Transfusion Evidence Library

1. Comparative Efficacy of Rivaroxaban and Immunoglobulin Therapy in the Treatment of Livedoid Vasculopathy: A Systematic Review

Ramphall S, Rijal S, Prakash V, Ekladios H, Mulayamkuzhiyil Saju J, Mandal N, Kham NI, Shahid R, Naik SS, Venugopal S

Cureus. 2022;14(8):e28485

Abstract

Livedoid vasculopathy (LV) is an uncommon chronic coagulation disorder whose underlying etiology is not yet fully understood. It predominantly affects females, especially those in late adolescence. There is currently limited research on treatment options for those with this diagnosis. The present systematic review aims to compare the efficacy of rivaroxaban and intravenous immunoglobulin (IVIG) therapy in the treatment of livedoid vasculopathy. A detailed search was conducted from April 20, 2022, to May 1, 2022, using four databases: Elsevier, Medline Complete, Medline Ovid, and PubMed. Out of these, 20 relevant articles were used, and the data was extracted and analyzed. Both rivaroxaban and IVIG were shown to be effective treatment options with similar treatment response times. However, future large-scale clinical trials are needed to determine an established treatment regimen for these patients.

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2. Treatment of immune thrombocytopenia (ITP) secondary to malignancy: a systematic review

Podda GM, Fiorelli EM, Birocchi S, Rambaldi B, Di Chio MC, Casazza G, Cattaneo M

Platelets. 2020;:1-7

Abstract

Immune thrombocytopenia (ITP) can be associated with lymphoproliferative diseases (LPD) or solid tumors. A systematic review of published literature was conducted to evaluate response to treatment of ITP secondary to malignancy. Primary outcome was overall response (complete response+response) to first-line treatments [steroids alone or in combination with intravenous immunoglobulins (IVIg)]. Among secondary outcomes, overall response to second-line treatments [splenectomy, rituximab or thrombopoietin receptor agonists (TPO-RA)] and death were evaluated. Of the retrieved 238 text articles, 108 were analyzable, for a total of 154 patients: 142 in 105 case reports and 12 in 3 observational studies. Thirty-nine patients had solid tumors, 114 LPD, and 1 both. The median follow up was 19 months (IQR, 9-40). The overall response was 50% (62% in solid tumors, 46% in LPD) after steroids and 47% (67% in solid tumors, 36% in LPD) after steroids+IVIg, which are lower than historical responses observed in primary ITP (≈80%). The overall responses to rituximab (used in LPD only), splenectomy and TPO-RA (70%, 73% and 92%, respectively) were similar to those observed in primary ITP. Seven patients (6%) died due to bleeding events. ITP secondary to malignancy appears to be associated with unsatisfactory response to first-line treatments.

Taylor & Francis

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3. Effectiveness of intravenous immunoglobulin use in heparin-induced thrombocytopenia

Aryal MR, Gosain R, Donato A, Katel A, Chakradhar R, Dhital R, Kouides PA

Blood Coagul Fibrinolysis. 2020

Abstract

: Heparin-induced thrombocytopenia (HIT) syndrome is an immune-mediated disorder producing thrombocytopenia and thrombosis, with or without prior exposure to heparin. Although avoidance of heparin products and nonheparin anticoagulants are used, immune-based therapies including intravenous immunoglobulin (IVIg) have been tried when the thrombocytopenia persists or there is breakthrough thrombosis. We sought to systematically review and analyze the published literature on use of IVIg in the treatment of HIT. A systematic search of PubMed, Google Scholar, EMBASE and SCOPUS for all study designs and reports were carried out from inception until April 2019. Statistical analysis was done using Microsoft Excel and Stata version 13. In 34 patients with HIT, the mean age was 60 years. About 70% cases were by unfractionated heparin exposure and 30% by low-molecular weight heparin. The most common precipitant in the patients without heparin exposure was recent surgery. Average nadir platelet count for which IVIg was used was 28 000/mul. Time from resolution of the thrombocytopenia after IVIg treatment was 3 days with average platelet count recovery to 159 000/mul. Mean time from diagnosis to administration of IVIg was day 18. Thrombosis was identified in 32% of patients. About 77% patients improved (platelet count >100 000/mul or cessation of thrombosis) following use of IVIg. Logistic regression did not identify any factors that predicted IVIg response (P > 0.05). No thrombotic events or other adverse events were noted with use of IVIg. IVIg appears to be a safe and effective treatment option for HIT-related thrombocytopenia and for refractory thrombosis.

