The objective of this study was to compare total thromboembolic complications between 4-factor prothrombin complex concentrate (4F-PCC) with factor VIII inhibitor bypassing activity (FEIBA) when utilized during cardiac surgery.

This study aimed to create an f9l mutant zebrafish using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and characterize its coagulation properties to investigate its functional similarity to human FX and explore the potential synergy between f9l and f10 .

In recent years, there has been a growing interest in the activated partial thromboplastin time clot waveform analysis (APTT-CWA), which reflects clot formation. It was mainly studied in hemophilia and disseminated intravascular coagulation. The aim of this study was to evaluate the usefulness of APTT-CWA in hemophilia carriers. This was a cross-sectional study including hemophilia carriers and healthy women volunteers. Bleeding assessment was performed using the ISTH-BAT. Laboratory assessment included APTT, APTT-CWA and FVIII:C or FIX:C. Thirty-two hemophilia carriers and 30 women as a control group were recruited. APTT was prolonged in 14 carriers and none of controls. Tmax 1 and Tmax 2 were significantly prolonged in hemophilia carriers compared to controls. Max 1 and Max 2 were significantly lower in carriers. Using ROC analysis, APTT-CWA parametrs cut-offs showed good sensitivity and specificity in discriminating between carriers and controls. When comparing bleeders and nonbleeders carriers, a significant difference was noted in Max 2, Min 2, Tmax 1 and Tmax 2. No correlation was found between APTT and bleeding score, nor between FVIII:C and Max 1. A positive significant correlation of FVIII:C with Max 2 was found. A negative and significant correlation of FVIII:C with Tmax 1, Tmax 2 and Min 2 was noticed. The APTT-CWA seems to be a good tool to evaluate bleeding tendency or detecting coagulation factor deficiency. Additional research efforts are warranted to explore the potential of APTT-CWA for identifying hemophilia carriers.

Immune thrombocytopenic purpura (ITP), the most common cause of thrombocytopenia, is clinically classified as acute and chronic. This study aimed to distinguish between acute/chronic ITP parameters examined at diagnosis via complete blood count (CBC), peripheral blood (PB) and bone marrow aspirate (BMA) smears. It would also contribute to early treatment options, cost-effective policies, and the life quality of patients.

Enhanced fibrinolysis or hyperfibrinolysis may lead to life-threatening blood loss, while reduced activity may contribute to thrombosis. Euglobulin clot lysis time (ECLT) is a manual method that measures plasma fibrinolytic activity and is considered the gold standard. However, the data on reference interval is scarce and outdated. We have employed one-sided reference interval (>3 h) since the implementation of ECLT in our laboratory; therefore, we aimed to establish reliable ECLT reference interval and to explore the possible preanalytical influence of different blood collection tubes on the established ECLT reference interval. Establishing a reference interval for fibrinolysis was performed according to CLSI EP28-A3c guidelines by employing a posteriori direct sampling technique. The predefined exclusion criteria included a history of malignant or hepatobiliary disease, a history of deep vein thrombosis/pulmonary embolism (DVT/PE), an acute inflammatory state at the time of the venipuncture. We collected vein blood samples in Vacutest plastic coagulation tubes (Kima, Italy) and Vacutainer glass coagulation tubes (Beckton Dickinson, USA) containing 0.109 mol/l buffered trisodium citrate as an anticoagulant at a blood-to-anticoagulant ratio 9 : 1. We calculated two-sided reference interval and presented as 2.5th and 97.5th percentiles. ECLT values did not differ between sexes or the types of tubes enrolled in the study ( P  = 0.8979). The established reference interval ranged from 130 to 297 min for the KIMA Vacutest tube and from 120 to 292 min for the BD Vacutainer tube. The established ECLT reference interval differed significantly from the currently used cut-off value in our laboratory, thus enabling the assessment of hyperfibrinolysis by employing double-sided reference interval.

