Therapeutic Hypothermia and the Risk of Hemorrhage

Wang, Chih‐Hung; Chen, N. C.; Tsai, Min‐Shan; Yu, Ping; Wang, An Yi; Chang, Wei‐Tien; Chen, Wen‐Jone

doi:10.1097/md.0000000000002152

Cited by 31 publications

(12 citation statements)

References 76 publications

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“…Given the small cohort we examined, it is possible that our observations could be accidental. In previous reports, bleeding complications were more often observed in hypothermia-treated patients only in smaller studies [41,42] similar to ours, as opposed to observations of larger populations [16,43,44]. One potential mechanism behind the increased risk of bleeding in MTH-treated patients could be a decreased platelet count in blood serum persisting after re-warming.…”

Section: Discussionsupporting

confidence: 85%

Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia

et al. 2023

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Background: Mild therapeutic hypothermia (MTH) is believed to reduce the effectiveness of antiplatelet drugs. Effective dual-antiplatelet therapy after percutaneous coronary intervention (PCI) is mandatory to avoid acute stent thrombosis (ST). The effectiveness of ticagrelor in MTH-treated out-of-hospital cardiac arrest (OHCA) survivors is still a matter of debate. The aim of the study was to evaluate the impact of MTH on the platelet-inhibitory effect of ticagrelor in comatose survivors of OHCA treated with primary PCI.Methods: Eighteen comatose survivors of OHCA with acute coronary syndrome undergoing immediate PCI treated with MTH were compared with 14 patients with uncomplicated primary myocardial infarction after PCI, matched for gender and age, in a prospective, single-center, observational study. Platelet aggregation was evaluated using VerifyNow P2Y12 pointof-care testing at 3 time points: admission (T0), during MTH (T1), and 48-72 h after rewarming (T2).Results: Ticagrelor effectively inhibits platelet aggregation in OHCA patients subjected to MTH and in all patients in the control group. The effectiveness of ticagrelor did not differ between the MTH group and the control group (p = 0.581). In 2 cases in the MTH population, the platelet response to ticagrelor was inadequate, and in one of them it remained insufficient during the re-warming phase. There was no stent thrombosis in these patients. Conclusions:The present study confirmed the effectiveness of ticagrelor to inhibit platelets in myocardial infarction patients after OHCA treated with primary PCI undergoing hypothermia. The use of cooling was not associated with an increased risk of stent thrombosis.

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Section: Discussionsupporting

confidence: 85%

Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia

et al. 2023

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“…Hence, the effect of lowered body temperature on margination of platelets, which can lead to the drop in circulating platelet count, seems a widely conserved phenomenon that is not specific for hibernating species. Since accidental and therapeutic hypothermia in humans are also associated with thrombocytopenia (Jacobs et al 2013 ; Mallet 2002 ; Mikhailidis and Barradas 1993 ; Morrell et al 2008 ; Vella et al 1988 ; Wang et al 2015 ), knowledge of its underlying mechanism may aid in (hemostatic) management of hypothermia. Furthermore, the ability to pharmacologically induce reversible storage of platelets might be exploited for development of novel reversible antithrombotic strategies.…”

Section: Discussionmentioning

confidence: 99%

Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids

et al. 2021

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Immobility is a risk factor for thrombosis due to low blood flow, which may result in activation of the coagulation system, recruitment of platelets and clot formation. Nevertheless, hibernating animals—who endure lengthy periods of immobility—do not show signs of thrombosis throughout or after hibernation. One of the adaptations of hemostasis in hibernators consists of a rapidly reversible reduction of the number of circulating platelets during torpor, i.e., the hibernation phase with reduction of metabolic rate, low blood flow and immobility. It is unknown whether these platelet dynamics in hibernating hamsters originate from storage and release, as suggested for ground squirrel, or from breakdown and de novo synthesis. A reduction in detaching forces due to low blood flow can induce reversible adhesion of platelets to the vessel wall, which is called margination. Here, we hypothesized that storage-and-release by margination to the vessel wall induces reversible thrombocytopenia in torpor. Therefore, we transfused labeled platelets in hibernating Syrian hamster (Mesocricetus auratus) and platelets were analyzed using flow cytometry and electron microscopy. The half-life of labeled platelets was extended from 20 to 30 h in hibernating animals compared to non-hibernating control hamsters. More than 90% of labeled platelets were cleared from the circulation during torpor, followed by emergence during arousal which supports storage-and-release to govern thrombocytopenia in torpor. Furthermore, the low number of immature platelets, plasma level of interleukin-1α and normal numbers of megakaryocytes in bone marrow make platelet synthesis or megakaryocyte rupture via interleukin-1α unlikely to account for the recovery of platelet counts upon arousal. Finally, using large-scale electron microscopy we revealed platelets to accumulate in liver sinusoids, but not in spleen or lung, during torpor. These results thus demonstrate that platelet dynamics in hibernation are caused by storage and release of platelets, most likely by margination to the vessel wall in liver sinusoids. Translating the molecular mechanisms that govern platelet retention in the liver, may be of major relevance for hemostatic management in (accidental) hypothermia and for the development of novel anti-thrombotic strategies.

