Oonagh Gilligan

A multi-centre retrospective study of rituximab use in the treatment of relapsed or resistant warm autoimmune haemolytic anaemia.

This retrospective analysis assessed the response, safety and duration of response to standard dose rituximab 375 mg/m2 weekly for four weeks as therapy for patients with primary or secondary warm autoimmune haemolytic anaemia (WAIHA), who had failed initial treatment. Thirty‐four patients received rituximab for WAIHA in seven centres in the Republic of Ireland. The overall response rate was 70·6% (24/34) with 26·5% (9/34) achieving a complete response (CR). The time to response was 1 month post‐initiation of rituximab in 87·5% (21/24) and 3 months in 12·5% (3/24) of patients. The median duration of follow‐up was 36 months (range 6–90 months). Of the patients who responded, 50% (12/24) relapsed during follow up with a median time to next treatment of 16·5 months (range 6–60 months). Three patients were re‐treated with rituximab 375 mg/m2 weekly for four weeks at relapse and responded. There was a single episode of neutropenic sepsis. Rituximab is an effective and safe treatment for WAIHA but a significant number of patients will relapse in the first two years post treatment. Re‐treatment was effective in a small number of patients, suggesting that intermittent pulse treatment or maintenance treatment may improve long‐term response.

Potentially avoidable inpatient nights among warfarin receiving patients; an audit of a single university teaching hospital

BackgroundWarfarin is an oral anticoagulant (OAT) that needs active management to ensure therapeutic range. Initial management is often carried out as an inpatient, though not requiring inpatient facilities. This mismatch results in financial costs which could be directed more efficaciously. The extent of this has previously been unknown. Here we aim to calculate the potential number of bed nights which may be saved among those being dose optimized as inpatients and examine associated factors.MethodsA 6 week prospective audit of inpatients receiving OAT, at Cork University Hospital, was carried out. The study period was from 11th June 2007 to 20th July 2007. Data was collected from patients medications prescription charts, medical record files, and computerised haematology laboratory records. The indications for OAT, the patient laboratory coagulation results and therapeutic intervals along with patient demographics were analysed. The level of potentially avoidable inpatient nights in those receiving OAT in hospital was calculated and the potential cost savings quantified. Potential avoidable bed nights were defined as patients remaining in hospital for the purpose of optimizing OAT dosage, while receiving subtherapeutic or therapeutic OAT (being titred up to therapeutic levels) and co-administered covering low molecular weight heparin, and requiring no other active care. The average cost of €638 was taken as the per night hospital stay cost for a non-Intensive Care bed. Ethical approval was granted from the Ethical Committee of the Cork Teaching Hospitals, Cork, Ireland.ResultsA total of 158 patients were included in the audit. There was 94 men (59.4%) and 64 women (40.6%). The mean age was 67.8 years, with a median age of 70 years.Atrial Fibrillation (43%, n = 70), followed by aortic valve replacement (15%, n = 23) and pulmonary emboli (11%, n = 18) were the commonest reasons for prescribing OAT. 54% had previously been prescribed OAT prior to current admission.It was confirmed that, there are potentially avoidable nights in patients receiving OAT. The majority of this group were those being commenced on OAT for the first time (p = 0.00002), in the specialities of Cardiology, Cardiothoracic surgery and Care of the Elderly. The potential number of bed nights to be saved is 13 per week for the hospital or 1.1 bed nights per 10,000 general hospital admissions. These were predominantly weekday nights. The estimated cost of avoidable inpatient OAT dose optimization was approximately €8300 per week.ConclusionWith rising costs and the increasing demands for acute hospital beds, alterations to inpatient management for this group of patients should be considered. Alternatives include increasing the size of current anticoagulation clinics, introduction of POCT (point of care testing) devices and increased GP management. POCT can be justified based upon the publication by Gardiner et al, who showed that 87% of patients find self testing straightforward, 87% were confident in the result they obtained using the devices and 77% preferred self testing.

