Management Of Coagulopathy Research Articles

From blood transfusion to patient blood management: a new paradigm for patient care and cost assessment of blood transfusion practice

The ageing population in developed countries, including Australia, is putting increasing demands on blood transfusion services. With a falling donor pool there is likely to be a shortage of blood and blood products in the next 20 to 30 years unless there are significant changes in medical practice. The National Health and Medical Research Council/Australasian Society of Blood Transfusion Clinical Practice Guidelines on the Use of Blood Components from 2001 are being redeveloped by the National Health and Medical Research Council/Australian and New Zealand Society of Blood Transfusion as evidence-based patient-focused Patient Blood Management guidelines with the aim of improving patient outcomes by reducing inappropriate blood and blood product use and targeting therapies for improving the management of anaemia and coagulopathies.

Decision to transfuse comfort zones: move out or get pushed out

Decision to transfuse comfort zones: move out or get pushed out

Possible Anaphylaxis Due to Recombinant Factor VIIa Administration During Thoracic Aortic Surgery

Possible Anaphylaxis Due to Recombinant Factor VIIa Administration During Thoracic Aortic Surgery

Blood Component Therapy in Trauma Guided with the Utilization of the Perfusionist and Thromboelastography

25–35% of all seriously injured multiple trauma patients are coagulopathic upon arrival to the emergency department, and therefore early diagnosis and intervention on this subset of patients is important. In addition to standard plasma based tests of coagulation, the thromboelastogram (TEG®) has resurfaced as an ideal test in the trauma population to help guide the clinician in the administration of blood components in a goal directed fashion. We describe how thromboelastographic analysis is used to assist in the management of trauma patients with coagulopathies presenting to the emergency department, in surgery, and in the postoperative period. Indications for the utilization of the TEG® and platelet mapping as point of care testing that can guide blood component therapy in a goal directed fashion in the trauma population are presented with emphasis on the more common reasons such as massive transfusion protocol, the management of traumatic brain injury with bleeding, the diagnosis and management of trauma in patients on platelet antagonists, the utilization of recombinant FVIIa, and the management of coagulopathy in terminal trauma patients in preparation for organ donation. The TEG® allows for judicious and protocol assisted utilization of blood components in a setting that has recently gained acceptance. In our program, the inclusion of the perfusionist with expertise in performing and interpreting TEG® analysis allows the multidisciplinary trauma team to more effectively manage blood products and resuscitation in this population.

Initial experiences with point‐of‐care rapid thrombelastography for management of life‐threatening postinjury coagulopathy

Massive transfusion (MTP) protocol design is hindered by lack of accurate assessment of coagulation. Rapid thrombelastography (r-TEG) provides point-of-care (POC) analysis of clot formation. We designed a prospective study to test the hypothesis that integrating TEG into our MTP would facilitate goal-directed therapy and provide equivalent outcomes compared to conventional coagulation testing. Thiry-four patients who received more than 6 units of red blood cells (RBCs)/6 hours who were admitted to our Level 1 trauma center after r-TEG implementation (TEG) were compared to 34 patients admitted prior to TEG implementation (Pre-TEG). Data are presented as mean±SEM. Emergency department pre-TEG versus TEG shock, and coagulation indices, were not different: systolic blood pressure (94 mmHg vs. 101 mmHg), temperature (35.3°C vs. 35.9°C), pH (7.16 vs. 7.11), base deficit (-13.0 vs. -14.7), lactate (6.5 vs. 8.1), international normalized ratio (INR; 1.59 vs. 1.83), and partial thromboplastin time (48.3 vs. 57.9). Although not significant, patients with Injury Severity Score range 26 to 35 were more frequent in the pre-TEG group. Fresh-frozen plasma (FFP):RBCs, platelets:RBCs, and cryoprecipitate (cryo):RBC ratios were not significantly different at 6 or 12 hours. INR at 6 hours did not discriminate between survivors and nonsurvivors (p=0.10), whereas r-TEG "G" value was significantly associated with survival (p=0.03), as was the maximum rate of thrombin generation (MRTG; mm/min) and total thrombin generation (TG; area under the curve) (p=0.03 for both). Patients with MRTG of more than 9.2 received significantly less components of RBCs, FFP, and cryo (p=0.048, p=0.03, and p=0.04, respectively). Goal-directed resuscitation via r-TEG appears useful for management of trauma-induced coagulopathy. Further experience with POC monitoring could result in more efficient management leading to a reduction of transfusion requirements.

