Patients With Thrombocytopenia. The subcommittee on hemostasis and malignancy for the Scientific and Standardization Committee of the International Society on Thrombosis and haemostasis has recently recommended that anticoagulation be administered if the platelet count can be maintained above 50 x 109/L.53 For platelet counts between 20 and 50 x 109/L, half-dose LMWH can be administered with close monitoring for possible bleeding. If the platelet count is less than 20 x 109/L therapeutic doses of anticoagulation should be held. In these cases, the placement of an IVC filter is recommended to prevent PE. Once thrombocytopenia has resolved, it is recommended to initiate or resume therapeutic anticoagulation.2-4,42
Patients With Bleeding. In view of life-threatening bleeding complications, all patients should be assessed on a case-by-case basis and careful monitoring of additional bleeding risk is recommended. In patients with minor bleeding, anticoagulation may be continued as long as close follow-up is available; whereas, in patients with absolute contraindications to anticoagulation, the risk of bleeding likely outweighs the benefit of treatment, and anticoagulants should be withheld.3 The use of IVC filters are also recommended in this population—at least until the bleeding risk subsides and anticoagulation can be initiated.2-4,42
Patients With Brain Tumors. As per the national and international guidelines,3,42 a brain tumor per se is not a contraindication for anticoagulation. Anticoagulation is more effective and safer than filters when maintained in the therapeutic range in patients with brain metastases and VTE.54 Although LMWH is the preferred drug of choice in this group of patients, a decision should be made based on individual clinical assessment. Consideration should also be made for the primary tumor type since brain metastases from certain malignancies, such as melanoma, have higher tendencies to bleed.55
Patients With Renal Failure. Since LMWHs and fondaparinux are dependent on significant renal clearance, these agents should be avoided in patients with a creatinine clearance ≤30 mL/minute. Unfractionated heparin is the drug of choice in this setting and vitamin K antagonists can be started as early as on day 1.42 Fixed-dose or adjusted-dose subcutaneous UFH is also an option of outpatient management of VTE in patients with renal failure.5
Patients With Recurrent VTE on Anticoagulants. Extension of or a new DVT or PE despite being on anticoagulation therapy is defined as anticoagulation failure. Recurrent VTE is common in cancer patients, as seen in 9% of patients from the CLOT trial. Management strategies for recurrent VTE include optimizing or increasing the dose, switching agents, or placing an IVC filter. If patients are currently on once-daily enoxaparin regimens, this should be switched to the twice-daily regimen. Patients on agents other than LMWH should be switched to LMWH if possible, and dosed accurately based on the most recent total body weight and renal function. Although not useful in the emergency setting, an anti-Xa level should be drawn for patients who present with recurrent VTE on LMWH to assess whether patients are in therapeutic range. Peak anti-Xa levels should be checked 4 to 6 hours after the last dose. Lastly, dosing of LMWH could be increased by 20% to 25%, based on safety and efficacy data from a retrospective cohort study.56
Patients With Symptomatic Catheter-Related Thrombosis. For the treatment of symptomatic catheter-related thrombosis in cancer patients, the international clinical practice guidelines recommend use of anticoagulants for a minimum of 3 months.42 The CHEST guidelines suggest that the catheter not be removed if it is functional, not infected, and there is an ongoing need for the catheter.5 Little data exist in this subgroup of patients, but LMWHs are suggested.
Factors one should consider before commencing anticoagulation treatment include patient refusal, lack of therapeutic benefit, quality of life and life expectancy, bleeding risk, and whether anticoagulation is associated with an unreasonable burden.
Outpatient Treatment Criteria. In the absence of renal impairment, high risk of bleeding, or poor social circumstances, patients with DVT can be treated as an outpatient.57 Although recent studies support the safety and efficacy of outpatient PE management in noncancer patients,58,59 there is no study to support this in cancer patients. Several prognostic tools exist to aid the clinician in deciding whether cancer patients with PE can be treated as outpatients or require hospitalization. These prediction tools identify patients at a low in-hospital mortality in which outpatient management is reasonable. A few examples include the Geneva Pulmonary Embolism Prognostic Index, Pulmonary Embolism Severity Index, and the Aujesky and Murugappan prediction tools.57
The Decision Not to Treat
Acute intervention is not the only option in this unique population. Factors one should consider before commencing anticoagulation treatment include patient refusal, lack of therapeutic benefit, quality of life and life expectancy, bleeding risk, and whether anticoagulation is associated with an unreasonable burden.
Conclusion
In view of an increased risk of VTE in cancer patients, an increased level of clinical suspicion should be maintained. Risk factors related to patient, cancer type, treatment, and biochemical markers should be assessed, and the clinician should also consider using the modified Khorana score. Diagnostic imaging studies should also be performed in cases in which there is a high clinical suspicion of VTE.
Regarding treatment, the preferred drug of choice in the acute phase of treatment is LMWH—unless contraindications exist. In cancer patients with VTE who have severe renal failure, thrombocytopenia, brain tumors, or catheter related thrombosis, recommendations are based on best clinical practice, and the clinician should balance the desirable and undesirable effects depending on the bleeding risk versus VTE risk.