2. Case 1
• A 60 years old chronic heavy smoker
hypertensive male patient presents
with right-sided weakness. CT brain
revealed non-hemorrhagic
infarction.
• His lab reveal marked dyslipidemia
& IFG.
• Anticardiolipin IgM is positive, 20
MPL.
• How to manage this patient?
3. Case 2
• A 60 years old female patient
presents with right LL acute tender
swelling. Rt LL venous duplex
revealed acute DVT.
• She gives history of total hip
replacement 1 week ago with no
postoperative anticoagulation.
• Anticardiolipin IgM is positive, 24
MPL.
• How to manage this patient?
4. APS should be suspected if
Arterial thrombosis especially before the age of 50 years.
Unprovoked venous thrombosis especially before the age of 50 years.
Recurrent thrombosis.
Both arterial & venous thromboses in the same patient.
Thrombosis at unusual sites (e.g. renal, hepatic, cerebral sinuses, mesenteric, vena
cava, retinal & subclavian).
Obstetrical: fetal loss or recurrent miscarriages; early or severe preeclampsia;
unexplained intrauterine growth restriction; HELLP syndrome.
6. Case 3
• A 35 years old female
patient with no significant
past medical history has
undergone extensive lab
screening which turned out
negative except for:
• ACL (Anti-cardiolipin) IgM
positive, 26 MPL.
• What is the diagnosis?
• What is best next step?
8. The updated International Consensus
Classification Criteria for definite APS
At least 1 of the
clinical criteria
Vascular
thrombosis
Pregnancy
morbidity
At least 1 of the
laboratory criteria
IgG &/or
IgM aCL
LA activity
9. Case 4
•A 35 years old female patient with no significant
past medical history has undergone extensive lab
screening which turned out negative except for:
•ACL IgM, positive, 50 MPL.
•What is the diagnosis?
•What is the best next step?
10. Not APS
• Follow up after 12 weeks ACL IgM,
positive, 56 MPL.
• So, primary prevention is indicated. Which
line?
• Low dose aspirin (LDA). Which dose?
• (75–100 mg daily)
11. Medium-high aPL titres
• Anticardiolipin (aCL) antibody of IgG and/or IgM
isotype in serum or plasma present in titres >40 IgG
phospholipid (GPL) units or >40 IgM phospholipid
(MPL) units, or >the 99th percentile, measured by a
standardised ELISA.
• Antibeta2 glycoprotein I antibody of IgG and/or IgM
isotype in serum or plasma in titre >the 99th
percentile, measured by a standardised ELISA
12. Case 5
•A 35 years old female patient with no
significant past medical history has
undergone extensive lab screening which
turned out negative except for:
•LAC positive.
•What is the diagnosis?
•What is best next step?
14. •1.In asymptomatic aPL carriers (not fulfilling
any vascular or obstetric APS classification
criteria) with a high-risk aPL profile with or
without traditional risk factors, prophylactic
treatment with low-dose aspirin (LDA) (75–
100 mg daily) is recommended.
15. High-risk aPL profile: The presence (in 2 or more
occasions at least 12 weeks apart) of
LAC
(measured
according
to ISH
guidelines)
double (any
combination
of LAC, aCL
antibodies
or antibeta2
GP I
antibodies)
triple (all
three
subtypes)
aPL
positivity
persistently
high aPL
titres.
16. Low-risk aPL profile.
Isolated aCL or antibeta2 GP I antibodies
at low, medium titres
particularly if transiently positive.
17. Case 6
• A 34 years old female patient with recurrent oral ulcers, fever and
discoid rash.
• Her labs are negative except for:
• ANA,IF, positive, 1/160
• ACL, positive, 50 MPL.
• Anti-dsDNA, anti-Smith, LAC are negative.
• What is the diagnosis?
• What is the treatment?
20. Case 7
• A 34 years old female patient with recurrent oral ulcers, fever and
discoid rash. She gives history of unprovoked Rt LL DVT.
• Her labs are negative except for:
• ANA,IF, positive, 1/160
• ACL, positive, 50 MPL.
