PDF icon PDF herunterladen
Semin Thromb Hemost 2025; 51(04): 471-473
DOI: 10.1055/s-0044-1788697
Commentary

Heparin and Posttraumatic Stress Disorder

Giuseppe Lippi
1   Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy
,
Emmanuel J. Favaloro
2   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia
3   Faculty of Science and Health, Charles Sturt University, Wagga Wagga, New South Wales, Australia
4   School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia
› Institutsangaben
› Weitere Informationen
   Lizenzen und Reprints
Preview

Posttraumatic stress disorder (PTSD) reflects a mental illness that can develop after a person has experienced or witnessed a traumatic event such as a natural disaster, accident, terrorist attack, war/combat, sexual assault, or other violent acts.[1] Symptoms usually begin within 3 months of experiencing the traumatic episode(s), although these may occasionally develop earlier, and last for over a month. The most typical symptoms fall into four categories, encompassing intrusive memories (e.g., periodic distressing reminders of the traumatic episode), avoidance behaviors (avoidance of people or places reminiscent of the traumatic episode), negative changes in thinking and mood, along with changes in physical and emotional responses (i.e., arousal symptoms).[1] The historical epidemiology of PTSD suggests that between 5 and 10% of the general population may be affected by this condition at some point in their lives,[2] although coronavirus disease 2019 (COVID-19) has contributed to significantly increase the prevalence of PTSD, with almost 20% of COVID-19-discharged patients showing symptoms.[3] Given this concerning epidemiology, the search for effective treatment options for patients with PTSD has become increasingly important in recent years. Among the various agents that have been proposed, heparin represents an intriguing perspective.

Kondashevskaya conducted a study with 40 sexually mature male Wistar rats that were randomly divided into four groups[4]: a first control group, a second untreated group including modeled PTSD rats, a third group consisting of modeled PTSD rats treated with 64 U/kg low-molecular-weight heparin (LMWH), and a fourth group with normal rats that received only 64 U/kg LMWH. PTSD was achieved by maintaining the animals under a permanent “predator stress” (i.e., cat urine odor) for 10 minutes daily for 10 days. The behavioral disturbances were associated with persistent increase in psychoemotional symptoms, accompanied by a decrease in serum corticosterone levels. In the PTDS-LMWH-treated group, behavioral and psychoemotional parameters (e.g., number of entries and time spent into the open arm of the maze as the more anxious rodents are less likely to do this, number of active and passive defensive responses) improved significantly, to the point of normalization, while at the same time corticosterone increased to levels comparable to those of the control group.

The same author conducted another study in adult male Wistar rats, which were divided into three groups, i.e., a control group (n = 20), a group with untreated modeled PTSD (n = 30), and a third group with modeled PTSD receiving 36 mg/kg unfractionated heparin (UFH).[5] PTSD was again reproduced by the validated “predator stress” model (exposure to cat urine). Consistent with previous findings, the authors found a consistent reduction in plasma corticosterone levels in the PTSD rats, which was reversed with complete normalization in the group of rats receiving UFH. All psychoemotional responses were also profoundly altered in PTDS rats, while they did not differ significantly between UFH-administered PDTS rats and the control group. Of note, there was a consistent reduction in the thickness of the adrenal cortex (particularly the zona fasciculata and zona reticularis) in the untreated PDTS group, whereas this abnormality was not observed in the UFH-treated PDTS group. Finally, plasma levels of some inflammatory cytokines (namely interleukin [IL]-2 and IL-6), that were consistently elevated in the untreated PDTS group, were similar in the control and UFH-treated PDTS groups.

Although the exact mechanisms by which heparin (both LMWH and UFH) could contribute to the relief of symptoms of PTSD are not precisely known, some hypotheses can be proposed. Based on the assumption that the mechanisms responsible for alteration of the central nervous system in PTSD patients are relatively similar to those causing lipopolysaccharide-induced disorders,[6] it is conceivable that the anti-inflammatory effect of heparin,[7] exerted mainly through the modulation (downregulation) of various proinflammatory cytokines,[8] would be effective in attenuating the systemic low-grade inflammatory state characteristic of PTSD.[9] Another possible mechanism is the heparin-dependent increase in brain-derived neurotrophic factor,[8] which was found to be significantly decreased in human patients with PDTS in the recent meta-analysis by Mojtabavi et al.[10]

Of further interest, there is now consolidated evidence that PTSD is an independent risk factor for cardiovascular disease (CVD), other than a common psychiatric sequela of CVD events that may negatively impact the prognosis of these patients.[11] Moreover, the large Nurses' Health Study II, which included nearly 50,000 young and middle-aged women,[12] estimated that those with multiple PTSD symptoms (i.e., 6/7) had a more than 2.4-fold higher risk of venous thromboembolism compared with women without PTSD symptoms. These findings were recently confirmed by preliminary data published by Lau et al,[13] who followed more than 11,000 subjects over a 10-year period, and found that those diagnosed with PTSD had a nearly 1.7-fold higher risk of developing deep vein thrombosis.

Nevertheless, the preliminary findings from the two studies by Kondashevskaya et al[4] [5] should be interpreted with caution, as further independent studies are required to replicate and validate the possible clinical efficacy of heparin in improving PTSD symptoms, and potentially averting subsequent thrombotic sequalae ([Fig. 1]). However, regardless of the mechanistic relationship between heparin and the pathogenesis of PTSD, there are some plausible biological mechanisms and promising therapeutic implications that would warrant the design of clinical trials to investigate the potential benefits of heparin in (human) patients with PTSD.

Zoom
Fig. 1 Potential influence of heparin in reducing the risk of developing post-traumatic stress disorder (PDTS).


Publikationsverlauf

Artikel online veröffentlicht:
24. Juli 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA