platelet aggregation inhibitors such as acetylsalicylic acid , adenosine diphosphate ( adp ) receptor inhibitors , and vitamin k antagonists are a fixed constant in the treatment of acute and chronic atherothrombotic vascular diseases , including myocardial infarction , acute coronary syndrome , peripheral arterial obstructive disease , and atrial fibrillation [ 1 , 2 ] . the prescribing data for platelet aggregation inhibitors and sales figures for acetylsalicylic acid suggest that their use is becoming more widespread ( figure 1 ) . their prescription and use are dependent on comorbidities and age , however , which can increase the attendant risk of haemorrhage . these drugs , which are being used increasingly in the elderly , are of neurological importance in the event of intracranial haemorrhage , for instance . the types of intracranial haemorrhage deserving special mention are intracerebral , acute , and chronic subdural haemorrhage , and spontaneous subarachnoid haemorrhage . approximately 20% of all patients admitted with traumatic brain injury are found to have acute subdural haematoma , which primarily occurs between the age of 31 and 47 years . chronic subdural haematoma ( figure 2 ) is one of the most common forms of traumatic intracranial haemorrhage   and is often caused by a mild traumatic incident only seldom recalled by the patient . common to all these types of haemorrhage is the fact that more extensive and prolonged bleeding , as well as a greater risk of secondary haemorrhaging , can be expected if the patient is already taking a platelet aggregation inhibitor [ 8 , 9 ] ( figure 3 ) . when faced with the dilemma of prohemostatic measures for minimising the complications of intracranial haemorrhage and an indication for platelet aggregation inhibition , the question of the best possible treatment arises . desmopressin acetate , which is known to attenuate the effect of acetylsalicylic acid , has been studied in cardiac diseases [ 1014 ] . desmopressin ( 1-deamino-8-d - arginine vasopressin ) increases plasma factor levels due to the endogenous release of coagulation factor viii ( fviii ) , von willebrand factor ( vwf ) and tissue plasminogen activator ( tpa ) , enhanced platelet adhesion , and reduced bleeding time [ 1013 , 15 ] . the exact mechanism of action of acetylsalicylic acid , however , has not been fully explained . here we discuss the possibility of attenuating the effect of acetylsalicylic acid based on an observational study in patients with intracranial haemorrhage . the local ethics committee approved the laboratory and haematological tests in patients with traumatic brain injury and impaired consciousness . between 2008 and 2014 , patients who had been admitted for acute intracranial haemorrhage and were already using acetylsalicylic acid , along with control patients , were enrolled in the study . enrolment depended on the possibility to perform laboratory tests and so took place only during the day rather than at night and also depended on the availability of suitable patients , who were selected if they were available for analysis between 8.00 a.m. and 3.30 p.m. in addition , patients were only enrolled by three neurosurgical members of the study team . the inclusion criteria required patients to be over 18 years of age and have a diagnosis of isolated spontaneous or traumatic intracranial haemorrhage confirmed by computed tomography . the haemorrhage alone had to be a correlate of a neurological deficit such as coma , hemiparesis , or aphasia and thus presents a surgical indication , or the progressive size had to suggest that a clinically relevant deterioration was likely ( compression of basal cisterns , midline shift ) . a further inclusion criterion was evidence ( communicated personally or in writing ) of the intake of acetylsalicylic acid within 24 hours prior to admission . the exclusion criteria comprised intake of other anticoagulants or platelet aggregation inhibitors , known coagulation disorders , alcoholism , known hypercoagulable tendency , renal failure , hypothermia ( < 35c ) , multiple trauma , or polytrauma . in doing so , a distinction was made between patients having taken acetylsalicylic acid once within 24 hours prior to admission ( patsin ) and those having taken the drug regularly ( daily ) or more than once ( patmul ) . patients who