Normal Coagulation Research Articles

Thrombodynamics Test in Assessing the Risk of Thrombus Formation in Patients with Atrial Fibrillation Taking Direct Oral Anticoagulants

Aim. To evaluate thrombus characteristics in patients with atrial fibrillation (AF) taking different direct oral anticoagulants (DOACs) using Thrombodynamics test.Materials and methods. Thrombodynamics test was performed in 100 patients with paroxysmal and permanent forms of AF taking different DOACs, dose choice was done in accordance with the instructions for drugs use. For analysis samples of fresh citrated platelet-free plasma were taken just before regular DOACs dose intake (trough concentration). Statistical data processing was carried out using R software packages.Results. All patients had no history of thrombosis or bleeding before inclusion in this study. All parameters of Thrombodynamics test taken at residual concentration of DOACs were in general within reference values, that is in the area of normal coagulation: spatial clot growth rate (V) – 26.56 (25.0; 29.2) μm/min, the time to the start of clot growth (Tlag) – 1.05 (0.85; 1.27) min, initial spatial clot growth rate (Vi) – 44.3±7.7 μm/min, stationary spatial clot growth rate (Vst) – 26.5 (24.9; 28.4) μm/min, clot size (CS) – 999.7 (912.9; 1084.7) μm, clot density (D) – 22883.1±3199.9 arb. units. D was appeared to be higher in women [22947.7 (21477.5; 22947.7) vs men [22124.8 (19722.8; 22124.8), p=0.035] and Tlag was significantly higher in patients with chronic heart failure [1.2 (1.0; 1.2) vs 1.0 (0.8; 1.0), p=0.008]. A correlation was found between level of creatinine and Tlag parameter, glomerular filtration rate (GFR) and clot density. With an increase in the level of creatinine in the blood and a decrease in GFR, respectively, there was an increase in Tlag parameter (p-value 0.038); with an increase in GFR, clot density decrease (p-value 0.005).Conclusion. All parameters of Thrombodynamics test on residual concentration of DOACs were within reference values that indicated optimal anticoagulant effect of all DOACs. The obtained data of normal coagulation at the residual concentration of the anticoagulant are consistent with the previously obtained data on the safety and effectiveness of DOACs using other methods. Further studies with clinical end points are needed to assess the clinical value of this method.

Study of fetomaternal outcomes in eclampsia in correlation to coagulation profile in a tertiary care center in Mumbai

Background: Eclampsia is the leading cause of maternal and perinatal mortality as well as morbidity. The present study was conducted to assess the severity of eclampsia and coagulopathy by a method that is rapid, cheaper, and easily available and to assess the clinical evaluation and comparison of the fetomaternal outcomes in eclampsia with normal and deranged coagulation profiles. Aims and Objectives: This study aims to assess the severity of eclampsia and coagulopathy by a method that is rapid, cheaper, and easily available and to assess the clinical evaluation and comparison of the fetomaternal outcomes in eclampsia with normal and deranged coagulation profiles. Materials and Methods: A hospital-based prospective case–control study was done at tertiary care institute in the department of obstetrics and gynecology over a period of 1½ years from February 2018 to August 2019. Template was generated in MS Excel sheet and analysis was done on SPSS software. Results: Overall incidence of eclampsia was found to be 2.4%. Majority of the eclampsia patients in both normal coagulation profile group and deranged coagulation profile group were in the age group of 21–25 years (42.8% and 46.6%, respectively). The most common maternal outcome in the eclampsia patients with both normal (50%) and deranged (36.6%) coagulation profile was operative intervention, that is, lower segment cesarean section, followed by the requirement of maternal intensive care in critical care unit or medical intensive care unit. The least common fetal outcome among those with normal coagulation profile being neonatal death and still birth accounting for 2.85% of cases each whereas among those with deranged coagulation profile, the least common outcome being very low birth weight accounting for 3.33% of cases. Of the 46 eclampsia mothers who underwent operative intervention, 93.47% had normal platelet counts and 6.52% had thrombocytopenia. Of the eight neonatal deaths, 50% were among those of eclampsia mothers with normal platelet count and 50% among those with thrombocytopenia. Conclusion: In the present study, eclampsia accounted for 2.3% of all deliveries. Hence, relevant investigations need to be promptly done to identify the derangement of the coagulation profile in cases of eclampsia and pre-eclampsia which can alert the obstetrician of the severity of the disease so that appropriate and timely management can be initiated to prevent adverse outcomes.

