Confidential: For Review Only - BMJ · Confidential: For Review Only 1 Bloodcurdling movies truly curdle the blood: Results from the Fear F8ctor Crossover Trial Banne Nemeth Medical

Confidential: For Review O

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Bloodcurdling movies truly curdle the blood: Results From

the Fear F8ctor Crossover Trial.

Journal: BMJ

Manuscript ID BMJ.2015.029359

Article Type: Christmas

BMJ Journal: BMJ

Date Submitted by the Author: 14-Sep-2015

Complete List of Authors: Nemeth, Banne; Leiden University Medical Center, Clinical Epidemiology; Leiden University Medical Center, Orthopedic Surgery Scheres, Luuk; Leiden University Medical Center, Department of Clinical Epidemiology; Academic Medical Center, Department of Vascular Medicine Lijfering, Willem; Leiden University Medical Center, Clinical Epidemiology

Rosendaal, Frits; Leiden University Medical Center, Clinical Epidemiology; Leiden University Medical Center, Einthoven Laboratory for Experimental Vascular Medicine

Keywords: Fear, Venous Thrombosis, Crossover Trial, Bloodcurdling, Factor VIII

https://mc.manuscriptcentral.com/bmj

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Bloodcurdling movies truly curdle the blood: Results from the

Fear F8ctor Crossover Trial

Banne Nemeth Medical doctor1,2

, Luuk JJ Scheres Medical doctor1,3

, Willem M Lijfering

Postdoctoral researcher1, Frits R Rosendaal Professor of Clinical Epidemiology 1,4

1.Department of Clinical Epidemiology, Leiden University Medical Center, 2300 RC, Leiden, The

Netherlands.

2.Department of Orthopaedic Surgery, Leiden University Medical Center, 2300 RC, Leiden, The

Netherlands.

3.Department of Vascular Medicine, Academic Medical Center, 1105 AZ, Amsterdam, The

Netherlands.

4.Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center,

2300 RC, Leiden, The Netherlands.

Address for correspondence: F.R. Rosendaal, Department of Clinical Epidemiology, Leiden

University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Tel.: +31 71 526 4037; Fax: +31 71 526 6994

Email: [email protected]

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Abstract

Objectives – To unravel if acute fear curdles the blood as has been hypothesized since medieval

times.

Design – A crossover trial in which one group of participants was exposed to a frightening (scary)

movie followed by a non-frightening (flat) movie. Another group of participants watched the movies

in opposite order. The second movie was watched at least one week after the first movie on the same

time of the day.

Setting – The movies were shown to participants who were seated in comfortable chairs, at the Home

Cinema of the Department of Epidemiology, which generally carries a non-frightening and relaxed

atmosphere.

Participants – 24 healthy participants, not on any medication, aged ≤30 years were recruited among

students, alumni and employees of the Leiden University Medical Center.

Interventions – A frightening movie, with potential of inducing acute fear and a non-frightening

(although educational), flat movie were carefully selected. Both movies had a length of approximately

90 minutes.

Main outcome measures – Primary outcome measures were markers of coagulation activity (i.e.,

potential coagulation fear factors): Factor VIII (FVIII:C), D-dimer, Thrombin and Antithrombin

complexes (TATc) and Prothrombin fragments 1 + 2 (F1+2). Secondary outcomes were pulse rates

measured during both movies and a Visual Analogue Fear Scale (VAFS) on fear experienced during

each movie.

Results – All study participants completed the study. The frightening movie was perceived more

frightening than the non-frightening movie (VAFS mean difference 5.4 [95%CI 4.7 – 6.1]). FVIII:C

levels (i.e., the difference between levels before and after the movie) were higher after the frightening

movie than after the non-frightening movie (mean difference of differences 11.2 IU/dL [95%CI 1.8 to

20.7]). There was no difference in effect of either type of movies on levels of TATc, D-dimer and

F1+2.

Conclusions – Fear is bloodcurdling.