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4. Intravenous Immune Globulin (IVIG) for Treatment of Autoimmune Heparin-Induced Thrombocytopenia: A Systematic Review

Dougherty JA, Yarsley RL

Ann Pharmacother. 2020;:1060028020943542

Abstract

Objective: To evaluate intravenous immune globulin (IVIG) for autoimmune heparin-induced thrombocytopenia (aHIT), including platelet recovery, IVIG dose, dosing weight, IVIG product used, and complications reported. Data Sources: PubMed and EMBASE were searched from inception through June 21, 2020. Search terms included heparin-induced thrombocytopenia, HIT, intravenous immune globulin, IVIG, autoimmune HIT, aHIT, and immune globulin. Study Selection and Data Extraction: Patients administered IVIG for HIT and diagnosed by immunoassay (optical density ≥2) or positive activation assay were included. Data Synthesis: Twenty-four cases were reviewed; 92% had persistent aHIT. Time to IVIG administration post-nonheparin anticoagulant initiation was 9 days (median). Most common IVIG cumulative dose was 2 g/kg (dosed as 1 g/kg/d for 2 consecutive days); 75% had a favorable platelet increase (≥50 × 10(9)/L) within 5 days of initial IVIG dosing. Relevance to Patient Care and Clinical Practice: aHIT is characterized by critically low platelets, thrombosis, and a persistent delay in platelet recovery despite treatment with a nonheparin anticoagulant. An immunoassay and subsequent confirmatory activation assay (at low, high, and 0 IU/mL unfractionated heparin levels) is recommended to confirm diagnosis. Patients nonresponsive to nonheparin anticoagulants within 5 days of initiation should be evaluated for IVIG treatment (2 g/kg cumulative dose). More data are needed to clarify appropriate IVIG dosing weight, although based on current published literature, it is recommended to use actual body weight. Conclusions: Data reported support use of IVIG as adjunctive therapy for patients with aHIT. Judicious IVIG use based on key clinical and laboratory findings is critical.

Atypon

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5. What Is the Burden of Immunoglobulin Replacement Therapy in Adult Patients With Primary Immunodeficiencies? A Systematic Review

Jones GL, Vogt KS, Chambers D, Clowes M, Shrimpton A

Frontiers in Immunology. 2018;9:1308

Abstract

Background: Primary immunodeficiency disorders (PIDs) are a group of heterogeneous rare disorders, whereby the immune system is missing or not functioning adequately. For patients requiring treatment, the most common option is immunoglobulin replacement therapy (Ig). Treatment of PIDs is simultaneously associated with both improvements in health-related quality of life (HRQoL) and increased treatment burden. Objectives: This review sought to review studies investigating the burden of Ig treatment, synthesize evidence in relation to administration routes (subcutaneous or intravenous) and instruments used, as well as make recommendations for clinical and research applications in this area for patients aged 16 years and older. Methods: We searched Medline, EMBASE, and The Cochrane Library. Sifting of titles was performed by two reviewers, and the assessment of full-text articles by three. From a database which contained 3,770 unique results, 67 full texts were reviewed. Eventually, 17 studies were found to meet the inclusion criteria, and included in this review. Due to data heterogeneity, a narrative, descriptive synthesis of the evidence was undertaken. Results: Most studies were carried out in the USA/North America, used a prospective observational design and involved patients with common variable immune deficiency. Four studies measured the burden of receiving IVIg therapy and 13 measured SCIg therapy. A wide range of measures, primarily designed to measure aspects of treatment satisfaction (e.g., life quality index or a slightly modified version) and HRQoL (e.g., The Short Form-36) had been used. Conclusion: Lack of a parallel control group in most studies meant that changes in outcomes could be due to factors other than changes in the treatment regimen. However, overall, PID patients appeared to report little Ig treatment burden and were satisfied with either modality. However, patient preference appeared to be the delivery of the Ig treatment in the patient's home and SCIg was preferred after switching from IVIg therapy. Individual differences appeared to affect treatment preference and therefore understanding the decision support needs of PID patients facing IG treatment choices would be valuable. Using a questionnaire specifically designed to measure the burden of Ig treatment from the patient's perspective is recommended in future research.

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6. Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

Heitink-Polle KM, Nijsten J, Boonacker CW, de Haas M, Bruin MC

Blood. 2014;124((22):):3295-3307.

