Administration Of Cryoprecipitate Research Articles

Targeted cryoprecipitate transfusion in severe traumatic haemorrhage

BackgroundSevere traumatic haemorrhage is the leading cause of death in young adults. Trauma Induced Coagulopathy is a complex and multifactorial phenomenon associated with severe traumatic haemorrhage. Fibrinogen is one of the first coagulation factors to become depleted in TIC and evidence suggests that severely injured trauma patients with hypofibrinogenaemia have poor outcomes. It is postulated that early fibrinogen replacement can improve clinical outcomes. This study investigated cryoprecipitate transfusion in hyopfibrinogeneamic trauma patients. MethodsThis retrospective, single center, observational study investigated the use of cryoprecipitate in severely injured trauma patients admitted to an Australian Level I Trauma Centre. The primary outcome was time to administration of cryoprecipitate after identification of hypofibrinogenaemia using ROTEM (FIBTEM A5). Data collected included demographics, ISS, laboratory values of coagulation and blood product usage. Results71 patients received cryoprecipitate with a median time of 61 minutes [IQR 37-93] from FIBTEM A5 result to initial cryoprecipitate administration. At 24 hours following admission to ED, Clauss Fibrinogen levels increased by 1.30g/L [IQR 0.45-1.85] and FIBTEM A5 assay increased by 8mm [IQR 3.0-11.3]. Changes in both variables were highly significant (p<0.001) and Clauss Fibrinogen versus FIBTEM A5 values showed moderate to strong correlation (R=0.75-0.80). ConclusionThis study demonstrated that early administration of cryoprecipitate was both feasible and efficacious in fibrinogen replacement in severe traumatic haemorrhage. High-level evidence supporting cryoprecipitate or fibrinogen concentrate replacement with regards to efficacy and feasibility is required to guide future clinical practice. This study provided baseline data to inform the design of further clinical trials investigating fibrinogen replacement in traumatic haemorrhage.

Effect of cryoprecipitate on neoangiogenesis in patients with purulent pyelonephritis

The aim of the study is to investigate the effectiveness of conservative therapy with the inclusion of cryoprecipitate in its composition and its effect on the angiogenesis of renal blood vessels in patients with purulent pyelonephritis.&#x0D; Materials and methods. The study included 30 patients aged from 20 to 45 years (6 men, 24 women) with acute purulent pyelonephritis. All patients were assessed for markers of angiogenesis in blood plasma: vascular endothelial growth factor (VEGF-A), angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2). The patients were divided into two groups. Patients of group 1 (n = 15) received conservative therapy with the inclusion of cryoprecipitate, patients of group 2 (n = 15) received surgical treatment. The control group consisted of 10 healthy donors aged 2035 years, whose blood angiogenesis markers were determined to obtain reference values.&#x0D; Results. In the course of preliminary studies, the blood content of angiogenesis markers was determined in 10 healthy donors. The level of VEGF-A in patients of both groups and the level of Ang1 in patients of group 1 at admission to the hospital significantly exceeded the corresponding values in the control group. In group 2 patients, the level of VEGF-A and Ang1 remained elevated during treatment, which indirectly indicated an ongoing inflammatory process. The level of Ang2 in patients of both groups did not change significantly. Conservative treatment of group 1 patients showed high efficiency, which was confirmed by positive dynamics of clinical and laboratory indicators, as well as data from instrumental examination.&#x0D; Conclusions. The results obtained indicate the effectiveness of conservative therapy with the administration of cryoprecipitate in patients with purulent pyelonephritis, and the effectiveness of such treatment is comparable to the effectiveness of surgical treatment . The use of cryoprecipitate has an endothelioprotective and anti-inflammatory effect on blood vessels, stabilizes the processes of angiogenesis, which contributes to limiting the inflammatory process and its regression.

Empirical transfusion strategies for major hemorrhage in trauma patients: A systematic review

Major hemorrhage is a significant cause of mortality and morbidity around the world. There is currently no consensus on the best empirical transfusion strategy. The current National Institute for Clinical Excellence (NICE) guidelines suggest a ratio of 1:1 of red blood cells and plasma. The aim of this study is to compare this to alternative strategies identified through review of the available literature with the objective of identifying the best protocol for mortality outcomes and complication rates. A systematic review of the literature was conducted using four databases. Inclusion and exclusion criteria were applied to produce a suitable list of randomized control trials for review. Critical appraisal of each article was then performed, using a Scottish Intercollegiate Guidelines Network-approved checklist, in duplicate and was subject to further independent scrutiny when required. Evidence suggests that early administration of cryoprecipitate within the standard practiced major hemorrhage protocol is associated with a lower risk of mortality. Other strategies suggested a negative impact. Complications including incidence of thromboembolic events, multiple organ failure and sepsis as well as length of stay in hospital following activation of the different protocols and overall transfusion requirements were assessed. No clear optimal protocol was identified from our analysis. This project demonstrates that there is no significant clarity regarding morbidity and mortality. As a preliminary recommendation, cryoprecipitate supplementation suggests more favorable mortality over the current protocol. Due to the limited sample populations, we recommend the inclusion of retrospective/prospective cohort studies to bolster the statistical power of any future reviews until randomized control trials of sufficient power are available. Systematic review, Level III.

