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PeerJ 2024Protein C (PC) is an anticoagulant that is encoded by the PROC gene. Validation for the function of PC was carried out in mouse models.
OBJECTIVES
Protein C (PC) is an anticoagulant that is encoded by the PROC gene. Validation for the function of PC was carried out in mouse models.
METHODS
In this study, autosomal recessive PC deficiency (PCD) was selected as the target, and the specific mutation site was chromosome 2 2q13-q14, PROC c.1198G>A (p.Gly400Ser) which targets G399S (GGT to AGC) in mouse models. To investigate the role of hereditary PC in mice models, we used CRISPR/Cas9 gene editing technology to create a mouse model with a genetic PCD mutation.
RESULTS
The two F0 generation positive mice produced using the CRISPR/Cas9 gene editing technique were chimeras, and the mice in F1 and F2 generations were heterozygous. There was no phenotype of spontaneous bleeding or thrombosis in the heterozygous mice, but some of them were blind. Blood routine results showed no significant difference between the heterozygous mice and wild-type mice ( > 0.05). Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged in the heterozygous mice, while the level of fibrinogen content (FIB) decreased, suggesting secondary consumptive coagulation disease. The protein C activity of heterozygous mice was significantly lower than that of wild-type mice ( < 0.001), but there was no significant difference in protein C antigen levels ( > 0.05). H&E staining showed steatosis and hydrodegeneration in the liver of heterozygous mice. Necrosis and exfoliated epithelial cells could be observed in renal tubule lumen, forming cell or granular tubules. Hemosiderin deposition was found in the spleen along with splenic hemorrhage. Immunohistochemistry demonstrated significant fibrin deposition in the liver, spleen, and kidney of heterozygous mice.
CONCLUSION
In this study, heterozygotes of the mouse model with a PC mutation were obtained. The function of PC was then validated in a mouse model through genotype, phenotype, and PC function analysis.
Topics: Animals; Protein C; Mice; Disease Models, Animal; Protein C Deficiency; Mutation; Male; Female; Blood Coagulation; Heterozygote; Gene Editing; CRISPR-Cas Systems; Partial Thromboplastin Time
PubMed: 38680896
DOI: 10.7717/peerj.17261 -
Frontiers in Oncology 2024In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may...
In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may provide a greater guarantee of safety and comfort to APL patients. However, CVCs have seldom been attempted in APL patients during induction therapy because of concerns about increasing the risk of hemorrhagic complications after this invasive procedure. To evaluate the hemorrhagic risk after CVC placement in APL patients during induction therapy, we retrospectively analyzed 95 newly diagnosed patients with APL from January 2010 to December 2022. Among these patients, 39 patients in the CVC group and 56 patients in the non-CVC group were included. Laboratory and clinical parameters of the two groups were collected and compared. There were no significant differences in median platelet, fibrinogen (Fbg), D-dimer, prothrombin time (PT), white blood count (WBC) and hemoglobin (Hb) between the CVC and non-CVC groups on the first day of the visit (day 0) and the following days (day 4, day 7, day 11, day 14, day 18 and day 21) ( = 0.382, = 0.805, = 0.456, = 0.902, = 0.901 and = 0.097, respectively). The consumption of transfused platelets and Fbg was not significantly different between the CVC group and non-CVC group (5.0 vs. 4.5 units, = 0.34, and 6.8 vs. 6.0, = 0.36, respectively). The last day of platelet and Fbg transfusion was also not significantly different (21 vs. 19, = 0.238 and 7.5 vs. 8.5, = 0.684, respectively). The incidences of total hemorrhagic events and hemorrhagic death were lower in the CVC group than in the non-CVC group (17.9% vs. 37.5%, = 0.04 and 0% vs. 16.1%, = 0.01, respectively). The 30-day survival rate was not significantly different (92.3% vs. 82.1%, respectively, = 0.145) for the CVC group compared with the non-CVC group. Our study suggested that CVCs did not increase the hemorrhagic risk in APL patients during induction therapy and that a CVC should be considered in this type of clinical situation.
PubMed: 38680857
DOI: 10.3389/fonc.2024.1332372 -
Journal of Photochemistry and... Jun 2024Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted...
