DOCSLIB.ORG

Tinzaparin for Venous Thromboembolism in Patients with Renal Impairment – a Single-Centre, Prospective Pilot Study

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tinzaparin for Venous Thromboembolism in Patients with Renal Impairment – a Single-Centre, Prospective Pilot Study Tinzaparin for venous thromboembolism in patients with renal impairment – a single-centre, prospective pilot study Author details: James Yeung1,2, Caroline H. K. Dix1,2, Angus G. Ritchie3,4,5, Marian Kow6, Vivien M. Y. Chen1,4 1. Department of Haematology, Concord Cancer Centre, Concord Repatriation General Hospital, Concord West, NSW 2139 2. Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW 2050 3. Department of Renal Medicine, Concord Repatriation General Hospital, Concord West, NSW 2139 4. Concord Clinical School, The University of Sydney, Sydney, NSW 2006 5. Menzies Centre for Health Policy, The University of Sydney, Sydney, NSW 2006 6. Pharmacy Department, Concord Repatriation General Hospital, Concord West, NSW 2139 Corresponding author: James Yeung Address: Department of Haematology, Concord Cancer Centre, Concord Repatriation General Hospital, Concord West, NSW 2139 Telephone: +61 2 9767 6648 Email: [email protected] Acknowledgements: No financial grants, funding, industrial links or conflicts of interest to declare This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/imj.15010 This article is protected by copyright. All rights reserved. Abstract Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin, and standard of care in cancer-associated VTE. Tinzaparin has the highest molecular weight of all LMWH, and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20ml/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20ml/min and in cancer-associated VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50ml/min with an indication for anticoagulation. Tinzaparin anti-Xa levels were tested at days 2, 7 and 14 (+/- one day) and transition to oral anticoagulants were allowed at clinician discretion. No accumulation of tinzaparin was seen into day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor), and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and BSA-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on day 2, and this effect was lost when patients with CrCl >50ml/min were excluded. Data from our cohort confirms previous pharmacokinetic studies using therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50ml/min with no signs of accumulation. Bleeding and death outcomes were also comparable to other trials using tinzaparin in cancer-associated VTE. Tinzaparin is an attractive alternative anticoagulant with once-daily administration in a range of potential indications. This article is protected by copyright. All rights reserved. Introduction Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin, and until recently, as sole standard of care in cancer- associated VTE (CA-VTE). There is an unmet need for appropriate LMWH use in patients with CA-VTE and chronic kidney disease (CKD), particularly towards creatinine clearance of 30mL/min where accumulation may occur. In Australia, enoxaparin and dalteparin are widely available and standard dosing is recommended in patients with Cockcroft-Gault creatinine clearance (CrCl) >30mL/min with some centers recommending dose adjustment in moderate renal impairment (CrCl 30-50mL/min).1 Dose-reductions and anti-factor Xa (anti-FXa) monitoring are recommended for CrCl <30mL/min within the product information for enoxaparin.2 Tinzaparin has the highest molecular weight of all LMWH at 6500 Da, resulting in a lower reliance on renal clearance than other LMWHs.3 This expands the use of tinzaparin to CrCl 20mL/min without requirement for dose-adjustment.4 Direct comparison between enoxaparin and tinzaparin in patients with renal impairment (CrCl 20-50mL/min) within the prophylaxis setting demonstrated accumulation of enoxaparin but not tinzaparin.4 Outside of Australia, tinzaparin is widely used in both CA-VTE and CKD, with multiple trials showing safety and efficacy in both settings. In CA-VTE, the CATCH and LITE trials compared tinzaparin to warfarin, demonstrating reduced clinically-relevant, non-major bleeding (CRNMB) and reduced CA-VTE recurrence in the tinzaparin arms respectively.5, 6 In CKD, the TRIVET trial showed no accumulation using tinzaparin for patients with CrCl >20mL/min, but there remains concern over elderly patients with diminished renal function.7, 8 Another trial, IRIS, evaluated elderly patients with CKD and VTE using tinzaparin as a bridge to vitamin K antagonist and initially there was concern about increased deaths in the tinzaparin arm.9 This was later attributed to an uneven distribution of risk factors, and a sub-study from IRIS showed no accumulation of tinzaparin and no signal for increased bleeding.10 Further prospective trials in patients aged 75 and above with CKD (mean CrCl 35mL/min) showed no evidence of accumulation using prophylactic dose, and use in patients aged 70 and above with CKD (mean CrCl 51mL/min) also demonstrated safety at therapeutic dose for 30 days.4, 11 However, in Australia, tinzaparin is not widely available – it can