Archive for the ‘Inherited’ Category
Stephan Moll, MD and Damon Houghton, MD write … In patients with antiphospholipid syndrome (APS) who require anticoagulation for the treatment of DVT or PE, warfarin or a low molecular weight heparin have traditionally been used. A question that comes up is whether one of the new oral anticoagulants (DOACs) can be effectively and safely used instead.
It is not known at this point whether DOACs are equally, more or less effective as/than warfarin in patients with APS. Data from clinical trials directly comparing DOACs with warfarin are not yet available. Given the absence of data, no formal recommendations or guidelines exist on this topic. It is an individualized decision between a physician and patient with APS whether to use warfarin or a DOAC for the treatment of DVT or PE.
Several case reports and case series of patients with APS treated with a DOAC have been published. All data (from a total of 122 patients) have recently been summarized : Sixteen percent of patients had a recurrent clot on a DOAC. Given this relatively high rate of DOAC failure, the authors caution about the use of DOACs in APS. However, it is also known that warfarin has a high failure rate [references 2,3]. In addition, due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is possible as to how DOACs compare to warfarin or LMWH in the treatment of DVT and PE in patients with APS.
Several studies on APS and the use of DOACs are ongoing, with details available at clinicaltrials.gov:
- NCT02157272: A Prospective, Randomized Clinical Trial Comparing Rivaroxaban with Warfarin in High Risk Patients With Antiphospholipid Syndrome (TRAPS)
- NCT02295475: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
- NCT02116036: Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)
We discuss with patient with APS who needs to be on an anticoagulant:
- … that no solid data exist regarding the use of DOACs in APS, and that it is not known whether the DOACs are as effective as warfarin, less effective or more effective.
- … that some patients with APS develop new clots in spite of being on warfarin and that recurrent clots may also occur on a DOAC.
If we decide to use a DOAC, then our preference is typically a twice daily dosed anticoagulant (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®), as the twice daily dosed drug leads to more steady drug levels throughout the day. The hypothesis is that this may lead to a more effective anticoagulant effect. However, this theory is unproven and whether this truly leads to a lower risk of anticoagulant failure in patients with APS is not known. A recent publication (case report plus discussion on drug pharmacokinetics/-dynamics) also suggests a twice daily rather than a once daily dosed drug in patients with APS if a DOAC is used [ref 4]. However, feasibility/practicality of once daily versus twice daily medication and, thus, patient preference, is also important to consider.
- Dufrost V et al. Direct oral anticoagulants use in antiphospholipid syndrome: Are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016;18:74.
- Crowther M et al. A Comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.
- Finazzi G et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) J Thromb Haemost 2005;3: 848–853.
- Schofield JR et al. Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome. J Clin Pharm Ther. 2017 Jun 27. doi: 10.1111/jcpt.12582. [Epub ahead of print].
Disclosure: Dr. Moll has consulted for Janssen Pharmaceuticals and Boehringer-Ingelheim. Dr. Houghton has no disclosures.
Last updated: July 5th, 2017
Stephan Moll, MD writes… An information article on various aspects of thrombophilia, written for patients and family members, was published today – available here – as a Vascular Disease Patient Information Page in the journal Vascular Medicine. It addresses (a) in which patient with venous thromboembolism to consider thrombophilia testing, (b) what tests might be appropriate to do, (c) how the test results might influence length of anticoagulation therapy (d), what contraceptives are safe to use in women with a history of DVT or PE or thrombophilia, and (e) in which family members to consider thrombophilia testing. This article can be used as an education handout for patients in clinic or the hospital who have DVT, PE, venous thrombosis in unusual locations, or an established thrombophilia.
Last updated: April 1st, 2015
Stephan Moll, MD writes… A major international coagulation conference, the bi-annual meeting of the International Society for Thrombosis and Haemostasis (ISTH; www.isth.org), took place in Amsterdam, Holland, from June 29th to July 4th, 2013. The clinically relevant highlights about thrombosis and anticoagulation are summarized below. Read the rest of this entry »
Stephan Moll, MD writes… The decision how long to treat a patient with venous thromboembolism (VTE) with anticoagulants can often be made based on the patient’s history alone, i.e. the circumstances of the VTE event (provoked versus unprovoked). Often, no thrombophilia testing is needed. However, if one were to do thrombophilia testing, what is the right time to test? Read the rest of this entry »
Liz Varga, Certified Genetic Counselor, Nationwide Children’s Hospital, Columbus OH writes….
Some patients or their family members may be concerned about genetic testing for thrombophilias for fear of genetic discrimination. Fortunately in the United States, laws are in place that can alleviate this concern. Read the rest of this entry »
Inherited protein C deficiency is considered a stronger thrombophilia. It increases the risk for venous and arterial thromboembolism, and possibly for early and late pregnancy loss and other adverse pregnancy outcomes (preeclampsia, IUGR, placental abruption). There are 2 major causes for low protein C values: Read the rest of this entry »
How common is pregnancy loss? What are the causes?
Pregnancy loss in the general population is common. Most losses occur in the first trimester. As many as 5 % of women have 2 or more early losses; 1-2 % have 3 or more early losses [ref 1]. Well established risk factors for pregnancy loss are: (a) advanced maternal age, (b) anatomic uterine abnormalities (fibroids, septum, etc), (c) chromosome abnormalities of fetus, mother or father, (d) comorbid diseases of the mother (endocrine, immunologic). The acquired antiphospholipid antibody syndrome is also a risk factor for pregnancy loss. The role of inherited thrombophilias contributing to pregnancy loss is less clear. Read the rest of this entry »
If a thrombophilia (clotting disorder) has been identified in a patient with blood clots (venous thromboembolism = VTE), the question arises whether other family members should be tested for the same thrombophilia.
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