Resuscitation and Care in the Trauma Bay.

Start balanced resuscitation early (pre-hospital if possible), either in the form of whole blood or 1:1:1 ratio. Minimize resuscitation with crystalloid to minimize patient morbidity and mortality. Trauma-induced coagulopathy can be largely avoided with the use of balanced resuscitation, permissive hypotension, and minimized time to hemostasis. Using protocolized "triggers" for massive and ultramassive transfusion will assist in minimizing delays in transfusion of products, achieving balanced ratios, and avoiding trauma induced coagulopathy. Once "audible" bleeding has been addressed, further blood product resuscitation and adjunct replacement should be guided by viscoelastic testing. Early transfusion of whole blood can reduce patient morbidity, mortality, decreases donor exposure, and reduces nursing logistics during transfusions. Adjuncts to resuscitation should be guided by laboratory testing and carefully developed, institution-specific guidelines. These include empiric calcium replacement, tranexamic acid (or other anti-fibrinolytics), and fibrinogen supplementation.

Alternative blood products in trauma.

PURPOSE OF REVIEW: Hemorrhage and trauma-induced coagulopathy cause significant morbidity and mortality in trauma patients. Although blood products are the cornerstone of resuscitation, these resources are scarce, necessitating alternatives. This review examines the use of alternative blood products in trauma as well as the literature supporting their use. RECENT FINDINGS: There is no single true blood product alternative. In recent years, there has been great progress in understanding trauma-induced pathophysiology and blood component alternatives. Products such as tranexamic acid and prothrombin complex concentrate have become well established and are frequently utilized in trauma centers, and many more alternatives are still undergoing further research and development. SUMMARY: Stabilization of hemorrhage and resuscitation is priority in trauma-induced coagulopathy treatment. Alternative products such as tranexamic acid, recombinant factors, prothrombic complex concentrate, fibrinogen concentrates, and desmopressin may also be considered based on the clinical context. Viscoelastic hemostatic assays such as rotational thromboelastometry and thromboelastography can help guide these efforts. Following initial stabilization, additional interventions such as iron supplementation, erythropoietin stimulating agents, and vitamin D may help with chronic sequela.

A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report.

RATIONALE: Congenital dysfibrinogenemia (CD) is a rare coagulation system disease that is often treated without unified management. Individualized treatment thereof presents clinicians with great challenges. PATIENT CONCERNS: A patient who was about to undergo total knee arthroplasty was found to have CD. DIAGNOSES: Coagulation screening revealed low fibrinogen, prolonged thrombin time, minor prolonged prothrombin time, and normal activated partial thromboplastin time were detected during admission, but no abnormal personal and family history findings were observed. Therefore, CD and hypofibrinogenemia were suspected. The gene sequencing confirmed the diagnosis of CD. INTERVENTIONS: The patient received plenty and low level of fibrinogen concentrate during 2 perioperative periods, respectively. OUTCOMES: Successful clinical outcomes were obtained using different treatment strategies. LESSONS: In contrast to prior case reports, this case illustrates the feasibility of low dosing of fibrinogen supplements within an asymptomatic patient in a selective operation. Changes in the level of fibrinogen and fibrin degradation product are of great importance for individualized treatment after supplementation.

Neglected vitamin K deficiency causing coagulation dysfunction in an older patient with pneumonia: a case report.

