Correlates of survival after autoantibody reduction therapy for acute IPF exacerbations.

BACKGROUND: No medical treatment has proven efficacy for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), and this syndrome has a very high mortality. Based on data indicating humoral autoimmune processes are involved in IPF pathogenesis, we treated AE-IPF patients with an autoantibody reduction regimen of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin. This study aimed to identify clinical and autoantibody determinants associated with survival after autoantibody reduction in AE-IPF. METHODS: Twenty-four(24) AE-IPF patients received the autoantibody reduction regimen. Plasma anti-epithelial autoantibody titers were determined by HEp-2 indirect immunofluorescence assays in 22 patients. RESULTS: Mean age of the patients was 70 + 7 years old, and 70% were male. Beneficial clinical responses that occurred early during therapy were a favorable prognostic indicator: supplemental O2 flows needed to maintain resting SaO2>92% significantly decreased and/or walk distances increased among all 10 patients who survived for at least one year. Plasma anti-HEp-2 autoantibody titers were ~-three-fold greater in survivors compared to non-survivors (p<0.02). Anti-HEp-2 titers >1:160 were present in 75% of the evaluable one-year survivors, compared to 29% of non-survivors, and 10 of 12 patients (83%) with anti-HEP-2 titers <1:160 died during the observation period (Hazard Ratio = 3.3, 95% Confidence Interval = 1.02-10.6, p = 0.047). CONCLUSIONS: Autoantibody reduction therapy is associated with rapid reduction of supplemental oxygen requirements and/or improved ability to ambulate in many AE-IPF patients. Facile anti-epithelial autoantibody assays may help identify those most likely to benefit from these treatments.

Granulocyte Transfusion: Clinical Updates and a Practical Approach to Transfusion.

Neutrophils are an integral component of the innate immune system and key regulators of cell-mediated defense against bacterial and fungal pathogens. The potential of granulocyte transfusions has been investigated to temporarily replenish innate immune function to prevent and/or treat infections in patients with severe neutropenia or neutrophil dysfunction. However, evidence has been largely theoretical, experimental, and/or inconclusive. Clinical efficacy has yet to be confirmed by large-scale randomized controlled clinical trials. Performing such trials has been hampered by low granulocyte collection yield and poor patient accrual. We provide a practical summary of the current literature surrounding the practice of granulocyte transfusion.

Potential impact of a delayed ADAMTS13 result in the treatment of thrombotic microangiopathy: an economic analysis.

BACKGROUND: A pre-plasma exchange ADAMTS13 measurement differentiates thrombotic thrombocytopenic purpura (TTP) from other forms of thrombotic microangiopathy (TMA). Given that many hospitals do not perform the ADAMTS13 assay in-house and that the turnaround time (TAT) differs among reference laboratories, we performed an analysis investigating the potential impact of a delay in obtaining the results on the healthcare system. METHODS: An economic model was developed to estimate the impact of a delay in obtaining the pretreatment ADAMTS13 results on patients admitted with TMA with cost (US dollars) as the primary outcome. Incremental cost-effectiveness ratio (ICER) as a composite outcome was calculated from both cost and life days [LDs], an effectiveness surrogate marker. Model parameters were gathered from the medical literature, except for the institutional cost of the ADAMTS13 test. RESULTS: In patients with TMA, during the 6-day study period, the incremental cost to the healthcare system ranged from approximately $4155 to $5123 for every 1-day delay in obtaining the pre-exchange ADAMTS13 results with virtually no change in the effectiveness marker. The ICER composite outcome established the cost-effectiveness of having a fast TAT for pre-exchange ADAMTS13 results. Probabilistic sensitivity analyses also confirmed the robustness of the model. CONCLUSIONS: In patients with clinical presentations of TMAs, having a rapid TAT for pre-exchange ADAMTS13 measurement appeared to be cost-effective. If testing cannot be performed in-house, then our findings support the necessity of contracting with a reference laboratory that can reliably provide the result, preferably within 1 day of admission.

An economic analysis of different treatments for bleeding in patients with acquired haemophilia.

BACKGROUND: Acquired haemophilia A (AHA), with potentially high risk of morbidity and mortality, occurs as a result of inhibitors against factor VIII. Bleeding due to AHA can be treated with activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa) or recently, recombinant porcine-sequence factor VIII (rpFVIII). We extended our previous cost-effectiveness analysis (CEA) comparing rpFVIII against the available traditional options. METHODS: For high-titred, haemorrhaging AHA patients treated with either aPCC, rFVIIa or rpFVIII, over the course of 6-days, a Markov simulation was conducted to evaluate the outcomes when these patients transitioned into any of the four following health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. All model parameters were obtained from the medical literature, except the costs of aPCC, rFVIIa and the factor VIII assay, which came from our institutional data. RESULTS: Excluding the cost of the initial treatment on day 0, the total subsequent treatment cost of rFVIIa was substantially more than the costs of aPCC and rpFVIII ($13 925 vs. $1778 vs. $6957, respectively). The average quality-adjusted life days (QALDs) gained from rpFVIII was lowest (4·89 vs. 4·9 for rFVIIa and 4·91 for aPCC). Overall, aPCC dominated the other two treatments. The model was determined to be robust across the tested ranges for all input variables. CONCLUSION: Based on this economic model, for AHA patients with high titres who were bleeding, aPCC was the most cost-effective treatment option and may be considered for use if there is no clinical contraindication.

Frequency of Alterations in Apheresis-Related Abstracts Prior to Publications as Peer-Reviewed Articles.

High-quality evidence supporting clinical practice is lacking in apheresis. A potential source of evidence is provided by abstracts submitted to the Annual Meetings of the American Association of Blood Banks (AABB) and the American Society for Apheresis (ASFA). However, there is potential for study conclusions to be altered significantly following abstract presentations prior to publications in peer-reviewed journals. Therefore, we evaluated the discordance rate between apheresis-related meeting abstracts and their corresponding published articles. Abstracts accepted to either AABB or ASFA Annual Meetings from 2005 to 2012 and corresponding PubMed-indexed peer-reviewed articles' abstracts published prior to 9/2014 were reviewed for altered methods, results, and conclusions. When present, changes were evaluated for clinical significance. During the 8-year period, 198 out of 1152 abstracts were published as peer-reviewed articles. Of these, 36 (18.2%) presented discordant results, six of which (16.7%) were potentially clinically significant. An alteration in results (58.3%) was the leading reason for discordance. The discordance rate for ASFA abstracts was significantly higher (HR = 4.69, P = 0.0028) than the AABB ones. However, clinically significant alterations occurred more frequently among AABB abstracts (P = 0.025). Approximately 18% of meeting abstracts demonstrated alterations prior to publication in peer-reviewed journals. Given that approximately one in six changes represented clinically significant alterations, potentially affecting clinical practice, we recommend caution when modifying one's clinical practice based on abstract presentations at Annual Meetings. Future studies involving abstracts from both the International Society for Apheresis and the World Apheresis Association should also be performed.

Monitoring Fondaparinux in the Setting of Antithrombin Deficiency.

Heparin-induced thrombocytopenia (HIT) is a not-uncommon adverse effect of heparin exposure, with potentially serious and/or fatal thrombotic consequences. Recent studies looking at the off-label use of fondaparinux for HIT show similar efficacy and adverse-effect profiles, as well as improved costs, compared with some commonly used direct thrombin inhibitors. Although routine laboratory monitoring of fondaparinux-specific anti-Xa levels typically is not recommended, we present a case report that suggests fondaparinux monitoring may be needed in patients with hepatic impairment causing acquired antithrombin deficiency. We performed daily assessment of antithrombin- and fondaparinux-specific anti-Xa levels in a 50-year-old female of unknown ethnicity to ensure that fondaparinux dosing was maintained within an acceptable range. With this management strategy, the patient experienced no thrombotic or hemorrhagic complications during the hospital admission or the following 2 months in outpatient treatment.

aPCC vs. rFVIIa for the treatment of bleeding in patients with acquired haemophilia - a cost-effectiveness model.

BACKGROUND: Acquired haemophilia A (AHA) is an autoimmune bleeding disorder with significant morbidity and mortality. Bleeding AHA patients with high titre inhibitors can be treated with either activated prothrombin complex concentrate (aPCC) or recombinant activated factor VII (rFVIIa). Given that both replacement therapies have inherent benefits and limitations, a cost-effectiveness analysis (CEA) was performed in this population to compare rFVIIa with aPCC. METHODS: In high-titered AHA patients with bleeding treated with either aPCC or rFVIIa, during a 5-day study period, a Markov model was developed such that these patients were transitioned into four different health states: (1) continuous bleeding, (2) thrombosis, (3) stop bleeding and (4) death, with states (2), (3) and (4) modelled as absorbing states. Model parameters, including probabilities, health utility index and costs, were gathered from the medical literature, except for the costs of aPCC and rFVIIa, which were obtained from our institutional data. RESULTS: During the 5-day period, the total treatment cost of rFVIIa was substantially more than the cost of aPCC ($13 635 vs. $1741). The average quality-adjusted life days (QALDs) gained for rFVIIa were slightly lower compared to aPCC (4·08 vs. 4·09). Overall, aPCC prevailed over rFVIIa. Sensitivity analysis confirmed the robustness of the model across tested ranges of all input variables. CONCLUSION: In high-titered AHA patients with bleeding, aPCC is a cost-effective treatment option when compared to rFVIIa. Thus, aPCC may be considered in these patients, if available, and provided there is no clinical contraindication.

Rat Poisoning: A Challenging Diagnosis With Clinical and Psychological Implications.

