Gerald Bates

A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy.

Abstract.  Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268: 286–295.

D-Dimer levels at different stages of pregnancy in Australian women: a single centre study using two different immunoturbidimetric assays.

BACKGROUND To date there is minimal data available on D-Dimer levels at different stages of pregnancy. PATIENTS AND METHODS We prospectively measured D-Dimer levels in 632 consecutive pregnant women from March 2007 to January 2009. The median age of the participants was 31 years (range; 18-42) with a median weight of 78 kilograms (range; 46-137). All subjects were investigated during each trimester with two different immunoturbidimetric assays; D-Dimer PLUS and INNOVANCE D-Dimer. D-Dimer levels were determined using a Sysmex® CA 1500 analyser. RESULTS Our data demonstrate that D-Dimer levels in pregnancy show different patterns of rise within the first trimester, depending on the assay used; D-Dimer PLUS=0.88 (SD: mean ratio), INNOVANCE D-Dimer=0.72 (SD: mean ratio). Furthermore, the rise in mean results was greater for the INNOVANCE D-Dimer assay compared to the D-Dimer PLUS assay as shown by the ratio of third to first trimester results of 3.68 and 1.96 respectively. Both D-Dimer assays demonstrated moderate levels of intra-subject variability, with overall mean CVs of 16.5% (D-Dimer PLUS) and 16.9% (INNOVANCE D-Dimer). Furthermore, we studied the association between D-Dimer levels and occurrence of diseases of pregnancy. For both assays, there was no consistently interpretable evidence of an association between raised mean D-Dimer levels or rising D-Dimer levels and any of the diseases or conditions associated with pregnancy. CONCLUSION Our data suggest that the INNOVANCE D-Dimer assay increases significantly with the advancement of pregnancy, and is more sensitive than D-Dimer PLUS assay in the pregnant population.

Massive intravascular haemolysis after high dose intravenous immunoglobulin therapy.

A 58-year-old Caucasian female was known to have had autoimmune thrombocytopenia purpura (ITP) since childhood and had undergone splenectomy when she was 16 years old. She presented with a platelet count of 15 x 109/l with bleeding manifestations and high dose intravenous immunoglobulin (IVIG) was therefore administered. The IVIG administered was Intragam-P (CSL Ltd., Parkville, Victoria, Australia). Her platelet count showed good improvement and had normalized by 48 h. However 48 h after a second dose of IVIG, the patient complained of reddish urine and her haemoglobin concentration (Hb) was found to have dropped from 122 g/l to 100 g/l, falling to 80 g/l after a further three days. Severe haemolysis was evidenced by polychromasia, spherocytes and nucleated red cells in her blood film (top). High lactate dehydrogenase (LDH), high bilirubin and low haptoglobin levels were also noted. A direct antiglobulin test (DAT) was strongly positive (4 + ), anti-IgG was strongly positive (4 + ) and anti-C3d was negative. Anti-A antibody was eluted from the red cells. The plasma was dark red in colour due to intravascular haemolysis (bottom left). Urine was also red in colour due to haemoglobinuria (bottom right), with no red cells on urine microscopy. There was no renal impairment. The patients blood group was A RhD-positive. Tests for antinuclear antibody (ANA), anti-double stranded DNA and anti-extractable nuclear antigen were negative.

Effect of immunoglobulin therapy on the rate of infections in multiple myeloma patients undergoing autologous stem cell transplantation or treated with immunomodulatory agents.

Multiple myeloma (MM) is associated with a significant risk of infection due to immune dysfunction. Infections are a major cause of morbidity and mortality in MM patients. There are few data available regarding the prevalence of infection in MM patients, especially in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide) or post autologous stem cell transplantation (ASCT). Intravenous immunoglobulin (IVIG) has been used successfully to reduce infection rates in the stable phase of MM, with limited data in other stages. We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequent to thalidomide, because of disease progression, and 22 patients underwent ASCT. The median age was 64 years (range 37–86), with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe bacterial infections, including the ASCT group. Fifteen patients suffered from different degrees of viral infections. All patients except 3 received IVIG therapy with a significant decline of the rate of infection thereafter (p<001). Our analysis shows that patients with MM treated with the new immunomodulatory drugs in conjunction with steroids are at significant increased risk of infection. Employing IVIG therapy appears to be an effective strategy to prevent infection in this cohort of patients. Further studies to confirm these findings are warranted.

Evaluation of the Innovance d-Dimer Assay for the Diagnosis of Disseminated Intravascular Coagulopathy in Different Clinical Settings

Disseminated intravascular coagulopathy (DIC) is a serious disease with fatal consequences. We prospectively analyzed Innovance d-dimer immunoturbidimetric assay in 68 patients diagnosed with DIC on the background of malignancy (22), severe infection (20), or multitrauma (26) at a single institution between January 2010 and January 2011. Median age was 61 years (range 20-89). All patients were assessed according to the International Society of Thrombosis and Haemostasis (ISTH) DIC score. Applying a threshold of Innovance d-dimer of 10 mg/L fibrinogen equivalent unit (normal <0.5) was correlated with the highest sensitivity in malignancy (86%) and trauma/surgery (80%) compared to 54% in infection. The specificity remained high at 97% in infection, 81% in trauma and 77% in malignancy with a negative predictive value of 97% in trauma and malignancy, and 88% in infection. Our data suggest that Innovance d-dimer is a useful and simple tool that enhances the ISTH DIC diagnostic criteria. Further studies to confirm these findings are warranted.