• Anti-dsDNA, anti-Smith, LAC are negative.
• What is the diagnosis?
• What is the treatment?
23. What are the “main” types of diseases
associated with increased aPL ab production?
• M—Medications: most commonly phenothiazines (chlorpromazine),
procainamide, quinidine, hydralazine, phenytoin, α-interferon, interleukin-2,
tumor necrosis factor-α inhibitors, others.
• A—Autoimmune diseases: SLE (40%–50%), rheumatoid arthritis,
dermatomyositis, Sjögren’s syndrome, systemic sclerosis, others.
• I—Infectious diseases: acute infections (bacteria, viral, especially herpes),
chronic infections (hepatitis C, HIV).
• Usually transient IgM aCL abs without clot risk.
• N—Neoplasms: lymphoma most commonly.
24. Case 8
• A 34 years old female patient with recurrent oral ulcers, fever and
discoid rash.
• Her labs are negative except for:
• ANA,IF, positive, 1/160
• Anti-Smith positive.
• ACL, positive, 30 MPL.
• Anti-dsDNA & LAC are negative.
• What is the diagnosis?
• What is the treatment?
25.
26. 2.In patients with SLE & no history of thrombosis or pregnancy
complications, prophylactic treatment with LDA
With high-risk aPL
profile
is recommended.
With low-risk aPL
profile
may be considered.
27. (“one-in-five rule”)
20% of women who experience recurrent
miscarriages/placental ischemic complications
20% of unprovoked DVTs
20% of young patients (age, <50 years) who get
strokes
have
APS
28. Case 9
•A 28 years old female with a history of abortion in the
second trimester and high titer of anticardiolipin twice
12 weeks apart. Now, she is non-pregnant & with low
bleeding risk. How will you manage her?
•Give her enoxaparinn 40 mg SC daily.
•Give her enoxaparin 60 mg SC twice daily.
•Give her 81 mg aspirin.
•Give her nothing.
29. Case 9 answer
•A 28 years old female with a history of abortion in the
second trimester and high titer of anticardiolipin twice
12 weeks apart. Now, she is non-pregnant & with low
bleeding risk. How will you manage her?
•Give her enoxaparinn 40 mg SC daily.
•Give her enoxaparin 60 mg SC twice daily.
•Give her 81 mg aspirin.
•Give her nothing.
30. 3. In non-pregnant women with a history of obstetric APS only (with or without
SLE), prophylactic treatment with LDA after adequate risk/benefit evaluation is
recommended.
31. 1. In asymptomatic aPL carriers (not fulfilling any vascular or obstetric APS
classification criteria) with a high-risk aPL profile with or without traditional risk
factors, prophylactic treatment with LDA (75–100 mg daily) is recommended (2a/B).
2. In patients with SLE and no history of thrombosis or pregnancy complications:
A. With high-risk aPL profile, prophylactic treatment with LDA is recommended(2a/B).
B. With low-risk aPL profile, prophylactic treatment with LDA may be considered (2b/C).
3. In non-pregnant women with a history of obstetric APS only (with or without SLE),
prophylactic treatment with LDA after adequate risk/benefit evaluation is
recommended (2b/B).
Primary thromboprophylaxis in aPL-positive subjects
32. Case 10
•A 35 years old female patient with no significant
past medical history presents with acute BCS
(Budd-Chiari syndrome):
•LAC: negative.
•ACL IgM, IgG: negative.
•Does she have APS?
•What is best next step?
Unusual site
33. She is not fulfilling the criteria. Yet, APS is the
commonest acquired thrombophilic condition.
The updated International Consensus Classification Criteria for definite APS
At least 1 of the
clinical criteria
Vascular
thrombosis
Pregnancy
morbidity
At least 1 of the
laboratory criteria
IgG &/or
IgM aCL
abs in
moderate
or high titer
• IgG and/or
IgM
antibody to
β2GPI at
>99th
percentile
for lab.
LA activity
34. • Her anti- β2GPI IgM is negative.
