Recent Advances in Biology, Biomedicine and Bioengineering

Bemiparin and acenocoumarol home treatment for severe extensive recurrent DVT: should we still be dubious about it?

CARLOS RIVAS ECHEVERRÍA1,2,3,4,5, JESÚS JODRA2,3, LUIS LAPUERTA2,3, LIZMAR MOLINA3,5, PAULINA IGLESIAS4,5, CELESTE THIRLWELL5,6 Unidad Docente de Medicina Familiar y Comunitaria1 Hospital Santa Bárbara de Soria2 Salud Castilla y León3 Universidad de Los Andes; Mérida, Venezuela4 Clínica del Sueño y Terapia Respiratoria SLEEPCARE, Venezuela5 Centre for Sleep and Chronobiology, Toronto, Canada6 Paseo Santa Bárbara, Hospital Santa Bárbara, Soria, 42004 SPAIN [email protected], http://www.saludcastillayleon.es , www.clinicadelsueno.com.ve , www.ula.ve

Abstract: - A 65 YO male, who had suffered Deep Venous Thrombosis (DVT) and (PE) 25 years before, was hospitalized in Soria, Spain, after 5 days of pain and swelling of the right calf; which worsened until swelling, redness, tenderness and pain extended throughout the whole right lower limb. A high probability DVT Wells score was found. No clinical signs or symptoms of PE were observed and CT scan excluded it. D-dimer test was 10.21 and venous ultrasonography confirmed the diagnosis of extensive DVT and thrombi from the popliteal up to the external iliac . Following our guideline, Bemiparin was immediately administer and was continued until optimal INR range was achieved acenocoumarol (4 days after being discharged home). Good outcome was observed over a 2 years follow up period. Despite the severity and magnitude of the DVT this patient did not develop PE with Bemiparin treatment, as he previously did with heparin.

Key-Words: - Deep Venous Thrombosis, Pulmonary Embolism, bemiparin, Low Molecular-Weight Heparins, acenocoumarol, case report, therapy, guidelines

1 Introduction side effects have been observed. Should we be Recurrent Deep Venous Thrombosis (DVT) and doubtful about its appropriateness? We will briefly Pulmonary Embolism (PE) are frequent pathologies, discuss this matter. and a major cause of morbidity and mortality if they are not effective and safely treated.(1,2) Clinical research has provided diagnostic-therapeutic 2 Personal and/or Family History of strategies and guidelines which have improved the the Patient (3-7) outcome in a safer way. Currently, Low A Caucasian 65 YO male was admitted to Santa Molecular-Weight Heparins (LMWHs) and oral Barbara Hospital in Soria, Spain after 5 days of pain anticoagulants are prophylactic-therapeutic choices and swelling of the right calf, which worsened until (3-7) for these diseases. Selected DVT patients could swelling, redness, tenderness and pain extended be safely treated at home, which would reduce costs throughout the whole right leg up into the inguinal (8) and improve patient comfort. Our hospital in area. No , dyspnea, hemoptysis or any (3-7) Soria, Spain, follows these guidelines and most other symptom were observed. He was obese, patients with DVT are safe and effectively treated, smoker and hypertensive, with no other relevant risk sometimes at home, with acenocoumarol and factor, who 25 years before had developed DVT and (9,10) LMWHs, such as Bemiparin. We present a case PE two month after a conservatively treated right of severe extensive recurrent DVT who was tibia-fibula fracture. Nevertheless he was discharged home with bemiparin until INR with acenocoumarol was achieved. Good outcome and no

ISBN: 978-960-474-401-5 76 Recent Advances in Biology, Biomedicine and Bioengineering

immediately treated with subcutaneous heparine he with confirmatory ultrasonography for severe developed DVT and PE at that time. extensive DVT venous. Moderate risk on Wells and low risk on PESI scores, the patient remained hemodynamically stable, there was no clinical evidence of PE and echocardiogram and MDCTA 3 3 Physical Exam and Other Tests excluded it. Absence of fever and other clinical His BMI was 41. DVT Wells Score was 6, with signs of cellulitis or erysipelas, no leukocytosis, unilateral, 3+ pitting erythematic edema, pain and normal CRP and negative cultures ruled out tenderness over swollen thickened palpable infectious diseases. popliteal and pretibial veins (Positive Pratt sign and Pratt test). Homans and Olow signs were negative. D-dimer test was 10.21 and Dupplex venous 5 Treatment and Follow-Up ultrasonography confirmed the diagnosis showing Abdominal subcutaneous Bemiparin (Hibor®) non-compressibility of the venous lumen under 10,000 IU qd (at an approximate dose of 115 gentle probe pressure, slowed venous flow, and IU/Kg/day) was administered upon admission, and extensive thrombi located at right popliteal, continued for 4 days when oral acenocoumarol saphenous, femoral and external iliac veins. (Sintrom ®) was overlapped until INR 2-3 range Subcutaneous edema and superficial was achieved (4 days after being discharged with a thrombophlebitis were also observed (Fig 1). The total of 11 days with bemiparin). Bemiparin was patient was hemodynamically stable, PE Wells stopped and dose-adjusted acenocuomarol has been score of 4.5 (moderate risk), PESI (PE Severity administered throughout 2.5 year follow up period. Index) score was 75 (class II, low risk), clinical Lisinopril 20 mg qd, and acetaminophen 1 g q 8h signs of PE were absent, normal ECG, no suggestive was also administered. images were observed in the echocardiogram and Multidetector CT Angiography (MDCTA) excluded Daily Elastic compression stockings, lifestyle it. HAS-BLED score was 1 (intermediate risk). modification, healthy diet, regular aerobic exercise, weight reduction, and tobacco and alcohol cessation were also recommended. The patient recovered remarkably well and is being assessed every three months until day of publication. Venous ultrasound, CBC, Plt, INR, D-Dimer, stool occult blood test are monitored with each visit. Ultrasounds show persistence of thrombi and partially obstructed flow of saphenous, femoral and external iliac veins (Fig 2). Popliteal, tibia and fibular veins are compressible with preserved normal flow and free of echogenic images in their lumen (Fig 3). Although acenocoumarol under or overdosing have sometimes been observed no bleeding or adverse effects have complicated this patient. No signs of Fig 1. Dupplex venous ultrasound at admission. post-thrombotic syndrome (pain, swelling, skin Non-compressibility of the venous lumen, slowed discolouration, or venous ulceration) have been venous flow, and extensive thrombi located at observed. external iliac .