BACKGROUND: The development of coagulation disorders can be dangerous and fatal in the older people, especially those with multiple medical conditions. Vitamin K-dependent coagulation disorders are easily overlooked when anticoagulant drugs are not used and the patient shows no signs of bleeding. CASE PRESENTATION: We report a case of a 71-year-old male suffering from pulmonary infection with severe coagulation disorder without bleeding symptoms. He also had a history of Parkinson's disease, Alzheimer's disease and cardiac insufficiency. Coagulation tests were normal at the time of admission, prothrombin time (PT) is 13.9 (normal, 9.5-13.1) seconds and the activated partial thromboplastin time (APTT) is 30.2 (normal, 25.1-36.5) seconds. But it turned severely abnormal after 20 days (PT: 136.1 s, APTT: 54.8 s). However, no anticoagulants such as warfarin was used and no bleeding symptoms were observed. Subsequent mixing studies with normal plasma showed a decrease in prothrombin times. Vitamin K deficiency was thought to be the cause of coagulation disorders considering long-term antibiotic therapy, especially cephalosporins, inadequate diet and abnormal liver function. After supplementation with 20 mg of vitamin K, coagulation dysfunction was rescued the next day and serious consequences were effectively prevented. CONCLUSIONS: Overall, timely vitamin K supplementation with antimicrobials that affect vitamin K metabolism requires clinician attention, especially in older patients who are multimorbid, frail or nutritionally compromised, and are admitted to hospital because of an infection that needs antimicrobial therapy are at risk of clotting disorders due to abnormal vitamin K metabolism secondary to altered gut flora, which can exacerbate existing nutritional deficiencies.

Fibrinogen supplementation for the trauma patient: Should you choose fibrinogen concentrate over cryoprecipitate?

BACKGROUND: Trauma-induced coagulopathy is frequently associated with hypofibrinogenemia. Cryoprecipitate (Cryo), and fibrinogen concentrate (FC) are both potential means of fibrinogen supplementation. The aim of this study was to compare the outcomes of traumatic hemorrhagic patients who received fibrinogen supplementation using FC versus Cryo. METHODS: We performed a 2-year (2016-2017) retrospective cohort analysis of the American College of Surgeons Trauma Quality Improvement Program database. All adult trauma patients (≥18 years) who received FC or Cryo as an adjunct to resuscitation were included. Patients with bleeding disorders, chronic liver disease, and those on preinjury anticoagulants were excluded. Patients were stratified into those who received FC, and those who received Cryo. Propensity score matching (1:2) was performed. Outcome measures were transfusion requirements, major complications, hospital, and intensive care unit lengths of stay, and mortality. RESULTS: A matched cohort of 255 patients who received fibrinogen supplementation (85 in FC, 170 in Cryo) was analyzed. Overall, the mean age was 41 ± 19 years, 74% were male, 74% were white and median Injury Severity Score was 26 (22-30). Compared with the Cryo group, the FC group required less units of packed red blood cells, fresh frozen plasma, and platelets, and had shorter in-hospital and intensive care unit length of stay. There were no significant differences between the two groups in terms of major in-hospital complications and mortality. CONCLUSION: Fibrinogen supplementation in the form of FC for the traumatic hemorrhagic patient is associated with improved outcomes and reduced transfusion requirements as compared with Cryo. Further studies are required to evaluate the optimal method of fibrinogen supplementation in the resuscitation of trauma patients. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Trauma-induced hypocalcemia.

BACKGROUND: Trauma-induced hypocalcemia is an underappreciated complication of severe injury but is well known to result in the derangement of an array of physiological regulatory mechanisms. Existing literature provides a compelling link between hypocalcemia and worse trauma-induced coagulopathy and increased mortality after injury. STUDY DESIGN AND METHODS: This narrative review evaluates available data related to the risk factors, mechanisms, and treatment of hypocalcemia after severe injury. The authors did not perform a systemic review or meta-analysis. RESULTS AND DISCUSSION: The interplay of acidosis, hypothermia, and coagulopathy with hypocalcemia potentiates the bloody vicious cycle of hemorrhagic shock which has been the paradigm of trauma resuscitation for over half a century. However, current screening and treatment of postinjury hypocalcemia are relegated to a secondary consideration in trauma resuscitation. We conclude calcium supplementation should be a primary tier intervention for life-threatening injury.

The prophylactic effects of vitamin K supplementation on coagulopathies associated with type 2 diabetes mellitus: A protocol for a systematic review and meta-analysis.