Bleeding and management of coagulopathy

Bleeding after cardiac surgery remains a significant problem, increasing both length of stay and mortality, and is caused by multiple factors including dilutional changes, ongoing fibrinolysis, and platelet dysfunction. The evaluation of coagulopathy is problematic because of the long turnaround time of standard coagulation tests. Algorithms involving point of care testing, including thromboelastography and thromboelastometry, have been published; all have the potential to reduce transfusion requirements. Massive transfusion coagulopathy that occurs in trauma can also be seen in complex aortic surgery and other massive bleeding patients and should prompt consideration of a transfusion protocol involving fixed ratios of fresh frozen plasma, platelets, and red blood cells. Pharmacologic agents such as antifibrinolytics are commonly administered, but a multimodal approach to management is important. Recombinant and purified coagulation products are being studied and provide clinicians specific agents to treat targeted deficiencies. A general multi-modal approach is required and recommendations are made for the management of bleeding and coagulopathy in cardiac surgical patients.

Review of Current Practice of Blood and Component Transfusion: Critical Issues for the Critically Ill Patient

Major haemorrhage continues to be a leading cause of morbidity and mortality in a number of situations such as trauma, ruptured aneurysms, obstetrics, liver transplantation and gastrointestinal blood loss.1 In modern day clinical practice, clinicians have a range of blood components and specific clotting products at their disposal in the management of such patients. However, recent evidence is driving change in the optimal management of coagulopathy in major haemorrhage. The critically ill patient often exhibits deranged coagulation as assessed by laboratory tests. It is unclear the extent to which this is an epiphenomenon, and to what extent coagulation requires correction prior to either bedside or surgical intervention. There is increasing evidence to suggest that blood and component transfusions carry significant though poorly quantified risks. It is therefore prudent to exercise a selective approach to transfusion, avoiding ‘correction of the numbers’ when the risk of clinically important bleeding is small. In this article, we review current UK practice and evidence for use of blood and its components in the ICU setting. We also appraise more recent concepts such as the new coagulation model, acute coagulopathy of trauma and novel treatment strategies. We will discuss current guidelines and recommendations, and highlight potential areas for future research.

The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion

Introduction Clinical observations together with recent research highlighted the role of coagulopathy in acute trauma care and early aggressive treatment has been shown to reduce mortality. Methods Datasets from severely injured and bleeding patients with established coagulopathy upon emergency room (ER) arrival from two retrospective trauma databases, (i) TR-DGU (Germany) and (ii) Innsbruck Trauma Databank/ITB (Austria), that had received two different strategies of coagulopathy management during initial resuscitation, (i) fresh frozen plasma (FFP) without coagulation factor concentrates, and (ii) coagulation factor concentrates (fibrinogen and/or prothrombin complex concentrates) without FFP, were compared for morbidity, mortality and transfusion requirements using a matched-pair analysis approach. Results There were no major differences in basic characteristics and physiological variables upon ER admission between the two cohorts that were matched. ITB patients had received substantially less packed red blood cell (pRBC) concentrates within the first 6 h after admission (median 1.0 (IQR 25–75 0–3) vs 7.5 (IQR 25–75 4–12) units; p < 0.005) and the first 24 h as compared to TR-DGU patients (median 3 (IQR 25–75 0–5) vs 12.5 (8–20) units; p < 0.005). Overall mortality was comparable between both groups whilst the frequency for multi organ failure was significantly lower within the group that had received coagulation factor concentrates exclusively and no FFP during initial resuscitation ( n = 3 vs n = 15; p = 0.015). This translated into trends towards reduced days on ventilator whilst on ICU and shorter overall in-hospital length of stays (LOS). Conclusion Although there was no difference in overall mortality between both groups, significant differences with regard to morbidity and need for allogenic transfusion provide a signal supporting the management of acute post-traumatic coagulopathy with coagulation factor concentrates rather than with traditional FFP transfusions. Prospective and randomised clinical trials with sufficient patient numbers based upon this strategy are advocated.

