Alcohol induces profuse reversible decrease in platelet function and delayed initiation of coagulation

Moderate alcohol consumption may influence platelet aggregation, reduce fibrinogen concentration or increase clot dissolution. Since the binge-drinking pattern observed among some Northern people leads to exposure of traumatic brain injury and the immediate effects of alcohol on platelet function and whole blood coagulation are partly unknown, we performed an experiment aiming to characterize coagulation capacity during substantial intake of alcohol. A 49-year old volunteer man drank 1 bottle of sparkling wine within one hour: during the first 15 minutes–0.24 L, during the next 15 minutes–0.24 L more, and finally the rest of bottle (0.27 L) within 30 minutes. Rotational thromboelastometry and platelet function analysis have been performed. Platelet aggregation decreased at 30 minutes, but at 60 minutes the aggregation exceeded the 0 minutes values. Maximum clot firmness remained stable, but clot formation time was prolonged at 30 and 60 minutes. Fibrinolysis has been increased at 30 and 60 minutes. A momentary disturbance of platelet function followed by hyperaggregation, delayed initiation of coagulation and increase in fibrin clot lysis are seen during the early phase of alcohol intake. Since the effects of alcohol may be individual, a combination of detailed history of drinking and point of care evaluation of coagulation and platelet function may shed light on various treatment options in trauma patients on alcohol.


Introduction
Moderate alcohol consumption may influence platelet aggregation, reduce fibrinogen concentration or increase clot dissolution [1].Unfortunately, alcohol intake is a risk factor for traumatic brain injury (TBI).After TBI the development of intracranial haemorrhagic or ischaemic lesions are major determinants of outcome [2] and the risk of bleeding is highest in those patients with inadequate coagulation capacity.Since the binge-drinking pattern observed among some Northern people leads to exposure of TBI and the immediate effects of alcohol on platelet function and whole blood coagulation are partly unknown, we performed an experiment aiming to characterize coagulation capacity during substantial intake of alcohol.

Methods
After one week total abstinence of alcohol or drugs with theoretical effects on platelets or coagulation, and after 6-hour fast, a 49-year old volunteer man drank in the sitting position 1 bottle (0.75 L) of cool (+4-6°C) sparkling wine (2008 Cava Gramona, Brut Nature, Gran Reserva , Catalonia, Spain) within one hour: during the first 15 minutes-0.24L, during the next 15 minutes-0.24L more, and finally the rest of bottle (0.27 L) within 30 minutes.

Results
All the coagulation tests were normal before the experiment.Platelet count decreased at 30 and 60 minutes, but Hb concentration remained unchanged (Table 1).Platelet aggregation (all three activators) decreased at 30 minutes, but at 60 minutes the aggregation exceeded the 0 minutes values.Maximum clot firmness remained stable, but clot formation time was prolonged at 30 and 60 minutes in EXTEM® and FIBTEM® an-alyses ( 30 and 60 minutes.The alcometer showed 0, 0.92, and 0.94% at 0, 30, and 60 minutes, respectively.In vitro 15% vol.endconcentration of wine in the whole blood induced comparable findings with the observations regarding the volunteer.

Discussion
The present study demonstrates the immediate biphasic character of the coagulation capacity after substantial intake of alcohol in a man.The observations of the collapse of platelet function follows a rebound hyperaggregability with the simultaneous increase in fibrinogen clot dissolution.However, the most important parameter regarding traumatic coagulopathy, clot strength, remained stable although the development of whole blood clot was delayed and clot lysis enhanced.
The current findings may have direct clinical implications in TBI patients if the dynamic history of alcohol intake is known.It may be speculated that there is an increased risk of bleeding if TBI, or other trauma, occurs shortly after the start of drinking.At this phase, the three pathways of platelet activation are depressed by 72% (ASPI), 58% (ADP) and 69% (TRAP).This platelet inhibition is comparable with the combined effects of acetylsalisylic acid, clopidogrel and a glycoprotein-inhibitor on platelets and may be indicative of substantial increase risk of bleeding.However, this platelet dysfunction is short lived and later the platelets hyperaggregated even the alcometer results were unchanged.This finding may also indicate that to become a trauma victim later, i.e., 1 hour, after the start of drinking alcohol may be safer regarding only the platelet function and bleeding risk.
Traumatic hypocoagulopathy is defined by decrease in clot strength [3].Interestingly, in the current study the clot strength of the volunteer, and also in vitro with the 15% vol.end-concentration of wine, remained unchanged with simultaneous delay in clot formation.This finding is in accordance with previous studies [3,4], and clinically important, since the present guidelines regarding the treatment of traumatic coagulopathy are based on viscoelastic determination of clot strength.However, an attempt to counteract the particular effect of alcohol on clot formation may not be indicated since the developing clot representing combined function of extrinsic coagulation pathway and platelets (EXTEM), will be finally firm enough.In contrast, early administration of tranexamic acid to correct the increased alcohol induced lysis is supported by our study if a drunk man is a trauma victim, since the early administration of tranexamic acid in TBI or in spontaneous intracranial haematoma patients, prevents the development of intracranial bleeding.In the present observations, FIBTEM® maximum lysis was 8% at 30 minutes and 25% at 60 minutes, and in vitro 22% indicating hyperfibrinolysis which has also been shown to be present in 2.5-7% of TBI patients [5].Furthermore, the administration of tranexamic acid is in particular supported by the fact that the FIBTEM® clot strength was at the critical level of 8 mm doi: 10.7243/2052-6229-2-4 for bleeding at 30 minutes although the general weakening of clot strength was minimal.

Conclusion
A momentary disturbance of platelet function followed by hyperaggregation, delayed initiation of coagulation and increase in fibrin clot lysis are seen during the early phase of alcohol intake.Since the effects of alcohol may be individual, a combination of detailed history of drinking and point of care evaluation of coagulation and platelet function may shed light on various treatment options in trauma patients on alcohol.

Table 2 . ROTEM parameters at study intervals, results of breath analysis test and in vitro with 15% vol. end-concentration of wine.
CFT: Clot formation time; MCF: Maximum clot firmness; ML: Maximal lysis