be accessed via the Special Access Scheme (SAS), but is not subsidized by the Pharmaceutical Benefits Scheme (PBS) and is not generally available on formulary in NSW hospitals. This article is protected by copyright. All rights reserved. In our ageing population, there is an increasing demand for anticoagulation in patients with CKD, with longer-term anticoagulation required in CA-VTE. We explored the ability to deliver short and long term therapeutic tinzaparin in patients with CrCl 20-50mL/min using a prospective study at Concord Hospital, with measurement of anti-FXa levels to test for accumulation within the first fourteen days and outcomes of bleeding, recurrent thrombosis and mortality. Methods A tinzaparin pilot program was implemented at Concord Repatriation General Hospital, Sydney under ethics approval (CH62/6/2018-077). Inclusion criteria were requirement for therapeutic anticoagulation with CrCl between 20- 50mL/min or Chronic Kidney Disease Epidemiology (CKD-EPI) estimated glomerular filtration rate (eGFR) 20- 50mL/min/1.73m2. Patients with CrCl or CKD-EPI eGFR outside this range were included at physician discretion. Patients were excluded if they had a history of allergy or anaphylaxis to heparin or other LMWH products, a history of heparin induced thrombocytopenia, or if subcutaneous injections could not be administered for the duration of the treatment. Patients were selected via recommendations from inpatient hematology consultation or the outpatient thrombosis management clinic. CrCl was calculated using the Cockcroft-Gault equation, and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation.12, 13 Body surface area was calculated using the Du Bois formula.14 CrCl was standardized (St-CrCl) against the patient’s BSA using the following equation – = 1.73/ . A dose level of 175units/kg once daily tinzaparin was used rounded to nearest syringe strength size. SAS applications were submitted to the Therapeutic Goods Administration (TGA) for approval. After commencement, tinzaparin anti-FXa levels were taken at days 2, 7 and 14 (+/- one day), 3-5 hours after dosing. Choice of day and peak levels were in line with Pautas et al.11 These were measured according to local protocols using the Stago STA-R Max (Diagnostica Stago, Paris, France) with a chromogenic anti-FXa assay. Dose-adjustment was made at the physician’s discretion or outside the therapeutic tinzaparin anti-FXa level of 0.5-1.5 units/mL.11 Further tinzaparin anti-FXa levels were taken after dose-adjustment to ensure ongoing safety and efficacy. Physicians had the option to transition patients to warfarin or direct oral anticoagulants (DOACs) depending on the degree and progress of renal impairment. Data on baseline characteristics (age, gender, height, weight and serum creatinine) and follow-up (duration of treatment, complications, outcomes and cause of death) were collected and analyzed using Prism 7 (GraphPad Software, La Jolla, California, USA). Complications were assessed by Common Terminology Criteria for Adverse Events (version 5.0) using electronic medical record review.15 This article is protected by copyright. All rights reserved. Results Twenty patients (ten males and ten females) received tinzaparin between June 2017 and September 2018. Demographic data is summarized in Table 1. Median age was 78 years (range 60-90 years). Eight patients were placed on tinzaparin until bridged to an alternative anticoagulant with a median duration of 0.2 months, and twelve patients were placed on extended duration LMWH therapy (median 6.3 months, range 0.2 – 15.1 months). Seventeen patients had CrCl or CKD-EPI eGFR 20-50mL/min/1.73m2 between 20-50mL/min, and within this group, five patients had active
Load more

Recommended publications
  • Package Leaflet: Information for the User Innohep® 10,000 IU/Ml Solution for Injection Tinzaparin Sodium
    Package leaflet: Information for the user innohep® 10,000 IU/ml solution for injection tinzaparin sodium Read all of this leaflet carefully before you start using this medicine because it contains important information for you. • Keep this leaflet. You may need to read it again. • If you have any further questions, ask your doctor, pharmacist or nurse. • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4. • In this leaflet innohep 10,000 IU/ml will be called innohep. What is in this leaflet 1. What innohep® is and what it is used for 2. What you need to know before you use innohep® 3. How to use innohep® 4. Possible side effects 5. How to store innohep® 6. Contents of the pack and other information 1. What innohep® is and what it is used for innohep is a type of heparin – a low molecular weight heparin – and belongs to a group of medicines called anticoagulants; these medicines affect how your blood clots. innohep prevents clotting, allowing normal blood flow through the arteries and veins. innohep is used to: Prevent blood clots in adults before and after an operation. Prevent blood clots in adults who have an increased risk of blood clots e.g. due to an acute illness with limited mobility. Prevent blood clots being formed in haemodialysis equipment in patients undergoing haemodialysis or haemofiltration.
