) of “unprovoked” DVT
cases associated with hereditary thrombophilia
• 60% of DVT cases in pregnant women associated
with factor V Leiden mutation (A1698G)
• DVT often associated with multiple genetic and
acquired risk factors
• DVT responds to prolonged anticoagulant therapy
(eg, low molecular weight heparin)
8
Bucciarelli P, et al. Arterioscler Thromb
Vasc Biol. 1999;19:1026-1033.
DVT…What’s New?
• New anticoagulants available for non-responsive
patients and those who experience side-effects
from standard anticoagulants
• Family members request DVT screening prior to
being placed in a “high-risk” situation
• Elevated D-dimer level often indicates thrombosis
• Normal D-dimer level has strong NPV
NPV, negative predictive value..
9
What Else is New?
• Pulmonary embolism
– 4 million patients present to U.S. emergency
departments with shortness of breath each year
– Shortness of breath = heart failure or pulmonary
embolism (PE)
– 60% of patients who die in the hospital have PE
– PE diagnosis missed in 70% of hospital cases
– 10% of patients with acute PE die within first 60
minutes
Clagett GP. Chest. 1998;114(Suppl 5):531S-560S.
10
Thrombophilia Is Often Multigenic
Multiple risk factors raises the risk of thrombosis
11
Outline
•
•
•
•
Thrombophilia (Impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
12
Clinical DVT Risk Factors
• Surgery for malignant
disease
• Postoperative sepsis
• Major medical illness
• Age >60 y
• Extensive surgery*
• Marked immobility,
pre- or postoperative
– Heart failure
– Inflammatory bowel
disease
– Sepsis
– Myocardial infarction
– Stroke
• Major orthopedic
surgery (eg, hip, knee)
• Fracture of pelvis,
femur, or tibia
*Risk of postoperative thrombosis increases as
patient’s age and surgery duration increases; risk also
increases with presence of varicose veins and obesity.
13
Frequency of Biological Risk Factors
Other (<1%)
LA (3%)
Antithrombin (4%)
Unknown (5%)
Factor VIII
excess (30%)
Protein S (10%)
Protein C (10%)
Hyperhomocysteinemia
(10%)
APCR, Factor V
mutation (20%)
Prothrombin (factor II)
mutation (15%)
14
Synergistic Effects of
Thrombotic Risk Factors
Factor V Leiden
Factor IIa
Normal
Normal
1.0
Abnormal
Normal
2.8
Normal
Abnormal
2.4
Abnormal
Abnormal
22.8
aProthrombin
20210GA mutation.
15
Thrombotic Risk
Synergistic Effects of
Thrombotic Risk Factors
Factor V Leiden
Normal
MTHFR
Normal
Thrombotic Risk
1.0
Abnormal
Normal
2.8
Normal
Abnormal
1.8
Abnormal
Abnormal
16.5
16
Synergistic Effects of
Thrombotic Risk Factors
Factor V
Leiden
Factor IIa
MTHFR
Thrombotic
Risk
Normal
Normal
Normal
1.0
Abnormal
Normal
Normal
2.8
Normal
Normal
Abnormal
1.8
Normal
Abnormal
Normal
2.4
Abnormal
Abnormal
Abnormal
56.5
aProthrombin
20210GA mutation.
17
Risk of Recurrent Venous Thromboembolism
Risk of recurrent venous thromboembolism (VTE) in individuals with a thrombophilic
defect relative to risk in those with a first episode of VTE and no thrombophilic defect.
Weitz J, et al. Hematology Am Soc Hematol Edu Program. 2004;424-438.
18
Age of Thrombosis Onset in Patients
with Common Thrombotic Risk Factors
Age of Thrombosis Onset
Risk Factor
Homozygote
Heterozygote
Protein C deficiency
Birth
26 years
Protein S deficiency
Birth
31 years
APCR*
28 years
63 years
Antithrombin
Embryonic death
33 years
APCR, activated protein C resistance.