Chemical and UV light-based pathogen reduction technologies are currently in use for human platelet concentrates (PCs) to enhance safety from transfusion-transmitted infections. Relative to UV light, 405 nm violet-blue light in the visible spectrum is known to be less harmful. Hence, in this report for the first time, we have assessed the global hemostasis activity of PCs stored in plasma and the activities of six plasma coagulation factors (CFs) as a measure of in vitro hemostatic activity following exposure to the microbicidal 405 nm light. Apheresis PC samples collected from each screened human donor (n = 22) were used for testing of PCs and platelet poor plasma (PPP). Both PCs and PPPs were treated for 5 h with 405 nm light to achieve a previously established microbicidal light dose of 270 J/cm. Activated partial thromboplastin time and prothrombin time-based potency assays using a coagulation analyzer and hemostatic capacity via Thromboelastography were analyzed. Thromboelastography analysis of the light-treated PCs and plasma present in the PCs showed little difference between the treated and untreated samples. Further, plasma present in the PCs during the light treatment demonstrated a better stability in potency assays for several coagulation factors compared to the plasma alone prepared from PCs first and subjected to the light treatment separately. Overall, PCs stored in plasma treated with 405 nm violet-blue light retain activity for hemostasis.
Topics: Humans; Blood Platelets; Hemostasis; Ultraviolet Rays; Thrombelastography; Light; Partial Thromboplastin Time; Prothrombin Time; Blood Coagulation; Blood Coagulation Factors
PubMed: 38677260
DOI: 10.1016/j.jphotobiol.2024.112922 -
BMC Pulmonary Medicine Apr 2024Coronavirus disease 2019 (COVID-19) has been proved as a significant risk factor for deep vein thrombosis (DVT) after several waves of pandemic. This study aims to...
BACKGROUND
Coronavirus disease 2019 (COVID-19) has been proved as a significant risk factor for deep vein thrombosis (DVT) after several waves of pandemic. This study aims to further investigate impact of COVID-19 on prognosis of DVT following anticoagulation treatment.
METHODS
A total of 197 patients with initially detected DVT and meanwhile accomplishing at least 3 months anticoagulation treatment were identified from our hospital between January 2021 and December 2022. DVT characteristics, clinical data, and exposure to COVID-19 were recorded for multivariable logistic regression analysis to identify DVT aggravation related risk factors. Propensity score matching (PSM) was used to balance baseline covariates. Kaplan-Meier curves and Log-Rank test were performed to exhibit distribution of DVT aggravation among different subgroups.
RESULTS
In 2022, patients exhibited higher incidence rates of DVT aggravation compared to those in 2021 (HR:2.311, P = 0.0018). The exposure to COVID-19, increased red blood cell count, increased D-dimer level and reduced prothrombin time were found to be associated with DVT aggravation (P < 0.0001, P = 0.014, P < 0.001, P = 0.024), with only exposure to COVID-19 showing a significant difference between two years (2022:59/102, 57.84%, 2021:7/88, 7.37%, P < 0.001). In PSM-matched cohorts, the risk for DVT aggravation was 3.182 times higher in COVID-19 group compared to the control group (P < 0.0001). Exposure to COVID-19 increased the risk of DVT aggravation among patients who completed three months anticoagulant therapy (HR: 5.667, P < 0.0001), but did not increase incidence rate among patients who completed more than three months anticoagulant therapy (HR:1.198, P = 0.683). For patients with distal DVT, COVID-19 was associated with a significant increased risk of DVT recurrence (HR:4.203, P < 0.0001). Regarding principal diagnoses, incidence rate of DVT aggravation was significantly higher in COVID-19 group compared to the control group (Advanced lung cancer: P = 0.011, surgical history: P = 0.0365, benign lung diseases: P = 0.0418).
CONCLUSIONS
Our study reveals an increased risk of DVT aggravation following COVID-19 during anticoagulation treatment, particularly among patients with distal DVT or those who have completed only three months anticoagulant therapy. Adverse effects of COVID-19 on DVT prognosis were observed across various benign and malignant respiratory diseases. Additionally, extended-term anticoagulant therapy was identified as an effective approach to enhance DVT control among patients with COVID-19.
Topics: Humans; COVID-19; Venous Thrombosis; Female; Male; Anticoagulants; Retrospective Studies; Middle Aged; Prognosis; Aged; Risk Factors; SARS-CoV-2; Incidence; Propensity Score; Fibrin Fibrinogen Degradation Products; China
PubMed: 38671424
DOI: 10.1186/s12890-024-03036-3 -
Biochemia Medica Jun 2024This study aimed to investigate the effects of lipemia on clinical chemistry and coagulation parameters in native ultralipemic (NULM) and intravenous lipid emulsion... (Comparative Study)
Comparative Study
INTRODUCTION
This study aimed to investigate the effects of lipemia on clinical chemistry and coagulation parameters in native ultralipemic (NULM) and intravenous lipid emulsion (IVLE) spiked samples.