BACKGROUND: The impact of vitamin K in ameliorating diabetes-associated complications, especially those linked with platelet activation and coagulation remains unclear. The current study aims to systematically explore and discuss the available evidence on the impact of vitamin K on the diabetes-cardiovascular disease (CVD)-associated complications. METHODS: A systematic review of studies published on the MEDLINE (PubMed), EMBASE, and Google Scholar electronic database will be conducted. The review will include studies published from inception until May 25, 2020, reporting on the effect of vitamin K on CVD-related markers, especially coagulation factors and platelet activation in type 2 diabetes mellitus. Before the full-text screening, all studies will be screened by title, abstract, and keywords. The Downs and Black checklist will be used to assess the quality of the studies. Additionally, the Cochrane collaboration tool will also be used to evaluate the risk of bias across the included studies. Kappa Cohen's calculator will be used to assess the level of agreement between the authors. DISCUSSIONS: This systematic review will not require ethical approval, and the results will be distributed through conference and peer-reviewed publications. Our results will assist current and future research scientists on the potential use of vitamin K as a protective therapy against CVD-related complications. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on the International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42020151667.

Neonatal subgaleal hemorrhage unrelated to assisted vaginal delivery: clinical course and outcomes.

PURPOSE: The purpose of the study was to evaluate the occurrence of subgaleal hemorrhage (SGH) following non-assisted vaginal delivery (normal vaginal delivery or cesarean delivery), and to characterize associated factors, clinical course, and outcomes, compared to attempted assisted vaginal delivery (AVD)-associated SGH METHODS: A retrospective cohort study was conducted. All cases of SGH encountered following delivery of a singleton neonate at Hadassah, Hebrew University Medical Center during 2011-2018 were included. Maternal, fetal, intrapartum, and neonatal characteristics and outcomes were compared between AVD-related and non-AVD-related SGH groups. RESULTS: The overall incidence of SGH was 4.5/1000 (369/82,256) singleton deliveries. The incidences of AVD- and non-AVD-related SGH were 44.6/1000 (350/7852) and 0.3/1000 (19/74,404) singleton deliveries, respectively. Ten (53%) of the 19 non-AVD-related SGH were diagnosed after vaginal delivery and 9 (47%) after an urgent cesarean section. SGH severity was mild, moderate, and severe in 68%, 16%, and 16% of the cases, respectively. SGH severity did not differ between the attempted AVD group and the non-AVD-related SGH group. A higher proportion of neonates with non-AVD SGH required phototherapy treatment than did those diagnosed with AVD-related SGH (56% vs. 24%, P = 0.003). Other neonatal outcomes, including Apgar scores, maximal bilirubin level, length of stay, and the rate of composite adverse outcomes, did not differ between the groups. CONCLUSIONS: SGH, although rare, may be diagnosed after unassisted vaginal or cesarean delivery in the absence of an AVD attempt. We advocate continuing education for all medical staff who participate in peripartum and neonatal care, regarding the possible occurrence of non-AVD-related SGH.

Interventional vitamin C: A strategy for attenuation of coagulopathy and inflammation in a swine multiple injuries model.

BACKGROUND: Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the proinflammatory and procoagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of multiple injuries and hemorrhage. METHODS: Male Sinclair swine (n = 24; mean body weight, 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiologic monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500 mL of hydroxyethyl starch, and randomized to receive either intravenous normal saline (NS), low-dose VitC (50 mg/kg; LO), or high-dose VitC (200 mg/kg; HI). Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours postresuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung. RESULTS: Compared with VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue proinflammatory mediators (IL-1ß, IL-8, TNFα), plasminogen activation inhibitor-1 and tissue factor. There were no statistically significant differences between treatment groups on mean arterial pressure or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours. CONCLUSION: Although correction of coagulation dysfunction was modest, intravenous high-dose VitC may mitigate the proinflammatory/procoagulant response that contributes to multiple organ failure following acute severe multiple injuries. LEVEL OF EVIDENCE: Prospective randomized controlled blinded trial study, Preclinical (animal-based).

Coagulology, biochemical profile and muscle pathology in calves diagnosed with nutritional muscular dystrophy.

