Changes in coagulation and fibrinolysis occurring in dogs during hypothermia

doi:10.1016/0049-3848(85)90096-9

Thrombosis Research

Volume 37, Issue 4, 15 February 1985, Pages 503-512

https://doi.org/10.1016/0049-3848(85)90096-9 Get rights and content

Abstract

Changes in fibrinolysis, platelets and coagulation during hypothermia were investigated in anesthetized dogs. Strong activation of plasma fibrinolysis was observed in the hypothermia group. The maximum fibrinolytic activity determined with standard fibrin plates was markedly higher than that of the control sample (mean values: 67 and 15 mm²/0.03 ml plasma, respectively). On the other hand, no fibrinolysis was observed by the plasminogen free plate method. Activation was not observed in the control group or the hypothermia group premedicated with chlorpromazine. The platelet count was decreased from 100% to 14.7% and the collagen induced platelet aggregability from 61% to 2.3% during hypothermia. Recovery from both reductions occurred on rewarming. In the control and premedicated groups, the recalcification time was reduced progressively (from 93.6 to 60.9 sec and from 101.1 to 71.8 sec as mean times, respectively). The tendencey towards shortening of the recalcification time was not related to the core temperature.

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Cited by (111)

Heated Humidified Breathing Circuit Rewarming in Hypothermic Patients Post-Cardiopulmonary Bypass—Pilot Study
2022, Journal of Cardiothoracic and Vascular Anesthesia
Hypothermia on intensive care unit (ICU) admission after cardiac surgery and cardiopulmonary bypass is common. It contributes to postoperative complications including shivering, coagulopathy, increased blood loss and transfusion requirements, morbid cardiac events, metabolic acidosis, increased wound infections, and prolonged hospital length of stay. The current standard of care for rewarming ICU patients is forced air warming blankets. However, high-quality evidence on additional benefit rendered by other warming methods, such as heated humidified breathing circuits (HHBC), is lacking. Therefore, the authors conducted a pilot study to examine whether the addition of HHBC to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass reduced time to normothermia.
Prospective study conducted at a single large academic medical center.
The study group was composed of 14 patients who were enrolled prospectively between April 1 and June 14, 2019. The study group was compared with a 2:1 matched retrospective control group. The matched group consisted of 28 patients from a 12-month period from July 1, 2018 June 30, 2019.
Study patients received warming via forced air warming blankets and HHBC and were compared with patients in a control group who received only warming blankets. Time to normothermia, time to extubation, time to normal pH, blood loss, blood transfusions, and coagulation profile laboratory values were compared between the study and control groups.
The present study found no statistical difference in time to normothermia, for which the standard-of-care retrospective group achieved normothermia after a median (Q1-Q3) 4.8 (4.0-6.0) hours compared with 4.4 (3.5-5.5) hours in the prospective group receiving HHBC. All secondary outcomes, including time to extubation, time to normal pH, ICU blood product transfusion, chest tube output, and coagulation profile, were similar.
The present pilot study detected a similar time to normothermia, extubation, and normal pH when HHBC were added to standard forced air warming blankets in hypothermic patients (≤35°C) admitted to the ICU after cardiac surgery using cardiopulmonary bypass. A future larger prospective study designed to detect smaller, but clinically meaningful, reductions in the time to key clinical events for patients treated with HHBC is feasible and warranted.
Extracorporeal cardiopulmonary support may be an efficient rescue of patients after massive pulmonary embolism. An experimental porcine study
2012, Thrombosis Research
Citation Excerpt :
According to previous studies tissue plasminogen activator (t-PA) is less effective in vivo at a subnormal temperature [8]. On the other hand an increased autogenic fibrinolytic activity in hypothermic dogs probably caused by an increased secretion of t-PA has been shown long time before CPS was an option [9]. Therapeutic induced mild hypothermia with a core temperature of 32-34 °C for 24 hours after cardiac arrest in comatose survivors has improved neurologic outcome [10,11].
Treatment of massive pulmonary embolism leading to cardiac arrest is controversial but restitution of circulation within a shorter time is crucial. Cardiopulmonary support and therapeutic hypothermia is an option for cardiac arrest and could be used to treat massive PE. However, hypothermia may influence the effect of the ongoing intrinsic fibrinolysis.
To establish a porcine model of massive pulmonary embolism, to show that cardiopulmonary support can rescue pigs with massive pulmonary embolism and to examine the effect of hypothermia on fibrinolysis.
