Experience of Danaparoid to Treat Vaccine-Induced Immune Thrombocytopenia and Thrombosis, VITT

Abstract Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT. Methods: We diagnosed six hospitalized cases of definite or probable VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics. Results: Predominately women in their late forties developed VITT on average 24 days (range 9-59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days (2-18). One patient died but the other five recovered completely. Conclusions: The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.

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Fondaparinux Pre-, Peri-, and/or Postpartum for the Prophylaxis/Treatment of Venous Thromboembolism (FondaPPP)

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211014575 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110145

Author(s):

Carl-Erik Dempfle ◽

Jürgen Koscielny ◽

Edelgard Lindhoff-Last ◽

Birgit Linnemann ◽

Irene Bux-Gewehr ◽

...

Keyword(s):

Venous Thromboembolism ◽

Adverse Events ◽

Drug Hypersensitivity ◽

Low Molecular Weight ◽

Premature Births ◽

First Line ◽

Bleeding Events ◽

Heparin Induced Thrombocytopenia ◽

First Line Therapy ◽

Heparin Allergy

We analyzed data for women who received fondaparinux for ≥7 days during pregnancy. The study retrospectively included women who received fondaparinux pre-, peri- and/or postpartum for ≥7 days for prophylaxis/venous thromboembolism (VTE) treatment at German specialist centers (2004-2010). Data on pregnancy, VTE risk factors, anticoagulant treatment, pregnancy outcome and adverse events were extracted from medical records. 120 women (mean age 31.5 years) were included. Among 84 women with prior pregnancies, 41.0% had ≥1 abortion. Anticoagulation was indicated for prophylaxis in 92.5% cases, including 82.5% women with an elevated VTE risk (82.8% thrombophilia, 34.2% VTE history). All women received low-molecular-weight heparin (LMWH) as first-line therapy; 3 also unfractionated heparin. Treatment changed to fondaparinux, due to heparin allergy (41.7%) or heparin-induced thrombocytopenia (10.0%). Fondaparinux was generally well tolerated. Adverse events included bleeding events (n = 5), abortion (n = 2), premature births (n = 2), stillbirth (n = 1), arrested labors (n = 2), injection site erythema (n = 4) and unspecified drug hypersensitivity (n = 6). No VTE events or increased liver enzymes occurred during treatment. In this retrospective study, fondaparinux was effective and well tolerated. Trial registration: ClinicalTrials.gov NCT01004939.

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Association between Platelet-Associated Immunoglobulin G Levels and Response to Corticosteroid Therapy in Patients with Newly Diagnosed Immune Thrombocytopenia

Acta Haematologica ◽

10.1159/000511698 ◽

2020 ◽

pp. 1-6

Author(s):

Masuho Saburi ◽

Masao Ogata ◽

Yasuhiro Soga ◽

Takako Satou ◽

Kazuhito Itani ◽

...

Keyword(s):

Corticosteroid Therapy ◽

Immunoglobulin G ◽

Immune Thrombocytopenia ◽

High Dose ◽

First Line ◽

Laboratory Findings ◽

Platelet Production ◽

First Line Therapy ◽

Line Therapy ◽

Immature Platelet Fraction

Objective: Platelet-associated immunoglobulin G (PA-IgG) refers to IgG attached to the surface of platelets, while the immature platelet fraction (IPF) reflects the state of platelet production in bone marrow. Since PA-IgG and IPF are increased in patients with immune thrombocytopenia (ITP), reflecting amounts of platelet antibodies and compensatory platelet production, respectively, we hypothesized that these laboratory findings may provide useful markers for predicting treatment response in patients with ITP. We therefore retrospectively investigated associations between levels of these markers at diagnosis and response to first-line therapy in patients with ITP. Methods: Forty-three patients diagnosed with ITP at Oita Kouseiren Tsurumi Hospital between May 2010 and November 2018 were included. Patients were divided into 2 groups based on response to corticosteroid as first-line therapy. Laboratory findings were compared between responders and nonresponders. Results: Median PA-IgG was 285 ng/107 cells (range, 45.5–18,200 ng/107 cells), and median IPF was 15.5% (range, 5.4–62.1%). Median levels were higher than the respective upper limits of normal range (PA-IgG, 0–46 ng/107 cells; IPF, 1.1–9.5%). First-line therapy was performed using standard-dose prednisolone (0.5–1.0 mg/kg/day) in 32 patients and high-dose dexamethasone (40 mg/day, 4 days) or methylprednisolone (125–1,000 mg/day, 3–4 days) in 11 patients. Twenty-four patients (55.8%) responded to first-line therapy. In univariate analysis, type of corticosteroid (p = 0.17) tended to differ between groups but did not differ significantly, and no difference in IPF level was apparent between responders (15.35%; range, 5.4–41.5%) and nonresponders (16.7%; range, 6.3–62.1%; p = 0.15). PA-IgG was significantly higher among nonresponders (430 ng/107 cells; range, 101–18,200 ng/107 cells) than among responders (254.5 ng/107 cells; range, 45.5–470 ng/107 cells; p = 0.004). Multivariate analysis revealed PA-IgG was independently associated with response to first-line therapy (odds ratio, 1.000; 95% confidence interval, 1.000–1.010; p = 0.029). Conclusion: Our data suggested that PA-IgG at diagnosis could offer a useful predictor of response to first-line corticosteroid therapy for ITP.