Case report: Kaposi hemangioendothelioma of the right upper limb with the Kasabach–Merritt phenomenon: A potentially lethal diagnostic challenge

Kaposi hemangioendothelioma (KHE) is a rare vascular neoplasm that presents usually within the first year of life. Because of its rarity and complexity, there is often a delay in diagnosis. KHE could be associated with a life-threatening consumptive coagulopathy named the Kasabach-Merritt phenomenon (KMP). Here, we present the case of a 2-month-old girl who presented with progressive redness and swelling of her right upper limb over 6 weeks. Multiple health practitioners misdiagnosed her condition as an insect bite, cellulitis, and necrotizing fasciitis and gave treatment accordingly, which proved futile. A full blood count revealed bicytopenia of anemia and thrombocytopenia, a normal coagulation cascade, low fibrinogen, and raised D-Dimer levels. The imaging was suggestive of a high-flow vascular tumor likely to be a KHE. Subsequently, she was started on single-agent oral sirolimus with a dose increment to achieve satisfactory therapeutic levels and was treated for 1 year. She successfully completed the treatment regimen and had only transient hypertriglyceridemia, which resolved upon the completion of treatment. Currently, she is in remission 3 years after treatment. Keeping her case as an example, we would like to highlight the potentially lethal misdiagnosis of KHE with KMP, the importance of an early diagnosis of this condition, and the successful treatment outcome with single-agent sirolimus.

Association between isolated abnormal coagulation profile on transfusion following major surgery: A NSQIP analysis of individuals without bleeding disorders.

Preoperative coagulation screening for patients without bleeding disorders remains controversial. The combinatorial risk of INR, aPTT, and platelet count (PLT) abnormalities leading to bleeding requiring transfusion is not known in these patients. We examined the association between abnormal coagulation profile and the risk of transfusion following common elective surgery in patients without bleeding disorders. We utilized the National Surgical Quality Improvement Program (NSQIP) database from 2004 to 2018 to identify patients without a history of bleeding disorders undergoing common 23 major elective procedures across 10 specialties. Multivariable logistic regression was used to assess the association between coagulation profile and bleeding requiring packed red blood cell transfusion intra-/post-operatively. Of the 672,075 patients meeting inclusion criteria, 53.7% presented with normal coagulation profile preoperatively. Overall, 12.2% (n=82,368) received transfusion. In the setting of normal aPTT/PLT, both Equivocal INR of 1.1-1.5 (aOR 1.41, 95% CI 1.38-1.44) and Abnormal INR of >1.5 (aOR 1.81, 95% CI 1.71-1.93) were significantly associated with an increased risk of transfusion. Equivocal (60-70) and Abnormal (>70) aPTT with normal INR/PLT did not demonstrate a comparable risk of transfusion. We observed a synergistic effect of combinatorial lab abnormalities on the risk of transfusion when both Abnormal INR/aPTT and Low PLT of <100,000 were present (aOR 5.18, 95% CI 3.04-8.84), compared to the effect of Abnormal INR/aPTT and normal/elevated PLT (aOR 1.90, 95% CI 1.48-2.45). The preoperative presence of abnormal findings in INR or PLT was significantly associated with the risk of bleeding requiring transfusion during intraoperative and postoperative periods.

