Patients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether... Show morePatients with severe infection have an increased risk of cardiovascular events. A possible underlying mechanism is inflammation-induced platelet aggregation. We investigated whether hyperaggregation occurs during infection, and whether aspirin inhibits this. In this multicentre, open-label, randomised controlled trial, patients hospitalised due to acute infection were randomised to receive 10 days of aspirin treatment (80 mg 1dd or 40 mg 2dd) or no intervention (1:1:1 allocation). Measurements were performed during infection (T1; days 1-3), after intervention (T2; day 14) and without infection (T3; day > 90). The primary endpoint was platelet aggregation measured by the Platelet Function Analyzer (R) closure time (CT), and the secondary outcomes were serum and plasma thromboxane B2 (sTxB2 and pTxB2). Fifty-four patients (28 females) were included between January 2018 and December 2020. CT was 18% (95%CI 6;32) higher at T3 compared with T1 in the control group (n = 16), whereas sTxB2 and pTxB2 did not differ. Aspirin prolonged CT with 100% (95%CI 77; 127) from T1 to T2 in the intervention group (n = 38), while it increased with only 12% (95%CI 1;25) in controls. sTxB2 decreased with 95% (95%CI - 97; - 92) from T1 to T2, while it increased in the control group. pTxB2 was not affected compared with controls. Platelet aggregation is increased during severe infection, and this can be inhibited by aspirin. Optimisation of the treatment regimen may further diminish the persisting pTxB2 levels that point towards remaining platelet activity. This trial was registered on 13 April 2017 at EudraCT (2016-004303-32). Show less
Scheres, L.J.J.; Selier, N.L.D.; Nota, N.M.; Diemen, J.J.K. van; Cannegieter, S.C.; Heijer, M. den 2021
Background The transgender population that uses gender-affirming hormone therapy (GAHT) is rapidly growing. The (side) effects of GAHT are largely unknown. We examined the effect of GAHT on... Show moreBackground The transgender population that uses gender-affirming hormone therapy (GAHT) is rapidly growing. The (side) effects of GAHT are largely unknown. We examined the effect of GAHT on coagulation parameters associated with venous thromboembolism (VTE) risk.Methods Factor (F)II, FIX, FXI, protein (p)C and free pS, fibrinogen, hematocrit, sex hormone-binding globulin, and normalized activated protein C ratio were measured in 98 transwomen (male sex at birth, female gender identity) and 100 transmen (female sex at birth, male gender identity) before and after 12 months of GAHT (oral or transdermal estradiol and anti-androgens in transwomen, transdermal or intramuscular testosterone in transmen). Mean paired differences in coagulation measurements were estimated with 95% confidence intervals (95% CI). Differences for route of administration and age were assessed with linear regression.Results After GAHT, transwomen had more procoagulant profiles with a mean increase in FIX: 9.6 IU/dL (95% CI 3.1-16.0) and FXI: 13.5 IU/dL (95% CI 9.5-17.5), and a decrease in pC: -7.7 IU/dL (95% CI -10.1 to -5.2). Changes in measures of coagulation were influenced by route of administration (oral vs. transdermal) and age. A higher sex-hormone binding globulin level after 12 months was associated with a lower activated protein C resistance. In transmen, changes were not procoagulant overall and were influenced by age. Differences for route of administration (transdermal vs. intramuscular) were small.Conclusions GAHT in transmen was not associated with apparent procoagulant changes, which provides some reassurance regarding VTE risk. In transwomen, GAHT resulted in procoagulant changes, which likely contributes to the observed increased VTE risk. Show less
Diemen, J.J.K. van; Madsen, M.C.; Vrancken, P.; Bie, K. de; Bom, J.G. van der; Veen, G.; ... ; Thijs, A. 2020
Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which... Show moreCardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B-2(sTxB(2)) levels, the Platelet Function Analyzer (PFA)-200 (R) Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow (R)), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB(2)levels were the lowest after OD-evening in comparison with OD-morning (p= <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p= .01) and BID (p= .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk. Show less
Diemen, J.J.K. van; Dijk, A. van; Racca, C.; Knol, T.; Bonten, T.N.; Numans, M.E.; ... ; Thijs, A. 2019