The aim of this study was to explain the correlations between selenium deficiency, hemostatic and biochemical disorders, and the progression of pathological changes in calves diagnosed with nutritional muscular dystrophy (NMD). The study was performed on 20 calves with supplementation of 8 ml selenium and vitamin E preparation and 20 calves with symptoms of NMD. Blood was sampled from calves aged 5, 12 and 19 days. On day 19, samples of the biceps femoris muscle were collected from 6 animals in each group for histopathological analysis. The following blood parameters were determined: PLT, PT, TT, APTT, fibrinogen and D-dimer concentrations, antithrombin III activity, glucose, selenium and vitamin E concentrations, activity of CK, LDH and GSH-Px. Muscle sections were stained with H&E and HBFP. Platelet counts were significantly lower in calves with symptoms of NMD. No significant differences in coagulation parameters were observed between the groups. Sick calves were diagnosed with hyperglycemia and elevation of CK and LDH activity. Selenium and vitamin E concentrations in the blood serum were significantly lower in the experimental group together with significant drop in GSH-Px activity. Changes characteristic of Zenker's necrosis were observed in a muscle of the sick animals. To our best knowledge this is the first study in which the attempt was made to explain the relationship between selenium deficiency and changes in the coagulation system in ruminants.

Coagulation after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a retrospective cohort analysis.

PURPOSE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) benefit patients with peritoneal carcinomatosis. Nevertheless, this therapy is associated with considerable postoperative pain due to the extensive abdominal incision. While epidural analgesia offers efficacious pain control, CRS and HIPEC therapy is associated with perioperative coagulopathy that may impact its use. The purpose of this retrospective study is to characterize the postoperative coagulopathy in this patient subset and to develop a model that will help predict those at risk. METHODS: Our database of patients treated with CRS and HIPEC (n = 171) was reviewed to assess perioperative changes in platelet count, international normalized ratio (INR), and partial thromboplastin time (PTT). Abnormal coagulation was defined by platelet count < 100 × 10-9·L-1, INR ≥ 1.5, or PTT ≥ 45 sec. Severe abnormality in coagulation was defined by platelet count < 50 ×10-9·L-1, INR > 2.0, and/or PTT > 60 sec. A logistic regression model was developed to determine if patient, disease, and/or surgical factor(s) were associated with the development of postoperative coagulopathy. Epidural catheter management in this patient population was also reviewed. RESULTS: Significant differences (adjusted P < 0.007) were noted between median preoperative and postoperative platelet and INR values on postoperative days (POD) 0 through 6 and days 0 through 3, respectively. Highest observed median differences between preoperative and postoperative values showed a decrease in platelet count of 94 × 10-9·L-1 (POD 2 and POD 3), an increase in INR of 0.2 (POD 0 to POD 2), and a decrease in PTT of 3.1 sec (POD 5). Coagulopathy and severe coagulopathy occurred in 38% and 4.7% of patients, respectively. Predictors of coagulopathy included intraoperative transfusion of packed red blood cells (PRBCs) and perhaps the peritoneal carcinomatosis index (PCI). Epidural catheters were inserted in 26 patients for a median [IQR] duration of 7.0 [5.0-7.0] days without complication. At the time of their removal, no blood products were required to correct abnormal coagulation values. CONCLUSIONS: Altered coagulation may appear during the postoperative period in approximately 40% of our patients treated with CRS and HIPEC. Intraoperative transfusion of RBCs and possibly increased PCI are associated with abnormal postoperative coagulation. Close monitoring of coagulation parameters is required to help ensure safe removal of an epidural catheter.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Bleeding and Coagulation Management in Neurostimulation Devices.

