Functional enhancement of platelet activation and aggregation by erythrocytes: role of red cells in thrombosis

Platelets expose phosphatidylserine (PS), a component of the prothrombinase complex, on the outer surface of the plasma membrane when activated. [ref 1] The prothrombinase complex catalyzes the conversion of prothrombin to thrombin, and it has been demonstrated that an increase in PS exposure is correlated with an increase in thrombin generation by platelets. [refs 2,3] Similarly, erythrocyte (RBC) activation, or eryptosis, is also characterized by PS exposure on the plasma membrane. [ref 4] Although PS exposure on RBCs is considered a signal for splenic macrophage destruction, eryptosis may allow RBCs to contribute to thrombosis.[ref 4] The aims of this study were to determine whether the addition of RBCs to platelets increased functional platelet aggregation and coagulation properties. A ratio of 4 RBCs to 1 platelet (4:1) was evaluated for aggregation and coagulation compared to platelet control. Platelet aggregation and coagulation properties were evaluated with impedance aggregometry and thromboelastography, respectively. The 4:1 experimental group had significant increases in aggregation and coagulation relative to the platelet control. These results indicate that RBCs increase platelet aggregation and coagulation properties. This suggests that RBCs play a role in diseases traditionally thought of as associated solely via dysregulated platelet activation.

Functional enhancement of platelet activation and aggregation by erythrocytes: role of red cells in thrombosis

Platelets expose phosphatidylserine (PS), a component of the prothrombinase complex, on the outer surface of the plasma membrane when activated. [ref 1] The prothrombinase complex catalyzes the conversion of prothrombin to thrombin, and it has been demonstrated that an increase in PS exposure is correlated with an increase in thrombin generation by platelets. [refs 2,3] Similarly, erythrocyte (RBC) activation, or eryptosis, is also characterized by PS exposure on the plasma membrane. [ref 4] Although PS exposure on RBCs is considered a signal for splenic macrophage destruction, eryptosis may allow RBCs to contribute to thrombosis.[ref 4] The aims of this study were to determine whether the addition of RBCs to platelets increased functional platelet aggregation and coagulation properties. A ratio of 4 RBCs to 1 platelet (4:1) was evaluated for aggregation and coagulation compared to platelet control. Platelet aggregation and coagulation properties were evaluated with impedance aggregometry and thromboelastography, respectively. The 4:1 experimental group had significant increases in aggregation and coagulation relative to the platelet control. These results indicate that RBCs increase platelet aggregation and coagulation properties. This suggests that RBCs play a role in diseases traditionally thought of as associated solely via dysregulated platelet activation.

The Influence of Diet and Nutrients on Platelet Function

Cardiovascular disease (CVD) is the leading cause of death worldwide. Platelet activation and aggregation play an integral role in hemostasis and thrombosis. Diets and nutrients play a potential role in modifying CVD progression, particularly in platelet function, and have the potential of altering platelet function tests. Diets such as Mediterranean diet, high in omega-3 polyunsaturated fatty acids (PUFA), and vegetarian diets have inverse relationships with CVD. Dark chocolate, foods with low glycemic index, garlic, ginger, omega-3 PUFA, onion, purple grape juice, tomato, and wine all reduce platelet aggregation. Dark chocolate and omega-3 PUFA also reduce P-selectin expression. In addition, dark chocolate reduces PAC-1 binding and platelet microparticle formation. Berries inhibit platelet function (PFA-100). Energy drinks have been shown to increase platelet aggregation and caffeine increases platelet microparticle formation. Therefore, repeat testing of platelet function may be required, not only after exclusion of known antiplatelet medications but also potentially after exclusion of dietary substances/nutrients that could have plausibly affected initial test data.

Effect of Cigarette Smoking on Platelet Aggregation

Background: Cigarette smoking may increase platelet aggregation and cause atherothrombotic cardiovascular events. We aimed to investigate the impact of cigarette smoking on platelet function in patients with ischemic coronary heart disease (CHD).Methods: Twenty patients with ischemic stable CHD under aspirin therapy (300 mg/d), who continue to smoking despite all warnings, and 20 nonsmokers with CHD are enrolled in the study. Platelet function is studied at the morning, before and 15 minutes after the first cigarette, by the Platelet Function Analyzer (PFA)-100, with collagen and epinephrine and collagen and adenosine diphosphate cartridges. Post aspirin platelet hyperactivity is defined as having a closure time (CT) shorter than 186 seconds despite regular aspirin intake. Serial CT measurements are analyzed by paired samples t test.Results: Persistent platelet activity was present in 4 smoker (20%) and 3 nonsmoker (15%) patients at the beginning. Platelet activity measured by the PFA-100 is been increased significantly after cigarette smoking ( P = .004). Shorter CTs were determined after smoking in all patients with and without baseline persistent platelet activity, and 4 more participants became aspirin nonresponder ( P = .004). No significant differences in demographic, hematological, and biochemical parameters were determined between aspirin responders and nonresponders.Conclusions: We determined that cigarette smoking may increase platelet aggregation in patients with ischemic CHD in an aspirin nonresponsive manner. Our results emphasize the importance of quitting cigarette smoking in patients with CHD.

Dextran and postoperative thromboembolism

Two preparations of dextran have been tried for prevention of venous thromboembolic disease, dextran-40 (average m. w. 40,000) and dextran-70 (average m.w. 70,000). Dextrans reduce platelet aggregation and lower blood viscosity.1 Dextran may also reduce the peri-operative rise in the coagulation factors V and VIII.2 However, in some tests dextrans increase platelet aggregation3 and accelerate fibrin formation,4 so that only clinical trial can show whether dextran reduces the incidence of either deep-vein thrombosis or of pulmonary embolism.

The Potentiation of Platelet Aggregation and Adhesion by Heparin in Vitro and in Vivo

1. Heparin has been shown to increase platelet aggregation by ADP and adrenaline and to enhance the platelet release reaction when tested in citrated platelet-rich plasma (P.R.P.). This activity is present when heparin is added to P.R.P. or when P.R.P. is prepared after intravenous injection of heparin, and when heparin is added to non-anticoagulated native P.R.P. 2. Retention of platelets by cellophane membranes within a specially designed test-cell was significantly increased when heparin was added to citrated whole blood. 3. Though aspirin blocks the release reaction with and without heparin, it does not prevent the potentiation of initial ADP or first wave adrenaline aggregation caused by heparin.