Summary. Malignancy affects the hemostatic system and the hemostatic system affects malignancy. In cancer patients there are a number of coagulation abnormalities which provide the background for an increased tendency of these patients to both thrombosis and hemorrhage. The causes of this coagulation impairment rely on general risk factors which are common to other categories of patients, and other factors which are specific to cancer, such as tumor type and disease stage. In addition, data from basic research indicate that the hemostatic components and the cancer biology are interconnected in multiple ways. Notably, while cancer cells are able to activate the coagulation system, the hemostatic factors play a role in tumor progression. This opens the way to the development of bifunctional therapeutic approaches that are both capable of attacking the malignant process and resolving the coagulation impairment. On the other hand, the management of thrombosis and hemorrhages in cancer patients can be different. To approach these problems, some guidelines have been released by prominent international scientific societies. Also actively investigated is the issue of identifying new biomarkers to classify the subjects at a higher risk, thus improving the prevention of thrombohemorrhagic events in these patients. Finally, novel prophylactic and therapeutic approaches are currently under development. This review provides an overview of the hemostatic complications in cancer, together with new insights into the interaction between hemostasis and cancer biology. We also review the assessment of the risk of thrombohemorrhagic events in cancer patients, and the prophylaxis and treatment of such manifestations.

Patients with hematologic malignancies are at high risk of thrombotic or hemorrhagic complications. The incidence of these events is greatly variable and is influenced by many factors, including the type of disease, the type of chemotherapy, and the use of a central venous device. As in solid tumors, a number of clinical risk factors have been identified and contribute to the increasing thrombotic rate in hematologic malignancies. Biologic properties of the tumor cells can influence the hypercoagulable state of patients with these malignancies by several mechanisms. Of interest, oncogenes responsible for neoplastic transformation in leukemia also may be involved in clotting activation. Epidemiologic data allow an estimate of the incidence of venous thromboembolism (VTE) in acute leukemia, lymphomas, and multiple myeloma (MM). In this review, we focus on the epidemiology, pathogenesis, and VTE management in these three hematologic malignancies. No recommendation for routine thromboprophylaxis in these conditions, with the exception of MM, is available. Large, prospective, randomized clinical trials are needed to establish the best practice for thromboprophylaxis and treatment of VTE in these types of cancers.

We used the thrombin generation assay to evaluate the hypercoagulable state according to JAK2^V617F mutational status in essential thrombocythemia (ET) and polycythemia vera (PV) patients. Thrombin generation was determined in the presence and absence of activated protein C (APC), and APC resistance was expressed as normalized APC sensitivity ratio (nAPCsr). Tissue factor pathway inhibitor (TFPI), total and free protein S (PS), prothrombin (FII), factor V (FV), and neutrophil elastase were measured in plasma; CD11b was measured on neutrophils. Compared with normal controls, patients had a lower endogenous thrombin potential in the absence of APC but had a higher endogenous thrombin potential in the presence of APC, showing the occurrence of APC resistance. The nAPCsr increased in JAK2^V617F carriers compared with noncarriers and was highest in JAK2^V617F homozygous patients. FII, FV, free PS, and TFPI levels were reduced in patients, mainly in JAK2^V617F carriers. Multiple regression analysis indicated the low free PS level as major determinant of the increased nAPCsr. Elastase was increased in patients and inversely correlated with free PS. In conclusion, these data indicate the occurrence of acquired APC resistance in ET and PV patients, probably because of a reduction in free PS levels. The APC-resistant phenotype is influenced by the JAK2^V617F mutational load.