Spontaneous Recurrent Pneumothorax during Pregnancy Secondary to Ectopic Deciduosis.

Background Ectopic deciduosis is a benign presence of endometrial tissue outside of the uterus during pregnancy that rarely presents with pleuropulmonary manifestations and recurrent pneumothorax. Case Description We report a 35-year-old woman at 15 weeks' gestation with a history of recurrent intrapartum right pneumothorax found to have pleural, pulmonary, and diaphragmatic lesions and a middle lobe air leak. Wedge resection of the middle lobe and mechanical pleurodesis was performed. Histopathological analysis was progesterone receptor and PAX8 positive consistent with ectopic deciduosis. Conclusion Ectopic deciduosis is a rare cause of recurrent pneumothorax in pregnancy and should be considered when evaluating these patients.

The α-globin chain of hemoglobin potentiates tissue plasminogen activator induced hyperfibrinolysis in vitro.

BACKGROUND: Severe injury predisposes patients to trauma-induced coagulopathy, which may be subdivided by the state of fibrinolysis. Systemic hyperfibrinolysis (HF) occurs in approximately 25% of these patients with mortality as high as 70%. Severe injury also causes the release of numerous intracellular proteins, which may affect coagulation, one of which is hemoglobin, and hemoglobin substitutes induce HF in vitro. We hypothesize that the α-globin chain of hemoglobin potentiates HF in vitro by augmenting plasmin activity. METHODS: Proteomic analysis was completed on a pilot study of 30 injured patients before blood component resuscitation, stratified by their state of fibrinolysis, plus 10 healthy controls. Different concentrations of intact hemoglobin A, the α- and ß-globin chains, or normal saline (controls) were added to whole blood, and tissue plasminogen activator (tPA)-challenged thrombelastography was used to assess the degree of fibrinolysis. Interactions with plasminogen (PLG) were evaluated using surface plasmon resonance. Tissue plasminogen activator-induced plasmin activity was evaluated in the presence of the α-globin chain. RESULTS: Only the α- and ß-globin chains increased in HF patients (p < 0.01). The α-globin chain but not hemoglobin A or the ß-globin chain decreased the reaction time and significantly increased lysis time 30 on citrated native thrombelastographies (p < 0.05). The PLG and α-globin chain had interaction kinetics similar to tPA:PLG, and the α-globin chain increased tPA-induced plasmin activity. CONCLUSIONS: The α-globin chain caused HF in vitro by binding to PLG and augmenting plasmin activity and may represent a circulating "moonlighting" mediator released by the tissue damage and hemorrhagic shock inherent to severe injury. LEVEL OF EVIDENCE: Prognostic, level III.

Prospective assessment of fibrinolysis in morbid obesity: tissue plasminogen activator resistance improves after bariatric surgery.

BACKGROUND: Morbid obesity is associated with an increased risk of thrombotic events, which has been attributed to increased thrombotic activity. Multiple mechanisms have been proposed to explain this increased risk, including an inflammatory state with upregulation of procoagulant and antifibrinolytic proteins. We therefore hypothesize that patients with morbid obesity are hypercoagulable and will revert to normal after bariatric surgery. OBJECTIVES: To evaluate changes in the hypercoagulable state after bariatric surgery. SETTING: University Hospital, Bariatric Center of Excellence, United States. METHODS: Thromboelastography (TEG) data were collected on 72 subjects with morbid obesity, with 36 who had 6 months of follow-up after bariatric surgery. TEG data of 75 healthy subjects (HS) without obesity, recent trauma or surgery, acute infection, or chronic conditions (e.g., liver, cardiovascular, or kidney disease; cancer; diabetes; autoimmune or inflammatory disorders; and disorders of coagulation) were used for comparison. TEG was performed alone and with the addition of 75 and 150 ng/mL tissue plasminogen activator (tPA) to quantify fibrinolysis resistance (tPA-challenged TEG). RESULTS: The bariatric surgery cohort had a median age of 40.5 years, a median body mass index of 44.6 kg/m2, and 90% female patients. Median body mass index reduced significantly 6 months post surgery but remained elevated compared with the HS group (31.4 versus 25.4 kg/m2, P < .0001). At 6 months post surgery, subjects had longer reaction time (mean difference, 1.3; P = .02), lower maximum amplitude (-2.4, P = .01), and increased fibrinolysis with low-dose (3.1, P < .0001) and high-dose tPA-challenged TEG (9, P < .0001). Compared with HS, the postsurgery TEG values were still more likely to be abnormal (all P < .05). CONCLUSIONS: Patients with morbid obesity form stronger clots more rapidly and are more resistant to fibrinolysis than subjects without obesity. Bariatric surgery significantly improved the hypercoagulable profile and fibrinolysis resistance of morbid obesity.