• Her anti-β2GPI IgG is highly positive twice.
APS
35. Case 11
•A 35 years old female patient with no significant
past medical history presents with acute CRVO
(central retinal vein occlusion):
•LAC: negative.
•ACL IgM, IgG: negative.
•Anti- β2GPI IgM, IgG: negative.
•Does she have APS?
•What is best next step?
Unusual site
37. Case 12
•A 35 years old female patient with no significant past
medical history presents with acute cerebral sinus
thrombosis & history of acute myocardial infarction 1
year ago:
•LAC: negative.
•ACL IgM, IgG: negative.
•Anti- β2GPI IgM, IgG: negative
•Does she have APS?
•What is best next step?
Both arterial & venous
38. Seronegative APS
• Thrombophilia screen negative.
• Other causes (inherited hypercoagulable
states) for thrombosis should always be
assessed in patients with negative aPL ab
tests.
• The concept of “seronegative” APS is not
recognized unless other causes of
thrombosis and antibodies against other
candidate antigens are rigorously excluded.
Does it
matter so
much?
39. Case 13
• Mrs. Fatma, a 22 years old female presents to the ER with acute
dyspnea & hemoptysis. She has red tender swollen RT LL.
• Temp: 37.2.
• BP: 110/80.
• RR: 22/min.
• HR: 114 bpm.
• ECG: sinus tachycardia.
• What is the best next step?
40. Well’s score for PE
CTPA
Pulmonary
embolism
What is next?
Dup
lex
RT LL acute DVT
42. What is next?
1. Start warfarin (VKA).
2. Initial therapy with unfractionated heparin (UFH) or
LMWH & bridging therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start dabigatran.
5. Start low dose aspirin.
43. What is next?
1. Start warfarin.
2. Initial therapy with unfractionated heparin (UFH) or
LMWH & bridging therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start dabigatran.
5. Start low dose aspirin.
44. What is the target?
•INR target 1:2.
•INR target 2:3.
•INR target 3:4.
•aPTT 2:3 ULN.
•aPTT 3:4 ULN.
•No lab target, only guided clinically.
45. What is the target?
•INR target 1:2.
•INR target 2:3.
•INR target 3:4.
•aPTT 2:3 ULN.
•aPTT 3:4 ULN.
•No lab target, only guided clinically.
46. •If she had a long travel prior to the DVT &
PE. For how long would you continue VKA?
•For the duration recommended for patients
without APS according to international
guidelines (5/D).
47. •If she had no provocation to the DVT & PE.
For how long would you continue VKA?
•It should be continued long term
(2b/B).
48. •Mrs. Fatma came later with a red tender
swollen LT LL & duplex revealed acute DVT.
•What is the next step?
•INR: 1.2.
•What is the next step?
•Check for adherence & precautions for VKA.
49. • She wasn’t adherent to VKA with loss of follow up for 3 months.
• After councelling her on the importance of adherence. What is the next step?
1. Restart warfarin.
2. Initial therapy with unfractionated heparin (UFH) or LMWH & bridging
therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start dabigatran.
5. Start low dose aspirin.
50. Switching from treatment with VKA to DOACs due to low
adherence to VKA or INR monitoring should be avoided.
• She wasn’t adherent to VKA with loss of follow up for 3 months.
• After councelling her on the importance of adherence. What is the next step?
1. Restart warfarin.
2. Initial therapy with unfractionated heparin (UFH) or LMWH & bridging
therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start dabigatran.
5. Start low dose aspirin.
51. • Mrs. Fatma came 6 months later
with a red tender swollen RT LL &
duplex revealed acute DVT.
• What is the next step?
• INR: 1.2.
• What is the next step?
• Check for adherence &
precautions for VKA.
52. • She is adherent to therapy & after revising her INR, you find unstable INR.
• What is the next step?
1. Increase warfarin dose.
2. Initial therapy with unfractionated heparin (UFH) or LMWH & bridging
therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start low dose aspirin.
