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European Journal of Haematology May 2023Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and... (Review)
Review
Intranasal, subcutaneous, or intravenous desmopressin can be utilized to release von Willebrand Factor and Factor VIII into circulation, enhance platelet adhesion and shorten bleeding time. Due to these properties, desmopressin can be effective in controlling bleeding in mild hemophilia A, certain subtypes of von Willebrand disease and in acute bleeding from uremia, end stage renal disease, and liver disease. Its use, however, can be complicated by hyponatremia and rarely arterial thrombotic events. While desmopressin has also been used as a prophylactic blood sparing agent in orthopedic, renal, and hepatic procedures, clinical studies have shown limited benefit in these settings. The purpose of this article is to review the evidence for desmopressin in primary hematologic disorders, discuss its mechanism of action and evaluate its utility as a hemostatic and blood sparing product in various bleeding conditions.
Topics: Humans; Hemostatics; Deamino Arginine Vasopressin; Hemostasis; von Willebrand Diseases; Hemorrhage; von Willebrand Factor
PubMed: 36656570
DOI: 10.1111/ejh.13930 -
Medicine Jul 2016Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs... (Meta-Analysis)
Meta-Analysis Review
Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies.A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707).In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P < 0.00001) compared with the control groups. Group II demonstrated a significant difference in vaginal bleeding time (P < 0.00001), the amount of vaginal bleeding (P = 0.0002), menstruation recovery period (P < 0.00001), and endometrial thickness at 2 (P = 0.003) and 3 (P < 0.00001) weeks postabortion compared with the control group. Similarly, a significant difference was observed in group III for reducing vaginal bleeding time (P < 0.00001) and the amount of vaginal bleeding (P < 0.00001), shortening the menstruation recovery period (P < 0.00001), and increasing endometrial thickness 2 and 3 weeks after surgical abortion (P < 0.00001, all).Immediate administration of OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies.
Topics: Abortion, Induced; Contraceptives, Oral; Female; Humans; Postoperative Complications; Pregnancy
PubMed: 27399060
DOI: 10.1097/MD.0000000000003825 -
Clinical and Applied... 2021The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range...
The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal's method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.
Topics: Aged; Anticoagulants; Atrial Fibrillation; Bleeding Time; Blood Coagulation; COVID-19; Dose-Response Relationship, Drug; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Hypertension; International Normalized Ratio; Male; Medication Adherence; Middle Aged; Pandemics; Patient Acceptance of Health Care; Pulmonary Embolism; Retrospective Studies; SARS-CoV-2; Self Medication; Thrombophilia; Warfarin
PubMed: 34142564
DOI: 10.1177/10760296211021495 -
Journal of the American Heart... Feb 2023Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT...
Background Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT. It has recently been shown that mast cells play a crucial role in a DVT murine model. The underlying mechanism involved in the prothrombotic properties of mast cells, however, has yet to be identified. Methods and Results C57BL/6 mice and mouse mast cell protease-4 (mMCP-4) genetically depleted mice (mMCP-4 knockout) were used in 2 mouse models of DVT, partial ligation (stenosis) and ferric chloride-endothelial injury model of the inferior vena cava. Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY-51469) inhibited mMCP-4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo Recombinant chymases, mMCP-4 (mouse) and CMA-1 (human), were used to characterize the interaction with murine and human plasmin, respectively, by mass spectrometry and enzymatic activity assays. Inhibiting mast cell-generated mMCP-4, genetically or pharmacologically, resolves and prevents venous thrombus formation in both DVT models. Inferior vena cava blood flow obstruction was observed in the stenosis model after 6 hours of ligation, in control- but not in TY-51469-treated mice. In addition, chymase inhibition had no impact on bleeding times of healthy or DVT mice. Furthermore, endogenous chymase limits plasmin activity in thrombi ex vivo. Recombinant mouse or human chymase degrades/inactivates purified plasmin in vitro. Finally, mast cell-containing immunoreactive chymase was identified in human DVT. Conclusions This study identified a major role for mMCP-4, a granule-localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity.
Topics: Mice; Humans; Animals; Chymases; Bleeding Time; Fibrinolysin; Disease Models, Animal; Constriction, Pathologic; Mice, Inbred C57BL; Venous Thrombosis; Anticoagulants
PubMed: 36752268
DOI: 10.1161/JAHA.122.028056 -
Journal of Thrombosis and Thrombolysis Apr 2015Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including... (Review)
Review
Anticoagulants are highly effective at preventing thrombosis across a variety of clinical indications. However, their use can also lead to devastating effects, including major bleeding and death. Anticoagulation providers strive to balance the benefits of anticoagulant therapy with the risks of major bleeding. A measure of quality care can be used to assess the strengths and potential weaknesses in any system of coordinated care delivery. Quality measures in anticoagulation include patient-centered outcomes (e.g. major bleeding, time in the therapeutic range) and provider- or process-focused outcomes (e.g. compliance with guideline recommendations and response times to out-of-range laboratory values). Engaging in quality improvement activities allows anticoagulation providers to assess their own performance and identify areas for targeted interventions. This review summarizes the justification for engaging in quality improvement for anticoagulation management and describes a number of example programs. Interventions benefiting the management of both warfarin and the direct oral anticoagulants are included. The review also details potential quality measures and resources for any anticoagulation provider looking to begin a quality improvement process.
