Table 2

Platelet changes and acute stress.

Study Sample Mental Stressor(s) Measures FindingsAndrén et al., 1983 (1)

10 healthy men 10-minutes 100 dBA noise

PF4 PF4 was unaffected by noise stress.

Fitchett et al., 1983 (2)

12 patients with CHD; 7 healthy controls

Cold pressor Arterial and venous βTG, platelet count

Venous βTG increased significantly in both groups during stress, but no change was observed in arterial βTG and platelet count.

Levine et al., 1985 (3)

34 medical residents Public speaking PF4, βTG PF4 levels were higher just prior to public speaking compared to baseline (11 months prior to speech) and recovery (5-21 days post-speech). βTG levels at stress were higher than baseline but not recovery.

Jern et al., 1989 (4)

29 healthy young men Mental arithmetic Platelet count Platelet count increased significantly from baseline to stress and returned to baseline levels after a 10-minute recovery period.

Larsson et al., 1989 (5)

16 healthy men Stroop Ex vivo platelet aggregability, PF4, βTG

Aggregability increased during Stroop but there were no changes for PF4 or βTG.

Larsson et al., 1989 (6)

9 healthy volunteers Stroop PDGF PDGF increased during Stroop.

Larsson et al., 1990 (7)

10 healthy men Stroop Ex vivo platelet aggregability

Aggregability was not affected by Stroop.

Rostrup et al., 1990 (8)

29 mildly hypertensive men

Awareness of hypertension status, cold pressor

βTG Baseline βTG was significantly higher among those who were informed of hypertension status than in those who were uninformed. βTG levels remained significantly higher in the informed group than the uninformed group during stress.

Grignani et al., 1991 (9)

25 post-infarction patients; 10 healthy controls

Mental arithmetic Platelet aggregation, platelet aggregate to ADP ratio, TXB2

TXB2 and platelet aggregate to ADP ratio increased during stress in patients and controls.

Grignani et al., 1992 (10)

10 post-infarction patients

Mental arithmetic Platelet aggregation, platelet aggregate to ADP ratio, TXB2

TXB2 and platelet aggregate to ADP ratio increased during stress.

Malkoff et al., 1993 (11)

40 healthy men Stroop Platelet aggregation and secretion

Platelet secretion increased during stress but aggregation did not.

Naesh et al., 1993 (12)

8 healthy men Stroop βTG, platelet concentration

βTG levels were not significantly higher during stress than at baseline, but were higher 30 and 60 minutes post-stress. Platelet concentration increased during stress, but correcting for hemoconcentration rendered this effect non-significant. However, the method for adjusting for hemoconcentration effects was not described.

Patterson et al., 1994 (13)

55 healthy men Mental arithmetic; Stroop; viewing surgery videos

PF4 Compared to control participants, PF4 levels were higher in those who performed the stressors.

Mundal & Rostrup, 1995 (14)

26 healthy 19-year old males; Half of the sample was falsely informed of having elevated blood pressure

Mental arithmetic; cold pressor

βTG, platelet count, mean platelet volume

βTG levels increased significantly during the cold pressor in all participants, but the increase was significantly higher in the uninformed group. Platelet count and volume did not change.

Patterson et al., 1995 (15)

27 healthy men Mental arithmetic; cold pressor

PF4, βTG PF4 and βTG levels increased during both stressors but to a greater extent during mental arithmetic.

Markovitz et al., 1996 (16)

14 post-infarction patients; 15 healthy controls

Structured interview; speech task

βTG βTG levels increased significantly in the control group but not in the post-infarction group.

Wallén et al., 1997 (17)

103 angina patients; 50 healthy controls

Stroop Ex vivo platelet aggregability, in vitro platelet aggregation, PF4, βTG

βTG levels increased significantly and PF4 levels increased marginally during stress among angina patients, whereas there was no change in βTG levels and PF4 levels decreased during stress among controls.

Tomoda et al., 1999 (18)

24 patients with WHO stage I hypertension; 13 patients with stage 2 hypertension; 14 normotensive controls

Mental arithmetic Platelet aggregation, βTG

In normotensives, aggregation and βTG did not change during stress. Both hypertensive groups showed increased aggregation and βTG during stress, but stage 1 had larger increases.

Wallén et al., 1999 (19)

11 healthy men Modified Stroop Platelet-fibrinogen binding, ex vivo platelet aggregability, platelet count, platelet volume

Platelet-fibrinogen binding, platelet aggregability, platelet count and platelet volume were unaffected by the stressor.

