Heparin induced thrombocytopenia

2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas

SummaryHeparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

2020 ◽  
Vol 120 (07) ◽  
pp. 1128-1136 ◽  
Author(s):  
Michela Giustozzi ◽  
Giancarlo Agnelli ◽  
Jorge del Toro-Cervera ◽  
Frederikus A. Klok ◽  
Rachel P. Rosovsky ◽  
...  

Abstract Background International guidelines have endorsed the use of edoxaban or rivaroxaban as an alternative to low-molecular-weight heparin (LMWH) for the treatment of acute venous thromboembolism (VTE) in cancer patients. Recently, a large randomized controlled trial of apixaban versus dalteparin in patients with cancer was completed. We performed an updated meta-analysis to assess the efficacy and safety of direct oral anticoagulants (DOACs) versus LMWH in patients with cancer-associated VTE. Methods MEDLINE, EMBASE, and CENTRAL (Cochrane Controlled Trials Registry) were systematically searched up to March 30, 2020 for randomized controlled trials comparing DOACs versus LMWH for the treatment of VTE in patients with cancer. The two coprimary outcomes were recurrent VTE and major bleeding at 6 months. Data were pooled by the Mantel–Haenszel method and compared by relative risk ratios (RRs) and 95% confidence intervals (CIs). Results Four randomized controlled studies (2,894 patients) comparing apixaban, edoxaban, or rivaroxaban with dalteparin were included in the meta-analysis. Recurrent VTE occurred in 75 of 1,446 patients (5.2%) treated with oral factor Xa inhibitors and in 119 of 1,448 patients (8.2%) treated with LMWH (RR 0.62; 95% CI 0.43–0.91; I 2, 30%). Major bleeding occurred in 62 (4.3%) and 48 (3.3%) patients receiving oral factor Xa inhibitors or LMWH, respectively (RR 1.31; 95% CI 0.83–2.08; I 2, 23%). Conclusion In patients with cancer-associated VTE, oral factor Xa inhibitors reduced the risk of recurrent VTE without a significantly higher likelihood of major bleeding at 6 months compared with LMWH.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23156-e23156
Author(s):  
Harry E Fuentes ◽  
Robert McBane ◽  
Waldemar Wysokinski ◽  
Alfonso Javier Tafur ◽  
Charles L. Loprinzi ◽  
...  

e23156 Background: A direct meta-analysis was performed to explore the efficacy and safety of direct oral factor Xa inhibitors with dalteparin in patients with cancer associated acute venous thromboembolism (VTE). Also, the comparative efficacy and safety of apixaban, rivaroxaban, and edoxaban was assessed with a network meta-analysis. Methods: MEDLINE, CENTRAL, and EMBASE were searched for trials comparing direct oral anticoagulants (DOACs) to dalteparin for the management of cancer associated acute VTE. A network meta-analysis using both frequentist and Bayesian methods was performed to analyze VTE recurrence, major and clinically relevant non-major bleeding (CRNMB). Results: Three randomized control trials, at low risk of bias, enrolled 1,739 patients with cancer associated VTE. Direct comparison showed a lower rate of VTE recurrence in DOAC compared to dalteparin groups (odds Ratio [OR]:0.48, 95% Confidence interval [CI]:0.24-0.96; I2:46%). Indirect comparison suggested that apixaban had greater reduction in VTE recurrence compared to dalteparin (OR: 0.10; 95% CI: 0.01–0.82), but not rivaroxaban or edoxaban. Apixaban also had the highest probability of being ranked most effective. By direct comparisons, there was an increased likelihood of major bleeding in the DOAC group compared to dalteparin (OR: 1.70; 95% CI: 1.04–2.78). CRNMB did not differ. Indirect estimates were imprecise. Subgroup analyses in gastrointestinal cancers suggested that dalteparin may have the lowest risk of bleeding whereas estimates in urothelial cancer were imprecise. Conclusions: DOACs appear to lower the risk of VTE recurrence compared to daltaparin while increasing major bleeding. Apixaban may be associated with the lowest risk of VTE recurrence compared to the other DOACs.


Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 612-619 ◽  
Author(s):  
Andrew W. Shih ◽  
Mark A. Crowther

Abstract Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered. Laboratory testing has limited utility in the acute management of bleeding; thrombin time and activated partial thromboplastin time may be useful for excluding clinically relevant levels of dabigatran. Prothrombin time is potentially useful for rivaroxaban and edoxaban, but calibrated anti-Xa assays are optimal for determining clinically relevant levels of factor Xa inhibitors. Because specific reversal agents are not widely available, supportive care and interventions for local hemostasis remain the cornerstones of therapy in the patient with DOAC-associated bleeding. Nonspecific reversal agents should be considered only in the event of severe bleeding because their efficacy is unknown, and they are associated with risk of thrombosis. Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors). A universal reversal agent (ciraparantag) for many anticoagulants, including the DOACs, shows promise in results from phase 1 and 2 studies.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Tania Ahuja ◽  
Kelly Sessa ◽  
Cristian Merchan ◽  
John Papadopoulos ◽  
David Green

Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm ( p = 0.498 ). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.


Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Adam Cuker ◽  
Deborah Siegal

Abstract Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.


Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Adam Cuker ◽  
Deborah Siegal

Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.


Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 129-133
Author(s):  
Karen A. Moser ◽  
Kristi J. Smock

Abstract Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.


2021 ◽  
Vol 13 (4) ◽  
Author(s):  
Thilina Gunawardena

Thrombin inhibitors and direct factor Xa inhibitors represent a major breakthrough in the field of anticoagulation pharmacotherapy. These novel agents have replaced warfarin as the oral anticoagulant of choice in certain indications, as they possess equal or superior efficacy and better safety profiles. They have a quick onset of action, predictable pharmacokinetic properties and minimal drug and food interactions. So they do not require frequent blood monitoring and dose adjustments as with warfarin. Considering all the advantages, there seems to be a rapid increase in the number of patients who are started on these novel anticoagulants. In this review, we highlight the pharmacology of these direct oral anticoagulants and the evidence-based indications for their use. We aim to provide a clinical overview for the non-specialist who may be called upon to manage a patient who is currently on one of these novel anticoagulants.


Author(s):  
Н.А. Воробьева ◽  
Е.Ю. Мельничук ◽  
А.И. Воробьева

Введение. Для пролонгированной профилактики тромбозов после операций, при фибрилляции предсердий, терапии тромбозов глубоких вен и/или тромбоэмболии легочной артерии широко используются прямые пероральные антикоагулянтные препараты (ПОАК). Считается, что ПОАК лишены недостатков, присущих антагонистам витамина К (АВК) и обладают предсказуемыми фармакокинетическими и фармакодинамическими эффектами и следовательно не требуют рутинного лабораторного контроля для коррекции и подбора дозы препарата. Отдельного внимания, на наш взгляд, заслуживает вопрос приверженности к терапии ПОАК. Цель исследования: оценка приверженности к терапии прямыми пероральными ингибиторами фактора Ха путем определения концентрации ПОАК в плазме крови пациентов. Материалы и методы. Выполнено проспективное клинико-лабораторное исследование, включены 50 пациентов с продленной антитромботической терапией ПОАК. Для оценки приверженности к терапии проведено определение пиковой концентрации прямых ингибиторов фактора Ха хромогенным методом. Результаты. До 10% пациентов в реальной клинической практике не принимали назначенную антитромботическую терапию и скрыли этот факт от врача. Таким образом, с помощью определения концентрации прямых ингибиторов фактора Ха хромогенным методом можно выявить отсутствие приверженности к терапии ПОАК. Заключение. Для определения приверженности к антикоагулянтной терапии прямыми ингибиторами фактора Ха возможно использование метода оценки концентрации ПОАК в плазме крови, что позволяет оценить приверженность пациента к данному виду терапии и, как следствие, эффективность и безопасность продленной антитромботической терапии. Background. For prolonged prophylaxis of thrombosis after surgery, of atrial fibrillation, therapy of deep vein thrombosis and/or pulmonary embolism, direct oral anticoagulants (DOACs) are widely used. It is believed that DOACs lack the deficiencies inherent in antagonists of vitamin K (AVK), have predictable pharmacokinetic and pharmacodynamic effects, and therefore do notrequire routine laboratory monitoring to adjust and select the dose of the drug. We pay special attention to the issue of adherence to DOACs therapy. Objectives: to assess compliance to therapy with direct oral factor Xa inhibitors by determining plasma DOACs concentration. Patients/Methods. A prospective clinical and laboratory study was performed, 50 patients with prolonged antithrombotic therapy by DOACs were included. To assess compliance to therapy, the peak concentration of direct factor Xa inhibitors was determined by the chromogenic method. Results. In real clinical practice up to 10% of patients did not take the prescribed antithrombotic therapy and hid this fact from the doctor. Thus, by determining the concentration of direct factor Xa inhibitors by the chromogenic method, it is possible to identify a lack of compliance to therapy. Conclusions. Determination of plasma DOACs concentration allows assessing the patient’s adherence to anticoagulant therapy with direct factor Xa inhibitors and the efficacy and safety of prolonged antithrombotic therapy.


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