Abstract

Childhood immune thrombocytopenia (ITP) is a rare autoimmune bleeding disorder. Most children recover within 6 to 12 months, but individual course is difficult to predict. We performed a systematic review and meta-analysis to identify predictors of chronic ITP. We found 1399 articles; after critical appraisal, 54 studies were included. The following predictors of chronic ITP in children, assessed in at least 3 studies, have been identified: female gender (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.04-1.31), older age at presentation (age >11 years; OR 2.47, 95% CI 1.94-3.15), no preceding infection or vaccination (OR 3.08, 95 CI 2.19-4.32), insidious onset (OR 11.27, 95% CI 6.27-20.27), higher platelet counts at presentation (>20 x 10(9)/L: OR 2.15, 95% CI 1.63-2.83), presence of antinuclear antibodies (OR 2.87, 95% 1.57-5.24), and treatment with a combination of methylprednisolone and intravenous immunoglobulin (OR 2.67, 95% CI 1.44-4.96). Children with mucosal bleeding at diagnosis or treatment with intravenous immunoglobulin alone developed chronic ITP less often (OR 0.39, 95% CI 0.28-0.54 and OR 0.71, 95% CI 0.52-0.97, respectively). The protective effect of intravenous immunoglobulin is remarkable and needs confirmation in prospective randomized trials as well as future laboratory studies to elucidate the mechanism of this effect. 2014 by The American Society of Hematology.

Silverchair Information Systems

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7. The use of immunoglobulin therapy for patients with primary immune deficiency: an evidence-based practice guideline

Shehata N, Palda V, Bowen T, Haddad E, Issekutz TB, Mazer B, Schellenberg R, Warrington R, Easton D, Anderson D, et al

Transfusion Medicine Reviews. 2010;24((Suppl 1):):S28-S50.

Abstract

The standard treatment for patients with primary antibody deficiency is immunoglobulin (IG), but the care of these patients is complex. These guidelines, initiated by the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products, have been developed to facilitate and standardize the care of these patients by the various physician specialties that are responsible for their care. A panel of national expert immunologists and methodologists developed salient clinical questions; and a systematic, expert, and bibliography literature search up to July 2008 was conducted. One thousand eighty-seven citations were retrieved, and 102 reports were used in the preparation of this guideline. The recommendations provide guidance (1) on the complexity of the treatment of these patients; (2) the established benefits of IG on morbidity and mortality; (3) dosage, routes of administration, and management of reactions; (4) the various IG formulations available; (5) vaccination of these patients; and (6) research priorities.

Elsevier Science

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8. The efficacy of different dose intravenous immunoglobulin in treating acute idiopathic thrombocytopenic purpura: a meta-analysis of 13 randomized controlled trials

Qin YH, Zhou TB, Su LN, Lei FY, Zhao YJ, Huang WF

Blood Coagulation & Fibrinolysis. 2010;21((8):):713-21.

Abstract

The purpose of this study was to compare the effects of different dose intravenous immunoglobulin for treatment of acute idiopathic thrombocytopenic purpura. Randomized controlled trials (RCTs) comparing high-dose intravenous immunoglobulin (HD-IVIG) with low-dose intravenous immunoglobulin (low-IVIG) for acute idiopathic thrombocytopenic purpura (ITP) were identified using a predefined search strategy. Effective rate, time of cessation of bleeding, time of platelet count beginning to rise, platelet count by the first week of treatment, the number of platelets after 2 weeks of treatment, time of platelet count to reach peak, peak value of platelet count after treatment, side-effects and rate of developing into chronic ITP were extracted and compared by RevMan 4.2.8 (The Cochrane Collaboration, Oxford, UK). Thirteen RCTs (646 patients) were identified. Meta-analysis showed that effective rate, time of cessation of bleeding, time of platelet count beginning to rise, platelet count by the first week of treatment, the number of platelets after 2 weeks of treatment, time of platelet count to reach peak, peak value of platelet count after treatment and rate of developing into chronic ITP were not statistically different between the two different treatment administrations. However, low-IVIG was associated with a significantly reduced risk of side-effects {odds ratio (OR) 0.39 [95% confidence interval (CI) 0.18-0.83]; P = 0.01]. In conclusion, low-IVIG can be performed as effectively as HD-IVIG without increasing the rate of developing into chronic ITP. Furthermore, the low-IVIG regimen can have fewer side-effects than HD-IVIG administration in patients with acute ITP.

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9. Guidelines on the use of intravenous immune globulin for hematologic conditions

Anderson D, Ali K, Blanchette V, Brouwers M, Couban S, Radmoor P, Huebsch L, Hume H, McLeod A, Meyer R, et al

Transfusion Medicine Reviews. 2007;21(2 (Suppl 1):):S9-56.