*May be responsible for venous thrombosis in individuals older than 55-60 years.
19
Relative Frequency of Various
Thrombosis Types
Type of
Thrombosis
Patient with APCR Patient with Protein
C or S Deficiency
DVT and/or PE
82%
76%
Abdominal
6%
11%
Stroke/MI
4%
6%
Other
8%
7%
Total
100%
100%
Salomon O, et al. Arterioscler Thromb
Vasc Biol. 1999;19:511-518.
20
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
21
Coagulation Cascade
Crowther MA, Kelton JG. Ann Intern Med. 2003;138:128-134.
22
Coagulation Cascade
Factor VIIa binds to tissue factor (TF) at sites of vascular
injury, causing a cascade that ultimately leads to factor IIa
(thrombin) generation. Thrombin activates platelets;
converts fibrinogen to fibrin; leads to generation of
additional thrombin through an autocatalytic loop; converts
factor XIII to factor XIIIa, which stabilizes the thrombus;
inhibits fibrinolysis; and acts as an anticoagulant by
activating protein C. The principal inhibitors of coagulation
are activated protein C (which, in concert with protein S,
inactivates factors Va and VIIIa), antithrombin (which
forms an inactive covalent complex with thrombin and
factors Xa, IXa, and XIa), and tissue factor pathway
inhibitor (which bonds with and inactivates the tissue
factor-factor VIIa complex).
Crowther MA, Kelton JG. Ann Intern Med. 2003;138:128-134.
23
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
24
Whom to test?
How to test?
Why test?
Thrombophilia Testing
When to test?
What to test?
25
Antithrombin Deficiency
Genetic deficiency
• Rare
– <1% of general population
– ~1% - 8% of those with VTE
• Heterozygotes
– VTE by ~30 years of age
– 5- to 50-fold increased risk of VTE
– High risk of VTE during pregnancy and
postpartum
26
Antithrombin Deficiency
Acquired deficiency
• Causes
–
–
–
–
–
–
–
–
Liver disease
Malnutrition
Inflammatory bowel disease
Prematurity
DIC
Transfusion reactions
Chemotherapy
Heparin therapy
27
AT
IIa
Role of antithrombin
IIa
AT
Heparin
IIa
AT
• Direct inhibitor of IIa
• Inhibits other factors
leading to indirect
inhibition of IIa formation
Xa
AT
IXa
AT
XIa
AT
XIIa
AT
28
 Inactive Complexes
Therapeutic Monitoring with Antithrombin III
Normal antithrombin III
Antithrombin III deficient
29
Factors Affecting Test Results
Antithrombin
Protein C and S
Heparin
Long-term
therapy  results
False  in results from clot-based
assays (>1.0 IU/mL)
OAC or vitamin
K deficiency
No effect
Vitamin K dependent proteins;
OAC will  levels
FVIII
No effect
High levels will falsely  results
from clot-based assays
Circulating
inhibitors
No effect
May falsely  results from clotbased assays
OAC, oral anticoagulant.
30
Factors Affecting Test Results
Antithrombin
Protein C
Protein S

No effect

Oral contraceptives
 or no change
No effect

Hormone replacement
therapy
 or no change
No effect




Pregnancy
Liver disease, DIC, active
thrombosis, recent surgery
31
Protein C Deficiency – Genetic Mechanism
Autosomal inheritance
• Complete penetrance (dominant mutation)
– Heterozygotes
– Primary symptom: venous thrombosis
• Mild or no penetrance (recessive mutation)
– Homozygotes: symptomatic (purpura fulminans)
– Heterozygotes: asymptomatic
32
Protein C Deficiency
• Genetic deficiency
– Rare
– Heterozygotes
•
•
•
•
<1% of population
~1-11% of patients with VTE
30% will have an event during lifetime
~50% experience VTE by age 40
• Acquired deficiencies
– Warfarin, vitamin K deficiency, liver disease,
DIC, renal insufficiency
33
Which Protein C Functional Assay?
