Heat stress–induced platelet dysfunction is associated with loss of fibrinogen and is improved by fibrinogen supplementation
Hung-Yen Ke a), Jye-Hann Chen b), Shih-Yao Kao c), Cheng-Ming Tsao d), Chia-Wen Kuo e), Chin-Chen Wu b), Chih-Chin Shih b)
a-Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
b-Department and Graduate Institute of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC
c-Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
d-Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, ROC
e-Department of Nephrology, Taichung Armed Forces General Hospital, Taichung, Taiwan, ROC
Abstract
Introduction
Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbβ3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model.
Materials and methods
Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed.
Results
The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation.
Conclusions
An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke.