Consumption Of Coagulation Factors Research Articles

TRIM28 regulates the coagulation cascade inhibited by p72 of African swine fever virus.

In 2018, African swine fever virus (ASFV) emerged in China, causing extremely serious economic losses to the domestic pig industry. Infection with ASFV can cause disseminated coagulation, leading to the consumption of platelets and coagulation factors and severe bleeding. However, the mechanism of virus-induced coagulation has yet to be established. In our study, ASFV downregulated the coagulation process, as detected by D-dimer (D2D) and Factor X (F10) expression in pigs challenged with ASFV HLJ/18. In vitro, ASFV infection increased Factor IX (F9) and Factor XII (F12) expression while downregulating F10 expression in porcine alveolar macrophages (PAMs). African swine fever virus induced both intrinsic and extrinsic coagulation cascades. In addition, several encoded proteins affect the expression of the crucial coagulation protein F10, and among the encoded proteins, p72 inhibits the activity and expression of F10. Proteomic analysis also revealed that p72 is involved in the coagulation cascade. p72 can interact with F10, and its inhibitory functional domains include amino acids 423-432 and amino acids 443-452. Finally, we found that F10 and p72 interact with tripartite motif-containing protein 28 (TRIM28). TRIM28 knockdown resulted in a decrease in F10 expression. Importantly, TRIM28 contributes to the reduction in F10 protein expression regulated by p72. Our findings revealed an inhibitory effect of the viral protein p72 on the ASFV infection-induced coagulation cascade and revealed a role of TRIM28 in reducing F10 expression, revealing a molecular mechanism of ASFV-associated coagulation.

The effects of an aggressive breast tumor on thrombosis after antithrombin downregulation in a hypercoagulable mouse model

BackgroundDespite improvements in therapy, breast cancer still contributes to high mortality rates. Survival of these patients becomes progressively worse upon diagnosis with cancer-associated thrombosis (CAT). Unfortunately, the mechanism causing CAT has remained unclear. ObjectiveSet up an acute and non-invasive hypercoagulable mouse model with an aggressive breast cancer and study the mechanism of cancer-associated thrombosis. MethodsMice were grafted with the aggressive breast cancer cell line MDA-MB-231 or sham-treated. Subsequently, an acute imbalance in coagulation was introduced by injecting a synthetic small interfering (si) RNA targeting hepatic Serpinc1 to knockdown antithrombin – a condition known to predispose to cause a hypercoagulant state in vivo. ResultsSilencing Serpinc1 with siRNA decreased plasma antithrombin levels. siRNA treatment had no short-term effects on tumor characteristics, but increased distant metastasis within the timeframe of this study. The systemic pro-inflammatory status, with elevated platelet counts and fibrinogen levels in tumor-bearing mice, was also not affected by antithrombin silencing. While elevated fibrin deposition in the liver upon Serpinc1 targeting was not significantly affected by the presence of breast cancer, knockdown of antithrombin did significantly increase intratumoral fibrin deposition and inflammation. Surprisingly, in the presence of an aggressive tumor, a protective outcome with less clinical features coinciding with venous thrombosis were observed in mice with antithrombin knockdown. ConclusionWe conclude that the presence of a breast tumor protects hypercoagulant mice from severe consumption of coagulation factors after lowering hepatic antithrombin levels, possibly due to elevated platelet counts. However, the consequences on cancer-associated thrombosis remained inconclusive.

Thromboinflammation in COVID-19: Unraveling the interplay of coagulation and inflammation.

The coronavirus disease 2019 (COVID-19) pandemic has not only challenged global health systems but also spurred intense scientific inquiry into its pathophysiology. Among the multifaceted aspects of the disease, coagulation abnormalities have emerged as a significant contributor to morbidity and mortality. From endothelial dysfunction to dysregulated immune responses, various factors contribute to the hypercoagulable state seen in severe COVID-19 cases. The dysregulation of coagulation in COVID-19 extends beyond traditional thromboembolic events, encompassing a spectrum of abnormalities ranging from microvascular thrombosis to disseminated intravascular coagulation (DIC). Endothelial injury induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers a cascade of events involving platelet activation, coagulation factor consumption, and fibrinolysis impairment. Moreover, the virus direct effects on immune cells and the cytokine storm further exacerbate the prothrombotic milieu. Unraveling this intricate web of interactions between viral pathogenesis and host responses is essential for elucidating novel therapeutic targets and refining existing management strategies for COVID-19-associated coagulopathy. In the quest to unravel the complex interplay between coagulation and COVID-19, numerous clinical and laboratory studies have yielded invaluable insights into potential biomarkers, prognostic indicators, and therapeutic avenues. Anticoagulation therapy has emerged as a cornerstone in the management of severe COVID-19, although optimal dosing regimens and patient selection criteria remain subjects of ongoing investigation. Additionally, innovative approaches such as targeting specific components of the coagulation cascade or modulating endothelial function hold promise for future therapeutic development.

Study on the procoagulant characteristics of microparticles in acute myocardial infarction

To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation. A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators. A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016). The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.

Tocilizumab administration in cytokine release syndrome is associated with hypofibrinogenemia after chimeric antigen receptor T-cell therapy for hematologic malignancies.

Chimeric antigen receptor (CAR) T-cell therapy causes serious side effects including cytokine release syndrome (CRS). CRS-related coagulopathy is associated with hypofibrinogenemia that has up to now been considered the result of disseminated intravascular coagulation (DIC) and liver dysfunction. We investigated the incidence and risk factors for hypofibrinogenemia in 41 consecutive adult patients with hematologic malignancies (median age 69 years, range 38-83 years) receiving CAR T-cell therapy between January 2020 and May 2023 at the University Medical Center Regensburg. CRS occurred in 93% of patients and was accompanied by hypofibrinogenemia already from CRS grade 1. Yet DIC and liver dysfunction mainly occurred in severe CRS (≥ grade 3). After an initial increase during CRS, fibrinogen levels dropped after administration of tocilizumab in a dose-dependent manner (r = -0.44, P=0.004). In contrast, patients who did not receive tocilizumab had increased fibrinogen levels. Logistic regression analysis identified tocilizumab as an independent risk factor for hypofibrinogenemia (odds ratio = 486, P<0.001). We thus hypothesize that fibrinogen synthesis in CRS is up-regulated in an interleukin-6-dependent acute phase reaction compensating for CRS-induced consumption of coagulation factors. Tocilizumab inhibits fibrinogen upregulation resulting in prolonged hypofibrinogenemia. These observations provide novel insights into the pathophysiology of hypofibrinogenemia following CAR T-cell therapy, and emphasize the need for close fibrinogen monitoring after tocilizumab treatment of CRS.

Blood Transfusion for Major Trauma in Emergency Department.

Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are related to neurological dysfunction and typically happen within two days of trauma; and approximately 20% of patients died of multiorgan failure and sepsis within days to weeks of the traumatic event. Over the past ten years, there has been an increased understanding of the underlying mechanisms and pathophysiology associated with traumatic bleeding leading to improved management measures. Traumatic events cause significant tissue damage, with the potential for severe blood loss and the release of cytokines and hormones. They are responsible for systemic inflammation, activation of fibrinolysis pathways, and consumption of coagulation factors. As the final results of this (more complex in real life) cascade, patients can develop tissue hypoxia, acidosis, hypothermia, and severe coagulopathy, resulting in a rapid deterioration of general conditions with a high risk of mortality. Prompt and appropriate management of massive bleeding and coagulopathy in patients with trauma remains a significant challenge for emergency physicians in their daily clinical practice. Our review aims to explore literature studies providing evidence on the treatment of hemorrhage with blood support in patients with trauma admitted to the Emergency Department with a high risk of death. Advances in blood transfusion protocols, along with improvements in other resuscitation strategies, have become one of the most important issues to face and a key topic of recent clinical research in this field.

CT-001, a novel fast-clearing factor VIIa, enhanced the hemostatic activity in postpartum samples