Chromogenic
Clotting
• Pro
• Pro
– Measures cleavage of
natural substrates (factor
Va or VIIIa)
– Fewer interfering
substances
• Con
• Con
– Measures cleavage of
synthetic substrate
– Many interfering
substances
– Rare mutations not
detected by this method
 High factor VIII levels
 Lupus anticoagulants
 Heparin >1.0 IU
 Direct thrombin inhibitors
34
Functional Protein C Assay
2 patients missed
by clot assay
80
Clot Assay
70
60
50
40
30
20
8 patients missed by
chromogenic assay
10
0
0
20
40
80
60
100
Chromogenic Assay
35
120
140
160
Protein C Testing Algorithm
Protein C Clot Assay
Decreased
(<70%)
Borderline
(70% - 75%)
Normal or 
Protein C
Antigen
Repeat Clot
Assay
No further
testing
Decreased
(<70%)
Borderline
(70% - 75%)
Increased
(70%)
Chromogenic
Assay
Normal adult reference range: 70%
36
Therapeutic Monitoring with Protein C
Normal protein C
Protein C deficient
37
Protein S Deficiency
Genetic deficiency
• Homozygous (rare)
– Purpura fulminans
• Heterozygous
– < 1% of general population
– ~1% to 3% of VTE population
– ~50% experience first VTE by 45 years of age
Acquired deficiency
• Pregnancy and oral contraceptive/HRT use
• Inflammation and acute thrombosis
38
C4b-BP
PS
Free PS
TM
IIa
Role of
protein C & S
IIa
TM
APC
fPS
• Inhibition of IIa
formation
Protein C
PC
Va or VIIIa
TM
VIIIai
or Vai
Inactive Cofactors
39
Therapeutic Monitoring with Protein S
Normal protein S
Protein S deficient
40
APC Resistance in Patient with Thrombosis
APC, when added to
plasma from a middleaged man with
recurrent thrombosis,
did not result in a
prolongation of the
clotting time (APC
resistance). In
contrast, when added
to normal plasma
(control), APC
prolongs the clotting
time in a dosedependent manner.
Dahlback B. J Thromb Haemost. 2003;1:3-9.
41
APC Resistance – Genetic Mechanism
• Molecular cause
Mutation of APC cleavage site within Factor Va
• Mutation site
Amino acid #506 (arginine) mutates to a
glutamine
Amino acid: Arg506→ Gin
Nucleotide:
CGA→ CAA
42
APC Resistance – Genetic Mechanism
• Molecular function
– APC cleaves bond between arginine and
glycine
– If Arg506 residue is mutated
Bond not cleaved
Factor Va not inactivated by APC
Continued generation of thrombin and clot
formation
Thrombosis
43
Acquired APC Resistance
Associated with:
• Increased plasma levels of FVIIIa
• Presence of antiphospholipid antibodies
• 3rd generation oral contraceptives, relative to
2nd generation oral contraceptives
• Pregnancy
44
Incidence of APC Resistance
in “Normals”
Ethnicity
Percent (%)
Caucasian
4
African American
0.8
Asian American
0.6
Hispanic/Latino
2.3
Native American
0.2
45
Prothrombin (Factor II) 20210GA Mutation
A, adenine; G, guanine.
Zoller B, Svensson PJ, He X, et al. J Clin Invest. 1994;94:2521-2524.
46
Lupus Anticoagulant Screening
• Screening tests
–
–
–
–
LA sensitive aPTT reagent
Kaolin clotting time (KCT)
Dilute russell viper venom time (dRVVT)
Dilute prothrombin time (dPT)
• Minimum of 2 screening tests
47
Factor VIII Excess
Factor VIII Level
Relative Risk
>150% (>1.5 IU/mL)
3.0
>200% (>2.0 IU/mL)
5.5
O’Donnell J, et al. Thromb Haemost. 1997;77:825-828.