    [Show full text]
  • SPECIALTY MEDICATIONS Available Through Accredo Health Group, Inc., Medco’S Specialty Pharmacy Call Toll-Free (800) 803-2523, 8:00 A.M
    SPECIALTY MEDICATIONS available through Accredo Health Group, Inc., Medco’s specialty pharmacy Call toll-free (800) 803-2523, 8:00 a.m. to 8:00 p.m., eastern time, Monday through Friday, to confirm that your medication is covered. Effective as of July 1, 2011 Abraxane® (paclitaxel protein-bound particles) Berinert® (C 1 esterase inhibitor [human])* (PA) (QD) Actemra ™ (tocilizumab) (PA) Betaseron® (interferon beta-1b) (PA) Actimmune® (interferon gamma-1b) (PA) Botox® (botulinum toxin type A) (PA) Adagen® (pegademase bovine) Carbaglu ™ (carglumic acid) Adcirca® (tadalafil) (ST) (QD) Carimune® NF (immune globulin intravenous [human]) (PA) Advate® (antihemophilic factor [recombinant]) (CPA) Cerezyme® (imiglucerase) (CPA) (ST) Afinitor® (everolimus) (PA) (QD) Cimzia® (certolizumab pegol) (ST) Aldurazyme® (laronidase) (CPA) Copaxone® (glatiramer acetate) (PA) Alphanate® (antihemophilic factor [human]) (CPA) Copegus® (ribavirin) (ST) AlphaNine® SD (coagulation factor IX [human]) (CPA) Corifact® (factor XIII [human]) (CPA) Amevive® (alefacept) (PA) Cystadane® (betaine) Ampyra ™ (dalfampridine) (PA) CytoGam® (cytomegalovirus immune globulin Apokyn® (apomorphine hydrochloride) (PA) (QD) intravenous [human])* (CPA) Aralast® (alpha[1]-proteinase inhibitor [human]) Cytovene® IV (ganciclovir sodium)* Aranesp® (darbepoetin alfa) (PA) Dacogen® (decitabine) Arcalyst® (rilonacept) (PA) (QD) Dysport® (abobotulinumtoxinA) (PA) Arixtra® (fondaparinux sodium)* Egrifta ™ (tesamorelin) (PA) Arranon® (nelarabine) Elaprase® (idursulfase) (CPA) Arzerra® (ofatumumab)
    [Show full text]
  • Hemosil ® Liquid Anti-Xa
    H E M O S I L® LIQUID ANTI-XA Measuring heparin and apixaban: Simple, fast, 24/7 • Liquid formulation, ready-to-use • One-stage, chromogenic anti-Xa assay • Universal calibration for unfractionated heparin (UFH) and low molecular weight heparin (LMWH) • Drug specific calibrators and controls for measurement of apixaban Measuring heparin and apixaban Unfractionated and low molecular weight heparin Heparin is a highly sulfated polysaccharide Laboratory monitoring is extremely important to characterized by a wide molecular weight range and assess the appropriate level of anticoagulation in potent anticoagulant activity. It exists either as UFH patients receiving UFH. Anti-Xa is recommended for or as depolymerized LMWH. UFH and LMWH have measuring both UFH and LMWH. a rapid anticoagulant effect and are used in the prevention and treatment of venous thrombosis and Anti-Xa testing for measuring UFH helps improve acute coronary syndrome. quality of care and patient experience while reducing costs, when compared with APTT testing.1 UFH and LMWH anticoagulant activity occurs when The advantages include: a complex with antithrombin (AT) is formed, • Higher precision potentiating its anticoagulant activity up to • Lower levels of discordant results1,2,4 1,000-fold, which inactivates both thrombin (FIIa) • Faster time to achieve therapeutic levels1,3,4 and Factor Xa (FXa). UFH acts through both FIIa 1,3,4,5 and FXa inhibition, while LMWH is a more efficient • Fewer tests and dosage changes catalyst for FXa inhibition. Direct Xa inhibitors Anticoagulation for patients with venous DOACs do not require routine monitoring. However, thromboembolism (VTE) previously included there are specific instances when an understanding heparin, heparin derivatives and/or oral vitamin K of the DOAC concentration in a patient sample may antagonists.
    [Show full text]
  • TITLE: Tinzaparin Versus Dalteparin Or Enoxaparin for the Treatment of Venous Thromboembolism in Adults: Safety and Guidelines
    TITLE: Tinzaparin versus Dalteparin or Enoxaparin for the Treatment of Venous Thromboembolism in Adults: Safety and Guidelines DATE: 12 March 2013 RESEARCH QUESTION 1. What is the clinical evidence for the safety of tinzaparin versus dalteparin or enoxaparin for the treatment of venous thromboembolism in adults with a glomerular filtration rate (eGFR) less than 30 ml/min? 2. What is the clinical evidence for the safety of tinzaparin versus dalteparin or enoxaparin for the treatment of venous thromboembolism in adults who require dialysis? 3. What are the evidence-based guidelines for the use of tinzaparin for adults with venous thromboembolism and a glomerular filtration rate less than 30 mL/min or adults who require dialysis? KEY MESSAGE Two meta-analyses, one randomized controlled trial, and one non-randomized study were identified regarding the safety of tinzaparin versus dalteparin or enoxaparin for the treatment of venous thromboembolism. No evidence-based guidelines were identified. METHODS A limited literature search was conducted on key resources including Pubmed, The Cochrane Library (2013, Issue 2), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No methodological filters were applied. Where possible, retrieval was limited to the human population. The search was also limited to documents published between January 1, 2003 and March 1, 2013. Internet links were provided, where available. Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews.
    [Show full text]
  • What You Need to Know About Deep Vein Thrombosis (DVT)
    What You Need to Know About Deep Vein Thrombosis What is a Deep Vein Thrombosis? A deep vein thrombosis (DVT) is a blood clot that forms in the veins in the body (usually in the leg or pelvis). What causes a Deep Vein Thrombosis? Deep vein thrombosis (DVT) sometimes occurs for no apparent reason. However, certain factors can increase the chance of developing a DVT: • Inactivity • Hospital stays and surgery • Damage to your blood vessel from an injury or trauma • Medical and genetic conditions • Pregnancy • Taking estrogen-based medicine such as hormonal birth control or hormone replacement therapy • Overweight or obese • Family history of DVT • Older age What are the symptoms of DVT? Only about half of the people who have a DVT have signs and symptoms. These signs and symptoms of a deep vein clot include: • Pain or tenderness, often starting in the calf. • Swelling, including the ankle & foot. • Warmth and redness of the area or a noticeable discoloration Vascular Surgery -1- How is a DVT diagnosed? Your doctor will ask you questions about your symptoms and if your symptoms suggest that a blood clot is likely, you could have one or all of the following tests: • Blood test for a D-dimer: this test measures the level of a compound released when blood clots are dissolving. A high level may mean you have Deep Vein Thrombosis (DVT). • Imaging studies: o Ultrasound – This is the most common test for diagnosing deep vein blood clots. This test uses sound waves to create pictures of blood flowing through the arteries and veins in the affected leg.
