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.

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 

Contributed by Hanny Al-Samkari, MD, Mass General Hospital, Boston, MA

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

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

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

 

Patients with atrial fibrillation (AF) who need percutaneous coronary intervention (PCI) after acute coronary syndrome or for stable angina pose a treatment challenge as oral anticoagulants (OACs) and dual antiplatelet therapy (DAPT) are often used concurrently to decrease the risk of systemic thromboembolism and stent thrombosis. However, “triple therapy”, including aspirin, a P2Y12 inhibitor, and an OAC (eg, warfarin or a direct oral anticoagulant-DOAC), also increases the risk of bleeding, necessitating several recent landmark trials to better address the subject.

Two modest-sized RCTs (WOEST and ISAR-TRIPLE) reported that when compared to triple therapy (DAPT plus warfarin), double therapy (single antiplatelet agent plus INR-targeted warfarin) is associated with reduced risk of bleeding complications without an increased risk of thrombotic events. 1,2

Two larger RCTs, PIONEER AF-PCI and RE-DUAL PCI, studied rivaroxaban and dabigatran, respectively, in patients with non-valvular AF undergoing PCI and found a reduction in bleeding events in patients receiving double therapy (single antiplatelet agent plus DOAC) compared to triple therapy (DAPT plus warfarin), without an increased risk of thrombotic complications. 3,4

Collectively, these studies suggest that it may be safe to treat patients with increased risk of bleeding with double therapy (even immediately following PCI) without an increase in thrombotic events. If triple therapy is elected, duration should be minimized, clopidogrel should be preferred over more potent P2Y12 inhibitors, and a PPI should be considered.

 

References:

  1. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-15. https://www.ncbi.nlm.nih.gov/pubmed/23415013
  2. Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-29. https://www.ncbi.nlm.nih.gov/pubmed/25908066
  3. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1611594
  4. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. Published online, Aug, 27, 2017. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1708454

 

Contributed by Amulya Nagarur, MD, Mass General Hospital, Boston, MA

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

Is anticoagulation (AC) therapy recommended for treatment of vein thrombosis of upper extremities?

The short answer is “yes” when deep veins, such as brachial, axillary or subclavian are involved; cephalic and basilic veins are superficial. Although some have suggested that isolated brachial vein thrombosis may be considered at low risk of complication, this assumption has not been corroborated by objective research (1).

There are no randomized trials of AC therapy in patients with upper extremity deep vein thrombosis (UEDVT).  However,  the American College of Chest Physicians has recommended a 3-month course of AC therapy similar to that of leg DVT for several reasons (1,2):

  •  UEDVT has generally been reported to have complications and consequences comparable to that of leg DVT
  •  Several small cohort studies suggest lower rates of recurrent DVT, PE, and bleeding when UEDVT is treated similar to leg DVT
  •  Known demonstrated benefit of AC therapy in leg DVT

In addition, post-thrombotic syndrome is relatively common (~1 in 5) among patients with UEDVT (3)

References

1.  Hingorani A, Ascher E, Marks N, et al. Morbidity and mortality associated with brachial vein thrombosis. Ann Vasc Surg 2006; 20:297-299. https://www.ncbi.nlm.nih.gov/pubmed/16779509

2. Kearon C, Akl EA, Comerato AJ, et al. Antithrombotic therapy for VTE disease: American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141(suppl):419S-494S. https://www.ncbi.nlm.nih.gov/pubmed/22315268

3. Maynard G. Upper extremity deep vein thrombosis:A call to arms. JAMA Intern Med 2014;696-698. https://www.ncbi.nlm.nih.gov/pubmed/24638129

Is anticoagulation (AC) therapy recommended for treatment of vein thrombosis of upper extremities?