NHS FORTH VALLEY GUIDELINE ON THROMBOPHILIA INVESTIGATION AND TESTING

Date of First Issue 01/ 01/2010 Approved 01/01/2010 Current Issue Date 28/12/2016 Review Date 28/12/2018 Version 2.1 EQIA Yes 30/06/2012 Author / Contact Group Committee – Dr Roderick Neilson & Thrombosis Interest Group Final Approval This document can, on request, be made available in alternative formats

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Consultation and Change Record – for ALL documents Contributing Authors:

Dr Roderick Neilson

Consultation Process:

Thrombosis Interest Group and MedLine Review

Distribution: Change Record

Date

Author

Change

Version

30/6/12

Dr R Neilson

Minor Textual Changes

2.1

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THROMBOPHILIA INVESTIGATION AND TESTING

Introduction Testing for thrombophilia is available through the haematology service in NHS Forth Valley. However, indiscriminate application of thrombophilia tests is clinically inappropriate and can be clinically misleading. The following document is guidance for clinicians considering undertaking testing for thrombophilic abnormalities in their patients. The Guidance is derived from the British Committee for Standards in Haematology Clinical Guidelines for testing for heritable thrombophilia (2009). A full copy of this document and supporting references can be found at: http://www.bcshguidelines.com/pdf/ThrombophiliaGuideline_101209.pdf

Tests Available and Sample Requirements: The following tests comprise the thrombophilia screen: Antithrombin Assay Protein S assay (Total & Free) assays Modified activated protein C sensitivity APC:SR ratio as marker for Factor V Leiden

Protein C assay Lupus anticoagulant and anticardiolipin Prothrombin G20210A mutation

Genetic analysis for Factor V Leiden will only be undertaken if the APC:SR is abnormal. Screening should be requested on a routine haematology request form. The request form should be marked ‘THROMBOPHILIA SCREEN’ in the ‘other tests’ part of the form. The request form MUST include full patient and family history details and drug therapy, especially oral contraceptive use or HRT, where appropriate. Samples required for a thrombophilia screen are: 4 x 5ml citrate samples (blue topped tubes) ALL REQUESTS FOR THROMBOPHILIA SCREENING WILL BE SCRUTINISED BY A CONSULTANT HAEMATOLOGIST. INCOMPLETE OR CLINICALLY INAPPROPRIATE REQUESTS WILL BE REJECTED AND THE REQUESTING CLINICIAN INFORMED.

In all cases, if there is a doubt about who and when to test please contact a consultant haematologist to discuss prior to sending the samples.

When and Who to Test

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1.

When to Test

The laboratory interpretation of thrombophilia tests is difficult and fraught with pitfalls, which occasionally lead to under diagnosis and frequently to over diagnosis of defects. Some tests for heritable thrombophilia are affected by the acute and sub acute post-thrombotic state and by anticoagulant use. Also, the finding of a thrombophilic abnormality almost never influences the management of an acute thrombotic event. Accordingly there is NO virtue in testing when the patient presents with an acute thrombotic event, and samples sent at the time of the acute event will NOT routinely be analysed. Testing is usually best delayed until at least one month after the acute event or completion of anticoagulant therapy. If possible testing for heritable thrombophilia should be avoided during intercurrent illness, pregnancy or recent gestation, or use of oral contraceptive pill or HRT. 2.

Who to Test

 Acute VTE (DVT+/- PE)  Venous thrombosis of Upper Limb/Eye/Venous Sinus of Brain/Intra-abdominal Veins  Coronary, cerebral and peripheral arterial thrombosis  Woman being considered for HRT/COCP  Prevention of VTE in hospitalised patients  Relatives of patients with a history of VTE  Children

A

See sec A (p2) See sec B (p3) See sec C (p3) See sec D (p4) See sec E (p4) See sec F (p5) See sec G (p5)

Patients with Acute VTE (DVT or PE)

It is now apparent that testing for heritable thrombophilia typically does not predict likelihood of recurrence in unselected patients with symptomatic venous thrombosis and testing for inherited thrombophilia did not reduce recurrence of venous thrombosis in a large cohort study. There is a low risk of thrombosis in affected asymptomatic relatives followed prospectively and the results of thrombophilia tests are frequently misinterpreted. Guidance:   Initiation and intensity of anticoagulant therapy following a diagnosis of acute venous thrombosis should be the same in patients with and without heritable thrombophilia (1B). 

Indiscriminate testing for heritable thrombophilias in unselected patients presenting with a first episode of venous thrombosis is not indicated (1B).

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

Decisions regarding duration of anticoagulation (lifelong or not) in unselected patients should be made with reference to whether or not a first episode of venous thrombosis was provoked or not, other risk factors, and risk of anticoagulant therapy-related bleeding, regardless of whether a heritable thrombophilia is known (1B).



Testing for heritable thrombophilias in selected patients, such as those with a strong family history of unprovoked recurrent thrombosis, may influence decisions regarding duration of anticoagulation (C). It is not possible to give a validated recommendation as to how such patients should be selected.

B

Venous Thrombosis in Upper Limb/Eye/Cavernous Venous System of Brain 

Testing is not recommended in unselected patients with upper limb venous thrombosis (1B).