Standards of fracture care in polytrauma: results of a Europe-wide survey by the ESTES polytrauma section

IntroductionFixation of major fractures plays a pivotal role in the surgical treatment of polytrauma patients. In addition to ongoing discussions regarding the optimal timing in level I trauma centers, it appears that the respective trauma systems impact the implementation of both, damage control and safe definitive surgery strategies. This study aimed to assess current standards of polytrauma treatment in a Europe-wide survey.MethodsA survey, developed by members of the polytrauma section of ESTES, was sent online via SurveyMonkey®, between July and November 2020, to 450 members of ESTES (European Society of Trauma and Emergency Surgery). Participation was voluntary and anonymity was granted. The questionnaire consisted of demographic data and included questions about the definition of “polytrauma” and the local standards for the timing of fracture fixation.ResultsIn total, questionnaires of 87 participants (19.3% response rate) were included. The majority of participants were senior consultants (50.57%). The mean work experience was 19 years, and on average, 17 multiple-injured patients were treated monthly. Most of the participants stated that a polytrauma patient is defined by ISS ≥ 16 (44.16%), followed by the “Berlin Definition” (25.97%). Systolic blood pressure < 90 mmHg, tachycardia or vasopressor administration (86.84%), pH deviation, base excess shift (48.68%), and lactate > 4 mmol (40.79%) or coagulopathy defined by ROTEM (40.79%) were the three most often stated indicators for shock. Local guidelines (33.77%) and the S-3 Guideline by the DGU® (23.38%) were mostly stated as a reference for the treatment of polytrauma patients. Normal coagulation (79.69%), missing administration of vasopressors (62.50%), and missing clinical signs of “SIRS” (67.19%) were stated as criteria for safe definite secondary surgery.ConclusionDifferent definitions of polytrauma are used in the clinical setting. Indication for and the extent of secondary (definitive) surgery are mainly dependent on the polytrauma patient`s physiology. The «Window of Opportunity» plays a less important role in decision making.

DYSPNEA DURING PREGNANCY REVEALING MULTIPLE PULMONARY ARTERIOVENOUS MALFORMATIONS AND A NEW DIAGNOSIS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA

DYSPNEA DURING PREGNANCY REVEALING MULTIPLE PULMONARY ARTERIOVENOUS MALFORMATIONS AND A NEW DIAGNOSIS OF HEREDITARY HEMORRHAGIC TELANGIECTASIA

ACQUIRED VON WILLEBRAND SYNDROME SECONDARY TO MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: LONG-TERM REMISSION AFTER TREATMENT WITH BORTEZOMIB

To describe a case report of a patient with monoclonal gammopathy of undetermined significance (MGUS) who progressed to Acquired von Willebrand syndrome (AVWS) and was successfully treated with bortezomib. Case report with literature review. A 54-years-old woman presented at our center to investigate an M-spike. She had been treated for chronic kidney disease due to glomerulonephritis for eight years and was on peritoneal dialysis waiting for a kidney transplant. During laboratory workup, a serum M-protein (0.3 g/dL) was detected by protein electrophoresis and a monoclonal IgG kappa was identified. After one year of follow-up, and with stable M-protein levels, the patient started complaining of increased bleeding from minor wounds, bruises in inferior limbs and repeated episodes of epistaxis. The patient had no personal or family history of bleeding disorders. Laboratory testing included normal blood and platelet counts, normal prothrombin and thrombin time but increased activated partial thromboplastin time (APTT ratio 1.62). Mixing study results showed APTT correction. Factor VIII coagulant activity (FVIII:C) was 12% but no inhibitor was detected. Von Willebrand factor antigen (vWF:Ag) was 10% and ristocetin cofactor activity (vWF:RCo) was 3%, with a vWF:RCo/vWF:Ag ratio of 0.3. Given the absence of previous personal and family history of bleeding and the diagnosis of MGUS, the diagnostic hypothesis of AWVS was made. To confirm this hypothesis, we performed a recovery test after infusion of von Willebrand factor (vWF 50 UI/kg), which results were suggestive of increased vWF clearance. The patient required treatment only after three years of AVWS diagnosis due to severe lingual hematoma. She was treated with two units of packed red blood and immunoglobulin (0.4g per kg for five days), with successful bleeding control. vWF:Ag, vWF:RCo and FVIII:C levels were also increased but returned to baseline values after three weeks. Because the patient was scheduled to undergo a kidney transplantation and the high risk of bleeding could lead to graft loss, it was decided to treat the MGUS-associated AVWS. She was treated with three cycles of dexamethasone 20 mg and cyclophosphamide 300 mg with no response. A second line treatment was started with dexamethasone 12 mg and bortezomib 1.5mg/m2 for a total of five cycles. After the end of the treatment, APTT, vWF:Ag, vWF:RCo results normalized and monoclonal paraprotein was eradicated. The patient was submitted to a kidney transplantation without bleeding complications. Two years after the end of the treatment, she remains in remission, with undetectable monoclonal paraprotein and normal coagulation and VWF tests. MGUS-associated AWVS is a rare bleeding disorder, and few data is available on the best treatment approach. We reported a case that transiently responded to immunoglobulin. This response, however, was not sufficient to warrant hemostatic levels of vWF required for kidney transplantation. Treatment of MGUS with bortezomib and dexamethasone led to eradication of the M-spike and normalization of the coagulation parameters. This response was durable, as the patient remains in remission of both MGUS and AWVS two years after the end of the treatment. This particular case highlights the importance of treating the underlying cause of the coagulopathy once the remission of AVWS only occurred after monoclonal gammopathy was controlled.