were conscious could be questioned ; otherwise , information was taken from the records of other hospitals , documentation from previous stays at our hospital , or documentation obtained from a care facility or the general practitioner . the control group comprises 3 patients ( one woman aged 52 years with spontaneous subarachnoid haemorrhage ; one man aged 79 years with traumatic brain injury ; one man aged 56 years with traumatic brain injury ) . since  unlike the patients with intracranial haematoma predominantly normal values were found initially and the values for platelet aggregation inhibition were normal , no further blood tests were performed over the course . all patients were monitored intensively for intracranial haemorrhage and their potential ( cardiac and circulatory ) risks following administration of desmopressin . there are numerous recommendations to also use desmopressin acetate as a treatment for platelet function disorders or mild thrombocytopenia . desmopressin acetate is used to improve primary haemostasis  not because of the enhanced aggregability of the platelets , but rather due to their increased adhesiveness . platelet function was tested using platelet function analysis ( pfa-100 , dade behring , germany ) , which measures the time required for a platelet plug to form and seal a semipermeable membrane . as under physiological conditions , it serves as an initial matrix for platelet adhesion in relation to the von willebrand factor found in the tested blood . during the test , the platelets bind directly with the collagen , which in turn leads to platelet activation adherent platelets are degranulated on contact with the agonists ' epinephrine and adenosine phosphate , which are also found in the membrane . the standard values for membrane closure range from 68 to 120 seconds for adenosine phosphate and 54 to 165 seconds for epinephrine . desmopressin acetate was administered over a period of 30 minutes so as to avoid flushing and hypotension . the platelet function was then analysed half an hour ( t2 ) and three hours ( t3 ) after administration . all patients were given 24  g in 100  ml physiological saline solution over a period of 30 minutes . the time between sampling and starting the test was less than 15 minutes and did not hinder the procedures with respect to potential surgery . statistical analysis comprised the wilcoxon and mann - whitney u tests , with a significance level of p  0.05 . during the specified period , 10 patients on acetylsalicylic acid with the following conditions were enrolled : intracerebral haemorrhage ( n = 3 ) , cerebral infarctions ( n = 2 ) , traumatic brain injury with contusion or acute subdural haematoma ( n = 2 ) , spontaneous subarachnoid haemorrhage with hydrocephalus ( n = 1 ) , and chronic subdural haemorrhage ( n = 2 ) . acetylsalicylic acid had been taken once by 4 patients and multiple times by 6 patients . seven of these 10 patients underwent surgery immediately after admission ( patsin  n = 3 , patmul  n = 4 ) ; the remaining 3 patients were monitored under intensive care conditions . the exact dose of acetylsalicylic acid could not always be determined , especially in those patients having taken only one dose . in the others , the dose did not exceed 100  mg.the platelet function was found to be impaired in both patient groups ( patsin and patmul ) at t1 . figures 5 and 6 illustrate the mean membrane occlusion times for time point t1 , with results exceeding the norm of 120 seconds ( adenosine phosphate ) and 165 seconds ( epinephrine).in the adenosine phosphate samples , the mean time at t1 was 122.7 seconds ( sd 21.8 ) for patsin and 126.6 seconds ( sd 89.0 ) for patmul ( p = 0.394).the epinephrine samples revealed a mean occlusion time at t1 of 249.5 seconds ( sd 59.94 ) for patsin ( p = 0.068).the mean value at t1 in the epinephrine tests was more than 300 seconds for patmul ( figure 5).platelet function had returned to normal or close to normal in both groups at t2 after administration of desmopressin acetate ( figures 5 and 6).in the adenosine phosphate samples , the mean time at t2 was 86.3 seconds ( sd 32.06 ) for patsin and 73.83 seconds ( sd 9.45 ) for patmul ( p = 0.831).the epinephrine samples revealed a mean occlusion time at t2 of 170.5 seconds ( sd 92.16 ) for patsin and 192.8 seconds ( sd 92.86 ) for patmul ( p = 0.829).the platelet function was again impaired in both groups at t3 , though the values were worse in the patmul group under epinephrine ( figures 5 and 6).in the adenosine phosphate samples , the mean time at t3 was 99.5 seconds ( sd 30.73 ) for patsin and 86.3 seconds ( sd 7.91 ) for patmul ( p = 0.829).the epinephrine samples revealed a mean occlusion time at t3 of 234 seconds ( sd 83.53 ) for patsin and 212.7 seconds ( sd 94.78 ) for patmul ( p = 0.998).there were no relevant deviations from the reference values in the control group : mean adp was 106 seconds ( sd 18.5 ) and epinephrine 135,6 seconds ( sd 16.5 ) . there was one case of a relevant , secondary increase in intracranial haemorrhage with clinical deterioration . the platelet function was found to be impaired in both patient groups ( patsin and patmul ) at t1 . figures 5 and 6 illustrate the mean membrane occlusion times for time point t1 , with results exceeding the norm of 120 seconds ( adenosine phosphate ) and 165 seconds ( epinephrine ) . in the adenosine phosphate samples , the mean time at t1 was 122.7 seconds ( sd 21.8 ) for patsin and 126.6 seconds ( sd 89.0 ) for patmul ( p = 0.394).the epinephrine samples revealed a mean occlusion time at t1 of 249.5 seconds ( sd 59.94 ) for patsin ( p = 0.068 ) . in the adenosine phosphate samples , the mean time at t1 was 122.7 seconds ( sd 21.8 ) for patsin and 126.6 seconds ( sd 89.0 ) for patmul ( p = 0.394 ) . the mean value at t1 in the epinephrine tests was more than 300 seconds for patmul ( figure 5 ) . platelet function had returned to normal or close to normal in both groups at t2 after administration of desmopressin acetate ( figures 5 and 6 ) . in the adenosine phosphate samples , the mean time at t2 was 86.3 seconds ( sd 32.06 ) for patsin and 73.83 seconds ( sd 9.45 ) for patmul ( p = 0.831).the epinephrine samples revealed a mean occlusion time at t2 of 170.5 seconds ( sd 92.16 ) for patsin and 192.8 seconds ( sd 92.86 ) for patmul ( p = 0.829 ) . in the adenosine phosphate samples , the mean time at t2 was 86.3 seconds ( sd 32.06 ) for patsin and 73.83 seconds ( sd 9.45 ) for patmul ( p = 0.831 ) . the epinephrine samples revealed a mean occlusion time at t2 of 170.5 seconds ( sd 92.16 ) for patsin and 192.8 seconds ( sd 92.86 ) for patmul ( p = 0.829 ) . the platelet function was again impaired in both groups at t3 , though the values were worse in the patmul group under epinephrine ( figures 5 and 6 ) . in the adenosine phosphate samples , the mean time at t3 was 99.5 seconds ( sd 30.73 ) for patsin and 86.3 seconds ( sd 7.91 ) for patmul ( p = 0.829).the epinephrine samples revealed a mean occlusion time at t3 of 234 seconds ( sd 83.53 ) for patsin and 212.7 seconds ( sd 94.78 ) for patmul ( p = 0.998 ) . in the adenosine phosphate samples , the mean time at t3 was 99.5 seconds ( sd 30.73 ) for patsin and 86.3 seconds ( sd 7.91 ) for patmul ( p = 0.829 ) . the epinephrine samples revealed a mean occlusion time at t3 of 234 seconds ( sd 83.53 ) for patsin and 212.7 seconds ( sd 94.78 ) for patmul ( p = 0.998 ) . there were no relevant deviations from the reference values in the control group : mean adp was 106 seconds ( sd 18.5 ) and epinephrine 135,6 seconds ( sd 16.5 ) . there was one case of a relevant , secondary increase in intracranial haemorrhage with clinical deterioration . the mean serum sodium and potassium levels , as well as urine volume , remained within the reference range or remained clinically irrelevant and so did not necessitate intervention . taking traumatic brain injury as an example , there have been numerous reports of expansion in intracerebral haemorrhage within hours to days without the additional influence of external factors [ 19 , 20 ] . impaired coagulation in traumatic brain injuries is reported at an incidence of up to 26% . survival and outcome after traumatic brain injury depend on any expansion in the preexisting haemorrhage . haemorrhagic volume also plays an influential role in survival in the case of spontaneous intracerebral haemorrhage . the more extensive the haemorrhage , the poorer the treatment outcome when measured on the glasgow outcome scale . desmopressin acetate is capable of significantly reducing blood loss and thus minimising the haemorrhagic risk [ 12 , 14 , 20 ] . as an antihemorrhagic agent with enhanced