scholarly journals “Almost Bleeding to Death”: The Conundrum of Acquired Amegakaryocytic Thrombocytopenia

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Gabrielle Elena Brown ◽  
Hani M. Babiker ◽  
Carlos L. Cantu ◽  
Andrew M. Yeager ◽  
Ravitharan Krishnadasan
Keyword(s):  
Antithymocyte Globulin ◽  
Case Reports ◽  
Immunosuppressive Treatment ◽  
Severe Bleeding ◽  
Severe Thrombocytopenia ◽  
Disease Entity ◽  
Excessive Bleeding ◽  
Substantial Risk ◽  
Acquired Amegakaryocytic Thrombocytopenia

Acquired amegakaryocytic thrombocytopenia (AAT) is a rare hematological disorder causing severe thrombocytopenia and bleeding. Previous in vitro studies postulated both cell-mediated suppression of megakaryocytopoiesis in early megakaryocytic progenitor cells and humoral-mediated suppression by anti-thrombopoietin antibodies as possible etiologies of AAT. Patients with AAT usually present with severe bleeding and thrombocytopenia that is unresponsive to steroids and intravenous immunoglobulin (IVIG). Although standard guidelines have not been established for management of AAT, a few case reports have indicated a response to immunosuppressive treatment. The prompt recognition of this disease entity is essential in view of the substantial risk of morbidity and mortality from excessive bleeding. We report a case of AAT successfully treated with equine antithymocyte globulin (ATG) and cyclosporine (CSP).

A Case of Acquired Amegakaryocytic Thrombocytopenia with Anti-c-mpl Autoantibody: Comparison with Idiopathic Thrombocytopenic Purpura

2019 ◽  
Vol 142 (4) ◽  
pp. 239-243
Author(s):  
Bora Son ◽  
Hee sue Park ◽  
Hye Sook Han ◽  
Hee Kyung Kim ◽  
Seung Woo Baek ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Rare Disease ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Immunosuppressive Treatment ◽  
Severe Bleeding ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Acquired Amegakaryocytic Thrombocytopenia

Acquired amegakaryocytic thrombocytopenia (AAMT) is a rare disease that causes severe bleeding. The pathogenesis and treatment of AAMT have not yet been defined. We report the case of a 60-year-old woman diagnosed with AAMT, who presented with severe thrombocytopenia, gastroin­testinal bleeding, and significantly reduced bone marrow megakaryocytes. The patient was treated with methylprednisolone, cyclosporin, and intravenous immunoglobulin. After 2 weeks of treatment, her platelet count started to increase, and her bone marrow megakaryocyte count had normalized 3 months after diagnosis. At the time of diagnosis, the patient was seropositive for anti-c-mpl antibody but was seen to be seronegative once the platelet count recovered. In contrast, anti-c-mpl antibodies were not detected in the serum of 3 patients with idiopathic thrombocytopenic purpura. This case study suggests that anti-c-mpl antibody plays an important role in the development of AAMT, and that intensive immunosuppressive treatment is required for autoantibody clearance and recovery of megakaryocyte count.

scholarly journals Acquired amegakaryocytic thrombocytopenia: Three case reports and a literature review

2004 ◽  
Vol 57 (5-6) ◽  
pp. 292-297 ◽  
Author(s):  
Nebojsa Antonijevic ◽  
Tatjana Terzic ◽  
Vesna Jovanovic ◽  
Nada Suvajdzic-Vukovic ◽  
Rajko Milosevic ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Rare Disease ◽  
Case Reports ◽  
Selective Reduction ◽  
Lithium Carbonate ◽  
Therapeutic Effects ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Acquired Amegakaryocytic Thrombocytopenia