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“…[ 15 ] This may be attributed to that the hypothermia induces reversible platelet membrane dysfunction, partially inhibits platelet aggregation, and reduces platelet count and function rate also disordered fibrinolytic cascade activity has been observed in patients undergoing hypothermic CPB, thus reducing the blood clotting process, anticoagulation substances also may be released during hypothermia, which specifically inhibits factor Xa. [ 16 ]…”

Section: Discussionmentioning

confidence: 99%

Normothermia versus hypothermia during cardiopulmonary bypass in cases of repair of atrioventricular septal defect

et al. 2020

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Background: Cardiopulmonary bypass (CPB) used for cardiac surgery is now uniformly carried out under normothermic conditions in adult patients; however, the temperature applied in pediatric CPB vary significantly, ranging from deep hypothermia to normothermia due to the lack of a consistent approach to CPB temperature in pediatric cardiac surgery, which is related to a lack of supportive evidence. Organs protection aim to decrease metabolic requirement and provide energy and oxygen, hypothermia has reached these goals by arresting and cooling the heart, delivering oxygen, and modifying reperfusion. Recently, a large number of studies investigated effect of hypothermia to decrease the negative impact of hypothermia. It has been suggested that the degree of hypothermia affects the inflammatory responses triggered by CPB. However, the use of normothermia during CPB had been introduced and resulted in acceptable results. We hypothesized that the use of normothermia during corrective surgery of AV septal defects improves the outcome of the CPB. Objective: The study aimed to compare the outcome of normothermic technique and mild hypothermic technique during (CPB) in pediatric cardiac patients undergoing repair of atrioventricular (AV) septal defect and their effect on tissue perfusion, serum lactate level, duration of patient intubation, and postoperative hospital stay. Patients and Methods: Forty patients presented for repair of AV defect aged from 1 month to 36 months were divided randomly into two equal groups (20 patients in each): Group I (Normothermic group) of body temperature more than 35°C up to 37°C and Group II (mild Hypothermic group) body temperature between (32°C–35°C). Basal data include complete blood count, electrolytes, arterial blood gases (ABGs), coagulation profile, and liver function tests were collected. Hemodynamic variables, ABG, serum lactate, and activated clotting time (ACT) measured in different time intervals related to CPB. With the termination of CPB, aortic cross-clamping time (minutes), CPB time (minutes), spontaneous regaining of the heart function, need for inotropic administration, and/or vasopressor requirements to wean the heart from CPB were reported in all patients. Results: This study showed statistically significant lower PH and HCO3 levels and significantly higher serum lactate levels in Group II (hypothermic) than Group I (normothermic) after weaning from CPB. Furthermore, ACT level was statistically significantly higher in Group II than Group I after weaning of CPB. During postoperative period, hypothermic group showed significantly higher liver enzymes than the normothermic group. The duration of inotropes administration and duration of intubation were significantly longer in Group II than Group I. Conclusion: Normothermia during CPB showed better global tissue perfusion than hypothermia in elective surgeries for repair of AV defects in the f...

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Therapeutic Hypothermia and the Risk of Hemorrhage

Abstract: Supplemental Digital Content is available in the text

Cited by 31 publications

References 76 publications

Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia

Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia

Reversible thrombocytopenia during hibernation originates from storage and release of platelets in liver sinusoids

Normothermia versus hypothermia during cardiopulmonary bypass in cases of repair of atrioventricular septal defect

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