    [Show full text]
  • Innohep® Is and What It Is Used for • If You Have Kidney Problems
    Scale Get-up Material No Sent by e-maiL l 5. RBE 100% GB 066478-XX Subject Date Date 14/09/20 066478 INS 205 x 315 mm with 2 foils 27/05/20 066478-XX Colour Sign. Sign. SOP_000647, SOP_000962, SOP_000647, SOP_000962 Black OMA SOP_003993 and and SOP_008676 SOP_008676 Preparation Place of production Strength ® Packsize innohep syringe 20,000 IU/ml France Comments: Page 1 of 2 Font size: 9 pt Headings 10 pt Mock-up for reg. purpose IFR012-01 - 205 x 315 mm Page 4 of 4 Page 1 of 4 066478-XX Package leaflet: Information for the user syringe 20,000 IU/ml tinzaparin sodium Read all of this leaflet carefully before you start using this medicine because it contains important information for you. • Keep this leaflet. You may need to read it again. 066478 • If you have any further questions, ask your doctor, pharmacist or nurse. • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. • If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4. • In this leaflet innohep 20,000 IU/ml syringe will be called innohep. What is in this leaflet • If you have an artificial heart valve. 1. What innohep® is and what it is used for • If you have kidney problems. 2. What you need to know before you use innohep® • If you have asthma, as this medicine contains sodium 3.
    [Show full text]
  • Thromboembolic Disease in Pregnancy and the Puerperium: Acute Management
    Thromboembolic Disease in Pregnancy and the Puerperium: Acute Management Green-top Guideline No. 37b April 2015 Thromboembolic Disease in Pregnancy and the Puerperium: Acute Management This is the third edition of this guideline. The first edition was published in April 2001 under the same title (numbered Green-top Guideline No. 28) and the second edition was published in February 2007 and reviewed in 2010. Thromboprophylaxis during pregnancy and the puerperium is addressed in Green-top Guideline No. 37a. Executive summary of recommendations Diagnosis of acute venous thromboembolism (VTE) How is acute VTE diagnosed in pregnancy? Any woman with symptoms and/or signs suggestive of VTE should have objective testing performed C expeditiously and treatment with low-molecular-weight heparin (LMWH) given (see section 6) until the diagnosis is excluded by objective testing, unless treatment is strongly contraindicated. Individual hospitals should have an agreed protocol for the objective diagnosis of suspected VTE during pregnancy. This may recommend the involvement of obstetricians, radiologists, physicians P and haematologists. What investigations are needed for the diagnosis of an acute DVT? Compression duplex ultrasound should be undertaken where there is clinical suspicion of DVT. B If ultrasound is negative and there is a low level of clinical suspicion, anticoagulant treatment can C be discontinued. If ultrasound is negative and a high level of clinical suspicion exists, anticoagulant treatment should be discontinued but the ultrasound should be repeated on days 3 and 7. [New 2015] What investigations are needed for the diagnosis of an acute pulmonary embolism (PE)? Women presenting with symptoms and signs of an acute PE should have an electrocardiogram C (ECG) and a chest X-ray (CXR) performed.
    [Show full text]
  • Is Impaired Renal Function a Contraindication to the Use of Low-Molecular-Weight Heparin?
