-
Internal Medicine (Tokyo, Japan) 2015
Topics: Aged, 80 and over; Hematoma; Hemophilia A; Hemorrhagic Disorders; Humans; Male
PubMed: 25832961
DOI: 10.2169/internalmedicine.54.3862 -
British Journal of Haematology Nov 2019
Topics: Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Hemorrhagic Disorders; Humans; Thrombosis
PubMed: 31364157
DOI: 10.1111/bjh.16110 -
ILAR Journal 2016More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains... (Review)
Review
More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species.
Topics: Animals; Elephants; Genome, Viral; Hemorrhagic Disorders; Herpesviridae; Herpesviridae Infections; Host-Pathogen Interactions; Viral Load
PubMed: 26912715
DOI: 10.1093/ilar/ilv041 -
Genetics in Medicine : Official Journal... Jul 2011Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a disorder of development of the vasculature characterized by telangiectases and arteriovenous... (Review)
Review
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) is a disorder of development of the vasculature characterized by telangiectases and arteriovenous malformations in specific locations. It is one of most common monogenic disorders, but affected individuals are frequently not diagnosed. The most common features of the disorder, nosebleeds, and telangiectases on the lips, hands, and oral mucosa are often quite subtle. Optimal management requires an understanding of the specific presentations of these vascular malformations, especially their locations and timing during life. Telangiectases in the nasal and gastrointestinal mucosa and brain arteriovenous malformations generally present with hemorrhage. However, complications of arteriovenous malformations in the lungs and liver are generally the consequence of blood shunting through these abnormal blood vessels, which lack a capillary bed and thus result in a direct artery-to-vein connection. Mutations in at least five genes are thought to result in hereditary hemorrhagic telangiectasia, but mutations in two genes (ENG and ACVRL1/ALK1) cause approximately 85% of cases. The frequency of arteriovenous malformations in particular organs and the occurrence of certain rare symptoms are dependent on the gene involved. Molecular genetic testing is used to establish the genetic subtype of hereditary hemorrhagic telangiectasia in a clinically affected individual and family, and for early diagnosis to allow for appropriate screening and preventive treatment.
Topics: Activin Receptors, Type II; Antigens, CD; Endoglin; Genetic Predisposition to Disease; Genetic Testing; Humans; Mutation; Receptors, Cell Surface; Telangiectasia, Hereditary Hemorrhagic
PubMed: 21546842
DOI: 10.1097/GIM.0b013e3182136d32 -
British Journal of Haematology May 2014Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, required for the degradation of... (Review)
Review
Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, caused by deficiency of the enzyme glucocerebrosidase, required for the degradation of glycosphingolipids. Clinical manifestations include hepatosplenomegaly, thrombocytopenia, bone disease and a bleeding diathesis, frequently resulting in presentation to haematologists. Historically managed by splenectomy, transfusions and orthopaedic surgery, the development of specific therapy in the form of intravenous enzyme replacement therapy in the 1990s has resulted in dramatic improvements in haematological and visceral disease. Recognition of complications, including multiple myeloma and Parkinson disease, has challenged the traditional macrophage-centric view of the pathophysiology of this disorder. The pathways by which enzyme deficiency results in the clinical manifestations of this disorder are poorly understood; altered inflammatory cytokine profiles, bioactive sphingolipid derivatives and alterations in the bone marrow microenvironment have been implicated. Further elucidating these pathways will serve to advance our understanding not only of GD, but of associated disorders.
Topics: 1-Deoxynojirimycin; Anemia; Combined Modality Therapy; Disease Management; Enzyme Replacement Therapy; Gaucher Disease; Genetic Predisposition to Disease; Glucosylceramidase; Glycosphingolipids; Hemorrhagic Disorders; Humans; Inflammation; Lewy Body Disease; Lysosomes; Macrophage Activation; Multiple Myeloma; Parkinson Disease; Splenectomy; Splenomegaly; Thrombocytopenia; Unfolded Protein Response
PubMed: 24588457
DOI: 10.1111/bjh.12804 -
Thrombosis Research May 2017Hereditary hemorrhagic telangiectasia (HHT) is characterized by frequent severe bleeding, particularly epistaxis, and life-threatening complications including stroke,...
INTRODUCTION
Hereditary hemorrhagic telangiectasia (HHT) is characterized by frequent severe bleeding, particularly epistaxis, and life-threatening complications including stroke, brain abscess and heart failure. The psychological impact of HHT is not known. We conducted this cross sectional study to determine the prevalence of depression and post-traumatic stress disorder (PTSD) related to HHT.
METHODS
A survey tool comprising demographic and clinical information and two validated self-administered questionnaires, the PTSD checklist for DSM-5 (PCL-5) and Beck Depression Inventory-II (BDI-II), was distributed to individuals with HHT. Associations with clinical and demographic variables with depression and PTSD were evaluated in a logistic regression model.