AbstractThe hemostatic system is upregulated to protect pregnant mothers from hemorrhage during childbirth. Studies of the details just before and after delivery, however, are lacking. Recombinant factor VIIa (rFVIIa) has recently been granted approval by the European Medicines Agency for the treatment of postpartum hemorrhage (PPH). A next-generation molecule, CT-001, is being developed as a potentially safer and more efficacious rFVIIa-based therapy. We sought to evaluate the peripartum hemostatic status of pregnant women and assess the ex vivo hemostatic activity of rFVIIa and CT-001 in peripartum blood samples. Pregnant women from 2 study sites were enrolled in this prospective observational study. Baseline blood samples were collected up to 3 days before delivery. Postdelivery samples were collected 45 (±15) minutes after delivery. Between the 2 time points, soluble fibrin monomer and D-dimer increased whereas tissue factor, FVIII, FV, and fibrinogen decreased. Interestingly, the postdelivery lag time and time to peak in the thrombin generation assay were shortened, and the peak thrombin generation capacity was maintained despite the reduced levels of coagulation proteins after delivery. Furthermore, both rFVIIa and CT-001 were effective in enhancing clotting activity of postdelivery samples in activated partial thromboplastin time, prothrombin time, thrombin generation, and viscoelastic hemostatic assays, with CT-001 demonstrating greater activity. In conclusion, despite apparent ongoing consumption of coagulation factors at the time of delivery, thrombin output was maintained. Both rFVIIa and CT-001 enhanced the upregulated hemostatic activity in postdelivery samples, and consistent with previous studies comparing CT-001 and rFVIIa in vitro and in in vivo, CT-001 demonstrated greater activity than rFVIIa.

GO-8: Stable Expression of Factor VIII over 5 Years Following Adeno-Associated Gene Transfer in Subjects with Hemophilia a Using a Novel Human Factor VIII Variant

Background: GO-8 (ClinicalTrials.gov: NCT03001830) is a study of liver-directed adeno-associated virus (AAV) gene therapy for haemophilia A (HA) that uses a factor VIII (FVIII) variant containing a 17 amino-acid peptide comprising six N-linked glycosylation motifs from the human FVIII B-domain (AAV-HLP-hFVIII-V3). In preclinical studies, AAV-HLP-hFVIII-V3 mediated a 3-fold higher FVIII expression when compared to an identical AAV construct encoding the hFVIII-SQ variant used in most HA gene therapy trials. Methods: In a multi-centre, open-label, non-randomised, phase I/II clinical trial, we assessed the safety and efficacy of escalating doses of AAV-HLP-hFVIII-V3 pseudotyped with an AAV8 capsid in adults with severe haemophilia A (FVIII activity ≤1%). All participants received prophylactic glucocorticoids, with or without tacrolimus, with the aim of reducing the risk of vector-related transaminase elevation. The primary endpoints were safety and efficacy. Efficacy was assessed by measuring FVIII activity (FVIII: C) using both chromogenic and one-stage clotting assays and factor consumption pre and post-gene therapy. Results: As of May 31 2023, 12 participants were enrolled sequentially into one of four vector doses: 6×1011 vector genomes (vg)/kg body weight (n=1), 2×1012 vg/kg (n=3), 4×1012 vg/kg (n=3), or 6×1012 vg/kg (n=5). All participants were on FVIII prophylaxis prior to gene therapy. The most common vector-related adverse event was an elevation in liver aminotransferase levels, which occurred in 10 of 12 participants. In 7 of the 8 participants treated at doses ≥4×1012 vg/kg, recurrent elevation in aminotransferase levels was observed during the first 12 months, often associated with tapering of immunosuppression. This resulted in a reduction in transgene expression from peak levels in all participants, with a complete loss of transgenic protein in one participant. Vector-related elevation in aminotransferase was not observed after the 12-month time point in long-term follow-up. Mean chromogenic FVIII: C levels at 12 months after gene therapy were 3 IU/dL in the 6×1011 vg/kg cohort, 13±9IU/dL (range: 2-19 IU/dl) in the 2×1012 vg/kg cohort, 8±1IU/dl in the 4×1012 vg/kg cohort (range: 7-9 IU/dl) and 22±34 IU/dl in the 6×1012 vg/kg cohort (range 1-82 IU/dl). Transgene expression was then stably maintained over a median follow-up of 3 years (range: 0.2-5 years) from the level achieved 1-year post-infusion, best illustrated by the data from the 2×1012 and 4×1012 vg/kg cohorts shown in Figure 1. FVIII: C was, on average 2-fold higher when measured using a one-stage clotting assay compared to the chromogenic method. Nine of the 12 participants remained off prophylaxis after gene therapy for the duration of the follow-up period. Baseline mean and median annualised factor VIII use was 4097 and 4657 IU/kg per year before gene therapy. Following gene therapy, the mean and median annualised factor VIII concentrate use reduced across all participants to 1186 and 61 IU/kg (One sample t-test p=0.0009), respectively. No FVIII inhibitors or thrombotic events were reported for the duration of the study. Conclusion: A single infusion of AAV-HLP-hFVIII-V3 resulted in stable FVIII expression over a follow-up period of up to 5 years in participants with severe haemophilia A. A high rate of liver aminotransferase elevation following gene transfer impacted transgene expression. However, 9 of the 12 participants were able to discontinue FVIII prophylaxis over the duration of the study, resulting in a significant reduction in FVIII concentrate usage.