Osmotic demyelination syndrome: are patients with end-stage liver disease a special risk group?

The osmotic demyelination syndrome (ODS) is a serious neurological complication associated with the rapid correction of chronic hyponatremia and is associated with high morbidity and mortality. The incidence of ODS after liver transplantation (LT) is 0.8% to 1.4% and is higher than in the general population. Patients with end stage liver disease (ESLD) are very susceptible to ODS primarily because chronic hyponatremia is the most common electrolyte disorder in these patients. Impaired liver function also leads to disruption of astrocyte metabolism resulting in abnormalities of blood-brain barrier function and a decreased ability to generate new intracellular osmotically active compounds (osmolytes) in response to osmotic changes. LT is the only definitive treatment for hyponatremia in ESLD. Massive fluid shifts that occur intraoperatively can change serum sodium concentration (sNa) significantly. The severity of preoperative chronic hyponatremia is an important risk factor for ODS after LT. ODS after LT is most likely due to unintentional sodium administration intraoperatively. Measures to prevent ODS should cover the entire perioperative period. Chronic symptomatic hyponatremia should be carefully treated if LT is imminent. An intraoperative management strategy to minimize increases in sNa is vital and includes limiting fresh frozen plasma and cryoprecipitate administration by using concentrated clotting factors, administering hypotonic intravenous fluids and sodium-free buffering solutions, as well as using low-sodium continuous renal replacement therapy. sNa levels and urine output should be monitored frequently intraoperatively as well as postoperatively. Neurological symptoms are common after LT, and a high index of suspicion must be maintained to diagnose ODS.

Empiric transfusion strategies during life-threatening hemorrhage

Resuscitation guided by thrombelastography improves survival after injury. If bleeding is rapid, however, or if no thrombelastography data are available, the optimal strategy remains controversial. Our current practice gives fresh frozen plasma and red blood cells (1:2) empirically in patients with life-threatening hemorrhage, with subsequent administration based on rapid thrombelastography. We identified patients at risk of massive transfusion at 1 hour, examined their initial rapid thrombelastography, and used this value to provide empiric recommendations about transfusions. Massive transfusion was defined as >4 units of red blood cells in the first hour. Patients managed by a trauma activation (2014-2017) had an admission rapid thrombelastography analyzed to determine what proportion met thresholds for administration of cryoprecipitate or platelets. Overall, 35 patients received >4 units of red blood cells in the first hour. Based on the admission rapid thrombelastography, 37% met criteria for both platelets and cryoprecipitate, 35% for either platelets or cryoprecipitate and 29% for neither. Kaplan-Meier analysis showed a significant delay in the administration of cryoprecipitate and platelets compared to fresh frozen plasma. Patients who require >4 units of red blood cells within the first hour should receive cryoprecipitate and platelets if thrombelastography results are not available. Point-of-care devices are needed for optimal care of trauma-induced-coagulopathy, but these data offer guidance in their absence.

Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study.

We aimed to compare hypofibrinogenaemia prevalence in major bleeding patients across all clinical contexts, fibrinogen supplementation practice, and explore the relationship between fibrinogen concentrations and mortality. This cohort study included all adult patients from 20 hospitals across Australia and New Zealand who received massive transfusion between April 2011 and October 2015. Of 3566 patients, 2829 (79%) had fibrinogen concentration recorded, with a median first and lowest concentration of 2·0g/l (interquartile range [IQR] 1·5-2·7) and 1·8g/l (IQR 1·3-2·4), respectively. Liver transplant (1·7g/l, IQR 1·2-2·1), trauma (1·8, IQR 1·3-2·5) and vascular surgery (1·9g/l, IQR 1·4-2·5) had lower concentrations. Total median fibrinogen dose administered from all products was 7·3g (IQR 3·3-13·0). Overall, 1732 (61%) received cryoprecipitate and 9 (<1%) fibrinogen concentrate. Time to cryoprecipitate issue in those with initial fibrinogen concentration <1g/l was 2·5h (IQR 1·2-4·3h). After adjustment, initial fibrinogen concentration had a U-shaped association with in-hospital mortality [adjusted odds ratios: fibrinogen <1g/l, 2·31 (95% confidence interval (CI) 1·48-3·60); 1-1·9g/l, 1·29 (95% CI 0·99-1·67) and >4g/l, 2·03 (95% CI 1·35-3·04), 2-4g/l reference category]. The findings indicate areas for practice improvement including timely administration of cryoprecipitate, which is the most common source of concentrated fibrinogen in Australia and New Zealand.