4 Differential Diagnosis We present a case of a, previously asymptomatic, high probability for DVT patient with multiple risk factors (obesity, smoking, older age, and previous history of thromboembolism), classic clinical features (unilateral edema, pain and tenderness over palpable popliteal veins), and high D-dimer levels

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Fig 2. Venous Ultrasound at day of publication. subtherapeutic dose could precipitate diabetic Thrombi and partially obstructed flow of external ketoacidosis; but nobody would question the iliac vein appropriateness of subcutaneous insulin home treatment instead of in-hospital treatment. What we have learnt with all these publications is that a systematic assessment of all patients: risk factors, clinical presentation, comorbidities, socioeconomic-educational status, family support, feasibility to establish and follow a particular therapeutic regime, access to close emergency services, among others; must be made before deciding the therapeutic home-based regime. Our case-study patient, as most of hundreds of TVP-PE patients/year in our small hospital, is doing well at home with better clinical conditions but the same underlying risks factors as those at the time he was admitted. For more than 2.5 years he still has Fig 3. Venous ultrasound at day of publication. extensive venous thrombosis and high risk for PE, Compressible Popliteal, tibia and fibular veins with but regular assessment and follow up as well as a preserved normal flow and free of echogenic images very well establish and compliant therapy have in their lumen decreased the probability of an adverse outcome and clinical relevant side effects. He is able to 6 Discussion appropriately react if symptoms suggest the In this paper we present a case report illustrating our development of an adverse outcome, and he knows experience with bemiparin and acenocoumarol on and understands exactly how to deal with this, the ambulatory treatment of Deep Venous including seeking for help (medical attention, going Thromboembolism. Should we have presented one to the hospital). Availability of scores such as Wells, of our “rarely” complicated cases with DVT? “Rare PESI, HAS-BLED; laboratory tests such as D- or unusual patients may merit description, but rarity Dimer, Plt, CBC, INR; inexpensive and non- is not itself, however, cause of publication. A case invasive images tests such as ultrasound have must have a message for the reader”.(11) Should we dramatically improved the formerly dreadful spend time to read a case report about DVT and PE panorama of a patient with DVT or PE. Due to its if these are very prevalent pathologies? In recent excellent pharmacological profile (the lowest years, with the emphasis on evidence based molecular weight, the longest half-life and the medicine, the case report appears to have become highest anti-Factor Xa/anti-Factor IIa activity ratio) less valued in scientific literature. But this is our Bemiparin can be safely used in most cases and “message for the reader” and reason why we have even among special categories of patients (children, prepared this fairly common case: Dozens of recent elderly, patients with renal impairment and articles (12-15) are still suggesting a controversy about congestive heart failure). New oral anticoagulants the appropriateness of home treatment for these could also soon become a safe alternative. conditions. Nearly a century after discovering the anticoagulant properties of heparin, clinical trials about the safety and effectiveness of LMWH and References: oral anticoagulant for venous thromboembolic [1] Hansson PO, Sörbo J, Eriksson H. diseases are still being published. This is Recurrent venous thromboembolism after understandable because these medications in these : incidence and risk conditions need to achieve a very narrow factors. Arch Intern Med. 2000 Mar 27; therapeutic range in order to prevent the 160(6):769-74. development of potentially fatal outcomes of these medical emergencies without developing possible [2] Treatment of DVT: how long is enough and lethal side effects. But an analogy to this how do you predict recurrence. Agnelli G, controversy is to ask ourselves if there is rationale Becattini C.J Thromb Thrombolysis. 2008 for home treatment with insulin for diabetes. Feb; 25(1):37-44. Certainly, an insulin overdose could develop hypoglycemic coma, and not enough or

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[3] Andras A, Sala Tenna A, Crawford F. [10] Gómez-Outes A, Rocha Vitamin K antagonists or low-molecular- E, Martínez-González J, Kakkar VV. weight heparin for the long term treatment Cost effectiveness of bemiparin sodium of symptomatic venous thromboembolism. versus unfractionated heparin and oral Cochrane Database Syst Rev. 2012 Oct anticoagulants in the acute and long-term 17;10:CD002001. doi: treatment of deep vein thrombosis. 10.1002/14651858.CD002001.pub2. Pharmacoeconomics. 2006;24(1):81-92.

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