Trauma-induced coagulopathy: What you need to know.

Trauma-induced coagulopathy (TIC) is a global inflammatory state accompanied by coagulation derangements, acidemia, and hypothermia, which occurs after traumatic injury. It occurs in approximately 25% of severely injured patients, and its incidence is directly related to injury severity. The mechanism of TIC is multifaceted; proposed contributing factors include dysregulation of activated protein C, increased tPA, systemic endothelial activation, decreased fibrinogen, clotting factor consumption, and platelet dysfunction. Effects of TIC include systemic inflammation, coagulation derangements, acidemia, and hypothermia. Trauma-induced coagulopathy may be diagnosed by conventional coagulation tests including platelet count, Clauss assay, international normalized ratio, thrombin time, prothrombin time, and activated partial thromboplastin time; viscoelastic hemostatic assays such as thrombelastography and rotational thrombelastography; or a clinical scoring system known as the Trauma Induced Coagulopathy Clinical Score. Preventing TIC begins in the prehospital phase with early hemorrhage control, blood product resuscitation, and tranexamic acid therapy. Early administration of prothrombin complex concentrate is also being studied in the prehospital environment. The mainstays of TIC treatment include hemorrhage control, blood and component transfusions, and correction of abnormalities such as hypocalcemia, acidosis, and hypothermia. Therapeutic/Care Management; Level III.

An approach to reducing blood loss during reconstructive operations on the bones of the skull in children with craniosynostosis

Background. Radical reconstructive operations on the bones of the skull in children with craniostenoses are always accompanied by significant intraoperative blood loss. The range of blood saving methods for children is narrower than for adults. Unfortunately, the incidence of post-transfusion reactions and complications remains high, and for infants who have undergone traumatic surgery, the occurrence of such a complication can be fatal. This dictates the need to search for new and effective methods of blood saving for children, which is especially important in the surgical treatment of various forms of craniosynostosis.The objective was to evaluate the effectiveness of the developed approach to reducing blood loss during radical reconstructive operations on the bones of the skull in children. Study design: cohort, prospective studyMaterials and methods. Design: a cohort, prospective study, which included 50 children diagnosed with craniosynostosis who underwent radical reconstructive surgery on the bones of the skull. To reduce blood loss, the developed approach was used, which included hypervolemic hemodilution, the introduction of an antifibrinolytics and infiltration of the skin flap with a local anesthetic before surgical incision. During the operation, the volume of blood loss, the level of hemoglobin, hematocrit, acid-base state were recorded at 3 stages of surgical treatment. The international normalized ratio, activated partial thromboplastin time, fibrinogen concentration were evaluated before surgical treatment and at the end of surgery. A comparative analysis of approaches to replacement of intraoperative blood loss before and after the introduction of the proposed method of blood saving was carried out.Results. The level of blood loss in most cases corresponded to 1 and 2 degrees. Hemotransfusions were performed in 23 children (46%). Prior to the introduction of the proposed method of blood saving, intraoperative blood transfusion was performed in 100% of patients. Comparison of the coagulation system indicators before the operation and at the end of the 3rd stage of the operation showed statistically significant differences and corresponded to their active consumption. Evaluation of SO2, ctO2, P50 indicators at all stages of the operation showed no deviation from normal valuesConclusion. The average level of blood loss in the surgical treatment of craniosynostosis in children corresponds to 1–2 degrees. The level of consumption of blood clotting factors increases by the end of the main stage of surgical treatment, but does not reach the indicators at which there is a need to use freshly frozen plasma (NWF). A developed approach to the correction of blood loss in children with craniosynostosis, including: the use of hypervolemic hemodilution, the introduction of tranexamic acid, infiltration of the skin flap with a local anesthetic with epinephrine before surgical incision, infusion therapy in a restrictive mode after surgical incision allowed minimizing the use of blood preparations.

Parole chiave. Appropriatezza prescrittiva, consumi farmaceutici, emofilia, fattori della coagulazione, malattia di von Willebrand, malattie emorragiche congenite.