Abstract TP220: Is Fibrinogen a Reliable Lab to Follow in Acute Ischemic Stoke After Thrombolysis

Background: American Heart Association suggests empirical therapies (cryoprecipitate, FFP and platelets) for post-IVtpa hemorrhage but acknowledges the lack of evidence to support any specific therapy. Different institutions have developed care pathways for post-IVtpa sICH involving frequent fibrinogen level checks. During thrombolysis, circulating fibrinogen is decreased, and thus rapid administration of cryoprecipitate is recommended. A marker of fibrinogen of &lt;100-150 mg/dL has been traditionally used as a cutoff to suggest effective thrombolysis or administration of cryoprecipitate or to assess the risk of bleeding complications. Monitoring of fibrinogen level has been used to guide the reversal therapy in the setting of post-IVtpa hemorrhage. This practice is not fully addressed in the literature. Purpose: To determine the significance of fibrinogen level in relation to thrombolysis in acute ischemic stroke (AIS) based on our single center experience. Methods: We retrospectively reviewed fibrinogen levels in two groups of patients with AIS who presented to our comprehensive stroke center. First group included 50 patients who received IVtpa including two patients w/ post-IVtpa sICH and second group included 50 patients with AIS who could not receive IVtpa due to contraindication. Fibrinogen level was checked in immediate post-IVtpa period usually within 2hr of IVtpa or 6hr from onset. Results: The mean fibrinogen level in first group with patients with AIS who received IVtpa is 321.65 mg/dl with range from 102 to 533 mg/dl. Normal reference range is 220-410mg/dl. The mean fibrinogen level in second group without IVtpa is 376mg/dl with range from 124 to 583mg/dl. The fibrinogen level in two patients with post-IVtpa sICH was 216 and 282 mg/dl. Conclusions: No significant correlation is found between fibrinogen level (&lt;100mg/dl) and IVtpa use. We also found no significant change in fibrinogen level in patients with post-IVtpa sICH even though there are only two cases included so far. Above finding suggests that we should focus our research on mechanism other than decrease fibrinogen level to be an underlying cause of post-IVtpa hemorrhage in order to develop agent for better reversal and to prevent continued hematoma expansion.

A Systems-Based Approach to Improve Fibrinogen Testing and Treatment of Low Fibrinogen in Patients Receiving Massive Transfusions: A Quality Improvement Initiative

Background: Uncontrolled hemorrhage is the most common treatable cause of death and four of every ten trauma patients die as a results of exsanguination, or its late effects (Curry et al. Scand J Trauma 2014). There is an increasing understanding of the state of acute coagulopathy and the role that fibrinogen plays in major hemorrhage (Wikkelso A et al. Cochrane Syst Rev 2013). Fibrinogen is a critical protein for hemostasis and clot formation. Low fibrinogen is a risk factor for hemorrhage in patients with major hemorrhage including surgical, obstetrics and trauma patients. Observational studies have reported improved survival with higher fibrinogen:RBC transfusion ratios in trauma.At Regions Hospital, St. Paul, MN, the Transfusion Committee observed that many patients receiving massive transfusions did not have fibrinogen activity tested.Aim: To improve fibrinogen testing and treatment of low fibrinogen in patients receiving massive transfusions by using a hospital-wide, electronic medical record (EMR)-based Massive Transfusion Protocol (MTP) order set. Outcomes, including survival and transfusion requirements will also be evaluated.Methods: Retrospective analysis of data from existing databases identified 127 patients who had massive hemorrhage as defined by activation of the massive transfusion protocol (MTP) at Regions Hospital between 2014-2016. We performed chart reviews to assess fibrinogen replacement practice 6 months before (n=68) and 6 months (n=59) after implementation of an EMR-based MTP order set in a quality improvement model. The order set automatically orders fibrinogen activity, in addition to hemoglobin, platelet count, INR, and PTT. Once the order set is activated, it will alert the provider to a low fibrinogen activity result using a best practice alert. The alert then directs therapy by opening the order for administration of cryoprecipitate. To evaluate the impact of this order set on fibrinogen testing and clinical outcomes, we constructed multivariable logistic regression models.Results: During the study period, 127 patients had the MTP activated. The median age was 51 years and 67% were male. The majority of MTPs were activated for trauma (57%) located primarily in ED (64%). The common admitting diagnoses were motor vehicle accident (29%), heart surgery/procedure (18%), or GI bleed (16%). The admitting hemoglobin, platelet count, INR, and PTT were similar pre and post-intervention. Prior to the use of the MTP order set, only 32% of patients receiving the MTP had fibrinogen tested. Of the patients with a fibrinogen activity tested, over one-third had a low fibrinogen and of those 56% did not receive cryoprecipitate. Fibrinogen testing increased after the intervention (61% vs 32%, p=0.001), and among patients with low fibrinogen, transfusion of cryoprecipitate occurred more often (70% vs 44%, p=0.370). Blood transfusion requirements for red blood cells (7.0 vs 9.9, p=0.133), fresh-frozen plasma (4.9 vs 6.7, p=0.063), and platelets (1.2 vs 1.6, p=0.068) decreased post-intervention. In multivariate analysis, patients were approximately 3 times more likely to have fibrinogen activity tested after the intervention (OR 3.06, p=0.003). Deaths within 24 hours of MTP were more likely to occur among patients in the pre-intervention period (OR=1.45; 95% CI 0.42-5.00) and those with low fibrinogen (OR=1.34; 95% CI 0.26-7.08), however, due to the limited number of events, these estimates did not reach statistical significance.Conclusions: A systems-based approach with a hospital-wide EMR order set for the MTP improved the testing for and treatment of low fibrinogen in patients with massive hemorrhage. This resulted in a trend towards improved outcomes. We did not achieve 100% fibrinogen testing after the intervention because the MTP can still be activated without using the order set, and this will be corrected in a future update. The treatment of patients with traumatic hemorrhage remains challenging and varies widely between trauma centers. Standardized treatment, automation of lab ordering, and the use of alerts can help providers improve the quality of care and clinical outcomes for patients. DisclosuresNo relevant conflicts of interest to declare.