Protein C deficiency is a rare autosomal recessive disorder associated with a high risk of thromboembolic complications. This case report describes the challenges in managing a 23-year-old woman with severe homozygous protein C type 1 deficiency diagnosed since early infancy. Her medical history included misdiagnosed cellulitis, recurrent thrombosis, and permanent vision loss in one eye. The laboratory workup confirmed a diagnosis of severe protein C deficiency. Management involved a combination of fresh frozen plasma (FFP), protein C concentrate, warfarin, and heparin, with ongoing challenges due to recurrent thrombosis and anaphylaxis to FFP. This case highlights the challenges in the diagnosis and management of severe protein C deficiency. Although current treatment options provide partial control, further research is crucial to develop safer and more effective therapies to improve long-term outcomes for affected patients.

Hereditary antithrombin (AT) deficiency due to mutations in SERPINC1 is known to be the most severe form of thrombophilia. We report three members in a family with hereditary AT deficiency with a novel mutation in exon 2 of SERPINC1, that is c.119 G>A (p.Cys40Tyr). Two brothers presented with acute pulmonary thromboembolism (PTE) at 18 and 21 years of age, whereas their 58-year-old father did not have any thrombotic episode till date. The in-silico prediction of the variant was found to be highly damaging by PolyPhen-2, SIFT and MutationTaster. Clinical exome sequencing did not show any strong coinherited thrombophilia genes, except SERPINE1 -844 G>A variant in homozygous state in the two affected brothers as compared to the father who was heterozygous for this variant. The additive effect of SERPINE1 variant in the clinical expression in two siblings cannot be ruled out, in the absence of any other known environmental triggering factors.

The purpose of this study was to determine the molecular basis of a Chinese family with factor XI (FXI) deficiency.

Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.

Congenital factor VII (FVII) deficiency is a genetic disorder characterized by decreased FVII activity, which sometimes leads to fatal bleeding. Numerous variants have been found in FVII deficiency, but mutations vary among patients. Each mutation deserves further exploration for each patient at risk of bleeding. We previously reported a Chinese patient with p.L68R∗37 and p.T241N compound heterozygous mutations. In this study, we further investigated the impact of these two mutations on the FVII expression through in vitro expression experiments.

Venous thromboembolism (VTE) risk in pregnant women is four to five-fold higher than in nonpregnant women, and the risk of VTE is an additional four-fold higher after Cesarean section compared to normal vaginal delivery. Recommendations regarding anticoagulant prophylaxis are inconsistent across international guidelines, and VTE remains one of the leading causes of maternal morbidity and mortality. This study aimed to compare the need for postcesarean anticoagulation for VTE prophylaxis based on three major guidelines and our own institutional protocol. It was a retrospective cohort study that reviewed the medical records of patients who underwent a cesarean section at a tertiary-level care hospital in the United Arab Emirates (UAE). The need for anticoagulation was assessed using clinical tools from the American College of Obstetricians and Gynecologists (ACOG), Royal College Obstetricians and Gynecologists (RCOG), American College of Chest Physicians (ACCP), and the study site hospital protocol. A total of 1134 postcesarean women, aged 18-55 years, were included in the study. Most patients (87%) were at moderate risk for VTE. According to the study site hospital tool, 90.7% qualified for anticoagulant prophylaxis, while the ACOG, RCOG, and ACCP tools indicated that 0.5, 90.9, and 36.7% qualified, respectively. Enoxaparin was the primary anticoagulant used in 95% of cases. Only one patient developed VTE during the follow-up period. Anticoagulation needs assessment tools vary extensively in their estimations, highlighting the need for a uniform tool across multiple societies to establish a consistent standard of care and guide the development of evidence-based, site-specific protocols.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.

Low dose of dabigatran paradoxically increased thrombin generation through inhibition of protein C activation. Protein S is a co-factor in the activation of protein C. However, the role of protein S in the enhancement of thrombin generation has not been addressed. Firstly, we measured thrombin generation by calibrated automated thrombinography (CAT) and prothrombin fragments 1+2 (F 1+2 ) assays. Secondly, we assessed activated protein C (APC) formation in normal or protein S-deficient plasma spiking with dabigatran. Then, protein C activation was measured. Finally, heavy chain of factor Va (FVa) and its degradation products were detected by western blot. CAT assay showed that 70-141 ng/ml dabigatran paradoxically increased thrombin generation in normal plasma. However, higher concentrations of dabigatran (283 ng/ml) suppressed the level of ETP. F 1+2 assay showed the similar results. In protein S-deficient or protein C-deficient plasma, the paradoxical increase in thrombin generation was absent. Level of generated APC was to a similar extent inhibited by dabigatran in normal and protein S-deficient plasma. Low-dose dabigatran inhibited the protein S-dependent inactivation of factor Va. Protein S participated in the paradoxical enhancement of thrombin generation in normal plasma spiking with low concentrations of dabigatran. Increased thrombin generation at low dabigatran can be explained by reduced thrombin-thrombomodulin mediated APC formation and subsequent reduced FVa inactivation that is protein S-dependent.

