Susan Nahirniak

Activated prothrombin complex concentrate for dabigatran-associated bleeding

A humanized antibody fragment to reverse the oral thrombin inhibitor dabigatran is currently under development (Schiele et al, 2013). The absence of a specific reversal agent has caused apprehension over the use of this anticoagulant (Cotton et al, 2011). Prothrombin complex concentrate (PCC) and activated factor VII seemed ineffective in recently reported cases (Lillo-Le Louet et al, 2012), and animal models and ex vivo studies have provided conflicting results Majeed & Schulman, 2013). Although dabigatran has a low degree of binding to plasma proteins and is dialyzable (Khadzhynov et al, 2013), it may take many hours to eliminate this drug from the circulation. We treated four patients with potentially life-threatening dabigatran-associated bleeding with activated PCC (FEIBA, Baxter AG, Vienna, Austria), two in Hamilton, Ontario and two in Edmonton, Alberta. The laboratory and transfusion data are shown in Fig 1. Creatinine clearance was estimated with the Cockroft-Gault formula. An 84-year-old male (Hamilton 1) with a medical history of atrial fibrillation, hypertension and chronic renal insufficiency was urgently referred to our tertiary care hospital with subdural haematoma. He had fallen at home 1 month earlier and, at the time of presentation, had a 3-day history of headache and progressive left sided weakness. Computed tomography (CT) showed acute on chronic right parietal subdural haematoma with associated midline shift (Fig 2). The last dose of dabigatran, 110 mg, was 2 d before transfer to our hospital. On admission the thrombin time (TT) was 127 s (normal range 20–30 s), activated partial thromboplastin time (aPTT) was 46 s (normal 22–35 s), prothrombin time – international normalized ratio (INR) was 1 2, dabigatran concentration (with Hemoclot ) was 50 ng/ml, and creatinine 135 lmol/l with calculated creatinine clearance of 45 ml/min. The neurosurgeon elected to defer haematoma drainage until dabigatran had been eliminated. The patient received 4600 units (50 units/kg) of aPCC, whereafter the weakness improved without immediate change in the coagulation profile. The thrombin time normalized 3 d later and he underwent uneventful craniotomy with evacuation of 100 ml of blood. Repeat imaging demonstrated resolution of the bleed and he was discharged home the next day. At 1month follow-up, there was complete resolution of the weakness. An 81-year-old female (Hamilton 2) with atrial fibrillation and hypertension woke up in the morning, 12 h after her last dabigatran dose (110 mg), and felt normal but 1 h later she fell off the toilet and was disoriented, unsteady and had right-sided weakness and slurred speech. When the paramedics arrived, 20 min later, her blood pressure was 196/100. CT, 70 min after onset showed acute intra-axial haemorrhage

Flow cytometric detection of CD79a expression in T-cell acute lymphoblastic leukemias

We evaluated the lineage specificity of CD79a in acute leukemias using 3-color flow cytometry in 58 consecutive cases. A panel of cell-surface antigens, including myeloid-associated markers, B-cell-associated markers, and T-cell-associated markers, was used. All cases of acute myeloid leukemia were CD79a-, whereas all cases of B-lineage acute lymphoblastic leukemia (ALL) were CD79a+. Three of 8 cases of T-cell ALL showed variable CD79a expression, indicating the presence of a blast subset expressing a relatively high level of CD79a. We investigated the clinical and pathologic characteristics of these 3 cases. All 3 cases had L1 or L2 morphology and expressed surface CD3. None of the other B-cell-associated markers were positive, although 1 case expressed CD13 and CD33. Uncommon random karyotypic abnormalities were identified in all 3 cases. Molecular studies demonstrated monoclonal gene rearrangement of T-cell receptor gamma in 2 of 3 cases. All 3 patients were 18 years old or younger; 1 patient did not enter remission, and 1 had disease relapse in 8 months. Our findings provide further support for the existence of a subset of T-cell ALL coexpressing CD3 and CD79a. Further study of the clinical and biologic significance of this subset may be warranted.

