Neurological injury is associated with an acute episode of microangiopathy, but only recently have persistent deficits in memory, concentration, mood and mental endurance been reported in patients who have long recovered from an acute episode of Thrombotic Thrombocytopenia Purpura (TTP). The mechanism for these findings remains unclear. To date, no studies have addressed the frequency or severity of headaches in patients with a previous history of TTP or atypical hemolytic uremic syndrome (aHUS). Based upon the longitudinal follow-up of our TTP and aHUS patients, we hypothesize that headaches are more incapacitating in patients with a history of TTP or aHUS than has been appreciated previously.

Adult patients >3 months since their last acute episode of TTP/aHUS were approached to take a Headache Impact Test (HIT-6) survey in an outpatient office setting. HIT-6 was developed to screen and monitor patients with headaches in both clinical practice and clinical research. Yang et al. has shown that HIT-6 is a reliable and valid tool for discriminating headache impact across episodic and chronic migraine headaches. The questionnaire covers 6 aspects of functioning most impacted by headache (pain, role functioning (the ability to carry out usual activities), social functioning, energy/fatigue, cognition and emotional distress). Scores range from 36 to 78, with higher scores reflecting greater impact and severity (Table 1). Our objective was to determine if headaches were more severe in patients with a previous diagnosis of TTP or aHUS compared to the general population. We used clinical and demographic features of patients including age, race, sex, number of microangiopathy hemolytic anemia episodes and time since last thrombotic microangioagropathy episode for subset analysis.

Between June 1, 2013 and May 30, 2014, 31 patients completed the HIT-6 survey. Of the patients surveyed, 28 were female and 3 were male. Median age was 51 years (range 19-69) and 8 of 31 (26%) subjects were African American. The average HIT-6 score for all 31 subjects was 57.3, significantly higher than sex-matched controls with a HIT-6 score of 51.7 (SD 10.2, p value 0.005, Table 2). Overall, TTP patients had a significantly higher average HIT-6 score of 59.9 vs 51.7 for sex matched controls (SD 9.6, p value 0.002, Table 3). There was no significant difference in HIT-6 scores of aHUS patients and sex matched controls (HIT-6 of 51.9 vs 51.7). Of TTP patients studied, the majority had 3 or more acute episodes and were >24 months since last acute TTP episode. The study was not powered to detect the significance of episodes among only TTP patients; however these data suggest that the number of episodes and time since the last episode did not predict higher scores (Table 4).

Survivors of TTP in remission have increased headache severity compared to the general female population. There was no difference in headache severity among aHUS patients. An awareness of increased headache severity in patients with a previous history of TTP may lead to earlier interventions to minimize the morbidity associated with chronic headaches. Additional research is needed to help elucidate the cause of headaches in times of remission.

Table 1:

HIT-6 interpretation

HIT-6 ScoreInterpretation
60 or more Headaches are severely impacting the patient’s ability to function in everyday life. 
56 to 59 Headaches are substantially impacting the patient’s ability to function in everyday life. 
50 to 55 Headaches are having some impact on the patient’s life but are probably not causing the patient to miss time from family, work, school, or social activities because of headache. 
49 or less Headaches are having little or no impact on the patient’s life. 
HIT-6 ScoreInterpretation
60 or more Headaches are severely impacting the patient’s ability to function in everyday life. 
56 to 59 Headaches are substantially impacting the patient’s ability to function in everyday life. 
50 to 55 Headaches are having some impact on the patient’s life but are probably not causing the patient to miss time from family, work, school, or social activities because of headache. 
49 or less Headaches are having little or no impact on the patient’s life. 
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Table 2:

Norms for the general US population

(N=1,016)HIT -6 Score
Mean 50.00 
Females (N=795) HIT Scale 
Mean 51.74 
Males (N=221) HIT Scale 
Mean 47.55 
(N=1,016)HIT -6 Score
Mean 50.00 
Females (N=795) HIT Scale 
Mean 51.74 
Males (N=221) HIT Scale 
Mean 47.55 
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Table 3:

Summary of HIT-6 score by disease (aHUS vs. TTP)

TTP-aHUSNmeansdp -value1
aHUS 10 51.9 9.9  
TTP 21 59.9 9.6 0.002 
Total 31 57.3 10.2 0.005 
1 p-value based on one-sample t-test comparing the HIT-6 score to the female US norm value of 51.74 for HIT-6. P-values have been adjusted in ordered to conserve the overall type I error rate at 0.05. 
TTP-aHUSNmeansdp -value1
aHUS 10 51.9 9.9  
TTP 21 59.9 9.6 0.002 
Total 31 57.3 10.2 0.005 
1 p-value based on one-sample t-test comparing the HIT-6 score to the female US norm value of 51.74 for HIT-6. P-values have been adjusted in ordered to conserve the overall type I error rate at 0.05. 
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Table 4:

Summary of TTP HIT-6 score by episodes and by months since last episode

Months since last episode Nmeansd
3-6 3 59.3 9.0 
7-12 3 57.0 6.6 
13-24 3 69.3 2.3 
>24 12 58.4 10.6 
Total 21 59.9 9.6 
 
Episodes N mean sd 
1 7 61.3 10.3 
2 2 52.5 7.8 
3 or >3 12 60.3 9.5 
Total 21 59.9 9.6 
Months since last episode Nmeansd
3-6 3 59.3 9.0 
7-12 3 57.0 6.6 
13-24 3 69.3 2.3 
>24 12 58.4 10.6 
Total 21 59.9 9.6 
 
Episodes N mean sd 
1 7 61.3 10.3 
2 2 52.5 7.8 
3 or >3 12 60.3 9.5 
Total 21 59.9 9.6 
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Disclosures

No relevant conflicts of interest to declare.

Topics:
atypical hemolytic-uremic syndrome, headache, disease remission, chronic migraine, fatigue, follow-up, headache, chronic, hemolytic anemia, nervous system trauma, pain

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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