scholarly journals Thrombophilias: therapeutic employment of direct oral anticoagulants in venous hypercoagulable states

2020 ◽  
Vol 14 (3) ◽  
pp. 136-142
Author(s):  
Federico Cacciapuoti
Keyword(s):  
Arterial Thrombosis ◽  
Methylenetetrahydrofolate Reductase ◽  
Contraceptive Use ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Factor V ◽  
Venous Thromboembolic Events

Thrombophilia or hypercoagulable state is a predisposition to form clots. Thrombophilia can be inherited or acquired, and prevalently involves venous vessels. Inherited thrombophilia consists of congenital conditions, as methylenetetrahydrofolate reductase polymorphism, Factor V Leiden and prothrombin gene mutations, natural anticoagulant deficiencies, high level of factor VIII, or dysfibrinogenemia. These congenital disorders can be responsible for venous thromboembolism, particularly deep venous thrombosis, pulmonary embolism, and, less frequently, mesenteric veins thrombosis, kidneys’ veins thrombosis or retinal vein occlusion. Acquired thrombophilia can be associated both with venous and arterial thrombosis and may be caused by antiphospholipid syndrome, aging, some malignancies, oral contraceptive use, heparin-induced thrombocytopenia, and human immunodeficiency virus. Antiplatelets’ drugs are employed in arterial thrombosis, while, heparins/oral vitamin K antagonists are indicated for acute and long-term anticoagulation. However, new oral anticoagulants can be usefully used for venous thromboembolic events. Recent experiences demonstrated that their employment is useful in some thrombophilias only, whereas other investigations are requested to evaluate their use in all hypercoagulable disorders.

scholarly journals Massive Pulmonary Embolism Associated With Factor V Leiden, Prothrombin, and Methylenetetrahydrofolate Reductase Gene Mutations in a Young Patient on Oral Contraceptive Pills: A Case Report

2009 ◽  
Vol 16 (5) ◽  
pp. 594-598 ◽  
Author(s):  
Khalil M. Charafeddine ◽  
Rami A. Mahfouz ◽  
Georges Y. Ibrahim ◽  
Ali T. Taher ◽  
Jamal J. Hoballah ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Oral Contraceptive ◽  
Methylenetetrahydrofolate Reductase ◽  
Oral Anticoagulants ◽  
Gene Mutations ◽  
Factor V Leiden ◽  
Massive Pulmonary Embolism ◽  
Factor V ◽  
Oral Contraceptive Pills ◽  
Contraceptive Pills

Factor V Leiden (Factor V G1691A), prothrombin gene mutation G20210A, and homozygous C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene are known to predispose venous thromboembolism (VTE). We present herein a rare case of a young woman heterozygous for these mutations and taking oral contraceptive pills for less than 2 months, diagnosed to have massive deep venous thrombosis and bilateral pulmonary embolism. The patient was managed for 10 days in the hospital and discharged home on oral anticoagulants. This case suggests that screening for these factors in people with family history of thrombosis and in relatives of patients with these mutations is highly recommended to prevent fatal consequences. In addition, a new guideline for treatment and prophylaxis with anticoagulant for these patients and others who are at risk of developing VTE (American College of Chest Physicians [ACCP] guidelines-Chest 2008) has been published recently. Our recommendation is to promote for the internationally published algorithms through their application, where necessary, to prevent any future thrombotic morbidity or mortality incidents.

scholarly journals DIRECT ORAL ANTICOAGULANTS IN PATIENTS AFFECTED BY MAJOR CONGENITAL THROMBOPHILIA

2019 ◽  
Vol 11 (1) ◽  
pp. e2019044 ◽  
Author(s):  
Alessandra Serrao ◽  
Benedetta Lucani ◽  
Davide Mansour ◽  
Antonietta Ferretti ◽  
Erminia Baldacci ◽  
...  
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Factor V Leiden ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Factor V ◽  
Thrombotic Risk ◽  
Factor Ii

Introduction: Thrombophilia is a condition that predisposes to a higher incidence of venous thromboembolisms (VTE), some also in atypical sites. Direct oral anticoagulants (DOACs) have proven to be effective in the treatment of deep vein thrombosis (DVT). However, their use can be sometimes challenging in particular settings of patients such as those with major thrombophilia - antithrombin, protein C and protein S deficiency, homozygous mutation of Factor V Leiden, homozygous mutation of Factor II G20210A, combined heterozygous mutation of factor V Leiden and Factor II G20210A – carrying a high thrombotic risk. Patients and methods: At our Center, 45 patients with major thrombophilia were treated with DOACs: 33 after an initial treatment with vitamin K antagonists (VKA) and 12 as first line therapy for VTE. The median follow-up of DOACs treatment was 29 months. Conclusions: No patient presented hemorrhagic or thrombotic complications during DOAC therapy. DOACs have proven to be effective and safe in this real-life series of patients with major thrombophilia.      

