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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.
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PMID:Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. 915 80

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal bleeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and coagulation factors V, VIII, and XI and causes release of von Willebrand factor from vascular endothelium. Thrombin can also downregulate the hemostatic system by inducing formation of platelet inhibitory agents, such as nitric oxide and prostacyclin, and release of tissue plasminogen activator, facilitating activation of protein C, and releasing tissue factor pathway inhibitor. Excessive thrombin activity may also result in substantial consumption of platelets, fibrinogen, and labile coagulation factors and abnormal bleeding. Elevated tissue plasminogen activator levels secondary to activation of the contact system and surgery catalyze the formation of plasmin, which also consumes or internalizes platelet glycoprotein receptors and coagulation factors V, VIII, and fibrinogen. Heparin can reduce the generation of and mediate neutralization of excessive and CPB-associated thrombin activity. Heparin anticoagulation is commonly monitored with the activated clotting time (ACT). However, the ACT may be prolonged by factors other than heparin during CPB, such as hemodilution and hypothermia, and therefore may not accurately reflect the extent of anticoagulation by heparin. Aprotinin, a nonspecific serine protease inhibitor used with CPB, can also prolong celite-based ACT values, rendering it less reliable for monitoring heparin anticoagulation. Therefore, several alternative anticoagulation strategies have been recommended when aprotinin is used, such as a higher celite ACT trigger (>750 seconds), monitoring of whole blood heparin concentrations (eg, >2.7 U/mL), or administration of heparin based on a CPB duration-dependent, fixed-dose regimen. Administration of heparin doses higher than those generally recommended, as guided by predetermined, patient-specific whole blood heparin concentration measurements during bypass, can reduce excessive thrombin-mediated consumption of platelets and coagulation factors as well as post-CPB blood loss and blood component transfusions. New modalities of improving suppression of excess thrombin generation during CPB include use of heparin-bonded CPB circuits, heparin cofactor II or related analogs, supplemental antithrombin III, direct thrombin inhibitors (eg, hirudin, argatroban), and inhibitors of the contact and tissue factor pathways. The safety and efficacy of these approaches remains to be established by additional, appropriately powered, prospective studies.
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PMID:Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: an update. 1046 45

Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on a patient with chronic pulmonary thromboembolism accompanied by protein C deficiency. The patient was a woman aged 68 years who had protein C deficiency. The preoperative condition was New York Heart Association functional class IV. Hypoxemia, marked pulmonary hypertension, and low cardiac output were observed. After a median sternotomy, moderate hypothermia was induced using a cardiopulmonary bypass, and thromboendarterectomy in the pulmonary artery was performed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased. The cardiac output also increased, and New York Heart Association functional class improved to I. Pulmonary thromboendarterectomy under cardiopulmonary bypass was effective for chronic pulmonary thromboembolism accompanied by protein C deficiency.
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PMID:[Surgical treatment for chronic pulmonary thromboembolism in a patient with protein C deficiency]. 1124 58

The roles of inflammation and coagulation in the pathophysiology of sepsis are described. Sepsis results when an infectious insult triggers a localized inflammatory reaction that then spills over to cause systemic symptoms of fever or hypothermia, tachycardia, tachypnea, and either leukocytosis or leukopenia. These clinical symptoms are called the systemic inflammatory response syndrome. Severe sepsis is defined by dysfunction of one of the major organ systems or unexplained metabolic acidosis. The inflammatory reaction is mediated by the release of cytokines, including tumor necrosis factor-alpha, interleukins, and prostaglandins, from neutrophils and macrophages. The cytokines activate the extrinsic coagulation cascade and inhibit fibrinolysis. These overlapping processes result in microvascular thrombosis; thrombosis is one potential factor producing organ dysfunction. Activation of the coagulation system leads to consumption of endogenous anticoagulants (e.g., protein C and antithrombin); this may be an important factor in the development of microvascular coagulation. Antiinflammatory mediators as well as inflammatory mediators have a role in sepsis, and an excess of either can result in poor patient outcomes. Sepsis is a complex syndrome involving activation of a variety of systems.
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PMID:Pathophysiology of sepsis. 1188 12

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
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PMID:Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts. 1611 32

Pulmonary thromboendarterectomy was performed on a patient with chronic pulmonary thromboembolism showing thrombophilia. The patient was a 56-year-old female with the above condition complicated by congenital protein C deficiency. She was admitted to our hospital with severe dyspnea accompanied by right ventricular failure. A pulmonary arteriogram showed occlusion and stenosis from lobar to segmental arteries. Cardiac catheterization showed marked pulmonary hypertension. A lung perfusion scintigram revealed multiple defects in the right and left lungs. After the insertion of an inferior vena cava filter, she was operated on. Following a median sternotomy, thromboendarterectomy of the bilateral pulmonary arteries was performed using deep hypothermia and intermittent circulatory arrest. Circulatory arrest was employed in three periods totaling up to 36 minutes. After surgery, she had improvements in pulmonary hypertension and pulmonary vascular resistance. She maintained improved lung functions, and remained in the New York Heart Association functional class I for more than two years and eight months after surgery.
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PMID:Pulmonary thromboendarterectomy for chronic pulmonary thromboembolism in protein C deficiency. 1651 32

