Direct oral anticoagulants or vitamin K antagonists in emergencies: comparison of management in an observational study.

Background: Restoring hemostasis in patients on oral anticoagulants presenting with major hemorrhage (MH) or before surgical intervention has changed, with the replacement of vitamin K antagonist (VKA) with direct oral anticoagulants (DOACs). Objectives: To observe the difference in urgent hemostatic management between patients on VKA and those on DOACs. Methods: A multicenter observational study evaluated the variation in laboratory testing, hemostatic management, mortality, and hospital length of stay (LOS) in patients on VKA or DOACs presenting with MH or urgent hemostatic restoration. Results: Of the 1194 patients analyzed, 783 had MH (61% VKA) and 411 required urgent hemostatic restoration before surgery (56% VKA). Compared to the international normalized ratio (97.6%), plasma DOAC levels were measured less frequently (<45%), and the time taken from admission for the coagulation sample to reach the laboratory varied widely (median, 52.3 minutes; IQR, 24.8-206.7). No significant plasma DOAC level (<50 ng/mL) was found in up to 19% of patients. There was a poor relationship between plasma DOAC level and the usage of a hemostatic agent. When compared with patients receiving VKA (96.5%) or dabigatran (93.7%), fewer patients prescribed a factor Xa inhibitor (75.5%) received a prohemostatic reversal agent. The overall 30-day mortality for MH (mean: 17.8%) and length of stay (LOS) (median: 8.7 days) was similar between VKA and DOAC patients. Conclusion: In DOAC patients, when compared to those receiving VKA, plasma DOAC levels were measured less frequently than the international normalized ratio and had a poor relationship with administering a hemostatic reversal agent. In addition, following MH, mortality and LOS were similar between VKA and DOAC patients.

Retrospective Analysis of the Efficacy and Tolerability of Gemcitabine-Based Chemotherapy in Relapsed/Refractory Lymphoma Patients Not Eligible for Stem Cell Transplant.

INTRODUCTION: Gemcitabine-based regimens are effective salvage therapy for RR lymphoma patients eligible for ASCT, but there is limited data in transplant-ineligible (TIE) patients. Here, we present a retrospective analysis on the outcome of TIE adult patients with RR lymphoma treated with gemcitabine, cisplatin or carboplatin and dexamethasone (GDP/GDCarboP) +/- rituximab regimen in our center. PATIENTS: We identified 33 patients: 54.5% diffuse large Bcell lymphoma (DLBCL), 6.1% double/triple hit lymphoma, 15% follicular lymphoma, 18% T-cell lymphoma, and 6% classical Hodgkin lymphoma. Majority of the patients had advanced-stage disease and raised LDH at relapse. The cohort's median age was 71 years. The median number of prior lines of treatment was 2, and 60.6% were refractory to their last line of treatment. RESULTS: The overall response rate was 33% (complete response 15%) for the entire cohort and 62.5% for DLBCL patients not refractory to prior line of treatment. At median follow-up of 25 months, the median duration of response and overall survival in the responders were not reached. Conversely, the median overall survival for the non-responders was dismal at 5 months. Fifty-five percent required treatment alteration (dose attenuation or omission and treatment delay for >1 week) due to adverse events, 73% needed transfusion, and 70% had at least 1 hospital admission during treatment. CONCLUSION: Our real-world data showed that GDP/GDCarboP provides meaningful efficacy and durability, especially among the responders. However, dose modification and inpatient support are frequently needed, indicating the need for good supportive care and close follow-up in this frailer population.

Electronic FRAIL score as a predictor of treatment outcomes in older patients with diffuse large B-cell lymphoma.

INTRODUCTION: Frailty is a significant risk factor for poor outcomes among older patients with diffuse large B-cell lymphoma (DLBCL). We present an automatically derived electronic frailty screening tool (FRAIL score) as a predictor of patient outcomes. METHODS: Patients aged 70 or over who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for DLBCL between 2010 and ` were retrospectively assessed for their FRAIL scores. Measured treatment outcomes included overall survival (OS), progression-free survival (PFS), and treatment-limiting toxicity from chemotherapy. RESULTS: A total of 96 patients were analysed. When stratified by FRAIL score, the estimated 5-year PFS was 58%, 48% and, 0% for those with scores of 0-1, 2, and 3-5, respectively (p = 0.012). Similarly, the estimated 5-year OS for these respective groups was 60%, 60% and 0% (p = 0.010). Patients with a FRAIL score of 3-5 were also more likely than those with a score of 0-1 to need dose reduction or treatment delay due to toxicity (odds ratio [OR] 12.5, 95% confidence interval [CI] 10.42-109.72) and less likely to complete the six planned cycles of treatment (OR 0.14, 95% CI 0.03-0.77). CONCLUSION: The FRAIL score is independently predictive of OS, PFS, and treatment-related toxicity in older patients with DLBCL receiving R-CHOP chemotherapy. Once implemented, it provides a quick and accessible method to stratify disease and treatment-related risk among these patients.