53. DOACs could be considered in patients not able to achieve
a target INR despite good adherence to VKA or those with
contraindications to VKA (eg, allergy or intolerance to VKA)
(5/D).
• She is adherent to therapy & after revising her INR, you find unstable INR.
• What is the next step?
1. Increase warfarin dose.
2. Initial therapy with unfractionated heparin (UFH) or LMWH & bridging
therapy of heparin plus VKA.
3. Start rivaroxapan.
4. Start low dose aspirin.
54. Case 14
• Ahmed is 30 years old has PAPS & is on
VKA & developed recurrent DVTs despite
being within the target INR (2 - 3) & good
adherence to VKA all through.
• How to manage this situation?
1. Add LDA.
2. Increase INR target to 3–4.
3. Change to LMWH.
4. Any of the above.
5. None of the above. Only continue VKA.
55. Case 14
• Ahmed is 30 years old has PAPS & is on VKA & developed recurrent DVTs despite
being within the target INR (2 - 3) & good adherence to VKA all through.
• How to manage this situation?
1. Add LDA.
2. Increase INR target to 3–4.
3. Change to LMWH.
4. Any of the above.
5. None of the above. Only continue VKA.
Based on the individual’s characteristics & preference :
Aspirin intolerance/contraindication ,
cost & side effects of continuous LMWH use
56. Case 15 for discussion
• Ali is 30 years old has PAPS & is on VKA & developed recurrent DVTs despite good
adherence to VKA all through but failed to be within the target INR (2 - 3).
• His aPL profile is positive for ACL IgG, LAC & anti-beta2 GP1.
• How to manage this situation?
1. Increase warfarin dose.
2. Initial therapy with unfractionated heparin (UFH) or LMWH & bridging therapy
of heparin plus VKA.
3. Start rivaroxapan.
4. Add LDA.
5. Increase INR target to 3–4.
6. Change to LMWH.
59. Case 17
• Amany is a 70 years old male patient,
diabetic 20 years ago presents with
bilateral calf cramps on climbing stairs.
• What is the next investigations?
Plasma lipid & diabetes workup.
Bilateral LL arterial duplex: mild diffuse
atherosclerosis, arterial wall irregular
thickening with no hemodynamically
significant stenosis.
60. • What next?
• Assess for vasculitis (Clinically & by investigations).
61. The updated International Consensus Classification Criteria for definite APS
At least 1 of the clinical criteria
Vascular thrombosis: 1 or
more clinical episodes of
arterial, venous, or small
vessel thrombosis in any
tissue or organ confirmed
by imaging studies,
Doppler studies or
histopathology that cannot
be attributed to another
cause.
Pregnancy morbidity
At least 1 of the laboratory criteria
IgG &/or IgM aCL abs in
moderate or high titer (>40
units of either, or >99th
percentile for laboratory
tests).
LA activity
62. Case 18
• Asmaa is a 60 years old female patient, diabetic 20 years ago
presents with acute RT LL ischemia.
•What is the next investigations?
Plasma lipid & diabetes workup.
Bilateral LL arterial duplex: mild diffuse atherosclerosis with
no hemodynamically significant stenosis, acute thrombus
infrapopliteal.
63. So, she has APS.
• Is she candidate for thrombophilia screening?
• Yes. Vascular thrombosis: 1 or more clinical episodes of arterial,
venous, or small vessel thrombosis in any tissue or organ confirmed
by imaging studies, Doppler studies or histopathology that cannot be
attributed to another cause.
• Her aPL turned only positive for ACL IgG, 60 GPL,
• ACL IgM, LAC, anti-beta2 GP1 IgG & IgM: negative.
64. What is next?
1. Start warfarin with target INR 2-3.
2. Start warfarin with target INR 3-4.
3. Start warfarin with target INR 2-3 plus LDA.
4. Start rivaroxapan.
5. Start dabigatran.
6. Start low dose aspirin.
65. What is next?
1. Start warfarin with target INR 2-3.
2. Start warfarin with target INR 3-4.
3. Start warfarin with target INR 2-3 plus LDA.
4. Start rivaroxapan.
5. Start dabigatran.
6. Start low dose aspirin.
67. 6. In patients with definite APS and first
arterial thrombosis
A. Treatment with VKA is recommended over treatment with LDA only (2b/C).
B. Treatment with VKA with INR 2–3 or INR 3–4 is recommended, considering
the individual’s risk of bleeding and recurrent thrombosis (1b/B).