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Inhibition of platelet phagocytosis as an in vitro predictor for therapeutic potential of RBC antibodies in murine ITP

Blood ◽

10.1182/blood.2019003646 ◽

2020 ◽

Vol 135 (26) ◽

pp. 2420-2424 ◽

Cited By ~ 1

Author(s):

Ramsha Khan ◽

Melissa Menard ◽

Chao-Ching Jen ◽

Xi Chen ◽

Peter A. A. Norris ◽

...

Keyword(s):

Blood Cells ◽

Immune Thrombocytopenia ◽

Therapeutic Potential ◽

Sufficient Condition ◽

First Line ◽

Phagocytosis Assay ◽

First Line Therapy ◽

Line Therapy

Abstract Polyclonal anti-D is a first-line therapy for immune thrombocytopenia (ITP). Monoclonal antibodies are desirable alternatives, but none have yet proven successful despite their ability to opsonize erythrocytes (or red blood cells, RBCs) and cause anemia. Here, we examined 12 murine erythrocyte–specific antibodies of different specificity and subtypes and found that 8 of these antibodies could induce anemia in antigen-positive mice. Of these 8 antibodies, only 5 ameliorated ITP. All antibodies were examined for their in vitro ability to support macrophage-mediated phagocytosis of erythrocytes. Antibodies which supported erythrocyte phagocytosis in vitro successfully ameliorated ITP in vivo. To examine the ability of each antibody to inhibit phagocytosis of platelets, the antibodies were used to sensitize erythrocytes in vitro and these were added to a platelet phagocytosis assay. Antibodies that inhibited platelet phagocytosis in vitro also all ameliorated ITP in vivo. We conclude that inducing anemia is not a sufficient condition for amelioration of ITP but that the antibody’s ability to prevent platelet phagocytosis in vitro predicted its ability to ameliorate ITP. We suggest that inhibition of in vitro platelet phagocytosis may prove to be a valuable tool for determining which erythrocyte antibodies would likely be candidates for clinical use in ITP.

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A Computer-Based Laboratory Record System in an Endocrinology Laboratory

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/000456328101800308 ◽

1981 ◽

Vol 18 (3) ◽

pp. 169-176 ◽

Cited By ~ 1

Author(s):

J Mosley

Keyword(s):

Laboratory Work ◽

Work Schedules ◽

Laboratory Result ◽

Record System ◽

Computer Based ◽

Laboratory Record

A computer-based system for maintaining cumulative laboratory result records is described. The system is also intended to help in the organisation of laboratory work schedules. The system has been in use for over a year and has proved to be successful in improving the service offered by the laboratory.

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Pierwotna małopłytkowość immunologiczna u dzieci

Nowa Pediatria ◽

10.25121/np.2018.22.4.122 ◽

2018 ◽

Vol 22 (4) ◽

Author(s):

Anna Dusza ◽

Michał Matysiak

Keyword(s):

Immune Thrombocytopenia ◽

Clinical Symptoms ◽

Pediatric Population ◽

Current Data ◽

Current Investigation ◽

Surgical Interventions ◽

Hematological Disorders ◽

Primary Immune Thrombocytopenia

In this article we present current investigation on primary immune thrombocytopenia in children. There are described pathomorphology, clinical symptoms, diagnosis and treatment. We also present current data from literature about genetic tests and latest data on treating options in children. Primary immune thrombocytopenia (ITP) is one of the most frequent hematological disorders in pediatric population. Although the majority of children have a self-limited and short duration of the disease. However, approximately 20-30% of those patients can develop chronic ITP, which can cause significant complications and higher mortality and reduced quality of life. Especially regarding to long-term immunosupression or surgical interventions, such like splenectomy and restrictions on daily activities to avoid trauma. Over the past decades a lot of informations has been reported about pathogenic features of ITP. Nowdays, we know that it is not only caused by increased platet destruction and decreased platet production, but also complex, multifactorial immune dysregulation, like loss of immune tolerance and generation of platelet autoantibodies. In this article we present current investigation on ITP including clinical symptoms, diagnosis, pathomorphology and latests options on treatment in children. We also present current data about genetic biomarker, such as Vanin-1 (VNN-1) which has been suggested as one of predictors of chronic disease and potentially can offer early prognosis estimation.