Therapeutic strategies for the treatment of congenital bleeding disorders. Congenital hemorrhagic diseases (CHDs) are a group of rare disorders caused by quantitative or qualitative deficiency of one or more coagulation factors. Haemophilia A, Haemophilia B, and von Willebrand disease are the most common congenital bleeding disorders. Over the past decades, the evolution of CHDs treatments has resulted in an increase in the average life expectancy of patients and in an improvement in their quality of life; it has also enabled the prevention of bleeding complications much more effectively than in the past. This has been possible, especially for haemophilia, mainly because of earlier diagnosis, introduction of recombinant factors, especially long-acting factors, and availability of new non-substitutive therapies. In 2021, there was an increase in the overall expenditure and consumption of coagulation factors in Italy; the increase concerned especially the long-acting recombinant factors used in the treatment of Haemophilia A and B and the monoclonal antibody emicizumab. Waiting for innovative therapies that can enable individually tailored therapies, special attention must be paid to prescriptive appropriateness and to identify the best diagnostic and therapeutic care pathways for patients.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

Expert Consensus on the Use of Human Serum Albumin in Adult Cardiac Surgery.

The History of Extracorporeal Membrane Oxygenation and the Development of Extracorporeal Membrane Oxygenation Anticoagulation.

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the "Father of ECMO"-Dr. Robert Bartlett, describe the history and advances of ECMO.

Management of massive transfusion and coagulation during bilateral hand transplantation surgery

Dear Editor, Massive transfusion (MT) aims to limit hypoperfusion till surgical hemostasis could be attained and takes into account volume status, tissue oxygenation, management of bleeding, and coagulation abnormalities.[1] However, it may not be possible to follow recommended protocols of MT strictly during hand transplant surgeries as, in addition to restoring blood volume, ensuring good perfusion and avoidance of thrombus formation in transplanted hands is critical. A 46 year-old-female, bilateral hand amputee, was posted for bilateral upper extremity allotransplantation (supracondylar level on the right side and mid-arm level on the left side). The donor was a 45 year-old-female who was declared brain dead following trauma. The recipient received standardized general anesthesia and immunosuppressants as per protocol. Femoral arterial, internal jugular, femoral venous, and two 16G saphenous catheters were placed. Her initial hemoglobin was 13.2 g/dL. Reperfusion of transplanted hands was done around 6 h intraoperatively following which there was major surgical bleeding and hemoglobin dropped <5 g/dL multiple times despite aggressive fluid replacements. The surgery lasted 15 h, and she received 12 units of packed red blood cells (PRBCs), 4 units of fresh frozen plasma (FFP), 2 L of hydroxyethyl starch, 600 mL albumin, 15 L of Kabilyte (acetated intravenous fluid), and 40 mL of 10% calcium gluconate. Intraoperative fluid management was guided by continuous arterial and central venous pressure monitoring, frequent arterial blood gas analysis including electrolyte levels, platelet count, prothrombin time, and thromboelastography (TEG). She required noradrenaline infusion up to 0.2 mcg/kg to maintain mean arterial pressure >65 mmHg, and urine output was >1 mL/kg/h. Intraoperatively, perfusion of transplanted hands was impeded by arterial and venous thrombi which required multiple thrombectomy and reanastomoses and fasciotomies for decompression. Therefore, a certain degree of coagulopathy was accepted to prevent further thrombus formation and hence MT protocols were not strictly followed. The aim was to maintain good perfusion of hands with target hemoglobin of 10 g/dL with hemodilution to facilitate perfusion across anastomoses. In 48 h, she had received a total of 21 units of PRBC and 9 units of FFP. Coagulation parameters were maintained at safe acceptable levels [Table 1]. Other than hypothermia, she did not develop any major complications such as renal or lung injury secondary to MT.Table 1: Laboratory investigation results and interventionsMT is defined as replacement of one entire blood volume within 24 h, transfusion of >10 units of PRBCs in 24 h, transfusion of >4 units of PRBCs in 1 h, or replacement of 50% of total blood volume within 3 h.[2] Consumption of coagulation factors during massive bleeding and dilution of remaining factors due to volume expanders add to coagulopathy and altered hemostasis.[3] Coagulation tests are usually time-consuming and may not greatly help in guiding therapy during ongoing massive bleeding. TEG tests the entire hemostatic system including platelet function and fibrinolytic system. Therefore it is useful in managing complicated coagulopathies with timely intervention.[2] Ideally, MT protocols are to be activated after transfusion of 4–10 units which have a predefined ratio of RBCs, FFP/cryoprecipitate, and platelet units (1:1:1 or 2:1:1 ratio).[4,5] It is concluded that during bilateral hand transplantation surgeries, management of MT should be individualized taking into account hemoglobin levels, coagulation profile, and perfusion of transplanted hands. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Traumatic coagulopathy in the older patient: analysis of coagulation profiles from the Activation of Coagulation and Inflammation in Trauma-2 (ACIT-2) observational, multicenter study