Steptoe et al., 2003 (20)

37 healthy men Color/word interference task; mirror tracing

Total PLAs, PMAs, platelet-leukocyte aggregates, platelet-neutrophil aggregates

All aggregates increased immediately post-stress, but the highest levels were attained at 30 minutes post-stress. By 75 minutes post-stress, all aggregates returned to baseline levels.

Lederbogen et al., 2004 (21)

9 depressed psychiatric inpatients; 10 age- and sex-matched controls

Computer-based detection task

Platelet count, P-selectin expression, GP53 expression

Platelet count and P-selectin expression significantly increased during stress in both groups, but GP53 expression did not. There were no group differences.

Strike et al., 2004 (22)

17 male patients with CHD; 20 healthy age-matched controls

Color/word interference task; mirror tracing

Total PLAs There were no differences between the two groups in PLAs at baseline and the increases in PLAs during stress. PLAs remained significantly elevated after 75 min recovery in the patients with CHD.

Sestito et al., 2005 (23)

30 patients with syndrome X; 20 patients with unstable angina; 11 patients with stable angina; 22 controls

Mental arithmetic Ex vivo platelet reactivity (adhesion and aggregability)

Platelet reactivity decreased among patients with syndrome X and increased among patients with stable angina. No change was observed for patients with unstable angina or for controls

Bacon et al., 2006 (24)

72 patients with CHD (57 men, 15 women)

PASAT Platelet count; PF4 Neither platelet count nor PF4 changed.

Hamer et al., 2006 (25)

91 healthy men Speech task and mirror tracing, completed twice 4 weeks apart

Total PLAs, PMAs PLAs and PMAs increased 10-min after the tasks in both sessions, but the overall levels of PLAs and PMAs decreased from session 1 to session 2. Blood was not drawn during or immediately after stress.

Aschbacher et al., 2009 (26)

149 elderly individuals Three 3-minute impromptu speeches one year apart

% platelet aggregates formed, % fibrinogen expression on platelet surfaces, % P-selectin expression

All markers of activation increased during stress with no habituation effects.

Reid et al., 2009 (27)

249 patients with CHD Mental arithmetic; anger recall

Six platelet activation marker sets including PLAs, βTG

Platelet activation marker sets increased significantly during stress, but βTG did not change.

Note. ADP, adenosine diphosphate, βTG, beta-thromboglobulin; PF4, platelet factor 4; PDGF, platelet-derived growth factor; PLA, platelet-

leukocyte aggregate; PMA, platelet-monocyte aggregate; TXB2, thromboxane B2; WHO, World Health Organization

Table 3

Coagulation and acute stress.

Study Sample Mental Stressor(s) Recovery Period

Measures Findings

Jern et al., 1989 (4)

10 healthy young men Stroop; mental arithmetic

10 min Hct, Fib, FVII:C, FVII:ag, FVIII:C, vWF:ag

Hct, Fib, FVII:C, FVIII:C and vWf:ag increased significantly from baseline to stress. vWF:ag decreased significantly from stress to recovery, but Hct, Fib, FVII:C, and FVIII:C remained elevated. No effects for FVII:ag.

Jern et al., 1991 (28)

9 healthy young women Stroop; mental arithmetic

10 min Hct, Fib, FVII:ag, FVII:C, vWF:ag

Hct and Fib increased significantly from baseline to stress, but FVII:ag, FVII:C and vWF:ag did not. Recovery depended on menstrual cycle phase.

Muldoon et al., 1995 (29)

44 healthy young adults Stroop vs. control None Fib, Hct, Hgb, PV

The increase in Fib in stressed subjects was not significantly different compared to controls.

Davis, 1999 (30)

52 healthy young female smokers and nonsmokers either taking or not taking oral contraceptives

Speech; mental arithmetic

10 min Fib, Hct Fib increased significantly from baseline to stress across all women. Recovery measures not reported.

von Känel et al., 2001 (31)

53 elderly caregivers of patients with Alzheimer's disease (11 with and 42 without vascular disease)

Two speeches None D-dimer, vWF:ag

D-dimer increased significantly in those with vascular disease compared to those without vascular disease. No effects for vWF.

von Känel et al., 2002 (32)

13 normotensive and 6 mildly hypertensive adults

Speech; mirror tracing

None D-dimer D-dimer increased significantly.

Steptoe et al., 2003 (33)

221 middle-aged adults (125 men, 96 women)

Stroop; mirror tracing

45 min Hct, Fib Hct and Fib increased significantly from baseline to stress and remained elevated after recovery.

