heparin treatment
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Author(s):  
Syahfori Widiyani ◽  
Irsalina Rahmawati ◽  
W. Yohannes Widodo ◽  
Dian Zamroni ◽  
Fajar L. Gultom ◽  
...  

Introduction: Bullous haemorrhagic dermatosis is a rare clinical disorder which is usually related to a treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH), characterized by multiple intra-epidermal haemorrhages distant from the site of injection. Presentation of Case: A 62-year-old male patient with coronary heart disease who received heparin treatment experienced several tense, haemorrhagic bullae located on the right arm area, close to the injection site, and followed by the formation of several hematomas on his back trunk 2 days after he had received UFH. The lesions regressed after discontinuation of heparin and supportive topical treatments. Discussion: The lesions in this patient have similar characteristic with heparin-induced skin necrosis and demonstrate thrombocytopenia probably related to heparin. There are some proposed hypotheses of pathophysiology which include hypersensitivity reaction and idiosyncratic dose-related reaction. Given the clinically course, the discontinuation of heparin treatment was essential for lesion regression in addition other supportive measures. Conclusion: Heparin-induced skin lesions may indicate the presence of life-threatening heparin-induced thrombocytopenia. An early diagnosis is crucial to enable discontinuation of heparin if required.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1045-1045
Author(s):  
Thomas J. Girard ◽  
Irem Eldem ◽  
Kenneth E Remy ◽  
Monty Mazer ◽  
Jorge Di Paola

Abstract Objective: Identify a plasma-based activity, or biomarker, that defines the mechanism(s) by which Covid-19 disease triggers excessive coagulation. Introduction: While acute respiratory syndrome is the fundamental feature of severe Covid-19 disease, having a high level of the coagulation biomarker D-dimer upon admission is associated with increased thrombosis and mortality. As such, hospitalized patients are often placed on anticoagulant heparins. How Covid-19 triggers excessive coagulation is unresolved. Sars-CoV-2 infection could expose existing tissue factor (TF) to blood or, via cytokines, induce TF expression on cells that are in direct contact with blood. Extracellular vesicles (EV) are lipid bound microparticles released by all types of healthy and damaged cell and Covid-19 patient plasma EV TF activity has been recently reported. Cellular activation and damage due to SARS-CoV-2 could also release polyanionic nucleic acids and polyphosphates and generate neutrophil extracellular traps as contact surfaces for clot formation. Methods: Study 1. We attempted to identify excessive coagulation pathway activities in Covid-19 plasma-based, Ca++-induced thrombin generation assays. Assays were performed in the absence and presence of selective extrinsic (TF) and intrinsic (contact activation) pathway inhibitors (n=296 plasma samples). D-dimer levels were also determined. In a smaller study, Covid-19 patient samples were collected directly into citrate or citrate plus corn trypsin inhibitor, then processed for analysis. Study 2. We conducted studies to evaluate the extent to which EV TF activity contributes to the Covid-19-associated coagulopathies. Plasma EVs were isolated and EV TF activity determined by the difference in FXa activity in the absence vs presence of anti-TF antibody. D-dimer and tissue factor pathway inhibitor a (TFPIa) antigen levels were measured. Data from 232 samples collected from 96 Covid-19 positive patients and 18 samples from 14 healthy controls were analyzed. For each study analysis, patient samples were organized into groups based on the disease severity outcomes as follows: hospitalization (Hospitalization; n=37); intensive care (ICU; n=16); mechanical ventilation (Ventilation; n=22); or fatality (Deceased; n=22). Result: Study 1. Covid-19 samples showed considerable thrombin generation variability with some samples failing to generate thrombin; pathway selective inhibitors reduced thrombin generation while heparinase treatment increased thrombin generation. Upon analysis, thrombin generation parameters showed no significant correlations to either D-dimer levels or disease severity. Instead, plasma prepared from blood collected directly into corn trypsin inhibitor revealed that contact activation that occurred post-sample collection dominates procoagulant activity. Study 2. Figure 1, shows EV TF activities, D-dimer and TFPIα levels obtained for Covid-19 samples, with data segregated based on disease severity outcomes. Statistically significant difference versus the Hospitalized group are shown. TFPIa levels were highest in heparin IV patients (24.4+1.5 nM) vs Heparin-SQ (12.8+0.9 nM) vs enoxaparin (10.8 +0.7 nM) (p value:<0.0001). It is known that heparin treatment increases circulating TFPIα, however an increase in TFPIα might also further increase circulating TF/FVIIa/XaTFPI inhibitory complex, which would dissociate in citrated plasma, and might account for the increase in EV TF in other studies. Conclusions: Contact activation that occurs post-sample collection is sufficient to obscure endogenous triggers of coagulation, if present, in Covid-19 patients' plasma. D-dimer and TFPIα strongly correlate with disease severity although the latter is likely affected by heparin treatment. The most severe Covid-19 patients with high D-dimer did not show detectible plasma EV TF activity. Plasma EV TF activity does not appear to adequately represent the mechanism responsible for elevated D-dimer levels in Covid-19 cases. Figure 1 Figure 1. Disclosures Di Paola: CSL Behring: Consultancy, Honoraria.