scholarly journals Noncanonical Effects of Oral Thrombin and Factor Xa Inhibitors in Platelet Activation and Arterial Thrombosis

2020 ◽  
Author(s):  
Amin Polzin ◽  
Lisa Dannenberg ◽  
Manuela Thienel ◽  
Martin Orban ◽  
Georg Wolff ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Platelet Activity ◽  
Vein Thrombosis

AbstractNonvitamin K oral anticoagulants (NOACs) or direct oral anticoagulants comprise inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban) or factor IIa (dabigatran). Both classes efficiently interfere with the final or penultimate step of the coagulation cascade and showed superior net clinical benefit compared with vitamin K antagonists for prevention of thromboembolic events in patients with AF and for prevention and therapy of deep vein thrombosis and pulmonary embolism. None the less, accumulating data suggested, that there may be differences regarding the frequency of atherothrombotic cardiovascular events between NOACs. Thus, the optimal individualized NOAC for each patient remains a matter of debate. Against this background, some basic and translational analyses emphasized NOAC effects that impact on platelet activity and arterial thrombus formation beyond inhibition of plasmatic coagulation. In this review, we will provide an overview of the available clinical and translational evidence for so-called noncanonical NOAC effects on platelet activation and arterial thrombosis.

Danger of false negative (exclusion) or false positive (diagnosis) for ‘congenital thrombophilia’ in the age of anticoagulants

2019 ◽  
Vol 57 (6) ◽  
pp. 873-882 ◽  
Author(s):  
Emmanuel J. Favaloro
Keyword(s):  
False Positive ◽  
Ex Vivo ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
False Negative ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Increased Risk

Abstract Background Most guidelines and experts recommend against performance of thrombophilia testing in general, and specifically against testing patients on pharmacological anticoagulants, due to substantially increased risk of false positive identification. For example, vitamin K antagonist (VKA) therapy affects protein C (PC) and protein S (PS), as well as some clotting assays (e.g. as used to investigate activated PC resistance [APCR]). Although heparin may also affect clotting assays, most commercial methods contain neutralisers to make them ‘insensitive’ to therapeutic levels. Direct oral anticoagulants (DOACs) also affect a wide variety of thrombophilia assays, although most reported data has employed artificial in vitro spiked samples. Methods In the current report, data from our facility for the past 2.5 years has been assessed for all ‘congenital thrombophilia’ related tests, as evaluated against patient anticoagulant status. We processed 10,571 ‘thrombophilia’ related test requests, including antithrombin (AT; n=3470), PC (n=3569), PS (n=3585), APCR (n=2359), factor V Leiden (FVL; n=2659), and prothrombin gene mutation (PGM; n=2103). Results As expected, VKA therapy affected PC and PS, and despite manufacturer claims, also APCR. Most assays, as suggested by manufacturers, were largely resistant to heparin therapy. DOACs’ use was associated with falsely low APCR ratios (i.e. FVL-like effect) and somewhat unexpectedly, anti-Xa agents apixaban and rivaroxaban were also associated with lower AT and higher PS values. Conclusions It is concluded that ex-vivo data appears to confirm the potential for both false positive and false negative ‘thrombophilia’ events in patients on anticoagulant (including DOAC) treatment.

scholarly journals Direct oral anticoagulants (DOAC) for prevention of recurrent arterial or venous thromboembolic events (ATE/VTE) in myeloproliferative neoplasms

2020 ◽  
Author(s):  
Karlo Huenerbein ◽  
Parvis Sadjadian ◽  
Tatjana Becker ◽  
Vera Kolatzki ◽  
Eva Deventer ◽  
...  
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Thromboembolic Events ◽  
Number Of Patients ◽  
Increased Risk ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic

AbstractIn patients with BCR-ABL-negative myeloproliferative neoplasms (MPN), arterial or venous thromboembolic events (ATE/VTE) are a major burden. In order to control these complications, vitamin K antagonists (VKA) are widely used. There is no robust evidence supporting the use of direct oral anticoagulants (DOAC) in MPN patients. We therefore compared the efficacy and safety of both anticoagulants in 71 cases from a cohort of 782 MPN patients. Seventy-one of 782 MPN patients (9.1%) had ATE/VTE with nine ATE (12.7%) and 62 VTE (87.3%). Forty-five of 71 ATE/VTE (63.4%) were treated with VKA and 26 (36.6%) with DOAC. The duration of anticoagulation therapy (p = 0.984), the number of patients receiving additional aspirin (p = 1.0), and the proportion of patients receiving cytoreductive therapy (p = 0.807) did not differ significantly between the VKA and DOAC groups. During anticoagulation therapy, significantly more relapses occurred under VKA (n = 16) compared to DOAC treatment (n = 0, p = 0.0003). However, during the entire observation period of median 3.2 years (0.1–20.4), ATE/VTE relapse-free survival (p = 0.2) did not differ significantly between the two anticoagulants. For all bleeding events (p = 0.516) or major bleeding (p = 1.0), no significant differences were observed between VKA and DOAC. In our experience, the use of DOAC was as effective and safe as VKA, possibly even potentially beneficial with a lower number of recurrences and no increased risk for bleedings. However, further and larger studies are required before DOAC can be routinely used in MPN patients.

scholarly journals Comparative Analysis of Direct Oral Anticoagulants and Vitamin K Antagonists in Antiphospholipid Syndrome Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2135-2135
Author(s):  
Maha AT Elsebaie ◽  
Zoe Alexandra Wickham ◽  
Stephanie Debragga ◽  
Juan Li ◽  
Manila Gaddh
Keyword(s):  
Venous Thrombosis ◽  
Vitamin K ◽  
Patient Population ◽  
Arterial Thrombosis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
P Value ◽  
Recurrent Thrombosis ◽  
Vascular Thrombosis

Abstract Introduction Antiphospholipid syndrome (APS) is a major acquired thrombophilia in which vascular thrombosis (venous or arterial) and/or pregnancy losses occur. Despite the use of vitamin K antagonists (VKAs), the annual risk for recurrent thrombosis among APS patients ranges between 2-5% (Crowther et al. NEJM 2003). The evidence for direct oral anticoagulants (DOAC) use in APS patients is still lacking. Therefore, we conducted a retrospective cohort study to explore the efficacy and safety of DOACs vs. VKAs in this patient population. Methods The electronic medical records at Emory University Hospitals were queried for patients ≥18 years old with APS diagnosis, according to the Sydney international census criteria (Miyakis et al. JTH 2006). Included patients must have experienced acute thrombosis between 01/01/2012 and 12/31/2018 and started anticoagulation therapy with DOACs or VKAs. We reviewed patient charts from the index thrombosis date till the end of the study period (12/31/2019). Clinical endpoints were: recurrent vascular thrombosis, clinically relevant bleeding (CRB), which included major and non-major bleeding events as defined by the ISTH society, and composite outcome of thrombosis and bleeding (Kaatz et al. JTH 2015). Patients presenting with pregnancy complications only during the identification period were excluded. Results A total of 153 patients with confirmed APS diagnosis were included in the study. Mean age was 51 (range, 18-79 y.o.). 94 patients (61.4%) were females and 80 patients (52.3%) were white. The most common sites of index thrombosis were pulmonary embolism (N=62, 40.5%), proximal lower extremity deep venous thrombosis (N=49, 32%), and stroke/TIA (N=29, 19%). The majority of patients had a single positive antiphospholipid antibody (aPL) (N=83, 54.2%). 35 (22.9%) had double positive and 24 (15.7%) had triple positive disease. Following index thrombosis, 75 patients started DOAC, whereas 72 started warfarin. Six patients started subcutaneous heparin for a short duration before starting an oral form of anticoagulation. Of those on DOAC, 50 started rivaroxaban while 22 started apixaban. After a mean of 19.8 months (range, 0.68 - 69.8) from the index thrombosis, 62 patients (40.5%) switched to a different class of anticoagulation. The most common reasons for switching therapy were recurrent thrombosis (N=16, 25.8%), followed by patient preference (N=13, 20.9%), side effects including bleeding (N=9, 14.5%), and other reasons, such as confirmed APS diagnosis or renal insufficiency (N=12, 19.3%). We found no statistically significant differences in risk of recurrent thrombosis or CRB events among patients who were started on DOAC vs. VKAs (Figure). The number of arterial thrombosis events was minimal and similar in both treatment groups: N=3 in DOAC group vs. N=5 in the VKA group. Patients treated with rivaroxaban had a similar risk of recurrent thrombosis (log rank, p-value=0.629) and CRB events (log rank, p-value=0.631) compared to those treated with apixaban. The risk of recurrent thrombosis was not affected by degree of aPL positivity or previous history of arterial thrombosis in multivariate models (HR 0.791, 95% CI 0.357 - 1.751) (Table). Discussion and Conclusion Our experience suggests that DOACs -particularly rivaroxaban / apixaban- could be an effective and safe alternative to warfarin in APS patients. We realize that patients with triple aPL positivity constitute a special population with a substantial risk of arterial and venous thrombosis. Given the retrospective nature of our data and that triple aPL positive patients compromised only 15% of our patient population, we conclude that the use of DOACs in these high risk patients remains uncertain. Prospective and large-scale multicenter studies are highly encouraged to explore DOAC use in APS patients with various background profiles. We build on our current experience by starting a multicenter collaboration that will facilitate meaningful subgroup comparisons in APS patients. Figure 1 Figure 1. Disclosures Gaddh: Agios: Consultancy, Other: Advisory board.