Cryoprecipitate administration after trauma.

Haemorrhage remains among the most preventable causes of trauma death. Massive transfusion protocols, as part of 'haemostatic resuscitation', have been implemented in most trauma centres. Relative to the attention to the ideal ratio of red blood cells to fresh frozen plasma and platelets, cryoprecipitate treatment has been infrequently discussed. We aimed to outline the use of cryoprecipitate during trauma resuscitation and analyse outcomes in patients who received cryoprecipitate after hypofibrinogenaemia detection. A retrospective review of registry data on all major trauma patients (Injury Severity Score>15) presenting to a level I trauma centre over a 4-year period (2008-2011) was conducted. We selected all patients who had received cryoprecipitate and then analysed patients who had received cryoprecipitate following the detection of hypofibrinogenaemia (<1.0 g/l). Mortality at hospital discharge among hypofibrinogenaemic patients who had received cryoprecipitate was compared with that among patients who had not received cryoprecipitate. Of 3996 trauma patients, 3571 had fibrinogen levels recorded. Most patients (n=3517, 98.5%) had initial fibrinogen counts of 1.0 g/l or higher, and cryoprecipitate was administered to a small proportion of these patients (n=126, 3.6%). Of the 54 patients with hypofibrinogenaemia on arrival, one patient died immediately and was excluded from further analysis. Of the 53 patients, 30 received cryoprecipitate and 28/53 died (53%). There was no difference in mortality between those who had received and those who had not received cryoprecipitate (14/30 vs. 14/23, P=0.31). Administration of cryoprecipitate was uncommon during trauma resuscitation, even among patients with hypofibrinogenaemia on presentation. This study provides no evidence towards improved outcomes from administration of cryoprecipitate.

Congenital von Willebrand factor deficiency in single Iraqi teaching hospital: A descriptive study

Background: Von Willebrand disease (vWD) is a common, inherited hemorrhagic disorder caused by a deficiency or dysfunction of the protein von Willebrand factor (vWF). Objectives: The aim of this study is to assess the diagnosis and treatment of vWD in a single Iraqi teaching hospital. Patients and Methods: This descriptive study was conducted on 778 patients with bleeding tendency, 107 patients were diagnosed to have vWD, and from the first of October 2013 to the first of August 2015. The diagnosis of the disease was made by a wide spectrum of characteristics including family history, clinical manifestations, and laboratory tests. Results: The common manifestations of the disease at the time of the diagnosis were epistaxis (39.2%), gum bleeding (24.2%), and menorrhagia (23.4%) in female patients. The age of patients at time of presentation was between 1 and 10 years. Family history was positive in most patients. Hepatitis C was rare in the patients after cryoprecipitate administration. Conclusions: It is a common inherited hemorrhagic disease in Iraq, mostly presented as minor bleeding involving mainly mucocutaneous regions which appears at an early childhood with positive family history in most cases.