Venous Thromboembolism in Patients With Myeloma: Incidence and Risk Factors in a “Real-World” Population

Myeloma has a well-described association with venous thromboembolism (VTE). There are few dedicated studies investigating the incidence and risk factors. Many assessment scores have been suggested to estimate the risk of VTE in patients with cancer but these have been validated in solid organ tumors. The records of patients with myeloma attending a university hospital between January 2007 and December 2012 were reviewed to investigate the incidence of VTE and the associated risk factors. In all, 217 patients with a mean (standard deviation) age at diagnosis of 65 (12) years were included. Of 217 patients, 12% had an episode of VTE, 69% received at least 1 immunomodulatory agent, and 95% had low or intermediate risk of VTE according to the Khorana score. Venous thromboembolism was a frequent occurrence in this cohort. Patients had many risk factors for VTE but no one was predictive. As myeloma outcomes continue to improve, a dedicated prospective study is warranted to investigate the most appropriate thromboprophylaxis strategy.

Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance

The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.

Fatal babesiosis in an asplenic patient.

An 87-year-old man from the south of Ireland was transferred to the Intensive Care Department following a 3-d history of fevers and discoloured urine. His background medical history was significant for splenectomy at the time of an anterior resection for colorectal carcinoma in 2002. Prior to admission, he was farming and sustained insect bites on his lower extremities. His initial temperature was 39Æ2 C. He had several insect bites and a live tick was retrieved from his body. This was identified as a species of Ixodes tick. His laboratory results were consistent with haemolytic anaemia, disseminated intravascular coagulation, acute kidney injury and severe lactic acidosis. Blood film showed intraerythrocytic oval and pear shaped parasites and pathognomonic tetrads of merozoites, the so-called Maltese cross, making a definitive diagnosis of babesiosis. 50% parasitemia was noted. Howell-Jolly bodies and target cells were present, consistent with known asplenism. He was intubated, ventilated and commenced on inotropes and renal replacement therapy. The patient was treated with intravenous quinine 600 mg t.d.s. and clindamycin 1Æ2 g b.d. and also received several units of red cell concentrate, solvent detergent-washed fresh frozen plasma, and platelets. He was unfit for exchange transfusion. Despite maximal organ support he suffered a cardiac arrest and subsequently died. Laboratory findings of haemolytic anaemia, thrombocytopenia and conjugated hyperbilirubinemia with parasite exposure should raise suspicion for babesiosis. A Wright or Giemsa stained thin blood smear is the definitive diagnostic test. The most common appearance of parasites within red blood cells is round or oval rings with pale blue cytoplasm and a red staining nucleus. Ring forms can be confused with Plasmodium falciparum malaria. Distinguishing features of Babesia include classic, but rarely seen, tetrads of merozoites forming ‘Maltese crosses’, the presence of exoerythrocytic parasites and the absence of pigment granules within infected erythrocytes. Babesiosis although rare, if clinically suspected can be rapidly and inexpensively diagnosed on the basis of a peripheral blood smear. We describe a particularly severe case of babebiosis in a high-risk patient given his age, high parasite count and asplenism.

CALR mutation profile in Irish patients with myeloproliferative neoplasms

Insertion and/or deletion mutations of the CALR gene have recently been demonstrated to be the second most common driver mutations in the myeloproliferative neoplasms (MPNs) of essential thrombocythemia (ET) and primary myelofibrosis (PMF). Given the diagnostic and emerging prognostic significance of these mutations, in addition to the geographical heterogeneity reported, the incidence of CALR mutations was determined in an Irish cohort of patients with MPNs with a view to incorporate this analysis into a prospective screening program. A series of 202 patients with known or suspected ET and PMF were screened for the presence of CALR mutations. CALR mutations were detected in 58 patients. Type 1 and Type 1-like deletion mutations were the most common (n=40) followed by Type 2 and Type 2-like insertion mutations (n=17). The CALR mutation profile in Irish ET and PMF patients appears similar to that in other European populations. Establishment of this mutational profile allows the introduction of a rational, molecular diagnostic algorithm in cases of suspected ET and PMF that will improve clinical management.