Rat poisoning should be considered in the differential diagnosis of a patient presenting with signs and symptoms of vitamin K deficiency without a more likely explanation. However, confirming this diagnosis may be difficult due to the varying sensitivities of available assays. A 40-year-old Caucasian woman presented to our hospital with chronic abdominal pain, hematuria, and a history of diarrhea of unknown etiology, despite an extensive work-up. Her laboratory evaluation results were consistent with vitamin K deficiency. Because she reported that she had not ingested warfarin, rat poisoning was suspected; however, the results of the first assay were negative. A second specimen was sent to another reference laboratory with a more sensitive assay, and the diagnosis of brodifacoum poisoning was confirmed. The patient was treated with oral vitamin K. If a patient presents with unexplained signs and symptoms of vitamin K deficiency, toxicological evaluation should be performed and repeat testing may be warranted, depending on the sensitivity of the original testing method.

Management of chronic myeloid leukemia in the setting of pregnancy: when is leukocytapheresis appropriate? A case report and review of the literature.

BACKGROUND: Chronic myeloid leukemia (CML) is a common hematologic malignancy; however, its occurrence during pregnancy is unusual due to its low prevalence in females of childbearing age. There are conflicting reports of how to best manage CML in pregnancy, particularly in the setting of leukocytosis. HEMAPHERESIS: A 30-year-old female was diagnosed with CML at 18 weeks' estimated gestational age. On initial presentation she reported fatigue, night sweats, and early satiety, and was found to have a white blood cell (WBC) count of 69.3 × 109 /L and platelet count of 366 × 109 /L. Her disease was managed during pregnancy using interferon-α alone despite persistent leukocytosis. CONCLUSION: CML may be effectively managed during pregnancy, even in the setting of leukocytosis, without the application of leukocytapheresis. Management relies not only upon the coordination of drug therapy and fetal monitoring, but requires close communication between multiple medical disciplines. Leukocytapheresis has been safely performed during pregnancy and may be a suitable adjunct management strategy in pregnant patients diagnosed with CML with specific clinical presentations, such as hyperleukocytosis (WBC count > 150 × 109 /L) and/or symptomatic leukostasis.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

BACKGROUND: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. STUDY DESIGN AND METHODS: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. RESULTS: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. CONCLUSIONS: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center.

Culture-Proven Thorn-Associated Infections in Arizona: 10-Year Experience at Mayo Clinic.

BACKGROUND: Thorn injuries are common in the desert Southwest; however, the frequency and microbiology of thorn-associated infections have not been systematically described. Most information comes from case reports describing infections from atypical or environmental microorganisms. Our aim was to summarize the spectrum of thorn-associated infections. METHODS: We conducted a retrospective review of electronic health records for patients presenting to our institution from January 1, 2005 to December 31, 2014 for treatment of thorn-associated injuries and then focused on the patients with cultures. RESULTS: Of 2758 records reviewed, 1327 patients had thorn-associated injuries; however, only 58 (4.4%) had cultures. Of these patients, 37 (64%) had positive findings; 5 had polymicrobial infection. The most commonly identified organisms were Staphylococcus aureus (n = 22, 59.0%) and coagulase-negative Staphylococcus species (n = 8, 21.6%). Other pathogens included Nocardia species (n = 3, 8.1%), Streptococcus species (n = 2, 5.4%), Gram-negative bacteria (n = 2, 5.4%), Aspergillus species (n = 2, 5.4%), Paecilomyces lilacinus (n = 1, 2.7%), and Candida species (n = 1, 2.7%). There were no infections caused by Pantoea agglomerans, Sporothrix schenckii, or Coccidioides spp. CONCLUSIONS: In contrast to most published case reports, we found that typical cutaneous microorganisms, such as Staphylococcus species, caused the majority of culture-positive, thorn-related infections.

Antinuclear Antibody-Negative Lupus Nephritis with Full House Nephropathy: A Case Report and Review of the Literature.

Lupus nephritis (LN) is a serious and common complication of systemic lupus erythematosus (SLE) that predisposes to significant morbidity and mortality. Studies show that prompt diagnosis and treatment improves patient survival. We present a case of a 49-year-old female with an atypical presentation of LN who initially presented with new-onset hypertension, edema, arthritis, serositis and recently diagnosed leukocytoclastic vasculitis who later developed acute kidney injury, hematuria and nephrotic syndrome. Laboratory testing showed mixed cryoglobulinemia and elevated perinuclear anti-neutrophil cytoplasmic (p-ANCA) and myeloperoxidase (MPO) antibodies. SLE-related serologies were negative. Kidney biopsy showed diffuse proliferative global glomerulonephritis with a full-house nephropathy pattern on immunofluorescence suggestive of LN. Due to high clinical suspicion and renal biopsy findings, she was treated for LN with prompt renal response to immunosuppression. Cryoglobulins, p-ANCA and MPO titers normalized and the negative SLE serologies remained negative. Literature review on antinuclear antibody (ANA)-negative and seronegative LN revealed the following patient presentations: (1) renal-limited or renal and extra-renal manifestations of SLE with negative serologies and (2) renal and extra-renal manifestations of SLE with negative serologies at presentation who develop positive serologies later in follow-up. Both groups represent a unique and challenging cohort of patients who may require longer follow-up and further testing to rule out other glomerular diseases that may mimic LN on renal biopsy. The absence of SLE-related serologies should be weighed against a high pre-test probability of ANA-negative or seronegative LN. If highly suspected, the patient should be treated promptly with close monitoring.