    ORIGINAL INVESTIGATION Is Impaired Renal Function a Contraindication to the Use of Low-Molecular-Weight Heparin? Jeff Nagge, BScPhm, BSc; Mark Crowther, MD, MSc; Jack Hirsh, MD, FCCP Background: Because of the risk of accumulation of an- dress our primary objective did not support the use of a ticoagulant effect, it has been suggested that patients with 30-mL/min (0.50-mL/s) cutoff of creatinine clearance to a creatinine clearance of 30 mL/min or less (Յ0.50 mL/s) select individuals at risk of accumulation when LMW hep- should be excluded from treatment with low-molecular- arin is used. Four of the 5 trials support the notion that weight (LMW) heparin, or have anti–factor Xa heparin anti–factor Xa activity of some LMW heparin prepara- level monitoring performed. tions accumulates in patients with impaired creatinine clearance. Tinzaparin sodium, an LMW heparin with a Objective: To assess the appropriateness of this rec- higher-than-average molecular weight distribution, ap- ommendation. pears to be the exception, since it did not exhibit accu- mulation in patients with creatinine clearances as low as Methods: We performed a systematic search of 20 mL/min (0.33 mL/s). MEDLINE, EMBASE, and International Pharmaceutical Abstracts to identify prospective articles comparing dif- Conclusions: The use of a 30-mL/min (0.50-mL/s) cut- ferences in the pharmacokinetics of LMW heparins in non- off is not justified, on the basis of currently available evi- dialyzed patients with varying degrees of renal func- dence, to select individuals at increased risk of accumula- tion.
    [Show full text]
  • Livedoid Vasculopathy: a French Observational Study Including
    Livedoid Vasculopathy: A French Observational Study Including Therapeutic Options Emma Gardette, Philippe Moguelet, Jean David Bouaziz, Dan Lipsker, Olivier Dereure, François Le Pelletier, Catherine Lok, Thierry Maisonobe, Didier Bessis, Jacqueline Conard, et al. To cite this version: Emma Gardette, Philippe Moguelet, Jean David Bouaziz, Dan Lipsker, Olivier Dereure, et al.. Live- doid Vasculopathy: A French Observational Study Including Therapeutic Options. Acta Dermato- Venereologica, Society for Publication of Acta Dermato-Venereologica, 2018, 98 (9), pp.842 - 847. 10.2340/00015555-2965. hal-01901846 HAL Id: hal-01901846 https://hal.sorbonne-universite.fr/hal-01901846 Submitted on 23 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License 842 CLINICAL REPORT Livedoid Vasculopathy: A French Observational Study Including DV Therapeutic Options Emma GARDETTE1, Philippe MOGUELET2, Jean David BOUAZIZ3, Dan LIPSKER4, Olivier DEREURE5, François LE PELLETIER6, cta Catherine LOK7,
    [Show full text]
  • PDF Download
    Review Article 201 How Do I Reverse Oral and Parenteral Anticoagulants? Wie Reversiere ich die Wirkung von Oralen und Parenteralen Antikoagulanzien? Jürgen Koscielny1 Edita Rutkauskaite1 Christoph Sucker2 Christian von Heymann3 1 Charité, Universitätsmedizin Berlin, Gerinnungsambulanz mit Address for correspondence Jürgen Koscielny, Charité, Hämophiliezentrum im Ambulanten, Gesundheitszentrum (AGZ), Universitätsmedizin Berlin, Gerinnungsambulanz mit Berlin, Germany HämophiliezentrumimAmbulantenGesundheitszentrum(AGZ), 2 Gerinnungszentrum Berlin Dr. Sucker, Berlin, Germany Berlin, Germany (e-mail: [email protected]). 3 Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Vivantes Klinikum, Im Friedrichshain, Berlin, Germany Hämostaseologie 2020;40:201–213. Abstract An understanding of reversal strategies alone is important to safely and effectively care for patients in cases of bleeding or invasive procedures. The recent diversification in the number of licensed anticoagulants makes an understanding of drug-specific reversal strategies essential. Intravenous or oral vitamin K can reverse the effect of vitamin K antagonists (VKAs) within 12 to 48 hours and is indicated for any bleeding or an international normalized ratio >10 or 4.5 to 10 in patients with additional risk factors for bleeding. Furthermore, an additional administration of prothrombin complex concentrate (PCC) may be necessary in cases of major bleeding related to VKA. Protamine (chloride or sulfate) fully reverses the effect of unfractionated heparin and partially in low-molecular-weight heparin. Idarucizumab has been approved for dabigatran reversal, whereas andexanet alfa is approved for the reversal of some oral factor Xa inhibitors (apixaban, rivaroxaban). PCC seems to enhance the haemo- static potential for the reversal of the effect of FXa-inhibitors. So far, there are promising but only limited data on the efficacy of this approach available.