Direct Oral Anticoagulants in Select Patients With Hypercoagulable Disorders

2020 ◽  
pp. 106002802096855
Author(s):  
Sara M. Valanejad ◽  
Kyle A. Davis
Keyword(s):  
Antiphospholipid Syndrome ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor V Leiden ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Protein C Deficiency ◽  
Antithrombin Deficiency ◽  
Safety And Efficacy ◽  
Hereditary Thrombophilia

Objective: To summarize the literature assessing the safety and efficacy of direct oral anticoagulants (DOACs) for the acute treatment and secondary prevention of venous thromboembolism (VTE) in select patients with hypercoagulable disorders. Data Sources: An electronic PubMed literature search was conducted from January 2010 to July 2020 using the following keywords: DOAC, rivaroxaban, apixaban, dabigatran, edoxaban, thrombophilia, cancer, antiphospholipid syndrome, protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden, prothrombin G20210A gene mutation, congenital thrombophilia, hypercoagulable, hereditary thrombophilia, acquired thrombophilia. Study Selection and Data Extraction: Articles were included if they reported clinical outcomes associated with cancer-associated VTE, antiphospholipid syndrome (APS), and other hereditary thrombophilias. Data Synthesis: The safety and efficacy of using a DOAC is highly dependent on the type of hypercoagulable disease state. Current trials support the use of edoxaban, rivaroxaban, and apixaban for the treatment of cancer-associated thrombosis (CAT), with apixaban being preferred because of lower bleeding rates compared with standard of care. The use of DOACs, especially rivaroxaban, have been associated with worse outcomes in patients with APS, whereas data on DOAC use in hereditary thrombophilia remains scarce and limited to low-risk patients. Relevance to Patient Care and Clinical Practice: This review evaluates the literature assessing the safety and efficacy of DOACs in patients with various hypercoagulable disorders. Conclusions: The current body of evidence supports the use of select DOACs for the treatment of CAT. In contrast, DOAC use in patients with APS and hereditary thrombophilia should be avoided at this time.

scholarly journals Treatment and secondary prophylaxis of venous thromboembolism with direct oral anticoagulants in patients with severe hereditary thrombophilia

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Pasquale Madonna ◽  
Anna Guida ◽  
Maria Gabriella Coppola ◽  
Paolo Tirelli ◽  
Ernesto Grasso
Keyword(s):  
Venous Thromboembolism ◽  
Early Onset ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor V Leiden ◽  
Secondary Prophylaxis ◽  
Factor V ◽  
Efficacy And Safety ◽  
Hereditary Thrombophilia ◽  
At Iii

Deficiency of protein C (PC), protein S (PS), antithrombin III (AT III), and homozygosity or combined heterozygosity for Factor V Leiden (FVL) and Factor II (FII) 20210A mutation represent severe hereditary thrombophilia (SHT) and are associated with a higher risk of early-onset venous thromboembolism (VTE). In literature, few papers have described the efficacy and safety of therapy with direct oral anticoagulants (DOACs) in VTE occurring in patients with SHT. In our setting, we identified 8 patients who have suffered from early-onset VTE and underwent therapy with DOACs (6 rivaroxaban, 2 apixaban). Among them, 2 AT III deficiency, 2 PC deficiency, 3 PS deficiency, 1 combined heterozygosity for FVL, and FII 20210A were detected. During the follow-up, neither recurrences of VTE nor hemorrhagic episodes were observed. This report describes the efficacy and safety of therapy with anti-Xa in the treatment and secondary prophylaxis of VTE in patients with SHT.

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