Dealing With Failure.

Dealing With Failure.

Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: Results from a laboratory sub-study of the FEISTY trial.

BackgroundFibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms.MethodsClot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma.ResultsFibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness.ConclusionsIn summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13054-022-04167-x.

CT-157 Another Rare Case of COVID-19 Vaccine Induced Acquired Hemophilia

Context: Acquired hemophilia A is an autoimmune bleeding disorder that results from autoantibodies against coagulation factor VIII. Failure to recognize AHA as a cause of bleeding results in delayed management. Objective: Case report of acquired hemophilia after receiving COVID-19 vaccines (Pfizer-BioNTech SARS-CoV-2 mRNA vaccine). Design and Patient Criteria: A case report of a lady who attended the haematology clinic at the University College London hospital. This included history taking, physical examination, full blood count, coagulation screen and factor assay, factor VIII inhibitor assay, immune workup, and CT scan. Main Outcome: We reported this 40-year-old lady with no previous medical history. She presented with massive vaginal bleeding and anemia which needed a blood transfusion. This coincided with her first dose of the Pfizer vaccine. Investigations showed high APTT at 45 sec, Factor VIII level at 0.3 IU/ml, Factor VIII Bethesda antibodies assay at 0.8 with normal other coagulation work up. Immune profile (ANA, Anti-dsDNA, C3, C4, and lupus workup) was negative and CT whole body showed no abnormalities. She was started on prednisolone 60 mg after which her bleeding improved and factor VIII level increased to 0.5 IU/ml. Once she started steroid withdrawal bleeding re-occurred and factor VIII level dropped to 0.21 IU/mL with APTT prolongation to 45 sec. Subsequently, she received 4 weeks of rituximab resulting in Factor VIII level normalization at 1.51 IU/ml, normal clotting screen and resolution of bleeding which has been sustained since November 2021. Conclusions: While thrombosis is a side effect of COVID-19 infection, bleeding can still happen in the setting of COVID-19 infection/vaccination. Till recently, only a few cases of acquired hemophilia have been reported after receiving mRNA-derived COVID-19 vaccines. Related Haematologic autoimmune disease may involve stimulation of auto-antibody production from preexisting B cells by triggering autoimmunity. It is crucial to raise awareness about this side effect that may be directly induced by the mRNA COVID-19 vaccine. We highly recommend screening for an antibody inhibitor with unexplained bleeding and/or isolated activated partial thromboplastin time prolongation following the COVID vaccine.