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Introduction

“Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so

that we may fear less.” Marie Curie, 1867-1934.[1]

For centuries the term “bloodcurdling” has been used to describe extreme frightening situations.[2] It

is known in several other languages of which “das blut in den Adern erstarrt”, “à vous glacer le sang”,

“que hiela la sangre” and “bloedstollend” are examples in German, French, Spanish and Dutch,

respectively. The term dates back to the concepts in medieval physiology, where it was believed that

the human body contained four chief fluids, blood, phlegm, bile and black bile. It was thought that

fear or horror would ‘run the blood cold’ or ‘curdle’ (solidify).[3] To date large parts of the complex

mechanism of the coagulation cascade have been unravelled and many risk factors for thrombosis

have been identified. However, the origin of this medieval theory has never been studied and it

remains unknown if fear truly induces the coagulation system and thereby curdles the blood.

Several studies explored the effects of physical stress on the coagulation system.[4] Chronic anxiety

in psychiatric patients was associated with increased levels of coagulation markers in several

studies.[5,6] However, chronic anxiety in psychiatric patients (with associated therapies) markedly

differ from a state of acute fear in the community. In another study investigators studied coagulation

markers before and after bungee jumping, and reported increased coagulation activity in apparently

healthy volunteers after the jump. [7] However, the effects of excitement and profound physical

activity are not necessarily equal to those of acute fear, in particular because, as was pointed out, these

individuals performed these jumps voluntarily, which was seen as deviating from an ideal design.[8]

To our knowledge, till date no studies investigated acute fear without physical exercise and the effects

on the coagulation system. We hypothesize that acute fear induces activation of the coagulation

system as this would pose an important evolutionary benefit, which is preparing for blood loss in

frightening and life-threatening situations.

People often experience fear in acute situations in which coagulation plays a crucial role, such as

events of severe bleeding due to trauma or haemorrhagic diathesis. Fear may also play a role in other

unexplained disturbances of the coagulation cascade that might lead to venous thrombosis, as is the

case in aviation.[9]

Here we present results from a crossover trial which was conducted to unravel the effect of acute fear

on the coagulation cascade (and to identify candidate fear factors), and to investigate whether fear is

truly bloodcurdling, as was hypothesized centuries ago.

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Methods

Study design

Between, the 29th of June and the 20th of August, 2015, a crossover trial was performed. Twenty-four

healthy volunteers were recruited. One group (n=14) of participants first watched a frightening movie

(i.e. bloodcurdling) followed by a non-frightening movie. The other group (n=10) watched the same

movies in opposite order. Group allocation was based on availability of the study participants as

movie nights were set on specific dates. Figure 1 is a flow chart of the study design. Both movies

lasted for approximately 90 minutes and were watched at least one week apart, on the same time of

day (see flow chart). Both groups were seated in the same comfortable chairs. The participant

information leaflet revealed that this was a study in which the coagulation effects of sitting still and

watching movies was analysed. However, participants were not aware of the movie genre in advance.

Participants were also not informed that the actual goal was to determine if a frightening movie could

curdle the blood. A frightening movie was selected carefully on fear provoking potential with an

external expert and was agreed upon by the two investigators. The non-frightening movie was

selected by two investigators for its non-emotional provoking capacity and was (although

educational), a flat (and rather dull) movie (The authors’ Christmas movie reviews are provided in

supplementary text 1 and supplementary figure 1). Before and after each movie, blood was drawn

through venepuncture of the cubital vein (in the contralateral arm for the second draw). The movies

were shown at the main meeting room, which was transformed into the Home Cinema of the

Department of Clinical Epidemiology of the Leiden University Medical Center, which emits a non-

frightening and welcoming atmosphere. Participants were instructed not to consume alcohol, smoke

or use any drugs on both movie days. In order to avoid any confounding by superstition, no movies

were shown during full moon or on Friday the 13th. All participants provided written informed

consent. This study was approved by the Medical Ethical Committee of the Leiden University

Medical Center in Leiden, The Netherlands.

Study population

Healthy volunteers, aged < 30 years were recruited among students, alumni and employees of the

Leiden University. Participants were not on any medication, not pregnant (or up to 6 weeks after

pregnancy), used no hormonal contraceptives (excluding intra-uterine devices), had no history of

venous thrombosis, had no major surgery or cast-immobilization of the lower extremity in the past

two months and did not have a malignancy or inflammatory disease.