Topics: Anticoagulants; Delivery of Health Care; Drug Monitoring; Health Personnel; Humans; Quality Control
PubMed: 25772116
DOI: 10.1007/s11239-015-1184-8 -
Methods in Molecular Biology (Clifton,... 2022Evaluating prospective anticoagulant therapies in animal thrombosis and bleeding models are standard pre-clinical approaches. Mice are frequently used for initial...
Evaluating prospective anticoagulant therapies in animal thrombosis and bleeding models are standard pre-clinical approaches. Mice are frequently used for initial evaluations because a variety of models have been developed in this well-characterized species, and mice are relatively inexpensive to maintain. Because mice seem to be resistant to forming "spontaneous" thrombosis, vessel injury is used to induce intravascular clot formation. For the purpose of testing heparin-based drugs, we adapted a well-established model in which thrombus formation in the carotid artery is induced by exposing the vessel to ferric chloride. For studying anticoagulant effects on venous thrombosis, we use a model in which the inferior vena cava is ligated and the size of the resulting clots are measured. The most common adverse effect of anticoagulation therapy is bleeding. We describe a simple tail bleeding time that has been used for many years to study the effects of anticoagulants on hemostasis. We also describe a more reproducible, but more technically challenging, saphenous vein bleeding model that is also used for this purpose.
Topics: Animals; Anticoagulants; Disease Models, Animal; Hemorrhage; Heparitin Sulfate; Mice; Prospective Studies; Thrombosis
PubMed: 34626423
DOI: 10.1007/978-1-0716-1398-6_59 -
Open Access Macedonian Journal of... Apr 2018The invasive dental procedures usually result in wounds accompanied by physiological bleeding. Even though the bleeding is easily manageable, it is still one of the... (Review)
Review
BACKGROUND
The invasive dental procedures usually result in wounds accompanied by physiological bleeding. Even though the bleeding is easily manageable, it is still one of the major concerns of the patients and a reason for their subjective discomfort. Recently, a novel approach with light-emitting diode (LED) was introduced to control the bleeding. This study aims to examine the effectiveness of the irradiation with blue-violet light LEDs on the haemostasis.
MATERIAL AND METHODS
The study included 40 patients with an indication for tooth extraction, divided into two groups: examination group (n = 30) and a control group (n = 10). The site of the extraction socket in the examination group was irradiated with LED (410 nm) until the bleeding stopped. The patients from the control group were treated by conventional gauze pressure to stop the bleeding (control group). The duration of irradiation and gauze pressure was measured and compared. The statistical analysis was performed with Student T-test.
RESULTS
The examination group showed the shorter duration of bleeding compared to the control group for 13.67 seconds and 156 seconds, respectively. The most of the cases in the examination group were irradiated in 10 seconds (70%), followed by irradiation of 20 seconds (23.3%) and 30 seconds (6.6%). In the control group, the average time to stop the bleeding by the conventional method was 156 second.
CONCLUSION
The blue-violet LED light shortens the bleeding time from the extraction socket after tooth extraction and may be a promising method for achieving haemostasis.
PubMed: 29731942
DOI: 10.3889/oamjms.2018.181 -
American Journal of Veterinary Research Jul 2022To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration.
OBJECTIVE
To assess the safety and efficacy of the platelet-like nanoparticle (PLN), and to assess its safety in repeated administration.
ANIMALS
6 purpose-bred dogs.
PROCEDURES
The PLN was administered IV at 3 different doses using a randomized crossover design. Each dog received a full dose of 8 X 1010 particles/10 kg, half dose, and 10 times the dose, with a 14-day washout period between doses. Biochemical, prothrombin time, partial thromboplastin time, and fibrinogen analyses were performed at baseline and 96 hours postinfusion. A CBC, kaolin-activated thromboelastography, platelet function assay closure time, and buccal mucosal bleeding time were performed at baseline and 1, 6, 24, 48, 72, and 96 hours postinfusion.
RESULTS
No significant changes were observed over time in the thromboelastography parameters, closure time, and buccal mucosal bleeding time. After the administration of the half dose, hematocrit levels decreased significantly at 1, 6, 24, 48, and 96 hours, with all values within the reference range. The platelet count was decreased significantly at hours 1, 6, 24, 48, and 72 after administration of the half dose, with values less than the reference range at all hours but hour 72. No significant changes in serum biochemistry, coagulation panel, and fibrinogen were observed for all doses. No adverse events were noted during the first infusion. Three dogs experienced transient sedation and nausea after repeat infusion.