Introduction Acquired amegakaryocytic thrombocytopenia (AAT) is a rare disease characterized by thrombocytopenia due to selective reduction/absence of bone marrow (BM) megakaryocytes. In the BM culture isolated reduction of colony-forming units-megakaryocyte (CFU-Mk) may occur. Material and methods BM aspirates and trephine biopsies were obtained from all patients and processed by routine methods. In vitro BM culture and cytogenetic analysis was performed in one patient. Results This article presents three patients with manifested signs of hemorrhagic syndrome due to severe thrombocytopenia caused by an absence/significant reduction of BM megakaryocytes. Eexistence of systemic or any other disease was excluded in all patients. BM culture of the second patient showed reduction of all hematopoietic progenitors. In the subsequent course of the disease in this patient, signs of dysplastic erythrocytic series and megakaryocytes were also noted, although there were no positive proofs of evolution into myelodysplastic syndrome. Discussion AAT is a disease of hematopoietic stem cells manifesting in a certain period as amegakaryocytic thrombocytopenia which subsequently may progress into aplastic anemia or myelodysplastic syndrome. Patients were treated with corticosteroids, lithium carbonate, androgens, vincristine, immunoglobulins, folic acid, platelet and erythrocyte transfusions along with plasma substitution. The first patient reacted positively to the therapy. In two other patients a minimal, short-term therapeutic effect was achieved, followed by improvement of hemorrhagic syndrome and an insignificant increase in platelet count. In one patient the treatment was stopped after 4 months and the other died of bleeding after 4 months. Conclusion AAT is a rare disease with unpredictable course. This is a case report of three patients with AAT and different therapeutic effects.

scholarly journals Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura

Blood ◽  
2012 ◽  
Vol 120 (17) ◽  
pp. 3603-3610 ◽  
Author(s):  
Filip Callewaert ◽  
Jan Roodt ◽  
Hans Ulrichts ◽  
Thomas Stohr ◽  
Walter Janse van Rensburg ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Therapeutic Option ◽  
Bleeding Risk ◽  
Severe Bleeding ◽  
Severe Thrombocytopenia ◽  
Efficacy And Safety ◽  
Excessive Bleeding ◽  
Thrombocytopenic Purpura ◽  
Baboon Model

Abstract ALX-0681 is a therapeutic Nanobody targeting the A1-domain of VWF. It inhibits the interaction between ultra-large VWF and platelet GpIb-IX-V, which plays a crucial role in the pathogenesis of thrombotic thrombocytopenic purpura (TTP). In the present study, we report the efficacy and safety profile of ALX-0681 in a baboon model of acquired TTP. In this model, acute episodes of TTP are induced by administration of an ADAMTS13-inhibiting mAb. ALX-0681 completely prevented the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia. After induction of TTP, platelet counts also rapidly recovered on administration of ALX-0681. This effect was corroborated by the full neutralization of VWF activity. The schistocytic hemolytic anemia was also halted and partially reversed by ALX-0681 treatment. Brain CT scans and post mortem analysis did not reveal any sign of bleeding, suggesting that complete neutralization of VWF by ALX-0681 under conditions of thrombocytopenia was not linked with an excessive bleeding risk. The results obtained in this study demonstrate that ALX-0681 can successfully treat and prevent the most important hallmarks of acquired TTP without evidence of a severe bleeding risk. Therefore, ALX-0681 offers an attractive new therapeutic option for acquired TTP in the clinical setting.

Experimental Studies on a Recombinant Hirudin, CGP 39393

1991 ◽  
Vol 65 (04) ◽  
pp. 355-359 ◽  
Author(s):  
E Gray ◽  
J Watton ◽  
S Cesmeli ◽  
T W Barrowcliffe ◽  
D P Thomas
Keyword(s):  
Thrombin Generation ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Venous Stasis ◽  
Antithrombotic Agent ◽  
Recombinant Hirudin ◽  
Excessive Bleeding ◽  
Generation Test

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.

Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro–aged or –injured mouse platelets

Blood ◽  
2003 ◽  
Vol 102 (12) ◽  
pp. 4229-4235 ◽  
Author(s):  
Wolfgang Bergmeier ◽  
Peter C. Burger ◽  
Crystal L. Piffath ◽  
Karin M. Hoffmeister ◽  
John H. Hartwig ◽  
...  
Keyword(s):  
Shape Change ◽  
Surface Expression ◽  
Severe Thrombocytopenia ◽  
Aged Mouse ◽  
Platelet Concentrates ◽  
Duration Of Treatment ◽  
Mitochondrial Injury ◽  
Metalloproteinase Activity ◽  
Platelet Transfusions

Abstract Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury, provoked by incubation of platelets with carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to reduced posttransfusion recovery in mice, an effect that directly correlated with the duration of treatment. Damaged platelets were characterized by shape change, disruption of membrane asymmetry, surface expression of P-selectin, and profound proteolysis of GPIbα. Using our model, we identified a key role for endogenous metalloproteinase(s) in platelet clearance, as their inhibition markedly improved posttransfusion recovery of both the mitochondria-injured and in vitro-aged mouse platelets. Metalloproteinase inhibition also prevented proteolysis of GPIbα on damaged platelets, thereby improving the hemostatic function of these cells in vivo. We propose that inhibition of metalloproteinase activity during storage could significantly improve the effectiveness of platelet transfusions. Surface expression of GPIbα might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro. (Blood. 2003;102: 4229-4235)

Evidence-based management of epistaxis in hereditary haemorrhagic telangiectasia

2015 ◽  
Vol 129 (5) ◽  
pp. 410-415 ◽  
Author(s):  
I Syed ◽  
V S Sunkaraneni
Keyword(s):  
Assessment Tool ◽  
Case Reports ◽  
Treatment Algorithm ◽  
Case Series ◽  
Team Approach ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Questionnaire Studies ◽  
Randomised Controlled ◽  
Specific Management

AbstractBackground:There are currently no guidelines in the UK for the specific management of hereditary haemorrhagic telangiectasia related epistaxis. The authors aimed to review the literature and provide an algorithm for the management of hereditary haemorrhagic telangiectasia related epistaxis.Method:The Medline and Embase databases were interrogated on 15 November 2013 using the search items ‘hereditary haemorrhagic telangiectasia’ (title), ‘epistaxis’ (title) and ‘treatment’ (title and abstract), and limiting the search to articles published in English.Results:A total of 46 publications were identified, comprising 1 systematic review, 2 randomised, controlled trials, 27 case series, 9 case reports, 4 questionnaire studies and 3in vitrostudies.Conclusion:There is a lack of high-level evidence for the use of many of the available treatments for the specific management of epistaxis in hereditary haemorrhagic telangiectasia. Current management should be based on a multidisciplinary team approach involving both a hereditary haemorrhagic telangiectasia physician and an ENT surgeon, especially when systemic therapy is being considered. The suggested treatment algorithm considers that the severity of epistaxis merits intervention at different levels of the treatment ladder. The patient should be assessed using a reproducible validated assessment tool, for example an epistaxis severity score, to guide treatment. More research is required, particularly in the investigation of topical agents targeting the development and fragility of telangiectasiae in hereditary haemorrhagic telangiectasia.

Collagenous Sprue: A Rare, Severe Small-Bowel Malabsorptive Disorder

2011 ◽  
Vol 135 (6) ◽  
pp. 803-809
Author(s):  
Xiangrong Zhao ◽  
Rebecca L. Johnson
Keyword(s):  
Celiac Disease ◽  
Medical Literature ◽  
Case Reports ◽  
Disease Entity ◽  
Review Of The Literature ◽  
Molecular Features ◽  
Refractory Sprue ◽  
Exact Etiology ◽  
Sporadic Cases ◽  
Small Intestinal

Abstract Collagenous sprue is a severe malabsorptive disorder, histologically characterized by small intestinal villous and crypt atrophy, and a subepithelial collagen deposit, thicker than 12 µm, that entraps lamina propria cellular elements. Collagenous sprue is a rare disease entity, with only about 60 sporadic cases reported worldwide since it was first described in 1947. Its exact etiology is still under investigation, and its relationship with classic celiac disease and other refractory, spruelike intestinal disorders remains controversial. Two larger-scale studies, in 2009, brought new insights into this elusive, yet emerging, topic. Here, we present a review of the literature on the possible etiology of collagenous sprue, its proposed links to classic celiac disease and to refractory sprue, and its clinical, biochemical, histologic, and molecular features. To our knowledge, all case reports on collagenous sprue in the medical literature to date are summarized.