Hemoglobin-based oxygen carriers promote systemic hyperfibrinolysis that is both dependent and independent of plasmin.

BACKGROUND: Hyperfibrinolysis plays an integral role in the genesis of trauma-induced coagulopathy. Recent data demonstrate that red blood cell lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOCs) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy because of the presence of free hemoglobin. MATERIALS AND METHODS: WB was sampled from healthy donors (n = 6). The clotting profile of each citrated sample was evaluated using native thromboelastography. Serial titrations were performed using both HBOC (PolyHeme) and normal saline (NS; 5%, 25%, and 50%) and evaluated both with and without a 75-ng/mL tissue plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin-dependent fibrinolysis. Fibrinolysis was measured and recorded as lysis at 30 min (LY30), the percentage of clot LY30 after maximal clot strength. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman rho coefficients. Groups were also compared using a Friedman test and post hoc analysis with a Bonferroni adjustment. RESULTS: tPA-provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, and 50% titrations: 11%, 21%, and 44%, respectively; Spearman = 0.94; P < 0.001) and NS (11%, 28%, and 58%, respectively; Spearman = 0.790; P < 0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%, 4%, 5%; Spearman = 0.735; P = 0.001) and NS did not (1%, 2%, 1%; r = 0.300; P = 0.186. Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB versus 50% HBOC: 1.8% versus 5.7%, P = 0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC versus 50% HBOC + TXA: 5.6% versus 5.7%, P = 0.92). In addition, the increased fibrinolysis seen with NS was reversed when TXA was present (WB versus 50% NS: 1.8% versus 1.7%, P = 1.0). CONCLUSIONS: HBOCs enhance fibrinolysis both with and without addition of tPA; moreover, this mechanism is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings indicate the hemoglobin molecule or its components stimulate fibrinolysis by both tPA-dependent and innate mechanisms.

Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock.

The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia, and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here, we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma versus normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections.

Shock-induced systemic hyperfibrinolysis is attenuated by plasma-first resuscitation.

BACKGROUND: We developed a hemorrhagic shock animal model to replicate an urban prehospital setting where resuscitation fluids are limited to assess the effect of saline versus plasma in coagulopathic patients. An in vitro model of whole blood dilution with saline exacerbated tissue plasminogen activator (tPA)-mediated fibrinolysis, while plasma dilution did not change fibrinolysis. We hypothesize that shock-induced hyperfibrinolysis can be attenuated by resuscitation with plasma while exacerbated by saline. METHODS: Sprague-Dawley rats were hemorrhaged to a mean arterial pressure of 25 mm Hg and maintained in shock for 30 minutes. Animals were resuscitated with either normal saline (NS) or platelet-free plasma (PFP) with a 10% total blood volume bolus, followed by an additional 5 minutes of resuscitation with NS to increase blood pressure to a mean arterial pressure of 30 mm Hg. Animals were observed for 15 minutes for the assessment of hemodynamic response and survival. Blood samples were analyzed with thrombelastography paired with protein analysis. RESULTS: The median percentage of total blood volume shed per group were similar (NS, 52.5% vs. PFP, 55.7; p = 0.065). Survival was 50% in NS compared with 100% in PFP. The change in LY30 and tPA levels from baseline to shock was similar between groups (LY30 PFP, 10; interquartile range [IQR], 4.3-11.2; NS, 4.5; IQR, 4.1-14.2; p = 1.00; tPA PFP, 16.6 ng/mL; IQR, 13.7-27.8; NS, 22.4; IQR, 20.1-25.5; p = 0.240). After resuscitation, the median change in LY30 was greater in the NS group (13.5; IQR, 3.5-19.9) compared with PFP (-4.9%; IQR, -9.22 to 0.25 p = 0.004), but tPA levels did not significantly change (NS, 1.4; IQR, -6.2 to 7.1 vs. PFP, 1.7; IQR, -5.2 to 6.8; p = 0.699). CONCLUSION: Systemic hyperfibrinolysis is driven by hypoperfusion and associated with increased levels of tPA. Plasma is a superior resuscitation fluid to NS in a prehospital model of severe hemorrhagic shock as it attenuates hyperfibrinolysis and improves systemic perfusion.

