Management of the multiple phases of heparin-induced thrombocytopenia

2016 ◽  
Vol 116 (11) ◽  
pp. 835-842 ◽  
Author(s):  
Adam Cuker
Keyword(s):  
Platelet Count ◽  
Key Management ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vena Cava ◽  
Hepatic Function ◽  
Heparin Induced Thrombocytopenia ◽  
Increased Risk ◽  
Count Recovery

SummaryThe clinical course of heparin-induced thrombocytopenia (HIT) may be separated into five sequential phases: 1. suspected HIT, 2. acute HIT, 3. subacute HIT A, 4. subacute HIT B, and 5. remote HIT. Each phase confronts the clinician with a unique set of management questions. In this review, the phases of HIT are defined and key management questions associated with each phase are discussed. Among patients with Suspected HIT, I use the 4Ts score to determine which patients have a sufficiently high probability of HIT to justify discontinuation of heparin and initiation of a non-heparin parenteral anticoagulant. An algorithm for selecting an appropriate non-heparin anticoagulant based on the patient’s clinical stability, renal and hepatic function, drug availability, and physician comfort is provided. In patients with Acute HIT, I generally avoid prophylactic platelet transfusion and inferior vena cava filter insertion because of a potential increased risk of thrombosis. I perform 4-limb screening compression ultrasonography. In patients with symptomatic thromboembolism or asymptomatic proximal deep-vein thrombosis, I treat with anticoagulation for three months. In patients without thrombosis, I discontinue anticoagulation upon platelet count recovery. I do not transition patients to an oral anticoagulant until platelet count recovery (i. e. Subacute HIT A). I increasingly choose direct oral anticoagulants over vitamin K antagonists in this setting because of their greater convenience and safety. In Subacute HIT B and Remote HIT, I use heparin for cardiovascular surgery, whereas I use bivalirudin in patients with Acute HIT and Subacute HIT A in whom surgery cannot be delayed.

Low-Molecular-Weight Heparin in Cancer Patients: Overview and Indications

2019 ◽  
Vol 39 (01) ◽  
pp. 067-075 ◽  
Author(s):  
Minna Voigtlaender ◽  
Florian Langer
Keyword(s):  
Molecular Weight ◽  
Cancer Patients ◽  
Anticancer Agents ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Low Molecular Weight ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

AbstractAlthough venous thromboembolism (VTE) is a well-known cause of death in patients with cancer, both its treatment and prevention remain a challenge in daily practice. Direct oral anticoagulants have emerged as safe and efficacious alternatives to vitamin K antagonists in the general population, and recent clinical trials also support their use in select patients with cancer-associated VTE. Despite this, low-molecular-weight heparins (LMWHs), a comparatively ancient class of antithrombotic drugs, remain the anticoagulants of choice in many indications relevant to modern haematology and oncology. In addition to the treatment of established VTE, these indications include VTE prophylaxis in surgical or acutely ill, hospitalized medical cancer patients as well as the prevention of VTE in high-risk patients undergoing ambulatory chemotherapy. In a constantly changing landscape of approved anticancer agents, this review article summarizes pivotal clinical trial data and guideline recommendations regarding the use of LMWH in haematological and oncological patients, who constitute a highly vulnerable patient population due to their increased risk for both bleeding and VTE recurrence.

Direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism

Phlebologie ◽  
2017 ◽  
Vol 46 (06) ◽  
pp. 340-351
Author(s):  
M. Voigtlaender ◽  
F. Langer
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Phase ◽  
Standard Of Care ◽  
Longterm Treatment ◽  
Increased Risk ◽  
Direct Head

SummaryCancer patients with venous thromboembolism (VTE) are at increased risk for both bleeding and VTE recurrence. Anticoagulation with low-molecular-weight heparin (LMWH) is the standard of care during the initial and longterm treatment phase (i.e. during the first 3–6 months of therapy) based on its overall beneficial safety and efficacy profile compared to vitamin K antagonists (VKAs). The direct oral anticoagulants (DOACs) rivaroxaban, apixaban, edoxaban, and dabigatran are approved for the treatment of acute VTE, and the combined six phase-3 trials have included > 1 500 patients with active cancer, as defined by variable selection criteria. Subgroup analyses of these patients, either pooled or separately reported, suggest that DOACs could be a safe and efficacious alternative to VKA therapy for the treatment of cancer-associated VTE. However, the populations of cancer patients included in the DOAC and LMWH trials are not comparable with regard to mortality and VTE risk, and no specific data from direct head-to-head comparisons of DOACs with LMWHs are currently available. The use of DOACs for the management of VTE in cancer is thus not recommended by clinical practice guidelines.

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.