    [Show full text]
  • What You Need to Know About Blood Clots
    What You Need to Know About Blood Clots What is a blood clot? There are two types of clots: • Deep Vein Thrombosis (DVT) is a blood clot that forms in the veins deep in the body (usually in the leg or pelvis). • Pulmonary embolus (PE) is a blood clot that breaks off from a vein deep in the body and travels in the bloodstream to your lungs Reproduced with permission from OrthoInfo. ©American Academy of Orthopaedic Surgeons. What are the symptoms of a blood clot? http://orthoinfo.aaos.org. Sign and Symptoms of a Deep Vein Sign and Symptoms of a Pulmonary Thrombosis (DVT): Embolus (PE): Only about half of the people who Some people aren't aware of a deep have a DVT have signs and vein clot until they have signs and symptoms. symptoms of a PE. Call 911 if you notice these signs of a These signs and symptoms occur in PE: the leg affected by the deep vein • Unexplained, shortness of breath clot: • Rapid breathing • Pain or tenderness, often starting • Chest pain (may be worse with deep in the calf. breathing). • Swelling, including the ankle & • Rapid heart rate foot. • Unexplained cough and coughing up • Warmth and redness of the area blood or a noticeable discoloration. • Dizziness, lightheadedness or fainting Cardiovascular Center What You Need to Know About Blood Clots - 1 - How is a DVT or PE blood clot diagnosed? Your doctor will ask you questions about your symptoms and if your symptoms suggest that a blood clot is likely, you could have one or all of the following tests: Blood Test for a D-dimer: This test measures the level of a compound released when blood clots are dissolving.
    [Show full text]
  • Livedoid Vasculopathy; Peripheral Neuropathy; Globulins, Agood Producing Response in 6Patients
    842 CLINICAL REPORT Livedoid Vasculopathy: A French Observational Study Including DV Therapeutic Options Emma GARDETTE1, Philippe MOGUELET2, Jean David BOUAZIZ3, Dan LIPSKER4, Olivier DEREURE5, François LE PELLETIER6, cta Catherine LOK7, Thierry MAISONOBE8, Didier BESSIS5, Jacqueline CONARD9, Camille FRANCES1 and Stéphane BARETE10,11 1 3 4 5 A Departments of Dermatology: CHU Tenon, APHP, CHU Saint Louis, APHP, Paris, CHU de Strasbourg, Strasbourg, CHU de Montpellier, Montpellier, 7CHU d’Amiens, Amiens, Departments of Histopathology: 2CHU Tenon, APHP and 6Groupe Hospitalier Pitié-Salpêtrière, APHP, 8Department of Neurophysiology, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, 9Department of Hemostasis and Vascular Biology, CHU Cochin, APHP, 10Unit of Dermatology, Groupe Hospitalier Pitié-Salpêtrière, APHP, and 11Inflammation-Immunopathology-Biotherapy Department, Sorbonne Universités, UPMC Univ Paris, INSERM-UMRS 959, DHU i2B, Paris, France Livedoid vasculopathy is a rare thrombotic cutaneous SIGNIFICANCE disease. This observational study aimed to assess the clinical and biological features of livedoid vasculopa­ Livedoid vasculopathy is a chronic thrombotic disease of the thy and the efficacy of treatments. Patients enrolled skin microcirculation resulting in painful ulcers mainly af- enereologica had typical livedoid vasculopathy both clinically and fecting the lower legs. This study presents a French cohort V histologically. Investigation of thrombophilia was per­ of patients with livedoid vasculopathy. It describes clinical, formed. Electromyography was undertaken in the pre­ histological characteristics and outcome of patients. It no- sence of symptoms suggesting peripheral neuro pathy. tably shows a frequent thrombophilia background. Nerve damage can be associated with cutaneous manifestations. ermato- Eighteen women and 8 men were included, with a mean age of 35.5 years at onset.
    [Show full text]