The "Death Diamond": Rapid thrombelastography identifies lethal hyperfibrinolysis.

BACKGROUND: Postinjury hyperfibrinolysis (HF), defined as LY30 of 3% or greater on rapid thrombelastography (rTEG), is associated with high mortality and large use of blood products. We observed that some cases of HF are reversible and are associated with patients who respond to hemostatic resuscitation; however, other cases of severe HF seem to be associated with these patients' inevitable demise. We therefore sought to define this unsurvivable subtype of HF as a recognizable rTEG tracing pattern. METHODS: We queried our trauma registry for patients who either died or spent at least 1 day in the intensive care unit, received at least 1 U of packed red blood cells, and had an admission rTEG. Within this group of 572 patients, we identified 42 pairs of nonsurvivors and survivors who matched on age, sex, injury mechanism, and New Injury Severity Score (NISS). We inspected the rTEG tracings to ascertain if any pattern was found exclusively within the nonsurviving group and applied these findings to the cohort of 572 patients to assess the predictive value for mortality. RESULTS: Within the matched group, 17% of the patients developed HF. Within the HF subgroup, a unique rTEG pattern was present in 14 HF patients who died and in none of the survivors. This pattern was a "diamond-shaped" tracing with a short time to maximum amplitude of 14 minutes or shorter and complete lysis before the LY30 point. When these criteria are applied to the 572 unmatched patients, this pattern had a 100% positive predictive value for mortality. CONCLUSION: Patients displaying the "death diamond" pattern on their admission rTEG are at higher risk for mortality. Given the volume of blood products and other resources that these patients consume, this thrombelastography pattern may represent an objective criterion to discontinue efforts at hemostatic resuscitation. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Revisiting early postinjury mortality: are they bleeding because they are dying or dying because they are bleeding?

BACKGROUND: Intense debate continues in the search of the optimal ratio of blood components to deliver preemptively in the critically injured patient anticipated to require a massive transfusion. A major challenge is distinguishing patients with refractory coagulopathy versus those with overwhelming injuries who will perish irrespective of blood component administration. The hypothesis of this clinical study is that a predominant number of early deaths from hemorrhage are irretrievable despite an aggressive transfusion policy. MATERIALS AND METHODS: During the 7-y period ending in December 2009, there were 772 in-hospital trauma deaths. Each of these deaths had been assigned a cause of death via concurrent review by the multidisciplinary hospital trauma quality improvement committee. Emergency department deaths and patients arriving from outside facilities were excluded from this study. RESULTS: Of the 382 patients (49.5% of total) who died secondary to acute blood loss, 84 (22.0%) survived beyond the ED; of these 84, 68 (81%) were male, mean age was 31 y, and 30 (36%) sustained blunt trauma. Cause of death was determined to be exsanguination in 63 (75%), coagulopathy in 13 (15%), metabolic failure in 5 (6%), and indeterminate in 3 patients (4%). CONCLUSION: These data indicate that 75% of patients who succumb to postinjury acute blood loss are bleeding because they are dying rather than dying because they are bleeding. Conversely, only 13 (2%) of the hospital deaths were attributed to refractory coagulopathy. These critical facts need to be considered in designing studies to determine optimal massive transfusion protocols.