Trauma-Induced Coagulopathy—A Review of the Systematic Reviews: Is There Sufficient Evidence to Guide Clinical Transfusion Practice?

Systematic reviews are accepted as a robust and less biased means of appraising and synthesizing results from high-quality studies. This report collated and summarized all the systematic review evidence relating to the diagnosis and management of trauma-related coagulopathy and transfusion, thereby covering the widest possible body of literature. We defined 4 key clinical questions: (1) What are the best methods of predicting and diagnosing trauma-related coagulopathy? (2) Which methods of clinical management correct coagulopathy? (3) Which methods of clinical management correct bleeding? and (4) What are the outcomes of transfusion in trauma? Thirty-seven systematic reviews were identified through searches of MEDLINE (1950-July 2010), EMBASE (1980-July 2010), The Cochrane Library (Issue 7, 2010), National Guidelines Clearing House, National Library for Health Guidelines Finder, and UKBTS SRI Transfusion Evidence Library (www.transfusionevidencelibrary.com). The evidence from the systematic review literature was scanty with many gaps, and we were not able to conclusively answer any of our 4 questions. Much more needs to be understood about how coagulopathy and bleeding in trauma are altered by transfusion practices and, most importantly, whether this translates into improved survival. There is a need for randomized controlled trials to answer these questions. The approach described in this report provides a framework for incorporating new evidence.

Management of Coagulopathy in Patients with Decompensated Liver Cirrhosis

Patients with decompensated liver cirrhosis have significantly impaired synthetic function. Many proteins involved in the coagulation process are synthesized in the liver. Routinely performed tests of the coagulation are abnormal in patients with decompensated liver cirrhosis. This has led to the widespread belief that decompensated liver cirrhosis is prototype of acquired hemorrhagic coagulopathy. If prothrombin time is prolonged more than 3 seconds over control, invasive procedures like liver biopsy, splenoportogram, percutaneous cholangiography, or surgery were associated with increased risk of bleeding, and coagulopathy should be corrected with infusion of fresh frozen plasma. These practices were without any scientific evidence and were associated with significant hazards of fresh frozen plasma transfusion. Now, it is realized that coagulation is a complex process involving the interaction of procoagulation and anticoagulation factors and the fibrinolytic system. As there is reduction in both anti and procoagulant factors, global tests of coagulation are normal in patients with acute and chronic liver disease indicating that coagulopathy in liver disease is more of a myth than a reality. In the last few years, surgical techniques have substantially improved, and complex procedures like liver transplantation can be done without the use of blood or blood products. Patients with liver cirrhosis may also be at increased risk of thrombosis. In this paper, we will discuss coagulopathy, increased risk of thrombosis, and their management in decompensated liver cirrhosis.