Testing is not recommended in patients with CVC-related venous thrombosis (1C).



Testing for heritable thrombophilias after a first episode of Cavernous venous Thrombosis has uncertain predictive value for recurrence (C). Decisions regarding duration of anticoagulant therapy in relation to the results of testing are not evidence based.



Testing is not indicated in patients with retinal vein occlusion (1B).



Testing for heritable thrombophilias after a first episode of intra-abdominal vein thrombosis has uncertain predictive value for recurrence (C). Decisions regarding duration of anticoagulant therapy in relation to the results of testing are not evidence based.

C

Coronary, cerebral and peripheral arterial thrombosis

In arterial artery thrombosis the material contribution of heritable thrombophilia, as compared with established cardiovascular risk factors, is not proven and is not sufficient to change therapy for primary and secondary prevention. Despite this, young patients are sometimes tested after an arterial occlusive event. As there is no established causal relationship and as treatment and secondary prevention should be in relation to established cardiovascular risk factors thrombophilia testing is not recommended. Guidance: 

Testing for heritable thrombophilia is not indicated in patients with arterial thrombosis (1B).

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D Women being considered for oestrogen containing hormone preparations (COCP/HRT) In some women heritable thrombophilia has already been established whilst in others it is perceived that testing would enable informed decision making regarding use of a combined oral contraceptive (COCP) or hormone replacement therapy (HRT). However, the absolute risk of thrombosis is low and the fact that venous thrombosis has a polygenic basis with incomplete penetrance makes counselling in relation to genetic testing uncertain. Similar principles apply to HRT, although the baseline risk is higher as the population is older. If HRT is considered essential then a non-oral formulation is associated with a significantly lower risk of venous thrombosis. Guidance: 

If a first degree relative with venous thrombosis has not been tested then suggest woman considers an alternative contraceptive or transdermal HRT. Testing for heritable thrombophilia will provide an uncertain estimate of risk and is not recommended



If a first degree relative with venous thrombosis has been tested and the result is negative then suggest woman considers an alternative contraceptive or transdermal HRT. Testing for heritable thrombophilia will provide an uncertain estimate of risk and is not recommended (1C).



If a first degree relative with venous thrombosis has been tested and the result is positive then suggest woman considers an alternative contraceptive or transdermal HRT before offering testing as a negative test result does not exclude an increased risk of venous thrombosis. Testing for heritable thrombophilia may assist counselling of selected women particularly if a high risk thrombophilia has been identified in the symptomatic relative (C).

E

Prevention of venous thrombosis in hospitalised patients

Thromboprophylaxis for hospitalised patients should be in accordance with a structured risk assessment based on procedural and personal risk factors for venous thrombosis. Screening for heritable thrombophilia is not indicated although a previously identified heritable thrombophilia may influence the assessment of risk. Guidance: 

Thrombophilia screening of hospitalised patients to identify patients at risk of hospital-acquired venous thrombosis is not indicated (1A).



All hospitalised patients should be assessed for risk of venous thrombosis regardless of heritable thrombophilia based on a clinical risk assessment (1B). The presence of a previously known heritable thrombophilia may influence the assessment of risk.

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F

Asymptomatic relatives of patients with a history of venous thrombosis

Guidance: 

Case finding of asymptomatic relatives with low risk thrombophilia, such as FV Leiden or F2G20210A, is not indicated (1B).



Case finding of asymptomatic relatives with high risk thrombophilia, such as deficiency of antithrombin, protein C or protein S, should only be considered in selected thrombosis-prone families (1B). If testing is performed the risks, benefits and limitations of testing should be discussed in the context of explained inheritance and disease risk.



Case finding for very rare homozygosity or compound heritable thrombophilia is not indicated as these defects are so rare, they are not predicted by family history, and the risk of unprovoked thrombosis is low (2C).

G

Children

Guidance: 

Neonates and children with purpura fulminans should be tested urgently for protein C and S deficiency (1B).



It is suggested that testing for heritable thrombophilia is not indicated in children with stroke (2C). ---------------------------------------------------------------------------------------

In all cases, if there is a doubt about who and when to test please contact a consultant haematologist to discuss prior to sending the samples. Dr R F Neilson Dr Chris Brammer

Dr Marie Hughes Dr Rachel Boulton - Jones

Dates of Publication: Jan 2010, Jul 2012.

Date of Review: Jul 2014

Criteria used to quote levels and grades of evidence are according to the GRADE system (Guyatt, et al 2006). Strong recommendations (grade 1, 'recommended') are made when there is confidence that the benefits either do or do not outweigh the harm and burden and costs of treatment. Where the magnitude of benefit or not is less certain a weaker grade 2 recommendation ('suggested') is made. Grade 1 recommendations can be applied uniformly to most patients whereas grade 2 recommendations require judicious application. The quality of evidence is graded as A (high quality randomised clinical trials), moderate (B) or low (C)

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Publications in Alternative Formats NHS Forth Valley is happy to consider requests for publications in other language or formats such as large print. To request another language for a patient, please contact 01786 434784. For other formats contact 01324 590886, text 07990 690605, fax 01324 590867 or e-mail - [email protected]

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