Large Head in Asymptomatic Child: A Subtle Presentation of Connective Tissue Disorder With Spontaneous Significant Intracerebral Bleed

Three years old boy with reassuring development had presented to the Pediatric Neurology clinic with a referral due to a large head. Occipito-frontal circumference was more than 97th centile with an unremarkable neurological examination. MRI brain exhibited an acute on chronic large right frontoparietal subdural hematoma with prominent mass effect. Consequentially, the hematoma was evacuated by the neurosurgeon. Postoperative recovery stayed satisfactory. Hematology workup showed normal coagulation and clotting factors levels. Whole exome sequencing (WES) study revealed heterozygous variant c.5187G>A p.(Trp1729*) in gene FBN1 - pathogenic for Marfan syndrome. However, this variant has not yet been reported in association with cerebral arteritis/intracerebral bleed. On follow-up, the child remained asymptomatic clinically with static head size. This drags us towards the fact that significant yet asymptomatic spontaneous intracerebral hemorrhage can be an infrequent presentation in pediatrics in regard to connective tissue disorders. Moreover, children with Marfan syndrome having variant c.5187G>A p.(Trp1729*) of gene FBN1 can have a rare presentation with cerebral arteritis or intracerebral bleed.

Vitamin K as a Simple but Efficient Add-on to the Current Treatment Regime of COVID-19: A Narrative Review

Background: Intravascular thrombosis and pulmonary fibrosis in COVID-19 patients with pneumonia are significantly associated with the severity of the disease. Vitamin K is known to balance the coagulation mechanisms and also prevent calcification and fibrosis of the extrahepatic soft tissues. This narrative review focuses on the role of vitamin K as a linking factor for thrombotic as well as pulmonary complications of COVID-19. Methods and Results: Article search was performed in databases of WHO, PubMed, Scopus and Clinical Trial Registry using appropriate keywords. Original articles included very few observational studies which showed a reduced level of vitamin K as well as activated extrahepatic vitamin K Dependent Proteins (VKDP) in COVID-19 patients when compared to healthy controls. Chronic treatment with vitamin K Antagonists did not reduce the risk of in-hospital death. Docking study was performed using Swiss dock, and it demonstrated a significant interaction between menaquinone and SARS-CoV-2 main protease (SARS-CoV-2 Mpro). Discussion: Deficiency of vitamin K in COVID-19 can be due to excessive use of antagonists or defective ingestion or absorption. This triggers an imbalance in the normal coagulation- anticoagulation mechanism by channeling the available vitamin K to the liver, thereby causing a deficiency of the same in extrahepatic tissues, thus finally leading to thrombosis. This also prevents carboxylation and activation of extrahepatic VKDP required to prevent the calcification of soft tissues, thus leading to lung fibrosis. Conclutions: Supplementation of vitamin K should be considered as a potentially modifiable risk factor in severe COVID-19. Randomized control trials are highly recommended to provide clearer evidence on the same.

Autoimmune disorders of platelet function: systematic review of cases of acquired Glanzmann thrombasthenia and acquired delta storage pool disease.

Acquired platelet function disorders (PFD) are rare bleeding diseases that should be suspected in all patients with unexplained mucocutaneous bleedings of recent onset, with no previous history of haemorrhages, and with normal coagulation test and platelet count. Drug-induced platelet function bleeding disorders are the most frequent PFDs and can easily be identified on the basis of recent administration of platelet-inhibiting drugs. Apart from these, the most challenging acquired PFDs are those caused by autoimmune mechanisms. In fact, demonstration of autoantibodies inhibiting platelet function may be difficult in most non-specialised centres. Among autoimmune PFDs (aPFDs), acquired Glanzmann thrombasthenia (aGT), which is caused by autoantibodies that bind to platelet αIIbβ3 integrin, inhibiting its function, is the most frequent. aGT can be associated with underlying haematological malignancies or autoimmune diseases but can also be idiopathic. More rarely, other immune-mediated PFDs can occur, such as acquired delta storage pool disease (aδSPD). Treatment of aPFDs must rely on the control of acute and chronic bleedings, treatment of the underlying disease in secondary forms, and immunosuppressive treatment for autoantibody reduction or eradication. aPFDs may completely resolve upon treatment of any underlying disease that may be present. In primary aPFDs, and in the majority of secondary forms, treatment relies on immunosuppressive therapies.Here we present a systematic review of previously described immune-mediated aGT and aδSPD cases. Clinical and laboratory characteristics, treatments for the control of bleedings and for the eradication of autoantibodies, and responses to treatments are also discussed. Although no guidelines are available for the management of these very rare conditions, presentation of all cases reported so far can help clinicians in the diagnosis and treatment of these life-threatening diseases.