MATERIALS AND METHODS
The evaluation of biochemistry (photometric, ion-selective electrode, immunoturbidimetric method), cardiac (electrochemiluminescence immunoassay method) and coagulation (the viscosity-based mechanical method for prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen and the immunoturbidimetric method for D-dimer) parameters were conducted. In addition to the main pools, five pools were prepared for both types of lipemia, each with triglyceride (TG) concentrations of approximately 2.8, 5.7, 11.3, 17.0 and 22.6 mmol/L. All parameters' mean differences (MD%) were presented as interferographs and compared with the desirable specification for the inaccuracy (bias%). Data were also evaluated by repeated measures of ANOVA.
RESULTS
Prothrombin time and APTT showed no clinically relevant interference in IVLE-added pools but were negatively affected in NULM pools(P < 0.001 in both parameters). For biochemistry, the most striking difference was seen for CRP; it is up to 134 MD% value with NULM (P < 0.001) at the highest TG concentration, whereas it was up to - 2.49 MD% value with IVLE (P = 0.009). Albumin was affected negatively upward of 5.7 mmol/L TG with IVLE, while there was no effect for NULM. Creatinine displayed significant positive interferences with NULM starting at the lowest TG concentration (P = 0.028). There was no clinically relevant interference in cardiac markers for both lipemia types.
CONCLUSIONS
Significant differences were scrutinized in interference patterns of lipemia types, emphasizing the need for careful consideration of lipemia interferences in clinical laboratories. It is crucial to note that lipid emulsions inadequately replicate lipemic samples.
Topics: Humans; Hyperlipidemias; Fat Emulsions, Intravenous; Prothrombin Time; Partial Thromboplastin Time; Triglycerides; Blood Coagulation
PubMed: 38665874
DOI: 10.11613/BM.2024.020701 -
Advances in Hematology 2024The lack of preceding research in Sudan emphasizes the importance of this study, which contributes critical data to the global understanding of sleep-related health...
BACKGROUND
The lack of preceding research in Sudan emphasizes the importance of this study, which contributes critical data to the global understanding of sleep-related health effects. This study investigates the complex relationship between sleep deprivation and blood-related factors, particularly focusing on full blood count and coagulation parameters.
METHODS
From January to March 2022, a case-control study was conducted in Kosti, Sudan. A control group of 11 healthy 23-33-year-olds (6 men and 5 women) had regular sleep patterns. Six men and five women ages 23-33 were chosen for this sleep-deprived case study. The case group was deprived of sleep from 7:00 p.m. to 7:00 a.m. for three days and allowed to sleep normally during the day. Daily at 7:00 a.m., antecubital vein blood was drawn. The ACL 7000 coagulation analyzer and Sysmex fully automated hematology analyzers were used for coagulation and whole blood count analysis. Data analysis included descriptive and inferential approaches like the Mann-Whitney test for group comparisons.
RESULTS
The study found no significant differences in total white blood cell counts reported between case and control groups (=0.898). The case group had a substantial drop in lymphocyte counts on day 3 (=0.016). The third day showed significant differences in neutrophil and eosinophil levels (=0.003 and 0.000, respectively). The difference in hemoglobin and hematocrit on day 3 was statistically significant (=0.023). Platelet counts were stable. Both groups' prothrombin times were unaffected. On all three days, groups had significant differences in activated partial thromboplastin time (APTT) (=0.004). Therefore, the intrinsic coagulation system may have changed.
CONCLUSION
This study demonstrates the complex link between sleep deprivation, coagulation indicators, and complete blood count. Monitoring blood indicators in poor sleep helps explain fundamental mechanisms and medicinal implications.
PubMed: 38665768
DOI: 10.1155/2024/1766578 -
Bioscience Reports May 2024During inflammation and situations of cellular stress protein disulfide isomerase (PDI) is released in the blood plasma from the platelet and endothelial cells to...
During inflammation and situations of cellular stress protein disulfide isomerase (PDI) is released in the blood plasma from the platelet and endothelial cells to influence thrombosis. The addition of exogenous PDI makes the environment pro-thrombotic by inducing disulfide bond formation in specific plasma protein targets like vitronectin, factor V, and factor XI. However, the mechanistic details of PDI interaction with its target remain largely unknown. A decrease in the coagulation time was detected in activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) on addition of the purified recombinant PDI (175 nM). The coagulation time can be controlled using an activator (quercetin penta sulfate, QPS) or an inhibitor (quercetin 3-rutinoside, Q3R) of PDI activity. Likewise, the PDI variants that increase the PDI activity (H399R) decrease, and the variant with low activity (C53A) increases the blood coagulation time. An SDS-PAGE and Western blot analysis showed that the PDI does not form a stable complex with either thrombin or antithrombin (ATIII) but it uses the ATIII-thrombin complex as a template to bind and maintain its activity. A complete inhibition of thrombin activity on the formation of ATIII-thrombin-PDI complex, and the complex-bound PDI-catalyzed disulfide bond formation of the target proteins may control the pro- and anti-thrombotic role of PDI.