48
Factor VIII Excess vs Other
Thrombophilia Markers
Frequency (%)
Abnormality
No Historya
With Historya
14-20
20-50
Prothrombin mutation
4-8
10-20
Hyperhomocysteinemia
5-10
NA
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
APCR/factor VIII mutation
1-4
1-4
1-3
25
3-12
3-12
1-6
NA
APCR
aHistory
of thromobophilia.
O’Donnell J, et al. Thromb Haemost. 1997;77:825-828.
49
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
50
Case Study #1
• 61 year-old white male with multiple myeloma
(in remission)
• Receiving no treatment
• Flies to Singapore for vacation
• Experiences discomfort in right leg, no
swelling, no rubor
• 2 days later, sudden dyspnea, left pleuritic
chest pain
• Hospitalized with DVT/PE
• Returns home 2 weeks later on coumadin
51
Case Study #1: Laboratory Workup
Test
Hemoglobin
Platelet count
WBC
INR
D-dimer
APCR
Antithrombin
Protein C
Protein S
Result
12.4 g/dL
177,000/L
3,100/L
2.2
<0.79 g/mL FEU
1.3 ratio
87%
<41%
22%
Factor V Leiden
Homozygous
Follow-up duplex ultrasound
Residual thrombus in iliac
system and IVC
52
Case Study #2
• 37 y/o, G1P1 W/F attempting to get pregnant
for the 2nd time
• 1st childbirth at age 21 y without incident
• Family history of protein S deficiency
– Mother on long-term coumadin
– Sister had DVT/PE while on birth control
• Lab results at 12 weeks
– Protein S
47% (normal, 60-120%)
– Protein C
141% (normal, 60-130%)
– Antithrombin III
78% (normal, 60-120%)
53
Case Study #2 (cont’d)
• 2 weeks later, concern raised about need for
prophylactic anticoagulant
• Lab results
–
–
–
–
C4 binding protein
Total protein S
Free protein S
Functional protein S
212 mg/L (normal, 75-140)
81%
53%
43%
54
Case Study #2 (cont’d)
• Physician discusses drug therapy
–
–
–
–
Coumadin
Unfractionated heparin
Low molecular weight heparin
Arixtra (fondaparinux)
• Decision made to use graded elastic
stockings and aspirin
• Lab results at 20 weeks
– Protein S
– Protein C
33%
162%
55
Case Study #2 (cont’d)
• Lab results at 36 weeks
– Protein S
21%
• Enoxaparin initiated: 40 mg s.c. daily
• Delivery of baby uneventful
• Lab results 4 weeks postpartum
– Protein S
31%
• Patient told she probably has hereditary protein
S deficiency.
• Restarts enoxaparin for 4 weeks, daily 40 ng s.c.
56
Case Study #2 (cont’d)
Months postpartum
Protein S (%)
3
74
6
81
12
80
Protein S deficiency unlikely
57
Case Study #3
• 39 year-old, physically active, white male bicyclist
develops rapidly progressive drawing pain in right
calf after 40-mile event
• History of DVT in left lower extremity after
laparoscopic knee surgery at age 21
• Mother on coumadin
• Father died mysteriously of unknown causes at age
51 years
• Sister has had recurrent miscarriages
58
Case Study #3 (cont’d)
Test
Result
PTa
10.4 sec. (normal, 10 – 12)
aPTTa
33.0 sec. (normal, <36 sec.)
Factor V Leiden
R506Q heterozygous
Prothrombin gene
G20210A heterozygous
MTHFR
Heterozygous
Lupus anticoagulant screen
Negative
Protein Cb
31% (normal, 62 – 124)
Protein Sb
19% (normal, 58 – 112)
Antithrombin IIIb
77% (normal, 62 – 114)
MRI, vena cava
Thrombus to vena cava; duplicate
cava; old thrombosis noted
aTested
prior to initiation of anticoagulant therapy.
bTested after initiation of coumadin therapy; INR 3.1.
