Blood Coagulation & Fibrinolysis最新文献

Objectives: Ligneous conjunctivitis (LC) is a chronic conjunctivitis characterized by recurrent, firm, fibrin-rich, woody pseudomembranes on the palpebral conjunctiva. It is an ultrarare autosomal recessive disease associated with congenital plasminogen (PLG) deficiency due to mutations in the PLG gene (6q26). Immunoglobulin G4-related disease (IgG4-RD) is an idiopathic, systemic fibroinflammatory disease characterized by elevated serum IgG4 concentration and tissue infiltration of IgG4-positive plasma cells leading to organ enlargement, fibrosis and damage.

Case report: A 7-year-old girl with LC was hospitalized for recurrent pancreatitis and diagnosed as IgG4-RD. PLG activity level was 15% (normal range 55-145%). Co-segregation analysis indicated that the patient was homozygous for the c. NG_016200.1(NM_000301.5):c.1465 T>C mutation in PLG gene. c. NG_016200.1(NM_000301.5):c.1465 T>C PLG variant was found to be heterozygous by NGS analysis in both parents. She also had plasminogen activator inhibitor - 1 (PAI-1) NG_013213.1(NM_000602.5):c.-816A>G (4G/4G) homozygous polymorphism and a heterozygote NG_001333.2 (NM_002769.5):c.292_293insC mutation in the serine protease 1 (PRSS-1) gene. However, heterozygous PRSS-1NG_001333.2 (NM_002769.5):c.292_293insC variant was found in the mother of the patient. All detected variants are currently considered as a variant of uncertain (or unknown) significance (VUS) according to the American College of Medical Genetics and Genomics (ACMG) classification. Oral steroid, oral azathioprine, topical fresh frozen plasma, topical heparin, topical steroid and topical cyclosporine were given. After 3 years of follow-up, IgG4-RD is under partial remission and no pseudomembranes.

Conclusion: She is the second case had both LC and IgG4-RD. We identified a NG_016200.1(NM_000301.5):c.1465 T>C novel homozygous mutation in PLG gene and a PAI-1 NG_016200.1(NM_000301.5):c.1465 T>C (4G/4G) homozygous polymorphism, which has been reported as a risk factor for thrombotic events.

Background: Oral contraceptives are commonly taken by women and are known to increase the risk of venous thromboembolism (VTE).

Objective: The aim of this study was to investigate the association between oral contraceptive use and natural anticoagulants, that is, protein C (PC), protein S (PS), and antithrombin in pregnant women with deep vein thrombosis (DVT).

Materials and methods: This case-control study was conducted on 330 pregnant women, that is, cases 165 (who used oral contraceptives) and controls 165 (who did not use oral contraceptives). The levels of PC, PS, and antithrombin were measured and compared between the two groups. The use of different types of oral contraceptives and their association with DVT and PC and PS were also analyzed.

Results: The study found that women with DVT had significantly lower levels of PC and PS compared with controls ( P  < 0.001). However, no significant difference was found in the levels of AT. Among the different types of oral contraceptives, first-generation progestin pills including Ethynodiol Diacetate, Norethindrone Acetate, Norethynodrel, and second-generation oral contraceptives (Lynestrenol, Levonorgestrel and Norgestrel) were not found to be associated with lower levels of PC and AT while Desogestrel, Norgestimate, and Gestodene (third-generation) were associated with lower levels of PS.

Conclusion: This study suggests that the use of contraceptives, particularly those containing Desogestrel, Norgestimate, and Gestodene, may be associated with a higher risk of thrombosis because of the associated lower levels of PS. Monitoring anticoagulant levels is crucial in preventing DVT in this population.

Introduction: Patients with systemic lupus erythematosus (SLE) have an increased risk of vascular thrombosis compared to the general population. Therefore, biomarkers for predicting the risk of thrombosis in patients with SLE are needed.