Improving Survival in Patients with Decompensated Cirrhosis

About 60% of patients with decompensated disease have oesophageal varices. One third of these patients will experience variceal bleed. Each bleeding episode compromises the decompensated state and is associated with a 20% to 30% mortality. Bleeding from ectopic varices is rare but is generally massive and life threatening. The first two articles, “Clinicopathological features and treatment of ectopic varices with portal hypertension” and “Application of endoscopy in improving survival of cirrhotic patients with acute variceal hemorrhage” discuss the management of variceal bleeding in cirrhotic patients. “Improved survival with the patients with variceal bleed” is a review article on how new treatment modalities have improved the outlook of patients with bleeding oesophageal varices. The hepatorenal syndrome (HRS) signifies advanced liver failure and is a bad prognostic factor in patients with decompensated cirrhosis. Management of this condition is discussed in “Management of renal failure and ascites in patients with cirrhosis”. One of the features of decompensated liver disease is the occurrence of recurrent or resistant ascites. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective therapy for refractory ascites and HRS at the expense of hepatic encephalopathy and may offer an effective bridge to liver transplantation, by improving short and medium term survivals, as discussed in “Role of TIPS in improving survival of patients with decompensated liver disease”. Bacterial infection is responsible for up to a quarter of the deaths of patients with decompensated liver disease. “Prevention and management of bacterial infections in cirrhosis” discuss the high index of suspicion that is needed to prevent bacterial infections in patients with decompensated cirrhosis. These patients are immunologically compromised, and prophylactic antibiotics can prevent fatal septicemia and HRS in those with gastrointestinal bleeding. Current thoughts on how to deal with the neuropsychiatric complication of cirrhosis are discussed in “Management of hepatic encephalopathy”. Cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and right-sided hydrothorax complications that are often overlooked in patients with decompensated liver disease are discussed in “Management of cardiopulmonary complications of cirrhosis”. Decompensated liver cirrhosis has been traditionally considered as a prototype of hemorrhagic coagulopathy, and routinely performed coagulation profile is abnormal in the majority of these patients. In “Management of coagulopathy in patients with decompensated liver disease”, the authors discussed recent thoughts on coagulation in end-stage liver disease. The related article entitled “Determination of ADAMTS13 and its clinical significance for ADAMTS13 supplementation therapy to improve the survival of patients with decompensated liver cirrhosis” reviews the role of the deficiency of the metalloproteinase ADAMTS13 in end-stage liver cirrhosis in inducing platelet clumping or thrombi and how the resulting sinusoidal microcirculatory disturbances causes further liver damage and is closely related to further deterioration of liver function, hepatic encephalopathy, hepatorenal syndrome, and intractable ascites in advanced liver cirrhosis. Fresh frozen plasma (FFP) is a source of ADAMTS13. Liver cirrhosis is the common end stage of persistent liver injury. In the Asia Pacific region, these injuries commonly result from chronic hepatitis B and C infections as well as alcohol. The following two articles, “Treatment of hepatitis B in decompensated liver cirrhosis and treatment of decompensated alcoholic liver disease” address the management of hepatitis B and alcoholic liver disease in end stage liver disease. Pharmacotherapy in patients with decompensated liver disease is not without complications and side effects and might compromise the decompensated state. The article entitled “Prescribing medications in patients with decompensated liver cirrhosis” addresses the above conundrum. A common complication of liver cirrhosis is liver cancer, and treatment of this condition is challenging in patients with liver decompensation to say the least. The paper entitled “Screening for hepatocellular carcinoma” discusses early detection of liver cancer in these patients so that appropriate management can be arranged. Finally, liver transplantation for end-stage liver failure is discussed in “Indications and contraindications for liver transplantation”. Deepak Amarapurkar Rajiv Jalan Richard Guan Paul Kwo

Whole blood thromboelastometry: another Knight at the Roundtable?

Thromboelastography and thromboelastometry represent viscoelastic diagnostic methodologies with promising application to diseases of altered coagulation. Their use in trauma-induced coagulopathy as a means of assessing the real-time status of the patient's functional coagulation profile in addition to its impact on effective and appropriate use of blood product support has been gaining acceptance among trauma surgeons, anesthesiologists, and transfusion medicine specialists. However, the ability of viscoelastic testing to augment or supplant conventional coagulation testing for the diagnosis and management of trauma-induced coagulopathy remains controversial. Many of these issues pertain to the differences in methodology, instrumentation, logic, accessibility, ease of use, operator variability, and the method's relationship to patient care, blood product use, cost, and conventional testing algorithms.

Resuscitation of the trauma patient: tell me a trigger for early haemostatic resuscitation please!

The management of trauma-related coagulopathy and haemorrhage is changing from a reactive strategy to a proactive early intervention with blood products and haemostatic agents. Although major haemorrhage and massive transfusion are associated with higher mortality, the pattern of this association with modern trauma care is poorly described. In addition, early predictors of massive transfusion, which might trigger a proactive haemostatic resuscitation strategy, are not currently available. We review recent literature relating to predictors of massive transfusions and the relationship between transfusion and mortality.