Preparation of Tablet from Naagdon Plant by Wet Granulation Method for Treatment of Excessive Bleeding in Piles

2021 ◽  
Vol 9 (12) ◽  
pp. 1654-1665
Author(s):  
Sushma Kamble
Keyword(s):  
The Body ◽  
Wet Granulation ◽  
Herbal Drugs ◽  
Excessive Bleeding ◽  
In Vitro Drug Release ◽  
Acceptable Range ◽  
Weight Variation ◽  
Natural Drugs ◽  
Evaluation Parameters

Abstract: The objective of present study was to formulate and evaluate the tablets for piles with different combination of herbal drugs. Material and Method: The tablet for piles containing lactose and mannitol as diluent and containing natural drugs like naagdon which was prepared by wet granulation method. The wet and compressed formulations were subject to several evaluation parameters like appearance, thickness, weight variation, hardness and friability. Results: The results of all evaluation parameters of piles tablet were within the acceptable limit. Pre-compression studies of piles tablet show satisfactory results. The thickness, hardness, weight variation, and friability of pilestablet were found to in acceptable range. The in-vitro drug release of eugenol from optimised for treatment piles formulation was found to be 90.23%. Significant results were obtained from present study. Discussion: The finding of current investigation clearly found that the health promotion of the body could be done by piles

Oral Terbinafine: A New Antifungal Agent

1997 ◽  
Vol 31 (4) ◽  
pp. 445-456 ◽  
Author(s):  
Susan M Abdel-Rahman ◽  
Milap C Nahata
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
Fungal Infections ◽  
Case Reports ◽  
Current Standard ◽  
Open Label ◽  
Double Blind ◽  
Pathogenic Yeast

Objective To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. Data Sources A MEDLINE search restricted to English language during 1966–1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86–327, dermatophytosis, dermatomycosis. Data Extraction The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. Data Synthesis Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. Conclusions Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

scholarly journals Latvian experience in conservative management of abnormally invasive placenta: two case reports

2020 ◽  
Vol 26 (3) ◽  
pp. 153-158
Author(s):  
Diana Bokučava ◽  
Sandra Vītiņa ◽  
Maira Jansone ◽  
Mara Tirāne ◽  
Zane Krastiņa ◽  
...  
Keyword(s):  
Conservative Management ◽  
Case Reports ◽  
Placental Tissue ◽  
University Hospital ◽  
Tertiary Referral Hospital ◽  
Excessive Bleeding ◽  
Section Operation ◽  
Invasive Placenta ◽  
New Treatment

Background. Abnormally invasive placentation (AIP) is a clinical term that describes situation when placenta does not separate spontaneously after delivery and its manual removal causes excessive bleeding (1). Historically, the treatment of choice for this condition is hysterectomy. Lately, the new treatment option, conservative management of the AIP, has proven itself an effective alternative to hysterectomy in carefully selected patients (2). However, the use of conservative AIP management is limited in many countries, the reasoning being the lack of doctors’ experience in this procedure and concerns regarding a high postpartum infection rate. Case reports. We present the first two cases of conservative management of AIP in Latvia. Most of prenatally diagnosed AIP cases country-wide are referred to the Paul Stradinš University Hospital, which is a tertiary referral hospital. The annual rate of AIP in the hospital varies from five to ten cases. Two pregnant women were diagnosed with AIP prenatally, both of them refused hysterectomy and therefore went for the conservative management of AIP. During Caesarean section operation, placentas were left in situ after delivery of the baby. During the follow-up period of 12 and 14 weeks, both women developed infection complications, but complete placental tissue resolution was diagnosed in the end. Conclusion. These two cases demonstrate that conservative management of AIP can be safely applied in small countries/areas with small AIP rate and management experience.

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