Methods: In the present study, a total of 66 patients with SLE (22 with and 44 without a history of thrombosis) were enrolled. The cases with thrombosis and the controls without thrombosis were matched for age (± 5 years) and sex. We assessed ADAMTS13 activity, D-dimer levels, and antiphospholipid antibodies. Clinical manifestations, SLE disease activity, classical risk factors, and medical history were collected.

Results: ADAMTS13 activity was significantly reduced, and D-dimer levels were significantly increased in patients with SLE with a history of thrombosis compared with those in patients without thrombosis. Receiver operating characteristic curve analysis revealed a good correlation between reduced ADAMTS13 activity and a history of thrombosis. Reduced ADAMTS13 activity was correlated with increased D-dimer levels only in the thrombotic group.

Conclusion: Reduced ADAMTS13 activity and high D-dimer levels are associated with thrombosis and may serve as prognostic markers for thrombosis in patients with SLE.

Extended half-life recombinant FIX (rFIX) molecules have been generated to reduce the dosing burden and increase the protection of patients with hemophilia B. Clinical pharmacology studies with recombinant factor IX Fc fusion protein (rFIXFc) report a similar initial peak plasma recovery to that of rFIX, but with a larger volume of distribution. Although the pegylation of N9-GP results in a larger plasma recovery, there is a smaller volume of distribution, suggesting less extravasation of the latter drug. In this study, we set out to compare the biodistribution and tissue localization of rFIX, rFIXFc, and glycoPEGylated rFIX in a hemophilia B mouse model. Radiolabeled rFIX, rFIXFc, and rFIX-GP were employed in in vivo single-photon emission computed tomography imaging (SPECT/CT), microautoradiography (MARG), and histology to assess the distribution of FIX reagents over time. Immediately following injection, vascularized tissues demonstrated intense signal irrespective of FIX reagent. rFIX and rFIXFc were retained in joint and muscle areas through 5 half-lives, unlike rFIX-GP (assessed by SPECT). MARG and immunohistochemistry showed FIX agents localized at blood vessels among tissues, including liver, spleen, and kidney. Microautoradiographs, as well as fluorescent-labeled images of knee joint areas, demonstrated retention over time of FIX signal at the trabecular area of bone. Data indicate that rFIXFc is similar to rFIX in that it distributes outside the plasma compartment and is retained in certain tissues over time, while also retained at higher plasma levels. Overall, data suggest that Fc fusion does not impede the extravascular distribution of FIX.

A 71-year-old female with heart failure who underwent left ventricular assist device (LVAD) placement presented for evaluation of low hemoglobin and dark stools. She also had leg pain, numbness, and weakness for which she was taking ibuprofen. She was found to have a gastrointestinal bleed, INR of 4.3, and arterial thrombi in the left leg. She was stabilized, had her anticoagulation held, and underwent mechanical thrombectomy. On hospital day 6, LVAD interrogation revealed signs of thrombosis, while subsequent labs revealed a persistently supratherapeutic INR of 5.2. The patient had the LVAD removed and underwent further hematologic workup. Her platelets remained normal throughout the admission, indicating this was not acute disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), or heparin induced thrombocytopenia (HIT). Echocardiography identified it as a primary thrombus. This case illustrates the importance of appropriate anticoagulation to balance the bleeding risk with the risk of thrombi, as well as the importance of maintaining high suspicion for LVAD thrombosis regardless of INR.

Objectives: Degradation of coagulation proteins in frozen plasma may influence assay results. The aims of this study were to explore the changes in coagulation parameters in patient plasma and internal quality control (IQC) after different freezing and storage conditions during the short-term and long-term periods.

Methods: Platelet poor plasma was prepared from citrated peripheral blood collected from a group of healthy donors. The plasma was pooled, frozen and stored in a variety of freezing and storage conditions. The changes were monitored using routine coagulation assays, as well as factor VIII (FVIII) and protein S (PS) assays.