Steptoe et al., 2003 (34)

238 middle-aged adults (129 men, 109 women)

Stroop; mirror tracing

45 min Hct, PV, FVIII:C, vWF:ag,D-dimer

Hct, FVIII:C and vWF:ag increased significantly from baseline to stress. After recovery, vWF:ag did not differ from baseline, but Hct and FVIII:C were still elevated. No effects for D-dimer.

von Känel et al., 2004 (35)

48 elderly adults (16 men, 32 women)

Two speeches 14 min D-dimer, vWF:ag

D-dimer increased significantly from baseline to stress and from stress to recovery. vWF:ag decreased significantly from baseline to sress.

von Känel et al., 2004 (36)

24 healthy, middle-aged men

TSST, performed 3 times with one-week intervals; coagulation measured at weeks 1 and 3

45 min and 105 min

Fib, FVII:C, FVIII:C, FXII:C, APTT, PT, vWF:ag,D-dimer

Fib, FVII:C, FVIII:C, FXI:a, and vWF:ag increased signficantly from baseline to stress and decreased significantly from stress to 45 min and 105 min recovery. D-dimer did not change from baseline to stress but significantly decreased from stress to 45 min recovery. No effects for APTT or PT. No habituation of responses from week 1 to week 3.

von Känel et al., 2005 (37)

21 healthy men over age 35

TSST 45 min and 105 min

Fib,D-dimer

Fib and D-dimer did not increase significantly from baseline to stress, but decreased significantly from stress to 45 min recovery.

Zgraggen et al., 2005 (38)

22 healthy men over age 35

TSST None Hct, Hgb, PV, Fib, FVII:C, FVIII:C, FXII:C, vWF:ag,D-Dimer

Hct, Hgb, FVII:C, FVIII:C, FXII:C and vWF:ag increased significantly and PV decreased significantly from baseline to stress. Correlations between changes in Hct, Hgb, PV and changes in coagulation measures were not significant, with the exception of Hgb and FXII:C (r=.39).

Bacon et al., 2006 (24)

72 patients with CHD (57 men, 15 women)

PASAT 20 min, followed by exercise

Fib Fib did not increase significantly from baseline to stress.

Hamer et al., 2006 (25)

91 healthy men Speech; mirror tracing, completed twice 4 weeks apart

10 min vWF In session 2 only, vWF increased significantly from baseline to 10 min recovery. Blood was not drawn during or immediately after stress.

Steptoe & Marmot, 2006 (39)

228 middle-aged adults (125 men; 103 women)

Stroop; mirror tracing

45 min Fib, FVIII:C, vWF:ag

Fib, FVIII:C and vWF:ag increased significantly from baseline to stress. FVIII:C and vWF:ag returned to baseline levels during recovery, but Fib was still significantly higher at recovery compared to baseline.

Wirtz et al., 2006 (40)

42 otherwise healthy men (17 hypertensive; 25 normotensive)

TSST 20 min and 60 min

Fib, FVII:C, FVIII:C,D-dimer

All factors increased significantly from baseline to stress and approached or returned to baseline levels by 60 min recovery.

Wirtz et al., 2006 (41)

47 healthy men TSST 20 min and 60 min

D-dimer D-dimer increased significantly from baseline to stress and 20 min recovery and returned to baseline levels at 60 min recovery.

de Boer et al., 2007 (42)

22 young men PASAT while watching themselves in a mirror

30 min Hct, APTT, PT Hct increased with stress and returned to baseline at approximately 15 min recovery. PT shortened marginally with stress and returned to baseline at 8 min recovery. APTT did not show any effects.

Wirtz et al., 2007 (43)

42 otherwise healthy men (17 hypertensive; 25 normotensive)

TSST 60 min Fib, FVII:C, FVIII:C,D-dimer

Reanalysis of Wirtz et al. (2006b). Compared to those without diastolic hypertension, those with diastolic hypertension had higher levels of FVII:C and D-dimer immediately post-stress, higher levels of FVII:C, FVIII:C and D-dimer at 20 min recovery and higher FVIII:C at 60 min recovery.

Note. APTT, activated partial thromboplastin time; Fib, Fibrinogen; FVII:C, Factor VII coagulant activity; FVII:ag, Factor VII antigen; FVIII:C,

Factor VIII coagulant activity; FXII:C, Factor XII coagulant activity; Hct, hematocrit; Hgb, hemoglobin; PASAT, paced auditory serial addition

test; PT, prothrombin time; PV, plasma volume; TAT, thrombin-antithrombin III complex; TSST, Trier Social Stress Test; vWF:ag, von

Willebrand factor antigen

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