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 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.

scholarly journals Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 344-344 ◽  
Author(s):  
Stephan Glund ◽  
Joachim Stangier ◽  
Michael Schmohl ◽  
Viktoria Moschetti ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulant Effect ◽  
Thrombin Time ◽  
Double Blind ◽  
Male And Female ◽  
Increased Risk ◽  
Pharmacologically Active

Abstract Introduction Oral anticoagulation is an effective therapy to prevent and treat thromboembolic events. So far, Vitamin K antagonists have been the main drug of choice. Recently, the advent of the direct oral anticoagulants (DOAC) has changed medical practice significantly; nevertheless all anticoagulants are associated with an increased risk of bleeding. Bleeding management can be achieved through established therapies; however specific antidotes are not yet available for these agents to further facilitate patient management in cases needed. Previously the dabigatran antidote (idarucizumab) has demonstrated immediate, complete and sustained reversal of dabigatran induced anti-coagulation in healthy male volunteers. In the present study it was determined whether and to what extent doses of up to 5 g idarucizumab would reverse the anticoagulant effects of dabigatran in male and female healthy mid-aged, elderly and renally impaired volunteers. In addition, it was tested whether oral intake of dabigatran etexilate 24 hrs after idarucizumab treatment could restore dabigatran related anticoagulation. It was further tested if a second administration of idarucizumab 2 months later was safe and well tolerated. Methods Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of idarucizumab were investigated in a randomized, double-blind, placebo controlled two-way cross-over study in 46 male and female volunteers. Dabigatran etexilate (DE), 220 mg bid in healthy subjects and 150 mg bid in subjects with mild or moderate renal impairment (CLCR60 to <90 or 30 to <60 [mL/min], respectively) was given over 4 days to achieve the steady state conditions. Idarucizumab doses of 1 g, 2.5 g, 5 g or 5 g given as 2x2.5 g one hour apart were administered as 5 min i.v. infusion 2 hrs after the last dose of DE. Concentrations of unbound dabigatran were determined as a measure of pharmacologically active dabigatran. The anticoagulant effect of dabigatran and its reversal were assessed by coagulation time measurements, including diluted Thrombin Time (dTT, Hemoclot® DTI assay), Ecarin Clotting Time (ECT) and activated Partial Thromboplastin Time (aPTT). Results All administered doses of idarucizumab were safe and well tolerated. PK measurements of unbound dabigatran indicated that idarucizumab binding and thus reversal of the anticoagulant effect of dabigatran occurred immediately after end of infusion. Prolongation of clotting times induced by dabigatran was reversed to baseline at the end of the 5 minute infusion of the antidote. This was consistently demonstrated by all clotting assays. Sustained reversal over the entire observation period was observed for idarucizumab doses of 2.5 g, 5 g and 2x2.5 g. For the 1g dose, there was partial return of dabigatran induced anticoagulation around 2-4 hours after i.v. infusion. Also a second administration of idarucizumab (two months after the first) was safe and resulted in complete reversal. In addition, PD and PK measurements at selected time points and in comparison to placebo treatment confirmed that effective dabigatran anticoagulation could be re-established 24 hours after administration of idarucizumab. Conclusions The dabigatran antidote, idarucizumab, was well tolerated under all conditions tested. The administration of 5 g or 2x2.5 g led to sustained reversal of dabigatran induced anticoagulation in male and female subjects of different age and renal function. In addition, idarucizumab administered 2 months apart achieved the same degree of reversal. Dabigatran anticoagulation could be re-established 24 hrs after idarucizumab dosing. These results support the use of a total dose of 5 g idarucizumab as an effective dose in further clinical testing. Disclosures Glund: Boehringer Ingelheim: Employment. Off Label Use: Idarucizumab, a specific antidote for dabigatran, is in clinical development.. Stangier:Boehringer Ingelheim: Employment. Schmohl:Boehringer Ingelheim: Employment. Moschetti:Boehringer Ingelheim: Employment. Haazen:SGS Life Science Services (contracted by Boehringer Ingelheim to conduct the study): Employment. De Smet:SCS Boehringer Ingelheim Comm. V.: Employment. Gansser:Boehringer Ingelheim: Employment. Norris:Boehringer Ingelheim: Employment. Lang:Boehringer Ingelheim: Employment. Reilly:Boehringer Ingelheim: Employment.

Heparins – DOACS – VKA

Phlebologie ◽  
2015 ◽  
Vol 44 (06) ◽  
pp. 307-315 ◽  
Author(s):  
H. Schinzel
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Prolonged Treatment ◽  
Bleeding Complications ◽  
Individual Risk ◽  
Additional Risk Factor ◽  
Vte Prophylaxis ◽  
Patients With Cancer ◽  
Increased Risk