BackgroundMost studies describing traumatic coagulopathy have used data from patient cohorts with an average age of between 35 and 45 years. The last 10 years has seen a steep increase in the number of patients admitted with significant injury and bleeding who are older than the age of 65 years. Many coagulation protein levels alter significantly with normal aging, and it is possible that traumatic coagulopathy has a different signature with age. ObjectivesThe aim of this study was to report the coagulation profiles, including standard and extended laboratory, as well as viscoelastic hemostatic assays, stratified according to age to explore age-related differences in hemostatic capability. MethodsIn total, 1576 patients were analyzed from 6 European level 1 trauma centers. ResultsAs age increased, there was evidence of higher fibrinogen, greater thrombin generation, greater clotting factor consumption, and greater activation of fibrinolysis. Despite this, shock and severe injury led to the same pattern of changes within age groups: lower procoagulant factors (including fibrinogen), increased fibrinolysis, and higher levels of activated protein C. Thromboelastography and rotational thromboelastometry tests detected traumatic coagulopathy with prolongation of R/clotting time and reductions in clot amplitudes in each age cohort. Advancing age strongly correlated with higher fibrinogen levels and greater fibrinolysis. ConclusionAge-related coagulation changes are evident in injured patients. Broadly, similar patterns of coagulation abnormalities are seen across age groups following severe injury/shock, but thresholds for single clotting factors differ. Age-related differences may need to be considered when clinical treatments (eg, transfusion therapy) are indicated.

Intermediate Results of the Cornell Blood Coagulation in Cancer Study (COBLOCA-Study)

Background Venous thromboembolism (VTE) and arterial thrombosis are common complications of cancer and cancer treatment. A history of VTE in cancer patients increases the mortality risk by more than 2-fold compared to patients without prior VTE. The risk of cancer-associated thrombosis depends on the type of cancer, anti-cancer treatment and patient related factors. Some cancers have a high risk of thrombosis including lung, pancreas, gastric and brain. Several cancer-related prediction scores, such as the Khorana score or the PROTECHT score are used to predict the risk of thrombosis. Many mechanisms have been proposed through which cancer-related thrombosis may occur, however it remains difficult to predict thrombotic events in individual patients. Thus, accurate prediction of thrombotic events would be useful in the clinic to identify which patient may benefit from pharmacologic thromboprophylaxis. Therefore, we aim to study whether VTE can be predicted in individual cancer patients using hematological parameters. Methods The Cornell Blood Coagulation in Cancer (COBLOCA) study is an ongoing prospective study of cancer patients seen in a large academic medical center with a follow-up duration of 2 years and a detailed documentation of thrombotic events. We aim to enroll 600 patients with cancer (500 without VTE and 100 with prior VTE). Demographics, type and stage of cancer, treatment, thrombotic events (prior and during study enrollment) and anticoagulation treatment are collected. The levels of fibrinogen, prothrombin, coagulation factor FV, FVII, FVIII, FIX, FX, FXI, FXII, and FXIII, antithrombin, protein C, protein S, von Willebrand Factor antigen and activity, and D-dimer levels were determined in the patient plasma samples. We present an intermediate analysis on the acquired data. Results A total of 76 patients with cancer have been enrolled in the study to date. The association of prior VTE and the levels of hematological variables in patients with cancer were explored in this intermediate analysis. At baseline, 24 patients (32%) had a prior VTE. Twenty-four patients were on anticoagulants at the time of enrollment, of which 54% were on apixaban, 21% on rivaroxaban, 21% on heparin, and 4% on warfarin. Seven patients used aspirin in addition to anticoagulants, and 10 patients only used aspirin. A history of VTE was most common in patients with lung or endometrial cancer. Patients with esophageal, gastric or hematologic neoplasm did not have a history of VTE at enrollment, although 1 patient with gastric cancer developed a VTE during follow-up. From the remaining patients, 67% of patients with pancreatic cancer, 50% of patients with breast, liver and renal cancer, 36% of patients with colon cancer, and 19% with prostate cancer, previously suffered from VTE (Figure 1). At the time of this intermediate analysis, 3 VTE events were reported during the ongoing follow-up period, 1 in a patient with lung cancer, 1 in a patient with gastric cancer and 1 in a patient with duodenal cancer and history of hereditary hemorrhagic telangiectasia. Pro- and anticoagulant factor levels were compared between patients with and without a prior VTE. Von Willebrand Factor (VWF) antigen (+31%) and activity (+36%) levels were significantly increased in cancer patients with a history of VTE. The plasma level of FXI was significantly decreased in cancer patients with prior VTE. Additionally, plasma levels of fibrinogen, prothrombin, FV, FVII, FVIII, FIX, FX, FXII, FXIII, antithrombin, protein C, and protein S showed a trend towards lower levels in patients with a prior VTE, although these differences did not reach statistical significance (Figure 2). Moreover, D-dimer levels were significantly higher in cancer patients with prior VTE (551 μg/mL ± 942 μg/mL) than cancer patients without a history of VTE (332 μg/mL ± 451 μg/mL). Conclusion Both VWF antigen and activity were significantly increased in cancer patients with a history of VTE, indicating that the vessel wall plays an important role in cancer-associated thrombosis. Likewise, elevated D-dimer levels, and reduced levels of available coagulation factors in cancer patients with a history of VTE indicate that these patients might be in a more pro-coagulant state, resulting in (sub-clinical) consumption of coagulation factors and ongoing low grade intra-vascular coagulation. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COCAINE INTOXICATION LEADING TO HYPERTHERMIA, DISSEMINATED INTRAVASCULAR COAGULATION, AND ACUTE RENAL FAILURE

