A Medline search was carried out using combinations of the terms “blood platelets”, “cancer”, and “neoplasm”. The references in each relevant paper were reviewed. The resultant articles were predominantly limited to journals published in English between 1960 and 2002.
ReviewPlatelets and cancer
Section snippets
Platelet structure and function
Maturation of the megakaryocyte generates anucleate platelets, which are the smallest circulating blood cells. What platelets lack in size they make up in number, being roughly 100 times more common in the circulation than white blood cells.
Platelets are surrounded by a membrane covered with glycoproteins, including integrins, which are essential for the adhesion and aggregation required for haemostasis (figure 3). The invaginating plasma membrane increases the available surface area for the
Mechanisms of tumour-associated platelet activation
In patients with advanced cancer, especially, the expression of adhesion molecules on platelets is increased, indicating an activated platelet state. Of all the pathophysiological platelet activators, thrombin is perhaps the most important. Thrombin may be derived from tumour cells by the synthesis of tumour-associated tissue factor, which itself stimulates platelets. Tumour-generated thrombin activates adhesion of circulating tumour cells to platelets while both activating the platelets and
Platelet involvement in metastasis
The bioactive products of arachidonate metabolism include prostacyclin and thromboxane A2. The ratio of prostacyclin to thromboxane A2 concentrations is disturbed in many cancers, and endothelial cells deficient in prostacyclin show increased tumour-endothelial adhesion.15 The success of circulating metastases relies on extravasation, which means that the tumour cell must slow down to attach to the vascular endothelium. However, in blood flowing at a normal rate, shear forces oppose cell
Thrombocytosis
Although the mechanisms are not clear, one of the most common abnormalities in the blood of cancer patients is a high platelet count. This feature may be thought of as paraneoplastic disorder. Clinically, cancer patients may be characterised by thromboembolic disorders or thrombocytosis. Though we associate thrombocytosis with malignancy, in fact, the likelihood of an underlying cancer in a patient newly found to have thrombocytosis is rare.31
Thrombocytopenia and platelet transfusion in cancer patients
When cancer cells are injected experimentally, the
Mechanisms of abnormal platelet count in cancer patients
Host responses to malignancy, possibly production of bone-marrow-stimulating or inhibiting cytokines, may have a role in regulation of platelet counts in cancer patients.51 This idea is supported by studies in animals; the infusion of pancreatic tumour cells into hamsters results in a 50% reduction in platelet count.52 Confusingly, another study found that a human pancreatic cancer, of all the cell lines examined, showed the greatest megakaryocyte-potentiating activity.53
Platelet activation
Therapeutic use of platelet inhibitors and anticoagulants
The interactions between platelets and the metastasis of cancer could be used to develop therapies aiming to disrupt the relation. The possible stages of inhibiting the platelet assistance of cancer growth and spread are summarised in figure 5.
Thrombin inhibitors may act to interrupt the positive feedback loop of thrombin-activated tumours adhering to and activating platelets, thus inhibiting release of platelet-secreted agents that nurture tumour invasion and growth.
Prostacyclin is one of the
Conclusion
We have presented evidence that unarguably associates platelets with the growth and spread of cancer. The two-way association between platelets and cancer is apparent from the abnormal platelet counts found in patients with cancer, which may even assist in diagnosis and prediction of prognosis. Whether a high platelet count is a product of host response to tumour-secreted growth factors or a factor that directly promotes a worsened prognosis by cancer spread is uncertain. Though a high platelet
Search strategy
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