Results: Plasma stored in liquid nitrogen (LN 2 ) or in -80°C showed long-term stable values for routine tests for a period of over 12 months, and 6 months for FVIII. Interestingly, the activated partial thromboplastin time (aPTT) showed a temporary significant prolongation over the first two weeks. Plasma frozen and stored in -40°C is not viable for aPTT and FVIII testing, otherwise it can be used for other parameters for up to 4 months. PS showed a significant increase in all frozen samples. Freezing rate has a significant impact on plasma quality and the final storage temperature influences the long-term stability.

Conclusion: The optimal storage conditions are ultra-low temperatures (LN 2 or -80°C) and the highest freezing rate possible. However, frozen plasma is not viable for IQC of aPTT during a period of two weeks after freezing. This study is unique in its conception as a practical guide for the handling of frozen plasma samples in modern laboratory settings.

Background: Placenta-related obstetric complications (PROCs) such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth are the major causes of maternal and fetal morbidity and mortality. The objective of this study was to search the relevance of plasminogen activator inhibitor-1 (PAI-1) polymorphisms and co-morbidities and the risk factors for PROCs such as miscarriage, fetal growth restriction, preeclampsia, and preterm birth.

Method: This retrospective study analyzed the PAI-1 genotype in a cohort of 268 multiparous women with poor obstetric history. Poor obstetric history was defined as the presence of at least one of the PROCs and/or poor gestational outcomes at the previous pregnancy/pregnancies.

Results: 5G allele frequency was higher than the 4G allele frequency in the cohort (0.767 vs. 0.233). The frequencies of having at least one risk factor are relatively similar among the different PAI-1 genotypes ( P  > 0.05). However, the presence of MTHFR polymorphisms (homozygous and compound heterozygous forms of C677T and A1298G) and hereditary thrombophilia (Factor V Leiden and prothrombin G20210A gene mutations, and FXIII deficiency) were found to be associated with PAI 4G/4G ( P  = 0.048) and 5G/5G ( P  = 0.022) genotypes, respectively. Significant differences were not observed in other risk factors and co-morbidities such as autoimmune disorders, chronic inflammatory diseases, history of venous thromboembolism, carbohydrate metabolism disorders, hyperlipidemia, cardiovascular and cerebrovascular diseases depending on PAI-1 genotypes ( P  > 0.05).

Conclusion: MTHFR polymorphisms were found to be associated with PAI 4G/4G genotype, while 5G/5G genotype was observed more frequently in hereditary thrombophilia cases.

Objectives: Angiographic high thrombus burden (HTB) is associated with increased adverse cardiovascular events in patients with ST-elevation myocardial infarction (STEMI). HbA1c and C-peptide are two interrelated bioactive markers that affect many cardiovascular pathways. HbA1c exhibits prothrombogenic properties, while C-peptide, in contrast, exhibits antithrombogenic effects. In this study, we aimed to demonstrate the value of combining these two biomarkers in a single fraction in predicting HTB and short-term mortality in patients with STEMI.

Methods: 1202 patients who underwent primary percutaneous coronary intervention (pPCI) for STEMI were retrospectively included in this study. The study population was divided into thrombus burden (TB) groups and compared in terms of basic clinical demographics, laboratory parameters and HbA1c/C-peptide ratios (HCR). In addition, short-term mortality of the study population was compared according to HCR and TB categories.

Results: HCR values were significantly higher in the HTB group than in the LTB group (3.5 ± 1.2 vs. 2.0 ± 1.1; P  < 0.001; respectively). In the multivariable regression analysis, HCR was determined as an independent predictor of HTB both as a continuous variable [odds ratio (OR): 2.377; confidence interval (CI): 2.090-2.704; P  < 0.001] and as a categorical variable (OR: 5.492; CI: 4.115-7.331; P  < 0.001). In the receiver operating characteristic (ROC) analysis, HCR predicted HTB with 73% sensitivity and 72% specificity, and furthermore, HCR's predictive value for HTB was superior to HbA1c and C-peptide. The Kaplan-Meier cumulative survival curve showed that short-term mortality increased at HTB. In addition, HCR strongly predicted short-term mortality in Cox regression analysis.

Conclusions: In conclusion, HCR is closely associated with HTB and short-term mortality in STEMI patients.