Fixed-dose three-factor prothrombin complex concentrates is safe and effective in warfarin reversal.

BACKGROUND: Reversal of warfarin with prothrombin complex concentrates (PCC) is required in cases of significant bleeding or need for urgent surgery. A weight-based regimen is commonly, but a fixed-dose approach is also feasible with clinically equivalent outcomes. The purpose of this audit is to review the clinical and laboratory outcomes of patients treated in our centre where fixed-dose PCC is used for warfarin reversal. AIMS: The primary objective was to evaluate the post-reversal international normalised ratio (INR). The secondary objectives were the proportion of patients requiring repeat PCC and 30-day complication rates (death, haemorrhage and thrombosis). A subgroup analysis was also performed to compare the outcomes of those who received a dose of ≤15 IU/kg (reduced dose) with those who received >15 IU/kg (standard dose). METHODS: Patients who received three-factor PCC for warfarin reversal between 1 January and 31 December 2016 were identified and analysed. Clinical data and PCC dosages were extracted from electronic patient records. RESULTS: A total of 144 patients were analysed. The median INR pre-reversal was 3.25 (range 1.4-10), which reduced to 1.5 (0.9-3.0) post-reversal. Eighty-seven percent of patients achieved a post-reversal INR of less than 2 and 55% less than 1.5. Sixteen patients required a repeat dose. Complications occurred in 22 (15.3%) patients, which consisted of 15 deaths, 7 thrombosis and 2 haemorrhage. No statistically significant differences in the primary and secondary outcomes were noted between reduced-dose and standard-dose subgroups. CONCLUSION: Our results support the use of fixed-dose PCC for warfarin reversal in a day-to-day clinical practice in a hospital setting.

Incidence of venous thromboembolism after total hip, total knee and hip fracture surgery at Waitemata District Health Board following a peer-reviewed audit.

AIM: The incidence of venous thromboembolism (VTE) following arthroplasty and hip fracture surgery remains an important metric for quality and financial reasons. An audit at our institution between 2006-2010 showed a higher VTE rate than international data did at the time. This study aims to determine rates of DVT and PE in patients undergoing hip and knee arthroplasty and hip fracture surgery at Waitemata District Health Board (Waitemata DHB) between 1 January 2013 and 31 December 2016. METHODS: This study is a retrospective review of all VTE within three months of elective hip or knee replacement or hip fracture surgery. Data were identified for the period between 2013 and 2016 from Waitemata DHB patient databases, including a dedicated VTE database. RESULTS: The current rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) at our institution following hip or knee arthroplasty or hip fracture surgery are 1.5% and 0.6% respectively, a lower rate than 2.3% and 0.9% respectively in 2006-2010. DVTs were significantly more prevalent after hip fracture surgery than after elective hip or knee arthroplasty, and 71% of DVTs were confined to the distal veins. Of the patients undergoing surgery, 93% received post-operative chemoprophylaxis, mainly aspirin or low molecular-weight heparin (LMWH). CONCLUSION: There has been a significant reduction in VTE rates following elective hip and knee joint replacement and hip fracture surgery between the time periods. This occurred over a period when Waitemata DHB introduced a multi-modal, interdisciplinary team approach to VTE prophylaxis utilising enhanced recovery after surgery (ERAS) pathways. These measures may therefore have contributed to the reduction in VTEs.

