Issues in the Investigation and Management of Thrombophilias

Issues in the Investigation and Management of Thrombophilias

Issues in the Investigation and Management of Thrombophilias Michelle Bryson Staff Specialist Haematology Gold Coast Hospital Introduction Background Components of thrombophilia tests Who and when to test

Pitfalls in testing Specific Management issues (contraception/HRT/travel/pregnancy) Background Worldwide incidence 1-2 events per 1000 persons/year Australian Incidence VTE 0.83 per 1000 persons per year DVT 0.52 per 1000 persons per year

PTE 0.31 per 1000 persons per year Approx. 17,400 new cases annually In keeping with figures from UK, lower than other areas in Europe Khoon Ho et al MJA 2008 Incidence of VTE by Age in Community based study, Perth, 2008 Khoon Ho et al MJA 2008 Non-Heritable Risk Factors Surgery/trauma particularly pelvic

Prolonged immobility whatever the cause Malignancy Obesity Pregnancy Hormonal therapy COCP/HRT

Air travel > 4hours Thrombophilia Incidence of first VTE (%/year) Incidenc e of Defect Relative Risk of VTE3 Factor V Leiden 0.1 (0.00.6)1

~5%2 3-8 fold (hetero) 80 fold (homo) ~5%2 3 fold Prothrombin G2010A Combined Defects 1.6 (0.53.7)1 ??? Higher than FVL homozygous Antithrombin deficiency

1.7 (0.83.3)1 0.02%3 25-50 fold Protein S deficiency 0.8 (0.31.9)1 unknown uncertain Protein C deficiency 0.7 (0.31.6)1 0.2-0.3%3

10-15 fold 1. EPCOT study, Vossen et al, J Throm Haem, 2005 2. RCPA Manual, 2004 Why are you doing the thrombophilia screen? Identify those individuals at high risk of first event or high risk of recurrence? To provide an intervention to reduce risk? To enable screening of family members?

Ultimately to reduce the incidence and mortality associated with thrombosis When to test? At presentation ? Not recommended Issues with counselling, and does not impact on duration of treatment

Recommend to perform 4-6 weeks after completion of anticoagulant therapy Pitfalls Free Protein S falls progressively during pregnancy Lower in those on COCP and possibly HRT Leads to over diagnosis of Protein S deficiency Testing in relation to anti-coagulants Falls in protein C and S on warfarin (6 weeks)

Changes in anti-thrombin on heparin Pitfalls What do you do with a positive result in an asymptomatic individual with no family history? Who to test? Not everyone who has had a thrombosis Not everyone with a positive family history Depends upon Circumstances of VTE both for individual and family member

Family history-nature of the thrombophilic defect Implications of Testing Positive in Asymptomatic Individuals Anxiety worried well Over estimation of risk Case finding as means to select those for testing NOT RECOMMENDED Asymptomatic relatives of those with low risk defects

(FVL/PT) Relatives of those with homozygous or compound heterozygotes (very rare) RECOMMENDED Asymtomatic relatives of those with high risk defects (AT, Protein C and S) Case finding as means to select those for testing Clinical scenario much more important Family history

82yo grandmother develops DVT following surgery for #NOF 36yo sister has PTE/DVT whilst on the COCP 27yo brother has unprovoked DVT Prevention of VTE associated with Oestrogen-containing preparations If first degree relative has had VTE whilst on COCP/HRT and not been tested advice to consider alternatives testing not recommended

First degree relative with VTE tested and negative advice to consider alternates testing not recommened First degree relative with VTE tested and positive advice consider alternative before undergoing testing. (May assist in counselling if high risk thrombophilic defect) Scenario 17 year old attends for COCP FH/ Mother had a DVT at 16/40 in her 2nd pregnancy Mother is heterozygous for FVL Daughter negative for FVL rest of screen

negative What would you do? Prevention of pregnancyassociated VTE Rare but still highest cause of maternal mortality in Developed World Associated with 5-10 fold increased risk of VTE 100 fold risk if prior VTE

