Platelet Activation after Presyncope by Lower Body Negative Pressure in Humans

Abstract

Central hypovolemia elevates hemostatic activity which is essential for preventing exsanguination after trauma, but platelet activation to central hypovolemia has not been described. We hypothesized that central hypovolemia induced by lower body negative pressure (LBNP) activates platelets. Eight healthy subjects were exposed to progressive central hypovolemia by LBNP until presyncope. At baseline and 5 min after presyncope, hemostatic activity of venous blood was evaluated by flow cytometry, thrombelastography, and plasma markers of coagulation and fibrinolysis. Cell counts were also determined. Flow cytometry revealed that LBNP increased mean fluorescence intensity of PAC-1 by 1959±455 units (P<0.001) and percent of fluorescence-positive platelets by 27±18%-points (P = 0.013). Thrombelastography demonstrated that coagulation was accelerated (R-time decreased by 0.8±0.4 min (P = 0.001)) and that clot lysis increased (LY60 by 6.0±5.8%-points (P = 0.034)). Plasma coagulation factor VIII and von Willebrand factor ristocetin cofactor activity increased (P = 0.011 and P = 0.024, respectively), demonstrating increased coagulation activity, while von Willebrand factor antigen was unchanged. Plasma protein C activity and tissue-type plasminogen activator increased (P = 0.007 and P = 0.017, respectively), and D-dimer increased by 0.03±0.02 mg l−1 (P = 0.031), demonstrating increased fibrinolytic activity. Plasma prothrombin time and activated partial thromboplastin time were unchanged. Platelet count increased by 15±13% (P = 0.014) and red blood cells by 9±4% (P = 0.002). In humans, LBNP-induced presyncope activates platelets, as evidenced by increased exposure of active glycoprotein IIb/IIIa, accelerates coagulation. LBNP activates fibrinolysis, similar to hemorrhage, but does not alter coagulation screening tests, such as prothrombin time and activated partial thromboplastin time. LBNP results in increased platelet counts, but also in hemoconcentration.

Coagulation changes during lower body negative pressure and blood loss in humans

“…Consistent with this idea, platelet activation, demonstrated by increased exposure of active glycoprotein 2b/3a, has been shown after LBNP (37). We observed an increase in platelet count after both LBNP and BL.…”

Viscoelastic Tissue Plasminogen Activator Challenge Predicts Massive Transfusion in 15 Minutes

“…Furthermore, shock promotes fibrinolysis from non-trauma patients with pre hospital circulatory collapse, who have a high incidence of hyperfibrinolysis (32). This is also evident in healthy subjects undergoing mimicked shock with lower body blood pooling that increase their tPA levels 10 fold from baseline (33). TEG also provides additional indices of coagulation abnormality, which can guide blood product resuscitation beyond plasma.…”

The target of vasovagal syncope is hemostasis and not heart protection

“…In both cases, the blood levels of von Willebrand factor and factor VIII increased dramatically after fainting. These findings could be replicated in two experimental studies [9,14] in normal subjects who suffered vasovagal pre-syncope during LBNP. Moreover, Zaar et al [14] demonstrated platelet activation and a significant acceleration of coagulation after LBNP-induced pre-syncope.…”

“…These findings could be replicated in two experimental studies [9,14] in normal subjects who suffered vasovagal pre-syncope during LBNP. Moreover, Zaar et al [14] demonstrated platelet activation and a significant acceleration of coagulation after LBNP-induced pre-syncope. A reduction in coagulation time is even present during lower levels of LBNP-induced decreases of central venous pressure (CVP) insufficient to induce presyncope.…”