A PILOT WITH DVT+FACTOR V
LEIDEN
Dr Fiona Rennie
Emirates Medical
Services
Dubai
1. DOES HE REQUIRE LIFE LONG
ANTICOAGULATION?
2. SHOULD HE BE LICENSED TO FLY ON
WARFARIN?
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OUTLINE
Factor V Leiden (FVL)
Audit of Emirates Pilots
Case History
Risk of Recurrence of VTE in
FVL
Anticoagulation in Aircrew
Answers!
Factor V Leiden
Mutation
• Autosomal Dominant
Hypercoaguability
Disorder
• Discovered in Leiden,
Netherlands in 1994
• Most common genetic
cause of VTE
Mechanism of
Hypercoaguability
• Factor V is a co-factor for the activation of thrombin
• Activated Protein C is a natural anticoagulant and by cleaving
Factor V arrests the clotting pathway because fibrin can no
longer be formed
• The Factor V Leiden molecule has an abnormal shape making
it resistant to APC
resulting in a hypercoaguable state.
Risk of VTE in Factor V Leiden
Mutation
• 4% of population heteroygotes
=8 x increased risk of initial VTE
(approx 10:1000 per year)
• 0.16% of population homozygotes
=80 x increased risk of initial VTE
• Risk is VENOUS only
• Up to 30% of diagnosed VTE have FVL mutation
Is This a Concern in The Pilot
Population?
Cases of VTE in EK pilots reviewed for a 5 year period:
• 6 cases of VTE
• 50% -Heterozygotes for Factor V Leiden mutation
-All 3 had recently travelled as passenger
=2 risk factors
• 50% -Recent history of surgery or trauma
=1 risk factor
• Currently 2248 pilots employed by Emirates
-There could be up to 89 pilots to be FVL HZ?
AGE
SEX
YR
THROMB
SCREEN
TRAUMA
SURGERY
BMI
DIAGNOSIS
WARFN
STAT
US
44 M
2004
FVL HZ
NO
27
DVT - HOLIDAY TRAVEL
3/12
RTF
2004
FVL HZ
NO
25
PE/SUBCLINICAL DVT
-SCUBA DIVING HOLIDAY
6/12
RTF
2008
FVL HZ
NO
28
DVT – AIR/CAR TRIP
6/12
RTF
2006
NEG
YES
27
DVT -GASTROCNEMIUS TEAR
3/12
RTF
2008
NEG
YES
27
DVT -ACL (knee) REPAIR
3/12
RTF
2009
NEG
YES
28
DVT –Cephalic vein CLAVICLE
FRACTURE
3/12
RTF
IND
44 M
GER
52 M
CAN
48 M
AUS
50 M
CAN
46 M
UK
Outcome
• None of the 6 have had a second episode
• None on long term anticoagulation
• Counselled regarding mobility and flight socks
for air travel
• LMW Heparin recommended for those with
FVL for travel as a passenger for flights over 4
hours
Incidence of VTE in Emirates Pilots
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0.7 : 1000 per year
(Gen Pop 1-2: 1000 per year)
100% had risk factors
50% had not flown between their injury and VTE
VTE unlikely occupationally related
CAA Professional Pilots 1990-2000 (R. Johnston/A. Evans)
• Incidence of VTE 0.21 : 1000 per year
• 59% risk factors such as surgery/trauma
• Concluded VTE multi-factorial, aircraft cabin does not pose an
occupational risk
Netherlands Commercial Pilot Study
• Incidence of VTE of 0.3 : 1000 per year
Case History
52 y.o. Canadian B777 Captain
History
• 3 day history
-Right thigh, groin, testicular pain & ankle swelling
• In the previous 3 weeks:
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Day 1 -Dubai to JFK to Dubai (as pilot)
Day 4 -Dubai to Toronto -pax (14 hrs)
Day 5 -2 hour flight, 2 hr drive,
Day 7 -14 hr car journey (two stops)
Day 9 - 5 hr flight (noticed soreness in leg)
Day 15 – Vancouver to Toronto to Dubai –pax (20hrs)
Day 17 –Dubai to Toronto to Dubai (as pilot)
Past History
1978
• Age 22 survived a DC3 crash