Prevention of pregnancyassociated VTE Testing based upon clinical risk factors If prior unprovoked, pregnancy or COCP related VTE testing not recommended does not alter management Previous major provoking factor related VTE e.g. due to trauma do not usually require testing or prophylaxis* Previous minor provoking factor related VTE e.g. travel consider testing and prophylaxis if defect found

First degree relative who has had unprovoked, or pregnancy/COCP related VTE testing recommended Pregnancy Complications Association between thrombophilic defects and pregnancy complications Recent study compared aspirin alone vs aspirin plus heparin in women with unexplained recurrent miscarriage. No improvement in live birth rate was noted in either arm

No difference between those with thrombophilic defect and those without At present not enough evidence to support routine thrombophilic testing as no intervention has been established to improve outcomes Kaandorp et al NEJM 2010 Contraception Alternatives to COCP should be sought if: Personal history of VTE

Family history of COCP/HRT/pregnancy associated VTE Known thrombophilic defect (evidence strong for FVL and AT, less so for other defects) What alternatives to use? Barrier contraception Surgical sterilisation

Progesterone only preparations Mirena IUD Gomes et al, Arch Intern Med 2004 WHO Guidance 2009 History History DVT/PTE On established A/C therapy Family History (1st degree relatives) Thrombogeneic mutations POP

Depot Implant s 2 2 2 2 2 2 1 1 1

2 2 2 POP- progesterone only pill 1- A condition for which there is no restriction for the use of contraceptive meth 2- A condition where the advantages of using the method generally outweigh t theoretical or proven risks Pregnancy Prophylaxis High risk thrombophilic defects Homozygotes/ compound heterozygote for FVL/PT Antithrombin deficiency* Lower risk defects

X Asymptomatic not indicated Depends upon personal and family history, and other risk factors such as obesity Previous VTE Recurrent miscarriages no role Adverse pregnancy outcomes uncertain benefit Pregnancy Prophylaxis When to start? As soon as is practical events in high risk women are

equally distributed throughout gestation When to interrupt for delivery? As soon as labour starts Day before induction/C-section No epidural/spinal for at least 12 hours post dose When to stop ? 6 weeks post-partum What to use? LMWH preferred choice

UFH associated with progressive bone loss Warfarin only in post-partum period, but most prefer to continue with LMWH If tolerated compression stocking throughout Pregnancy and Anticoagulant Therapy Access to early pregnancy assessment unit Early USS 5-6 weeks

Stop warfarin and switch to LMWH LMWH requirements increase throughout pregnancy anti-Xa levels ~4 weekly Post-partum re-establish on warfarin (can breast feed) Air Travel World Health Organisation Research Into Global Hazards of Travel (WRIGHT study, 2007) Risk Factor

Relative Risk - Travel Relative Risk + Air Travel Factor V Leiden 3.0 13.6 PT 20210A 2.6 7.9 Obesity

1.7 2.6 Short <1.6m 1.0 4.9 Tall >1.9m 1.0 6.8 Height Risk Assessment Very high risk previous VTE

some major thrombophilic abnormalities Other risks 1st degree relative with VTE Age > 50 years Recent major surgery Active cancer Oestrogens BMI > 30 Recommendations Low Risk Passengers (ie most passengers) Exercise legs & calves Keep legs straight: avoid getting legs in fixed position Keep well hydrated Do not drink alcohol (it dehydrates) Consider support stockings (Grade I, fitted)

Recommendations Moderate Risk Passengers (more than one risk factor) Prophylaxis as above, plus : X- Support stockings (Grade II, fitted, below-knee) NO ROLE FOR APSIRIN not recommended Recommendations High Risk Passengers Prophylaxis as above, plus the following: Low-molecular-weight heparin: Single subcutaneous injection at prophylactic dose e.g. enoxaparin 40mg, 2-4

hours before travel Patients on Warfarin should know they are in their therapeutic range before flying, Avoid sleeping tablets Summary Overview of common heritable thrombophilias Recommendations on testing Management of Contraception Some issues in Management of Pregnancy

Air travel risk and thromboprophylaxis Thank - You Any questions ? References: Khoon Ho, W., G. Hankey, et al. (2008). "The incidence of venous thromboembolism: a prospective, community-based study in Perth, Western Australia." MJA 189(3): 144-147. Walker, I., M. Greaves, et al. (2001). "Investigation and Management of Heritable Thrombophilia." B J Haem 114: 512-528.

