PRL as a Novel Potent Cofactor for Platelet Aggregation

Abstract

Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

Lack of relevant association between prolactin and immune responses in patients with chronic heart failure

“…CD62p was not correlated to PRL values ( r 2 = −0·012; P > 0·05). This finding is in contrast to our results in other patient‐groups [4] but can be explained by the low PRL values in our patients with CHF. Previously we have demonstrated in vitro that PRL enhances ADP‐stimulated CD62p expression in a dose‐dependent manner starting at PRL values greater than 10 ng mL −1 [4].…”

“…In our series of 50 patients with CHF (66·9 ± 12·6 years; EF: 22 ± 9%), we demonstrated significantly reduced serum levels of IL‐10, an anti‐inflammatory cytokine, revealing the inflammatory milieu in CHF [5]. To further elucidate the influence of hyperprolactinaemia in CHF on platelet activation, we retrospectively studied PRL values in the sera of our patients and compared these results with CD62p expression on platelets as previously described [4,6].…”

Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study

“…Similarly, drug induced atrial fibrillation would be an unlikely explanation for such a rapid increase in the risk of cerebrovascular adverse events. Potential mechanisms for cerebrovascular events related to atypical antipsychotics might include orthostatic hypotension in patients with pre-existing cerebrovascular disease, which might lead to “watershed” strokes,14 and antipsychotic induced hyperprolactinaemia, which might promote platelet aggregation 14 30. Others, however, have reported that risperidone may inhibit platelet aggregation (through serotonin receptor antagonism), rather than promote it 31.…”

Population-Based 5-Year Follow-Up Study in Taiwan of Dementia and Risk of Stroke

“…Furthermore, over-sedation induced by antipsychotic use may result in dehydration and hemoconcentration, which may be potential mechanisms for increased stroke risk [22]. The association of antipsychotics with stroke may be partially explained by their hyperprolactinemia effect, which may promote platelet aggregation [23], [24]. However, several studies have reported that antipsychotics may inhibit platelet aggregation through serotonin receptor antagonism rather than promote it [25].…”