Fetus in Fetu: An Unusual Case Study for the Neonatal Nurse Practitioner

Fetus in fetu is an extremely unusual occurrence where a rare congenital tumor containing a vertebral axis, often containing parts of other organs or limbs, is identified. Normally identified in the newborn period, the size and location of the mass may result in significant multiorgan compromise. This article presents the challenges encountered by the neonatal intensive care unit team in providing care for a late preterm female infant presenting with gross abdominal distension. Description of the case includes preoperative management along with management of severe coagulopathy and hemorrhage that arose during the intraoperative and postsurgical course of care. A brief overview of abdominal masses in the newborn is presented. The importance in determining the final diagnosis of fetus in fetu and its differentiation from teratoma is discussed.

Assisted reproduction in a patient with Klippel-Trenaunay syndrome: management of thrombophilia and consumptive coagulopathy

Klippel-Trenaunay Syndrome (KTS) is a rare, sporadic triad of congenital malformations involving an extensive port wine stain, soft tissue or bone hypertrophy and underlying venous and/or lymphatic malformation involving an extremity. Pregnancy is known to exacerbate KTS complications and can put women at increased obstetrical risk due to deep venous thrombosis and other thromboembolic events. Here we report a case of a patient with KTS who achieved a pregnancy through in vitro fertilization (IVF) using her own eggs and a gestational surrogate in the setting of hypercoagulability and chronic consumptive coagulopathy.

Management of warfarin-associated coagulopathy in patients with acute gastrointestinal bleeding: A cross-sectional physician survey of current practice

Background The management of vitamin K antagonists (VKAs) associated coagulopathy is a cornerstone of pre-endoscopic assessment of anticoagulated patients presenting with acute gastrointestinal bleeding. Aims To evaluate physician attitudes in the management of VKAs-associated coagulopathy in patients presenting with gastrointestinal bleeding and to assess their compliance to current practice guidelines. Design Cross sectional physician web-based survey amongst regional members of three Italian Gastroenterological Societies (AIGO, SIED, SIGE) practicing in academic medical centres or community hospitals. Physicians were asked to provide management preferences in four hypothetical case–scenarios describing patients with warfarin-associated coagulopathy presenting with gastrointestinal bleeding of varying severity. Results A total of 105 out of 238 (48%) members responded; mean age ± SD: 46.3 ± 9.8 years, 68% male. The adherence to practice guidelines for the reversal of warfarin-induced anticoagulation ranged from 24% to 86% and it was not dependent on age, years and type of specialisation, hospital setting and active performance of “on call” emergency endoscopy or not. Conclusions There is a considerable variability amongst physicians in the management of gastrointestinal bleeding patients with VKAs-associated coagulopathy and a poor compliance to practice guidelines. These data indicate that better education is needed in this area.

Amniotic fluid embolism – an update

Amniotic fluid embolism – an update

Acute coagulopathy and early deaths post major trauma

Introduction and aims Acute traumatic coagulopathy is observed in 10–25% of patients post major trauma and its management forms an integral part of haemostatic resuscitation. The identification and treatment of this coagulopathy is difficult and there is uncertainty regarding optimal therapeutic guidelines during the early phases of trauma resuscitation. This study aimed to examine the association between acute coagulopathy and early deaths post major trauma. Methods A retrospective review of data over a 5 year period was performed to determine the associations between variables considered to contribute to mortality for adult major trauma patients (Injury Severity Score (ISS) > 15) receiving blood transfusions as part of their initial resuscitation. Early death, defined as death in ED, or death in the operating theatre (OT), Intensive Care Unit (ICU) or wards within 24 h of admission was the primary end-point. Patients with non-survivable head injury on initial imaging were excluded. Univariate associations were calculated and multivariable logistic regression analysis was used to determine independent associations with mortality. Results There were 772 patients included in this study with a median ISS of 29 (19–41), with 91.7% blunt trauma. All-cause in-hospital mortality was 17.5%, while 77 (9.7%) patients died early. Increasing age (OR 1.04), a GCS of 3–8 (OR 5.05), and the presence of acute coagulopathy (OR 8.77) were significant independent variables associated with early death. Conclusions Acute traumatic coagulopathy, independent of injury severity, transfusion practice or other physiological markers for haemorrhage, was associated with early death in major trauma patients requiring a blood transfusion. Early recognition and management of coagulopathy, independent of massive transfusion guidelines, may improve outcome from trauma resuscitation. Further studies are required for the early recognition of acute traumatic coagulopathy to enable the development of an evidence base for management.