New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease and, globally, more than an estimated 10 million people have it yearly. It is a chronic and recurrent disease. The symptoms of VTE are non-specific and the diagnosis should actively be sought once considered. The mainstay of VTE treatment is anticoagulation, with few patients requiring additional intervention. A working group of experts in the area recently completed an evidence-based guideline for the diagnosis and management of DVT and PE on behalf of the Thrombosis and Haemostasis Society of Australia and New Zealand (www.thanz.org.au/resources/thanz-guidelines). MAIN RECOMMENDATIONS: The diagnosis of VTE should be established with imaging; it may be excluded by the use of clinical prediction rules combined with D-dimer testing. Proximal DVT or PE caused by a major surgery or trauma that is no longer present should be treated with anticoagulant therapy for 3 months. Proximal DVT or PE that is unprovoked or associated with a transient risk factor (non-surgical) should be treated with anticoagulant therapy for 3-6 months. Proximal DVT or PE that is recurrent (two or more) and provoked by active cancer or antiphospholipid syndrome should receive extended anticoagulation. Distal DVT caused by a major provoking factor that is no longer present should be treated with anticoagulant therapy for 6 weeks. For patients continuing with extended anticoagulant therapy, either therapeutic or low dose direct oral anticoagulants can be prescribed and is preferred over warfarin in the absence of contraindications. Routine thrombophilia testing is not indicated. Thrombolysis or a suitable alternative is indicated for massive (haemodynamically unstable) PE. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: Most patients with acute VTE should be treated with a factor Xa inhibitor and be assessed for extended anticoagulation.

PROTHROMBINEX(®)-VF (PTX-VF) usage for reversal of coagulopathy: prospective evaluation of thrombogenic risk.

INTRODUCTION: Prothrombin complex concentrates (PCCs) are used for the urgent reversal of oral vitamin K antagonists in patients with life-threatening bleeding or prior to urgent procedures/surgery. PCCs offer rapid and complete reversal without the disadvantages of volume overload and adverse reactions seen with fresh frozen plasma (FFP). There is concern about the risk of thrombosis associated with the use PCCs; data on this is limited at present. OBJECTIVES: To determine the incidence of objectively confirmed arterial or venous thromboembolism within 30 days following the administration of PROTHROMBINEX®-VF (PTX-VF) to acutely reverse a prolonged INR. MATERIALS/METHODS: A prospective observational study was conducted at two teaching hospitals in Auckland, NZ. All patients who received PTX-VF for the acute reversal of prolonged INR were eligible. Baseline patient demographics and reasons for PTX-VF administration were recorded. Patients were reviewed at days 7 and 30, to confirm/exclude thromboembolism or adverse events. RESULTS: 173 patients were enrolled from August 2008 to March 2009. The most frequent indication for reversal was acute bleeding. At 30 days 4.6% (8/173) patients had a definite/probable thrombotic event, and 16.7% had died either due to the presenting bleed (intracranial haemorrhage) or a complication of their presenting complaint (e.g. sepsis, renal failure). CONCLUSIONS: Acute reversal of anticoagulant therapy with PTX-VF is associated with a significant rate of thromboembolism (4.6%) within 30 days. These events can be explained by ongoing cessation of anticoagulant therapy in patients with ongoing risk factors for arterial or venous thrombosis, rather than directly attributable to PTX-VF therapy.

Successful treatment of transplant-associated microangiopathy with rituximab.

The microangiopathic anaemia with thrombocytopenia--which can occur after haematopoietic stem cell transplant--resembles thrombotic thrombocytopenic purpura but has different pathophysiology and does not respond to plasma exchange. We describe a patient with severe manifestations of this disorder who recovered promptly following treatment with rituximab, an anti-CD20 antibody.

A prospective double-blind randomized trial comparing intraluminal ethanol with heparinized saline for the prevention of catheter-associated bloodstream infection in immunosuppressed haematology patients.

OBJECTIVES: The aim of this study was to prospectively evaluate the use of intraluminal ethanol for the prevention of catheter-associated bloodstream infection (CABSI) in immunosuppressed haematology patients. PATIENTS AND METHODS: Patients receiving chemotherapy for haematological malignancy or haematopoietic cell transplantation were randomized in a double-blinded manner to receive either intraluminal 70% ethanol/water or heparinized saline locks on a daily basis throughout a prophylactic treatment period. The primary endpoint was an episode of CABSI (defined as 'bacteraemia in a febrile patient with a central venous catheter that was in use within the preceding 48 h and with no other identified focus of infection'). The trial was registered with the Australian Clinical Trials Register: number ACTRN012605000383662. RESULTS: There were 34 and 30 prophylactic treatment periods in the ethanol and control groups, respectively. CABSI occurred in 3 (9%, 0.60/100 catheter-days) and 11 (37%, 3.11/100 catheter-days) prophylactic treatment periods in the ethanol and control groups, respectively (OR = 0.18, 95% CI 0.05-0.65, P = 0.008). Eleven (32%) and 5 (17%) patients in the ethanol and control groups, respectively, remained afebrile throughout the prophylactic treatment (P = 0.18). CONCLUSIONS: The daily administration of ethanol locks into lumens of central venous catheters effectively reduces the incidence of CABSI.