Thrombophilia Screening

Thrombophilia Testing – Which Tests

Introduction

1. Thrombophilia testing is useful in determining the cause of a thrombosis and in some cases the length of treatment.
2. It can also be used to risk assess thromboprophylaxis in high risk periods.
3. Thrombophilia testing should only be done if it will change the patient’s management.
4. These recommendations are based in part on the British Society of Haematology Guidelines (https://b-s-h.org.uk/guidelines/guidelines/).
5. Unless the sample request card meets the criteria below thrombophilia testing will not be performed.

Common Thrombophilia Tests

1. Full blood count – raised red cell count, haemoglobin or platelet count may point towards a myeloproliferative condition. FBC should be done in all cases of thrombosis.
2. Factor V Leiden – an inherited condition which leads to activated protein C resistance, it is associated with an increased risk of venous thrombosis but does not predict risk of recurrence.
3. Prothrombin gene abnormality – an inherited condition which leads to excess prothrombin, it is associated with an increased risk of venous thrombosis but does not predict risk of recurrence.
4. Antithrombin deficiency – an inherited condition with reduces the level of this natural anticoagulant, it is associated with an increased risk of venous thrombosis but does not predict risk of recurrence. This cannot be tested when the patient is on anticoagulants.
5. Protein C deficiency – an inherited condition with reduces the level of this natural anticoagulant, it is associated with an increased risk of venous thrombosis but does not predict risk of recurrence. This cannot be tested when the patient is on anticoagulants or while pregnant.
6. Protein S deficiency – an inherited condition with reduces the level of this natural anticoagulant, it is associated with an increased risk of venous thrombosis but does not predict risk of recurrence. This cannot be tested when the patient is on anticoagulants or while pregnant.
7. Lupus anticoagulant – an acquired abnormality when associated with thrombosis or pregnancy complications leads to the diagnosis of antiphospholipid syndrome. This cannot be tested for when the patient is on anticoagulants.
8. Antiphospholipid antibodies (anticardiolipan IgG+IgM and anti-β2-glycoprotein) – an acquired abnormality when associated with thrombosis or pregnancy complications leads to the diagnosis of antiphospholipid syndrome.

Rarer Thrombophilia Tests

1. Paroxysmal nocturnal haemoglobinuria (PNH screen) – an acquired condition associated with arterial and venous thrombosis, iron deficiency and cytopenias.
2. JAK2 analysis – a diagnostic test for myeloproliferative conditions which increase the risk of thrombosis.
3. Homocysteine levels – high levels are associated with thrombosis but it is unclear what normal levels are and whether intervention is beneficial.
4. Fibrinogen analysis – certain dysfibrinogenaemias lead to increased risk of thrombosis

Thrombophilia Testing – When To Test

DVT/PE

1. DVT or PE with strong provoking factor (post-op, trauma, pregnancy, cancer, exogenous oestrogens) – no indication for thrombophilia testing
2. Unprovoked DVT or PE – antiphospholipid antibodies on diagnosis and lupus anticoagulant when off anticoagulation (at least 7 days), discuss with haematology if any positive result.
3. Family history of DVT/PE – there is no indication for thrombophilia testing for family studies. First degree relatives of patients with a DVT or PE have themselves an increased risk of DVT/PE regardless of the finding of a thrombophilic abnormality. First degree relatives should be counselled to avoid exogenous oestrogens (combined oral contraceptive pill and oral HRT) and to always inform medical staff of the family history if they become pregnant or are immobilised due to injury or illness.

Thrombophlebitis

1. No indication for thrombophilia testing
2. Unexplained arterial thrombosis under the age of 50
3. Antiphospholipid antibodies on diagnosis and lupus anticoagulant when off anticoagulation.

Unusual thrombosis

1. Any thrombosis at an unusual site, this includes any abdominal thrombosis and cerebral venous thrombosis, or arterial and venous thrombosis in the same patient – antiphospholipid antibodies, PNH screen and JAK2 analysis on diagnosis and lupus anticoagulant when off anticoagulation with. There should also be a high suspicion of malignancy in these patients.

Obstetric Complications

1. Lupus anticoagulant and antiphospholipid antibodies should be performed when there is:
   1. Three or more unexplained spontaneous miscarriages (<10 weeks gestation size)
   2. One or more fetal loss (>10 weeks gestational size)
   3. Severe or early pre-eclampsia
   4. Unexplained placental insufficiency
2. Purpura fulminans – protein C + S
3. There is no indication for thrombophilia testing in infertility.

Rheumatological Conditions

1. Lupus anticoagulant and antiphospholipid antibodies should be performed when there is:
   1. Diagnostic workup for SLE
   2. Pregnancy risk stratification in connective tissue disease
2. There is no indication for lupus anticoagulant testing in the diagnostic work-up for connective tissue disease unless there are features of secondary anti-phospholipid syndrome or pulmonary arterial hypertension.

Unusual Presentation of Antiphospholipid Syndrome

1. Lupus anticoagulant and antiphospholipid antibodies should be performed when there is:
   1. Illness with signs of microangiopathic haemolysis
   2. Unexplained multi-organ failure
   3. Non-rheumatic valve thickening or culture negative vegetations
   4. Thrombophilia testing is not indicated in the investigation of isolated cytopenias.

Links

• Thrombophilia Request Form [pdf]
  

Content updated by Dr Mark Crowther