Recent observational studies have identified an acute coagulopathy in trauma victims that is present on arrival in the emergency room. It has been associated with a four-fold increase in mortality and increased incidence of organ failure. Conventional trauma resuscitation and transfusion protocols are designed for dilutional coagulopathy and appear inadequate in the management of acute traumatic coagulopathy and massive transfusion. Acute Coagulopathy of Trauma Shock (ACoTS) is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. The mechanism through which acute coagulopathy develops is unclear but activation of the protein C pathway has been implicated. Standard coagulation tests do not identify cases in a timely fashion and ACoTS should be suspected in any trauma patient with a significant magnitude of injury and shock, as evidenced by an abnormal admission base deficit on blood gas. Development of point of care coagulometers and whole blood coagulation analysers, such as rotational thromboelastometry, may enable earlier laboratory identification of this group. Retrospective studies performed by the American military indicate that resuscitation of severely injured patients with higher ratios of plasma given early may improve outcome and reduce overall blood product use. The place of adjunctive pharmaceutical agents within this strategy remains unclear. There is an acute coagulopathy associated with trauma and shock that is an independent predictor of outcomes. Delineation of this entity, with directed management protocols should lead to a reduction in avoidable deaths from haemorrhage after trauma.
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PMID:The acute coagulopathy of trauma shock: clinical relevance. 2040 26

Abnormal coagulation parameters can be found in 25% of trauma patients with major injuries. Furthermore, trauma patients presenting with coagulopathy on admission have worse clinical outcome. Tissue trauma and systemic hypoperfusion appear to be the primary factors responsible for the development of acute traumatic coagulopathy immediately after injury. As a result of overt activation of the protein C pathway, the acute traumatic coagulopathy is characterised by coagulopathy in conjunction with hyperfibrinolysis. This coagulopathy can then be exacerbated by subsequent physiologic and physical derangements such as consumption of coagulation factors, haemodilution, hypothermia, acidemia and inflammation, all factors being associated with ongoing haemorrhage and inadequate resuscitation or transfusion therapies. Knowledge of the different mechanisms involved in the pathogenesis of acute traumatic coagulopathy is essential for successful management of bleeding trauma patients. Therefore, early evidence suggests that treatment directed at aggressive and targeted haemostatic resuscitation can lead to reductions in mortality of severely injured patients.
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PMID:New insights into acute coagulopathy in trauma patients. 2040 67

Trauma-induced coagulopathy (TIC) is a frequent complication of severely injured patients. The etiology of TIC is complex. Contributing factors include overwhelming generation of thrombin and activated protein C, consumption of coagulation factors and platelets, hyperfibrinolysis, and dilution of clotting factors through administration of fluids. In addition, hypothermia and shock-associated metabolic acidosis augment the clotting dysfunctions. The occurrence of TIC has been shown to be an independent risk factor for death after trauma warranting aggressive treatment. On admission to the emergency room patients with massive blood loss should be employed on basis of clinical and diagnostic variables to identify patients at high risk of coagulopathy. Patients at high risk should be treated with tranexamic acid (1 g bolus followed by 1 g/8 h), and critical factor and platelet deficiencies should be corrected by transfusion of factor concentrates and platelet concentrates. In addition, plasma should be administered in a 1:1 ratio with red cells. The use of recombinant factor VIIa should be considered if major bleeding persists despite best-practive use of blood products.
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PMID:Haemostasis management of massive bleeding. 2131 19

Acute traumatic coagulopathy (ATC) is an early endogenous process, driven by the combination of tissue injury and shock that is associated with increased mortality and worse outcomes in the polytrauma patient. This review summarizes our current understanding of the pathophysiology of ATC and the role of rapid diagnostics in the management of severe trauma hemorrhage. In particular we consider diagnostic and therapeutic strategies for bleeding trauma patients with short versus long prehospital times and the concept of remote damage control resuscitation. Endothelial activation of Protein C is a central mechanism of ATC, which produces rapid anticoagulation and fibrinolysis following severe trauma. Continued blood loss, hypothermia, acidosis, and hemodilution potentiate ATC and lead to a global derangement in all components of hemostasis. The contribution and interplay between platelet activity, fibrinogen utilization, endothelial dysfunction, and neurohormonal pathways remain to be defined in ATC pathogenesis but may offer novel therapeutic targets. Conventional laboratory-based tests of coagulation have a limited role in the early management of major trauma hemorrhage. TEG and ROTEM provide a rapid evaluation of clot dynamics in whole blood and are of greater value than coagulation screens in diagnosing and managing trauma hemorrhage.
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PMID:Pathogenesis of acute traumatic coagulopathy. 2330 69


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