Plasma thrombin generation kinetics in trauma patients across the age spectrum

• Trauma induces early changes in thrombin generation kinetics. • Initiation and time to peak thrombin generation positively correlate to age. • TBI and transfusion impact age related trends in both plasma coagulation markers. • Age-specific models of thrombin generation and TIC are needed. Injured patients have early changes to normal coagulation that can impact long term risk for thrombotic complications. There is little known about how age impacts biomarkers of coagulation after traumatic injury. In this pilot study, we aimed to characterize thrombin generation kinetics, a known predictor of venous thromboembolism, in trauma patients across the age spectrum. Citrated plasma samples were collected from 174 trauma patients (3–94 years old). Thrombin generation kinetics were measured using calibrated automated thrombogram (CAT) and expressed as lag time (LT – minutes) and time to peak (ttPeak – minutes). Kruskal-Wallis, Spearman correlation, and multivariable regression analysis were carried out. Data in median and quartiles [Q1, Q3]. P < 0.05 significant. Pediatric patients ( n = 14) had shortest LT and ttPeak compared to adult and geriatric ( n = 43), who had longest (LT: 2.67 [2.48, 3.00] vs. 2.93 [2.56, 3.48] vs. 3.15 [2.74, 3.67], p = 0.029; ttPeak: 4.98 [4.67, 5.67] vs. 5.53 [5.00, 6.56] vs. 5.94 [5.52, 6.91], p = 0.011). LT and ttPeak correlated with age (Spearman 0.285 and 0.305, both p < 0.001). Clinical factors, specifically, age, injury severity score, and transfusion status were associated with LT and ttPeak in multivariable models. Trauma patients exhibit prolonged initiation and time to peak thrombin generation with age. Further studies are needed to determine the age-specific role of thrombin generation kinetics in thrombotic complications after trauma.

Ureteral Inflammatory Myofibroblastic Tumor as a Cause of Gross Hematuria in Adults

At his first urological appointment, a 44-year-old male patient presented with gross hematuria and right lower back pain for one week. He had no history of smoking, occupational risks, trauma, urinary lithiasis, or any other comorbidities. The patient had no family history of malignancies. Laboratory tests revealed normal creatinine clearance, hemogram, coagulation tests, and negative urinary culture. Computed tomography imaging is shown in Figure 1. A diagnostic right ureteroscopy was performed, followed by a biopsy of the visible tumor and a double J stent placement.

A Pilot Study to Assess the Clinical Onset of IV Heparin in Interventional Cardiology and Cardiac Surgery