A national clinical scenario‐based survey of clinicians' attitudes towards fresh frozen plasma transfusion for critically ill patients

It is known that 20-30% of fresh frozen plasma (FFP) is used in intensive care units (ICUs), but little is known about variations in decision making between clinicians in relation to coagulopathy management. Our aim was to describe ICU clinicians' beliefs and practice in relation to FFP treatment of non-bleeding coagulopathic critically ill patients. Two patient-based scenarios were developed and sent to 2700 members of two UK intensive care professional societies. Scenario 1 was a non-bleeding septic patient with coagulopathy; scenario 2 was a non-bleeding critically ill patient with hepatic cirrhosis and coagulopathy. Responses were sought in relation to FFP prophylaxis, and prior to central venous cannulation. A supplementary question asked clinicians' view of prophylaxis in relation to other ICU procedures. Two-thousand-and-seven-hundred clinicians were surveyed from whom 601 responses were received (22·3% response rate). For scenario 1 52% of respondents stated that they would never routinely administer prophylactic FFP, but this decreased to 9% when central venous cannulation was planned (P < 0·01). There was wide variation in the 'trigger' INR (international normalised ratio) value used prior to central vein cannulation, the most common range being 2·0-2·4. For scenario 2, responses were very similar. More than 80% of clinicians stated that they would routinely treat coagulopathy prior to lumbar puncture, epidural catheterisation, intracranial pressure monitoring and tracheostomy; and 54% prior to chest drain insertion. Our survey demonstrated a wide range of responses consistent with important variations in clinical practice and substantial clinical uncertainty in relation to FFP treatment for non-bleeding ICU patients.

Management of massive postpartum haemorrhage and coagulopathy

Postpartum haemorrhage (PPH) continues to remain the leading cause of maternal morbidity and mortality worldwide. Whilst this is especially true in resource limited countries, it also remains a significant problem in developed countries. The traditional definition of primary PPH is blood loss from the genital tract of 500 ml or more within 24 h of delivery (or >1000 ml during caesarean section). Secondary PPH refers to an excessive blood loss between 24 h and 6 weeks, postnatally. Massive PPH refers to a blood loss of over 2000 ml (or >30% of blood volume) and hence, is an obstetric emergency that requires a systematic, multi-disciplinary approach to restore the volume, clotting system and the oxygen carrying capacity of blood, whilst steps are taken to arrest bleeding as quickly as possible. The last confidential enquiry into maternal deaths (CEMACH, 2003–2005) in the UK cited ‘haemorrhage’ as the third highest cause of direct maternal deaths with 6.6 deaths per million maternities. This report found that 58% of these deaths may have been preventable and ‘too little being done, too late’ (failure to appreciate clinical picture, delay in instituting appropriate treatment, delay is summoning senior help and system failures) continues to contribute to maternal morbidity and mortality, even in the developed world. Massive obstetric haemorrhage may occur in the antepartum (placenta praevia, placental abruption and placenta accreta) or postpartum period. It is has been observed that the incidence of massive PPH is likely to be increasing due to the increased incidence of risk factors such as morbidly adherent placenta secondary to previous caesarean sections and maternal obesity. However, massive obstetric haemorrhage and the resultant coagulopathy can occur in women deemed to be at ‘low risk’ and hence, all clinicians managing women during pregnancy and labour need to possess knowledge and skills to recognize symptoms, signs and complications of massive obstetric haemorrhage. This may ensure institution of timely and appropriate treatment that could save lives.