Alternative ‘universal’ plasma donor

February 19, 2013 by  
Filed under All Updates, EMS, ICU, Resus, Trauma

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The group usually considered the universal donor for fresh frozen plasma because it contains no anti-A or anti-B antibodies is Type AB. Due to its limited availability the trauma service of the Mayo Clinic in Minnesota has been issuing thawed group A plasma to its flight crews who retrieve major trauma casualties from rural centres. This is given with packed group O red cells to patients who meet their prehospital massive transfusion protocol criteria. Some patients will inevitably receive ABO-incompatible plasma (namely patients with Group B or AB blood) which could theoretically give rise to haemolytic transfusion reactions, in which donor antibodies bind host red cells, activate complement, and give rise to anaemia, disseminated intravascular coagulation, acute kidney injury, and death. However:

  • the transfusion of platelets containing ABO-incompatible plasma is common, with up to 2 units of incompatible plasma per apheresis platelet unit, whereas haemolytic reactions to platelets are rare (1 in 9,000 incompatible platelet transfusions);
  • all reports of haemolytic reactions are caused by products that contain Group O plasma and there has never been a documented case of haemolysis as a result of products containing Group A plasma

A retrospective review showed no increased rates of adverse events with Type A compared with AB or ABO-compatible plasma. Since only a small absolute number of patients received an ABO-incompatible plasma transfusion, it could be argued that the study is underpowered (a point acknowledged by the authors). However this is very important and useful information for resource-limited settings.

Emergency use of prethawed Group A plasma in trauma patients
J Trauma Acute Care Surg. 2013 Jan;74(1):69-74


BACKGROUND: Massive transfusion protocols lead to increased use of the rare universal plasma donor, Type AB, potentially limiting supply. Owing to safety data, with a goal of avoiding shortages, our blood bank exploited Group A rather than AB for all emergency release plasma transfusions. We hypothesized that ABO-incompatible plasma transfusions had mortality similar to ABO-compatible transfusions.

METHODS: Review of all trauma patients receiving emergency release plasma (Group A) from 2008 to 2011 was performed. ABO compatibility was determined post hoc. Deaths before blood typing were eliminated. p < 0.05 was considered statistically significant.

RESULTS: Of the 254 patients, 35 (14%) received ABO-incompatible and 219 (86%) received ABO-compatible transfusions. There was no difference in age (56 years vs. 59 years), sex (63% vs. 63% male), Injury Severity Score (ISS) (25 vs. 22), or time spent in the trauma bay (24 vs. 26.5 minutes). Median blood product units transfused were similar: emergency release plasma (2 vs. 2), total plasma at 24 hours (6 vs. 4), total red blood cells at 24 hours (5 vs. 4), plasma-red blood cells at 24 hours (1.3:1 vs. 1.1:1), and plasma deficits at 24 hours (2 vs. 1). Overall complications were similar (43% vs. 35%) as were rates of possible transfusion-related acute lung injury (2.9% vs. 1.8%), acute lung injury (3.7% vs. 2.5%), adult respiratory distress syndrome (2.9% vs. 1.8%), deep venous thrombosis (2.9% vs. 4.1%), pulmonary embolism (5.8% vs. 7.3%), and death (20% vs. 22%). Ventilator (6 vs. 3), intensive care unit (4 vs. 3), and hospital days (9 vs. 7) were similar. There were no hemolytic reactions. Mortality was significantly greater for the patients who received incompatible plasma if concurrent with a massive transfusion (8% vs. 40%, p = 0.044). Group AB plasma use was decreased by 96.6%.

CONCLUSION: Use of Group A for emergency release plasma resulted in ABO-incompatible transfusions; however, this had little effect on clinical outcomes. Blood banks reticent to adopt massive transfusion protocols owing to supply concerns may safely use plasma Group A, expanding the pool of emergency release plasma donors.

LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

London Calling – part 3

December 10, 2012 by  
Filed under All Updates, EMS, ICU, Resus, Trauma

Notes from Day 4 of the London Trauma Conference

The highlight for me was Mr Jonny Morrison speaking on Resuscitative Emergency Balloon Occlusion of the Aorta (REBOA). He is a British military surgeon currently out in Texas studying balloon occlusion of the aorta on pigs. Looking at trauma deaths, the next unexpected survivors will come from the uncontrollable haemorrhage group (truncal and junctional zones). This is by no means a new technique – described in the 1950’s during the Korean War – but like the early Star Wars chapters, needed to wait for technology to advance to make it feasible. It has the effect of cross clamping the aorta which provides afterload support, increases cerebral and coronary perfusion and provides proximal inflow control – without the mess of a resuscitative thoracotomy and greater access.