2021 ◽  
Author(s):  
Paola Lonati ◽  
Caterina Bodio ◽  
Mariangela Scavone ◽  
Giuliana Martini ◽  
Elisa Pesce ◽  
...  

Antibodies against cationic platelet chemokine, platelet factor 4 (PF4/CXCL4) have been described in heparin-induced thrombocytopenia (HIT) but also in patients positive for anti-phospholipid antibodies (aPL) even in the absence of heparin treatment and HIT-related clinical manifestations. Anti-PF4 antibodies have been recently described also in subjects who developed thrombosis with thrombocytopenia syndrome (TTS) in association with adenoviral vector-based, but not with mRNA-based COVID-19 vaccines. We investigated whether COVID-19 vaccination affects the production of anti-PF4 immunoglobulins detectable by solid-phase assay in aPL-positive patients and their ability to induce in vitro platelet activation. Anti-PF4 were found in 9/126 aPL-positive patients, 4/50 COVID-19, 9/49 other infections, and 1/50 aPL-negative systemic lupus erythematosus patients. Clinical manifestations of TTS were not observed in any aPL patient positive for anti-PF4, whose sera failed to cause platelet aggregations. The administration of COVID-19 vaccines did not affect the production of anti-PF4 immunoglobulins or their ability to cause platelet aggregation in 44 aPL-positive patients tested before and after vaccination. In conclusion, heparin treatment-independent anti-PF4 antibodies can be found in aPL-positive patients and asymptomatic carriers, but their presence, titer as well as in vitro effect on platelet activation are not affected by COVID-19 vaccination.


2021 ◽  
Author(s):  
Tomoko Ichikawa ◽  
Yasuyuki Negishi ◽  
Sayuri Kasano ◽  
Ryoko Yokote ◽  
Mirei Yonezawa ◽  
...  

Abstract Background Antiphospholipid antibody syndrome is the major cause of recurrent pregnancy loss (RPL) and associated with inflammation. Granulysin is a cytotoxic protein secreted by cytotoxic T cells, natural killer cells, and natural killer T cells that is present in abundance in the decidua. It activates innate and cellular immunity simultaneously, and also induces miscarriage. As a treatment, heparin is widely used for the patients with RPL, and exhibits the antithrombotic and anti-inflammatory activities, and angiogenesis. Methods We hypothesized that granulysin is an important factor in inducing miscarriage. Here, we evaluated the changes of serum granulysin level before and 1 week after the commencement of heparin treatment for the patients with RPL. Results The serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibody (2.75 ± 1.03 vs. 2.44 ± 0.69; P = 0.0341 by Welch’s t-test), particularly anti-phosphatidylethanolamine antibodies (IgG: 2.98 ± 1.09 vs. 2.51 ± 0.86; P = 0.0013, IgM: 2.85 ± 1.09 vs. 2.47 ± 0.77; P = 0.0024 by Welch’s t-test). After heparin treatment for 1 week, the serum granulysin levels were reduced significantly (P = 0.0017 by paired t-test). The miscarriage rate was significantly higher in women whose serum granulysin levels were not reduced by heparin treatment (P = 0.0086 by Fisher’s exact probability test). Conclusions These results suggest that heparin may reduce the incidence of miscarriages by suppressing the serum granulysin levels.