INTRODUCTION: The Neurostimulation Appropriateness Consensus Committee (NACC) was formed by the International Neuromodulation Society (INS) in 2012 to evaluate the evidence to reduce the risk of complications and improve the efficacy of neurostimulation. The first series of papers, published in 2014, focused on the general principles of appropriate practice in the surgical implantation of neurostimulation devices. The NACC was reconvened in 2014 to address specific patient care issues, including bleeding and coagulation. METHODS: The INS strives to improve patient care in an evidence-based fashion. The NACC members were appointed or recruited by the INS leadership for diverse expertise, including international clinical expertise in many areas of neurostimulation, evidence evaluation, and publication. The group developed best practices based on peer-reviewed evidence and, in the absence of specific evidence, on expert opinion. Recommendations were based on international evidence in accordance with guideline creation. CONCLUSIONS: The NACC has recommended specific measures to reduce the risk of bleeding and neurological injury secondary to impairment of coagulation in the setting of implantable neurostimulation devices in the spine, brain, and periphery.

Safety of Salvaged Blood and Risk of Coagulopathy in Cardiac Surgery.

Cardiac surgery patients are prone to anemia from several mechanisms: intraoperative blood loss, preexisting anemia, and hemodilution. Patients are very frequently transfused with allogeneic red blood cells (RBC), which in itself is associated with harm. The use of RBC salvage technology has been advocated to salvage blood lost in the operative field and to reduce the need of homologous blood transfusion. Direct cardiotomy suction from the surgical field and unprocessed blood retransfusion is a common practice during cardiopulmonary bypass, but which is associated with a powerful activation of the coagulation and inflammatory systems: thrombin generation, excessive fibrinolysis, and release of proinflammatory cytokines. Compared with direct cardiotomy suction, the use of RBC salvage technology is able to reduce the amount of microparticles and activated proteins of autologous blood before retransfusion. However, when compared with no retransfusion of blood from the operative field, processed blood also triggers coagulopathy and inflammation. Clinical studies are discordant regarding the benefit of RBC salvage use during and after cardiac operations. Meta-analysis suggests reduced need of homologous blood transfusion, but no effects on mortality and morbidity.

Effects of Shen-Fu injection on coagulation-fibrinolysis disorders in a porcine model of cardiac arrest.

OBJECTIVE: The objective of the study is to investigate the effects of Shen-Fu injection (SFI) on coagulation-fibrinolysis disorders in a porcine model of cardiac arrest. MATERIALS AND METHODS: Thirty Wuzhishan pigs were randomly assigned into the sham operation group (SO group, n = 6), epinephrine group (EP group, n = 12), and SFI group (n = 12). After 8 minutes of untreated ventricular fibrillation (VF), pigs in the EP group or SFI group were administered with either EP (0.02 mg/kg) or SFI (1.0 mL/kg), respectively. Plasma levels of tissue factor, thrombin-antithrombin complex, tissue factor pathway inhibitor, antithrombin III, protein C, tissue plasminogen activator, plasminogen activator inhibitor 1, soluble thrombomodulin, and soluble endothelial protein C receptor were measured at baseline, 1, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). In addition, arterial lactate levels were measured at baseline, 1, 6, 12, and 24 hours after ROSC, and lactate clearance was calculated at 1, 6, 12, and 24 hours after ROSC. RESULTS: Compared with the EP group, tissue factor, thrombin-antithrombin complex, tissue factor pathway inhibitor, tissue plasminogen activator, and plasminogen activator inhibitor 1 levels were significantly lower, whereas antithrombin III and protein C levels were significantly higher in the SFI group (all P < .05). In addition, soluble thrombomodulin and soluble endothelial protein C receptor levels in the SFI group were significantly lower in comparison to the EP group (all P < .01). Furthermore, arterial lactate levels were significantly lower, and lactate clearance was higher in the SFI group (all P < .01). CONCLUSIONS: This study demonstrates that SFI can inhibit coagulation-fibrinolysis disorders after cardiac arrest, which may be associated with alleviating endothelial damage and improving systemic metabolism.

Acute effects of calcium supplements on blood pressure and blood coagulation: secondary analysis of a randomised controlled trial in post-menopausal women.