• Multiple leg fractures
• Airlifted to hospital and in cast for 3 months
1983
• Age 27 severe chest pain, elevated cardiac enzymes and
abnormal ECG
• Diagnosis myocardial infarction
• Normal angiography
• Loss of medical 5 years
Mother “clot in neck” age 40
Investigations
• D-Dimer 2443ng/ml
(>500 positive)
(96.4% sensitivity for identifying VTE)
• Doppler Ultrasound Scan :
RIGHT LEG- “Hypoechoic, homogenous structure visible in all
veins from common femoral to peroneal vein. No venous flow
in these veins”
LEFT LEG –”venous stasis in popliteal, posterior tibial and
peroneal veins “
• Thrombotic Screen -Factor V Leiden Heterozygote,
-family screened, sister positive
Diagnosis and Management
• Right leg DVT confirmed
• Right Thrombectomy Day 3
Clot extending from right illiac veins to ankle, 25 g
thrombus removed above knee
• Warfarin 6 months
• Graduated Compression Stockings 2 years
• Suspension of Medical License
Risk of VTE Recurrence For This
Pilot
• Lifetime risk of recurrence was estimated to be 1520%
• Risk is highest in first 5 years
• Incidence between 2 – 4.4% per year in first 5 years
However
2 meta-analyses (Marchiori 2006, Ho 2007)
• Found risk of recurrence to be only slightly greater in FVL pts
than those with previous DVT in non FVL.
• RR 0.9 -2.4 (4 studies ,Ho 2006), RR 1.39 (Marchiori 2006)
Risk Stratification
•
High risk of recurrence
- FVL Heterozygotes as well as Prothrombin 20210 HZ
- Factor V Leiden Homozygotes
Good evidence life long warfarin after first VTE.
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Average Risk of Recurrence
-Factor V Leiden heterozygotes
Cessation or warfarin at 3-6 months
Factors Increasing his
Recurrence Risk
VIRCHOWS TRIAD
Hypercoaguability
-FVL heterozygote
Endothelial Lesion
-Damage to leg veins
Venous Stasis
- Immobility in flight?
Factors Decreasing his
Recurrence Risk
• Thrombectomy
Reduces damage to the vein, but no conclusive evidence that
it reduces the risk of recurrence of VTE
• Highly motivated individual,
Weight loss, exercise, compression stockings and will not be
immobile in flight
• First recorded episode of DVT
Is car journey (+ FVL) the cause?
Does His Work Environment
Contribute To Recurrence
Risk?
Risk of VTE approx doubles after a flight longer than 4
hours due to prolonged seated immobility. (WRIGHT
Phase 1)
Does this apply to pilots?
Risk contributed to by Obesity, Extremes of Height,
Oral Contraceptives and Prothrombotic Disorders
Maybe aircraft specific factors also???
Benefits vs Risks of Warfarin
• Reduces risk of recurrence of VTE by 80-95%
• But in Aviators consider the risk of INTRACRANIAL
bleed
• INR values are potent predictors of haemorrhagic
complications
• Low risk of major bleed if:
-INR is maintained between 2.0-3.0
-Risk profile low:
Young, >3/12 on Warfarin, no Co-Morbid Conditions
Risks of Warfarin if INR Stable
RCT, Non Valvular AF vs Untreated Controls ,Young and
Otherwise Fit.
• Risk of major bleed 1 – 1.5% per year (Warfarin) 0.5 – 1.0%
(Controls)
10,757 pts-Not Stratified for Risk
• 2.5% per year of major bleed
Meta Analysis of 29 RCT’s Warfarin Rx for DVT
• 2.2% per year risk of major bleed reducing to 1.9% after 3/12
on Warfarin ,
The risk seems acceptable in a multi crew environment
Is Life-Long Anticoagulation
Required?