The typical phenotype of hemophilia A (HA) is that of frequent bleeding episodes, up to several per month, unless prophylactic factor VIII (FVIII) replacement or alternatives are given. Related bleeding may be heightened in severity or frequency by co-morbid bleeding disorders. Based on the reported prevalence of von Willebrand disease (VWD) of up to 1% of the general population, the co-existence of HA and VWD occurs, but is likely less recognized. Prophylactic FVIII replacement may or may not adequately prevent bleeding in persons with HA and mild VWD, and plasma-derived concentrates containing FVIII and von Willebrand factor (VWF) may be used for more successful bleeding prophylaxis. However, therapy adherence remains problematic for many reasons, one being treatment via intravenous access. Emicizumab is a nonfactor subcutaneous prophylactic therapy for HA that may overcome this concern. We describe three patients, with severe HA and VWD, for whom regular FVIII/VWF prophylaxis was deemed inadequate. FVIII/VWF prophylaxis was replaced with weekly prophylactic injections of the bispecific monoclonal antibody, emicizumab. When the patients were transitioned to emicizumab, all experienced a significant reduction in their annualized bleed rate (ABR). Although the mechanism of action does not directly affect or replace VWF function, emicizumab may be an effective prophylaxis alternative to FVIII/VWF concentrate in patients with concomitant severe HA and VWD.

Factor XIII (FXIII), a plasma transglutaminase, is a coagulation factor that plays a crucial role in blood clotting and patient blood management. The studies have demonstrated that FXIII targets a wide range of additional substrates that have an important role in hemostasis, especially in posttraumatic patients, patients undergoing surgery or obstetrics, being involved in wound healing and tissue repair. Morover, FXIII deficiency has also been described and an extensive research has shown that FXIII deficiency is a rare coagulopathy that leads to longer bleeding time, perioperative and postoperative complications and slower wound healing. Present article aims to overview the diverse functions of FXIII and to highlight its role in patient blood management.

Factor VII deficiency is a rare hemostatic disorder that can lead to severe clinical outcomes. Due to the scarcity of reported cases, treatment guidelines for this condition remain unclear. In this report, we present a case of acquired factor VII deficiency (aFVII) in an elderly female with medullary aplasia. The initial clinical manifestation was hemarthrosis, accompanied by a rapid increase in prothrombin time. Prompt intervention involved supplementation to address the deficiency. Subsequent laboratory testing failed to detect any specific factor VII inhibitor. Considering the patient's frailty, immunosuppressive therapy comprising only corticosteroids was administered. The potential triggering mechanisms may include recurrent episodes of sepsis or an underlying autoimmune condition. Further research is necessary to better understand the etiology and optimal management of aFVII deficiency.

Nowadays, direct oral anticoagulants (DOACs) represent the gold standard for venous thromboembolism (VTE) treatment and VTE secondary prophylaxis; nevertheless, the percentage of elderly patients in major trials and literature data about DOACs usage for VTE secondary prophylaxis in the elderly are scant. Our retrospective study tried to evaluate low-dose DOACs efficacy and safety for elderly VTE secondary prophylaxis in a real-life setting. A cohort of 73 patients (≥ 75 years) considered at high risk of VTE recurrence was treated with apixaban 2.5 mg twice daily (b.i.d.) or rivaroxaban 10 mg daily as VTE secondary prophylaxis. The median low-dose DOACs administration time was 18.40 months. Three (4.1%) VTE recurrence events were observed, with four bleeding events registered (5.5%), including one major bleeding (MB) (1.4%) and two clinically relevant non major bleeding (CRNMB) (2.7%). Our data suggest that low-dose DOACs may be effective and well tolerated for secondary VTE prophylaxis in elderly patients at high risk of VTE recurrence.

