To The Editor:

I read with interest the Nov 2007 paper by Mitchell et al.(1) and would like to make the following points:

The second paragraph of the introduction quotes numerous published guidelines relating to thromboprophylaxis. A recent audit we have carried out (Rogers et al. unpublished data) has shown poor awareness and application of all guidelines in the UK. To date, no concensus has been achieved for the most appropriate method of thromboprophylaxis in joint arthroplasty surgery, let alone sarcoma surgery. One of the reasons we believe this is the case is the plethora of current guidelines including those of the the British Orthopaedic Association, the National Institute of Clinical Excellence(2) and the British Haematological Society(3).

The study rightly highlights the significant mortality and morbidity that is associated with venous thromboembolism. However, there are also significant risks associated with chemoprophylaxis using low molecular weight heparin particularly bleeding(2,4-7) (intrahepatic, intracranial and intraabdominal) and heparin induced thrombocytopenia (8-9). This is in addition to bleeding associated with soft tissue tumours and any possible related surgery.

The results show that the thirteen patients who developed venous thromboembolism had taken low-molecular weight heparin for a variable period of time (0 – 21 days), a shorter period of time than suggested for abdominal and pelvis cancer patients receiving enoxaparin (10). Future studies will need to evaluate the optimal duration of chemoprophlaxis in relation to the venous thromboembolism risk highest.

Since low molecular weight can be safely administered in a primary care setting(11), do the authors feel this would be suitable for the sarcoma patient cohort and, if so, who should monitor its use?

We agree with the final conclusion of this study that a further evaluation of the risk factors for thromboembolism in this patient group would be beneficial. However, there are numerous confounding factors inherent in these patients that can all influence the coagulation:

1. Patient factors: age, weight, co-morbidity

2. Tumour factors: location, histological type, grade, size

3. Treatment factors: adjuvant chemo- and radio –therapy

Any future study would need to include a large patient cohort in order to adjust for these confounding factors.

The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

References:

1. Mitchell,S.Y., Lingard,E.A., Kesteven,P., McCaskie,A.W., and Gerrand,C.H.: Venous thromboembolism in patients with primary bone or soft -tissue sarcomas. J Bone Joint Surg Am, 89:2433-2439, 2007.

2. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. National Institute of Clinical Excellence . 2007. 14-11-2007. Ref Type: Internet Communication

3. Baglin,T., Barrowcliffe,T.W., Cohen,A., and Greaves,M.: Guidelines on the use and monitoring of heparin. Br J Haematol, 133:19-34, 2006.

4. Dickinson,L.D., Miller,L.D., Patel,C.P., and Gupta,S.K.: Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors. Neurosurgery, 43:1074-1081, 1998.

5. Houde,J.P. and Steinberg,G.: Intrahepatic hemorrhage after use of low-molecular-weight heparin for total hip arthroplasty. J Arthroplasty, 14:372-374, 1999.

6. Shaieb,M.D., Watson,B.N., and Atkinson,R.E.: Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis. J Arthroplasty, 14:432-438, 1999.

7. Lilikakis,A.K., Papapolychroniou,T., Macheras,G., and Michelinakis,E.: Thrombocytopenia and intra-cerebral complications associated with low-molecular-weight heparin treatment in patients undergoing total hip replacement. A report of two cases. J Bone Joint Surg Am, 88:634-638, 2006.

8. Chong,B.H.: Heparin-induced thrombocytopenia. Br J Haematol, 89:431-439, 1995.

9. King,D.J. and Kelton,J.G.: Heparin-associated thrombocytopenia. Ann Intern Med, 100:535-540, 1984.

10. Bergqvist,D., Agnelli,G., Cohen,A.T., Eldor,A., Nilsson,P.E., Le Moigne-Amrani,A., and etrich-Neto,F.: Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med, 346:975-980, 2002.

11. Imberti,D., Ageno,W., Dentali,F., Giorgi,P.M., Croci,E., and Garcia,D.: Management of primary care patients with suspected deep vein thrombosis: use of a therapeutic dose of low-molecular-weight heparin to avoid urgent ultrasonographic evaluation. J Thromb Haemost, 4:1037-1041, 2006.