Is there any utility to laboratory testing for inherited thrombophilia or antiphospholipid syndrome in my hospitalized patient with unprovoked acute pulmonary embolism?

There is virtually no utility to obtaining heritable thrombophilia testing in acute hospital setting. In fact, there are potential harms due to false-positive and false-negative results which in turn may lead to increasing anxiety in the patient and added cost due to repeat testing.

As many tests obtained as part of this workup are functional assays—eg, the protein S, C, or antithrombin activity, and activated protein C resistance (often used to screen for factor V Leiden)— they are easily impacted by the physiologic effects of acute thrombosis as well as all anticoagulants.1

More importantly, testing for inherited thrombophilia will not impact management in the acute setting, as decisions regarding duration of anticoagulation are often made later in the outpatient setting. The proper time to evaluate the patient for inherited thrombophilias (if indicated) is at least one week following discontinuation of anticoagulation (minimum 3 months from the time of the index event). 2 

Testing for antiphospholipid syndrome (APS) may be considered in this setting though it should be noted that the lupus anticoagulant assay is impacted by nearly every anticoagulant, resulting in frequent false-positive results1, and therefore should be performed before initiation of these agents (or delayed until later if anticoagulation has already begun). A false-positive result has downstream implications as many patients with acute, uncomplicated venous thromboembolism (VTE) are discharged on a direct oral anticoagulant (DOAC), and antiphospholipid syndrome is currently considered a relative contraindication to the use of DOACs in VTE.

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 References
1. Moll, S. “Thrombophilia: Clinical-practical aspects.” J Thromb Thrombolysis 2015;39:367-78. https://www.ncbi.nlm.nih.gov/pubmed/25724822
2. Connors JM. “Thrombophilia Testing and Venous Thrombosis.” N Engl J Med 2017; 377:1177-1187. http://www.nejm.org/doi/full/10.1056/NEJMra1700365 

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Is there any utility to laboratory testing for inherited thrombophilia or antiphospholipid syndrome in my hospitalized patient with unprovoked acute pulmonary embolism?

What is the significance of a prolonged activated partial thromboplastin time (aPTT) in my patient with suspected antiphospholipid syndrome (APS)?

APS is an acquired hypercoagulable state which presents classically as recurrent arterial and/or venous thrombosis and is a major cause of late first- and second-trimester spontaneous fetal loss. In addition to thrombotic complications, diagnosis of APS requires the presence of ≥ 1 of the following antiphospholipid antibodies on 2 occasions ≥12 weeks apart: 1) anti-ß2-glycoprotein 1 antibodies; 2) anticardiolipin antibodies; and 3) lupus anticoagulant (LA)1.  

An unexpected prolongation of aPTT may be a clue to the presence of APS and may be explained by the in vitro prevention of the assembly of the prothrombinase complex—which catalyzes the conversion of prothrombin to thrombin— by LA2,3.  

Because the phospholipid component of the reagent used in aPTT tests determines its sensitivity to LA, aPTT results may vary, influenced by the type and concentration of phospholipids used in the assay. Other factors such as acute phase reaction associated with increased fibrinogen and factor VIII levels may also impact the results by shortening the aPTT and potentially masking a weak LA2.

 

 

References 

  1. Giannakopoulos B, Passam F, Ioannou Y, Krilis SA. How we diagnose the antiphospholipid syndrome.Blood. 2009;113:985-94.
  2. 2. Abo SM, DeBari VA. Laboratory evaluation of the antiphospholipid syndrome. Ann Clin Lab Sci 2007;37:3-14.
  3. Smock KJ, Rodgers GM. Laboratory identification of lupus anticoagulants. Am J Hematol. 2009;84(7):440-2.

 

 

Contributed by Ricardo Ortiz, medical student, Harvard Medical School

What is the significance of a prolonged activated partial thromboplastin time (aPTT) in my patient with suspected antiphospholipid syndrome (APS)?