Laboratory measurements

Measured markers of coagulation activity (e.g. potential fear factors) were factor VIII activity in

IU/dL (FVIII:C) , D-dimer in ng/mL, Thrombin and Antithrombin complexes (TATc) in ug/L and

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Prothrombin fragments 1 + 2 in in pmol/L (F1+2). Blood samples were drawn in vacuum tubes

containing 0.105M additive of Na Citrate. After blood collection, we centrifuged citrated blood at

2500 g for 10 minutes at 18°C within 1 hour of venepuncture. After aliquoting, samples were stored at

-80°C until laboratory analyses were performed. F1+2 and TATc laboratory analyses were performed

within one batch, all laboratory analyses were measured in duplicate. The clotting assay for FVIII:C

and D-dimer was performed using the TOP analyser (Werfen Group/Instrumentation Laboratory,

Barcelona Spain). TATc and F1+2 were assayed via sandwich-type ELISA (Siemens, Marburg,

Germany). The laboratory technicians were not aware of which movie corresponded to which blood

sample.

Fear scale and questionnaire

After each movie a Visual Analogue Fear Scale (VAFS), designed for this specific study,

(supplementary figure 2) was completed by every participant. The VAFS estimates fear experienced

by watching the movie, ranging from no fear at all (VAFS:0) to the worst fear imaginable (VAFS:10).

Additionally, participants reported whether they had already seen the movie and whether they enjoyed

the movie on a scale from 0 (worst movie ever) to 10 (best movie ever). Finally, participants

completed an questionnaire on demographics, lifestyle and favourite movie genre.

Heart rate monitoring

In one of the groups, heart rates were measured every 15 seconds in six randomly chosen participants

by means of an Actihearts device (CamnTech Ltd). Due to limited availability of these devices, heart

rates were not measured in all participants.

Sample size calculation

Sample size was calculated for the continuous outcome variables FVIII:C (2-sided test, alpha=0.05,

beta=0.9). In order to observe an increase of 10 IU/dL of more (leading to an increase in venous

thrombosis risk of around 17%)10

, a total of 23 participants were necessary. Anticipating possible

drop-out of participants, we included a total of 24 participants.

Statistical analyses

Demographic and baseline data (e.g., age, sex, weight and height) were summarized as means ±

standard deviation (SD) or proportions. Body Mass Index (BMI) was calculated based on self-

reported height and weight. Mean changes in the measured coagulation markers were assessed as

levels before and after each movie. The difference between the mean change in coagulation levels

(mean change of levels before and after frightening movie compared with the mean change before and

after non-frightening movie) were compared. A paired student t-test was used to compare the two

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mean changes in these coagulation markers. For the VAFS we reported the mean change and 95%

confidence intervals (95%CI). The coagulation factor levels were similar in the group who first

watched the frightening movie followed by the non-frightening movie as compared with the group

who watched these movies in opposite order (results not shown). Therefore, a carry-over effect was

considered absent. For this reason, results of both study arms were pooled by type of movie exposure.

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Results

Participants and recruitment

In total, 24 healthy volunteers were recruited between July 20 and August 12. Study days took place

on July 29, August 4, 5 and 11, all movies were shown between 19:00 and 21:00. Due to the

availability of participants, 14 volunteers were recruited for group A ( frightening movie first), and 10

volunteers for group B (non-frightening movie first). Table 1 shows baseline demographics. The

mean age of the participants was 25.9 years (SD 3.0), 16/24 (67%) were males. All volunteers were

healthy and did not use medication.

Table 1. Baseline characteristics

Table 1 | Study participant demographics

Demographics

Sex - male (%) 16 (67)

Age in years (mean (SD)) 25.9 (3.0)

Height in meters (mean (SD)) 1.81 (0.12)

Weight in kilograms (mean (SD)) 77.6 (11.8)

Body Mass Index 23.4 (2.5)

Smoking - Yes (%) 2 (8.3%)

Cigarettes per day

1-5 1

6-10 -

11-15 -

16-20 1

Alcohol - Yes (%) 19 (79.2)

Alcohol units per week

1-5 7

6-10 7

11-15 3

16-20 1

21-25 -

26-30 1

Coffee - Yes (%) 19 (79.2)

Cups of coffee per day

1-3 12

4-6 6

7-9 1

Favorite movie genre (number (%))

Action 7

Adventure 1

Thriller 3

Romantic Comedy 5

Science Fiction 2

Comedy 4

Fantasy 1

Drama 1

Horror movie fan - Yes (%) 5 (20.8)

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Frightening movie

VAFS (mean (SD)) 5.4 (1.7)

Movie Score (mean (SD)) 4.25 (4.3)

Already have seen movie - Yes (%) 3 (12.5)

Non-frightening movie

VAFS (mean (SD)) 0.0 (0.2)

Movie Score (mean (SD)) 5.1 (1.7)

Already have seen movie - Yes (%) 0 (0)

VAFS=Visual Analogue Fear Scale, SD=Standard deviation

Two participants were smokers and 80% consumed alcohol and coffee on a regular basis. Five

volunteers were horror movie fans. Action or romantic comedy were favourite movie genres for 7 and

5 participants, respectively.