Implementation of a Redistribution System for Near-Outdate Red Blood Cell Units

CONTEXT Many remote hospitals keep small on-site stocks of red blood cell (RBC) units for emergency use and to support patient care programs. In Canada, the blood supplier does not accept returned units into inventory. Discard rates can, therefore, be high. OBJECTIVE To transport near-outdate RBC units to a high-usage hospital site, which would reduce overall discard rates, thereby increasing overall stock levels available in the blood system. DESIGN A blood transportation system was developed and validated. The validation was presented to a high-usage site that agreed to accept near-outdate RBC units transported by this system. Stocks at the remote hospitals were optimized without increasing system-wide discard rates. The redistribution program was implemented in 4 remote sites in northern Alberta, Canada. The final disposition of each transported unit was tracked. Data from the first 2 years were analyzed. RESULTS Between April 1, 2003, and March 31, 2005, 106 RBC units were successfully transported to and transfused at the high-usage site. The majority of the units were group O. None of the transfused units were involved in any reported transfusion reactions. The success rate of the transportation system varied among the sites (59%-78% successfully transported and transfused). Changes to the transport system were implemented as problems were discovered. The use of a temperature monitor in each shipment allowed for concurrent revalidation after each change. CONCLUSIONS Redistribution systems can be an effective way to reduce RBC unit discard rates. Even simple transportation systems have many factors affecting the RBC unit temperature. Novel temperature stabilizing materials may make future transportation of RBC units more reliable.

Guidelines for the Use of Immunoglobulin Therapy for Primary Immune Deficiency and Solid Organ Transplantation

STATEMENT OF CONFLICT OF INTEREST: Funding T his is the second supplement dedicated to the publication of guidelines for the use of intravenous immunoglobulin (IVIG). Two guidelines, published in April 2007, provided recommendations for the use of IVIG in hematologic and neurologic conditions. The current supplement provides recommendations for the use of IVIG in primary immune deficiencies (PIDs) and solid organ transplantation. All four guidelines were developed as a collaborative initiative of Canadian Blood Services and Canadas National Advisory Committee on Blood and Blood Products (NAC—an advisory committee, composed of Canadian Blood Services representatives and hospital-based transfusion medicine experts chosen by their respective Provincial Ministries of Health, reporting to a joint Canadian Blood Services/Provincial and Territorial Ministries of Health committee). Several aspects of IVIG use in Canada that were addressed in the editorial accompanying the publication of the guidelines for the use of IVIG in hematologic and neurologic conditions merit repeating here. Since 1997 to 1998, IVIG use in Canada has increased dramatically—by approximately 260%—from 47 g per 1000 population in 1998 to 123 g per 1000 population in 2009. As shown in Figure 1, Canada now has one of the highest per capita uses of IVIG worldwide. This has occurred with only limited changes in the licensed indications for IVIG and is also accompanied by wide variations in per capita use among Canadian provinces. In a few cases, this increase in IVIGuse reflects the appropriate application of results of recently con-

Bedside to Bench: The Risk of Bleeding with Parenteral Omega-3 Lipid Emulsion Therapy

Our clinical experience led us to reassess the effect of sole omega-3 lipid therapy on hemostasis. We compared thromboelastography platelet mapping in neonatal piglets given sole omega-3 lipid. We identified abnormalities in reaction time (P = .025) and the arachidonic acid pathway (P = .025). The potential for bleeding complications from parenteral omega-3 lipid emulsion therapy in high-risk infants with liver disease has been dismissed but, on the basis of this data, should be reconsidered.