COCAINE INTOXICATION LEADING TO HYPERTHERMIA, DISSEMINATED INTRAVASCULAR COAGULATION, AND ACUTE RENAL FAILURE

COVID-19 and Blood Clots: A Report of Massive Pulmonary Embolism in COVID-19 Patient Supported on Veno-Venous ECMO and the Utility of Thrombolysis

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our hospital. She was in profound shock requiring multiple vasopressors for hemodynamic support with worsening clinical status on arrival. On bedside echocardiography, she was found to have a massive pulmonary embolism with clot-in-transit visualized in the right atrium and right ventricular outflow tract. After a multidisciplinary discussion, systemic thrombolytic therapy was administered. The patient’s hemodynamics improved and vasopressors were discontinued. This case illustrates the utility of bedside echocardiography in shock determination, the need for continued vigilance in the systematic evaluation of unstable patients in the intensive care unit, and the use of systemic thrombolytics during V-V ECMO in a novel disease process with evolving understanding.

Indices of complement activation and coagulation changes in trauma patients

ObjectivesEarly complementopathy and coagulopathy are shown often after trauma. However, the prevalence of any interplay between complement cascade (ComC) and coagulation cascade (CoaC) after trauma remains unclear. This study intended...

COVID-19 and Blood Clots: A Report of Massive Pulmonary Embolism in COVID-19 Patient Supported on Veno-Venous ECMO and the Utility of Thrombolysis.

COVID-19 morbidity and mortality are not equivalent to other etiologies of acute respiratory distress syndrome (ARDS) as fulminant activation of coagulation can occur, thereby resulting in widespread microvascular thrombosis and consumption of coagulation factors. A 53-year-old female presented to an emergency center on two occasions with progressive gastrointestinal and respiratory symptoms. She was diagnosed with COVID-19 pneumonia and admitted to a satellite intensive care unit with hypoxemic respiratory failure. She was intubated and mechanically ventilated, but her ARDS progressed over the next 48 hours. The patient was emergently cannulated for veno-venous extracorporeal membrane oxygenation (V-V ECMO) and transferred to our hospital. She was in profound shock requiring multiple vasopressors for hemodynamic support with worsening clinical status on arrival. On bedside echocardiography, she was found to have a massive pulmonary embolism with clot-in-transit visualized in the right atrium and right ventricular outflow tract. After a multidisciplinary discussion, systemic thrombolytic therapy was administered. The patient's hemodynamics improved and vasopressors were discontinued. This case illustrates the utility of bedside echocardiography in shock determination, the need for continued vigilance in the systematic evaluation of unstable patients in the intensive care unit, and the use of systemic thrombolytics during V-V ECMO in a novel disease process with evolving understanding.