The placement of the balloon is determined by the location of the injury (see photo) and falls into two zones. Zone 1 is the thoracic aorta and is used for truncal haemorrhage control, avoid Zone 2 where the celiac axis etc originates and Zone 3 is infrarenal, used for junctional bleeding and pelvic haemorrhage.

His studies have determined that for Zone 3 amenable bleeds balloon occlusion up to 60min is the optimal time. Any longer and the debt of the metabolic load is paid by increased inotropic support requirements. He also compared REBOA to the current standard treatment for junctional injuries, Celox™ gauze. If coagulation is normal then both treatments perform similarly, the benefit is seen in coagulopathic patients where REBOA outperforms the gauze.

Has REBOA been used on humans? Yes a case series of 13 – the technique improved the BP allowing time to get to definitive surgery (blogged here 2.5 years ago!).

The Zone 1 studies are looking at continuous vs intermittent balloon occlusion. The jury is still out as to which is better. With the intermittent occlusion (20min on, 1min off) there are inevitably some losses when the balloon is deflated, conversely the metabolic debt generated by continuous occlusion is too great in some also leading to deaths.

What was very clear is that for this technique to have an impact it must be delivered proactively and pre-hospital. The challenges that need to be overcome are access to the femoral artery and blind accurate placement.

Prof Karim Brohi brought the conference to a close with a summary of what we have learned about coagulation in trauma this year. Here are three things;

  • FFP is good but as 43% deaths due to trauma in the UK are secondary to bleeding and occur in the first 3hr we are failing our patients by administering the treatment on average at 2.5hrs.
  • Fibrinogen levels are low in coagulopathic trauma patients; we should give cryoprecipitate early and aim for Fib ≥2.0
  • And finally whilst TEG is recommended to guide treatment and can provide results within 5 min, there are some aspects of coagulation it does not detect i.e. fibrinolysis was only detected in 8% of coagulopathic trauma patients – when measured in the plasma it was then detectable in 80%.

These are the highlights of the 2012 London Trauma Conference. I hope this whistle stop tour through these days has been informative and though provoking. I can assure you telephone hacking was not used to bring you this information and to my knowledge is correct.

This is Lou Chan, roving reporter for Resus ME! signing off.

 

 

‘London raises her head, shakes off the debris of the night from her hair, and takes stock of the damage done. The sign of a great fighter in the ring is can he get up from a fall after being knocked down… London does this every morning.’

 

 

Red cell transfusion guidelines

April 7, 2012 by  
Filed under Acute Med, All Updates, ICU, Resus, Trauma

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The AABB (formerly the American Association of Blood Banks has issued guidelines on red blood cell transfusion1, providing some number-based targets which may be helpful for some practitioners or organisations. Editorialist and heavyweight intensivist Jean-Louis Vincent argues for a more individual patient-based assessment2, and highlights some of the weaknesses of existing studies, in particular the often quoted but now fairly old TRICC study3 which suffered from poor recruitment and the possible lack of applicability to modern practice now that leucodepleted products are used.

Prof Vincent states:

Transfusion decisions need to consider individual patient characteristics, including age and the presence of CAD, to estimate a specific patient’s likelihood of benefit from transfusion. The decision to transfuse is too complex and important to be guided by a single number.


Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.

Methods: These guidelines are based on a systematic review of the literature on randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay.

Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).

Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).

Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence).

Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).

1. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text

2. Indications for Blood Transfusions: Too Complex to Base on a Single Number?
Ann Intern Med. 2012 Mar 26. [Epub ahead of print] Full Text

3. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
N Engl J Med 1999; 340:409-417 Full Text

Clotbusting wisdom on tap – your questions answered

March 9, 2012 by  
Filed under Acute Med, All Updates, Guidelines, ICU, Kids, Resus

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The prevention and management of venous thromboembolic disease is a huge topic, which generates questions for emergency, critical care, and acute physicians during many shifts:

  • How long should someone requiring cardioversion for atrial fibrillation be anticoagulated for?
  • How should I provide thromboprophylaxis for this intubated patient?
  • This patient with submassive pulmonary embolism isn’t hypotensive yet. Can I thrombolyse them? Can I?
  • There’s a large superficial vein thrombosis in that limb – is anticoagulation indicated?
  • This asymptomatic patient on warfarin has an INR of 9.0 – should I reverse them?
  • Do I need to add Vitamin K if I’ve reversed warfarin with prothrombin complex concentrate?