Author(s):  
Tiffany Pascreau ◽  
Marie-Christine Ballester ◽  
Patrick Van Dreden ◽  
Sara Zia-Chahabi ◽  
Benjamin Zuber ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Youmin Zheng ◽  
Lingling Chen ◽  
Lingzi Zhang ◽  
Yongxia Liu

Pulmonary hemorrhage occurring in preterm newborns is a catastrophic event and is significantly associated with neonatal deaths. Low-weight-molecular heparin is a medical agent usually used as anticoagulants during pregnancy and has the advantages of good absorption, long half-life, and high bioavailability. This study evaluated the pulmonary function and coagulation function in neonates with pulmonary hemorrhage following intravenous drip of low-molecular-weight heparin and the effects of low-molecular-weight heparin on serum prealbumin and retinol-binding protein levels. A total of 96 neonates with pulmonary hemorrhage were included as study subjects and arranged into the control group and the observation group, 48 per group, based on intravenous drip of unfractionated heparin with or without low-molecular-weight heparin. The neonates receiving intravenous drip of unfractionated heparin and low-molecular-weight heparin exhibited elevated partial pressure of oxygen (PaO2) concomitant with declined partial pressure of carbon (PaCO2) compared to those receiving unfractionated heparin treatment alone. With regard to pulmonary function, neonates receiving combined treatment of unfractionated heparin and low-molecular-weight heparin displayed increased forced expiratory volume in the first second (FEV1), FEV1/forced expiratory vital capacity (FVC), and peak expiratory flow (PEF) ( P < 0.05 ) when comparable to neonates receiving unfractionated heparin treatment alone. As for coagulation function, neonates with pulmonary hemorrhage had decreased activated partial thromboplastin time (APTT), prothrombin time (PT), thromboplastin time (TT), and fibrinogen (FIB) after treatment. Expectedly, these decreases were more significantly in neonates undergoing unfractionated heparin coupled with low-molecular-weight heparin ( P < 0.05 ). The control group was given unfractionated heparin, and the observation group was given unfractionated heparin coupled with low-molecular-weight heparin. In addition to pulmonary function and coagulation function, it was also observed that neonates undergoing unfractionated heparin coupled with low-molecular-weight heparin exhibited higher serum levels of serum prealbumin and retinol-binding protein than those treated with unfractionated heparin alone. Finally, higher recovery rate and lower incidence rate of complications, such as pulmonary infection, intracranial hemorrhage, and respiratory distress, were found in the observation group than the control group ( P < 0.05 ). In conclusion, additional treatment with low-molecular-weight heparin could provide a better patient outcome for neonatal pulmonary hemorrhage with unfractionated heparin treatment, as it could notably improve pulmonary function and coagulation function and reduce the incidence of complications.


Author(s):  
Fumiaki Kanamori ◽  
Yoshio Araki ◽  
Kinya Yokoyama ◽  
Kenji Uda ◽  
Takashi Mamiya ◽  
...  

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110169
Author(s):  
Gianluca Sottilotta ◽  
Carmelo Mangano ◽  
Rosa Basile ◽  
Carmela Falcone ◽  
Francesca Luise ◽  
...  

Patients with COVID-19 are at high risk of thromboembolic events; for this reason, the use of heparin is largely recommended but, in addition to thrombotic complications, bleeding is a significant cause of morbidity in patients with COVID-19. Idiopathic iliopsoas hematoma is a very rarely described hemorrhagic complication in patients with COVID-19. We report here two cases of iliopsoas hematoma in male patients with COVID-19 and being treated with heparin.


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