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 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.

Spectrophotometric Assays of Prothrombin in Plasma of Patients Using Oral Anticoagulants

1979 ◽  
Vol 42 (04) ◽  
pp. 1296-1305 ◽  
Author(s):  
R M Bertina ◽  
W van der Marel-van Nieuwkoop ◽  
E A Loeliger
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Factor V ◽  
Anticoagulant Treatment ◽  
Factor Ii ◽  
K Deficiency

SummaryTwo spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of “subcarboxylation” of prothrombin (oral anticoagulation, vitamin K deficiency).For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio.It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

scholarly journals A Giant Right Heart Thrombus-in-Transit: The Challenge of Anticoagulation in Factor V Leiden Thrombophilia

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Andrew Chu ◽  
Thu Thu Aung ◽  
Minni Shreya Arumugam ◽  
Mauricio Danckers ◽  
Mohi Mitiek ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Single Point ◽  
Factor V Leiden ◽  
Single Point Mutation ◽  
Homozygous Mutation ◽  
Factor V ◽  
Right Heart ◽  
Blood Clots ◽  
History Of ◽  
In Transit

Factor V Leiden (FVL) is an autosomal dominant condition resulting in thrombophilia. Factor V normally acts as a cofactor for prothrombinase, helping cleave prothrombin to thrombin. A single point mutation in it disrupts factor V, making it unreceptive to protein C and increasing the risk of thrombosis. FVL mutation associated with right heart thrombus is a rare entity. Right heart thrombus or right heart thrombus-in-transit is associated with high mortality. We present a 51-year-old male with a past medical history of FVL homozygous mutation and recurrent blood clots, who has failed multiple different oral anticoagulants. He presented to the hospital with symptoms of shortness of breath and subsequently found to have a giant right heart thrombus. He was treated with surgical embolectomy. This case underscores the challenges faced by patients with FVL and recurrent blood clots.

scholarly journals Direct oral anticoagulants in patients with antiphospholipid syndrome: a cohort study

Lupus ◽  
2019 ◽  
Vol 29 (1) ◽  
pp. 37-44 ◽  
Author(s):  
K Malec ◽  
E Broniatowska ◽  
A Undas
Keyword(s):  
Cohort Study ◽  
Antiphospholipid Syndrome ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Double Positive ◽  
Increased Risk ◽  
Long Term Follow Up

Objectives Despite controversies, direct oral anticoagulants (DOACs) are increasingly used in antiphospholipid syndrome (APS). We investigated the safety and efficacy of DOACs versus vitamin K antagonists (VKAs) in real-life consecutive APS patients. Patients and methods In a cohort study of 176 APS patients, which included 82 subjects who preferred DOACs or had unstable anticoagulation with VKAs, we recorded venous thromboembolism (VTE), cerebrovascular ischemic events or myocardial infarction, along with major bleeding or clinically relevant non-major bleeding (CRNMB). Results APS patients were followed for a median time of 51 (interquartile range 43–63) months. Patients on DOACs and those on VKAs were similar with regard to baseline characteristics. APS patients treated with DOACs had increased risk of recurrent thromboembolic events and recurrent VTE alone compared with those on VKAs (hazard ratio (HR) = 3.98, 95% confidence interval (CI): 1.54–10.28, p = 0.004 and HR = 3.69, 95% CI: 1.27–10.68, p = 0.016, respectively) with no differences between rivaroxaban and apixaban or single- or double-positive and triple-positive APS. Thromboembolism on DOACs was associated with older age (median 52 versus 42 years, p = 0.008) and higher global APS score (median 13 versus 8.5, p = 0.013). Patients on DOACs had increased risk of major bleeding or CRNMB (HR = 3.63, 95% CI: 1.53–8.63, p = 0.003), but rates of gastrointestinal bleeds (HR = 3.36, 95% CI: 0.70–16.16, p = 0.13) and major bleeds or CRNMB other than heavy menstrual bleeding (HR = 2.45, 95% CI: 0.62–9.69, p = 0.2) were similar in both treatment groups. Conclusion During long-term follow-up of real-life APS patients, DOACs are less effective and less safe as VKAs in the prevention of thromboembolism.

