Impact of Transfusion on Cancer Growth and Outcome.

For many years, transfusion of allogeneic red blood cells, platelet concentrates, and plasma units has been part of the standard therapeutic arsenal used along the surgical and nonsurgical treatment of patients with malignancies. Although the benefits of these blood products are not a matter of debate in specific pathological conditions associated with life-threatening low blood cell counts or bleeding, increasing clinical evidence is nevertheless suggesting that deliberate transfusion of these blood components may actually lead to negative clinical outcomes by affecting patient's immune defense, stimulating tumor growth, tethering, and dissemination. Rigorous preclinical and clinical studies are needed to dimension the clinical relevance, benefits, and risks of transfusion of blood components in cancer patients and understand the amplitude of problems. There is also a need to consider validating preparation methods of blood components for so far ignored biological markers, such as microparticles and biological response modifiers. Meanwhile, blood component transfusions should be regarded as a personalized medicine, taking into careful consideration the status and specificities of the patient, rather than as a routine hospital procedure.

Platelets effects on tumor growth.

Unlike other blood cells, platelets are small anucleate structures derived from marrow megakaryocytes. Thought for almost a century to possess solely hemostatic potentials, platelets, however, play a much wider role in tissue regeneration and repair and interact intimately with tumor cells. On one hand, tumor cells induce platelet aggregation (TCIPA), known to act as the trigger of cancer-associated thrombosis. On the other hand, platelets recruited to the tumor microenvironment interact, directly, with tumor cells, favoring their proliferation, and, indirectly, through the release of a wide palette of growth factors, including angiogenic and mitogenic proteins. In addition, the role of platelets is not solely confined to the primary tumor site. Indeed, they escort tumor cells, helping their intravasation, vascular migration, arrest, and extravasation to the tissues to form distant metastasis. As expected, nonspecific or specific inhibition of platelets and their content represents an attractive novel approach in the fight against cancer. This review illustrates the role played by platelets at primary tumor sites and in the various stages of the metastatic process.

Regulation of tumor growth and metastasis: the role of tumor microenvironment.

The presence of abnormal cells with malignant potential or neoplastic characteristics is a relatively common phenomenon. The interaction of these abnormal cells with their microenvironment is essential for tumor development, protection from the body's immune or defence mechanisms, later progression and the development of life-threatening or metastatic disease. The tumor microenvironment is a collective term that includes the tumor's surrounding and supportive stroma, the different effectors of the immune system, blood platelets, hormones and other humoral factors. A better understanding of the interplay between the tumor cells and its microenvironment can provide efficient tools for cancer management, as well as better prevention, screening and risk assessment protocols.

Platelet-cancer interactions.

Platelets play a crucial role in the pathophysiological processes of hemostasis and thrombosis. Increasing evidence indicates that they fulfill much broader roles in balancing health and disease. The presence of tumor cells affects platelets both numerically, through a wide variety of mediators and cytokines, or functionally through tumor cell-induced platelet activation, the first step toward cancer-induced thrombosis. This induction results from signaling events through the different platelet receptors, or may be cytokine-mediated. Reciprocally, upon activation, the platelets will release a myriad of growth factors from their dense and α-granules and peroxisomes; these will directly impact tumor growth, tethering, and spread. A similar cross-talk is initiated between tumor microvesicles stimulating the platelets and platelet microparticles, promoting both thrombosis and tumor growth. A vicious loop of activation thereafter takes place. Platelets directly and indirectly promote tumor growth, and enable a molecular mimicry coating the malignant growth and allowing metastasizing cells to escape T-cell-mediated immunity and natural killer cell surveillance. Breaking this vicious activation loop with nonspecific platelet inhibitors, such as aspirin, or by targeting specific sites on the activation cascade may offer a mean to reduce both the risks of development and progression of cancer and the risk of thrombosis.

Histidine rich glycoprotein and cancer: a multi-faceted relationship.

A better understanding of the interplay between the tumor environment, the immune system, and hemostatic apparatus is essential to effectively improve cancer treatment. Histidine-rich glycoprotein (HRG) is an abundant plasma protein with a wide array of functions. HRG has the ability to bind multiple ligands thereby modulating immunity, cell adhesion, angiogenesis, and thrombosis. Many of these functions are involved in tumor progression and antitumor response. We outline current data on HRG as an important potential player and as a potential future target for cancer therapy.

The platelet-cancer loop.

The relationship between cancer and thrombosis has been established since 1865 when Armand Trousseau described superficial thrombophlebitis as forewarning sign of occult visceral malignancy. Platelets are the primary hemostatic tool and play a primordial role in cancer-induced thrombosis. Tumor-induced numerical and functional platelet abnormalities have been described in conjunction to changes in coagulation. Such changes are reported even in the absence of clinically detectable thrombosis and correlate with tumor progression and metastasis. Reciprocally, platelets seem to interplay with the tumors and the immune system, both directly and indirectly favoring tumor progressions, tethering and distant spread. A number of growth factors supporting tumor growth, angiogenesis and metastasis are released from the platelets. A reciprocating loop of tumor-induced platelet activation/platelet-induced tumor growth and dissemination is initiated, acting as a thrombosis trigger/tumor amplifier. Recent studies have demonstrated that the use of anti-platelet agents can break this loop resulting in a reduction of short-term risk for incident cancer, cancer mortality and metastasis. The beneficial effect in reduction in cancer-induced thrombosis remains to be established. The current review aims at shedding the light on the intimate reciprocal cross-talk between platelets and cancer and on exploring the potential beneficial effect of anti-platelet agents in breaking the deadly loop of tumor amplification.

Venous thromboembolism risk and prophylaxis in the acute hospital care setting: report from the ENDORSE study in Egypt.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of hospital-related deaths worldwide. However, the proportion of patients at risk of VTE who receive appropriate prophylaxis in Egypt is unknown. The ENDORSE study in Egypt is part of a global initiative to uncover the incidence of high-risk surgical and medical patients and determine what proportion of these patients receive appropriate VTE prophylaxis. METHODS: Ten Egyptian hospitals participated in this observational study, enrolling all surgical and medical patients that met the study criteria. This resulted in a cohort of 1,008 patients in acute care facilities who underwent a retrospective chart review. Each patient's VTE risk status and the presence or absence of appropriate prophylactic care was assessed according to the American College of Chest Physicians (ACCP) guidelines 2004. RESULTS: Of the 1,008 patients enrolled, 395 (39.2%) were found to be at high-risk for VTE. Overall, 227 surgical patients were at high-risk, although only 80 (35.2%) received ACCP-recommended prophylaxis. Similarly, 55/268 (32.75%) of high-risk medical patients received appropriate VTE prophylaxis. Low molecular weight heparin was the most commonly used anticoagulant, while mechanical prophylactic use was quite low (1.5%) in high-risk patients. CONCLUSIONS: In Egypt, more than one-third of all patients hospitalized for surgery or acute medical conditions are at high risk for developing VTE. However, only a small fraction of these patients receive appropriate VTE prophylaxis. Corrective measures are necessary for preventing VTE morbidity and mortality in these high risk patients.