Recent evidence suggests that Ca supplements increase the risk of cardiovascular events, but the mechanism(s) by which this occurs is uncertain. In a study primarily assessing the effects of various Ca supplements on blood Ca levels, we also investigated the effects of Ca supplements on blood pressure and their acute effects on blood coagulation. We randomised 100 post-menopausal women to 1 g/d of Ca or a placebo containing no Ca. Blood pressure was measured at baseline and every 2 h up to 8 h after their first dose and after 3 months of supplementation. Blood coagulation was measured by thromboelastography (TEG) in a subgroup of participants (n 40) up to 8 h only. Blood pressure declined over 8 h in both the groups, consistent with its normal diurnal rhythm. The reduction in systolic blood pressure was smaller in the Ca group compared with the control group by >5 mmHg between 2 and 6 h (P≤0·02), and the reduction in diastolic blood pressure was smaller at 2 h (between-groups difference 4·5 mmHg, P=0·004). Blood coagulability, assessed by TEG, increased from baseline over 8 h in the calcium citrate and control groups. At 4 h, the increase in the coagulation index was greater in the calcium citrate group compared with the control group (P=0·03), which appeared to be due to a greater reduction in the time to clot initiation. These data suggest that Ca supplements may acutely influence blood pressure and blood coagulation. Further investigation of this possibility is required.

Antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease.

BACKGROUND: Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. People with liver disease frequently have haemostatic abnormalities such as hyperfibrinolysis. Therefore, antifibrinolytic amino acids have been proposed to be used as supplementary interventions alongside any of the primary treatments for upper gastrointestinal bleeding in people with liver diseases. This is an update of this Cochrane review. OBJECTIVES: To assess the beneficial and harmful effects of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), LILACS (1982 to February 2015), World Health Organization Clinical Trials Search Portal (accessed 26 February 2015), and the metaRegister of Controlled Trials (accessed 26 February 2015). We scrutinised the reference lists of the retrieved publications. SELECTION CRITERIA: Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. Observational studies for assessment of harms. DATA COLLECTION AND ANALYSIS: We planned to summarise data from randomised clinical trials using standard Cochrane methodologies and assessed according to the GRADE approach. MAIN RESULTS: We found no randomised clinical trials assessing antifibrinolytic amino acids for treating upper gastrointestinal bleeding in people with acute or chronic liver disease. We did not identify quasi-randomised, historically controlled, or observational studies in which we could assess harms. AUTHORS' CONCLUSIONS: This updated Cochrane review identified no randomised clinical trials assessing the benefits and harms of antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver disease. The benefits and harms of antifibrinolytic amino acids need to be tested in randomised clinical trials. Unless randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute antifibrinolytic amino acids for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

Fibrinogen and prothrombin complex concentrate in trauma coagulopathy.

BACKGROUND: Coagulopathy after injury contributes to hemorrhage and death. Treatment with specific coagulation factors could decrease hemorrhage and mortality. Our aim was to compare fibrinogen and prothrombin complex concentrate (PCC) in a rabbit model of hemorrhagic shock. MATERIALS AND METHODS: New Zealand white rabbits were anesthetized. Blood was withdrawn to a mean arterial pressure (MAP) of 30-40 mm Hg for 30 min. Animals were resuscitated with lactated Ringer to a MAP of 50-60 mm Hg and randomized to receive 100 mg/kg of fibrinogen, PCC 25 IU/kg, or lactated Ringer. A liver injury was created. A MAP of 50-60 mm Hg was maintained for 60 min. The primary outcome was blood loss, and secondary outcomes were fluid administered and coagulopathy as measured by plasma-based tests. RESULTS: There were eight animals in each group. Median blood loss was significantly higher in the fibrinogen group, at 122 mL (95% confidence interval [CI], 75-194), when compared with that in the control group, 35 mL (95% CI, 23-46; P value = 0.001), and the PCC group, 26 mL (95% CI, 4-54; P value = 0.002). Resuscitation fluid requirement was highest in the fibrinogen group, at 374 mL (95% CI, 274-519), and lowest in the PCC group, at 238 mL (95% CI, 212-309) (P = 0.01). Plasma-based coagulation tests were not different among groups. CONCLUSIONS: In a rabbit model, PCC did not have a significant effect on blood loss. Fibrinogen increased blood loss and fluid requirements.