The frightening movie was experienced as quite frightening with a mean VAFS of 5.4 (SD 1.7). Only

three participants had already seen this movie. The mean VAFS of the non-frightening movie was 0.0

(SD 0.2) and not a single participant had already seen this movie. There was a difference in fear

experienced between the movies, with more fear experienced during the frightening movie (mean

difference of VAFS: 5.4 (95%CI 4.7 – 6.1).

Fear F8ctor analyses – primary outcome measures

Three participants were excluded from the primary fear f8ctor analyses. In the first two cases (group

B), of both participants one of the samples was visibly haemolytic as noted by the laboratory

technicians, and the results were considered to be unreliable. In the third case, the first two authors

noted (a-priori) that the participant was very tense before the first blood draw (before the non-

frightening movie) and in attempt to relax before the second blood draw he ingested an entire family

pack of chocolates after the first blood draw. He suffered from vasovagal reflexes and fainted during

the blood draw after the first movie. At the second movie (the frightening movie) these symptoms

were not noted. Since the assumption for a crossover trial, i.e. both instances similar except for the

intervention, was clearly not met for this individual, results were regarded as unusable (FVIII:C 132

IU/dL before the first movie and 346 IU/dL after, and 109 IU/dL before and 123 IU/dL after the

frightening movie, respectively).

After exclusion, the remaining 21 participants were included in the main analyses. Mean FVIII:C

baseline levels were similar before the frightening and the non-frightening movie (mean difference -

2.9 IU/dL (95%CI -10.1 ; 4.2). However, the mean change in FVIII:C levels (i.e., the difference

between levels before and after movie) was higher after the frightening movie than for the non-

frightening movie (mean difference 11.1 IU/dL [95%CI, 1.2 to 21.0]). Figure 2A shows the mean

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change in FVIII:C levels before and after the frightening and non-frightening movie. As can been

appreciated from this figure, FVIII levels increased in 12 (57%) participants during the frightening

movie, and in only 3 (14%) during the educational movie. In 18 (86%) participants, FVIII:C levels

declined during the non-frightening movie, which happened in only 9 (43%) participants during the

frightening movie.

Mean D-dimer levels before the frightening and non-frightening movie were similar. The mean

change in D-dimer levels before and after the non-frightening movie was -35.1 ng/mL (SD 63.0) and -

31.8 (SD 109.3) before and after the frightening movie. So, no effect of acute fear on D-Dimer levels

was observed (Figure 2B), mean difference 3.33 ng/mL [95%CI -37.1 to 43.8]).

There was also no effect on TATc levels, mean difference of differences -0.54 µg/L ; 95%CI -2.5 to

1.4), (Figure 2C). In these healthy participants, of all F1+2 measurements (before and after both

movies), all but two were below 200 pmol/L. The mean change in F1+2 levels (Figure 2D) before

and after the non-frightening movie was -10.2 pmol/L (median -1.0), the mean change after the

frightening movie was -23.7pmol/L (median -21).

Fear F8ctor analyses – validation of physiological effect of fear

Heart rates were monitored every 15 seconds in 6 study volunteers, both during the non-frightening

and frightening movie. Figure 3 represents the heart rate of two study participants during both

movies. One participant reported an 8 on the VAFS after experiencing a bloodcurdling movie and

scored, the other participant found the frightening movie rather non-frightening and scored a 1 on the

VAFS. Scary scenes were identified by one of the investigators before examining the heart rates. As

can be seen in the figure, the heart rate elevated during scary scenes in the participant which reported

to have experienced fear during the movie. This was not true for the participant who did reported a

low VAFS.

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Discussion

With this rigorously designed study we demonstrate that bloodcurdling fear, truly curdles the blood.

