Continued Use of Tinzaparin at Therapeutic Doses for Prophylaxis of Venous Thromboembolism in Patients with Intolerance to Antivitamins K
Authors: Garcia Ruiz Maria Almudena , Romero Martinez Francisco Jose , Morente Constantin Estefania , Gomez Morales Margarita , Jurado Manuel 
Published: October 2019

Abstract
OBJECTIVES
The low molecular weight heparins (LMWH) are typically administered at fixed doses like thromboprophylaxis or at doses adjusted to the weight of the patient in order to obtain a therapeutic effect. Generally they do not require laboratory monitoring, although it could be considered in special situations (renal failure, extreme weights, pregnant women). The LMWH do not affect the APTT, so it has been proposed to determine the anti-factor Xa activity when it is necessary to monitor its effect. The anti-factor Xa activity should be determined approximately 4 hours after sc administration of the LMWH that it is employed, concurring with the peak of activity. The therapeutic range of the anti-factor Xa activity is between 0.6 and 1 IU / mL when LMWH is administered every 12 hours. At single daily dose is less clear, although it seems that lies above 1 IU / mL.
Nowadays, LMWH are the anticoagulant of choice during pregnancy. Numerous in vitro and in vivo studies have shown the existence of an antineoplastic effect of heparin. LMWH is commonly used for prolonged treatment of thrombosis associated with cancer.
METHODS
The main aim of our study is to evaluate the efficacy of tinzaparin sodium at therapeutic doses in preventing VTE in renal failure, active cancer and/or patients with contraindications to oral anticoagulation. The dose has been therapeutic and adjusting it has been made in terms of anti-factor Xa levels obtained monthly. Hemorrhagic or thrombotic complications and other possible side effects have been assessed.
Until now, a total of 70 patients, 42 men and 28 women aged between 30 and 95 years old, have received tinzaparin sodium treatment. The main reason of anticoagulation are: atrial fibrillation and atrial flutter (with or without valve disease), VTE (with or without thrombophilia), stroke and transient ischemic attacks and mechanical prosthetic aortic and mitral valves (some of the patients carrying a double metal prosthesis). There was 1 resistance and 1 allergic reaction to anti-vitamin K. 4 of the patients were pregnant and 14 had renal failure. Prior to initiation of therapy, analytical determinations were performed, including: blood count, blood coagulation and biochemistry to assess renal function (urea and creatinine).
20 patients (14 were anticoagulated by atrial fibrillation, 2 for bearing a mechanical aortic prosthesis and 4 because of DVT, 1 of which had also a TEP) had active cancer or were in remission from their neoplasia (3 multiple myeloma, 1 LAM, 1 CMML, 4 renal tumors, 1 lung cancer, 5 prostate cancers, 1 hepatocellular carcinoma, 2 colon cancer, 1 endometrial adenocarcinoma and 1 retroperitoneal leiomyosarcoma). 1 with MDS was treated with LMWH because he had intra- and extrahepatic portal vein thrombosis.
RESULTS
Some of the patients had received prior treatment with anti-vitamin K (INR objective depending on pathology) but, in other cases, the low molecular weight heparin was the only treatment since the beginning of their anticoagulation. All the patients had received 175 IU / Kg of Tinzaparin Sodium once a day as initial dose, then the dose was adjusted according to the anti-factor Xa levels. They were controlled until 31/07/2015.
In terms of side effects, 8 patients presented complications: 3 mucosal bleeding, 2 episodes of stroke in a patient, hemoptysis, deep vein thrombosis and 2 bleeding at the puncture site of heparin, which have not required discontinuation of therapy. When these complications occurred, we proceeded to the corresponding heparin dose adjustment based on new determinations of anti-factor Xa.
CONCLUSIONS
Although only in 70 cases, the results obtained confirm the efficacy, safety and cost-effectiveness of the continuous use of LMWH. Determination of anti-factor Xa levels are considered very useful for dose adjustment parameter. In our study, tinzaparin sodium has proved to be very useful in preventing venous thromboembolism associated or not with cancer, in patients with conditions requiring anticoagulation and presenting contraindications to the use of anti-vitamin K.
The results obtained have demonstrated that tinzaparin is safe and, most likely, further studies will provide valuable confirmation data to support the use of low molecular weight heparins in the prolonged treatment of patients who require oral anticoagulation and can not receive it.

Disclosures
No relevant conflicts of interest to declare.