Platelets: The Balance between Aggregation and Bleeding

Platelets are the soldiers of the blood. After they have been released from the megakaryocytes in the bone marrow, they are very well equipped for their tasks: initiation of blood coagulation when there is an interruption of the vessel wall together with the coagulation factors in the blood. However, they cannot differentiate between an interruption of vessel integrity (bleeding) or denudation of the endothelial layer of the vessel wall (e.g., plaque rupture). Much effort has been directed into understanding mechanisms and targets for antiplatelet drugs, and prognostic implications.[1] [2] [3]

The good news is that nowadays we already have established medications that interfere with platelet adhesion and subsequent aggregation, and that we can measure platelet function ex vivo.[4] The closed balance between aggregation on one hand and bleeding on the other is the focus of the theme issue Platelets that has been released today.

The first two papers[5] [6] describe platelet function testing in hemostasis in arterial and venous thrombosis: the first on total antithrombotic effects of combination antithrombotic effects in various cardiovascular conditions, and the second on the role of platelet micro-ribonucleic acids in platelet function in stable and unstable coronary artery disease.

Following these papers, clinical issues in antithrombotic therapy are highlighted. First, the role of antiplatelet therapy in primary prevention of cardiovascular disease in a healthy but high-risk growing population: the diabetics.[7] Combining antiplatelet and anticoagulant therapy is the next topic, when dual or single antiplatelet therapy is combined in high-risk patients with stable coronary artery disease.[8]

Implantation of devices is now current practice in cardiology. Needless to say that the foreign body implants cause activation of the coagulation system including blood platelets. The current evidence is given in a paper on device implantation.[9]

Finally, the use of multiple antiplatelet agents may cause more bleeding than a single drug. The P2Y₁₂ receptor antagonists have found their way in several clinical thrombotic conditions, but they are associated with bleeding when used together with aspirin. Currently, there are reversal strategies available to antagonize the action of P2Y₁₂ receptor antagonists. This will be discussed in the last chapter of this issue.[10]

Conflict of Interest

F.W.A.V. reports personal fees from AstraZeneca, during the conduct of the study.

• References

• 1 Spronk HMH, Padro T, Siland JE. , et al. Atherothrombosis and thromboembolism: position paper from the Second Maastricht Consensus Conference on Thrombosis. Thromb Haemost 2018; 118 (02) 229-250
• 2 de Carvalho LP, Fong A, Troughton R. , et al. Prognostic implications of dual platelet reactivity testing in acute coronary syndrome. Thromb Haemost 2018; 118 (02) 415-426
• 3 Stratz C, Nührenberg T, Valina CM. , et al. Impact of reticulated platelets on the antiplatelet effect of the intravenous P2Y12-receptor inhibitor cangrelor. Thromb Haemost 2018; 118 (02) 362-368
• 4 Sibbing D, Angiolillo DJ, Huber K. Antithrombotic therapy for acute coronary syndrome: past, present and future. Thromb Haemost 2017; 117 (07) 1240-1248
• 5 Kaikita K, Hosokawa K, Dahlen JR, Tsujita K. Total Thrombus-Formation Analysis System (T-TAS): clinical application of quantitative analysis of thrombus formation in cardiovascular disease. Thromb Haemost 2019; 119 (10) 1554-1562
• 6 Stojkovic S, Nossent AY, Haller P. , et al. MicroRNAs as regulators and biomarkers of platelet function and activity in coronary artery disease. Thromb Haemost 2019; 119 (10) 1563-1572
• 7 Schrör K, Kristensen SD, Storey RF. , et al. Aspirin and primary prevention in patients with diabetes - a critical evaluation of available randomized trials and meta-analyses. Thromb Haemost 2019; 119 (10) 1573-1582
• 8 Sumaya W, Geisler T, Kristensen SD, Storey RF. Dual antiplatelet or dual antithrombotic therapy for secondary prevention in high-risk patients with stable coronary artery disease?. Thromb Haemost 2019; 119 (10) 1583-1589
• 9 Geisler T, Jorbenadze R, Popov A-F. , et al. Thrombogenicity and antithrombotic strategies in structural heart interventions and non-aortic cardiac device therapy – current evidence and practice. Thromb Haemost 2019; 119 (10) 1590-1605
• 10 Trenk D, Hille L, Leggewie S. , et al. Antagonizing P2Y12-receptor antagonists: current and future options. Thromb Haemost 2019; 119 (10) 1606-1616