59
Case Study #3 Conclusion
Long-term anticoagulation indicated
Schulman S, et al. N Engl J Med. 1997;336:393-398.
60
Case Study #4
• Active 49 year-old white male experienced
“charley horse” of right leg for >6 days
• Pain, swelling, and redness progressed to lower
thigh area
• 16-year history of smoking
• Episode of superficial phlebitis following IV
insertion during routine colonoscopy
61
Case Study #4 (cont’d)
• Thrombophilic workup negative for
–
–
–
–
–
Factor V G1691A
Prothrombin G20210A
Lupus anticoagulant
Protein C and S
Antithrombin
• Ultrasound duplex assessment demonstrated
DVT involving both lower extremities
• Patient hospitalized for IV heparin therapy
followed by coumadin therapy
62
Case Study #4 (cont’d)
Lab Results at Admission
Test
Result
Platelet count
515,000/L (normal, 147,000 – 390,000)
Prothrombin time
9.9 secs (normal, 10.3 – 12.7)
aPTT
20.7 secs (normal, 23.1 – 34.2)
Fibrinogen
584 mg/dL (normal, 200 – 400)
D-dimer
4000-8000 ng/mL (normal, <250)
63
Case Study #4 (cont’d)
Lab Results 30 d Post Discontinuation of
Coumadin Therapy
Test
Result
D-dimer
500 – 1000 ng/mL (normal, <250)
Thrombin-antithrombin
11.3 g/L (normal, <4.0)
Soluble tissue factor (CD142) 1114 pg/mL (normal, <250)
Prothrombin fragment 1.2
7.6 nM/L (normal, 0.32 – 2.45)
64
Case Study #4 Conclusions
1. Finding of unprovoked DVT and negative
thrombophilic workup requires closer look for
possible malignancy even without referable
symptoms
2. Development of superficial thrombophlebitis
after brief IV insertion and subsequent
development of unprovoked bilateral DVT is
significant
3. High level of fibrinogen, elevated platelet
counts, and shortened prothrombin time and
aPTT are suggestive of hypercoagulability
65
Case Study #4 Conclusions
4. Elevated thrombin generation markers 14
days post coumadin therapy are turning point
in this patient’s workup & eventual diagnosis
5. High level of thrombin generation markers and
presence of soluble tissue factor suggest
antithrombin or Xa inhibitors (eg, low
molecular weight heparins) would be more
appropriate therapy
6. CT scan of chest reveals 3 cm mass, and
bronchoscopic washing demonstrated
malignant cells, ie, bronchogenic carcinoma
66
Case Study #5
• 19 year-old ballet dancer strains left calf and
ankle
• Recently recovered from infectious
mononucleosis
• Negative ultrasound duplex exam
67
Case Study #5 (cont’d)
Test
Result
D-dimer
497 µg/mL (normal, <0.79)
Fibrin monomer
+/-
PT
11.4 sec (normal, 12)
aPTT
31.7 sec (normal, <34)
HAMA
Negative
Rheumatoid factor
Negative
Fibrinogen
232 mg %
ANA
Negative
Repeat ultrasound duplex
(post 7 d)
No DVT
68
Case Study #5 (cont’d)
•
Patient recovers, but D-dimer still elevated
(241 µg/mL)
•
False-positive identified
1. Demonstrated high heterophile antibody titer
in patient serum
2. Incubated serum w/ heterophile blocking
antibody, then repeated D-dimer test
3. Repeat D-dimer test normal
Medical Devices Agency 2002 Evaluation Report.
69
Heterophile antibodies may contribute to falsepositive D-dimer results in various methods
FEU, fibrinogen equivalent units; cut-off values are either those recommended by the
manufacturer or 95% VTE sensitivity.
Medical Devices Agency 2002 Evaluation Report.