Efficacy of Xuebijing for coagulopathy in patients with sepsis.

OBJECTIVES: To provide evidence of the clinical efficacy of Xuebijing (XBJ) on blood coagulation in patients with sepsis. METHODS: We conducted this meta-analysis in The People's Hospital of Liaoning Province, Shenyang, China between December 2013 and May 2014. We searched a number of databases for relevant randomized controlled trials (RCTs) published before December 2013 using the keywords 'Xuebijing', 'coagulation' and 'sepsis'. Statistical analysis was performed with Review Manager 5.2 from the Cochrane Collaboration. RESULTS: Fourteen RCTs involving 867 patients were included. Compared with placebo, XBJ injection significantly improved platelets (mean differences [MD] = 42.14, 95% confidence interval [CI]: 22.42 - 61.86, p<0.00001), shortened the activated partial thromboplastin time (MD = -4.81, 95% CI: -7.86 - [-1.76], p=0.002), shortened the prothrombin time (MD = -2.33, 95% CI: -4.15 - [-0.51], p=0.01), and shortened the thrombin time (MD = -2.05, 95% CI: -3.52 - [-0.58], p=0.006). However, no significant difference was found between the XBJ injection and the placebo group for fibrinogen (MD = 0.21, 95% CI: -0.38 - 0.81, p=0.48). CONCLUSION: Xuebijing injection may improve coagulopathy in patients with sepsis. High-quality and large sample clinical trials are needed for confirmation.

Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII.

An experimental model of hemothorax autotransfusion: impact on coagulation.

BACKGROUND: Traumatic hemothorax (HTX) has been demonstrated to predictably contain low fibrinogen, low hematocrit, and low platelet counts. When analyzed on its own, shed HTX demonstrates coagulopathy. However, when mixed with normal pooled plasma (NPP) at physiologically relevant dilutions, HTX demonstrates accelerated coagulation. We hypothesize that when HTX is mixed with a patient's own plasma, the mixture will demonstrate hypercoagulability. The accelerated coagulation of this mixture would have important implications for the autotransfusion of HTX as a method of resuscitating a trauma patient. METHODS: Adult trauma patients from whom greater than 140 mL of HTX was evacuated within 1 hour of tube thoracostomy were included. HTX was sampled at 1 hour after evacuation, and a portion of the sample was centrifuged and stored as frozen plasma for later analysis. The remainder of the sample was analyzed (coagulation, hematology, electrolytes), and values were compared with concurrent venous values extracted via chart review. A citrate tube containing the patient's venous blood was additionally spun down and frozen for subsequent mixing study analysis. Coagulation was further evaluated by mixing serial dilutions of the previously frozen HTX with NPP. Additionally, the previously frozen HTX was mixed in serial dilutions with the previously frozen sample of patient plasma (PTP). RESULTS: Subjects (10) were enrolled based on inclusion criteria and collection of a discarded venous sample. In HTX samples analyzed alone, no thrombus was formed in any coagulation test (activated partial thromboplastin time [aPTT] > 180). The median aPTT value of PTP alone was 25.5. In 1-hour specimens mixed at a clinically relevant dilution of 1:4, HTX mixed with NPP had a mediana PTT value of 26.0, whereas HTX mixed with PTP had a median aPTT value of 21.7. Thus, the mixture of HTX + PTP demonstrated a statistically significantly lower aPTT than the mixture of HTX + NPP (P = 0.01). Additionally, the mixture of HTX and PTP shows a statistically significantly lower aPTT value than PTP alone (P = 0.03), indicating a hypercoagulable state. CONCLUSIONS: HTX demonstrates coagulopathy when analyzed independently, but is hypercoagulable when mixed with NPP or PTP. Furthermore, mixing studies show a statistically significantly lower aPTT when HTX is mixed with PTP versus HTX mixed with NPP. Thus, autotransfusion of HTX would likely produce a hypercoagulable state in vivo, and should not be used in place of other blood products to resuscitate a trauma patient. The autotransfusion of HTX may, however, be of use in a resource-limited environment where other blood products are not available.