The answers to these – and many, many more – questions are provided in one of the most comprehensive guidelines I’ve ever come across. I can see myself clicking on the link below in future when on duty in the ED.

Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Chest. 2012 Feb;141(2 Suppl) Full Text

Xigris withdrawn

October 26, 2011 by  
Filed under Acute Med, All Updates, ICU, Resus

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Pharmaceutical company Eli Lilly has announced the withdrawal of its severe sepsis drug activated protein C, or drotrecogin alfa (proprietary name Xigris). This is because the PROWESS-SHOCK study, now complete, showed no benefit in its primary endpoint of 28 day mortality when compared with placebo in septic shock patients. There was also no benefit in a subgroup of patients with protein C deficiency, and no significant increased risk of severe bleeding.

The European Medicines Agency’s Instructions are:


At this stage physicians should not initiate treatment with Xigris in new patients and should stop ongoing treatment

The US Food and Drug Administration’s Instructions are:


Xigris treatment should not be started in new patients. Xigris treatment should be stopped in patients being treated with Xigris.

All remaining Xigris product should be returned to the supplier from whom it was purchased.

The UK Intensive Care Society’s Announcement contains a link to Eli Lilly’s press release.

The Xigris website looks like this at the time of posting

Reversing new oral anticoagulants

October 5, 2011 by  
Filed under Acute Med, All Updates, ICU, Resus, Trauma

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A small study on normal volunteers examined reversal of the new oral anticoagulants, Rivaroxaban and Dabigatran.

Rivaroxaban is a Factor Xa inhibitor and Dabigatran is a direct thrombin inhibitor.

Image from "Australian Prescriber" website. Click for Original

We should note that this was a study on the reversal of effects on various coagulation tests, not on reversal of bleeding, which is what we would be interested in for our ED/critical care patients.

Nevertheless, it’s helpful to note that prothrombin complex concentrate appeared to reverse the effects of Rivaroxaban, but not of Dabigatran.


Background Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs.

Methods and Results In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests.

Conclusion Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study.

Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate
Circulation. 2011 Oct 4;124(14):1573-9

So what do we do about bleeding patients who are taking Dabigatran? If you haven’t seen it already, take a look at this video from HQMEDED.com made by my heroes at Hennepin County Medical Centre:

Bleeding in the Patient on Dabigatran from hqmeded.com on Vimeo.

They have an algorithm for the patient who is bleeding on dabigatran therapy that you can download a PDF of here

Score to predict traumatic coagulopathy

September 4, 2011 by  
Filed under All Updates, EMS, ICU, Resus, Trauma

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Acute traumatic coagulopathy (ATC) is present in up to 25% of major trauma patients by the time they arrive in hospital. A predictive tool called the coagulopathy of severe trauma (COAST) score was retrospectively derived and then prospectively validated in major trauma patients in the state of Victoria, Australia. The definition of ATC was INR > 1.5 (1.0–1.3) or aPTT of > 60 s (25–38 s) on hospital presentation.

The study claims that a subgroup of patients with acute traumatic coagulopathy can be accurately identified based on simple observations in the pre-hospital phase or immediately on presentation to the ED, and that this could improve the feasibility of prospective interventional studies. Perhaps this will lead on to evaluation of pre-hospital tranexamic acid or even blood products?

At the cutoff score of ≥3, 40 coagulopathic patients would have been missed with 60 patients correctly predicted. The authors argue that while the low sensitivity of the score missed these coagulopathic patients, they had significantly better outcomes (and contained a significantly higher proportion of patients with isolated severe head injury).


Introduction: The inability to accurately predict acute traumatic coagulopathy (ATC) has been a key factor in the low level of evidence guiding its management. The aim of this study was to develop a tool to accurately identify patients with ATC using pre-hospital variables without the use of pathology or radiological testing.

Methods: Retrospective data from the trauma registry on major trauma patients were used to identify vari- ables independently associated with coagulopathy. These variables were clinically evaluated to develop a scoring system to predict ATC, which was prospectively validated in the same setting.