1. Risk of recurrence of VTE
2 - 4.4 % per year for first 5 years
But risk of sudden incapacitation less than 1%
2. Risk of bleeding on anticoagulation
1 – 1.5% per year with INR 2.0 -3.0
(with no other co-morbidities)
Outcome
• Reinstated when off Warfarin (6/12)
• Weight loss (10kg), Daily Exercise
• Educated regarding prevention
-Hydration, Mobility, Flight Socks for work flights >
4hrs
-Prophylactic LMW Heparin NOT required for work
flights
• Second VTE would require life long Warfarin –DQ
Regulators View on
Anticoagulation
• United Arab Emirates: No pilots have been licensed
on anticoagulation but acceptable for cabin crew.
• UK, Australia and New Zealand: Class 1 OML
 If the underlying indication for Warfarin does not preclude
flying
 Target INR of 1.8-2.5 (UK CAA)
 6/12 of stability before relicensing (2/12 INR’s)
 INR check with personal monitor within 12 hours of flying
Monitoring
• Hemosense INRatio®, Coaguchek ®,
ProTimeTest ®
• CoaguChek S ® INR Monitor (Australian Rural Study)
88% of dual INR measurements were within
0.5 INR units of each other
Answers
Does he require lifelong anticoagulation after 1 VTE?
NO
-Recurrence VTE 2- 4.4% per year decreasing with time
-But risk of sudden incapacitation < 1% per year
VS
-Risk of bleeding on Warfarin 1.0 - 1.5% per year
Should he be licensed to fly on warfarin ?
YES
But only OML because risk close to 2% per year
References…
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7.
Oral Contraceptives and venous thromboembolism –BMJ Editorial 15 September 2009,
Volume 339
WHO research into global hazards of travel (WRIGHT) project –Final report of phase 1
Ho et al. Risk of Recurrent Venous Thromboembolism in Patients with Common
Thrombophilia. Arch Intern Med / Vol 166 April 10 2006
Marchiori et al. The risk of recurrent venous thromboembolism among heterozygous
carriers of factor V Leiden or PT20210A mutation. A systematic review of prospective
studies. HAEMATOLOGICA 2007; 92(08)
Correspondence Dr Paul Gaingrande, Haematologist, Oxford Haemophilia and
Thrombosis Centre UK
Van Hylckama Vlieg et al; The venous thrombotic risk of oral contraceptives, effects of
oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 5
September 2009/Volume 339
Linkins LA et al; Major bleeding risk with warfarin for DVT, Cleveland Clinic Journal of
Medicine Vol 71 Number 4 April 2004
References (2)
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10.
11.
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13.
14.
15.
16.
Ganfyd; Therapeutic bleeding risk, www.ganfyd.org
Kuijer PM; Predicirion of the risk of bleeding during anticoagulation treatment
for venous thromboembolism. Arch Intern Med 1999; 159:457-60
Factors Affecting Bleeding Risk During Anticoagulant Therapy : Discussion
www.medscape.com
Harper C, Keeling D. Progestogen Only Contraception for Patients with
Thromboembolic Disease. Oxford Radcliffe Hospitals
Fitzmaurice D et al. ABC of antithrombotic therapy. Bleeding Risks of
antithrombotic therapy. BMJ 2002; 325: 828-831
Amy JJ, Tripathi V, Contraception for women: an evidence based overview BMJ
15 September 2009, Volume 339
Navathe, Pooshan. Show me the evidence: Atrial Fibrillation in an Airline Pilot
CAA NZ. Powerpoint presentation
Lidegaard O et al. Hormonal Contraception and risk of venous
thromboembolism: national follow-up study, BMJ 15 September 2009, Volume
339
Correspondence Paul Collins-Howgill, UK CAA, Pooshan Navathe CASA, Dougal
Watson CAA NZ
Questions?