# Presentation: 175678

## Laboratory Testing and the Thrombophilia Workup

- Thomas L. Ortel, M.D., Ph.D.
- Duke University Medical Center
- 8 May 2006

## Roles of the Clinical Laboratory

- Useful ancillary data for initial diagnosis (d-dimer).
- Monitoring antithrombotic therapy.
- Evaluation for underlying hypercoagulable state(s).
- Identifies individuals ‘at risk’ for thrombosis.
- Identifies individuals with an initial thrombosis who are at higher risk for recurrence.

## What laboratory tests are useful in the acute setting?

- D-dimer  supportive data to help rule out venous thromboembolism.
- Troponins/BNP  stratify severity of PE.
- PT, aPTT  essential baseline information prior to starting therapy.
- Hypercoagulable workup generally *not* useful in the acute setting.

## Who should be considered for thrombophilia testing?

- Patients with unexplained, or ‘idiopathic’ thromboembolism.
- Patients with thromboembolism that is unusually extensive, or in an unusual location (*e.g*., portal vein thrombosis).
- Patients with a striking family history for venous thromboembolism.

## What tests should be done?

- Activated protein C resistance, with analysis for factor V Leiden if positive.
- Prothrombin G20210A genotype analysis.
- Antithrombin functional assay.

- Protein C functional assay.
- Protein S functional assay, with antigenic assays if indicated.
- Antiphospholipid antibody testing.
- Homocysteine level.
- Factor VIII assay.

## Thrombophilic states and race

- Caucasian

- African-American

- Dowling, *et al*., J.Thromb.Haemost., 2003; Patel, *et al*., Thromb.Haemost., 2003

## Thrombophilia in the pediatric patient

- Many studies include children with central venous lines and other acquired disorders.
- Elevated factor VIII and D-dimer is also associated with recurrent thrombosis

- Nowak-Göttl, *et al*., Blood, 2001; Revel-Vilk, *et al*., J.Thromb.Haemost., 2003; Goldenberg, *et al*., NEJM, 2004.

- Age: neonate to 18 yrs

## Impact of thrombophilic disorders on recurrent thromboembolism

-            **Kyrle, P. A. *****et al*****. N Engl J Med 2000; 343:457-462.  ****© 2000 Massachusetts Medical Society.**
**           ****All rights reserved.**

## ACCP Guidelines

- 2.1.4.  For patients with first episode DVT and:
- Antiphospholipid antibodies;
- 2 or more thrombophilic conditions;
-  therapy for 12 months (1C+) or indefinite (2C).
- 2.1.5.  For patients with first episode DVT and:
- Antithrombin, protein C or protein S deficiency;
- Factor V Leiden or prothrombin G20210A;
- Elevated homocysteine or factor VIII levels
-  therapy for 6-12 months (1A) or indefinite (2C).

- Büller, et al., Chest, 2004

## Cost of thrombophilia testing

| Test | Approximate Cost* |
| --- | --- |
| Natural anticoagulants (antithrombin, protein C, protein S): | $450-750 |
| Genetic tests (factor V Leiden, prothrombin G20210A): | $600 |
| Antiphospholipid antibodies: | $1000-1500 |
| Other (factor VIII, homocysteine): | $200 |
| TOTAL: | $2250-3050 |

- * Duke Coagulation Laboratory

## What should healthcare providers do with this information?

- Individuals who test positive for a thrombophilic risk factor require counseling as to:
- risks of thrombosis to themselves *and their family members*.
- importance of early recognition of signs and symptoms of venous thromboembolism.
- risks and benefits of thromboprophylaxis in high-risk situations.

- Olson, Arch.Pathol.Lab.Med., 2002

## Should asymptomatic individuals be screened for thrombophilia?

- Screening of asymptomatic individuals, whether family members of a patient with thrombosis, or in a situation that places them at increased risk for thrombosis, is generally not recommended.
- However, in selected situations, knowledge of a specific thrombophilic state might guide therapeutic decision-making (*e.g*., decision concerning HRT usage).

## On the other hand, one doesn’t even need the doctor to order the test... 

- On the other hand, one doesn’t even need the doctor to order the test...

- http://www.dnadirect.com/

## Future directions forthrombophilia testing

_*Prospective*_ clinical studies to define:
- Role, if any, of screening asymptomatic family members or individuals in high-risk situations.
- Impact on optimal therapy for patients with venous thrombosis and thrombophilia.
- Better education for providers as well as consumers concerning risk factors, prevention strategies, need for genetic counseling, *etc*.