Caterpillar-induced bleeding syndrome in a returning traveller

The case: A 22-year-old woman who was previously healthy presented with a 4-day history of expanding ecchymoses. She had no other bleeding manifestations and denied any constitutional symptoms, myalgias, arthralgias or rashes. Her medical history was unremarkable. She was not taking any medication,

Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study

The reversal of dabigatran-associated major bleeding can now be achieved with the antidote idarucizumab. We evaluated activated prothrombin complex concentrate (aPCC) as an alternative for this purpose. Patients treated with dabigatran and suffering a major bleed were treated as per existing hospital protocol with aPCC. They were subsequently recruited for a 30-day follow-up. Effectiveness was evaluated by the treating physician, using an Assessment Guide. Safety outcomes were arterial or venous thromboembolism or death. A comparison was also made with historic cases with dabigatran-associated major bleeds treated with supportive care, by matching 1:2 for type of bleed, age and sex. We aimed at 32 evaluable cases but the study was prematurely discontinued after 14 cases due to the availability of the approved antidote. The effectiveness of aPCC was assessed as Good in 9 (64%), moderate in 5 (36%) and poor in none. There were no thromboembolic events and one death. In the secondary adjudication of effectiveness, using the same criteria and by the same adjudicators as previously done for the historic cases, the outcome was graded for the current cases versus the historic cases as Good, Moderate, or Poor in 10 (71%) versus 16 (57%), 3 (21%) versus 4 (14%), and 1 (7%) versus 8 (29%), respectively. Although supportive care is sufficient to manage many patients with dabigatran-associated bleeding, aPCC might provide an additional benefit to control life-threatening bleeding in selected cases and does not appear to cause an excess of thromboembolic events.

Viability of AS-3 and SAG-M red cells stored in plastic syringes for pediatric transfusion

BACKGROUND: Pediatric patients may require small‐volume transfusions necessitating splitting of red cell (RBC) units. This process usually involves temporary storage of aliquots in pediatric blood bags or, in some cases, plastic syringes, until they are transfused. While many studies have been published on the efficacy of storage in blood bags, there is little evidence to show that RBCs are safe and effective for transfusion after separation into plastic syringe aliquots.

Transfusion‐related acute lung injury after transfusion of pooled immune globulin: a case report

Transfusion‐related acute lung injury (TRALI) is a severe transfusion reaction that manifests as acute respiratory compromise within 6 hours of the infusion of blood products. Intravenous immune globulin (IVIG) is prepared from large pools of human plasma and is commonly administered in the outpatient setting for the treatment of a wide range of diseases. As a plasma‐derived blood product, IVIG may also cause TRALI, although reports of this are exceedingly rare.

Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study

Oral factor Xa inhibitors are increasingly used for anticoagulation, but there is no approved reversal agent. Prothrombin complex concentrate (PCC) for the management of Xa-inhibitor-associated bleeding has been described in small case series and one cohort study. Patients on apixaban or rivaroxaban, suffering a major bleed, were treated at nine Canadian hospitals as per existing hospital protocol with a fixed dose of PCC 2,000 units and subsequently recruited for a 30-day follow-up. The treating physician evaluated the haemostatic effectiveness as observed during the first day as good, moderate or poor/none, using an assessment guide. Safety outcomes were thromboembolism or death. We recruited 66 patients with major bleeding who were treated with PCC and who were receiving rivaroxaban (56%) or apixaban (44%). The effectiveness was assessed as good in 65% (95% confidence interval [CI], 53-77), moderate in 20% (95% CI, 10-30) and poor/none in 15% (95% CI, 6-24). For the 36 patients with intracranial haemorrhage, the corresponding ratings were 67, 17 and 17%, and for 16 patients with gastrointestinal bleeding they were 69, 12 and 19%, respectively. There were nine deaths (14%) by 30 days, and five (8%) major thromboembolic events. In a post hoc analysis, according to International Society on Thrombosis and Haemostasis criteria, reversal was effective in 68% and ineffective in 32%. For major bleeding associated with oral Xa inhibitors, PCC may have a beneficial effect. The risk of thromboembolism after reversal of anticoagulation in patients with a prothrombotic background has to be taken into account.