To determine the onset of heparin anticoagulation, using 2 different measures of activated clotting times (ACT), thromboelastography (TEG; R-time), and anti-Xa levels, after administering low- (100 U/kg) and high- (300 U/kg) dose intravenous (IV) heparin to patients undergoing transcatheter aortic valve replacement (TAVR) and cardiac surgery, respectively. Prospective study. Single academic institution. Patients with normal baseline coagulation presenting for TAVR or cardiac valve surgery. Coagulation studies were performed at baseline, 30 seconds, 90 seconds, and 180 seconds after IV heparin administration. The tests included iSTAT (iACT) and Hemochron ACT (hACT), TEG R-Time, and anti-Xa levels. At the authors' institution, anti-Xa is the preferred measure of heparin anticoagulation when time permits. ACT, a rapid point- of-care test, is used to assess intraprocedural anticoagulation. After both low- and high-dose heparin, there are peak increases in ACT and anti-Xa at 30 seconds, followed by a decline at 90 seconds and plateau at 180 seconds. The TEG R-time remained elevated (>80 minutes) throughout. For TAVR cases, all anti-Xa was >1.5 IU/mL, and was associated with an iACT >180 seconds and an hACT >200 seconds. For cardiac valve surgery cases, all anti-Xa was >2.4 and associated with an iACT >420 seconds and and hACT >340 seconds. Compared with hACT, iACTs were significantly lower at all time points after low-dose heparin, but not after high-dose heparin. In this pilot study, heparin anticoagulation was detected as early as 30 seconds after IV administration, based on ACT, anti-Xa levels, and TEG R-time.

Clinical Characteristics of Venous Thrombosis Associated with Peripherally Inserted Central Venous Catheter in Premature Infants.

Background: This study aimed to analyze clinical characteristics and risk factors for peripherally inserted central catheter (PICC) placement in premature infants. Materials: This study included seven premature infants who were hospitalized in the neonatal intensive care unit (NICU) of Peking University Third Hospital from 1 January 2014–30 June 2021, and suffered PICC-related venous thrombosis. The control group included premature infants (n = 56) matched (1:8) by the following: Did not experience venous thrombosis; born with a similar gestational age (±2 w), birth weight (±200 g); and received PICC catheterization in the same period (±4 w). Clinical neonatal data were collected through the hospital electronic medical record system and analyzed using SPSS version 23. Results: The incidence of PICC-related thrombus was 0.23% (7/3043. Univariate analysis revealed that, compared to the non-thrombotic group, mothers in the thrombosis group had autoimmune diseases (χ2 = 9.844, p = 0.030) and used anticoagulative drugs during pregnancy (χ2 = 8.036, p = 0.025). The corrected gestational age when PICC-related thrombosis occurred in the thrombosis group was 32 + 6 (30 + 1, 34 + 1) weeks. The average time from catheter placement to thrombosis was 5 (1, 12) days. Among infants, 85.7% (6/7) experienced deep vein thrombosis, of which four were in the lower extremity veins; three occurred within 2 days after central venous catheter extubation, and four occurred during central venous catheter indwelling. The clinical manifestations of thrombosis include skin edema, color changes, and skin temperature changes in the affected limbs. The seven neonates had normal coagulation at the time of thrombus diagnosis, but D-dimers significantly increased 1–2 days after thrombosis, returning to normal 5–8 days after thrombus. The thrombus persisted for 4.5 (3, 8) days. All seven neonates were treated with low molecular weight heparin calcium anticoagulation for 10 (3, 17) days and recovered completely. Conclusions: PICC-related thrombosis occurred within 1 week after catheter placement, and thrombosis more likely happened in infants whose mothers had autoimmune disease. When this high-risk factor exists and the patient has been intubated for 1 week and has sudden swelling in the intubated limb, venous ultrasound should be performed immediately to diagnose, and treatment should be provided in a timely manner to reduce adverse events.

Vitamin K content of cheese, yoghurt and meat products in Australia

Vitamin K is vital for normal blood coagulation, and may influence bone, neurological and vascular health. Data on the vitamin K content of Australian foods are limited, preventing estimation of vitamin K intakes in the Australian population. We measured phylloquinone (PK) and menaquinone (MK) -4 to -10 in cheese, yoghurt and meat products (48 composite samples from 288 primary samples) by liquid chromatography with electrospray ionisation-tandem mass spectrometry. At least one K vitamer was found in every sample. The greatest mean (± standard deviation for foods sampled in multiple cities) concentrations of PK (4.9 µg/100 g), MK-4 (58 ± 9 µg/100 g) and MK-9 (8 ± 2 µg/100 g) were found in lamb liver, chicken leg meat and Cheddar cheese, respectively. Cheddar cheese (1.1 ± 0.3 µg/100 g) and cream cheese (1.0 µg/100 g) contained MK-5. MK-8 was found in Cheddar cheese only (4 ± 2 µg/100 g). As the K vitamer profile and concentrations appear to vary considerably by geographical location, Australia needs a vitamin K food composition dataset that is representative of foods consumed in Australia.