Liver tissue regeneration under the influence of cryoprecipitate and alloplant

To study the effectiveness and impact of cryoprecipitate and alloplant on regeneration of liver tissue in patients with cirrhosis. 114 patients with liver cirrhosis have been treated at the Department of Faculty Surgery of I.M. Sechenov First Moscow State Medical University from 2007 to 2014. Cryoprecipitate and alloplant were injected into cirrhotic liver tissue in the first (72 patients) and second (42 patients) groups under ultrasound control respectively. Patients' age was 48.9±12.14 years (range 18-75). There were 66 men (58%) and 48 (42%) women. Mixed (toxic and viral) etiology of cirrhosis was observed in 40.3% of patients, viral--in 25.8%, toxic--in 34.2%. Minimally invasive treatment under ultrasound showed significant (p>0.05) positive dynamics of hepatocellular failure, cytolytic and cholestatic syndromes, hypersplenism in 3, 6 and 12 months after cryoprecipitate administration in most patients with cirrhosis Child-Pugh class A, B and C (group 1). Alloplant injected into hepatic tissue causes less regeneration of liver tissue. It improves clinical and laboratory parameters in patients with cirrhosis Child-Pugh classes A and B. In case of class C allopolant is not effective.

Fibrinogen recovery and changes in fibrin‐based clot firmness after cryoprecipitate administration in patients undergoing aortic surgery involving deep hypothermic circulatory arrest

Cryoprecipitate may be used to treat bleeding in cardiac surgery. Its effects on plasma fibrinogen and fibrin clotting in this setting are poorly defined. Patients undergoing on-pump aortic surgery with deep hypothermic circulatory arrest (DHCA) were recruited prospectively. After protamine reversal, cryoprecipitate was administered to patients with bleeding, and fibrin deficit was indicated by thromboelastometry (ROTEM)-based FIBTEM test. Coagulation was assessed using ROTEM-based tests and standard laboratory tests before and after cryoprecipitate. Thirteen patients were included. Cryoprecipitate significantly elevated EXTEM A10 from (mean ± standard deviation) 29.4 ± 5.8 to 34.8 ± 5.9 mm (p = 0.01), FIBTEM A10 from 3.5 ± 0.9 to 5.8 ± 1.7 mm (p = 0.04), and plasma fibrinogen concentration from 154.2 ± 25.6 to 193.4 ± 30.5 mg/dL (p = 0.01). EXTEM clot elasticity at 10 minutes (CE10) increased from 42.5 ± 12.0 to 54.7 ± 14.9 mm after cryoprecipitate (30.0% increase). FIBTEM CE10 increased from 3.7 ± 0.9 to 6.2 ± 2.0 mm (53.0% increase). A fibrinogen dose of 13.2 ± 5.2 mg/kg was required to increase FIBTEM A10 by 1 mm. In vivo recovery of fibrinogen was 61.6 ± 31.2%. Cryoprecipitate increased plasma fibrinogen levels and fibrin-based clotting in bleeding patients undergoing aortic surgery with DHCA. In vivo recovery of fibrinogen was considerably below 100% and fibrinogen content varied between cryoprecipitate units. Trials are needed to assess whether cryoprecipitate impacts clinical outcomes and to evaluate its safety.

Postoperative fibrinogen level is associated with postoperative bleeding following cardiothoracic surgery and the effect of fibrinogen replacement therapy remains uncertain

Traditionally, a fibrinogen level > 1 g L(-1) has been viewed as the critical plasma concentration required for hemostasis. No definitive trial has investigated the plasma fibrinogen hemostatic threshold and fibrinogen replacement in complex surgical patients with acquired bleeding. To explore the plasma fibrinogen level required for hemostasis in cardiothoracic surgery patients and assess the association of fibrinogen replacement therapy (using cryoprecipitate or fibrinogen concentrate) with reducing postoperative bleeding rate. Data from a prospectively collated database were used to examine the relationship between postoperative plasma fibrinogen level and the postoperative rate of bleeding within the hour of plasma fibrinogen measurement (n = 430) and to explore the effect of cryoprecipitate infusion (n = 76) or fibrinogen concentrate administration (n = 8) on postoperative bleeding rate. A low plasma fibrinogen level was significantly associated with bleeding, with an odds ratio of 3.06 for every 1 g L(-1) decrease in fibrinogen (95% confidence interval 1.05-8.90) with adjustment for confounders. A fibrinogen threshold associated with excess bleeding was not identified, but this relationship was a continuum. There was no reduction in bleeding following administration of cryoprecipitate or fibrinogen concentrate to raise the post-infusion fibrinogen level to a median of 2.00 and 1.70 g L(-1) , respectively. There is a continuum of bleeding severity with reducing fibrinogen concentration. Fibrinogen concentrate or cryoprecipitate infusion did not significantly reduce bleeding rate; however, confirmation by a randomized controlled trial is required. It remains uncertain whether low postoperative fibrinogen levels are causally associated with postoperative bleeding.

Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes

Low fibrinogen levels are known to occur in trauma. However, the extent of fibrinogen depletion during trauma hemorrhage, the response to replacement therapy and association with patient outcomes remain unclear. The study aims were to: characterize admission fibrinogen level and correlate it with factors associated with injury; describe the time course of fibrinogen depletion and response to replacement therapy; determine the correlation of fibrinogen level with rotational thromboelastography (ROTEM) parameters; evaluate the effect of fibrinogen supplementation ex vivo; and establish the association between fibrinogen level and clinical outcomes. This was a prospective cohort study of 517 patients. Blood samples were drawn on admission and after admistration of every 4 units of packed red blood cells. Fibrinogen levels were determined with the Clauss method, and global hemostatic competence was assessed with thromboelastometry. The effect of fibrinogen supplementation was assessed in a subgroup of coagulopathic patients. Low admission fibrinogen level was independently associated with injury severity score (P < 0.01), shock (P < 0.001), and prehospital fluid volume (P < 0.001). Fibrinogen supplementation during transfusion maintained but did not augment fibrinogen levels. Administration of cryoprecipitate was associated with improved survival. ROTEM parameters correlated with fibrinogen level, and ex vivo fibrinogen administration reversed coagulopathic ROTEM parameters. Fibrinogen level was an independent predictor of mortality at 24 h and 28 days (P < 0.001). Fibrinogen level is decreased in injured patients on admission and is associated with poor outcomes. ROTEM is a rapid means of assessing hypofibrinogenemia. Earlier administration of specific fibrinogen replacement may improve outcomes, and prospective controlled trials are urgently needed.

190Factor VIII inhibitor bypassing activity (FEIBA) as an adjunct in post-cardiotomy bleeding

Refractory bleeding after cardiac surgery continues to be a significant challenge. Post-bypass coagulopathy requiring multiple transfusions is associated with higher levels of morbidity and mortality. This problem has been exacerbated in recent years by the increased use of antiplatelet agents and the loss of aprotinin. Factor eight inhibitor bypassing activity (FEIBA) is a coagulation factor concentrate commonly used in haemophelia, but it has also shown some promise in postoperative hemostasis. We report on the largest known series of its use in post-cardiotomy coagulopathy. A retrospective review of 81 consecutive cases involving the use of FEIBA at a provincial cardiac surgical program was performed. From Jan 1, 2008 to Sep 30, 2010, a total of 81 patients received FEIBA for bleeding refractory to routine adjunct therapy such as platelets, fresh frozen plasma (FFP) and cryoprecipitate administration. 28 patients received intra-operative doses only, 44 received postoperative doses only, and 9 received both intra- and post-operative doses. Average age was 66.5 years, with 50 males and 31 females. 18 cases were isolated CABG with all other cases being concomitant procedures or complex urgent cases. For the 37 patients who received intra-operative FEIBA, average CPB time was 237 minutes (S.D. ± 82) and all patients were still bleeding after receiving standard coagulation factors. The average FEIBA dose was 939 Units (S.D. ± 203) and adequate hemostasis allowed for sternal closure in all patients. 28 patients did not receive additional FEIBA, average blood loss over first 12 hours was 677 mls (S.D. ± 314), and only 1 patient required re-exploration. 9 patients were given a second dose postoperatively and 4 patients required re-exploration (4/37, 10.8%). For patients receiving post-operative FEIBA only, average CPB time was 139 minutes (S.D. ± 57), average blood loss was 1271 mls ( ± 455) before FEIBA and 121 mls in the first hour after FEIBA. 9 of those patients required re-exploration. In all 81 patients, there were no strokes or perioperative myocardial infarctions, and 1 mortality (1.2%). Renal insufficiency developed in 12 patients (14.8%). Intra- or post-operative use of FEIBA appears to be effective in controlling refractory bleeding post-cardiotomy, with acceptable rates of complications in a high risk surgical cohort. A prospective randomized trial to further determine this drug's efficacy may be warranted.

Successful use of spinal anesthesia in a patient with severe Klippel–Trénaunay syndrome associated with upper airway abnormalities and chronic Kasabach–Merritt coagulopathy

Klippel-Trénaunay syndrome is a rare disorder characterized by the triad of capillary or cavernous hemangiomas, venous varicosities or malformations, and soft tissue or bone hypertrophy. Neuraxial anesthesia in patients with Klippel-Trénaunay syndrome has been infrequently described and has not been previously reported when accompanied by consumptive coagulopathy with thrombocytopenia (Kasabach-Merritt syndrome). The authors describe their clinical management of a 23 year-old woman with Klippel-Trénaunay syndrome who presented for elective total knee arthroplasty. Her past medical history was notable for chronic Kasabach-Merritt syndrome, hypersplenism with pancytopenia, and intermittent lower gastrointestinal bleeding resulting from colonic hemangiomas. The physical examination revealed several large cavernous hemangiomas located on her right face, neck, chest, arm, and leg. No hemangiomas were noted within the dermatomal levels innervated by the upper lumbar spine. The neck hemangioma was very large and filled with blood when the patient assumed a supine position, making it almost impossible for her to breathe. The oropharynx revealed markedly hypertrophied soft tissue, pharyngeal, and hypopharyngeal hemangiomas, and a Mallampati class IV airway. Spinal and epidural hemangiomas were excluded based on a magnetic resonance imaging study before surgery. Kasabach-Merritt coagulopathy was corrected preoperatively by administration of cryoprecipitate. These interventions allowed the authors to safely perform a spinal anesthetic for the operation. The current case illustrates that major conduction anesthesia may be safely performed in patients with Klippel-Trénaunay disease provided that preoperative imaging studies exclude neurovascular involvement and coexisting coagulopathy is appropriately corrected.