We successfully attempted to design a study to expose participants to undiluted and acute fear in the

absence of physical exertion. Without exception participants reported the frightening movie to be

more frightening than the educational movie. We attempted to identify coagulation fear factors,

entities which may mediate the effects of fear into curdling of the blood. We observed an increase in

one of the candidate fear factors, traditionally know as factor VIII of the coagulation cascade, when

exposing participants to a frightening movie. Increased factor VIII activity has been associated with

increased venous thrombosis risk.[10–12] Therefore, the mean increase in FVIII:C of 11.1 (IU/dL) in

these healthy participants exposed to acute fear could well be clinically relevant, as was previously

reported that for every 10 IU/dL increase in factor VIII:C levels the risk of venous thrombosis

increased 17% (95%CI 7-28).[10] Therefore, we consider factor VIII to be a blood curdling fear

factor. D-dimer, TATc and F1+2 levels were not different before and after both exposures, and did not

prove themselves to be an acute coagulation fear factor. As blood was drawn directly after the

exposures, it is possible that these latter coagulation markers were not increased due to a latent period.

Moreover, the role for increased F1+2 levels as a risk factor for venous thrombosis remains uncertain,

as there have been conflicting results from studies.[13–15]

As mentioned, in most participants FVIII:C dropped during the non-frightening movie. The

participants were sitting still while watching a flat and a non-emotion-provoking movie. This relaxed

circumstance may even have led to the decrease in FVIII:C that was observed. A similar, however

more extreme, example of this phenomenon was observed in animals during hibernation, which

causes a rapid reversible thrombocytopenia.[16] It has been hypothesized that decreased coagulation

activity in hibernators protects against thrombosis during prolonged immobilization.[17] Our study

was not designed to explore this phenomenon, and room temperature was maintained during the

study, but the finding in man is intriguing.

A strength of this study is its cross-over design, which allows each case to be its own control. By

showing the movies (one week apart) on the same day and time of the week, we expect no influence

of circadian rhythms and lifestyle on the study results. A limitation of the study could be the

magnitude of fear induced by the exposure. Although some participants scored a 7 or 8 on the VAFS,

there is definite room for fear enhancement. Perhaps an increasingly frightening situation would

provoke an even more blood curdling response. However, such designs might elicit ethical

controversy and would be likely to be confounded by increased physical activity.

The underlying biological mechanism of acute fear resulting in increased coagulation activity is still

to be unravelled. However, these results are biologically and evolutionary plausible. Increased activity

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of the coagulation system when experiencing frightening situations might pose an important

evolutionary benefit: preparing for blood loss in frightening situations. Desmopressin, a vasopressin

analogue, has been used to increase coagulation activity in a wide range of bleeding diathesis.[18]

Desmopressin stimulates von Willebrand factor release with increased factor VIII levels as a

result.[19] A biological mechanism explaining these study results might be related to this pathway.

Although not immediately obvious by which means our results could confer clinical benefits, a

broader implication of these study results is that after centuries the term: “bloodcurdling” in literature

is justified.

Conclusions

This study shows that acute fear truly curdles the blood.

“What this paper adds box”

1.What is already known on this subject

As early as in medieval times it was thought that fear induced curdling (solidifying) of the blood.

Several studies have reported increased coagulation profiles in times of physical or psychological

stress, however the effect of pure fear on the coagulation system is still unravelled.

2.What this study adds

Acute fear seems to be truly bloodcurdling, as evidenced by increases in coagulation factor VIII.

These findings may necessitate development of preventive strategies to reduce fear in individuals at

risk for thrombosis. In terms of the season, a true relaxing merry Christmas, without exposure to

fright, seems to be safe to prevent venous thrombosis.

Contributors

According to good epidemiological practice, the decision of who would be first and who would be

second author was made by randomization. All authors were involved in the study design, study

conduct, data analysis, and revision of the manuscript. All authors read and approved the final

manuscript.

Acknowledgements

We would like to thank Nine Nemeth, Maaike Hermans and Liesbeth Willems of Brilman – Tuinhof

de Moed for their help with blood collection. Petra Noordijk, Annelies Hoenderdos and Lejla Mahic

for laboratory analyses, Selina Wijbenga and Yanna van der Spek for accompanying frightened study

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participants and Eva Rosendaal for her expertise in horrorology. This study could not have been

performed without all participants, whom we would like to gratefully thank for their participation in

the study.