D-dimer is a fibrin degradation product and its measurement is affected by hemolysis. This study was designed to reveal the value of hemolysis affecting D-dimer in our laboratory. In this study, hemolysate samples obtained by both mechanical and freezing methods were used. D-dimer levels of all plasmas were measured with Improgen Diagnostic kit by immune-turbidimetric method. Numerical change in hemolyzed samples was evaluated by calculating the percentage difference, and clinically significant differences were evaluated by calculating the maximum acceptable bias (MAB). In the hemolysate study prepared by both freeze-thaw and mechanical methods, it was observed that low D-dimer levels did not exceed the total allowable error (TAE) (30%) up to +2 hemolysis (corresponds to hemoglobin = 1.01-2 g/l) and did not exceed the MAB (65%) even at +4 hemolysis (corresponds to hemoglobin = 1.01-2 g/l). High D-dimer levels did not exceed the limit values of both TAE (30%) and MAB (68%) even in +4 hemolysis. The D-dimer test was affected by lower levels of hemolysis compared to both other studies and the values in the kit insert (hemoglobin >5 g/l corresponds to +4 hemolysis index). We verified the hemolysis interference in the D-dimer test, which we thought was not compatible with the kit insert, under our own laboratory conditions. This is the first hemolysis interference study performed with the Improgen brand d-dimer kit. In samples with a hemolysis rate of +2 and above, it would be more accurate to reject the D-dimer result as a 'hemolyzed sample'.

Cancer-associated thrombosis (CAT) is a common complication and a major cause of morbidity and mortality in patients with active cancers. CAT is common in various malignancies, particularly pancreatic, ovarian, gastric, colorectal, and hematologic cancers. In fact, CAT is a complicated multifactorial complication that may be influenced by the type of cancer as well as by the genetic background and inheritance of thrombophilic variants and elevated concentrations of coagulation factors. Several studies have shown the prominent role of inherited thrombophilias, such as prothrombin 20210, factor V Leiden, factor XIII Val34Leu, MTHFR C677T, in the occurrence of CAT, while others have found no correlation between them and CAT. In the present review, we have attempted to investigate the possible role of inherited thrombophilia in the occurrence of CAT.

Thrombotic thrombocytopenic purpura (TTP) is one of the rare group disorders classified as thrombotic microangiopathies (TMAs). Approximately 90% of TTP developed immune-mediation by the formation of antibodies against the enzyme ADAMTS-13. The exact cause is unknown. To establish an association between human leukocyte antigen (HLA) and autoimmune basis, as susceptibility or protection against the disease, we contributed a study aiming to evaluate the role of HLA in immune-mediated TTP (iTTP). Considering epidemiological factors such as age, sex, ethnicity, and geographical origins, we contributed the study in our country, Turkey, which consist of a very heterogeneous population. Patients' data collection was retrospectively from electronic database on two University hospitals having big therapeutic apheresis service. Control arm was healthy people registered as stem cell donors matched in terms of age and sex. The frequency of HLA-DRB1 and HLA-DQB1 alleles between acquired TTP and the control group was compared using the chi-square method. Yates correction and logistic regression were performed on these results. A total of 75 iTTP patients and 150 healthy individuals enrolled to the study. HLA-DRB1∗11, HLA-DQB1∗03, HLA-DRB1∗11:01, HLA-DRB1∗14:01, HLA-DRB1∗13:05, HLA-DRB1∗11 + HLA-DQB1∗03 allele pair and HLA-DRB1∗15 + HLA- DQB1∗06 were proved to be susceptibility allele pairs for iTTP. HLA-DRB1∗15, HLA-DRB1∗01:01, HLA-DRB1∗07:01, HLA-DRB1∗13:01, HLA-DRB1∗14:54, HLA-DQB1∗05:01, HLA-DQB1∗02:02 and HLA-DRB1∗07 + HLA-DQB1∗02 allele pair were found to be protective against iTTP. Our findings support an association with iTTP across very heterogenous populations in Turkey.