factor viii coagulation activity , desmopressin acetate is authorised for use before surgery and tooth extraction and after traumas in mild to moderate haemophilia a and von - willebrand - jrgens disease . there have been no reports of approval with respect to stabilising the platelet function in intracranial haemorrhage or prior to intracranial interventions following intake of acetylsalicylic acid . aspirin has been identified as an independent predictor for death in patients suffering spontaneous intracranial haemorrhage . we found that desmopressin acetate is a safe way to stabilise the platelet function in patients with intracranial haemorrhage if they are only taking acetylsalicylic acid . we were not able to determine the exact dose of acetylsalicylic acid or the exact time between intake and administration of desmopressin acetate . however , this matter displays daily clinical life in which decisions must be done on the basis of just little information . the platelet function tended to return to normal relatively rapidly , that is , after 30 minutes , using a dose of 24  g . as a rule , this corresponds to the time it takes to admit the patient and prepare for emergency surgery . nevertheless , the question whether to administer desmopressin acetate immediately after diagnosing intracranial haemorrhage under acetylsalicylic acid or whether to only apply the drug preoperatively remains unanswered . further studies must be conducted to verify the benefit of intranasal or intravenous administration of desmopressin acetate [ 22 , 23 ] . we recommend administration of desmopressin in intracerebral haemorrhage so as to improve the coagulation status , as described in the literature ( 20  kg body weight = approximately 8  g , 50  kg body weight = approximately 20  g , 100  kg body weight = 40  g , or 0.3  g / kg body weight ) , followed by monitoring of the electrolyte and fluid balance [ 16 , 24 ] in order to optimise the surgical setting . administration of platelet concentrates can be considered after applying desmopressin acetate ; we would not recommend it , however , due to a lack of data [ 2528 ] . prolongation of normal platelet function is not immediately apparent as a result , and a more profound benefit would also appear doubtful given the fact that desmopressin acetate itself can stabilise the platelet function . simultaneous administration of tranexamic acid should stabilise the blood clot , but further studies should be conducted . desmopressin acetate can improve the platelet function after 30 minutes in intracranial haemorrhage following acetylsalicylic acid intake . the coagulative status can thus be restored to normal levels in terms of platelet function for between 30 minutes and 3 hours . when administering desmopressin acetate in intracranial haemorrhage under acetylsalicylic acid , cardiac function , electrolyte , and fluid balance must be closely monitored .
introduction . the secondary increase in the size of intracranial haematomas as a result of spontaneous haemorrhage or trauma is of particular relevance in the event of prior intake of platelet aggregation inhibitors . 
 we describe the effect of desmopressin acetate as a means of temporarily stabilising the platelet function . 
 patients and methods . 
 the platelet function was analysed in 10 patients who had received single ( n = 4 ) or multiple ( n = 6 ) doses of acetylsalicylic acid and 3 patients ( control group ) who had not taken acetylsalicylic acid . 
 all subjects had suffered intracranial haemorrhage . 
 analysis was performed before , half an hour and three hours after administration of desmopressin acetate . 
 statistical analysis was performed by applying a level of significance of p  0.05 . 
 results . 
 ( 1 ) platelet function returned to normal 30 minutes after administration of desmopressin acetate . 
 ( 2 ) the platelet function worsened again after three hours . 
 ( 3 ) there were no complications related to electrolytes or fluid balance . conclusion . 
 desmopressin acetate can stabilise the platelet function in neurosurgical patients who have received acetylsalicylic acid prior to surgery without causing transfusion - related side effects or a loss of time . 
 the effect is , however , limited and influenced by the frequency of drug intake . 
 further controls are needed in neurosurgical patients .