Funding

This study was sponsored by the Department of Clinical Epidemiology of the Leiden University

Medical Center.

Competing interest

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf

and declare: no support from any organisation for the submitted work; no financial relationships with

any organisations that might have an interest in the submitted work in the previous three years; no

other relationships or activities that could appear to have influenced the submitted work.

Ethical approval

All participants provided written informed consent. This study was approved by the Medical Ethical

Committee of the Leiden University Medical Center in Leiden, The Netherlands.

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17. Carey H V, Andrews MT, Martin SL. Mammalian hibernation: cellular and molecular

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Figures

Figure 1 title

Flow chart study design

Figure 1 Legend

Study flowchart: 24 participants were recruited, group allocation was based on availability of the

study participants as movie nights were set on specific dates. Fourteen participants were exposed to

the frightening movie and one week later to the non-frightening movie. The remaining 10 participants

saw the movies in opposite order, also one week apart. Blood was drawn before the first movie (T0),

directly after (T1) and before (T2) and directly after (T3) the second movie.

Figure 2 Title

Mean difference in coagulation fear factors before and after the frightening and non-frightening

movies.

Figure 2 Legend

2A: Absolute mean change in coagulation factor FVIII:C after exposure to a frightening and non-

frightening movie (ordered by change in FVIII:C levels during frightening movie). Vertical bars

represent individual participants, the order of participants is identical in all graphs (also for 2B, 2C

and 2D). *-96 FVIII IU/dL difference, ** -27 FVIII IU/dL difference.

2B: Absolute mean change in coagulation D-dimer (after frightening and non-frightening movie).

2C: Absolute mean change in coagulation TATc (after frightening and non-frightening movie).

2D: Absolute mean change in coagulation F1+2 (after frightening and non-frightening movie).

Figure 3 Title

Heart rates (beats per minute) of two participants

Figure 3 Legend

Heart rate (beats per minute) during frightening and non-frightening movie in two participants. The

top panel shows the heart rate for a participant that scored an 8 on the VAFS for the frightening

movie. The lower panel shows the heart rate for a participant that scored a 1 on the VAFS on the

frightening movie.

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16

Supplements

Supplementary text 1, Author’s Christmas Movie Suggestions

Frightening movie

A happy family moves into a new home and all is well. At an unfortunate moment, one of the children

falls from a ladder and suffers from an unexplained coma. The doctors at the hospital struggle to

figure out the cause of the coma, but did not consider that the boy has left his physical body and is

lost in a different dimension (authors note: a cause not yet listed in the differential diagnosis of

unexplained coma in children).[20] Evil spirits start haunting the family and events soon turn grim.

Will the boy be rescued? How will the family stand against these evil spirits? Cuddle under your

blanket around the Christmas tree and find out, but be sure to keep those calf veins pumping!


This movies’ plot revolves around an esteemed wine importer who visits several famous Champagne

houses in the Champagne region in France. The movie focusses on the production process of

Champagne and the rise of the champagne industry. An absolute recommendation for all who want to

learn more about the world’s favourite new years’ beverage. Be sure to impress your peers during the

soon to come New Year’s party with the know-how from this movie! (authors note: although alcohol

consumption was associated with decreased venous thrombosis risk,[21] we did not expect this movie

to curdle the blood.)

Supplementary figure 1 Title

The authors’ judgement

Supplementary figure 1 Legend

The Authors’ judgement of the movies are shown in this figure, based on blood curdling potential,

storyline and educational potential. Two authors critically reviewed both movies and attributed stars

to each category. More stars indicate higher appraisal.

Supplementary figure 2 Title

Visual analogue fear scale (VAFS)

Supplementary figure 2 Legend

The visual analogue fear scale (VAFS) developed by the authors to measure fear after each movie.

Participants indicated the amount of fear experienced during the movie, directly after watching both

movies. A higher number indicates more fear experienced.