World Health Organisation Research Into Global Hazards of Travel (WRIGHT study, 2007) Kaandorp, S., M. Goddijn, et al. (2010). "Aspirin plus heparin or aspirin alone in women with recurrent miscarriage." NEJM 362(17): 1586-96. Vossen, C., J. Conard, et al. (2005). "Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prosepctive Cohort on Thrombophilia (EPCOT)." J Thromb Haem 3: 459-464. Baglin, T., E. Gray, et al. (2010). "Clinical guidelines for testing for heritable thrombophilia." B J Haem 149: 209-220.

WHO (2009). "Medical eligibility criteria for contraceptive use. Fourth Edition." World Health Organisation. RCOG (2009). "Reducing the risk of thrombsis and embolism during pregnancy and puerperium. ." Royal College of Obstetricians and Gynaecologists Green-top guideline No.37.

Recently Viewed Presentations

  • Layers of the Earth - Issaquah Connect

    Layers of the Earth - Issaquah Connect

    Mantle - Thickest layer (makes up the bulk of the Earth's mass and volume). Made of molten rock (magma). How we know: Magma sometimes comes up from the mantle at volcanoes, s and p waves travel through the mantle. Layers...
  • Unit 1 Human Lifespan Development - Townsend Church of ...

    Unit 1 Human Lifespan Development - Townsend Church of ...

    Key Terms: - Abstract logical thinking - the ability to solve problems using imagination without having to be involved practically. This is an advanced form of thinking that does not always need a practical context in order to take place....
  • P U L M O N A RY

    P U L M O N A RY

    May be subtle oligaemia. Wester mark sign. Westermark's Sign. ECG: S1 Q3 T3 anterior T-wave inversion . Right bundle branch block (RBBB) ... Pulmonary infarction is an uncommon consequence because of the bronchial arterial collateral circulation.
  • 2013 DIR PM Lite Webinar

    2013 DIR PM Lite Webinar

    PMI PMBOK. Others. To develop a consistent approach for project management, we looked at the Texas Project Delivery Framework. The Framework is designed for large scale, IT projects. Many of the projects we work on are smaller, shorter term, and...
  • 2010 IEEE-SA Corporate Membership - Health Level Seven ...

    2010 IEEE-SA Corporate Membership - Health Level Seven ...

    Ballots in Progress P11073-30400 Standard for Health Informatics-POC Medical Device Communication-Interface profile-Cable Ethernet (ISO/IEEE) Comment resolution (ballot closed 6 Mar 2008) Malcolm Clarke elected LL WG Chair P11073-10472 Standard for Health informatics - Personal health device communication -Device specialization ...
  • Overview of ARIES ACT-1 Study Farrokh Najmabadi Professor

    Overview of ARIES ACT-1 Study Farrokh Najmabadi Professor

    PbLi self-cooled SiC/SiC breeding blanket with simple double-pipe construction . Brayton cycle with h~58%. Many new features and improvements. He-cooled ferritic steel structural ring/shield. Detailed flow paths and manifolding for PbLi to reduce 3D MHD effects* Elimination of water from...
  • General Features and Major Evolutionary Trends of Apes

    General Features and Major Evolutionary Trends of Apes

    adaptations for bipedalism . . . Hominids Hominids Hominidae (Hominids) Australopithecus . . . Paranthropus . . . (maybe) Homo . . . Hominids Over-all Comparisons Gibbon Orangutan Chimpanzee Gorilla Modern Human General Features / Trends of Apes / Humans...
  • Overview of Late First-Century New Testament Writings The

    Overview of Late First-Century New Testament Writings The

    the pastoral epistles (1 Timothy, 2 Timothy, and Titus): addressed to the pastors, or leaders, of various early Christian communities the catholic epistles (1 and 2 Peter, Jude, James, and 1, 2, and 3 John): addressed to a universal, or...