The effect of heparin on platelet aggregation was systematically examined on platelets in plasma (PRP), as well as on gel-filtered, washed, and formaldehyde-fixed platelets. Results indicate that, although heparin causes a mild potentiation of platelet aggregation in the PRP systems, a significant inhibitory activity is observed when heparin is added to isolated platelets. This inhibitory activity appears to be specific and not related to the impurities in the heparin preparations, as heparinase, as well as protamine, effectively neutralizes the heparin-mediated inhibitory activity on platelet aggregation. Although heparin-mediated inhibitory activity can be demonstrated in the presence of a number of different agonists (ADP, arachidonic acid, thrombin, Ionophore A23187, epinephrine, and ristocetin), the most pronounced inhibition is seen in the presence of ristocetin. Further studies show that heparin enhances thromboxane generation in isolated platelets. Platelets pretreated with heparin, however, fail to respond to preformed thromboxane. These findings suggest that, in addition to the potentiation of thromboxane production in platelets, heparin may also attribute some change(s) to the platelet(s)/platelet membrane, which interferes with their ability to respond to the agonists of platelet aggregation. This antiaggregatory activity of heparin was found to be inhibited by a factor(s) present in plasma but not in serum.

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Thromboembolic (TE) events preceding cancer have been observed. Some studies failed to find this correlation. We retrospectively examined the cancer incidence following thromboembolic events in patients at our medical center. Medical records of 183 patients with established thromboembolic events documented in their records were selected and reviewed. Time interval between primary, secondary, and recurrent TE events preceding cancer diagnosis was analyzed. Two hundred age-and sex-matched controls seen during the same period and without any evidence of TE were randomly selected and charts reviewed for malignancy. Cancer occurred after TE in 48 of 183 patients (26.2%). In controls, cancer was diagnosed in 23 (11.5%). This was statistically significant with an odds ratio of 2.736 (1.586, 4.720). In the 64 primary TE patients, the cancer incidence was 37.5%. The 63 patients with recurrent TE had an incidence of 35.4%, and 56 secondary TE patients had an incidence of 27.1%. Time between initial TE and cancer diagnosis was <6 months in 27 (56.3%) patients, between 6 months and 1 year in 12 (25.0%), 1-5 years in 5 (10.4%), and >5 years in 4 (8.3%). Fourteen (31.1%) TE patients presented with metastatic cancer. This study indicates that thromboembolic events are important predictors of cancer. Cancer in this population occurs within a year in the majority of patients. Cancer screening in patients without identifiable risk factors for thrombosis could be helpful for early detection, diagnosis, and management of cancer. Am. J. Hematol. 72: 109-114, 2003.