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 Primary Thromboprophylaxis in Patients with Malignancies: Daily Practice Recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO), the Society of Thrombosis and Hemostasis Research (GTH), and the Austrian Society of Hematology and Oncology (ÖGHO)

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2905
Author(s):  
Martin Kirschner ◽  
Nicole do Ó Hartmann ◽  
Stefani Parmentier ◽  
Christina Hart ◽  
Larissa Henze ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Working Party ◽  
Major Surgery ◽  
Thrombotic Risk ◽  
Indwelling Catheters ◽  
Increased Risk

Patients with cancer, both hematologic and solid malignancies, are at increased risk for thrombosis and thromboembolism. In addition to general risk factors such as immobility and major surgery, shared by non-cancer patients, cancer patients are exposed to specific thrombotic risk factors. These include, among other factors, cancer-induced hypercoagulation, and chemotherapy-mediated endothelial dysfunction as well as tumor-cell-derived microparticles. After an episode of thrombosis in a cancer patient, secondary thromboprophylaxis to prevent recurrent thromboembolism has long been established and is typically continued as long as the cancer is active or actively treated. On the other hand, primary prophylaxis, even though firmly established in hospitalized cancer patients, has only recently been studied in ambulatory patients. This recent change is mostly due to the emergence of direct oral anticoagulants (DOACs). DOACs have a shorter half-life than vitamin K antagonists (VKA), and they overcome the need for parenteral application, the latter of which is associated with low-molecular-weight heparins (LMWH) and can be difficult for the patient to endure in the long term. Here, first, we discuss the clinical trials of primary thromboprophylaxis in the population of cancer patients in general, including the use of VKA, LMWH, and DOACs, and the potential drug interactions with pre-existing medications that need to be taken into account. Second, we focus on special situations in cancer patients where primary prophylactic anticoagulation should be considered, including myeloma, major surgery, indwelling catheters, or immobilization, concomitant diseases such as renal insufficiency, liver disease, or thrombophilia, as well as situations with a high bleeding risk, particularly thrombocytopenia, and specific drugs that may require primary thromboprophylaxis. We provide a novel algorithm intended to aid specialists but also family practitioners and nurses who care for cancer patients in the decision process of primary thromboprophylaxis in the individual patient.

Major bleeding with vitamin K antagonists or direct oral anticoagulants in real-life

2017 ◽  
Vol 227 ◽  
pp. 261-266 ◽  
Author(s):  
Cecilia Becattini ◽  
Laura Franco ◽  
Jan Beyer-Westendorf ◽  
Luca Masotti ◽  
Cinzia Nitti ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life

Venous Thromboembolism and Renal Impairment: Insights from the SWIss Venous ThromboEmbolism Registry (SWIVTER)

2019 ◽  
Vol 45 (08) ◽  
pp. 851-858 ◽  
Author(s):  
David Spirk ◽  
Tim Sebastian ◽  
Martin Banyai ◽  
Jürg H. Beer ◽  
Lucia Mazzolai ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Renal Impairment ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Similar Rate ◽  
Increased Risk

AbstractRenal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41–3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57–2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41–2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14–0.94; p = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17–2.00; p = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI.

Direct oral anticoagulants (DOAC) – Management of emergency situations

2017 ◽  
Vol 37 (04) ◽  
pp. 257-266 ◽  
Author(s):  
Edelgard Lindhoff-Last
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Real Life ◽  
Bleeding Complications ◽  
Severe Bleeding ◽  
Emergency Operations ◽  
Reversal Agents ◽  
Life Threatening

SummaryThe worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on anti-platelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last intake of the DOAC and its residual concentration are also relevant. The site of bleeding should be immediately localized, anticoagulation should be interrupted, and local measures to stop bleeding should be taken. In life-threatening bleeding or emergency operations immediate reversal of the antithrombotic effect may be indicated. If relevant residual DOAC-concentrations are expected and surgery cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific antidote should be given. While idarucizumab, the specific antidote for dabigatran, has been recently approved for clinical use, the recombinant factor X protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation factor Xa, and ciraparantag, a universal antidote, are not available. Future cohort studies are necessary to assess the efficacy and safety of specific and unspecific reversal agents in “real-life” conditions. This was the rationale for introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non-interventional registry, which will evaluate the effects of specific and unspecific reversal agents in patients with life-threatening bleeding or emergency operations either treated with DOACs or vitamin K antagonists.

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