Treatment with VKA with INR 2–3 plus LDA may also be considered (4/C).
68. Case 18 continued
• Asmaa is now on warfarin & presents with acute left-sided
weakness. CT brain revealed a non-hemorrhagic infarction.
•What is the next step in her assessment?
Plasma lipid & diabetes workup.
Bilateral carotid & vertebrobasilar arterial duplex: mild
diffuse atherosclerosis with no hemodynamically significant
stenosis.
Can this be due to her APS with no evident thrombi?
69. The updated International Consensus Classification Criteria for definite APS
At least 1 of the clinical criteria
Vascular thrombosis: 1 or
more clinical episodes of
arterial, venous, or small
vessel thrombosis in any
tissue or organ confirmed
by imaging studies,
Doppler studies or
histopathology that cannot
be attributed to another
cause.
Pregnancy morbidity
At least 1 of the laboratory criteria
IgG &/or IgM aCL abs in
moderate or high titer (>40
units of either, or >99th
percentile for laboratory
tests).
LA activity
70. •How to manage this situation?
1. Add LDA.
2. Increase INR target to 3–4.
3. Change to LMWH.
4. Any of the above.
5. Add rivaroxapan.
6. None of the above. Only continue VKA.
71. •How to manage this situation?
1. Add LDA.
2. Increase INR target to 3–4.
3. Change to LMWH.
4. Any of the above.
5. Add rivaroxapan.
6. None of the above. Only continue VKA.
72. •C. Rivaroxaban should not be
used in patients with triple aPL
positivity and arterial events
(1b/B).
73. Prevention
Arterial
Identify other risk factors Manage them
Venous
Heparin at prophylactic
dosage, preferably LMWH, in
high-risk situations (surgery,
prolonged immobilization &
puerperium)
74.
75. The updated International Consensus Classification Criteria for definite APS
At least 1 of the clinical criteria
Vascular thrombosis Pregnancy morbidity
At least 1 of the laboratory criteria
IgG &/or IgM aCL abs in
moderate or high titer (>40
units of either, or >99th
percentile for laboratory
tests).
LA activity
76. Overarching principles for aPL-positive individuals
Primary thromboprophylaxis in aPL-positive subjects
Secondary thromboprophylaxis in APS
Obstetric APS
CAPS
77. Antiphospholipid Abs profile (aPL profile)
High risk
• The presence of (in 2 or more occasions at least 12 weeks apart(
• lupus anticoagulant, OR
• Double or triple aPL positivity, OR
• Persistently high aPL titres.
Low risk
• Isolated aCL or antibeta2 glycoprotein I antibodies at low-medium titres,
particularly if transiently positive
78. Overarching principles
Risk stratification in aPL-positive individuals should include:
• Determination of the presence of a high-risk aPL profile
• History of thrombotic and/or obstetric APS
• Coexistence of other systemic autoimmune diseases such as SLE
• The presence of traditional cardiovascular risk factors.
General measures for aPL-positive individuals should include:
• Screening for and strict control of cardiovascular risk factors
• Screening for and management of venous thrombosis risk factors
• Use of LMWH in high-risk situations such as surgery, hospitalization, prolonged immobilization and the
puerperium.
Patient education and counselling on:
Treatment adherence, INR monitoring in patients treated with VKA, use of perioperative bridging therapy
with LMWH for patients on oral anticoagulants, oral contraceptive use, pregnancy and postpartum period,
postmenopausal hormone therapy, and lifestyle recommendations (diet, exercise)
79. In patients with definite APS and first venous
thrombosis
Treatment with VKA with a target INR 2–3 is recommended (1b/B).