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Prevalence and Risk Factors Associated with First-Line Anti-Tuberculosis Induced Hepatotoxicity in Suratthani Hospital, Thailand

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2021.02.11550 ◽

2021 ◽

Vol 104 (2) ◽

pp. 233-239

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Clinical Symptoms ◽

Significant Risk ◽

Public Health Problem ◽

Major Public Health Problem ◽

First Line ◽

Drug Induced ◽

Factors Associated ◽

Drug Risk

ackground: Tuberculosis (TB) is a major public health problem, including Thailand. Anti-TB drugs are very effective treatment, but they can cause hepatotoxicity. Data on the prevalence of anti-TB drug-induced hepatotoxicity (DIH), as well as the contributing risk factors, are scarce in Thailand. Objective: To measure the prevalence and identify risk factors associated with first-line drugs (FLD) induced hepatoxicity in TB patients. Materials and Methods: The present study was a retrospective study design in TB clinic of Suratthani Hospital, in Southern Thailand. All patients diagnosed with TB and received FLD between January and December 2017, were eligible for the study. Hepatoxicity defined as the following criteria: serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >5x upper limit of normal (ULN) without symptoms, or AST or ALT >3x ULN with clinical symptoms. Results: Of all the 198 TB cases, 18 were identified as DIH. Prevalence of DIH was 9.1%. Hepatitis after FLD was independently associated with age>60 years (adjusted OR [aOR] 28.49, 95% CI 2.68 to 302.95, p=0.005) and serum albumin <3.5 g/dL (aOR 20.97, 95% CI 2.11 to 208.51, p=0.009). Conclusion: Age of more than 60 years and low serum albumin of less than 3.5 g/dL were significant risk factors associated with first-line anti-TB drugs induced hepatoxicity. Keywords: Hepatoxicity, Anti-tuberculosis drug, Risk factor, Thailand

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P19 Mycophenolate mofetil in paediatric uveitis: an early experience

Rheumatology ◽

10.1093/rheumatology/kez415.015 ◽

2019 ◽

Vol 58 (Supplement_4) ◽

Author(s):

Amany Tadrous ◽

Kishore Warrier ◽

Archana Pradeep ◽

Nikki Camina ◽

Satyapal Rangaraj

Keyword(s):

Mycophenolate Mofetil ◽

Conflicts Of Interest ◽

Cystoid Macular Oedema ◽

Favourable Result ◽

Topical Steroids ◽

Second Line ◽

First Line ◽

Small Cohort ◽

Third Line ◽

Paediatric Uveitis

Abstract Background Juvenile idiopathic arthritis (JIA) is the commonest cause of uveitis in children. Uveitis is a significant cause of visual impairment in children with potential complications such as band keratopathy, cataract, posterior synechiae, glaucoma, cystoid macular oedema and a retinal problems. Following the initial treatment with topical and systemic corticosteroids, a wide variety of immunosuppressant agents have been used in the treatment of non-infective uveitis including methotrexate (MTX) and biologic therapy, most of which are administered parenterally. Mycophenolate Mofetil (MMF) is an oral immunosuppressant that inhibits the proliferation of T and B lymphocytes, which has been tried in children with uveitis with mixed results. We started using MMF in children seen in our paediatric uveitis clinic initially as a third line agent when the inflammation is not well controlled despite therapeutic doses of MTX and Adalimumab, as the NHS England Clinical Commissioning Policy does not recommend the use of Infliximab in uveitis not associated with JIA. Buoyed by some favourable result, we have since then used MMF as second line and even first line agent in children with uveitis. Methods Retrospective analysis of the clinical profile of children with uveitis on MMF at a tertiary paediatric rheumatology centre with focus on response to treatment. Results Of the 8 patients who received MMF, six (75%) were girls. Half of them (4/8) had idiopathic uveitis and the rest, associated with JIA. 2/8 patients had MMF as third line agent on top of MTX and Adalimumab, while five of them had it as second line agent on top of Adalimumab due to either MTX intolerance or needle phobia. One patient was started on MMF as first line agent following topical steroids. 6 (75%) of the patients responded/stayed in remission following the addition of/switch to MMF. Conclusion MMF has shown initial promise in the treatment of uveitis in children with uveitis in this small cohort, in line with some existing evidence. It was initially used in patients who were not keen on injections/intolerant to MTX or had failed all existing options. This is a small cohort of patients and we would welcome more research in this area. Conflicts of Interest The authors declare no conflicts of interest.