RESULTS
A total of 222 individuals responded to the survey. Of these, 185 completed either the BDI II or PCL-5 and were included in the analysis. Median age was 54years and 142 (76.8%) were female. An existing diagnosis of depression, anxiety disorder and PTSD was present in 81 (43.8%), 59 (31.9%) and 16(8.6%) respondents, respectively. BDI-II scores>13 indicating at least mild depressive symptoms were present in 142 (88.7%) patients and 52 (28.1%) patients had a positive screen for PTSD (PCL-5 score≥38). On multivariable analysis, depression [OR 2.17 (95% CI 1.045-4.489), p=0.038], anxiety disorder [OR 2.232 (95% CI 1.066-4.676), p=0.033], and being unemployed [OR 2.234 (95% CI 1.46-4.714), p=0.019) were associated with PTSD.
CONCLUSION
We report a high prevalence of depressive and PTSD symptoms in individuals with HHT. While selection bias may lead to overestimation of prevalence in this study, our results are concerning and clinicians should remain vigilant for signs of psychological distress and consider screening for these disorders.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Depression; Depressive Disorder; Female; Humans; Male; Middle Aged; Prevalence; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Telangiectasia, Hereditary Hemorrhagic; Young Adult
PubMed: 28314138
DOI: 10.1016/j.thromres.2017.03.003 -
Radiation Research Sep 2021Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a... (Comparative Study)
Comparative Study
Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E2 (dmPGE2), a longer-acting analogue of PGE2, promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2, alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin-CD45-CD31+Sca-1- sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS.
Topics: 16,16-Dimethylprostaglandin E2; Acute Radiation Syndrome; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Platelets; Bone Marrow; C-Reactive Protein; Cesium Radioisotopes; Drug Evaluation, Preclinical; Endothelial Cells; Endothelium, Vascular; Female; Gamma Rays; Hemorrhagic Disorders; Lisinopril; Megakaryocytes; Mice; Mice, Inbred C57BL; P-Selectin; Platelet Aggregation; Platelet Factor 4; Radiation Injuries, Experimental; Thrombocytopenia; Thrombopoiesis; Whole-Body Irradiation; von Willebrand Factor
PubMed: 34153091
DOI: 10.1667/RADE-20-00113.1 -
Transfusion Aug 2022Transfusion of defective platelets could contribute to the inefficiency of platelet transfusion in preventing or stopping bleeding.
BACKGROUND
Transfusion of defective platelets could contribute to the inefficiency of platelet transfusion in preventing or stopping bleeding.
STUDY DESIGN AND METHODS
This single-center prospective study aimed to determine the prevalence of functional platelet abnormalities in a population of blood donors with a clinical history of bleeding diathesis or with history of hematoma (>4 cm) during blood donation. Donors with positive bleeding screening questionnaire were referred to the reference center for rare platelet diseases at La Timone University Hospital (Marseille) to confirm the bleeding tendency using a more extensive bleeding questionnaire (MCMDMscore) and to assess hemostasis, including a comprehensive platelet analysis.
RESULTS
One hundred and ninety-five donors identified based on a history of hematoma and 2434 blood donors were included in the study. Eighty-eight donors (3.6%) had a bleeding score indicating a potential bleeding disorder. Five donors with a history of hematoma (2.5%) and 15 (17%) donors with a confirmed bleeding score underwent hemostatic analysis, including two men and 18 women with average age of 33.9 years. Minor hemostatic abnormalities were observed in three donors. Two donors exhibited accelerated fibrinolysis with reduced euglobulin lysis time and increased D-dimer levels in serum. Two donors had a platelet granule defect, without identification of genetic abnormality.
CONCLUSION
The bleeding questionnaire proved to be a valuable tool to screen blood donors for potential platelet defects. Platelet dysfunction was rare in the blood donor population assessed. Additional studies are necessary to understand the clinical impact that the transfusion of platelets with qualitative defects has on recipients.
Topics: Adult; Blood Coagulation Disorders; Blood Donors; Blood Platelet Disorders; Blood Platelets; Female; Hematoma; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Hemostatics; Humans; Male; Prospective Studies
PubMed: 35748562
DOI: 10.1111/trf.16990 -
Blood Reviews Nov 2019Maintaining normal hemostasis relies on a regulated system of procoagulant and anticoagulant pathways, and disruption of these processes leads to the loss of hemostatic... (Review)
Review
Maintaining normal hemostasis relies on a regulated system of procoagulant and anticoagulant pathways, and disruption of these processes leads to the loss of hemostatic control, with the potential for excessive bleeding or thrombosis. Evaluation of bleeding disorders has conventionally been achieved by laboratory assays that measure the activity of individual coagulation factors. While such assays have proven effective for detecting abnormalities of the coagulation system and aiding diagnosis, inherent limitations prevent them from capturing a complete picture of hemostatic function. An improved understanding of thrombin activity and its central role in hemostasis and bleeding disorders has led to the clinical development of global assays that are more physiologically relevant than traditional assays; furthermore, these global assays are able to monitor responses to therapy. In this review, we provide an overview of the role of thrombin in hemostasis, and describe the clinical benefits of thrombin monitoring in patients with bleeding disorders. Moreover, we discuss recent advances in thrombin-targeting therapeutic strategies that aim to correct thrombin deficiency and prevent bleeding in patients with hemophilia and other rare bleeding disorders.
Topics: Animals; Blood Platelets; Hemophilia A; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Humans; Thrombin
PubMed: 31164248
DOI: 10.1016/j.blre.2019.05.006 -
Blood Apr 1955
Topics: Hemorrhagic Disorders
PubMed: 14363316
DOI: No ID Found