Fibrinogen Deficiency with Thrombotic Manifestations.

Fibrinogen deficiencies are very rare. Qualitative fibrinogen deficiencies (dysfibrinogenaemia and hypodysfibrinogenemia) are functional disorders that can present with both haemorrhagic symptoms and with thrombotic phenomena as unique and paradoxical manifestation. We present the case of a 77-year-old man being investigated for a partially thrombosed abdominal aortic aneurysm as well as an ischaemic stroke 20 years previously. Basic coagulation tests were normal but extended tests revealed a lengthened thrombin time (TT) combined with a significant drop in fibrinogen concentration measured with the Clauss assay and by nephelometry. After secondary fibrinogen deficiencies were ruled out, a heterozygous variant in the FGG gene was detected by next-generation sequencing, and congenital hypodysfibrinogenemia was diagnosed. Acenocumarol was initiated and no new thrombotic or haemorrhagic events had occurred after a year of follow-up.In almost 25% of cases, thrombotic events may be the only clinical manifestation of functional fibrinogen deficiencies. They are a rare cause of thrombophilia, and are probably underdiagnosed due to normal standard coagulation test results as well as a possible absence of haemorrhagic events. Consequently, a TT test (an initial ‘rule out’ test) should be requested in order to promptly identify these patients. Moreover, discrepancies in derived and Clauss fibrinogen test results should suggest a functional disorder. Finally, new coagulation techniques based on the functional characterization of clot formation, such as ROTEM or thrombin generation assay, could help characterize these entities and suggest new therapeutic approaches.LEARNING POINTSFunctional fibrinogen deficiencies can present with thrombotic manifestations only, and are a rare and probably underdiagnosed cause of thrombophilia.Thrombin time is a highly sensitive test to rule out other conditions as aPTT and PT results may be within normal ranges, especially in functional deficiencies.Discrepancies between derived and Clauss fibrinogen findings, fibrinogen protein measurements and the use of new techniques (ROTEM or thrombin generation) are important for correct approach.

In vitro evaluation of canine whole blood with the addition of Crotalus atrox (Western Diamondback Rattlesnake) venom and antivenom using thromboelastography.

To compare the efficacy of 2 equine-origin antivenom products on correction of coagulation abnormalities noted on thromboelastography (TEG) caused by Crotalus atrox venom in vitro. Prospective in vitro controlled study. Veterinary teaching hospital. Six healthy dogs. Blood from each dog was used for 4 separate kaolin-activated TEG analyses: A negative control (blood-saline) and positive control (blood-Crotalus atrox venom) were used to assess the dog's normal coagulation and the effect of venom on TEG parameters. Thromboelastographic analyses were then run with blood, venom, and either Argentinian or North American antivenom. All TEG analyses from each dog were compared for efficacy. The mean R values between the North American antivenom and negative controls were not significantly different (P=0.681), but were significantly different (P=0.024) between the Argentinian antivenom and negative controls. The mean fibrinolysis values measured 30minutes after maximum amplitude achieved between the North American antivenom and negative controls were not significantly different (P=0.198), but were significantly different (P<0.001) between the Argentinian antivenom and negative controls. The mean K values between the Argentinian antivenom and negative controls were not significantly different (P=0.274), but were significantly different (P=0.043) between the North American antivenom and negative controls. The North American antivenom normalized time to clot formation and fibrinolysis, while the Argentinian antivenom normalized rate of clot formation. Further studies in naturally envenomated patients are necessary to determine if these in vitro results would translate into different clinical outcomes.