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Reassessment of treatment modalities for paediatric patients with chronic immune thrombocytopenia

Hämostaseologie ◽

10.1055/s-0037-1617015 ◽

2009 ◽

Vol 29 (02) ◽

pp. 171-176 ◽

Cited By ~ 1

Author(s):

G. Janssen ◽

A. Borkhardt ◽

H. J. Laws

Keyword(s):

Lupus Erythematosus ◽

Immune Thrombocytopenia ◽

Spontaneous Recovery ◽

Treatment Modalities ◽

First Line ◽

Second Line Therapy ◽

Chronic Itp ◽

First Line Therapy ◽

Line Therapy ◽

Acute Form

SummaryApproximately 70% of children have the acute form of immune thrombocytopenia (ITP), which is defined by recovery within six months of presentation with or without treatment. Chronic ITP is to be reserved for patients with platelets < 100 000/μl for more than twelve months and exclusion of other diagnosis like systemic lupus erythematosus or bone marrow failures. In children, the chance of spontaneous recovery is 52% after diagnosis of chronic ITP. The Intercontinental Childhood ITP Study group recommends that children without bleeding may not require therapy regardless of their platelet count. Whereas in patients with bleeding symptoms first line therapy is defined and includes steroids or immunoglobuline, second line therapy in refractory patients with significant hemorrhagic problems is unclear. Guidelines recommend splenectomy, but for more than 50 years patients and physicians look for pharmacological alternatives. It may be that rituximab is a promising option which has been proven to be effective with few adverse effects. Till now the treatment has focused on immunomodulation. Research has now focused on stimulating platelet production. In this review we discuss old and new therapy modalities for children with cITP.

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Successful treatment of refractory secondary immune thrombocytopenia (antiphospholipid antibody syndrome-associated) with the combination of rituximab and romiplostim at the cost of severe bone pain: A case report and review of literature

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220935490 ◽

2020 ◽

pp. 107815522093549

Author(s):

Gizem Yassa ◽

Abdur R Shakir ◽

Kuppuswamy Jagarlamudi ◽

Ahmet E Yassa

Keyword(s):

Case Report ◽

Intravenous Immunoglobulin ◽

Immune Thrombocytopenia ◽

Clinical Manifestations ◽

Combination Regimen ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Second Line ◽

First Line ◽

Autoreactive T Cell

Introduction Immune thrombocytopenia is an autoimmune disorder associated with increased thrombocyte destruction and impaired production in the bone marrow. Proposed mechanisms include an antibody or autoreactive T-cell-associated autoimmunity and thrombopoietin deficiency among others. Clinical manifestations are predominantly mucocutaneous hemorrhages including petechiae, purpura, mucosal bleeding in the urinary or the gastrointestinal tracts, menorrhagia, and epistaxis. The purpose of the treatment is to prevent bleeding rather than normalizing the platelet counts. First-line treatments include corticosteroids ± intravenous immunoglobulin and Anti-D which mainly decrease antibody-mediated platelet destruction and increase the number of peripheral Tregs. Second-line and subsequent therapies include splenectomy, chimeric anti-CD20 antibody (rituximab), which eliminates B cells and act as an immunomodulatory agent, and Thrombopoietin receptor agonists (romiplostim), which promote platelet production. Case report We describe a 40-year-old male patient diagnosed with immune thrombocytopenia that was refractory to first-line corticosteroid and intravenous immunoglobulin and second-line romiplostim monotherapy treatments. Management and outcome: The patient was given the romiplostim and rituximab combination which not only successfully treated thrombocytopenia but also resulted in grade 3 bone pains and the patient’s subsequent refusal to continue therapy. Discussion Common adverse effects of rituximab are infusion reactions and prolonged immunosuppression; those of romiplostim include thrombosis, headaches, arthralgia–myalgia, and gastrointestinal symptoms. This case shows that romiplostim has not caused any discernible side effects when given alone, while combination with rituximab resulted in severe bone and joint pains. We hypothesize that this combination regimen shows a synergistic effect both in terms of efficacy and adverse-effect probability and/or severity.

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