Results: There were 1680 major trauma patients in the derivation dataset, with 151 patients being coagulopathic. Pre-hospital variables independently associated with ATC were entrapment (OR 1.85; 95% CI: 1.12–3.06), temperature (OR 0.60; 95% CI: 0.60–0.72), systolic blood pressure (OR 0.99; 95% CI: 0.98–0.99), abdominal or pelvic content injury (OR 2.0; 95% CI: 1.27–3.12) and pre-hospital chest decompression (OR 4.99; 2.77–8.99). The COAST score was developed, scoring points for entrapment, temperature <35 ◦ C, systolic blood pressure <100 mm Hg, abdominal or pelvic content injury and chest decompression. Prospectively validated using 1225 major trauma patients, a COAST score of ≥3 had a specificity of 96.4% with a sensitivity of 60.0%, with an area under the receiver operating characteristic curve of 0.83 (0.78–0.88).

Conclusions: The COAST score accurately identified a group of patients with ATC using pre-hospital obser- vations. This predictive tool can be used to select patients for inclusion into prospective studies examining management options for ATC. Mortality in these patients is high, potentially improving feasibility of outcome studies.

CRASH-2 and head injury

August 14, 2011 by  
Filed under All Updates, ICU, Resus, Trauma

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The overall effect of the antifibrinolytic drug tranexamic acid on outcome from major trauma was assessed in the CRASH-2 trial, reported here and here. Its effect on a nested cohort of 270 patients from the trial who had traumatic brain injury has now been published1.

Previous evaluation in nontraumatic subarachnoid haemorrhage patients showed tranexamic acid to be associated with cerebral ischaemia, whereas in CRASH-2 (in which a lower dose of tranexamic acid was used) there was a trend to fewer ischaemic lesions as well as smaller haematoma growth and decreased mortality. None of these outcomes were statistically significant so further research is warranted.

An accompanying editorial2 states:

…the CRASH-2 study also justifies a re-evaluation of the possible benefit of low dose short term TXA in patients with other types of intracranial haemorrhage. Many patients with aneurysmal subarachnoid haemorrhage still have to wait for one or two days before the aneurysm is occluded. In addition, at least 30% of patients with spontaneous intracerebral haemorrhage experience substantial haematoma growth in the first 24 hours after the onset of the haemorrhage. As well as the CRASH-2 trial we therefore need new trials investigating short course low dose TXA in patients with aneurysmal subarachnoid haemorrhage and intracerebral haemorrhage.

It looks like considerable enthusiasm for this drug will be around for a while. I look forward to more outcome data, particularly in regard to this challenging group of patients with traumatic and non-traumatic intracranial bleeding.


OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.

METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.

INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.

MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.

RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).

CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population

1. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
BMJ. 2011 Jul 1;343:d379 (free text available)

2. Tranexamic acid for traumatic brain injury
BMJ. 2011 Jul 1;343:d3958

Better than FFP in trauma?

August 3, 2011 by  
Filed under All Updates, ICU, Resus, Trauma

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Replacement of clotting factors in bleeding trauma patients seems to be of benefit, but are coagulation factor concentrates safer than fresh frozen plasma? This retrospective study suggests they might be; prospective studies are recommended.

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 6h after admission (median 1.0 (IQR(25-75) 0-3) vs 7.5 (IQR(25-75) 4-12) units; p

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.

The impact of fresh frozen plasma vs coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion.
Injury. 2011 Jul;42(7):697-701

Central lines in coagulopathic patients

June 21, 2011 by  
Filed under Acute Med, All Updates, Guidelines, ICU, Kids, Resus, Trauma, Ultrasound

If a patient needs a central line, he/she needs one. Often low platelets or a deranged coagulation profile are cited as reasons for omitting or delaying the procedure, but this is not based on evidence of increased complications. A recent Best Evidence Topic Review concludes:

…insertion of CVC lines do not require correction of haemostatic abnormalities prior to intervention. Rates of haemorrhage are low in patients with elevated PT, APTT or low thrombocyte count and appear to be closely related to the level of experience of the physician … rather than the defects of haemostasis.

Links to the abstracts of a couple of relevant articles reviewed are included below.

Central line insertion in deranged clotting
Emerg Med J. 2011 Jun;28(6):536-7 Full text

Low levels of prothrombin time (INR) and platelets do not increase the risk of significant bleeding when placing central venous catheters.
Med Klin (Munich). 2009 May 15;104(5):331-5

US-guided placement of central vein catheters in patients with disorders of hemostasis
Eur J Radiol. 2008 Feb;65(2):253-6

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