Chapter 8. Special cases

 [J1]Cette ref n’est pas dans la liste des réréfrence et je ne la trouve pas dans PubMed

 [J2]Cette ref n’est pas dans la liste des ref. Je pense que c’est celle-ci pouvez vous confirmer:

Altschuler E, Moosa H, Selker RG, Vertosick FT Jr. The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors. Neurosurgery. 1990 Jul;27(1):74-6;

 [J3]Cette ref n’est pas dans la liste des ref. Je pense que c’est celle-ci pouvez vous confirmer:

MACDONALD2003: Macdonald RL, Amidei C, Baron J, Weir B, Brown F, Erickson RK, Hekmatpanah J, Frim D. Randomized, pilot study of intermittent pneumatic compression devices plus dalteparin versus intermittent pneumatic compression devices plus heparin for prevention of venous thromboembolism in patients undergoing craniotomy. Surg Neurol 2003;59:363-72.

 [J4]Cette ref n’est pas dans la liste des réréfrence et je ne la trouve pas dans PubMed

 [J5]Cette ref n’est pas dans la liste des ref. Je pense que c’est celle-ci pouvez vous confirmer:

Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, D’Angelo A, Beltrametti C, Damiani M, Andrioli GC, Pugliese R, Iorio A, Brambilla G. Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med. 1998 Jul 9;339(2):80-5.

 [J6]Cette ref n’est pas dans la liste des ref. Je pense que c’est celle-ci pouvez vous confirmer:

GOLDHABER2002: Goldhaber SZ, Dunn K, Gerhard-Herman M, Park JK, Black PM. Low rate of venous thromboembolism after craniotomy for brain tumor using multimodality prophylaxis. Chest 2002;122:1933-7.

 [J1]ce n’est pas si évident quand on regarde les études concernées [NURMOHAMED1996] [AGNELLI1998] [DICKINSON1998] [GOLDHABER2002] [MACDONALD2003] et les méta-analyses ne semblent pas aborder ce point.

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8.4. Discussion

The treatment of VTE in patients with brain tumors varied among the selected studies: UFH +VKA, tinzaparin alone and vena cava filter insertion. Depending on the therapeutic options, therate of recurrence and bleeding varied from 0 to 12% and from 0% to 17%, respectively (intracerebral bleeding 0-7%). These figures appear to be quite similar to those noted in retrospective studies performed with the same drugs in patients with cancer other than brain tumors. In a small prospective non-randomized study assessing tinzaparin, no VTE recurrence and no bleeding were detected [SCHMIDT2002]. So the presence of a brain tumor is not a contraindication to a full anticoagulation provided that there is no other associated bleeding risk. In this setting, the experts prefer to prescribe LMWH that has been shown to be superior to VKA in patients with cancer other than brain tumors.
The studies available concerning the prophylaxis of VTE included in the majority of cases cancer patients undergoing elective intracranial neurosurgery, but also patients undergoing spinal surgery for tumors. In contrast to studies performed in surgical patients with no brain or spinal tumor, timing of prophylaxis varied but it seems reasonable to start anticoagulation after surgery. The duration of VTE prevention was limited to the hospitalization period and no study has been conducted with extended prophylaxis. LMWH and UFH have similar efficacy and safety (in terms of major bleeding and intracranial bleeding) and are superior to no treatment. LMWH are more efficacious than external compression devices and are associated with an increase in minor bleeding but not in major and intracranial bleeding; external compression devices can be prescribed alone in patients with a contraindication to pharmacological prophylaxis.
Severe renal failure has been defined as a creatinine clearance below 30 mL/min. In this case LMWH and fondaparinux are contraindicated. No data have been published on the management of anticoagulation in cancer patients with renal insufficiency. For the treatment of VTE, the working group suggests using UFH followed by early VKA (possible from Day 1) or LMWH adjusted on the basis of anti-Xa level according to each LMWH for the treatment of established VTE. Such monitoring of anticoagulation could be helpful, since non-therapeutic anti-Xa levels are common among medical patients treated with LMWH, especially cancer patients [SALIBA2011]. The pharmacological prophylaxis of VTE in such patients may be considered on a case-by-case basis, knowing that UFH is not contraindicated.
The bleeding risk is correlated with platelet count and is significantly higher when below 50 G/L. In most studies, anticoagulation was withheld from patients with a platelet count of less than 50 G/L and resumed at the scheduled dose when the count was 100 G/L or higher.
For the treatment of VTE, the risk of recurrence is higher than the bleeding risk and the working group chose the cut-off point of 50 G/L for treatment with a full-dose anticoagulant.
Between 30 and 50 G/L, the decision must be based on a case-by-case analysis with a careful evaluation of the benefit-risk ratio. For prophylaxis, the risk of VTE is lower than the bleeding risk and the experts decided to select the cut-off point of 80 G/L.
During pregnancy VKA are contraindicated. So standard treatment of established VTE with long-term LMWH and standard prophylaxis with LMWH or UFH should be implemented (best practice because the judgment is based on experts’ opinion in view of the lack of data).

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8.5 Recommendations: special cases

R1. A brain tumor per se is not a contraindication to anticoagulation for established VTE

R2. For the treatment of established VTE in cancer patients with brain tumors we prefer LMWH

R3. We recommend the use of LMWH or UFH commenced postoperatively for the prevention VTE in cancer patients undergoing neurosurgery

R4. In the presence of severe renal failure (creatinine clearance <30 mL/min) we suggest using UFH followed by early VKA (possible from Day 1) or LMWH adjusted to anti-Xa level for the treatment of established VTE

R5. In patients with severe renal failure (creatinine clearance <30 mL/min), an ECD may be applied, and pharmacological prophylaxis may be considered on a case-by-case basis. In patients with severe renal failure (creatinine clearance <30 mL/min), UFH can be used on a case-by-case basis.

R6. In cancer patients with thrombocytopenia, full doses of anticoagulant can be used for the treatment of established VTE
if the platelet count is >50 G/L and there is no evidence of bleeding. For patients with a platelet count below 50 G/L, decisions on treatment and dosage should be made on a case-by-case basis with extreme caution.

R7. In cancer patients with mild thrombocytopenia, platelet count >80 G/L, pharmacological prophylaxis may be used. If the platelet count is below 80 G/L, pharmacological prophylaxis may only be considered on a case-by-case basis and careful monitoring is recommended.

R8. In pregnant cancer patients, standard treatment for established VTE and standard prophylaxis should be implemented.