Hemostatic Dysfunction in Malignant Hematologic Disorders

 

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Trousseau first pointed out the association between cancer and thrombosis in 1865. His preaching has since been confirmed by both clinical observations that this is the second most common cause of death in cancer patients, and by numerous studies of the pathophysiology of thrombosis. Many causative factors are now known, including procoagulants, inhibitors of fibrinolysis derived from tumor cells, leukocyte and platelet activation, cytokine-mediated injury to endothelial cells, and the presence of thrombogenic microparticles in the circulation. Several recent issues of Seminars in Thrombosis and Hemostasis have been devoted to this topic. Attention is now being paid to a similar increased thrombotic risk in malignant hematologic disorders. This topic was chosen for review in this issue, highlighting many features of thrombogenesis that are different from those seen in malignant solid tumors.

Even though most solid tumors share the same thrombogenic factors, many hematologic disorders in addition possess their own individual prothrombotic characteristics. Although the incidence of thromboembolism in cancer is well recognized at present, it is not commonly appreciated that the incidence of thromboembolism is also as high or even higher in malignant hematologic disorders. The incidence and an overview of the pathogenesis of thrombosis and bleeding are reviewed by Kwaan and Vicuna. The myeloproliferative disorders, though strictly not malignant diseases, are included in this review, given that thrombosis and bleeding are major complications.

The prothrombotic features of myeloproliferative disorders are described in the article by Tefferi and Elliott, whereas issues of the antithrombotic management in polycythemia vera and essential thrombocytosis are discussed by Barbui and Finazzi. In several disorders, the prothrombotic risk is present along with a bleeding diathesis, posing a double hazard for the patient. The first example of this is seen in acute promyelocytic leukemia. Despite the tremendous advances in response rate to new therapeutic modalities, such as all-trans retinoic acid chemotherapy, both thrombosis and bleeding remain the most prominent causes of morbidity and early mortality, as pointed out by Tallman et al. Likewise, this is also seen in paraproteinemias and amyloidosis, as presented by Zangari et al.

Another feature that is less often seen in solid tumors, but more common in hematologic disorders, is the presence of hyperviscosity. This topic was featured recently in Seminars in Thrombosis and Hemostasis, and is updated in this issue by Blum and Porcu. Bleeding and thrombosis are often the profound adverse side effects of drugs, and again these adverse effects are more commonly seen in hematologic disorders, as discussed by Zakarija and Kwaan. Tigue et al present their views about improved means of detecting these adverse events, and provide several examples of the benefits of pharmacovigilance.

During the course of hematologic malignancies, several thrombotic syndromes are encountered frequently. One is the hepatic sinusoidal obstruction syndrome (veno-occlusive disease) often seen in hematopoietic transplantation, as discussed by Ho et al. Another common problem related to treatment procedures is thrombotic occlusion of venous access catheters, a subject that is often troublesome, but is now better understood, as detailed in the article by Freytes. Perhaps more common is the rapid breakdown of tumor cells in many hematologic malignancies, resulting in tumor lysis syndrome (both spontaneous and as a response to chemotherapy), as noted by Tiu et al.

This issue would not be complete without attending to the special features in hematologic malignancies in children, as reviewed elegantly by Athale and Chan. Finally, two experts provide their views on the management of bleeding, discussed by Green, and the management of thrombosis, described by Chong.

The improved survival and use of newer therapeutic modalities are perhaps more notable in hematologic malignancies than in solid tumors. This is concomitant with an increased awareness of the bleeding and thrombotic complications. With a better understanding of the pathophysiology and proper management, these complications can be prevented or reduced in severity, and can ensure continued improvement in both the rate and the quality of survival.