Rivaroxaban should not be used in patients with triple aPL positivity due to the high
risk of recurrent events(1b/B)
DOACs could be considered in patients not able to achieve a target INR despite good
adherence to VKA or those with contraindications to VKA (eg, allergy or intolerance to
VKA) (5/D)
In patients with unprovoked first venous thrombosis, anticoagulation should be
continued long term (2b/B)
In patients with provoked first venous thrombosis, therapy should be continued for a
duration recommended for patients without APS according to international guidelines.
Longer anticoagulation could be considered in patients with high-risk aPL profile in
repeated measurements or other risk factors for recurrence (5/D)
80. In patients with definite APS and recurrent venous
thrombosis despite treatment with VKA with target
INR of 2–3:
Investigation of, and education on, adherence to VKA treatment, along with frequent
INR testing, should be considered (5/D)
If the target INR of 2–3 had been achieved, addition of LDA, increase of INR target to
3–4 or change to LMWH may be considered (4-5/D)
81. In patients with definite APS and first arterial
thrombosis:
Treatment with VKA is recommended over treatment with LDA only (2b/C)
Treatment with VKA with INR 2–3 or INR 3–4 is recommended, considering the
individual’s risk of bleeding and recurrent thrombosis. (1b/B)
Treatment with VKA with INR 2–3 plus LDA may also be considered (4/C)
Rivaroxaban should not be used in patients with triple aPL positivity and arterial
events. (1b/B)
Based on the current evidence, we do not recommend use of DOACs in patients with
definite APS and arterial events due to the high risk of recurrent thrombosis (5/D)
82. In patients with recurrent arterial thrombosis despite
adequate treatment with VKA, after evaluating for
other potential causes,
1. an increase of INR target to 3–4,
2. addition of LDA or
3. switch to LMWH can be considered (4-5/D)
83. Which clinical syndromes are most commonly
associated with elevated levels of aPL abs?
• C—Clot: recurrent arterial and/or venous thrombosis (clots).
• Cardiac: valve lesions
• L—Livedo reticularis: lace-like rash over the extremities and trunk
exaggerated by cold conditions.
• O—Obstetrical complications: recurrent fetal loss, placental ischemic
conditions (preeclampsia, intrauterine
• growth restriction).
• T—Thrombocytopenia.
84. What are the “main” types of diseases
associated with increased aPL ab production?
• M—Medications: most commonly phenothiazines (chlorpromazine),
procainamide, quinidine, hydralazine, phenytoin, α-interferon, interleukin-2,
tumor necrosis factor-α inhibitors, others.
• A—Autoimmune diseases: SLE (40%–50%), rheumatoid arthritis,
dermatomyositis, Sjögren’s syndrome, systemic sclerosis, others.
• I—Infectious diseases: acute infections (bacteria, viral, especially herpes),
chronic infections (hepatitis C, HIV).
• Usually transient IgM aCL abs without clot risk.
• N—Neoplasms: lymphoma most commonly.
86. Primary prophylaxis
with LDA is given for
• Asymptomatic aPL carriers
with high risk aPL profile
• SLE patients with high risk
aPL profile and can be given
to whom with low risk
profile
• Non pregnant with history
of obstetric APS
Secondary
prophylaxis
• VKA with target INR 2-3
for both arterial and
venous thrombosis
• DOAC should not be
given in case of triple
aPL positivity or arterial
thrombosis
• Recurrence despite
treatment, increase INR
to 3-4, add LDA or
change to LMWH
Obstetric APS
• LDA for all pregnant women
with high risk aPL profile
• Adding prophylactic dose of
heparin for those with
obstetric APS only
• Heparin should be
continued 6 wks following
delivery
• Recurrence despite
treatment, add in 1st
trimester therapeutic dose
of heparin, HCQ or low
dose steroids, (IV Ig in
selected cases)
• Obstetric and thrombotic
APS, add therapeutic dose
of heparin and LDA
CAPS
• Combination therapy with
glucocorticoids, heparin and
plasma exchange or
intravenous
immunoglobulins
• Refractory CAPS give B cell
depletion or complement
inhibition
87. The ‘aPL profile’.
The aPL type,
Multiple (double or
triple) vs single aPL
type,
Titre (moderate-high
titre vs low)
The persistence of
aPL positivity in
repeated
measurements
The aPL profile is an important factor determining the risk of thrombotic and obstetric events, and consequently
the intensity of treatment.