Topics: Humans; Protein Disulfide-Isomerases; Thrombin; Blood Coagulation; Antithrombin III; Protein Binding; Antithrombins; Quercetin
PubMed: 38660763
DOI: 10.1042/BSR20231540 -
Cureus Mar 2024Combined factor V and factor VIII deficiency (F5F8D) is an exceedingly rare autosomal recessive disease that causes concomitantly low levels of factor V and factor VIII,...
Combined factor V and factor VIII deficiency (F5F8D) is an exceedingly rare autosomal recessive disease that causes concomitantly low levels of factor V and factor VIII, leading to mild to moderate bleeding tendencies. Within this disorder, mutations manifest in the lectin mannose-binding protein (LMAN1) or multiple coagulation factor deficiency 2 (MCFD2) genes. This report presents a case of a five-year-old Saudi female child who was referred from an otolaryngology clinic, with an incidental finding of prolonged prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (aPTT) detected during routine preoperative investigations for tonsillectomy, prompting further investigations. There was no prior history of bleeding symptoms in the patient. She was discovered to have low assays of factor V and factor VIII on subsequent investigations. Whole exome sequencing revealed the novel homozygous mutation c.604C>T in the LMAN1 gene, validating the diagnosis of F5F8D.
PubMed: 38659545
DOI: 10.7759/cureus.56858 -
Cureus Mar 2024Cerebral palsy (CP) is a neurodevelopmental disorder that affects motor function and is often accompanied by secondary musculoskeletal issues. Severe scoliosis, a...
Cerebral palsy (CP) is a neurodevelopmental disorder that affects motor function and is often accompanied by secondary musculoskeletal issues. Severe scoliosis, a lateral curvature of the spine over 40 degrees, poses a significant challenge for individuals with CP, impacting their mobility and overall well-being. While the association between scoliosis and gastrointestinal complications is acknowledged, the occurrence of colonic volvulus with necrosis in the context of CP and severe scoliosis is rare and complex. This case report emphasizes the importance of clinical awareness in managing gastrointestinal complications in patients with CP and severe scoliosis. An 11-year-old female presented with gastroenteritis and a concurrent viral upper respiratory tract infection. She experienced complications such as greenish vomiting, hematemesis, abdominal distention, and constipation. The patient has a medical history of epilepsy and was diagnosed with quadriplegic CP at four months old due to viral meningitis. She is currently on anti-epileptic medications and receives regular follow-ups with neurology. Severe lumbar scoliosis of more than 50 degrees Cobb angle is also noted. Physical examination revealed dehydration, bilious content in nasogastric tube (NGT) aspiration, tender abdomen, and an empty digital rectal examination. Some laboratory findings showed elevated levels of erythrocyte sedimentation rate (ESR), prothrombin time (PT), blood urea nitrogen (BUN), and sodium, while albumin levels were decreased, and white blood cell (WBC) count was mildly elevated. Abdominal computed tomography (CT) with contrast showed a distended ascending colon with air and swirling of the mesentery. The distal half of the large bowel was not dilated, and fecal matter was present. The small bowel appeared to be collapsed, and there was moderate free fluid in the peritoneal cavity, indicating colonic volvulus involving the proximal large bowel. The patient underwent surgery, which involved deflating and removing the distended colon, resecting the gangrenous colon, and performing an ilio-sigmoid anastomosis to restore gastrointestinal continuity. Postoperatively, the patient received close monitoring in the pediatric intensive care unit (PICU), received total parenteral nutrition (TPN) for five days, gradually progressed feeding, and showed overall improvement in her condition. In conclusion, this case report highlights a rare occurrence of colonic volvulus in a patient with CP and severe scoliosis. It emphasizes the complex relationship between neurological and musculoskeletal disorders in gastrointestinal complications. A multidisciplinary approach is important for optimal management. It shows the importance of musculoskeletal factors in patients with neurological conditions. Overall, it contributes to the medical literature and emphasizes tailored management strategies for gastrointestinal issues in such patients.
PubMed: 38650790
DOI: 10.7759/cureus.56743 -
BMC Anesthesiology Apr 2024The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.
The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg·h. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg, Na and K also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.
Topics: Humans; Male; Female; Laparoscopy; Hepatectomy; Ringer's Lactate; Middle Aged; Isotonic Solutions; Postoperative Complications; Adult; Ringer's Solution; Lactic Acid; Bicarbonates; Treatment Outcome
PubMed: 38649834
DOI: 10.1186/s12871-024-02529-2