A Prospective Randomized Controlled Trial to Assess the Effect of Intravenous versus Oral Iron Therapy in the Treatment of Orthopaedic Preoperative Anaemia

Background: Improving preoperative anaemia is associated with a better surgical outcome. There is lack of data regarding treatment of preoperative anaemia with intravenous versus oral iron. Objective: Assessment of efficacy of oral iron sulphate versus a single intravenous iron polymaltose and subsequent effect on perceived quality of life in both treatment groups. Patients and methods: We conducted a prospective randomised controlled trial with iron therapy for the treatment of Iron Deficiency Anaemia (IDA) patients who were undergoing elective joint arthroplasty. At a single institution, we recruited 44 patients who were randomized to a single intravenous iron polymaltose infusion (16/22) versus oral daily iron sulphate (17/22). Median age was 68 years (range, 45-91) with a male to female ratio of 14:19. Results: After iron therapy, the immediate mean preoperative Hb was increased to 128 g/L (SD ± 11.05) in the IV iron group versus 118 g/L (SD ± 9.23) in the oral iron group (p=0.01) compared to 116 g/L (SD ± 8.46) in the control group (p=0.001). The average length of stay in the hospital for the IV iron group was 6 days (SD ± 2.51) compared to 8 days (SD ± 3.62) in the oral iron group and 8 days (SD ± 4.18) in the control group (p=0.04). Average transfused blood units were 1.5 units in the IV iron group versus 2 units in the oral iron group (p=0.09) and 2.4 units in the control group (p = 0.04). There was a significant improvement of the symptoms of anaemia (p=0.03) after treatment in the IV versus oral iron group with further improvement at 3 months follow-up (p=0.003). Conclusion: Our data suggest that IV iron therapy is superior to oral iron in improving preoperative Hb and hence overall outcome for patients with preoperative IDA. Further trials that aim to improve and optimize preoperative and postoperative Hb are warranted.

An open-labelled, randomized, cross-over study of the effect of electromechanical pumps versus conventional gravity flow on platelet transfusion in adult haematology patients

Background: Only few data are available regarding the effect of the method of platelet transfusion on the platelet increment. Although administering platelets via either a free-flowing gravity or an electromechanical pump is common practice, there are no randomized trials addressing differences between these techniques. Objectives: Our study aimed to determine whether infusion methods influence the platelet increment. Methods: We studied the effect of 3 different electromechanical pumps that are used routinely for transfusion at our hospital; the Graseby 3000, Imed Gemini PC-1, and the Baxter Colleague in comparison to the free-flow gravity method. Between January 2007 and January 2011, we prospectively randomized the platelet transfusion method for 35 patients, in total 171 transfusion episodes. Most of the patients received platelets by each of the 4 different techniques. Patients with factors that may have influenced platelet recovery, such as infection, coagulopathy, platelet or HLA antibodies, were excluded. Results: The Baxter Colleague pump method was associated with the highest platelet increment at 1 h after transfusion (p = 0.03). This effect vanished after 24 h. The Gemini and Graseby pumps gave results similar to those of the gravity flow method. Conclusion: None of the different infusion pumps were inferior to the gravity flow method. Further studies to confirm these findings are warranted.

Application of Massive Transfusion Protocol is Associated with a Low Incidence of Coagulopathy and Mortality Rate

Background: Massive haemorrhage and subsequent Massive Transfusion (MT) are associated with serious, often fatal complications including intractable Disseminated Intravascular Coagulation (DIC). Historically undesirable outcomes demonstrate the need to improve the management approach of MT. It is clear that evidence-based guidelines and protocols should be developed with the aim of improving MT-outcome. Methods: We implemented an evidence-based MT-Protocol (MTP) in 2007 and studied all patients (105) from Jan 2008 to Jan 2011 who required MT and were treated with the MTP at our institution. The MTP includes two phases and incorporates a fixed volume of Fresh Frozen Plasma (FFP), cryoprecipitate and platelets in addition to Packed Red Blood Cells (PRBC). Results: The median age of patients was 57 years (range, 18-86). The male to female ratio was 74:31. Median Hb was 90 g/L (range, 44-110) and platelet count was 190/nl (range, 34-817). Thirteen patients developed mild DIC; 22 moderate DIC and one severe DIC. D-dimer showed average increase of 7.9 mg/L with a range between 0.6-35 mg/L (Normal <0.5). Average INR was 1.97, (range, 1.2-7.2), while average APTT was 36 seconds (range, 22-88s). The mortality rate was 11.4% (12/105) and these were mainly related to underlying trauma rather than DIC with the exception of 1 patient. The average number of transfused PRBC was 15 units (range, 6-42); cryoprecipitate, 20(range, 10-60); platelets, 2(range, 1-7) and FFP, 8(range, 2-20). Conclusion: Despite serious bleeding secondary to trauma or surgery, the implementation of MTP seems to have reduced the occurrence of severe DIC and was associated with a relatively low mortality-rate. Further studies to confirm these findings are warranted.

Recurrent life‐threatening reactions to platelet transfusion in an aplastic anaemia patient with a paroxysmal nocturnal haemoglobinuria clone

A 60‐year‐old woman was diagnosed with non‐severe aplastic anaemia when she presented with anaemia and thrombocytopenia. She developed recurrent life‐threatening hypotensive reactions during transfusion of leukodepleted platelet concentrates, and washed platelet concentrates prevented the development of such reactions subsequently. A paroxysmal nocturnal haemoglobinuria clone was detected on investigating for aplastic anaemia, which has been speculated to play a role in the recurrent hypotensive reactions.