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Flow chart study design /

Study flowchart: 24 participants were recruited, group allocation was based on availability of the study participants as movie nights were set on specific dates. Fourteen participants were exposed to the

frightening movie and one week later to the non-frightening movie. The remaining 10 participants saw the movies in opposite order, also one week apart. Blood was drawn before the first movie (T0), directly after

(T1) and before (T2) and directly after (T3) the second movie. 292x268mm (300 x 300 DPI)

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Mean difference in coagulation fear factors before and after the frightening and non-frightening movies. /

2A: Absolute mean change in coagulation factor FVIII:C after exposure to a frightening and non-frightening movie (ordered by change in FVIII:C levels during frightening movie). Vertical bars represent individual participants, the order of participants is identical in all graphs (also for 2B, 2C and 2D). *-96 FVIII IU/dL

difference, ** -27 FVIII IU/dL difference. 2B: Absolute mean change in coagulation D-dimer (after frightening and non-frightening movie). 2C: Absolute mean change in coagulation TATc (after frightening and non-frightening movie). 2D: Absolute mean change in coagulation F1+2 (after frightening and non-frightening movie).

402x148mm (300 x 300 DPI)

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Heart rates (beats per minute) of two participants /

Heart rate (beats per minute) during frightening and non-frightening movie in two participants. The top panel shows the heart rate for a participant that scored an 8 on the VAFS for the frightening movie. The lower panel shows the heart rate for a participant that scored a 1 on the VAFS on the frightening movie.

462x222mm (300 x 300 DPI)

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Frightening movie A happy family moves into a new home and all is well. At an unfortunate moment, one of the children falls from a ladder and suffers from an unexplained coma. The doctors at the hospital struggle to figure out the

cause of the coma, but did not consider that the boy has left his physical body and is lost in a different dimension (authors note: a cause not yet listed in the differential diagnosis of unexplained coma in

children).[20] Evil spirits start haunting the family and events soon turn grim. Will the boy be rescued? How will the family stand against these evil spirits? Cuddle under your blanket around the Christmas tree and find

out, but be sure to keep those calf veins pumping! Non-frightening movie

This movies’ plot revolves around an esteemed wine importer who visits several famous Champagne houses in the Champagne region in France. The movie focusses on the production process of Champagne and the rise of the champagne industry. An absolute recommendation for all who want to learn more about the

world’s favourite new years’ beverage. Be sure to impress your peers during the soon to come New Year’s party with the know-how from this movie! (authors note: although alcohol consumption was associated with

decreased venous thrombosis risk,[21] we did not expect this movie to curdle the blood.)

328x336mm (300 x 300 DPI)

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Visual analogue fear scale (VAFS) /

The visual analogue fear scale (VAFS) developed by the authors to measure fear after each movie. Participants indicated the amount of fear experienced during the movie, directly after watching both movies.

A higher number indicates more fear experienced. 213x34mm (300 x 300 DPI)

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nlySupplementary text 1, Author’s Christmas Movie Suggestions

Frightening movie

A happy family moves into a new home and all is well. At an unfortunate moment, one of the children

falls from a ladder and suffers from an unexplained coma. The doctors at the hospital struggle to figure

out the cause of the coma, but did not consider that the boy has left his physical body and is lost in a

different dimension (authors note: a cause not yet listed in the differential diagnosis of unexplained coma

in children).[20] Evil spirits start haunting the family and events soon turn grim. Will the boy be rescued?

How will the family stand against these evil spirits? Cuddle under your blanket around the Christmas tree

and find out, but be sure to keep those calf veins pumping!


This movies’ plot revolves around an esteemed wine importer who visits several famous Champagne

houses in the Champagne region in France. The movie focusses on the production process of Champagne

and the rise of the champagne industry. An absolute recommendation for all who want to learn more

about the world’s favourite new years’ beverage. Be sure to impress your peers during the soon to come

New Year’s party with the know-how from this movie! (authors note: although alcohol consumption was

associated with decreased venous thrombosis risk,[21] we did not expect this movie to curdle the blood.)

20. Anand G, Shefler A, McShane T. Diagnosis and outcome of children admitted to a paediatric

intensive care unit with unexplained coma. Arch Dis Child. 2011;96(11):1091.

21. Pomp ER, Rosendaal FR, Doggen CJM. Alcohol consumptionisassociated witha decreased risk of

venous thrombosis. Thromb Haemost. 2008;99(1):59–63.

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Documents

Confidential: For Review Only - BMJ · Confidential: For Review Only 1 Bloodcurdling movies truly curdle the blood: Results from the Fear F8ctor Crossover Trial Banne Nemeth Medical