Afibrinogenemia: a Disorder of Paradoxical Bleeding and Clotting.

Abstract 3477Poster Board III-414 BackgroundCongenital afibrinogenemia (CA) is a rare bleeding disorder. While thrombosis is a recognized complication of dysfibrinogemia, the risk for thrombosis in CA has not been well studied. Life-threatening thrombosis with onset shortly after puberty has developed in 2 of 3 patients with CA followed through the coagulation program at The Children's Hospital, Colorado. Patient 1 suffered recurrent peripheral arterial thrombosis following cryoprecipitate administration during adolescence, massive myocardial infarction (MI) at age 19 years and death from spontaneous intracranial hemorrhage at age 20 years. Patient 2 has had superficial thrombophlebitis following intravenous (IV) infusion of fibrinogen concentrate, as well as bilateral pulmonary embolism with infarction 1 month following last infusion, without further recurrence over the course of 6 months of judicious use of anticoagulation and fibrinogen replacement. Patient 3 is 14 years old and receives fibrinogen replacement episodically for bleeding events, without thrombotic complications to date. ObjectiveThe object of this study was to investigate overall thrombin and plasmin generation potential and overall coagulative and fibrinolytic potential in CA, in order to generate hypotheses regarding pathophysiology of bleeding and thrombotic complications. MethodsPlasma was collected from 2 CA patients at asymptomatic baseline states and following fibrinogen concentrate replacement. Plasma was isolated from whole blood within 1 hour, via double centrifugation at 2500 x g at 4°C x 15 minutes, and stored at -70°C until time of assay. Standard assays included fibrinogen activity by Clauss clotting assay and thrombin-antithrombin complexes (TAT) by ELISA (Siemens, Marburg, GE). Measurement of overall coagulative and fibrinolytic capacity in plasma was performed by Clot Formation and Lysis (CloFAL) global assay, as previously described (Goldenberg et al., Haemophilia, 2008). Simultaneous Thrombin and Plasmin generation assay (STP) was performed by fluorometric method with the same reagents as used in the CloFAL assay (dilute tissue factor, phospholipid, tissue plasminogen activator), as previously reported (Grunzke et al., J Thromb Haemost 2009 (abstract)). ResultsTAT was elevated to twice the upper limit of normal (9.4 mcg/L) in patient 1 six months following MI. In patient 2, TAT increased progressively from age 15 (2.9 mcg/L) to 20 years (13.7 mcg/L) while STP showed progressive shortening of time to peak thrombin generation by 60% over these 5 years (Figure 1). Baseline plasmin generation was nearly undetectable in both patients studied. As shown in Table I, TAT increased significantly at peak post infusion of fibrinogen concentrate in both patients evaluated during half-life and recovery studies. As shown in Figure 2, panels A and B, coagulative capacity by CloFAL assay and velocity of plasmin generation by STP showed dose dependence to fibrinogen following IV replacement with concentrate in patient 3.Table 1Patient 2: Time after fibrinogen concentrate (hrs)Fibrinogen (mg/dL)TAT (mcg/L)Patient 3: Time after fibrinogen concentrate (hrs)Fibrinogen (mg/dL)TAT (mcg/L)Pre-infusion<54.5Pre-infusion19.21.50.584.527.01.5285.52.11.378.83.048119.11.62447.02.29657.01.74835.71.87226.52.214413.02.2 DiscussionThese data suggest that baseline and post infusion thrombin generation may be increased in post pubertal patients with CA. Furthermore, given undetectable plasmin generation in the absence of fibrinogen, the hemostatic balance in CA is simultaneously hemorrhagic and prothrombotic. These preliminary findings call for further prospective evaluation in other identified patients with CA. [Display omitted] [Display omitted] Disclosures:Grunzke:National Hemophilia Foundation/Baxter Clinical Fellowship Award: Research Funding. Manco-Johnson:CSL Behring: Honoraria, Research Funding.

Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies

Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies

Fatal Thrombosis after Mitral Valve Replacement for Endocarditis: Aprotinin and Disseminated Intravascular Coagulation

We recently reported fatal aortic thrombosis in an adult undergoing repair of a thoracoabdominal aneurysm using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest in the setting of aprotinin and adequate heparinization.1We report a second case of fatal thrombosis after mitral valve replacement for endocarditis in the setting of aprotinin and disseminated intravascular coagulation.A 69-yr-old woman presented with fatigue and right-sided weakness. She had a history of breast carcinoma treated with mastectomy and high-dose chemotherapy. She was taking tamoxifen. Her physical examination was positive for purpura, right hemiplegia, and an apical holosystolic murmur with radiation to the axilla. She had no peripheral stigmata of endocarditis. Brain imaging showed multiple embolic cerebral infarcts. A transthoracic echocardiogram revealed multiple, large mitral vegetations and severe mitral regurgitation. Her laboratory studies revealed thrombocytopenia, hypofibrinogenemia, and disseminated intravascular coagulation. Blood cultures were sent, and empiric antibiotic therapy was commenced. After consultation with a hematologist, the patient was given cryoprecipitate. The patient was subsequently referred for mitral valve surgery.The patient underwent general endotracheal anesthesia. Anesthetic monitoring consisted of standard monitors (as per the American Society of Anesthesiologists), a radial arterial line, an oximetric pulmonary arterial catheter, and transesophageal echocardiograph. The patient was given aprotinin (Bayer Corporation, Pittsburgh, PA) as follows: 2 million kallikrein inhibitory units intravenously as a load, followed by an infusion of 0.5 million kallikrein inhibitory units per hour. The CPB crystalloid prime was also loaded with aprotinin (2 million kallikrein inhibitory units). The aprotinin was commenced just after induction of general anesthesia. Heparinization was with bolus bovine heparin to maintain the kaolin activated clotting time greater than 400 s. The patient underwent uncomplicated bioprosthetic mitral valve replacement on hypothermic CPB.Separation from CPB was uneventful. After protamine administration, there was still significant microvascular bleeding. This was treated with titrated administration of cryoprecipitate and platelets. Approximately 30 min after the commencement of this transfusion, there was sudden cardiogenic shock that required emergent CPB after reheparinization. During this time, transesophageal echocardiography demonstrated thrombus in the left atrium and descending aorta. Left atriotomy revealed significant thrombus on the mitral prosthetic valve as well. Separation from CPB thereafter was impossible because of refractory biventricular failure. Further resuscitative efforts were stopped.To our knowledge, this is the first reported case of fatal thrombosis after mitral valve surgery for endocarditis in the setting of aprotinin and disseminated intravascular coagulation. Aprotinin reduces transfusion burden in valve surgery for endocarditis and is possibly beneficial in disseminated intravascular coagulation.2–5Aprotinin has been associated with thrombosis after valve surgery for endocarditis despite adequate heparinization but in the setting of congenital afibrogenemia.6This recently reported case occurred in a young adult with multiple perioperative thrombotic events. There was cardiogenic collapse after separation from CPB due to coronary thrombosis. The patient survived after a prolonged hospital stay. The accompanying expert commentaries comprehensively discuss the role of aprotinin in this scenario, including disseminated intravascular coagulation and endocarditis. The reader is referred to these commentaries for further details.Clearly, in our case, there was a complex interaction of procoagulant and anticoagulant influences that ultimately resulted in a net fatal thrombotic result. It is not possible on the basis of one case to delineate the exact role of aprotinin in this complex pathophysiology. This case demonstrates, however, that fatal thrombosis is possible in association with aprotinin in the setting of cardiac surgery for endocarditis and acquired hypofibrinogenemia. Further research is required to understand and prevent this uncommon but important perioperative complication.*Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. yiandoc@hotmail.com

Autologous Platelet-Rich Plasmapheresis in Repeat Cardiac Surgery

To the Editor: Shore-Lesserson et al. [1] have concluded that autologous plateletrich plasmapheresis (PRP) has not reduced postbypass bleeding or transfusion requirements in patients undergoing repeat cardiac surgery. However, several points are raised by their study: 1. If the prothrombin time was similar in the two groups and the transfusion trigger was a prothrombin time greater than 150% of control, how did the PRP group receive more fresh frozen plasma? 2. If the fibrinogen levels were similar in the two groups (apart from initial values) and cryoprecipitate administration was based on fibrinogen levels less than 150 mg/dL, how did the PRP group receive more cryoprecipitate? 3. The authors have alluded to the lower preoperative hemoglobin in the PRP group. In the face of this 0.9-mg/dL difference, the 700 mL (approximately 2 units of packed red blood cells) greater blood loss in the control group, and transfusion to the same postoperative hemoglobin, one cannot conclude that PRP does not decrease blood loss. The fact that the control group lost more blood yet received fewer packed red blood cells supports this suggestion. Evan G. Pivalizza, MBChB, FFA David C. Abramson, MBChB, FFA Department of Anesthesiology University of Texas-Houston Medical School Houston, TX 77030