Editor's Notes
Diarrhea of anticoagulant prescription
LOE: Level Of Evidence: 1a: systematic review of RCTs; 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (and low-quality RCT); 3a:
systematic review of case–control studies; 3b: individual case–control study; 4: case series and poor-quality cohort and case–control studies; 5: expert opinion without explicit
critical appraisal, or based on physiology, bench research or ‘first principles
GOR: Grade Of Recommendation A: consistent level 1 studies; B: consistent level 2 or 3 studies, or extrapolations from level 1 studies; C: level 4 studies or extrapolations from
level 2 or 3 studies; D: level 5 evidence or troublingly inconsistent or inconclusive studies of any level.
According to the results of the TRAPS trial,7 rivaroxaban should not be used in triple aPL-positive patients with APS.
an ongoing trial of apixaban in APS (Apixaban for the Secondary
Prevention of Thromboembolism among patients with the AntiphosPholipid
Syndrome ((ASTRO-APS)) ( ClinicalTrials. gov
identifier: NCT02295475) was recently modified after evaluation
of their initial data to exclude patients with arterial thrombosis.
لكن ما نقدرش نحلف.
LOE: Level Of Evidence: 1a: systematic review of RCTs; 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (and low-quality RCT); 3a:
systematic review of case–control studies; 3b: individual case–control study; 4: case series and poor-quality cohort and case–control studies; 5: expert opinion without explicit
critical appraisal, or based on physiology, bench research or ‘first principles
GOR: Grade Of Recommendation A: consistent level 1 studies; B: consistent level 2 or 3 studies, or extrapolations from level 1 studies; C: level 4 studies or extrapolations from
level 2 or 3 studies; D: level 5 evidence or troublingly inconsistent or inconclusive studies of any level.
LOE: Level Of Evidence: 1a: systematic review of RCTs; 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (and low-quality RCT); 3a:
systematic review of case–control studies; 3b: individual case–control study; 4: case series and poor-quality cohort and case–control studies; 5: expert opinion without explicit
critical appraisal, or based on physiology, bench research or ‘first principles
GOR: Grade Of Recommendation A: consistent level 1 studies; B: consistent level 2 or 3 studies, or extrapolations from level 1 studies; C: level 4 studies or extrapolations from
level 2 or 3 studies; D: level 5 evidence or troublingly inconsistent or inconclusive studies of any level.
LOE: Level Of Evidence: 1a: systematic review of RCTs; 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (and low-quality RCT); 3a:
systematic review of case–control studies; 3b: individual case–control study; 4: case series and poor-quality cohort and case–control studies; 5: expert opinion without explicit
critical appraisal, or based on physiology, bench research or ‘first principles
GOR: Grade Of Recommendation A: consistent level 1 studies; B: consistent level 2 or 3 studies, or extrapolations from level 1 studies; C: level 4 studies or extrapolations from
level 2 or 3 studies; D: level 5 evidence or troublingly inconsistent or inconclusive studies of any level.
LOE: Level Of Evidence: 1a: systematic review of RCTs; 1b: individual RCT; 2a: systematic review of cohort studies; 2b: individual cohort study (and low-quality RCT); 3a:
systematic review of case–control studies; 3b: individual case–control study; 4: case series and poor-quality cohort and case–control studies; 5: expert opinion without explicit
critical appraisal, or based on physiology, bench research or ‘first principles
GOR: Grade Of Recommendation A: consistent level 1 studies; B: consistent level 2 or 3 studies, or extrapolations from level 1 studies; C: level 4 studies or extrapolations from
level 2 or 3 studies; D: level 5 evidence or troublingly inconsistent or inconclusive studies of any level.