Pigs ~ 80 kg were anesthetised and prepared for cardiopulmonary support. Repetitive injections of preformed blood thrombi into the right atrium were done until cardiac arrest. Cardiopulmonary support was established and eighteen pigs were randomised into 3 groups: Normothermia (38-39 °C); hypothermia (33-34 °C); or medication with recombinant tissue plasminogen activator. After three hours the pigs were weaned from cardiopulmonary support, and after 15 minutes with spontaneous circulation assassinated and autopsied. Remaining thrombi in the lungs were weighed.
The development of fatal pulmonary embolism was highly reproducible. All 18 pigs could be weaned from cardiopulmonary support and survived more than 15 minutes. The amount of remaining thromboemboli was substantial in all groups and not significantly different between groups. Normothermic group 20.0 ± 2.2 g, Hypothermic group 17.0 ± 3.7 g, and rt-PA group 14.3 ± 3.2 g.
Cardiopulmonary support could rescue pigs with massive pulmonary embolism. Hypothermia did not reduce the emboli but may for other reasons be beneficial. The optimal additional treatment is still unknown but treatment modalities can be tested in this model.
Acquired bleeding disorders
2011, Blood and Bone Marrow Pathology: Expert Consult
Impact of graded hypothermia on coagulation and fibrinolysis
2011, Journal of Surgical Research
Citation Excerpt :
Our finding that AT-III activity was significantly reduced at moderate hypothermia is in agreement with a relatively recent in vitro study, which showed that the rate of inhibition of thrombin by AT-III was reduced by 5% at 33°C and by 64% at 23°C compared with normothermia (37°C) [16]. On the contrary, Yoshihara et al. found that in dogs, AT-III activity was not affected by deep hypothermia 20°C, while Boldt et al. found that the thrombin/antithrombin III complex was increased in patients undergoing cardiopulmonary bypass at 27°C, indicating a tendency for bleeding diathesis [7, 20]. It is possible that the use of different animals or the different settings of the studies may explain the different findings of the above studies.
Hypothermia has a detrimental effect on hemostatic mechanism. The purpose of this experimental study was to investigate the effect of graded hypothermia on markers of the anticoagulant system (antithrombin III and protein C) and fibrinolytic system (plasminogen, α₂-antiplasmin), and on vascular wall and other tissue specimens.
Ten New Zealand rabbits were subjected to mild and then moderate core hypothermia of 32°C for 60 min. Blood samples were obtained at normothermic (T₁), mild (T₂), and moderate (T₃) hypothermic conditions. Chromogenic assay methods were used to determine quantitatively (%) the activity of antithrombin III, protein C, plasminogen, and α₂-antiplasmin. Hypothermic values were compared with the normothermic values. Tissue and vessel wall specimens were examined under light microscope.
Reduction of activity (%) from normothermia (T₁) to mild (T₂) and moderate (T₃) hypothermia was found for antithrombin III (103.40 ± 12.54, 87.40 ± 13.50, and 82.70 ± 20.78, respectively, with statistically significant difference between T₁–T₃: P=0.03), for protein C (70.1 ± 7.51, 56.30 ± 8.34, and 53.1 ± 7.34, with statistically significant difference between T₁–T₂ and T₁–T₃: P=0.015 for both comparisons) and α₂-antiplasmin (97 ± 9.63, 80.60 ± 11.73, and 83.70 ± 13.94, with statistically significant difference between T₁–T₂: P=0.006). Plasminogen activity was increased (14.50 ± 0.52, 16.30 ± 1.63, and 17.30 ± 2.45, with statistically significant difference between T₁–T₂ and T₁–T₃: P=0.033 for both comparisons). Histologic examination revealed no significant lesions on tissue and vessel wall specimens.
The results of our study suggest that even though the hypothermia period was relatively short, the processes of coagulation and fibrinolysis were altered with simultaneous changes.
Acquired bleeding disorders
2011, Blood and Bone Marrow Pathology
High Transoxygenator Pressure Gradient in a Patient With Polycythemia Vera
2010, Journal of Cardiothoracic and Vascular Anesthesia

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PaperChanges in coagulation and fibrinolysis occurring in dogs during hypothermia

Abstract

Changes in blood cellular elements during hypothermia

Surgery

Repair of arterial septal defects in man under direct vision with the aid of hypothermia

Surgery

Prolonged experimental occlusion of thoracic aorta during hypothermia

A. M. A. Arch. Surg.

Brain cooling in the prevention of brain damage during period of circulatory occlusion in dogs

Ann. Surg.

Coronary perfusion for longer period of cardiac occlusion under hypothermia

J. Thorac. Srug.

Hypothermia in surgery: Analysis of 100 clinical cases

Ann. Surg.

Changes in coagulation occurring in dogs during hypothermia and cardiac surgery

Surgery

Study of basic physiologic changes associated with hypothermia

A. M. A. Arch. Surg.

Experimental evaluation of prolonged hypothermia

A. M. A. Arch. Surg.

Plasma volume, bleeding and clotting time in hypothermic dogs

The fibrin plate method for estimating fibrinolytic activity

Archiv. Biochem. Biophys.

Plasminogen: Purification from human plasma by affinity chromatography

Science

Paper
Changes in coagulation and fibrinolysis occurring in dogs during hypothermia