SummaryPatients with cancer are at increased risk of venous thromboembolism (VTE). At the same time they have often an underlying bleeding risk. That can often make decisions surrounding the administration of anticoagulants complicate. Individual risk-benefit calculation is necessary. During hospital stage the patients get, if there are no contraindications, a medical VTE prophylaxis with low molecular weight heparin (LMWH). Whereas out-patients don’t get a prophylaxis because they are at low risk of thromboembolism. If additional risk factor for VTE exists a decision for medical VTE prophylaxis should be taken into account. In patients with cancer and acute VTE, LMWH is recommended as treatment of choice for initial and long-term management in a body weight adapted dosage. After a period of 3–6 month and if a prolonged treatment is necessary, guidelines allow to switch from LMWH to VKA for further anticoagulant therapy. Beside the established anticoagulants like heparin, vitamin K antagonists, fondaparinux new oral direct anticoagulants (DOACs) were established in the last years. These substances are evaluated in in clinical trials. They are approved for treatment of acute VTE, for secondary prophylaxis and for prevention of ischemic stroke in patients with arterial fibrillation. In the VTE trials, 4–10 % of the enrolled patients had a history of cancer. The data shows that DOACs can prevent recurrent VTE as good as standard therapy with enoxaparin/warfarin without more bleeding complications. The results are encouraging. Because of the limited data the direct oral anticoagulants are not recommended for treatment of VTE at this time. Further studies are necessary.

scholarly journals Broadening the Categories of Patients Eligible for Extended Venous Thromboembolism Treatment

2019 ◽  
Vol 120 (01) ◽  
pp. 014-026 ◽  
Author(s):  
Marc Schindewolf ◽  
Jeffrey Ian Weitz
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Profile Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Specific Risk ◽  
Increased Risk

AbstractTraditionally, venous thromboembolism (VTE) resulting from major transient risk factors (e.g., surgery or trauma) or a major persistent risk factor such as cancer, has been defined as being provoked, whereas unprovoked VTE encompasses events without an identifiable cause. These categorizations influence anticoagulant treatment duration; unlike VTE provoked by major transient risk factors, extended anticoagulation beyond 3 months is advised for patients with cancer or unprovoked VTE due to risk persistence after treatment cessation. However, some patients with VTE provoked by minor transient or minor persistent risk factors may also be candidates for extended anticoagulation therapy due to the continuing risk of recurrence. In patients who require extended therapy, vitamin K antagonists (VKAs) are effective but are associated with an increased risk of bleeding and various treatment burdens (e.g., anticoagulation monitoring and dose adjustment). Evaluations of extended VTE treatment with the less-burdensome direct oral anticoagulants such as apixaban, dabigatran, edoxaban, and rivaroxaban show that they are at least as safe and effective as VKAs in a broad range of patients. In addition, apixaban and rivaroxaban offer more than one dosing option, allowing tailoring of treatment to the patient's specific risk factor profile. Analysis of more granular definitions for risk factor groupings has also yielded vital information on the most appropriate strategies for the treatment of patients with specific risk factors, highlighting that extended anticoagulation treatment may benefit those with minor transient and persistent environmental and nonenvironmental risk factors who commonly receive shorter-duration therapy.

scholarly journals The role of direct oral anticoagulants (DOACs) in the treatment of heparin-induced thrombocytopenia (HIT): An evidence-based literature review

2019 ◽  
Vol 45 (2) ◽  
Author(s):  
Bright Huo ◽  
Marcel Surette ◽  
Aaron Kelly
Keyword(s):  
Literature Review ◽  
Large Scale ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Cochrane Library ◽  
Primary Therapy ◽  
Onset Of Action ◽  
Heparin Induced Thrombocytopenia ◽  
Risk Of Death

Heparin-induced thrombocytopenia (HIT) poses a risk of death secondary to thrombotic complications.Treatment options are limited for patients with poor IV access, as contemporary options are restricted to parenteral agents before switching to oral vitamin k antagonists. A literature review was conducted to examine the effectiveness of direct oral anticoagulants (DOACs) in the primary treatment of HIT. High quality evidence is scarce surrounding the use of DOACs for this indication, while past reviews have not critically appraised the evidence. Additionally, the most recent study from 2017 investigating the use of DOACs for this indication has not been reported in past literature reviews.The Cochrane Library, Embase, PubMed, Google Scholar and ClinicalTrials.gov were searched to identify and critically appraise the best available evidence. Salient literature demonstrates that DOACs are effective at raising platelet count to baseline after seven days, on average.Thrombosis and major bleeding are rarely observed when DOACs are used as primary therapy. While large scale studies are needed, patients with HIT that have poor IV access may benefit from the ease of administration, rapid onset of action and lack of routine monitoring associated with DOAC therapy.

scholarly journals Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome

2021 ◽  
Vol 23 (1) ◽  
pp. 93
Author(s):  
Julie Carré ◽  
Georges Jourdi ◽  
Nicolas Gendron ◽  
Dominique Helley ◽  
Pascale Gaussem ◽  
...  
Keyword(s):  
Retrospective Studies ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Current Treatment ◽  
Prothrombotic State ◽  
Heparin Induced Thrombocytopenia ◽  
Need For Treatment ◽  
Randomized Controlled ◽  
Anti Phospholipid Syndrome

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/- anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.

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