• **VTE in Myeloproliferative Neoplasms**

Life expectancy of patients with myeloproliferative neoplasms (MPNs) and particularly that of subjects with polycythemia vera (PV) and essential thrombocythemia (ET) has significantly increased over the last three decades, largely due to the use of cytoreductive treatments. Currently, PRV and ET are considered relatively benign diseases in which the main objective of treatment strategy is the prevention of thrombotic events. Widespread use of routine haematologic screening and novel diagnostic tools greatly facilitate disease recognition and treatment. This helps to prevent a significant number of early vascular events that still constitute the first disease manifestation in approximately one-third of patients (205). We can also expect that new therapeutic options and appropriate use of aspirin will result in a further reduction of morbidity and mortality. One of the unmet needs of PRV and ET is validated methods for vascular risk stratification. The evaluation of the thrombotic risk in the individual patients, as reported by Barbui et al. in their paper (206).

The pathogenesis of thrombosis in myeloproliferative neoplasms has been extensively investigated by focusing in particular on the possible contribution of disease related haemostatic abnormalities. However, the pathogenesis of thrombosis appears to be multifactorial. Red blood cell, platelet, and leukocyte abnormalities, both qualitative and quantitative, are likely to play a key-role in myeloproliferative neoplasm thrombophilia. High shear stress of the vessel wall, due to blood hyperviscosity, accounts for chronic endothelial dysfunction and platelet and leukocyte activation.

Platelets and endothelial cells play a pivotal role in regulating blood flow, both cells might contribute to determine a prothrombotic microenvironment in myeloproliferative neoplasm patients by producing more soluble selectins and less nitric oxide, likely as a consequence of inflammation (207).

According to the data of Barbui et al. (208) it is intriguing to consider the possibility that pentraxin 3 response to inflammation in subjects with high JAK2 burden might contribute to lower or enhance the thrombotic risk. More generally the association between JAK2 mutation, inflammation and thrombotic risk deserves scientific attention also for other speculative and practical purposes.

Venous Thromboembolism in Cancer Patients 95

Of 819 patients 61 (7.4%) experienced VTE during a median follow-up of 656 days. The cumulative VTE probability in the original risk model after 6 months was 17.7% in patients with the highest risk score (≥ 3, n = 93), 9.6% in those with score 2 (n = 221), 3.8% in those with score 1 (n = 229) and 1.5% in those with score 0 (n = 276). In the expanded risk model, the cumulative VTE probability after 6 months in patients with the highest score (≥ 5, n = 30) was 35.0% and 10.3% in those with an intermediate score (score 3, n = 130) as opposed to only 1.0% in patients with score 0 (n = 200); the hazard ratio of patients with the highest compared with those with the lowest score was 25.9 (8.0-84.6). The authors demonstrated that clinical and standard laboratory parameters with addition of biomarkers enable prediction of VTE and allow identification of cancer patients at high or low risk of VTE.

Ay C et al concluded that with expanded risk model, which included sP-selectin ≥53.1 mg/ml and D-Dimer ≥1.44 mg/ml, (2 biomarkers) the risk prediction can be considerably improved. In patients with the highest compared with patients with the lowest risk, the

The advantage of the "Khorana-Score" is that all parameters of this risk model are routinely

Using Khorana risk scoring model or Ay Cihan et al expanded scoring model, it is within the reach of the attending hematologist/oncologist to stratify his/her cancer patient into one of the VTE risk groups: very high, high, intermediate or low and consider the patient for

It also well understood that prophylaxis with antithrombotic agents can be problematic in cancer patients because they are at increased risk for anticoagulant induced bleeding. However, prophylaxis has been shown to be beneficial in certain high-risk populations such as post-surgical or hospitalized cancer patients but data in the ambulatory settings are

In general, surgery for cancer increases the risk of VTE and adequate prophylaxis has been shown to reduce VTE rates significantly [99,100]. A number of studies have shown that patients with cancer who undergo a specific type of major surgery have a 2-4 fold higher incidence of postoperative VTE compared with patients without cancer. The risk of venographically proven DVT varies from 20% to 40% and the risk of fatal PE is approximately 1%. Therefore, routine prophylaxis with anticoagulant therapy is strongly recommended, both in the immediate post-operative setting and in the extended period

The agents used most widely for prophylaxis in surgical patients are unfractionated heparin (UFH) and low-molecular- weight heparin (LMWH). Meta-analysis of randomized trials evaluating anticoagulant prophylaxis in general surgery, Mismetti et al. (211), found no significant difference between LMWH and UFH in symptomatic VTE, major bleeding, transfusion and death. This finding is supported by the ENOXACAN study (212). The

**7. Prevention of venous thromboembolism in cancer patients** 

probability for VTE was 26-fold higher.

conflicting.

following major surgery.

determined in cancer patients at diagnosis.

thromboprophylaxis in a patient-focused approach.

**7.1 Prophylaxis in surgical cancer patients** 