70
Outline
•
•
•
•
Thrombophilia (impact on DVT and PE)
Risk factors
Coagulation cascade
Thrombophilia testing
–
–
–
–
–
–
–
Antithrombin
Protein C
Protein S
Activated protein C resistance (APCR)
Prothrombin (factor II) mutation
Lupus anticoagulant
Factor VIII excess
• Case studies
• Recommended work-ups
71
Hereditary Thrombophilia Evaluation
Who
• Age 18-45 years
• Family history of HTD
• No other cause of HTD
When
• Asymptomatic
• Usually not receiving therapy, but may be on stable
oral anticoagulant therapy
How
• Work up in stages
• Most common factors first
72
HTD, hereditary thrombophilia evaluation.
Cost-Effective Hypercoagulation Workup
Below Age 45
•
•
•
•
APCR
Protein C
Protein S
Antithrombin
• Prothrombin mutation
• Homocysteine
• LA (aPTT) and
ACA/APS
If APCR is abnormal or borderline normal, perform
factor V Leiden mutation analysis.
If aPTT is abnormal, complete LA workup.
If homocysteine is abnormal, perform MTHFR
mutation analysis.
73
Cost-Effective Hypercoagulation Workup
Over Age 45
•
•
•
•
APCR
Homocysteine
Prothrombin mutation
LA (aPTT) and ACA/APS
If APCR is abnormal or borderline normal, perform
factor V Leiden mutation analysis.
If aPTT is abnormal, complete LA workup.
If homocysteine is abnormal, perform MTHFR
mutation analysis.
74
Thrombophilia Quiz
Thrombophilia Quiz
Which of the following statement(s) concerning
activated protein C resistance is/are true?
a. Activated protein C resistance is the most
commonly inherited thrombophilic condition.
b. Factor V Leiden mutation is reported in 3% to 7%
of the Caucasian population.
c. Approximately 20% to 60% of patients with
venous thromboembolism have the Factor V
Leiden mutation.
d. All of these
76
Thrombophilia Quiz
Which of the following statements concerning
prothrombin mutation are true?
a. A mutated 20210 allele is a risk factor for venous
and arterial thrombosis.
b. The increased thrombotic risk in patients with a
mutated 20210 allele appears to be caused by
excessive activation of the coagulation pathway.
c. In patients with a history of venous thrombosis,
there is a 9- to 11-fold increase in the presence
of the mutant 20210 allele.
d. All of these
77
Thrombophilia Quiz
All of the following statements concerning
antithrombin are true except:
a. Patients with homozygous antithrombin
deficiency usually present in the neonatal period
with purpura fulminans.
b. Antithrombin is a major regulator of coagulation
and inhibits activated Factor II, IX, X, XI, and XII.
c. Thrombosis is recurrent in approximately 60% of
antithrombin deficient patients.
d. There are multiple amino acid substitutions
responsible for congenital deficiencies of
antithrombin.
78
Thrombophilia Quiz
Of patients who experience venous thrombosis,
deficiencies of protein C, protein S, and
antithrombin are collectively present in:
a. Approximately 15% of patients
b. Approximately 30% of patients
c. Approximately 50% of patients
d. Approximately 70% of patients
79
Thrombophilia Quiz
Patients with deficiency of protein C, protein S,
or antithrombin usually present with:
a. Arterial thrombosis
b. Venous thrombosis
c. Recurrent arterial thromboembolic disease
d. All of these
80
Thrombophilia Quiz
Which of the following statement(s) concerning
methylene tetrahydrofolate reductase (MTHFR)
is/are true?
a. MTHFR and cystathionine β synthase are the
primary enzymes responsible for methionine
metabolism.
b. At least 7 mutations of MTHFR have been reported
to increase plasma homocysteine levels.
c. It is estimated that up to ½ of the North American
population is heterozygous for a MTHFR mutation.
d. All of these
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Thank You
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