Low molecular weight heparin: a practical approach in deep venous thrombosis in palliative care.

INTRODUCTION: Deep vein thrombosis (DVT) is one of the many cause of pain in advance cases of carcinoma cervix. The most widely used agent for combating DVT is unfractionated heparin. AIMS: Aims of this study is to see the efficacy of the use of low molecular weight (LMW) haparin and its practical utility in palliative care settings.
MATERIALS AND METHODS: Twelve cases of established DVT received enoxaparin at 40 mg/m with warfarin.
RESULTS: There was 70% resolution of limb swelling in seven cases. Out of remaining four cases took two months to resolve and one case did not resolve completely.
CONCLUSIONS: LMV heparin is effective in palliative care setting and also has added advantage of subcutaneous route of administration.

INTRODUCTION

Carcinoma cervix is the leading cause of cancer in the Indian female population[1] and more than 70% of the cases present in the advanced stages; out of which more than two-thirds need palliative care. More than 90% of these patients have distressing pain. Almost 10% patients with advanced disease suffer from swelling of the lower limbs, which is difficult to manage. In many of these cases the cause of swelling of legs is due to deep venous thrombosis of great vessels.

Aims and objective

The present study was carried out from June 2009 to March 2010, to find out an effective solution for the management of deep venous thrombosis.

MATERIALS AND METHODS

All cases of swelling of the lower limbs in patients of cervical carcinoma were evaluated immediately at presentation. Every case underwent an immediate Color Doppler compression ultrasound of the lower limbs to determine the cause of the swollen limb.

After establishing deep vein thrombosis (DVT) a detailed history of any previous blood transfusion, bleeding episode, abortion, or disseminated intravascular coagulation (DIC) was noted, and an immediate blood investigation of activated partial thromboplastin time (APTT), prothrombin index (PTI), international normalized ratio (INR), and platelet count were done along with a complete hemogram, liver function tests, renal function tests, and random blood sugar. Therapy started with a low molecular weight heparin injection.

All patients received LMW heparin (Enoxaparin). The dose given was at the rate of 1 mg / kg body weight (average 40 mg) subcutaneous (s.c.) at 12 hourly intervals, and APTT was monitored weekly. Compression bandage using a crepe bandage was used and maintained on all days of therapy. The foot end was elevated and attention was given to ensure there was no skin color change, any blood stasis, ulceration, or pain. During treatment, serial measurements of limb girth were done using tape, after treatment completion weekly and twice or thrice weekly.

RESULTS

Twenty-two cases presented with swelling of lower limbs in the palliative care outdoor, out of which deep venous thrombosis was established in 12 cases. The median time of presentation with limb swelling after treatment completion was seven months.

Right limb swelling due to DVT was present in six patients, left limb swelling was present in four patients, and bilateral DVT was present in the remaining two patients [Figure 1].

Figure 1

Presentation of limb swelling

After one month of therapy there was 70% resolution of limb swelling in seven cases. Out of remaining five cases, four cases took two months to resolve and one case did not resolve completely [Figure 2].

Figure 2

Results after treatment with LMW heparin

All cases took oral warfarin along with LMW heparin, which was stopped when the INR reached a value of 2 – 3. At the three-month post-treatment follow-up, all patients were again evaluated both clinically and by Doppler USG. All patients were symptomatically better than before. Partial resolution of thrombosis was seen in nine cases. No significant problems such as hemorrhage were observed.

DISCUSSION

Cancer increases the risk of thromboembolic events and the risk of recurrent thromboembolic events, while on anticoagulation. Moreover, most of the patients are poor and often out of reach of proper medical attention and advice in matters of venous thromboembolism management. Hence, the entire scenario of advanced cervical cancer with limb swelling revolves around the fact that if one has to diagnose deep vein thrombosis as the etiology and proceed accordingly, availability and accessibility of the color Doppler USG and judicious use of proper anticoagulation is a necessity. However the real problem arises with patients’ compliance to long-term treatment and monitoring of blood coagulation parameters. Use of unfractionated heparin (UFH) has been the common practice in managing DVT in resource-poor settings and has indeed proved useful in achieving palliation. However, the stringent and rigorous monitoring of APTT, INR, and PTI, while administering heparin often results in the patients’ discomfort during repeated punctures for drawing blood samples. Moreover UFH is not practical for long-term use, as it is to be administered intravenously, which poses a technical and psychological burden to the patient also.

Hence, considering all these practical limitations of using UFH, this study was conducted using LMWH in order to determine the real practical and effective solution to deal with DVT in the palliative care setting.

In an early report, Prandoni et al. had compared the initial treatment of patients with DVT either with LMWH or UFH.[2] The results showed that 44% of the patients with cancer in the UFH group died during the six months of follow-up, whereas, only 7% of those in the LMWH group died (P = 0.02). Similarly, Hettiarachchi et al., compared the mortality rates of patients who had received UFH versus those who had received LMWH.[3] Out of the 629 patients, 46 patients who had received LMWH died, compared to 71 patients who were treated with UFH. Several other studies were reported and meta-analyses of these trials reported a consistently improved survival in the patients who were randomly selected for LMWH therapy.[45] It is important to note that none of these studies were specifically designed to determine the effect of LMWH on survival and all the analyses were performed post hoc of the study groups. The observed differences in mortality could not be attributed to either fatal bleeding or thrombosis.

However, regardless of the issues of survival benefit LMWH has certain other important advantages. LMWH comes in pre-filled syringes, and hence, leads to the ease of dosing and administration, thus resulting in a less erroneous dose. Moreover its subcutaneous administration avoids repeated venepuncture as for UFH, and this makes its use easy and more acceptable to these kinds of patients.

Furthermore, LMWH can be given in an outpatient setting without the stringent need for laboratory monitoring and is infrequently associated with thrombocytopenia.[6] Most of the patients are able to perform self-injections when they are given adequate support and appropriate education, and cohort studies have shown that this can be carried out safely at home also. In many developed countries the standard of care for patients with DVT is outpatient LMWH treatment.[78]

Hence, even though the cost of UFH is lower than LMWH, the additional cost of hospitalization, coagulogram monitoring, and other expenses of patient's relatives, regarding their food and lodging for indefinite periods together adds up, and thus, the total cost of therapy associated with UFH is higher than with LMWH. However, the issues of high cost of LMWH can also be judiciously dealt with depending on the local drug reimbursement programs available, or making the drug more available as a hospital supply.

The results of the present study can help us to take a decision in choosing LMWH, while managing DVT in advanced cervical cancer patients. However, this can be better substantiated if regular availability of LMWH in government institutions is possible, as this can then add to achieve palliation in a better way.