CLINICAL RELEVANCE
The PLN resulted in a dilution of hematocrit and platelets, and did not significantly alter hemostasis negatively. The safety of repeated doses should be investigated further in dogs.
Topics: Animals; Dogs; Fibrinogen; Hemostasis; Nanoparticles; Partial Thromboplastin Time; Prothrombin Time; Thrombelastography
PubMed: 35895758
DOI: 10.2460/ajvr.22.04.0069 -
Clinical Chemistry and Laboratory... Apr 2023The platelet function analyser (PFA) is a prevalent platelet function screening instrument, and comes in two models-the original PFA-100 and the contemporary PFA-200.... (Review)
Review
The platelet function analyser (PFA) is a prevalent platelet function screening instrument, and comes in two models-the original PFA-100 and the contemporary PFA-200. The instruments have 'identical' output, being a 'closure time' (CT). Moreover, normal reference ranges provided by the manufacturer, for the specific test cartridges, are the same for both models. There are three different types of test cartridge: collagen/epinephrine (C/Epi), collagen/adenosine diphosphate (C/ADP), and "Innovance PFA P2Y" (only available in certain geographical locations). The PFA-100 was released in the mid 1990s, and so is approaching 50 years of age. The PFA-200, released in some locations in the mid 2010s, is destined to eventually replace the PFA-100, but is not yet available in the USA. The test system is highly sensitive to von Willebrand disease (VWD; C/Epi and C/ADP) and to aspirin therapy (C/Epi only), but only has moderate sensitivity to defects in platelet function and/or deficiencies in platelet number. Accordingly, recommendations for use for screening platelet function vary according to user experience. Some workers have alternatively used the PFA to assess thrombosis risk or pre-operative bleeding risk. In this review, we provide an overview of the history of PFA, and summarise its current clinical utility.
Topics: Humans; Sensitivity and Specificity; Platelet Function Tests; von Willebrand Diseases; Epinephrine; Adenosine Diphosphate; Collagen; Blood Platelets
PubMed: 35859143
DOI: 10.1515/cclm-2022-0666 -
Molecular Medicine (Cambridge, Mass.) Nov 2021Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for...
BACKGROUND
Thrombocytopenia is one of the most common hematological disease that can be life-threatening caused by bleeding complications. However, the treatment options for thrombocytopenia remain limited.
METHODS
In this study, giemsa staining, phalloidin staining, immunofluorescence and flow cytometry were used to identify the effects of 3,3'-di-O-methylellagic acid 4'-glucoside (DMAG), a natural ellagic acid derived from Sanguisorba officinalis L. (SOL) on megakaryocyte differentiation in HEL cells. Then, thrombocytopenia mice model was constructed by X-ray irradiation to evaluate the therapeutic action of DMAG on thrombocytopenia. Furthermore, the effects of DMAG on platelet function were evaluated by tail bleeding time, platelet aggregation and platelet adhesion assays. Next, network pharmacology approaches were carried out to identify the targets of DMAG. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to elucidate the underling mechanism of DMAG against thrombocytopenia. Finally, molecular docking simulation, molecular dynamics simulation and western blot analysis were used to explore the relationship between DAMG with its targets.
RESULTS
DMAG significantly promoted megakaryocyte differentiation of HEL cells. DMAG administration accelerated platelet recovery and megakaryopoiesis, shortened tail bleeding time, strengthened platelet aggregation and adhesion in thrombocytopenia mice. Network pharmacology revealed that ITGA2B, ITGB3, VWF, PLEK, TLR2, BCL2, BCL2L1 and TNF were the core targets of DMAG. GO and KEGG pathway enrichment analyses suggested that the core targets of DMAG were enriched in PI3K-Akt signaling pathway, hematopoietic cell lineage, ECM-receptor interaction and platelet activation. Molecular docking simulation and molecular dynamics simulation further indicated that ITGA2B, ITGB3, PLEK and TLR2 displayed strong binding ability with DMAG. Finally, western blot analysis evidenced that DMAG up-regulated the expression of ITGA2B, ITGB3, VWF, p-Akt and PLEK.
CONCLUSION
DMAG plays a critical role in promoting megakaryocytes differentiation and platelets production and might be a promising medicine for the treatment of thrombocytopenia.
Topics: Animals; Cell Differentiation; Cell Line, Tumor; Ellagic Acid; Female; Humans; Male; Mice; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Platelet Adhesiveness; Platelet Aggregation; Proto-Oncogene Proteins c-akt; Thrombocytopenia
PubMed: 34837956
DOI: 10.1186/s10020-021-00404-1